Miracle-dz/UniFAR-FTUs huggingface dataset:
Proliferation of Epidermal Growth Factor-stimulated Hepatocytes in a Hormonally Defined Serum-free Medium

The present study shows that adult rat hepatocytes in primary culture, which normally exhibit a restricted capacity to proliferate, can proceed through the cell cycle when cultured in a mixture of minimal essential medium (MEM) and Medium 199 (MEM–M199; 3:1, v/v), containing epidermal growth factor (EGF; 50ng/ml), low glucose (0.75g/l) and low levels of inorganic salts, amino acids and vitamins. Under these conditions, hepatocytes flatten and cell extensions appear. In contrast, Dulbecco's modified Eagle's medium (DMEM) containing high glucose (4.5g/l) levels enriched with inorganic salts, amino acids and vitamins favours maintenance of differentiated functional hepatocyte capacities (albumin secretion), but does not allow proliferation or cell spreading. Cultivation of hepatocytes in MEM–M199 (3:1, v/v) results in the onset of DNA synthesis at 48 hours of culture and a concomitant induction of cyclin D1 protein. Under these conditions, cells successively progress through the mitogen-dependent restriction point in mid-late G1 phase, G1/S transition and S phase, as evidenced by Western blot analysis of the markers cyclins E and A and cyclin dependent kinase (CDK)2 and CDK1, respectively. Progression through the cell cycle is accompanied by a decrease in albumin secretion, indicating a decline in differentiated capacities. This study demonstrates that hepatocytes cultured in a mixture of MEM–M199 (3:1) provide a useful in vitro model for studying the regulation of hepatocyte proliferation.
Elevation of serum c‐reactive protein in patients with OAB and IC/BPS implies chronic inflammation in the urinary bladder

Chronic inflammation has been implicated in the development of overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). An elevation of C‐reactive protein (CRP) has been associated with chronic inflammation and lower urinary tract symptoms. This study aims to elucidate the association between CRP and OAB or IC/BPS.
Penicillin-insensitive incorporation of D-amino acids into cell wall peptidoglycan influences the amount of bound lipoprotein in Escherichia coli

Certain D-amino acids, such as D-methionine and D-cystine, were incorporated into cells of Escherichia coli under conditions inhibiting protein and cell wall synthesis. Part of the radioactivity of D-14C-amino acids incorporated into the cells was found in the isolated cell wall peptidoglycan. A covalent linkage between the amino group of the D-amino acids and the peptidoglycan was presumed to be the main cause of the binding of the D-amino acids to peptidoglycan, because the amino group of the D-amino acids in the incorporation product was substituted. Whether the carboxyl terminus was substituted was unknown. The formation of the D-amino acid-peptidoglycan linkage was insensitive to beta-lactam antibiotics such as benzylpenicillin and ampicillin (500 micrograms/ml) and therefore was not due to the reaction of DD-transpeptidation which is involved in the biosynthesis of peptidoglycan. The D-amino acids also strongly inhibited the formation of peptidoglycan-bound lipoprotein in the E. coli cells. The results may suggest the correlation between binding of D-amino acid to peptidoglycan and inhibition of formation of the bound form of lipoprotein.
Preclinical Safety Pharmacological Studies on the Amorphous Formulation of Celecoxib

Abstract Safety pharmacological studies need to be performed according to ICH S7A Guidelines for finished formulations that substantially alter the pharmacokinetics and/or pharmacodynamics of the active substance in comparison to formulations previously tested (i. e. through active excipients such as penetration enhancers, liposomes, and other changes such as polymorphous system). In the present study, amorphous formulation of celecoxib (CAS 169590-42-5), a new patented formulation with altered pharmacokinetic profile was investigated in comparison with the standard crystalline celecoxib (CEL) for its undesirable pharmacodynamic effects using certain safety pharmacological studies. The effects of the new formulation on vital functions using safety pharmacology core battery like central nervous system (CNS) (functional observation battery, locomotor activity, and motor coordination) and cardiovascular system (CVS) (blood pressure, heart rate and QT interval) were investigated in laboratory rodents. In addition, supplementary safety pharmacology study on gastrointestinal system (GIT) (gastric injury potential, gastric secretion) was also carried out. Oral administration of a single dose of the amorphous celecoxib formulation (CF) varying of 50, 150 and 500 mg/kg was studied in comparison with vehicle treated control and crystalline celecoxib in animals. The maximum tolerated dose (MTD) was identified by administration of insufferable doses of amorphous formulation, extended up to 2 000 mg/kg during the experiments on physiological parameters. There were no CNS and GIT safety concerns raised with respect to use of CF except the arrythmogenic risk associated with QT interval prolongation upon the high dose of CF.
Dysfunction of subtelomeric methylation and telomere length in gallstone disease and gallbladder cancer patients of North Central India

