Miracle-dz/UniFAR-FTUs huggingface dataset:
Complications and treatment of patients with β-thalassemia in France: results of the National Registry

Background β-thalassemia is a rare disease in France, encountered mainly in patients originating from Italy and North Africa. In the setting of the recent French plan for rare diseases, a National Registry for thalassemia has been developed since 2005. Epidemiological and clinical data have been collected on living patients with β-thalassemia major or intermedia, including those who underwent hematopoietic stem cell transplantation. Design and Methods A standardized questionnaire was sent to clinicians throughout the national professional networks involved in the management of thalassemic patients and data were updated every 18 months. A cross-sectional study was performed in February 2009. Results Data on 378 patients (267 with thalassemia major) with a median age of 20 were recorded. Hematopoietic stem cell transplantation was performed in 52 patients. Stature, rates of parenthood, splenectomy, and cholecystectomy were no different between non-transplanted thalassemia major and thalassemia intermedia patients, after adjustment for age. Among the 215 non-transplanted thalassemia major patients, the median serum ferritin level was 1240 ng/mL and the rates of iron-related complications were 10%, 6%, 10% and 48% for cardiac failure, diabetes, hypothyroidism, and hypogonadism, respectively. From 2005 to 2008, a dramatic switch in chelation treatment, from deferoxamine to deferasirox, was observed. Conclusions The rates of complications of iron overload in French thalassemia major patients appeared similar to those reported in other developed countries in which this condition is not endemic. There were no significant differences in height and parenthood rates between patients with the major and the intermedia forms of the disease, underlining the progress in clinical care. Future developments will focus on mortality and morbidity under oral chelation treatment.
A single short stretch of homology between adenoviral vector and packaging cell line can give rise to cytopathic effect-inducing, helper-dependent E1-positive particles.

An undesirable byproduct from recombinant adenoviral vectors is the emergence of replication competent adenovirus (RCA) that result from rare homologous recombination events between the viral E1-containing (permissive) mammalian host cell genome and the virus itself, restoring the E1 gene to the viral genome. To reduce or eliminate the problem of RCA, we evaluated production of a first generation Ad5 vector (Ad5FGF4) in the cell line PER.C6. This E1-transformed human cell line contains only Ad5 nucleotides 459-3510, which precludes double crossover-type homologous recombination because the Ad5FGF-4 only contains 5' Ad5 sequence up to nucleotide 453. The Ad5FGF4 vector does, however, retain 177 nucleotides of the 3' end of the E1B-55K gene that are also present in PER.C6. With only this single region of homology between vector and cell line, we were surprised to detect virus-specific cytopathic effects (CPE) in our cell-based assay for RCA. This CPE-inducing agent was amplified in nonpermissive A549 cells but also supported amplification of the parental Ad5FGF-4. Because we were unable to isolate the CPE-inducing agent in pure form we first identified it as atypical RCA. Polymerase chain reaction (PCR) and Southern blot experiments identified viral DNA segments in which recombination had occurred between the 177 nucleotides of E1B present in both Ad5FGF-4 and PER.C6. The atypical RCA genomes contain a copy of the original (PGK promoter-E1 gene carrying) plasmid used in the construction of the PER.C6 cell line and they retained the parental FGF-4 transgene. However, significant deletions occurred within the recombined genomes in compensation for the large insertion from PER.C6 sequences and resulted in the loss of essential viral genes. This deletion renders these recombinant viruses replication defective, requiring helper functions from remaining parental Ad5FGF-4 for amplification. These atypical RCA entities may be more properly designated as helper-dependent E1-positive particles (HDEPs). This finding shows the importance of avoiding the use of "nonmatched" vectors where any overlap exists between the recombinant vector and E1 sequences in the packaging cell line. The cloning of the FGF-4 transgene into an adenoviral vector specifically "matched" for PER.C6 (lacking the 177 nucleotide region of homology) has allowed extensive virus propagation (Ad5.1FGF-4) with no CPE- or HDEP-like events yet detected.
Comparison of Push-Prone and Lateral-Bending Radiographs for Predicting Postoperative Coronal Alignment in Thoracolumbar and Lumbar Scoliotic Curves

