Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic differences between retinoma and retinoblastoma

Introduction. Genomic copy number changes are involved in the multi-step process transforming normal retina in retinoblastoma after RB1 mutational events. Previous studies on retinoblastoma samples led to a multi-step model in which after two successive RB1 mutations, further genomic changes accompany malignancy: 1q32.1 gain is followed by 6p22 gain, that in turn is followed by 16q22 loss and 2p24.1 gain. Retinoma is a benign variant of retinoblastoma that was initially considered a tumor regression, but recent evidences suggest that it rather represents a pre-malignant lesion. Genetic studies on retinoma tissue have rarely been performed. Materials and methods. We investigated by Real-Time qPCR, copy number changes of candidate genes located within the 4 hot-spot regions (MDM4 at 1q32.1, MYCN at 2p24.1, E2F3 at 6p22 and CDH11 at 16q22) in retina, retinoma and retinoblastoma tissues from two different patients. Results. Our results demonstrated that some copy number changes thought to belong to early (MDM4 gain) or late stage (MYCN and E2F3 gain) of retinoblastoma are already present in retinoma at the same (for MDM4) or at lower (for MYCN and E2F3) copy number variation respect to retinoblastoma. CDH11 copy number is not altered in the two retinoma samples, but gain is present in one of the two retinoblastomas. Discussion. Our results suggest that MDM4 gain may be involved in the early transition from normal retina to retinoma, while MYCN and E2F3 progressive gain may represent driving factors of tumor progression. These results also confirm the pre-malignant nature of retinoma.
Characterizing patterns of drug‐taking behavior with a multiple drug regimen in an AIDS clinical trial

Objective:To characterize drug-taking behavior using continuous electronic monitoring in an AIDS clinical trial. Setting:This was a substudy of AIDS Clinical Trials Group (ACTG) protocol 175, a phase II/III study of dideoxynucleoside monotherapy versus combination therapy in asymptomatic HIV-positive subjects. Participants were required to comply with regimens containing zidovudine, zalcitabine and didanosine, or matching placebos; the total daily pill count was 16. Design:For participants at two ACTG 175 sites, electronic devices were used to monitor drug-taking behavior of all study medications over a period of approximately 90 days. Measurements:Four indices of drug-taking behavior were calculated and their distributions and relationship to the prescribed regimen were examined. Results:Data from 41 subjects were analyzed. Of the prescribed doses of zidovudine, zalcitabine and didanosine, 88, 84 and 82%, respectively, were taken. Of these, 55, 66 and 79%, respectively, were taken at the prescribed dosing frequency. The median percentage of days on which participants failed to take any of the doses was 2–5%. There was a trend towards lower adherence in the combination therapy arms compared with those assigned to receive monotherapy. In this analysis, older patients demonstrated better adherence, although patient characteristics, in general, were poorly predictive of adherence. Conclusion:Drug-taking behavior for all three active study medications differed from that prescribed. One result of this erratic adherence was that study participants sustained little antiretroviral effect during more than 25% of the monitoring period.
Clinical Features of Superficially Located Brain Arteriovenous Malformations with Transdural Arterial Communication

Background: Contrary to deeply located brain arteriovenous malformations (AVMs), superficially located AVMs are more likely to have transdural arterial communications (TACs). However, the clinical and radiologic characteristics of patients presenting with AVMs and TACs are poorly understood. The purpose of this study is to determine whether clinicoradiological features of cerebral AVMs differ according to TAC. Methods: Between 2002 and 2012, 438 consecutive patients with a brain AVM were treated in our hospital. Among them were 124 patients with superficially located brain AVMs who met the inclusion and exclusion criteria of our study. We retrospectively reviewed the clinicoradiological features of their TACs to explore the variation in characteristics. Results: Thirty-two of the 124 patients with a superficially located AVM (25.8%) had TAC. Radiologic findings of brain AVM images with TAC showed that TAC occurred significantly more frequently among larger AVMs (with vs. without TAC, 11.2 vs. 4.0 ml) and among diffuse AVMs (56.3 vs. 28.3%, p = 0.004). Clinical findings indicate that TAC was associated with chronic headache (43.8 vs. 12.0%, p < 0.001) and older age (43.1 vs. 36.6 years, p = 0.037). Conclusions: Brain AVM with TAC seems to be accompanied by distinctive clinical features, such as chronic headache and older age. Larger size and diffuseness of the AVM were also associated with TAC. Findings from this study and the prognostic significance of TAC should be further explored in a large prospective study.
Ethnic Disparity in clinical outcome after heart transplantation is abrogated using tacrolimus and mycophenolate mofetil-based immunosuppression

