Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding remission in real-world lupus patients across five European countries

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased mortality and significant personal, psychological and socioeconomic consequences. An agreed definition of remission is needed and lacking. We sought to visualize ‘remission in SLE’ in European patients considered by their physicians to be ‘in remission’ by comparing the reported symptom burden as reported by treating physicians for patients considered to be ‘in remission’ and those not considered to be ‘in remission’. Data for 1227 patients drawn from a multinational, real-world survey of patients with SLE consulting practising rheumatologists and nephrologists in France, Germany, Italy, Spain, and the UK show that physicians classed their patients as ‘in remission’ despite a considerable ongoing symptom burden and intensive immunosuppressive medication. Patients considered to be ‘in remission’ still had a mean of 2.68 current symptoms vs 5.48 for those considered to be not ‘in remission’ (p < 0.0001). The most common symptoms among those seen to be ‘in remission’ were joint symptoms, fatigue, pain, mucocutaneous involvement, haematological manifestations and kidney abnormalities. The current analysis highlights important ongoing disease activity, symptom burden and immunosuppressive medication in European patients with SLE considered by their treating physician to be ‘in remission’. For a further improvement of outcome, there is an urgent need for an international consensus on the definitions for remission among patients with SLE.
Report of the American Society of Transplantation Conference on Immunosuppressive Drugs and the Use of Generic Immunosuppressants

Considerable economic and health‐related costs are associated with the life‐long maintenance immunosuppressive therapy required to prevent transplant rejection. Generic medications have the potential of providing equivalent therapeutic efficacy at a lower economic cost. In 2001, the American Society of Transplantation invited experts to review the data and issues associated with the approval and use of generic immunosuppressants. A summary of that meeting is reported here.
Phosphate Concentration and the Putative Sensor Kinase Protein CckA Modulate Cell Lysis and Release of the Rhodobacter capsulatus Gene Transfer Agent

ABSTRACT The gene transfer agent of Rhodobacter capsulatus (RcGTA) is a bacteriophage-like genetic element with the sole known function of horizontal gene transfer. Homologues of RcGTA genes are present in many members of the alphaproteobacteria and may serve an important role in microbial evolution. Transcription of RcGTA genes is induced as cultures enter the stationary phase; however, little is known about cis-active sequences. In this work, we identify the promoter of the first gene in the RcGTA structural gene cluster. Additionally, gene transduction frequency depends on the growth medium, and the reason for this is not known. We report that millimolar concentrations of phosphate posttranslationally inhibit the lysis-dependent release of RcGTA from cells in both a complex medium and a defined medium. Furthermore, we found that cell lysis requires the genes rcc00555 and rcc00556, which were expressed and studied in Escherichia coli to determine their predicted functions as an endolysin and holin, respectively. Production of RcGTA is regulated by host systems, including a putative histidine kinase, CckA, and we found that CckA is required for maximal expression of rcc00555 and for maturation of RcGTA to yield gene transduction-functional particles.
Effects of Topical Alkane Vapocoolant Spray on Pain Intensity Prior to Digital Nerve Block for Ingrown Nail Surgery

Needle penetration and local anesthetic infiltration are 2 painful steps that cause considerable stress and anxiety during digital nerve block, which is the most frequently used regional anesthesia for ingrown nail surgery. The purpose of this study was to evaluate the effectiveness of topical alkane vapocoolant spray in decreasing pain during digital nerve block for ingrown nail surgery. The authors conducted a prospective, randomized clinical trial with 62 patients who underwent big toenail surgery. Prior to the digital block, alkane vapocoolant spray was applied to patients who were selected by flipping a coin. A visual analog scale (VAS) was used for assessment of pain during the skin needle penetration and during the infiltration of the anesthetic product. VAS scores during needle penetration were significantly lower in the intervention group. However, VAS scores during infiltration were similar statistically. Alkane vapocoolant spray has no noticeable clinical benefit in decreasing pain intensity during digital nerve block in patients undergoing toenail surgery.
Primary headaches in childhood – A population-based study

