Miracle-dz/UniFAR-FTUs huggingface dataset:
Refining the phenotype of common mutations in Rett syndrome

Rett syndrome (RTT; MIM No 312750) is a neurodevelopmental disorder mainly affecting girls, with an incidence of 1:10 000 female births.1 The clinical features of the syndrome were first described in a series of publications2–5 during the decade after it was first reported in English language journals.6 At that time, in the absence of a biological marker, criteria to assist with the diagnosis were developed by an international working group.7 These criteria relate to the typical characteristics which are: normal prenatal and perinatal period and apparently normal development for the first six months of life; deceleration in head growth; loss of hand and communication skills between six and 30 months; apparent severe psychomotor retardation; acquisition of stereotypical hand movements; and evidence of gait or truncal apraxia between one and four years. These necessary criteria were supplemented by a set of supportive but not mandatory criteria, which help to delineate the phenotype further. These include breathing dysfunction, EEG abnormalities, seizures, spasticity, peripheral vasomotor disturbance, scoliosis, growth retardation, and hypotrophic small feet. In 1999 the association between Rett syndrome and mutations in the methyl-CpG binding protein 2 (MECP2; MIM No 300005) located on Xq28 was first identified.8 In the last decade there had already been much commentary about the expanding clinical spectrum of Rett syndrome and the occurrence of atypical forms.9 This culminated in 2001 in a meeting to revise the existing diagnostic criteria.10 It is now clear that, although this condition must be considered a severe neurodevelopmental disorder, there is still considerable variation in both functioning and associated morbidity, even in those cases with confirmed MECP2 mutations. We have been able to demonstrate this variability11 using a tool to measure functional ability12 and three clinical scales. The first was developed by …
Serum HBV DNA level at week 12 is superior to viral response at week 24 in predicting long‐term treatment outcome of telbivudine for chronic hepatitis B patients

Background Telbivudine, one of the five nucleos(t)ide antiviral drugs, was reported to be superior to lamivudine in a better biochemical, virological, and histological response for treatment‐naive patients in the GLOBE trial. The aim of this study was to determine the antiviral potency, viral resistance, and the significance of early response for long‐term telbivudine treatment. Methods We recruited 161 patients of chronic hepatitis B (CHB) on telbivudine between January 2009 and September 2011 in Macau, China. The serum hepatitis B virus DNA levels, hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) normalization, and viral resistance were analyzed. Results The median age and follow‐up duration were 48 years and 16.9 months. All patients were followed up for at least 6 months, while data were collected for 132, 120, 95, and 53 patients at 12, 24, 48, and 96 weeks respectively. The cumulative HBeAg seroconversion rate was 20.8% and only three patients (1.9%) presented with telbivudine low level resistance. The ALT normalization rates were 76.9% at 48 weeks and 77.6% at 96 weeks. Undetectable HBV DNA was achieved by 1.8%, 31.6%, 60%, and 74.1% in HBeAg positive patients and 29.3%, 60.3%, 84%, and 84.6% in HBeAg negative patients at each time point. Week 12 HBV DNA level <1000 copies/ml (<200 IU/ml) was a better predictor of viral suppression at 2‐year follow‐up (P=0.001, OR=27.00) than undetectable HBV DNA level at week 24 (P=0.120, OR=4.81). Conclusions Two‐year telbivudine treatment yielded high rates of viral suppression and ALT normalization. Serum HBV DNA level at week 12 is a superior predictor for long‐term viral suppression.
Field inversion gel electrophoretic analysis of Legionella pneumophila strains associated with nosocomial legionellosis in children

Two nosocomial cases of Legionnaires' disease occurred in children. Legionella pneumophila serogroup 1 was isolated from both patients and 30 of 39 plumbing system sites in the hospital. The patient and hospital environmental isolates yielded identical field inversion gel electrophoretic patterns which differed from patterns observed with epidemiologically unrelated strains.
Role of duodenogastroesophageal reflux in the pathogenesis of esophageal mucosal injury and gastroesophageal reflux symptoms.