Telomeres play an important role in cancer progression. Recently it has been shown that subtelomeric methylation negatively regulates telomere length in various diseases, including cancers. Here, we evaluated the influence of subtelomeric methylation in telomere dysfunction in gallbladder cancer (GBC), and whether this dysfunction is affected by the presence of gallstones.
Genital human papillomavirus infection among women recruited for routine cervical cancer screening or for colposcopy determined by Hybrid Capture II and polymerase chain reaction.

The purpose of this study was to evaluate the clinical use of the Hybrid Capture (HC)-II system for the detection of human papillomavirus (HPV) DNA to identify women at risk of progression to high grade squamous intraepithelial lesions (HGSIL) and carcinomas by differentiating low risk (LR) HPV types (6, 11, 42, 43, 44) and high/intermediate risk (HR) HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68). Five hundred and ninety-six women were enrolled in the study. Among them, 466 attended the hospital for routine cytologic screening and 130 were referred for colposcopy because of an abnormal Pap smear. The presence of HPV DNA was tested in cervical samples collected with the Digene Cervical Sampler in Digene Specimen Transport Medium (Digene Corporation, Silver Spring, MD, U.S.A.) using the HC-II assay. Results were compared with those obtained by polymerase chain reaction (PCR) using the MY09-MY11 primers followed by several hybridizations with specific probes. The overall HPV positivity was 32.9% by HC-II and 37.8% by PCR. Among cytologically normal smears, 19.5% were positive by HC-II (14.3% HR) and 25.1% by PCR. Of the atypical squamous cells of undetermined significance samples, 52.9% were positive by HC-II (41.1% HR) and 55.9% by PCR. Of the low grade SIL, 64.5% were positive by HC-II (59.4% HR) and 68.7% by PCR. The HPV positivity rate was found identical by both techniques in high grade smears (81.6%) and squamous cervical carcinomas (100%). By using PCR as the reference method, the sensitivity of HC-II was higher among women with abnormal cytology than with normal cytology (87.3% vs. 70%). Specificity was 80.8% and 97.5%, respectively. In summary, these results indicate that the HC-II method and MY-PCR identified nearly equivalent prevalences of HPV in cervical smear specimens.
Banking Stability Determinants in Africa

Purpose The purpose of this paper is to investigate the determinants of banking stability in Africa. Design/methodology/approach The authors present four measures of banking stability embedding banks’ loan loss coverage ratio, insolvency risk, asset quality ratio, and level of financial development, thereby allowing analysis of banking stability determinants from four complementary perspectives: protection for downside credit losses, distress arising from insolvency risk, non-performing loans, and financial development. The authors use the regression methodology to estimate the impact of financial structure, institutional, bank-level factors on bank stability. Findings The findings indicate that banking efficiency, foreign bank presence, banking concentration, size of banking sector, government effectiveness, political stability, regulatory quality, investor protection, corruption control and unemployment levels are significant determinant of banking stability in Africa and the significance of each determinant depends on the banking stability proxy employed and depends on the period of analysis: pre-crisis, during-crisis or post-crisis. Practical implications Banking supervisors in African countries should consider the role of financial structure and institutional quality for banking stability in the African region. Originality/value This study is the first to examine banking stability determinants in Africa that takes into account institutional quality and financial structure.
Impact of older age on the efficacy of newer adjuvant therapies in >12,500 patients (pts) with stage II/III colon cancer: Findings from the ACCENT Database.

