Miracle-dz/UniFAR-FTUs huggingface dataset:
What Has Been the Effect on Trial Outcome Assessments of a Decade of Patient Participation in OMERACT?

Objective. Since 2002, 58 patients have participated as collaborating partners in 6 Outcome Measures in Rheumatology (OMERACT) conferences. Little is known about how they engage with researchers and how they have influenced conference outcomes. Methods. A responsive evaluation was carried out, including a thematic document analysis of conference proceedings and gray literature, participant observation, and 38 interviews with patients and professionals representing research, industry, and regulators. Interview transcripts were subjected to an inductive content analysis. Results. The role of patients has evolved from a single focus group in 2002 to full integration in all parts of the conference in 2012. Longterm engagement has made a significant change in the scope and conduct of rheumatology research. It has enriched the research agenda by identifying previously neglected outcome domains such as fatigue, sleep disturbances, and flares, and it has contributed to more patient-relevant outcomes in clinical trials. Facilitating factors have been a strong commitment of the leadership, adequate selection procedure, inclusive conference design, interactive and encouraging moderation style, and self-organized support. The intensity of the program and doubts regarding the representativeness of the patient group were still seen as challenges for the future. Conclusion. Making patient participation an integral part of the vision and procedures of OMERACT has significantly contributed to the success of OMERACT. It has changed the perceptions and beliefs of many participants. Full use of patients’ experiential knowledge before and during the conference is still challenging.
Utility Scale Applications of Energy Storage

Power system operating conditions that are on the verge of being unsafe have encouraged utilities and power consumers to look for bulk energy storage systems. Various energy storage systems (ESSs) have excellent records and have been used for decades. This paper provides an overview of different energy storage technologies and their possible applications in power systems. The purpose of this analysis is to highlight combinations of technologies and applications with the highest benefit for the owner of the ESS. The analysis shows that frequency regulation and integration of renewables are the applications that most likely will be asked for by utilities in the future. Technologies which are most suitable for these applications include thermo-electric energy storage and batteries. These are technologies which are not restricted by their geographic footprint and offer payback times of five to ten years.
Comparative effectiveness of recommended versus less intensive drug combinations in secondary prevention of acute coronary syndrome

The secondary prevention treatment for acute coronary syndrome (ACS) is based on the combined use of drugs from four therapeutic classes (beta‐blockers, antiplatelet agents, statins, and angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers). The objective of this study was to compare the long‐term effectiveness of the recommended therapeutic combination with those of incomplete combinations in secondary prevention of ACS.
Detection of Dementia Cases in Two Swedish Health Registers: A Validation Study

Background: Population-based health registers are potential assets in epidemiological research; however, the quality of case ascertainment is crucial. Objective: To compare the case ascertainment of dementia, from the National Patient Register (NPR) and the Cause of Death Register (CDR) with dementia diagnoses from six Swedish population based studies. Methods: Sensitivity, specificity, and positive predictive value (PPV) of dementia identification in NPR and CDR were estimated by individual record linkage with six Swedish population based studies (n = 19,035). Time to detection in NPR was estimated using data on dementia incidence from longitudinal studies with more than two decades of follow-up. Results: Barely half of the dementia cases were ever detected by NPR or CDR. Using data from longitudinal studies we estimated that a record with a dementia diagnosis appears in the NPR on average 5.5 years after first diagnosis. Although the ability of the registers to detect dementia cases was moderate, the ability to detect non-dementia cases was almost perfect (99%). When registers indicate that there is a dementia diagnosis, there are very few instances in which the clinicians determined the person was not demented. Indeed, PPVs were close to 90%. However, misclassification between dementia subtype diagnoses is quite common, especially in NPR. Conclusions: Although the overall sensitivity is low, the specificity and the positive predictive value are very high. This suggests that hospital and death registers can be used to identify dementia cases in the community, but at the cost of missing a large proportion of the cases.
Comparison of papilla healing following sulcular full-thickness flap and papilla base flap in endodontic surgery.