Study Design. A comparative evaluation of supine right and left lateral-bending radiographs and push-prone radiographs in patients with thoracolumbar and lumbar scoliosis to determine postoperative correction of the curve. Objectives. To determine the difference in the ability of the push-prone radiograph and the supine lateral-bending radiograph to predict postoperative coronal alignment for primary thoracolumbar and lumbar curves managed with an anterior spinal instrumentation and fusion. Summary of Background Data. Right and left supine side-bending radiographs are the standard means of evaluating curve flexibility before surgery in idiopathic scoliosis. A push-prone radiograph also has been obtained at the authors’ institution as a single dynamic radiographic assessment of forced correction of the primary curve and resultant effects on compensatory curves above and below the fusion. Methods. Preoperative standing, supine right and left lateral-bending, and push-prone radiographs were performed in 40 patients who underwent anterior spinal instrumentation and fusion. Postoperative standing radiographs of the spine were obtained at 3 months after surgery. Measurements on all the radiographs included the coronal Cobb angle, the angle of the lowest instrumented vertebra to the horizontal, the rotation of the lowest instrumented vertebra, and the distance of the midpoint of the lowest instrumented vertebra from the center sacral line. Results. The lateral-bending and the push-prone radiographs predicted less correction of the Cobb angle and the angle of the lowest instrumented vertebra to the horizontal than was achieved after surgery. However, the push-prone radiograph was superior to the lateral-bending radiograph in accurately predicting the postoperative correction of the rotation of the lowest instrumented vertebra as well as the translation of the lowest instrumented vertebra from the center sacral line. Conclusions. The push-prone and lateral-bending radiographs are similar in predicting less correction of the Cobb angle after anterior spinal surgery. The push-prone radiograph helps in determining the effects that correction of the primary curve has on the curves above and below the level of fusion by better predicting the translational correction of the lowest instrumented vertebra and the rotation of the lowest instrumented vertebra.
Nonprice competition and quality of care in managed care: the New York SCHIP market.

OBJECTIVE To examine the effect of nonprice competition among managed care plans on the quality of care in the New York SCHIP market. DATA SOURCES U.S. Census 2000; 2002 New York State Managed Care Plan Performance Report; and 2001 New York State Managed Care Annual Enrollment Report. STUDY DESIGN Each market is defined as a county, and competition is measured as the number of plans in a market. Quality of care is measured in percentages using three Consumer Assessment of Health Plans Survey and three Health Plan Employer Data and Information Set scores. Two-stage least squares is applied to address the endogeneity between competition and the quality of care, using population as an instrument. PRINCIPAL FINDINGS We find a negative association between competition and quality of care. An additional managed care plan is significantly associated with a decrease of 0.40-2.31 percentage points in four out of six quality measures. After adjusting for production cost, a positive correlation is observed between price and quality measures across different pricing regions. CONCLUSIONS It seems likely that pricing policy is a constraint on quality production, although it may not be interpreted as a causal relationship and further study is needed.
In-Patient Treatment of Chronic Varicose Venous Ulcers. A Randomized Trial of Cadexomer Iodine versus Standard Dressings

A total of 67 patients with treatment resistant chronic venous ulcers were admitted to hospital for 6 weeks of bed rest and daily dressings. The patients came from a rural area in Poland with poor socio-economic conditions. They were randomized to treatment with either standard dressings or with cadexomer iodine. After 6 weeks all but four patients had shown a clear reduction of ulcer area; the mean reduction was 54% within the former group and 71% with cadexomer iodine. The latter treatment was significantly more effective than the standard hospital dressings in debriding the ulcer, accelerating healing and reducing pain. Elevation of serum concentrations of protein-bound iodine occurred after treatment with cadexomer iodine in patients with large ulcers, but tests of thyroid function showed no changes associated with the use of cadexomer iodine. It is concluded that cadexomer iodine significantly accelerates the healing of chronic, infected, treatment-resistant, venous ulcers in hospitalized patients.
Russian academic emigrants : academic lives disrupted and reconnected