4010 Background: Prior studies suggested that older and younger pts with colon cancer receive similar benefit from IV fluoropyrimidine (FU) adjuvant (adj) therapy (rx). Combination and/or oral FU rx are increasingly given as adj rx. We sought to determine the impact of pts age <70 v ≥70 yrs on colon cancer recurrence and mortality from adj rx with these newer options. METHODS We used data from 10,499 pts <70 yrs and 2,170 pts ≥70 yrs in 6 phase III adj rx trials comparing IV FU to combinations with irinotecan, oxaliplatin or oral FU (capecitabine and UFT/LV) in stage II/III colon cancer from the ACCENT database. Endpoints were overall survival (OS; time to death), disease-free survival (DFS; time to recurrence or death), and time to recurrence (TTR; censoring at last follow-up). Cox models were stratified by age and adjusted for gender and stage; interaction testing was used to explore the differential benefit by age. RESULTS Approximately 75% of pts had stage III disease (74% age<70, 77% age≥70). OS, DFS, and TTR were statistically significantly improved for those in the experimental v control arms among pts <70 but not those >70 ( table ); the interaction between age and rx was statistically significant for all endpoints (p=0.01 for OS, DFS, and TTR). These results were consistent whether experimental rx was oxaliplatin-based, irinotecan-based or oral FU. Deaths in first 6 month of adj rx were not statistically significantly different between experimental and control arm. CONCLUSIONS Our results show conclusively that pts >70 do not receive the same benefit from combination and/or oral FU as those <70. Any benefit, if present, compared to IV FU/LV would not be clinically meaningful. Outcomes of experimental (combination or oral FU) vs control (IV 5-FU) by treatment and age [Table: see text] [Table: see text].
Phase I/II trial of paclitaxel by 1‐hour infusion, carboplatin, and gemcitabine in the treatment of patients with advanced nonsmall cell lung carcinoma

The combination of paclitaxel and carboplatin is widely used in the treatment of patients with advanced nonsmall cell lung carcinoma. In this Phase I/II study the authors evaluated the feasibility, toxicity, and efficacy of adding a third active antineoplastic agent, gemcitabine, to the paclitaxel/carboplatin combination for the treatment of patients with advanced nonsmall cell lung carcinoma.
A dose-response study of levosimendan in a porcine model of acute ischaemic heart failure.

OBJECTIVES Levosimendan is a novel inotropic agent claimed to improve myocardial contractility by a calcium-sensitizing effect. Our aim was to evaluate dose-dependent effects of levosimendan on left ventricular (LV) contractility and energetic properties in an acute, ischaemic heart failure porcine model. METHODS Six pigs were used in an anaesthetized in vivo open-chest model. The time points of measurements were: baseline, after heart failure induction and after dose 1-4 (D1-D4). Heart failure was induced by microembolization of the left coronary artery before infusion of four different doses (D1: 2.5 µg/kg, D2: 10 µg/kg, D3: 40 µg/kg, D4: 80 µg/kg) of levosimendan. Haemodynamics were assessed by the pressure-conductance catheter technique. LV oxygen consumption was calculated from coronary flow measurements and coronary sinus blood gases. Mitochondrial respiration was studied in biopsies of the LV. RESULTS Levosimendan had no significant, load-independent effect on contractile force (slope of preload recruitable stroke work was 34 mmHg immediately following failure and 39 (P = 0.406), 42 (P = 0.219), 46 (P = 0.067) and 41 (P = 0.267) at D1-D4), although the more load-dependent contractility indicator of dP/dt(max) was slightly increased at dose 4 (P < 0.05). LV energy conversion efficiency (PVA-MVO2 relationship) remained unaltered at all doses. Maximal mitochondrial respiration decreased after induction of failure and remained at an unaltered low level during levosimendan infusion. CONCLUSIONS Surprisingly, levosimendan had no significant effect on contractility, energy efficiency and mitochondrial respiration of the LV, in a porcine model of acute heart failure. At high doses, levosimendan induced vasodilatation and increased heart rate and cardiac output.
Supplemental plan offerings and retirement saving choices: an analysis of North Carolina school districts* ‡

Abstract Unlike private sector employers, public school districts generally offer more than one type of supplemental retirement savings plan and allow multiple vendors to offer products. Using individual-level payroll data from over half of the public school districts in North Carolina coupled with data from an employer survey, this study examines how inter-district differences in supplemental plan administration are related to participation in these savings vehicles. We find wide variation in total participation rates and in 403(b) plan participation rates in particular, even among this population of public-sector workers with the same defined benefit pension plan, health plan, and retiree health coverage. Individual and district characteristics explain some, but not all, of the variation observed.
A Novel Method of Labeling and Characterizing Migrating Neurons in the Developing Central Nervous System