AIM To compare the loss of papilla height when using the papilla base incision (PBI) or the standard papilla mobilization incision in marginal full-thickness flap in cases with no evidence of marginal periodontitis. METHODOLOGY Twelve healthy patients referred for surgical treatment of persisting apical periodontitis, who were free from periodontal disease and had intact interdental papillae, were included in the study. The preoperative papilla height was recorded by measuring the distance between a reproducible coronal point on the tooth and the most coronal point of the papilla. The flap design consisted of two releasing incisions connected by a horizontal incision. The marginal incision involved the complete mobilization of the entire papilla in one interproximal space, and the PBI in the other interproximal space. The PBI consisted of a shallow first incision at the base of the papilla and a second incision directed to the crestal bone creating a split thickness flap in the area of the papilla base. Further, apically, a full-thickness flap was raised. In the other interproximal space, the buccal papilla was carefully incised and elevated completely. Following flap retraction, standard root-end resection and root-end filling were performed. Flap closure was achieved with microsurgical sutures. The PBI was sutured with two to three interrupted sutures (size 7/0) and the elevated papilla was reapproximated with vertical mattress sutures, which were removed 3-5 days after the surgery. The height of the interdental papilla was evaluated preoperatively and postoperatively after 1 month and at the 3-month recall, using plaster replicas. The loss of papilla height was measured using a laser scanner. Twelve papilla-paired sites were evaluated. The results were statistically analysed using the t-test. RESULTS Complete closure of the wound was achieved in all treated sites followed by uneventful healing in all patients. The total mobilization of the papilla resulted in loss of papilla height of 1.10 +/- 0.71 mm at 1 month and 1.25 +/- 0.81 mm at the 3-month recall. At the 3-month recall, the retraction had increased in nine sites, whereas in three sites, the loss of height had slightly diminished compared to 1 month. In contrast, after the PBI, only minor changes could be detected: 0.07 +/- 0.09 mm at 1 month and 0.10 +/- 0.15 mm at 3 months. There was a significant difference between the two incision techniques studied (P < 0.007). CONCLUSIONS In patients with healthy marginal periodontal conditions, the PBI allows rapid and predictable recession-free healing, whereas complete mobilization of the papilla led to a marked loss of the papilla height. In aesthetically relevant areas, the use of the PBI is recommended, to avoid opening of the interproximal space, when periradicular surgical treatment is necessary.
β-catenin and Gli1 are prognostic markers in glioblastoma

Glioblastomas (GBMs), the most common primary malignancies of the central nervous system, are highly aggressive and heterogeneous, and remain a dramatic therapeutic challenge. Markers mirroring the complex molecular profile of GBMs that are predictive of patient outcomes are needed to define novel multi-targeted treatment strategies. Resistance to current GBM therapies is partly due to a subpopulation of stem-like and other self-renewing cells (hereafter called glioma stem-like cancer cells, GSCC), which are therefore of key interest as therapeutic entry points. Wnt and Hedgehog are among the main pathways involved in GSCC renewal. β-catenin and Gli1 are markers of Wnt and Hedgehog activation respectively and both pathways are known to be altered in gliomas. To date, there are no investigations of Gli1 protein expression in GBM tissue, and recently a high expression of β-catenin has been found to have a poor prognostic impact in GBM patients in a study. We have therefore quantified the positivity for β-catenin, Gli1, as well as Ki-67, p53, and EGFR proteins on immunohistochemically-stained GBM sections from 106 patients in an investigation for potential predictive biomarkers. Correlation between these markers and survival was evaluated by pair-wise Pearson correlation coefficient and by bi-dimensional hierarchical clustering, followed by survival estimations using linear regression models and classification trees. We demonstrated that both β-catenin and, for the first time, Gli1 proteins are highly predictive markers of short survival, being found in 75 and 90% of the highly predictive trees, respectively, whereas Ki-67, p53 and EGFR were under 30% and thus, not considered as predictive. Our results indicate a role of β-catenin and Gli1 in GBM malignant behaviour, and suggest that inhibiting members of Wnt and Hedgehog pathways could be a valuable therapeutic strategy for GBM patients. See commentary: A magnifying glass on glioblastoma stem cell signaling pathways
Obesity, metabolic syndrome and sleep apnoea: all pro‐inflammatory states