The thesis takes as its starting point the idea of academic mobility, which is present in many policy texts and in discussions of the globalisation of higher education, and subjects that idea to critical scrutiny in the light of the lived experience of academics who have chosen to leave their homelands. In exploring the mobility issue, the particular concepts enable the illumination of academic work and life as disrupted and discontinuous. Discontinuity is related to such concepts as identity and exile, and I use a number of anthropological approaches to reassess the concept of academic career as a life journey that shapes identity through processes that may disrupt as well as advance careers and that corrode as well as affirm identities. The thesis uses biographical methods to explore and understand the experiences of Russian academics working in the UK and the USA, who may be understood as living to some extent in conditions of exile. These academics left Soviet or early post-Soviet Russia for Universities in the West, and constitute representatives of the international academic diaspora. This example serves to complicate the idea of academic mobility as a straightforward issue in which a global academic market produces opportunities for the free movement of talented labour, and to raise some critical issues about the extent to which this decontextualised vision of academic work is possible. The thesis also attempts to show the enduring effects of early career socialisation on later experiences, and to connect the specific context of Russia and Russian academic traditions to the shaping of the academy in globalising conditions. Finally, the thesis attempts, through this study of particular individuals, to add a degree of complexity and human experience to the literature on the globalisation of the academy, which often discusses developments at a very high level of abstraction, that is not sufficiently attentive to difference.
Controversy in the link between vitamin D supplementation and hypertension

Vitamin D affects a range of pathophysiological processes pertinent to the control of blood pressure, including endothelial function, inflammation and renin–angiotensin system activity. Observational data show a clear relationship between 25-hydroxyvitamin D levels and both current blood pressure and incident hypertension. However, recent trial data have shown no significant effect of vitamin D supplementation on blood pressure, even at high doses, low vitamin D levels and in patients with high baseline blood pressure. Vitamin D might still benefit cardiovascular health through mechanisms other than blood pressure reduction, but data from large trials are required to show this. In the meantime, vitamin D has no place in controlling blood pressure either at the individual or the population level.
How to practise Open Innovation today: what, where, how and why

ABSTRACT Open Innovation (OI), a paradigm coined by Chesbrough in 2003, is not only ‘openness towards innovation’, it also represents a firm-view-point-based innovation strategy, which suggests the involvement of external actors in the innovation process. The present paper is part of an on-going discussion on open issues related to OI and the advantages, strengths, challenges and limits of its implementation, dealing with the frequently debated topic of the future of this paradigm. What has emerged from this study is that a clear one-way outline of the OI implementation process does not exist, either in the literature or in practical cases, but common catalyst points, such as a general ‘open’ attitude, the existence of a technology transfer approach, an Intellectual Property protection strategy, and the frequent use of search routines, are identifiable. However, the future of this paradigm is not clear, as the concept may fade away because the process could be fully integrated in the innovation process.
Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl‐CoA dehydrogenation deficiency

Mutations in electron transfer flavoprotein (ETF) and its dehydrogenase (ETFDH) are the molecular basis of multiple acyl‐CoA dehydrogenation deficiency (MADD), an autosomal recessively inherited and clinically heterogeneous disease that has been divided into three clinical forms: a neonatal‐onset form with congenital anomalies (type I), a neonatal‐onset form without congenital anomalies (type II), and a late‐onset form (type III). To examine whether these different clinical forms could be explained by different ETF/ETFDH mutations that result in different levels of residual ETF/ETFDH enzyme activity, we have investigated the molecular genetic basis for disease development in nine patients representing the phenotypic spectrum of MADD. We report the genomic structures of the ETFA, ETFB, and ETFDH genes and the identification and characterization of seven novel and three previously reported disease‐causing mutations. Our molecular genetic investigations of these nine patients are consistent with three clinical forms of MADD showing a clear relationship between the nature of the mutations and the severity of disease. Interestingly, our data suggest that homozygosity for two null mutations causes fetal development of congenital anomalies resulting in a type I disease phenotype. Even minute amounts of residual ETF/ETFDH activity seem to be sufficient to prevent embryonic development of congenital anomalies giving rise to type II disease. Overexpression studies of an ETFB‐D128N missense mutation identified in a patient with type III disease showed that the residual activity of the mutant enzyme could be rescued up to 59% of that of wild‐type activity when ETFB‐D128N‐transformed E. coli cells were grown at low temperature. This indicates that the effect of the ETF/ETFDH genotype in patients with milder forms of MADD, in whom residual enzyme activity allows modulation of the enzymatic phenotype, may be influenced by environmental factors like cellular temperature. Hum Mutat 22:12–23, 2003. © 2003 Wiley‐Liss, Inc.
Inhibition of Neurosphere Formation in Neural Stem/Progenitor Cells by Acrylamide

