Miracle-dz/UniFAR-FTUs huggingface dataset:
The ABSORB EXTEND study: preliminary report of the twelve-month clinical outcomes in the first 512 patients enrolled.

AIMS The safety and performance of the Absorb Bioresorbable Vascular Scaffold (Absorb BVS) system (Abbott Vascular, Santa Clara, CA, USA) has been previously established in 131 patients from cohort A and cohort B of the first-in-man ABSORB trial. Following this trial, ABSORB EXTEND was initiated as a global continued access study (outside of the USA) to expand experience with the Absorb BVS system to different geographies with broader inclusion criteria to include the treatment of longer lesions and multiple vessels. We report in this manuscript the twelve-month clinical outcomes of the first 512 patients in this population. METHODS AND RESULTS ABSORB EXTEND is a prospective, single-arm, open-label clinical study which will enrol up to 800 patients at up to 100 sites. Included are patients with lesions ≤28 mm in length and reference vessel diameter of 2.0-3.8 mm (as assessed by on-line QCA or IVUS). Treatment of a maximum of two de novo native coronary artery lesions is permitted when each lesion is located in a different epicardial vessel. An independent clinical events committee adjudicates all endpoint-related events. At one year, for the first 512 patients enrolled in the study, the composite endpoints of ischaemia-driven MACE and ischaemia-driven target vessel failure were 4.3% and 4.9%, respectively. The cumulative rate of ARC defined definite and probable scaffold thrombosis for this population was 0.8% at one year. CONCLUSIONS This interim analysis of the ABSORB EXTEND study shows low rates of MACE and scaffold thrombosis. The study is registered on clinicaltrials.gov (unique identifier NCT01023789).
Should We Use Model-Based Methods for Phylogenetic Inference When We Know That Assumptions About Among-Site Rate Variation and Nucleotide Substitution Pattern Are Violated ?

An often-expressed concern regarding the use of maximum likelihood and other modelbased methods in phylogenetic analysis is that the assumed models are too simple, violating known aspects of sequence evolution in several ways (e.g., Sanderson and Kim, 2000). For example, we know that sites do not truly evolve independently, that the substitution process is not completely homogeneous across sites and through time, and that simple stochastic models fail to adequately represent the complexity of the nucleotide substitution process. Many advances have been made in an effort to model sequence evolution more realistically, including allowance for unequal base composition (Felsenstein, 1981), complex substitution patterns (e.g., Tavaré, 1986; Yang, 1994), among-site rate variation (Yang, 1993), compensatory base substitution (Schöniger and Von Haeseler, 1994), and heterogeneity of the substitution process across the tree (Galtier and Gouy, 1998). Nevertheless, even with these improvements, there is no reason to believe that even the most general and parameter-rich evolutionary models currently available capture all the nuances of the processes that have generated any particular set of sequences. Furthermore, accurate estimation of the parameters of complex evolutionary models can be very difcult, and data sets containing many taxa and sites may be needed for likelihood estimation to consistently yield reliable parameter estimates (Nielsen, 1997; Sullivan et al., 1999). Fortunately, perfect models are not necessarily a prerequisite for reliable statistical inference (e.g., Burnham and Andersen, 1998). Many statisticalmethods perform well in the face of violationof commondistributionalassumptions such as normality (e.g., Boneau, 1960; Donaldson, 1968). However, this observation does not guarantee the robustness of maximum likelihood when applied to the phylogenetic estimation problem. It is therefore important to examine the impact of various model violations on the accuracy of phylogenetic estimation (e.g., Huelsenbeck, 1995). In some cases, biases introduced by violation of a model’s assumptions can actually favor recovery of the true tree rather than an incorrect tree (Yang, 1997; Siddall, 1998). For example, Yang (1997) simulated data under a Jukes–Cantor (JC) model with variable rates across sites (following a gamma distribution) and demonstrated that estimation under the JC model with equal rates could be more efcient than estimation in which among-site rate variation was correctly modeled by a gamma distribution. However, the reasons for the improvement in efciency shouldbe disconcerting (Bruno andHalpern, 1999; Swofford et al., 2001). These results suggest that application of increasingly general and complex models would sometimes lead to decreased efciency, despite the fact that the more complex models almost always provide signicantly better t to real data than the simpler models. However, in Yang’s study, the improvement
Timing of loading--immediate, early, or delayed--in the outcome of implants in the edentulous mandible: a prospective clinical trial.