Obesity is associated with significant morbidity and mortality and is increasing in prevalence worldwide. Associated conditions include insulin resistance (IR), diabetes, hypertension and dyslipidaemia; a clustering of these has recently been termed as metabolic syndrome. Weight gain is a major predictor of the metabolic syndrome with waist circumference being a more sensitive indicator than body mass index as it reflects both abdominal subcutaneous adipose tissue and visceral adipose tissue (VAT). VAT has more metabolic activity and secretes a number of hormones and pro‐inflammatory cytokines which are linked with the metabolic abnormalities listed above. Central obesity also increases the risk of obstructive sleep apnoea syndrome (OSAS), where the sleep disordered breathing may also independently lead to/or exacerbate IR, diabetes and cardiovascular risk. The contribution of OSAS to the metabolic syndrome has been under‐recognized. The putative mechanisms by which OSAS causes or exacerbates these other abnormalities are discussed. We propose that activation of nuclear factor kappa B by stress hypoxia and/or by increased adipokines and free fatty acids released by excess adipose tissue is the final common inflammatory pathway linking obesity, OSAS and the metabolic syndrome both individually and, in many cases, synergistically.
Six kinds of anti-phospholipid antibodies (aPLs) in ovulatory mucus and seminal plasma from couples with repeated miscarriages.

OBJECTIVE Determination of aPLs in ovulatory mucus and in seminal plasma in 18 infertile couples (women, median age 33.2, range 28-39 years; men, median age 36.4, range 29-46 years) with repeated unexplained miscarriages (four to nine spontaneous abortions). Women with high levels of aPLs in sera were excluded from the study. METHODS aPL screening included cardiolipin (Sevac Prague), L-alpha-phosphatidic acid, L-alpha-phosphatidylethanolamine, L-alpha-phosphatidyl-DL-glycerol, L-alpha-phosphatidylinositol, and L-alpha-phosphatidyl/serine (Sigma, USA). These were determined in isotypes IgG and IgA by an ELISA method. Statistical analysis of aPL results was made by cut-off levels of aPLs for both Ig isotypes by using 3 SD or 95th percentile calculated by STATGRAPHICS. Control group was created from four fertile healthy couples. RESULTS Levels of aPLs in ovulatory cervical mucus were in the majority very low, except for IgA-aPLs-inositol. Very high interindividual differences in aPLs were found in seminal plasma. IgA-aPL-ethanolamine and -DL-glycerol, and IgG-aPL-L-serine and -DL-glycerol predominated in seminal plasma. Extremely high IgA levels of aPLs in all above-mentioned antigens, except cardiolipin, were found in one man of an infertile couple. CONCLUSION The passage of abnormal aPLs levels from seminal plasma into the site of conception during often repeated, unprotected intercourses is supported by the findings.
The role of the Ca2+‐sensitive tyrosine kinase Pyk2 and Src in thrombin signalling in rat astrocytes

We have recently demonstrated that multiple signalling pathways are involved in thrombin‐induced proliferation in rat astrocytes. Thrombin acts by protease‐activated receptor‐1 (PAR‐1) via mitogen‐activated protein kinase activity. Signalling includes both Gi/(βγ subunits)–phosphatidylinositol 3‐kinase and a Gq‐phospholipase C/Ca2+/protein kinase C (PKC) pathway. In the present study, we investigated the possible protein tyrosine kinases which might be involved in thrombin signalling cascades. We found that, in astrocytes, thrombin can evoke phosphorylation of proline‐rich tyrosine kinase (Pyk2) via PAR‐1. This process is dependent on the increase in intracellular Ca2+ and PKC activity. Moreover, in response to thrombin stimulation Pyk2 formed a complex with Src tyrosine kinase and adapter protein growth factor receptor‐bound protein 2 (Grb2), which could be coprecipitated. Furthermore, both thrombin‐induced Pyk2 phosphorylation and extracellular signal‐regulated kinase (ERK) 1/2 phosphorylation can be attenuated by Src kinase inhibitor 4‐amino‐5‐(4‐chlorophenyl)‐7‐(t‐butyl)pyrazolo[3,4‐d]pyrimidine. From these data we conclude that PAR‐1 uses Ca2+‐ and PKC‐dependent Pyk2 to activate Src, thereby leading to ERK1/2 activation, which predominantly recruits Grb2 in rat astrocytes.
Reporter gene transformation of the trunk disease pathogen Phaeomoniella chlamydospora and biological control agent Trichoderma harzianum