Previous studies showed that transplantation of cultured neural stem/progenitor cells (NSPCs) could improve functional recovery for various neurological diseases. This study aims to develop a stem cell-based model for predictive toxicology of development in the neurological system after acrylamide exposure. Treatment of mouse (KT98/F1B-GFP) and human (U-1240 MG/F1B-GFP) NSPCs with 0.5 mM acrylamide resulted in the inhibition of neurosphere formation (definition of self-renewal ability in NSPCs), but not inhibition of cell proliferation. Apoptosis and differentiation of KT98 (a precursor of KT98/F1B-GFP) and KT98/F1B-GFP are not observed in acrylamide-treated neurospheres. Analysis of secondary neurosphere formation and differentiation of neurons and glia illustrated that acrylamide-treated KT98 and KT98/F1B-GFP neurospheres retain the NSPC properties, such as self-renewal and differentiation capacity. Correlation of acrylamide-inhibited neurosphere formation with cell-cell adhesion was observed in mouse NSPCs by live cell image analysis and the presence of acrylamide. Protein expression levels of cell adhesion molecules [neural cell adhesion molecule (NCAM) and N-cadherin] and extracellular signal-regulated kinases (ERK) in acrylamide-treated KT98/F1B-GFP and U-1240 MG/F1B-GFP neurospheres demonstrated that NCAM decreased and phospho-ERK (pERK) increased, whereas expression of N-cadherin remained unchanged. Analysis of AKT (protein kinase B, PKB)/β-catenin pathway showed decrease in phospho-AKT (p-AKT) and cyclin D1 expression in acrylamide-treated neurospheres of KT98/F1B-GFP. Furthermore, PD98059, an ERK phosphorylation inhibitor, attenuated acrylamide-induced ERK phosphorylation, indicating that pERK contributed to the cell proliferation, but not in neurosphere formation in mouse NSPCs. Coimmunoprecipitation results of KT98/F1B-GFP cell lysates showed that the complex of NCAM and fibroblast growth factor receptor 1 (FGFR1) is present in the neurosphere, and the amount of this complex decreases after acrylamide treatment. Our results reveal that acrylamide inhibits neurosphere formation through the disruption of the neurosphere architecture in NSPCs. The downregulation of cell-cell adhesion resulted from decreasing the levels of NCAM as well as the formation of NCAM/ FGFR complex.
Epigenetic inactivation of the SFRP genes is associated with drinking, smoking and HPV in head and neck squamous cell carcinoma

The soluble frizzled receptor protein (SFRP) family encodes antagonists of the WNT pathway, and silencing of these genes, through promoter hypermethylation, leads to constitutive WNT signaling. In bladder cancers, hypermethylation of the SFRP genes occurs more often in current and former smokers and is a strong predictor of poor patient survival. Hence, we examined methylation of these genes in another tobacco‐related epithelial cancer, head and neck squamous cell carcinoma (HNSCC), to determine if the pattern of tobacco exposure again predicts the epigenetic alteration of these genes. Using methylation‐specific PCR, the prevalence of methylation of SFRP1, SFRP2, SFRP4 and SFRP5 was 35, 32, 35 and 29%, respectively among 350 HNSCC cases. Promoter methylation of SFRP1 occurred more often in both heavy (OR 3.5, 95% CI 0.9–13.7) and light drinkers (OR 3.7, 95% CI 1.0–14.3) compared to nondrinkers. SFRP4 promoter methylation, on the other hand, occurred at a higher prevalence in never smokers and former smokers than in current smokers, and also was independently associated with HPV16 viral DNA. A joint effects model of SFRP4 promoter methylation demonstrated that smoking status and HPV virus significantly interacted (p < 0.04) such that never smokers with HPV16 had an OR of SFRP4 methylation of 9.0 (95% CI 2.1–38.6). These results suggest that epigenetic alterations of the SFRP genes are highly prevalent in HNSCC, and that the clonal selection for these alterations is complex and may be related to the carcinogenic exposures that are known risk factors for this disease. © 2006 Wiley‐Liss, Inc.
Lessons from bankruptcy of Hanjin Shipping Company in chartering