PURPOSE To report on the implant outcome of delayed, early, and immediate loading of implants in the edentulous mandible in a prospective controlled study. MATERIALS AND METHODS On a consecutive basis, the first 10 patients received an overdenture retained by 2 ball attachments 4 months after implant insertion (delayed), and the next 10 patients received an overdenture 1 week after implant surgery (early). The next 10 patients were treated with a fixed prosthesis on 3 implants (Br6nemark Novum) either the day of or the day after surgery (immediate). All patients were followed for 1 year; half were followed for 2 years. Measures of assessment for this prospective clinical trial included monitoring of loading at prosthesis level (bite fork) as well as at the abutment level (strain gauges), 3-dimensional imaging of marginal bone remodeling, and implant stability. RESULTS AND DISCUSSION One patient in each OD group lost both implants. The losses occurred 6 months after loading in the delayed group and 1 month after loading in the early group. In the immediate group, 1 patient lost both distal implants 5 months after loading. In 2 other patients, 1 distal implant failed after 1 year of loading. Maximal bite forces increased over time for all groups. Marginal bone loss was the highest for the immediate group, while no differences in implants stability were observed between the 3 groups after 1 year of loading. CONCLUSIONS According to this prospective controlled clinical trial, the results achieved with implants loaded early were comparable to those achieved with implants loaded after a delay. Distal implants are at higher risk for failure in the immediate loaded protocol.
The Role of Organ Failure and Infection in Necrotizing Pancreatitis: A Prospective Study

Objective:To clarify the roles of organ failure and infection in the outcome of necrotizing pancreatitis. Background:Results of previous cohort studies that focused on the roles of infection and organ failure in acute pancreatitis are controversial. Methods:In this study, we collected the medical records of 447 patients with necrotizing pancreatitis from January 2009 to June 2012. Data associated with organ failure and infection were analyzed. Results:The overall mortality rate was 13% (58/447). Intervention was performed in 223 of 447 patients. Among these 223 patients, 134 were confirmed to be with infected necrosis by a positive culture. The mortality rate was 15% (13/89) in the sterile necrosis group and 18% (24/134) in the infected necrosis group (P = 0.52). A multivariate analysis of death predictors indicated that bacteremia (odds ratio [OR] = 2.76, 95% confidence interval [CI], 1.23–5.46, P < 0.001), age (OR = 1.07, 95% CI, 1.03–1.11, P < 0.001), American Society of Anesthesiologists class (OR = 3.56, 95% CI, 1.65–7.18, P = 0.001), persistent organ failure in the first week (OR = 16.72, 95% CI, 7.04–32.56, P < 0.001), and pancreatic necrosis (OR = 1.73, 95% CI, 1.14–2.98, P = 0.008) were significant factors. Conclusions:Among patients with necrotizing pancreatitis, the effects of organ failure on mortality are more critical than those of infection. Bacteremia, age, American Society of Anesthesiologists class, persistent organ failure in the first week, and pancreatic necrosis were identified as the predictors of mortality.
Synergistic effect of quorum sensing genes in biofilm development and PAHs degradation by a marine bacterium

ABSTRACT Quorum sensing (QS) is a prevalently found intercellular signaling system in bacteria. QS system bestows behavioral coordination ability in bacteria at high population density. QS via acylated homoserine lactone (AHL) is extensively conserved in Gram-negative bacteria and plays crucial role in regulating many biological processes. The role of QS genes coding for AHL synthase enzyme (lasI and rhlI) was established in bioremediation of polycyclic aromatic hydrocarbons (PAHs) viz. phenanthrene and pyrene. AHL producing biofilm forming marine bacterium Pseudomonas aeruginosa N6P6 was isolated by selective enrichment on PAHs. AHL production was confirmed using AHL bioreporters and GC-MS analysis. Biofilm development and its architecture was significantly (P < 0.05) affected by alterations in lasI/rhlI expression. The lasI/rhlI gene expression pattern significantly influences biofilm formation and subsequent degradation of PAHs. The integrated density of Pseudomonas aeruginosa N6P6 biofilm was highest for 48 h old biofilm and the PAHs (phenanthrene and pyrene) degradation was also found maximum (85.6 % and 47.56 %) with this biofilm. A significant positive correlation (P < 0.05) was observed between lasI expression and PAHs degradation. The role of QS genes in biofilm formation and degradation of PAHs was validated by blocking the transcription of lasI/rhlI by a QS inhibitor (QSI) tannic acid. Further, application of such QS positive isolates in PAHs contaminated sites could be a promising strategy to improve the PAHs bioremediation.
Sperm competition and ejaculate economics