The economically important trunk disease pathogen Phaeomoniella chlamydospora causes Petri disease in Vitis vinifera and is also associated with the Esca trunk disease complex. Not much is known about the pathogen’s epidemiology and interactions with the grapevine host, other trunk disease pathogens and biological control agents such as Trichoderma harzianum. Reporter gene labelling of plant pathogens and biocontrol agents can facilitate host-pathogen-biocontrol interaction studies. Therefore, the first aim of this study was to stably transform T. harzianum strain T77 and a South African isolate of P. chlamydospora with the Green fluorescent protein (GFP) and the Red fluorescent protein (DsRed-Express) reporter genes. Several stably transformed reporter gene labelled transformants were obtained for both fungi. The second aim was to evaluate these transformants and their respective wild type isolates for several in vitro biological characteristics, virulence (P. chlamydospora) and host colonisation (T. harzianum) on hydroponically grown grapevine cuttings. Additionally, a previously described New Zealand P. chlamydospora GFP transformant (pCT74-P7) and its wild type isolate were also biologically characterised. In vitro biological and virulence characteristics of P. chlamydospora transformants did not vary much from their respective wild type isolates. In vitro biological characterisation of T. harzianum transformants showed that one of the transformants exhibited a faster growth rate at lower temperatures. Nonetheless, characterisation of its host colonisation ability on grapevine cuttings showed no difference when compared with another transformant and the wild type isolate. All Trichoderma isolates showed differential colonisation of grapevine cultivars Chenin Blanc and Merlot.
Recombinant human activated protein C in the treatment of severe sepsis: An evidence-based review

Objective:In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for recombinant human activated protein C that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. Design:The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. Methods:The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. Conclusion:Recombinant human activated protein C is recommended in patients at high risk of death (septic shock, sepsis-induced acute respiratory distress syndrome, Acute Physiology and Chronic Health Evaluation II score of ≥25, and sepsis-induced multiorgan failure) and no absolute contraindication related to bleeding risk or relative contraindication that outweighs the potential benefit. The presence or absence of disseminated intravascular coagulation should not influence the decision to administer recombinant human activated protein C. Heparin should be withheld during administration of recombinant human activated protein C.
Minor Myocardial Damage and Prognosis: Are Spontaneous and Percutaneous Coronary Intervention–Related Events Different?

Background—The relevance of the adverse prognostic implications of CK-MB elevation after percutaneous coronary intervention (PCI) remains controversial. Therefore, we compared the relationship between the level of postprocedural CK-MB elevation and 6-month mortality in patients undergoing PCI with the relationship between the level of spontaneous, non–PCI-related CK-MB elevation and 6-month mortality in patients with acute coronary syndromes (ACS) treated medically. Methods and Results—In the PURSUIT trial, 5583 of 9461 patients who presented with a non–ST-elevation ACS did not undergo PCI or CABG and had at least 1 CK-MB sample collected during index-hospitalization. There was a gradual increase in 6-month mortality with higher CK-MB levels: 4.1%, 8.6%, 9.0%, 14.3%, 15.5% for CK-MB ratios 0 to 1, >1 to 3, >3 to 5, >5 to 10, and >10 times the upper limit of normal. A combined analysis in 8838 patients undergoing PCI in 5 large, clinical trials revealed a proportional relationship between postprocedural CK-MB levels (≤48 hours after PCI) and 6-month mortality. In patients with CK-MB ratios 0 to 1, >1 to 3, >3 to 5, >5 to 10, and >10, the risk of death was 1.3%, 2.0%, 2.3%, 4.3%, and 7.4%, respectively. The absolute mortality rates were lower after procedure-related infarcts compared with spontaneous infarcts. Yet, the relative increase in 6-month mortality with each increase in peak CK-MB level was similar for PCI-related myocardial necrosis and spontaneous myocardial necrosis, as all tests for heterogeneity of the odds ratios were nonsignificant. Conclusions—The present analysis indicates that the adverse prognostic implications of periprocedural myocardial necrosis should be considered similar to the adverse consequences of spontaneous myocardial necrosis.
Initial development of a work-related assessment of dysexecutive syndrome: the Complex Task Performance Assessment.