ABSTRACT This paper aims to analyze the charter contract management of major container shipping companies in response to fluctuations in shipping market conditions in terms of contract duration using data of containerships between 2010 and 2016. Duration analysis was conducted to examine the relationship between charter duration and shipping market conditions. Moreover, this paper explores the causes of Hanjin Shipping Company’s bankruptcy, drawing managerial implications. Test results from Cox PH (Proportional Hazard) model show that most container shipping companies in Europe having net earnings purchased large vessels instead of chartering vessels, while some ocean carriers featuring poor financial performance, in particular the Hanjin Shipping Company, chartered bigger ships with higher charter rates and longer duration. Contract charter rates and duration of Hanjin Shipping Company featured greater risk compared to competitors.
Chlamydia trachomatis genotypes: correlation with clinical manifestations of infection and patients' characteristics.

In 1994 Chlamydia trachomatis specimens from 175 men and 135 women attending a clinic for treatment of sexually transmitted disease were genotyped by polymerase chain reaction-based restriction fragment length polymorphism of the omp1 gene. Information about the patients was collected at their initial visit. The associations between C. trachomatis genotype and patients' self-reported symptoms, clinical signs, and characteristics were studied. Genotypes E, F, and D/D-predominated (men: 71%; women: 60%). Five specimens (1.6%) showed evidence of mixed infections. Among men, complaints of urethral discharge and dysuria were most commonly associated with genotypes H and J (100% vs. 59%-68% for the other genotypes; P = .03); in addition, > or = 10 leukocytes per microscopic field were least often observed for genotypes G/Ga (19% vs. 59%-65% for the other genotypes; P = .01). Women's reports of lower abdominal pain were more often associated with F, G group genotypes (32%) than with B-complex (6%) or C-complex (13%) genotypes (P = .02). Certain symptoms of genital C. trachomatis infection were related to the infecting genotype. Further work will be necessary and should involve markers of the host immune response.
Occupational Chronic Obstructive Pulmonary Disease in a Danish Population-Based Study

Abstract The aim was to explore the impact of occupation on chronic obstructive pulmonary disease (COPD) in a cross-sectional population-based study among subjects aged 45 to 84 years. In a stratified sampling 89 general practitioners practices (GPP) in Denmark recruited 3106 males and 1636 females through the Danish Civil Registration System. COPD was defined by spirometry by the 2.5th-centile Lower Limit of Normal of FEV1 and FEV1/FVC. Information about smoking, occupational exposure and the respective occupations were obtained from questionnaires. Occupations followed the Danish adaptation of The International Standard Classification of Occupations, revision 1988 (DISCO-88). Exposure to vapour, gas, dust (organic and inorganic), and fume (VGDF) in each occupation (yes/no) was evaluated by two independent specialist in occupational medicine. Exposures were divided in no, low, medium, and high exposure as 0, <5, 5–14, and ≥ 15 years in the job, respectively. Data was analysed by a mixed random effect logistic regression model. The age-standardised COPD study prevalence was 5.0%. Of 372 DISCO-88 codes 72 were identified with relevant exposure to VGDF. 46% of the participants reported at least one occupation with VGDF exposure. Adjusted for smoking, age, sex, and GPP a dose-dependent association of COPD was found among workers in jobs with high organic dust exposure, with OR 1.56 (95% CI 1.09–2.24). Restricted to agriculture the OR was 1.59 (95% CI: 1.08–2.33). No association was observed for workers in jobs with inorganic dust, fume/gas, or vapour exposures. In summary, occupational organic dust exposure was associated to the prevalence of COPD.