BACKGROUND AND AIM Patients with gastroesophageal reflux disease (GERD) usually suffer from acid reflux and duodenogastroesophageal reflux (DGER) simultaneously. The question of whether DGER has an important effect on the development of GERD remains controversial. The aim of the present study was to investigate the role of DGER in the pathogenesis of GERD and its value for the diagnosis of nonerosive reflux disease (NERD). METHODS GERD was initially diagnosed using the reflux disease questionnaire. For further diagnosis, results of the upper gastrointestinal endoscopy (excluding a diagnosis of Barrett's esophagus) were considered in conjunction with simultaneous 24 h esophageal pH and bilirubin monitoring. RESULTS According to endoscopic findings, 95 patients (43 men, 50+/-10 years of age) were divided into two groups: the reflux esophagitis (RE) group (n=51) and the NERD group (n=44). Three DGER parameters, the percentage of time with absorbance greater than 0.14, the total number of reflux episodes and the number of bile reflux episodes lasting longer than 5 min, were evaluated in the study. For the RE group, the values of the DGER parameters (19.05%+/-23.44%, 30.56+/-34.04 and 5.90+/-6.37, respectively) were significantly higher than those of the NERD group (7.26%+/-11.08%, 15.68+/-20.92 and 2.59+/-3.57, respectively, P<0.05 for all) but no significant difference was found in acid reflux. Of NERD patients, 18.5% were diagnosed with simple DGER. The positive diagnosis rate of NERD could be significantly elevated from 65.9% to 84.1% (P<0.05), if bilirubin monitoring was employed in diagnosis. CONCLUSIONS DGER may occur independently but plays an important role in the development of RE and GERD symptoms. Simultaneous 24 h esophageal pH and bilirubin monitoring is superior to simple pH monitoring in helping identify patients at risk for NERD.
Patient Characteristics Predicting Readmission Among Individuals Hospitalized for Heart Failure

Heart failure is difficult to manage and increasingly common with many individuals experiencing frequent hospitalizations. Little is known about patient factors consistently associated with hospital readmission. A literature review was conducted to identify heart failure patient characteristics, measured before discharge, that contribute to variation in hospital readmission rates. Database searches yielded 950 potential articles, of which 34 studies met inclusion criteria. Patient characteristics generally have a very modest effect on all-cause or heart failure–related readmission within 7 to 180 days of index hospital discharge. A range of cardiac diseases and other comorbidities only minimally increase readmission rates. No single patient characteristic stands out as a key contributor across multiple studies underscoring the challenge of developing successful interventions to reduce readmissions. Interventions may need to be general in design with the specific intervention depending on each patient’s unique clinical profile.
Six-month versus 24-month dual antiplatelet therapy after implantation of drug eluting stents in patients non-resistant to aspirin: ITALIC, a randomized multicenter trial

Martine Gilard , MD, PhD, Paul Barragan , MD, Arif AL. Noryani , MD, Hussam A. Noor , MD, Talib Majwal , MD, Thomas Hovasse , MD, Philippe Castellant , MD, Michel Schneeberger , MD, Luc Maillard , MD, PhD, Erwan Bressolette E , MD, Jaroslaw Wojcik , MD, Nicolas Delarche , MD, Didier Blanchard , MD, Bernard Jouve , MD, Olivier Ormezzano , MD, Franck Paganelli , MD, Gilles Levy , MD, Joel Sainsous , MD, Didier Carrie , MD, Alain Furber , MD, PhD, Jacques Berland , MD, Oliver Darremont , MD, Herve Le Breton , MD, Anne Lyuycx-Bore , MD, Antoine Gommeaux , MD, Claude Cassat , MD, Alain Kermarrec , MD, Pierre Cazaux , MD, Philippe Druelles , MD, Raphael Dauphin , MD, Jean Armengaud , MD, Patrick Dupouy , MD, Didier Champagnac , MD, Patrick Ohlmann , MD, Knut Endresen K , MD, Hakim Benamer , MD, Robert Gabor Kiss , MD, Imre Ungi , MD, Jacques Boschat J , MD, Marie-Claude Morice , MD
Catheter Ablation for Persistent Atrial Fibrillation: Antral Pulmonary Vein Isolation and Elimination of Nonpulmonary Vein Triggers Are Sufficient