UNLABELLED This article describes the initial development of the Complex Task Performance Assessment (CTPA) as a work-related assessment of dysexecutive syndrome. METHODS A cross-sectional case-control pilot study using the Complex Task Performance Assessment (CTPA) and a neuropsychological battery consisting of subtests from the Delis Kaplan Executive Function System (DKEFS) were used with a population of adults with mild stroke and a control group of healthy community participants (n = 9). RESULTS A correlation matrix between the DKEFS and the CTPA found no significant relationships between overall performance efficiency on the CTPA compared to the DKEFS scaled scores. In contrast, four of the six variables tested on the CTPA were found to have significant differences between the mild stroke group and the controls (p < 0.05). CONCLUSION The sensitivity of the CTPA in this pilot sample justifies future study to provide a link between traditional neuropsychological assessment and rehabilitation professionals' observation of performance related to return to work. Neuroperformance assessment such as the CTPA will provide clinicians with a way to identify dysexecutive syndrome and higher-level cognitive processing deficits in the context of care.
Short‐term treatment using insulin‐like growth factor‐1 (IGF‐1) improves life expectancy of the delta‐sarcoglycan deficient hamster

The hamster strain CHF147 presents a progressive dilated cardiomyopathy (DCM) due to a large deletion of the delta‐sarcoglycan gene that leads to heart failure. This cardiomyopathy induces premature death. We have previously shown that a short‐term treatment using IGF‐1 preserves cardiac structure and improves function of the CHF147 hamster.
Platelet tetraspanin complexes and their association with lipid rafts

Summary Tetraspanins are a superfamily of integral membrane proteins that facilitate the organization of membrane and intracellular signaling molecules into dynamic signaling microdomains, tetraspaninenriched microdomains (TEMs). Four tetraspanin family members have been identified in platelets: CD9, CD151 and TSSC6, which are constitutively associated with αIIb3, and CD63, which is present on granule membranes in resting platelets and associates with αIIbβ3-CD9 following platelet activation. CD63 and CD9 associate with a type II phosphatidylinositol 4-kinase, PI4K55, in both resting and activated platelets. Immunoelectron microscopic studies showed co-localization of CD63 and PI4K55 on internal membranes of resting platelets and on the filopodia of thrombin-activated platelets. Because TEMs in malignant cell lines appear to be distinct from prototypic lipid rafts, this study examined whether CD63-PI4K55 and CD9-PI4K55 complexes were resident in platelet-lipid rafts, or formed distinct microdomains. CD63, CD9 and PI4K55 were recovered from low-density membrane fractions (LDMFs) of sucrose gradients following platelet lysis in Brij 35, but unlike lipidraft proteins were not insoluble in Triton X-100, being absent from LDMFs of platelets lysed with Triton. In cubation of platelets with methyl-β-cyclodextrin, to deplete cholesterol and disrupt lipid rafts, shifted the complexes to higher density sucrose gradient fractions, but did not disrupt the tetraspanin-PI4K55 complexes. These results demonstrate that tetraspanin complexes in platelets form cholesterol-associated microdomains that are distinct from lipid rafts. It is probable thatTEMs and lipid rafts associate under certain conditions, resulting in the close proximity of distinct sets of signaling molecules, facilitating signal transduction.