The aim of this study was to estimate the prevalence of primary headaches in pre-adolescent children, as well as headache frequency and days of treatment in this population. Sample consisted of 1994 children (aged 5–12 years). Parents were interviewed by a paediatric headache specialist using a questionnaire that allowed the classification of headaches using the criteria of the Second Edition of the International Classification of Headache Disorders. The most severe headache type was classified (mutually-exclusive diagnoses). Prevalence and prevalence ratios were calculated overall, as well as by age, gender and race. The overall prevalence of migraine was 3.76%, non-significantly higher in boys (3.9%) than in girls (3.6%). Prevalence of probable migraine was significantly higher than the prevalence of migraine for all ages (overall prevalence of 17.1%). Chronic migraine (CM) happened in 0.8% (girls, 1.15%; boys, 0.5%). Infrequent episodic tension-type headache (ETTH) happened in 2.3% of the sample while prevalence of frequent ETTH was 1.6%. Probable TTH happened in 13.5%. Most children with migraine had consulted a medical doctor because of their headaches, and the proportion was higher among children with CM (93.7%). Prevalence of primary headaches is high in young children. Probable diagnoses are more common than full diagnoses. Consultation rates are elevated.
Combination of γ‐irradiation and dendritic cell administration induces a potent antitumor response in tumor‐bearing mice: Approach to treatment of advanced stage cancer

We investigated a new approach to the treatment of advanced stage cancer, a combination of apoptosis‐inducing therapy and dendritic cell (DC) administration. MethA sarcoma and C3 tumor containing defined tumor‐specific antigens in form of peptides' epitopes were selected as experimental mouse models. Sites of established subcutaneous tumors were γ‐irradiated with 10 Gy 3–5 times with 4–5 day interval. DCs generated from bone marrow of syngeneic mice were injected i.v. and s.c. after each irradiation. A large number of cell tracker‐labeled DCs accumulated at the site of the irradiated tumor after s.c. injections. This effect was not observed in non‐irradiated tumors. Almost all of these DCs bound GFP‐labeled MethA cells in tumor tissue. Interferon‐γ production by splenocytes in response to the tumor‐specific MHC class I matched peptides was determined by ELISPOT assays. The combination of γ‐irradiation and DC administration, but not each of the treatments alone resulted in a significant increase in T cell response to the specific, but not to the control peptides. An increased proportion of tumor peptide‐specific CD8+‐cells was found only in that group of mice using staining with tetramers. DCs with defective presentation of antigen via MHC class I or MHC class II pathways were unable to induce peptide‐specific T cell response. The combination of γ‐irradiation and DC administration but not each of the treatments alone resulted in a dramatic antitumor effect. A substantial proportion of mice completely rejected their tumors (80% in case of MethA sarcoma and 40% in case of C3 tumor). In the rest of the mice, tumor growth was notably suppressed or completely blocked. These data suggest that the combination of apoptosis‐inducing therapy and DC administration may be an attractive approach to the treatment of advanced cancer. © 2001 Wiley‐Liss, Inc.
Nucleotide sequence of a cloned duck hepatitis B virus genome: comparison with woodchuck and human hepatitis B virus sequences

The nucleotide sequence of an EcoRI duck hepatitis B virus (DHBV) clone was elucidated by using the Maxam and Gilbert method. This sequence, which is 3,021 nucleotides long, was compared with the two previously analyzed hepatitis B-like viruses (human and woodchuck). From this comparison, it was shown that DHBV is derived from an ancestor common to the two others but has a slightly different genomic organization. There was no intergenic region between genes 5 and 8, which were fused into a single open reading frame in DHBV. Genes for the surface and core proteins were assigned to open reading frames 7 and 5/8. Amino acid comparisons showed some structural relationship between gene 6 product and avian reverse transcriptase, suggesting either evolution from a common ancestor or convergence to some particular structure to fulfill a specific function. This should be correlated with the synthesis of an RNA intermediate during DNA replication. This is also taken as an argument in favor of the hypothesis that gene 6 codes for the DNA polymerase that is found within the virion. DNA sequence comparison also showed that the two mammalian hepatitis B viruses are more homologous to each other than they are to DHBV, indicating that DHBV starts to evolve on its own earlier than the two other viruses, as do birds compared with mammals. From this it is proposed that the viruses evolved in a fashion parallel to the species they infect.
Approaches to studying in people with hearing loss.