Since its original description in 1998, the technique of catheter-based atrial fibrillation (AF) ablation has undergone several modifications.1 Currently, many operators use an anatomic approach consisting of circumferential lesions encircling individual or ipsilateral pulmonary veins (PVs) with additional empirical left atrial (LA) ablation (lines), whereas others perform a more PV-specific approach using entrance/exit block to validate isolation, deferring any additional non-PV lesions unless clinically indicated.2–7 Despite these differences in technique, the outcome data for AF patients undergoing ablation seem remarkably consistent between centers, with overall single procedure efficacy of ≥70% in achieving long-term arrhythmia control for patients with paroxysmal AF but significantly lower success rates for patients with persistent or long-standing persistent AF. These observations imply that the mechanisms underlying persistent/long-standing persistent AF may be different from paroxysmal AF. It has been posited that once in the persistent stage, the underlying substrate rather than triggers alone maintains this arrhythmia. Although this hypothesis remains to be proven, it has nevertheless resulted in the development of adjunctive substrate modification strategies for patients with more established forms of AF.8–11 Among the various substrate modification strategies currently being used, complex fractionated electrogram (CFE) ablation is the most popular. This technique was originally described by Nademanee et al,8 where by targeting CFEs exclusively these investigators were able to achieve long-term arrhythmia control after a single procedure in up to 70% of patients with persistent AF. However, subsequent attempts by other investigators have not yielded comparable results.12,13 Despite this inconsistency, many centers are targeting CFEs as a part of the ablation strategy in this group of patients. Contrary to this practice and regardless of the type of AF, our group at the Hospital of the University of Pennsylvania has consistently used an approach comprising pulmonary …
International Prognostic Index, Type of Transplant and Response to Rituximab Are Key Parameters to Tailor Treatment in Adults With CD20‐Positive B Cell PTLD: Clues From the PTLD‐1 Trial

Tailoring treatment by patient strata based on the risk of disease progression and treatment toxicity might improve outcomes of patients with posttransplant lymphoproliferative disorder (PTLD). We analysed the cohort of 70 patients treated in the international, multicenter phase II PTLD‐1 trial (NCT01458548) to identify such factors. Of the previously published scoring systems in PTLD, the international prognostic index (IPI), the PTLD prognostic index and the Ghobrial score were predictive for overall survival. None of the scoring systems had a considerable effect on the risk for disease progression. Age and ECOG performance status were the baseline variables with the highest prognostic impact in the different scoring systems. Baseline variables not included in the scoring systems that had an impact on overall survival and disease progression were the type of transplant and the response to rituximab at interim staging. Thoracic organ transplant recipients who did not respond to rituximab monotherapy were at particularly high risk for death from disease progression with subsequent CHOP‐based chemotherapy. Patients in complete remission after four courses of rituximab and patients in partial remission with low‐risk IPI had a low risk of disease progression. We speculate that chemotherapy might not be necessary in this patient cohort.
Relation of anti‐TPO autoantibody titre and T‐lymphocyte cytokine production patterns in Hashimoto's thyroiditis

Objective Cytokines produced by cytotoxic T cells or autoantibodies lead to thyroid cell damage and/or cell death in Hashimoto's thyroiditis (HT). Anti‐TPO autoantibodies (TPOAb) are the most frequently represented autoantibodies in the sera of patients with HT. Data describing the quantitative correlation between TPOAb titre and cytokine pattern are missing so far. To our knowledge this is the first study systematically evaluating the correlation of possible parameters of disease activity such as changes in CD4 and CD8 T‐cell cytokine production and of TPOAb titre.
Mechanical lesion activates newly identified NFATc1 in primary astrocytes: implication of ATP and purinergic receptors

Ca2+‐dependent calcineurin is upregulated in reactive astrocytes in neuroinflammatory models. Therefore, the fact that the nuclear factor of activated T cells (NFAT) is activated in response to calcineurin qualifies this family of transcription factors with immune functions as candidates to mediate astrogliosis. Brain trauma induces a neuroinflammatory state in which ATP is released from astrocytes, stimulating calcium signalling. Our goal here is to characterize NFATc1 and NFATc2 in mouse primary astrocyte cultures, also exploring the implication of NFAT in astrocyte activation by mechanical lesion. Quantitative reverse transcriptase‐polymerase chain reaction, Western blot analysis and immunofluorescence microscopy identified NFATc1 in astrocytes, but not NFATc2. Moreover, NFATc1 was expressed in the cytosol of resting astrocytes, whereas activation of the Ca2+‐calcineurin pathway by ionomycin translocated NFATc1 to the nucleus, which is a requirement for activation. The implication of astrocytic NFAT in brain trauma was analysed using an in vitro scratch lesion model. Mechanical lesion caused a rapid NFATc1 translocation that progressed throughout the culture as a gradient and was maintained for at least 4 h. We also demonstrate that ATP, released by lesion, is a potent inducer of NFATc1 translocation and activation. Moreover, the use of P2Y receptor modulators showed that such ATP action is mediated by stimulation of several Gq‐protein‐coupled P2Y purinergic receptors, among which P2Y1 and P2Y6 are included. In conclusion, this work provides evidence that newly identified NFATc1 is translocated in astrocytes in response to lesion following a pathway that involves ATP release and activation of metabotropic purinergic receptors.
Dissociative Experiences of Vietnam Veterans with Chronic Posttraumatic Stress Disorder