Background. Black American heart transplant recipients receiving cyclosporine-based primary immunoprophylaxis suffer higher rates of allograft rejection with hemodynamic compromise, infections, and posttransplant coronary artery disease. We examined the hypothesis that a combination of tacrolimus and mycophenolate mofetil “resurrects” clinical outcome of black Americans to those seen in white heart transplant recipients. Methods. Sixty-three adult primary heart transplant recipients were included in this study. Twenty black American and 21 white patients who received tacrolimus-based primary immunoprophylaxis were enrolled in this prospective, observational parallel cohort investigation. A separate group of 22 black American patients were randomly allocated to receive cyclosporine–microemulsion-based primary prophylaxis and served as the control population for assessing outcomes in the black American group. Adjunctive immunosuppression included mycophenolate mofetil and corticosteroids. The primary end-point was the freedom from allograft rejection requiring treatment at 1 year. Secondary end-points included rejection with hemodynamic compromise, and patient or graft survival. Adverse events evaluated included development of infections requiring hospitalization and nonimmunological outcomes including hyperlipidemia, hypertension, and diabetes mellitus (new onset or worsened). Results. Tacrolimus-treated black American patients had greater freedom from allograft rejection requiring treatment at 1 year than those treated with cyclosporine (64% vs. 37%, P =0.01). No differences were noted between tacrolimus-treated black Americans and whites in the primary end point (64% and 67% respectively, P =nonsignificant [NS]). Tacrolimus-based immunosuppression was associated with better 1-year survival in black Americans compared with cyclosporine (95% vs. 73%, P =0.04), and this end point was similar to that achieved in tacrolimus-treated white heart transplant recipients (95%). No differences in infection rates were noted among either group. Cyclosporine-treated black Americans suffered more hyperlipidemia and worse hypertension than tacrolimus-treated patients. Conclusions. Compared with cyclosporine, an immunosuppressive strategy using tacrolimus in black Americans achieves superior efficacy with regard to allograft rejection, higher allograft survival, and similar safety. Furthermore, tacrolimus-based immunosuppression is similar in immunological efficacy and safety in black Americans and in white heart transplant recipients.
Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes.

In a panel of metastatic melanoma cell lines we found steady-state mRNA transcripts for multiple growth factors including basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A, PDGF-B, transforming growth factor (TGF)- beta 1, TGF- alpha, melanoma growth-stimulating activity (MGSA), interleukin (IL)-1 alpha, and IL-1 beta but not insulin-like growth factor (IGF)-1 or IGF-2. Expression of growth factor genes was constitutive because prior to RNA extraction melanoma cells were maintained in a chemically defined culture medium free of exogenous growth factors. Each of four cell lines had an individual pattern of expression of either two, four, five, or seven growth factors; however, all cell lines shared expression of the bFGF gene. Two strains of normal melanocytes expressed TGF- beta 1 but not bFGF, PDGF, TGF- alpha , or MGSA mRNA at detectable levels. We tested growth-modulatory effects of the growth factors most frequently expressed by melanoma cells (bFGF, TGF- alpha, TGF- beta, PDGF). None of these stimulated melanoma cell growth consistently, whereas exogenous, acid-activated TGF- beta inhibited melanoma growth at concentrations greater than 10 ng/ml, suggesting that bioactive TGF- beta may represent a physiologic growth inhibitor. Neither neutralizing antisera to PDGF or TGF- alpha nor a monoclonal antibody to the epidermal growth factor (EGF)-receptor inhibited melanoma cell growth. Our results indicate that multiple growth factors are expressed simultaneously and constitutively by melanoma cells but not normal melanocytes in culture. Expression of bFGF is a common feature underscoring the significance of bFGF as an autocrine factor for melanoma cells as described earlier. Secreted PDGF and TGF- alpha are apparently not involved in or not essential for autocrine growth stimulation of melanoma cells.
Analysis of tetracycline resistance encoded by transposon Tn10: deletion mapping of tetracycline-sensitive point mutations and identification of two structural genes