BACKGROUND There has been little research on the experiences of students with hearing loss in higher education. It has, however, been suggested that children with hearing loss adopt different strategies and styles and that this leads to differences in their academic performance. AIMS This investigation compared students in higher education with and without hearing loss in terms of their approaches to studying. SAMPLES We compared 382 students with hearing loss taking courses by distance learning with the Open University and a comparison group of 190 students taking the same courses with no declared form of disablement. METHODS A questionnaire containing a shortened and adapted version of the Approaches to Studying Inventory was distributed in a postal survey. RESULTS Students with postvocational hearing loss obtained higher scores than the comparison group on deep approach, and those with postvocational deafness also obtained higher scores on the use of evidence and logic. Students with prevocational deafness obtained higher scores on reproducing orientation than the comparison group, and in particular on improvidence. All of the subgroups of students with hearing loss obtained higher scores than the comparison group on fear of failure. CONCLUSIONS The impact of hearing loss on cognitive aspects of studying appears to be relatively slight. Future research might focus instead upon its affective consequences and its effects upon a student's self-concept.
Major Vault Protein, a Marker of Drug Resistance, Is Upregulated in Refractory Epilepsy

Summary: Purpose: The molecular basis of drug resistance in epilepsy is being explored. Two proteins associated with drug resistance in cancer, P‐glycoprotein and multidrug resistance–associated protein 1, are upregulated in human epileptogenic pathologies. Other proteins associated with resistance in cancer include major vault protein (MVP) and breast cancer resistance protein (BCRP). We hypothesized that these proteins would also be upregulated in human epileptogenic pathologies.
Randomized Trial of Family Therapy Versus Nonfamily Treatment for Adolescent Behavior Problems in Usual Care

A major focus of implementation science is discovering whether evidence-based approaches can be delivered with fidelity and potency in routine practice. This randomized trial compared usual care family therapy (UC-FT), implemented without a treatment manual or extramural support as the standard-of-care approach in a community clinic, to nonfamily treatment (UC-Other) for adolescent conduct and substance use disorders. The study recruited 205 adolescents (M age = 15.7 years; 52% male; 59% Hispanic American, 21% African American) from a community referral network, enrolling 63% for primary mental health problems and 37% for primary substance use problems. Clients were randomly assigned to either the UC-FT site or one of five UC-Other sites. Implementation data confirmed that UC-FT showed adherence to the family therapy approach and differentiation from UC-Other. Follow-ups were completed at 3, 6, and 12 months postbaseline. There was no between-group difference in treatment attendance. Both conditions demonstrated improvements in externalizing, internalizing, and delinquency symptoms. However, UC-FT produced greater reductions in youth-reported externalizing and internalizing among the whole sample, in delinquency among substance-using youth, and in alcohol and drug use among substance-using youth. The degree to which UC-FT outperformed UC-Other was consistent with effect sizes from controlled trials of manualized family therapy models. Nonmanualized family therapy can be effective for adolescent behavior problems within diverse populations in usual care, and it may be superior to nonfamily alternatives.
Identification of PCDH1 as a novel susceptibility gene for bronchial hyperresponsiveness.