Interest in dissociation has been renewed, and its relationship to Posttraumatic Stress Disorder is especially intriguing. In this study 57 consecutively admitted chronic, combat-related Posttraumatic Stress Disorder sufferers were grouped by scores on a dissociative scale (Dissociative Experiences Scale). The three groups (high, medium, and low) were compared on personality measures (MMPI basic scales and subscales, and Millon's MCMI), Posttraumatic Stress Disorder measures, and a psychophysiological index of heart rate under baseline trauma conditions. The results showed that the survivors with more dissociative experiences show distinctive and higher symptom levels—excessive fearfulness, symptoms of strange experiences, and high tonic psychophysiological states—as well as greater severity of ratings of Posttraumatic Stress Disorder (on the Mississippi Scale). The discussion addressed the possible role of dissociation in Posttraumatic Stress Disorder.
Novel genetic factors involved in resistance to Bacillus thuringiensis in Plutella xylostella

The widespread and sustainable exploitation of the entomopathogen Bacillus thuringiensis (Bt) in pest control is threatened by the evolution of resistance. Although resistance is often associated with loss of binding of the Bt toxins to the insect midgut cells, other factors have been implicated. Here we used suppressive subtractive hybridization and gene expression suppression to identify additional molecular components involved in Bt‐resistance in Plutella xylostella. We isolated transcripts from genes that were differentially expressed in the midgut of larvae from a resistant population, following ingestion of a Bt kurstaki HD1 strain‐based commercial formulation (DiPel), and compared with a genetically similar susceptible population. Quantitative real‐time polymerase‐chain reaction (RT‐PCR) analysis confirmed the differential basal expression of a subset of these genes. Gene expression suppression of three of these genes (P. xylostella cyclin‐dependent kinase 5 regulatory subunit associated protein 1‐like 1, stromal cell‐derived factor 2‐like 1 and hatching enzyme‐like 1) significantly increased the pathogenicity of HD1 to the resistant population. In an attempt to link the multitude of factors reportedly influencing resistance to Bt with the well‐characterized loss of toxin binding, we also considered Bt‐resistance models in P. xylostella and other insects.
Genetic Characterization of Albanian Sheep Breeds by Microsatellite Markers

Albania is a Mediterranean country, located in West of Balkan Peninsula. Albanian farmers have a long tradition in sheep breeding. Sheep comprise one of the most important domestic livestock species in Albania and play an important role in the livelihood of local community since they are a good source of meat, milk and coarse wool (Dobi et al., 2006; Porcu and Markovic, 2005). There are three important local sheep breed in Albania: Bardhoka, Ruda and Shkodrane, which are also the object of this study. The genetic characterization of a breed is very important for the evaluation of genetic variability, which is an important element in conservation of genetic resources and for breeding strategies. Genetic characterization can be done by different classes of molecular markers, such as Restriction Fragment Length Polymorphisms (RFLP) (Abdel-rahman et al., 2010), Single Stranded Conformation Polymorphisms (SSCP) (Bastos et al., 2001), Random Amplified Polymorphic DNA (RAPD) markers (Jawasreh et al., 2011; Kantanen et al., 1995; Paiva et al., 2005; Qasim et al., 2011), Amplified Fragment Length Polymorphisms (AFLP) (Xiao et al., 2009), Single Nucleotide Polymorphisms (SNP) (Pariset et al., 2006a,b), and microsatellites.
Effects of Iron on Vitamin D Metabolism: A Systematic Review