Deletions in the tet genes derived from Tn10 were formed from different tet::Tn5 insertion mutations by removing DNA sequences located between a HindIII site in Tn5 and a HindIII site adjacent to the tet genes. Tetracycline-sensitive point mutations were mapped in recombination tests with the deletions and were thus aligned with the genetic and physical map of the tet region. Plasmids carrying point mutations were tested for complementation with derivatives of pDU938, a plasmid carrying cloned tet genes derived from Tn10 which had been inactivated by Tn5 insertions. Complementation occurred between promoter-proximal tet point mutations and distal tet::Tn5 insertions, suggesting the existence of two structural genes, tetA and tetB. These results, together with the analysis of polypeptides in minicells harboring pDU938tet::Tn5 mutants, suggested that tetA and tetB are expressed coordinately in an operon. The tetB gene encodes the previously characterized 36,000-dalton cytoplasmic membrane TET protein, but the product of tetA was not identified. Point mutations in either tetA or tetB led to the defective expression of the resistance mechanism involving tetracycline efflux. It is suggested that the tetA and tetB products interact cooperatively in the membrane to express resistance.
Salt-induced renal injury in SHRs is mediated by AT1 receptor activation

Objective This study aimed to examine the effects of salt loading, with or without simultaneous angiotensin receptor blocker (ARB) treatment, on the systemic and tissue renin-angiotensin system (RAS) in spontaneously hypertensive rats (SHRs). Method Evaluation was performed early (4 weeks) in the course of salt loading in order to examine initial mediating events of cardiovascular and renal damage produced by salt excess. Four groups of rats were studied. Group 1 received regular rat chow (normal-salt diet); group 2 received normal-salt diet and an ARB (losartan, 30 mg/kg per day); group 3 received high-salt (8%) chow; and group 4 received high-salt diet and losartan. Results High-salt diet increased systolic pressure to 193 ± 1 mmHg compared to 180 ± 2 in normal-salt diet group. Losartan reduced SBP in SHRs fed normal-salt diet but did not reduce SBP in the SHRs fed high-salt diet (192 ± 2 mmHg). High-salt diet markedly increased urinary protein excretion from 27 ± 4 to 64 ± 13 mg/day and this increase was ameliorated by losartan (40 ± 9 mg/day). In SHRs on high-salt diet, plasma angiotensin II concentration increased three to four-fold, whereas urinary angiotensinogen excretion increased 10-fold; and these changes were significantly reduced by losartan. High-salt diet accelerated glomerular injury and interstitial fibrosis in SHRs which were reduced by losartan. Conclusion These results demonstrate that the activity of RAS was either not suppressed or, even augmented, after 4 weeks of salt loading despite high salt intake and increased SBP. The data suggest that an augmented intrarenal RAS during high-salt diet may contribute to the development of renal injury in this experimental model.
The Efficacy of the Combined Procedure in Involutional Entropion Surgery: A Comparative Study

Purpose To evaluate the efficacy of the combined procedure in the management of involutional entropion. Methods In this study, we reviewed 45 eyes of 36 patients who underwent the combined procedure (lateral tarsal strip, retractor tightening, and everting sutures) for the management of involutional lower eyelid entropion and compared the results with 31 eyes of 25 patients who underwent the Wies procedure. Exclusion criteria included previous lower eyelid surgery and follow-up of less than 6 months. Results No patients demonstrated entropion on the first postoperative day. The mean follow-up period was 18.4 months (6 to 52 months) in the Wies group and 22.6 months (6 to 59 months) in the combined procedure group. During the follow-up period, 9 of 31 eyes in the Wies group presented with recurrence and only 1 of 45 eyes in the combined procedure group presented with recurrence (p = 0.001). The average time of recurrence was 4.8 months in the Wies group. Recurrence occurred at 2 months postoperatively in the patient in the combined procedure group. Six of the 9 recurrences in the Wies group were managed by the combined procedure. None of these patients had further recurrence after correction. Three patients complained about a visible incision line after the Wies procedure. Conclusions The combined procedure seems to be more effective than the Wies procedure in the management of involutional entropion. The combined procedure addresses the three major causative factors in involutional entropion and makes it possible to perform the surgery using a small incision.
Nanopore analysis