RATIONALE Asthma is a chronic inflammatory airway disease that affects more than 300 million individuals worldwide. Asthma is caused by interaction of genetic and environmental factors. Bronchial hyperresponsiveness (BHR) is a hallmark of asthma and results from increased sensitivity of the airways to physical or chemical stimulants. BHR and asthma are linked to chromosome 5q31-q33. OBJECTIVES To identify a gene for BHR on chromosome 5q31-q33. METHODS In 200 Dutch families with asthma, linkage analysis and fine mapping were performed, and the Protocadherin 1 gene (PCDH1) was identified. PCDH1 was resequenced in 96 subjects from ethnically diverse populations to identify novel sequence variants. Subsequent replication studies were undertaken in seven populations from The Netherlands, the United Kingdom, and the United States, including two general population samples, two family samples, and three case-control samples. PCDH1 mRNA and protein expression was investigated using polymerase chain reaction, Western blotting, and immunohistochemistry. MEASUREMENTS AND MAIN RESULTS In seven out of eight populations (n = 6,168) from The Netherlands, United Kingdom, and United States, PCHD1 gene variants were significantly associated with BHR (P values, 0.005-0.05) This association was present in both families with asthma and general populations. PCDH1 mRNA and protein were expressed in airway epithelial cells and in macrophages. CONCLUSIONS PCDH1 is a novel gene for BHR in adults and children. The identification of PCDH1 as a BHR susceptibility gene may suggest that a structural defect in the integrity of the airway epithelium, the first line of defense against inhaled substances, contributes to the development of BHR.
Nitric Oxide as a Local Mediator of Prostaglandin F2α-Induced Regression in Bovine Corpus Luteum: An In Vivo Study

To test whether nitric oxide (NO) is involved in prostaglandin (PG) F2α-induced regression of the bovine corpus luteum (CL) in vivo, heifers were treated as follows: Group 1, saline (3 ml/h); Group 2, dinoprost, an analogue of prostaglandin F2α (aPGF2α; 5 mg/0.5 h); Group III, Nω-nitro-L-arginine methyl ester (L-NAME; 200 mg/4 h), an inhibitor of nitric oxide synthase; and Group IV, L-NAME (400 mg/4 h) and aPGF2α (5 mg/0.5 h). All treatments were administered by an intraluteal microdialysis system (MDS) on day 15 of the cycle. Perfusate and jugular plasma samples were collected at half-hour intervals; additionally, jugular plasma samples were collected once daily from day 16 to day 21 of the cycle. In the perfusate samples, aPGF2α increased P4 (P < 0.05), PGE2 (P < 0.001), and LTC4 (P < 0.05) concentrations; L-NAME increased P4 (P < 0.05) but did not change PGE2 and LTC4 (P > 0.05) concentrations as compared with the period before treatment. Simultaneous perfusion of CL with L-NAME and aPGF2α caused a further increase of P4 concentration (P < 0.05) induced by L-NAME or aPGF2α treatment and increased PGE2 and LTC4 (P < 0.001) concentrations to the level observed after aPGF2α treatment. Perfusion of CL with aPGF2α caused luteal regression within 24 h, while perfusion with L-NAME prolonged the life span of CL to day 21 (P < 0.05). Concomitant L-NAME and aPGF2α treatment partially counteracted (P < 0.05) the luteal regression caused by aPGF2α administration. These results show that NO is involved in the process of luteolysis in the bovine CL and suggest that the luteolytic effect of aPGF2α may be mediated by NO as an important component of an autocrine/paracrine luteolytic cascade.
Expansion and long‐term maintenance of induced pluripotent stem cells in stirred suspension bioreactors