Neuronal migration, a discrete event in the developing nervous system, is currently being intensively investigated using a variety of anatomical and molecular approaches. Using 4-chloromethyl benzoyl amino tetramethyl rhodamine (CMTMR) coated particles, we describe here a novel and efficient method of tracer labeling to investigate cell migration in embryonic and postnatal brain. Further, we demonstrate that application of CMTMR facilitates the labeling of a large number of migrating cells and enables the characterization of their phenotypes with immunohistochemical and in situ hybridization techniques. We also illustrate that CMTMR labeling is ideally suited for time-lapse imaging of the behavior and dynamics of migrating cells.
highlighted topics Physiological and Genomic Consequencesof Intermittent Hypoxia Selected Contribution: Pulmonary hypertension in mice following intermittent hypoxia

Pulmonary hypertension in mice following intermittent hypoxia. J Appl Physiol 90: 2502–2507, 2001. — Sleep apnea (intermittent periods of hypoxia with or without hypercapnia) is associated with systemic hypertension and increased mortality from cardiovascular disease, but the relationship to pulmonary hypertension is uncertain. Previous studies on intermittent hypoxia (IH) in rats that demonstrated pulmonary hypertension utilized relatively long periods of hypoxia. Recent studies that utilized brief periods of hypoxia have conﬂicting reports of right ventricular (RV) hypertrophy. In addition, many studies have not measured pulmonary hemodynamics to asses the severity of pulmonary hypertension in vivo. Given the increasing availability of genetically engineered mice and the need to establish a rodent model of IH-induced pulmonary hypertension, we studied the effect of IH (2-min cycles of 10% and 21% O 2 , 8 h/day, 4 wk) on wild-type mice, correlating in vivo measurements of pulmonary hypertension with RV mass and pulmonary vascular remodeling. RV systolic pressure was increased after IH (36 6 0.9 mmHg) compared with normoxia (29.5 6 0.6) but was lower than continuous hypoxia (44.2 6 3.4). RV mass [RV-to-(left ventricle plus septum) ratio] correlated with pressure measurements (IH 5 0.27 6 0.02, normoxia 5 0.22 6 0.01, and continuous hypoxia 5 0.34 6 0.01). Hematocrits were also elevated after IH and continuous hypoxia (56 6 1.6 and 54 6 1.1 vs. 44.3 6 0.5%). Evidence of neomuscularization of the distal pulmonary circulation was found after IH and continuous hypoxia. We conclude that mice develop pulmonary hypertension following IH, representing a possible animal model of pulmonary hypertension in response to the repetitive hypoxia-reoxygenation of sleep apnea.
Clinical presentations of 23 half‐siblings from a mosaic neurofibromatosis type 1 sperm donor

The Danish sperm donor number 7042 has fathered several offspring with neurofibromatosis type 1 (NF1) worldwide. NF1 is caused by loss‐of‐function mutations in the NF1 gene and more than 1000 NF1 mutations are identified. Analysis of the donor sperm demonstrated gonosomal mosaicism with an intragenic deletion involving exons 15–29 in the NF1 gene. At the two Danish reference centres for NF1 patients, we evaluated 23 half‐siblings from the donor. Nine were diagnosed with NF1. The severity grade of NF1 progressed from minimal to mild/moderate within 3 years of follow‐up. The NF1 phenotype shows great variability in intra‐ and inter‐family expressivity and to date only two NF1 genotype–phenotype correlations have been established. This rare possibility of a long‐term follow‐up of a cohort of half‐siblings with NF1 makes further studies including phenotypic variability and search for modifier genes possible. To achieve this goal, we have initiated The International Donor 7042 NF1 Offspring Registry. Research facilitated via this registry may reveal important new knowledge of clinical characteristics and prognostics for the specific NF1 genotype and thereby contribute to future individualised targeted clinical follow‐up and treatment.
[Life expectancy, strenuous work and pension system's fairness. First evidence from the Work Histories Italian Panel].