Sperm competition was identified in 1970 as a pervasive selective force in post‐copulatory sexual selection that occurs when the ejaculates of different males compete to fertilise a given set of ova. Since then, sperm competition has been much studied both empirically and theoretically. Because sperm competition often favours large ejaculates, an important challenge has been to understand the evolution of strategies through which males invest in sperm production and economise sperm allocation to maximise reproductive success under competitive conditions. Sperm competition mechanisms vary greatly, depending on many factors including the level of sperm competition, space constraints in the sperm competition arena, male mating roles, and female influences on sperm utilisation. Consequently, theoretical models of ejaculate economics are complex and varied, often with apparently conflicting predictions. The goal of this review is to synthesise the theoretical basis of ejaculate economics under sperm competition, aiming to provide empiricists with categorised model assumptions and predictions. We show that apparent contradictions between older and newer models can often be reconciled and there is considerable consensus in the predictions generated by different models. We also discuss qualitative empirical support for some of these predictions, and detail quantitative matches between predictions and observations that exist in the yellow dung fly. We argue that ejaculate economic theory represents a powerful heuristic to explain the diversity in ejaculate traits at multiple levels: across species, across males and within individual males. Future progress requires greater understanding of sperm competition mechanisms, quantification of trade‐offs between ejaculate allocation and numbers of matings gained, further knowledge of mechanisms of female sperm selection and their associated costs, further investigation of non‐sperm ejaculate effects, and theoretical integration of pre‐ and post‐copulatory episodes of sexual selection.
Assessing efficacy/effectiveness and safety/tolerability profiles of adjunctive pramipexole in bipolar depression: acute versus long-term data

Bipolar depression represents the most difficult-to-treat phase of bipolar disorder, mood-stabilizing compounds and second-generation antipsychotics being only partially effective, whereas the use of antidepressants is highly controversial because of risks of inefficacy, switching, rapid cycling, and increased suicidality. Among various augmentative pharmacological treatments, compounds with dopamine-enhancing activity have been shown to be variably beneficial in the treatment of bipolar depression with drug-resistance features. In particular, pramipexole – a dopamine D2/D3 receptor agonist – showed antidepressant properties in bipolar depressed patients in both randomized-controlled trials and open acute and follow-up reports. The present review aims to provide an updated perspective on the use of adjunctive pramipexole in bipolar depression, taking into account randomized-controlled trials, as well as open naturalistic studies, with a specific focus on the evaluation of acute versus long-term data in terms of effectiveness and tolerability. Despite methodological differences, short-term studies support the acute efficacy and tolerability/safety of adjunctive pramipexole, whereas open extended observations seem to confirm the effectiveness of the compound, with some additional concern in terms of safety and tolerability issues. Adjunctive pramipexole may be a valid option in both the acute and the long-term treatment of drug-resistant bipolar depression, with possible superior tolerability in the short term.
Functional studies of the small subunit of EcoHK31I DNA methyltransferase

Abstract EcoHK31I DNA methyltransferase recognizes the sequence 5′-YGGCCR-3′ and adds a methyl group to the fifth position of the internal cytosine to protect the DNA from cleavage by its cognate endonuclease. M.EcoHK31I is composed of polypeptides α and β. Polypeptide β only contains the conserved IX motif of the C5-MTase family, and provides a unique example to show that this motif alone may be dislocated to another polypeptide. By electromobility shift assay, we found that the α/β complex recognizes specific oligonucleotide substrates. Polypeptide α formed aggregates with DNA, while polypeptide β alone did not bind DNA. Therefore, polypeptide β assists in the proper binding of polypeptide α to DNA substrate. The complex of polypeptide α and a polypeptide β variant with an N-terminal deletion of 41 amino acids showed a 16-fold reduction in methylation activity. Further deletion resulted in an inactive methyltransferase. The dissociation equilibrium constant (K d) of the α/β complex was 56.4 nM, while the K d value for the α/ΔN46-polypeptide β complex was increased approximately 95-fold, caused by a drastic decrease in dissociate rate constant (k d) and an increase in the association rate constant (k a). This indicates that the N-terminal region of polypeptide β takes part in subunit interaction, while the C-terminal region is involved in DNA binding.
Preoperative Corticosteroid Oral Therapy and Intraoperative Bleeding during Functional Endoscopic Sinus Surgery in Patients with Severe Nasal Polyposis: A Preliminary Investigation

Objectives: The aim of the study was to investigate whether orally administered steroids might improve surgical field conditions during functional endoscopic sinus surgery. Methods: Total blood loss and visualization of the surgical field during the surgical procedure were compared in 2 groups of 18 patients each with severe nasal polyposis. The groups were similar in respect to age, body mass index, general health status, incidence of allergy, bronchial asthma, aspirin triad, and stage of disease. One group received 30 mg of prednisone daily for 5 consecutive days before the operation. The second group served as a control. Results: Although the total blood loss was only slightly less in the steroid group, the visual conditions of the surgical field improved significantly. Conclusions: Better surgical field conditions were the results of the powerful anti-inflammatory and antiedematous activity of the drug, which facilitated blood and secretion evacuation from the operated area and prevented the optic system from staining.
Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients

Background & objectives: Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent probe amplification (MLPA) techniques, many microdeletion/microduplication syndromes with DD/ID are now delineated. MLPA technique can probe 40-50 genomic regions in a single reaction and is being used for evaluation of cases with DD/ID. In this study we evaluated the clinical utility of MLPA techniques with different probe sets to identify the aetiology of unexplained mental retardation in patients with ID/DD. Methods: A total of 203 randomly selected DD/ID cases with/without malformations were studied. MLPA probe sets for subtelomeric regions (P070/P036) and common microdeletions/microduplications (P245-A2) and X-chromosome (P106) were used. Positive cases with MLPA technique were confirmed using either fluorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets. Results: The overall detection rate was found to be 9.3 per cent (19 out of 203). The detection rates were 6.9 and 7.4 per cent for common microdeletion/microduplication and subtelomeric probe sets, respectively. No abnormality was detected with probe set for X-linked ID. The subtelomeric abnormalities detected included deletions of 1p36.33, 4p, 5p, 9p, 9q, 13q telomeric regions and duplication of 9pter. The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome. Interpretation & conclusions: Our results show that the use of P245-A2 and P070/P036-E1 probes gives good diagnostic yield. Though MLPA cannot probe the whole genome like cytogenetic microarray, due to its ease and relative low cost it is an important technique for evaluation of cases with DD/ID.
Help seeking for mental health problems in an adolescent population: the effect of gender

Abstract Background: While the onset of many mental health problems occurs in adolescence, these problems are severely undertreated in this age group. To inform early intervention for adolescents, we investigated the effect of gender and education type on perception of barriers to help seeking, mental health literacy, and the awareness and use of mental health services. Method: A web-based survey using vignettes, open-ended and multiple choice items was administered to upper secondary school students in two counties in Norway. Results: The survey was completed by 1249 students (88% response rate) with an average age of 17.6 years and 56% were female. Compared to males, the females were better in identifying psychological problems of anxiety and trauma, awareness of mental health services (p < 0.001) and perceived more barriers for seeking help (cost and waiting time; p < 0.001). For use of all mental health services, the effect of education type was greater than the effect of gender. Conclusion: For adolescents, gender appears to play a significant, but not exclusive, role in the inclination to seek professional help for mental health problems. We hypothesise that the observed gender difference in use of services is related to the gender difference in awareness of referral pathway services and the influence of parents in help-seeking process.
Patient-Centered Care and Outcomes

Patient-centered care (PCC) has been studied for several decades. Yet a clear definition of PCC is lacking, as is an understanding of how specific PCC processes relate to patient outcomes. We conducted a systematic review of the PCC literature to examine the evidence for PCC and outcomes. Three databases were searched for all years through September 2012. We retained 40 articles for the analysis. Results found mixed relationships between PCC and clinical outcomes, that is, some studies found significant relationships between specific elements of PCC and outcomes but others found no relationship. There was stronger evidence for positive influences of PCC on satisfaction and self-management. Future research should examine specific dimensions of PCC and how they relate to technical care quality, particularly some dimensions that have not been studied extensively. Future research also should identify moderating and mediating variables in the PPC–outcomes relationship.
Effect of genetic variation on therapy with angiotensin converting enzyme inhibitors or angiotensin receptor blockers in dialysis patients.

INTRODUCTION The role of interaction of polymorphisms in the Renin-Angiotensin-System (RAS) with angiotensin converting enzyme (ACE) or angiotensin receptor (AGTR1) inhibitors (RAS inhibitors) is unknown, as is the role of such therapy in end stage renal disease (ESRD) patients. METHODS We enrolled all 445 prevalent patients with diabetic nephropathy receiving maintenance hemodialysis in 30 centers in Southern Germany from August 1999 to January 2000 for prospective survival analysis until December 2003. Blood pressure and medication was recorded at inclusion. We determined survival specific for allelic variants of the ACE (insertion/deletion), Angiotensinogen (M235T) and AGTR1 (A1166C) genes. The effect of therapy with RAS inhibitors at study inclusion was determined for the allelic variants of each gene. The primary end point was all cause mortality (ACM). RESULTS For all polymorphisms, and for therapy with RAS inhibitors there was no significant effect on survival in the complete collective (n = 445), though there was an insignificant trend for improved survival in patients on AGTR1 antagonists. Increased ACM risk was associated with treatment with RAS inhibitors only in patients homozygous for the wild type AGTR1 1166A allele (HR 1.65, p = 0.01). For all other polymorphisms, therapy with RAS inhibitors had no significant effect on ACM, irrespective of genotype. Similar results were obtained in patients with systolic ventricular dysfunction. CONCLUSION Our data do not show a survival advantage for type 2 diabetes hemodialysis patients receiving RAS inhibiting therapy. In addition, our data indicate that allelic variation in RAS genes and pharmacogenetic interaction with RAS inhibition does not affect mortality risk in diabetic hemodialysis patients.