Induced pluripotent stem cells (iPSCs) can provide an important source of cells for the next‐generation of cell therapies in regenerative medicine, in part due to their similarity to embryonic stem cells (ESCs). Patient‐specific iPSCs represent an opportunity for autologous cell therapies that are not restricted by immunological, ethical and technical obstacles. One of the technical hurdles that must be overcome before iPSCs can be clinically implemented is the scalable, reproducible production of iPSCs and their differentiated progeny. All of the iPSC lines established thus far have been generated and expanded with static tissue culture protocols, which are time‐consuming and suffer from batch‐to‐batch variability. Alternatively, stirred suspension bioreactors propose several benefits and their homogeneous culture environment facilitates the large‐scale expansion required for clinical studies at less cost. We have previously developed protocols for expanding murine and human ESCs as undifferentiated aggregates in stirred suspension bioreactors. The resulting cells were karyotypically normal, expressed pluripotency markers and could be differentiated into all three germ lineages, both in vitro and in vivo. In this study, we demonstrate that stirred suspension bioreactors yield 58‐fold expansion of undifferentiated pluripotent iPSCs over 4 days. In vitro differentiation into cartilage, bone and cardiomyocytes lineages, in addition to in vivo teratoma formation, further confirmed the existence of fully functional and undifferentiated pluripotent iPSC aggregates following long‐term passaging. Stirred suspension bioreactor culture represents an efficient process for the large‐scale expansion and maintenance of iPSCs, which is an important first step in their clinical application. Copyright © 2011 John Wiley & Sons, Ltd.
Benefit of antiretroviral therapy on survival of human immunodeficiency virus-infected patients admitted to an intensive care unit

Objective:To evaluate the impact of antiretroviral therapy (ART) and the prognostic factors for in-intensive care unit (ICU) and 6-month mortality in human immunodeficiency virus (HIV)-infected patients. Design:A retrospective cohort study was conducted in patients admitted to the ICU from 1996 through 2006. The follow-up period extended for 6 months after ICU admission. Setting:The ICU of a tertiary-care teaching hospital at the Universidade de São Paulo, Brazil. Participants:A total of 278 HIV-infected patients admitted to the ICU were selected. We excluded ICU readmissions (37), ICU admissions who stayed less than 24 hours (44), and patients with unavailable medical charts (36). Outcome Measure:In-ICU and 6-month mortality. Main Results:Multivariate logistic regression analysis and Cox proportional hazards models demonstrated that the variables associated with in-ICU and 6-month mortality were sepsis as the cause of admission (odds ratio [OR] = 3.16 [95% confidence interval [CI] 1.65–6.06]); hazards ratio [HR] = 1.37 [95% CI 1.01–1.88]), an Acute Physiology and Chronic Health Evaluation II score >19 [OR = 2.81 (95% CI 1.57–5.04); HR = 2.18 (95% CI 1.62–2.94)], mechanical ventilation during the first 24 hours [OR = 3.92 (95% CI 2.20–6.96); HR = 2.25 (95% CI 1.65–3.07)], and year of ICU admission [OR = 0.90 (95% CI 0.81–0.99); HR = 0.92 [95% CI 0.87–0.97)]. CD4 T-cell count <50 cells/mm3 was only associated with ICU mortality [OR = 2.10 (95% CI 1.17–3.76)]. The use of ART in the ICU was negatively predictive of 6-month mortality in the Cox model [HR = 0.50 (95% CI 0.35–0.71)], especially if this therapy was introduced during the first 4 days of admission to the ICU [HR = 0.58 (95% CI 0.41–0.83)]. Regarding HIV-infected patients admitted to ICU without using ART, those who have started this treatment during ICU stay presented a better prognosis when time and potential confounding factors were adjusted for [HR 0.55 (95% CI 0.31–0.98)]. Conclusions:The ICU outcome of HIV-infected patients seems to be dependent not only on acute illness severity, but also on the administration of antiretroviral treatment.
Component Processes in Voluntary Task Switching

The present study investigated the involvement of bottom-up and top-down control in task-switching situations in which tasks are selected on a voluntary basis. We tested for indices of both types of control in the reduction in switch cost that is observed when more time is available before executing a task. Participants had to indicate their task choice overtly prior to the actual task execution, and two time intervals were manipulated: the interval between the task-execution response of the previous trial and task-indication response of the current trial and the interval between task-indication response and task-execution response of a particular trial. In Experiment 1, the length of these intervals was manipulated orthogonally, and indices for top-down and bottom-up control were observed. Concerned with the validity of these results, Experiments 2–3 additionally discouraged participants from preparing the upcoming task before their task-indication response. Indices for bottom-up control remained, but not for top-down control. The characteristics of top-down and bottom-up control in voluntary task switching and task switching in general are discussed.