OBJECTIVE the study aims to estimate the differentials in life expectancy by income and work history in Italy during the 2000's, in order to evaluate the level of actuarial equity of the recent Italian retirement reform in computing benefits proportional to the contributions paid. DESIGN retrospective cohort study. SETTING AND PARTICIPANTS mortality follow up of a 1% sample of the Italian workforce employed or self employed in the private sector, retired between 1985 and 2003 (about 63,000 people), whose work history and income since 1985 is registered in the National Institute for Social Insurance (INPS) data base. MAIN OUTCOME MEASURE mortality differentials computed through Cox model. RESULTS social inequalities in survival in favour of the more advantaged categories of income and occupational classes are observed. CONCLUSION the principle of actuarial equity assumes that life expectancy varies only according to age and birth cohort; nevertheless inequalities in life expectancy exist also along other dimensions, like income and occupational class: this means that the system is producing an opposite redistribution, from the careers more socially disadvantaged to the less disadvantaged ones.
Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability.

CONTEXT Criteria for microsatellite instability (MSI) testing to rule out hereditary nonpolyposis colorectal cancer were recently revised and include parameters such as age and specific histologic features that can be identified by the pathologist, triggering reflex MSI testing. OBJECTIVE To review the performance of the revised Bethesda guidelines to identify MSI-positive colorectal cancers. DESIGN Seventy-five patients with colorectal cancer were included; 68 patients younger than 50 years and 7 patients between 50 and 60 years were selected based on histopathologic criteria. Microsatellite instability testing with the National Cancer Institute--recommended panel and immunohistochemistry for hMLH1 and hMSH2 were performed. Tumors were classified into microsatellite instability high (MSI-H), low (MSI-L), or stable (MSS) categories. RESULTS Overall, 17 (23%) of 75 colorectal cancer cases were classified as MSI-H, including 13 patients younger than 50 years and 4 patients between 50 and 60 years. Among the MSI-H tumors, 10 (59%) were characterized by loss of hMLH1 and 6 (35%) were hMSH2 negative. Histologic features suggestive of MSI-H phenotype were present in 80% of MSI-H and 35% of MSS/MSI-L tumors. The number of positive lymph nodes was higher in MSS/MSI-L adenocarcinomas (P = .04). CONCLUSIONS By selecting for age and histologic features, we detected MSI-H tumors in approximately one quarter of colorectal cancer cases meeting the revised Bethesda guidelines and identified 17 MSI-H cases, whereas only 8 would have been recognized by the prior guidelines. These data indicate that reflex testing requested by pathologists based on the revised Bethesda guidelines increases the detection of MSI-H and potential hereditary nonpolyposis colorectal cancer cases.
Effects of Carbohydrate Supplementation on Performance During 1 Hour of High-Intensity Exercise

The effects of carbohydrate supplementation on high-intensity exercise performance were examined in 5 moderately-trained subjects (age = 28.4 +/- 1.5 yr; ht = 171.0 +/- 4.3 cm; wt = 66.25 +/- 6.32 kg). High-intensity exercise tests (initiated at the power output (PO) associated with 90% VO2 peak [mean = 201 +/- 21 watts] x 60 min, with drop-off in PO allowed over time) were completed under the following randomized double blind conditions: 1) pre-exercise glucose polymer (G)/placebo during exercise (G/P), 2) G pre-exercise and during exercise (G/G), and 3) placebo pre-exercise and during exercise (P/P). Subjects ingested 300 ml of a sweetened placebo or a similarly flavored 10% G solution, immediately prior to and every 15 min during exercise. No differences were observed in PO among the 3 treatments until min 40-60 where PO was greater with G. This resulted in significantly greater total work (and less drop-off in PO) with G (G/P = 619 +/- 234kJ [14.5% lower than the value associated with 201 watts maintained for 60 min (724kJ)], G/G = 599 +/- 235 kJ [17.3% lower than the value associated with 201 watts maintained for 60 min]) compared with placebo (P/P = 560 +/- 198 kJ [22.7% drop-off in average PO]) (p < 0.05). VO2 followed a similar pattern with no difference in VO2 over min 0-40 and significantly higher VO2 in G/P and a trend for higher VO2 in G/G during min 40-60 compared to placebo. Results of the present study indicate that, compared to placebo, pre-exercise ingestion of G (30 g in 10% solution) results in less drop-off in PO during 1 hour of high-intensity exercise performance, and that no further benefit is observed when the same amount of G is also ingested every 15 min during exercise.