Nanopore analysis is an emerging technique that enables the investigation of the conformation of a single peptide or protein molecule. Briefly, a pore is inserted into a membrane under voltage clamp conditions. When a molecule interacts with the pore there is a change in the current, I, for a time, T. Small unfolded molecules can translocate the pore whereas folded or large molecules tend to simply bump into the pore and then diffuse away. Therefore, the parameters, I and T, are dependent on the conformation of the molecule at the instant at which it encounters the pore. Thus, multiple conformations can be detected simultaneously in a single sample. As well, the analysis can be performed under dilute conditions so that folding or dimerization of a peptide can be followed in real time, which is generally difficult to study for proteins that are prone to aggregate. In this report, we describe our initial analysis of (1) Aβ peptides, which are deposited as amyloid plaques in Alzheimer disease, (2) α-synuclein, which is implicated in Parkinson disease and (3) prion proteins whose misfolding is evident in transmissable spongiform encephalopathies. In each case conformational information can be obtained which may help in understanding the early steps in the misfolding pathways.
Identification of genomic biomarkers associated with the clinicopathological parameters and prognosis of esophageal squamous cell carcinoma.

BACKGROUND At present no objective prognostic biomarkers have been established in esophageal squamous cell carcinoma (ESCC). OBJECTIVE To identify the genomic biomarkers associated with clinicopathological factors and prognosis of ESCCs. METHODS Real-time PCR was used to analyze the copy number change and mRNA expression of genes. The survival curves were plotted according to Kaplan-Meier method and checked by log-rank test. RESULTS We revealed the copy number increase of CACNA1C (12p13.33) and MRPL21 (11q13.2) as well as decrease of VIPR2 (7q36.3) and MAP3K7 (6q15) in ESCC by Real-time PCR, and also found that MRPL21 was significantly overexpressed and VIPR2 was underexpressed in ESCC. Gain of CACNA1C was significantly associated with differentiation (P = 0.043), and loss of VIPR2 was significantly linked with good prognosis (P = 0.016). Most importantly, we revealed that loss of MAP3K7 was significantly correlated with good prognosis in ESCC patients (n = 159, P = 0.004), especially in Grade II and pN0 patients (n = 76, P = 0.005 and n = 74, P = 0.024). Multivariate analysis confirmed that MAP3K7 loss provided prognostic information in ESCC (HR, 0.454; 95% CI: 0.208-0.995; P = 0.048). CONCLUSIONS Loss of MAP3K7 may be a candidate prognostic factor in ESCC.
Mutations in Mre11 Phosphoesterase Motif I That Impair Saccharomyces cerevisiae Mre11-Rad50-Xrs2 Complex Stability in Addition to Nuclease Activity

The Mre11-Rad50-Xrs2 complex is involved in DNA double-strand break repair, telomere maintenance, and the intra-S phase checkpoint. The Mre11 subunit has nuclease activity in vitro, but the role of the nuclease in DNA repair and telomere maintenance remains controversial. We generated six mre11 alleles with substitutions of conserved residues within the Mre11-phosphoesterase motifs and compared the phenotypes conferred, as well as exonuclease activity and complex formation, by the mutant proteins. Substitutions of Asp16 conferred the most severe DNA repair and telomere length defects. Interactions between Mre11-D16A or Mre11-D16N and Rad50 or Xrs2 were severely compromised, whereas the mre11 alleles with greater DNA repair proficiency also exhibited stable complex formation. At all of the targeted residues, alanine substitution resulted in a more severe defect in DNA repair compared to the more conservative asparagine substitutions, but all of the mutant proteins exhibited <2% of the exonuclease activity observed for wild-type Mre11. Our results show that the structural integrity of the Mre11-Rad50-Xrs2 complex is more important than the catalytic activity of the Mre11 nuclease for the overall functions of the complex in vegetative cells.
The impact of smoking on marginal bone loss in a 10‐year prospective longitudinal study