Vitamin D is a prohormone nutrient, which is involved in skeletal and extra-skeletal functions. Iron is another essential nutrient that is necessary for the production of red blood cells and oxygen transport. This element plays important roles in enzymatic systems including those required for Vitamin D activation. To the best of our knowledge, there is no exclusive review on the relationship between iron deficiency anemia (IDA), as the most prevalent type of anemia, and Vitamin D deficiency and the effect of recovery from iron deficiency on Vitamin D status. The aim of this study was to conduct a systematic search of observational and clinical trials in this field. The databases of PubMed, ProQuest, Cochrane Library, ISI Web of Knowledge, and SCOPUS were searched comprehensively. English-language human studies conducted on iron deficient patients or interventions on the effect of iron therapy on Vitamin D were extracted (n = 10). Our initial search yielded 938 articles. A total of 23 papers met the inclusion criteria. Thirteen studies were excluded because they were not relevant or not defining anemia types. The final analysis was performed on ten articles (3 cross-sectional and 7 interventional studies). Observational data indicated a positive relationship between iron status and Vitamin D, while trials did not support the effectiveness of iron supplementation on improving Vitamin D status. The mechanism underlying this association may involve the reduction of the activation of hydroxylases that yield calcitriol. Future randomized controlled trials with large sample sizes and proper designs are needed to highlight underlying mechanisms.
Particulate Bone Grafting of Osteolytic Femoral Lesions Around Stable Cementless Stems

The purpose of the current study was to evaluate the effect of particulate grafting for proximal femoral osteolysis in the presence of a well-fixed cementless femoral stem at the time of acetabular liner change or revision. Sixteen patients (17 hips) who averaged 51 years of age underwent curettage and packing of proximal femoral osteolytic lesions with cancellous allograft. Modular acetabular liners were changed in 11 patients, acetabular revisions were performed in six patients, and femoral heads were exchanged in all patients. The femoral component was retained in all patients. The majority of patients were asymptomatic before revision surgery. The size of the femoral osteolytic lesions was measured preoperatively and postoperatively with anteroposterior and Lauenstein lateral radiographs of the hip. Preoperatively, the average lesion was 41 × 16 mm on the anteroposterior view and 18 × 7 mm on the lateral view. The average clinical and radiographic followup was 39 and 32 months, respectively, with a minimum followup of 24 months. All but one patient remained asymptomatic during the followup period and no femoral stem showed evidence of loosening. The size of the femoral osteolytic lesion averaged 16 × 6 mm on the anteroposterior view and 6 × 2 mm on the lateral view at most recent followup. In 15 of 17 patients, the size of the femoral lesion had regressed. This technique seems to be a viable means of preventing progressive osteolysis and femoral loosening while preserving bone stock for future reconstruction.
Dominant C2 Domain Epitope Specificity of Inhibitor Antibodies Elicited by a Heat Pasteurized Product, Factor VIII CPS-P, in Previously Treated Hemophilia A Patients without Inhibitors

Summary From June, 1990, to November, 1991, in The Netherlands and Belgium, 16 previously treated severe hemophilia A patients (PTP) developed inhibitors after exposure to factor VIII CPS-P, a new heat pasteurized product. A previously untreated patient (PUP) also developed an inhibitor to CPS-P. In inhibitor neutralization assays with recombinant fVIII C2 and A2 domain polypeptides, plasmas from 14 PTPs were ≥79% neutralized by C2 and <10% by A2, but the PUP plasma was partially neutralized by C2 (48%) and A2 (28%). Immunoprecipitation assays of the PTP and PUP plasmas with the fVIII heavy chain and with recombinant C2 and A3-C1 polypeptides confirmed that the C2 dominant immune response to CPS-P was found only in the PTPs. Competition of the binding of 2 inhibitors to 125I-CPS-P by unlabeled CPS-P and another plasma fVIII was similar, demonstrating that the antibody response was not directed to epitopes only present in CPS-P. We propose that the immunogenicity of the CPS-P C2 domain was altered by heat pasteurization.
Prisoners’ Perception of Legitimacy of the Prison Staff: A Qualitative Study in Slovene Prisons

The purpose of this article is to explore prisoners’ perception of legitimacy of prison staff and examine the compliance of prisoners with the authority of prison staff to highlight the differences between instrumental and normative compliance of prisoners. This study draws on data collected from a random sample of 193 prisoners in all Slovene prisons. Using a qualitative approach based on structured interviews, our findings suggest that distributive justice, procedural justice, the quality of relations with prison staff, and the effectiveness of prison staff influence prisoners’ perception of legitimacy in a prison environment. Several prisoners comply with prison rules because they fear sanctions, which indicates their instrumental compliance, while normative compliance was reported by prisoners who perceived the legitimacy of prison staff in a more positive manner. Overall findings indicate that both instrumental and normative compliance of prisoners can be observed in Slovene prisons.