OBJECTIVES The aim of this epidemiologic study was to determine the impact of smoking on marginal bone loss in a subsample derived from an original randomly selected adult sample, after adjusting for oral and general factors. METHODS The number of participants at baseline in this 10-year longitudinal study was 616 (mean age: 42 years, range 21-63 years). The participants underwent a full-mouth radiographic survey. After recall in 2003, 473 (77%) of the participants accepted and completed an identical survey. In 2008, the survey was repeated, and 301 (48.9%) individuals were included in this study. The marginal bone level of each tooth was measured in mm. Age, gender, smoking habits, number of teeth, apical periodontitis, crowns and initial marginal bone level were also recorded for each individual. Only individuals who did not report a change in smoking habits during the 10-year period were included in the study. Multiple regression analyses were used to evaluate crude and adjusted associations between smoking and marginal bone loss. RESULTS At the first, radiographic survey smokers had a statistically significantly more reduced marginal bone level (in average 0.9 mm) than nonsmokers. After 10 years, a progression of a mean marginal bone loss of > 2 mm was statistically significantly more common in smokers than in nonsmokers (7.1% and 0%, respectively). Furthermore, a marginal bone loss of 1-2 mm was observed in 29% of the smokers and 19% of the nonsmokers, and ≤ 1 mm marginal bone loss was found in 69% of smokers and 81% of nonsmokers. Even after adjusting for initial marginal bone level, gender, age, and also presence of apical periodontitis and crowns, the difference in progression of marginal bone loss was still statistically higher in smokers (on average 0.36 mm). CONCLUSIONS The smokers started out with a more reduced marginal bone level than nonsmokers. However, even after adjusting for the initial marginal bone level, the progression of marginal bone loss in smokers was more pronounced than in nonsmokers. This shows that smoking is a factor with significant impact on the marginal bone level and can be assumed to be a true risk factor for marginal bone loss.
Inference‐In‐Residuals as an Estimation Method for Earnings Management

The paper tests the assumptions underlying the inference‐in‐residuals method as an estimation framework for detecting and classifying suspects of earnings management. We derive several systematic biases that are shown to confound inference‐in‐residuals and, depending on the data, could render the method a futile exercise. This is not a matter of model specification, but a limitation of the statistical method. Also, it is shown that the method of using estimated residuals in a second stage regression on economic determinants of earnings management suffers considerably, especially when residuals are estimated by industry classification in the first stage. [ABSTRACT FROM AUTHOR]
Is investor sentiment a relevant factor in determining asset prices?

ABSTRACT The APT framework allows for a multitude of risk factors to be priced into asset returns, implying that it can be used to model returns using either macroeconomic or microeconomic factors. As such, the APT allows for non-traditional factors, such as investor sentiment, to be included. A macroeconomic APT framework was developed for nine countries using the variables outlined by Chen, Roll, and Ross (1986) and investor sentiment was measured by the FEARS index (Da, Engelberg, & Gao, 2015). Regression testing was used to determine whether FEARS is a statistically significant explanatory variable in the APT model for each country. The results show that investor sentiment is a statistically significant explanatory variable for market returns in five out of the nine countries examined. These results add to the existing APT literature as they show that investor sentiment has a significant explanatory role in explaining asset prices and their associated returns.
Advanced access appointments: Effects on family physician satisfaction, physicians' office income, and emergency department use.

OBJECTIVE To examine the effects of advanced access (same-day physician appointments) on patient and provider satisfaction and to determine its association with other variables such as physician income and patient emergency department use. DESIGN Patient satisfaction survey and semistructured interviews with physicians and support staff; analysis of physician medical insurance billings and patient emergency department visits. SETTING Cape Breton, NS. PARTICIPANTS Patients, physicians, and support staff of 3 comparable family physician practices that had not implemented advanced access and an established advanced access practice. MAIN OUTCOME MEASURES Self-reported provider and patient satisfaction, physician office income, and patients' emergency department use. RESULTS The key benefits of implementation of advanced access were an increase in provider and patient satisfaction levels, same or greater physician office income, and fewer less urgent (triage level 4) and nonurgent (triage level 5) emergency department visits by patients. CONCLUSION Currently within the Central Cape Breton Region, 33% of patients wait 4 or more days for urgent appointments. Findings from this study can be used to enhance primary care physician practice redesign. This research supports many benefits of transitioning to an advanced access model of patient booking.