In order to best conserve, as well as utilize, traditional apple germplasm in Norway, an apple heritage cultivar collection was established in Ullensvang, western Norway, which aims to become the National Clonal Germplasm Repository. The establishment of the apple heritage cultivar collection was preceded by a molecular study that aimed to genotype a large number of apple accessions maintained in various ex situ sites in western and south-eastern Norway, using a rather small set of eight SSR markers. However limited, the marker set managed to identify synonyms, homonyms, and duplicates within and among the investigated collections. In this study, 171 apple accessions from the Ullensvang apple heritage cultivar collection were genotyped using a set of 20 different SSR markers. Approximately half of the accessions have been previously genotyped using eight SSR markers, enabling an assessment of whether the use of a larger marker set would yield a more accurate characterization. Based on the obtained molecular data, the apple heritage cultivar collection was determined to hold a key part of the overall genetic diversity of the Norwegian apple germplasm. Furthermore, the twelve additional SSR markers were able to differentiate several accessions groups originally thought to be synonyms, as well as to provide a more detailed insight into the genetic structure of this germplasm.

Introduction In one third of all patients with epilepsy, seizure freedom is not achieved through anti-seizure medication (ASM). These patients have an increased risk of earlier death, poorer cognitive development, and reduced quality of life. Cenobamate (CNB) has recently been approved as a promising novel ASM drug for the treatment of adults with focal-onset epilepsy. However, there is little experience for its application in pediatric patients. Methods In a multicenter study we evaluated retrospectively the outcome of 16 pediatric patients treated “off label” with CNB. Results In 16 patients with a mean age of 15.38 years, CNB was started at an age of 15.05 years due to DRE. Prior to initiation of therapy, an average of 10.56 (range 3–20) ASM were prescribed. At initiation, patients were taking 2.63 (range 1–4) ASM. CNB was increased by 0.47 ± 0.27mg/kg/d every 2 weeks with a mean maximum dosage of 3.1 mg/kg/d (range 0.89–7) and total daily dose of 182.81 mg (range 50–400 mg). Seizure freedom was achieved in 31.3% and a significant seizure reduction of >50% in 37.5%. Adverse events occurred in 10 patients with fatigue/somnolence as the most common. CNB is taken with high adherence in all but three patients with a median follow-up of 168.5 days Conclusion Cenobamate is an effective ASM for pediatric patients suffering from drug-resistant epilepsy. In addition to excellent seizure reduction or freedom, it is well-tolerated. Cenobamate should be considered as a novel treatment for DRE in pediatric patients.

It is well established that academic performance (AP) depends on a number of factors, such as intellectual capacities, practice, and previous knowledge. We know little about how these factors interact as they are rarely measured simultaneously. Here we present mediated-Factors of Academic Performance (m-FAP) model, which simultaneously assesses direct and indirect, mediated, effects on AP. In a semester-long study with 118 first-year college students, we show that intelligence and working memory only indirectly influenced AP on a familiar, less challenging college course (Introduction to Psychology). Their influence was mediated through previous knowledge and self-regulated learning activities akin to deliberate practice. In a novel and more challenging course (Statistics in Psychology), intellectual capacities influenced performance both directly and indirectly through previous knowledge. The influence of deliberate practice, however, was considerably weaker in the novel course. The amount of time and effort that the students spent on the more difficult course could not offset the advantage of their more intelligent and more knowledgeable peers. The m–FAP model explains previous contradictory results by providing a framework for understanding the extent and limitations of individual factors in AP, which depend not only on each other, but also on the learning context.

ABSTRACT

The Electronic Medical Record (EMR) provides an opportunity to manage patient care efficiently and accurately. This includes clinical decision support tools for the timely identification of adverse events or acute illnesses preceded by deterioration. This paper presents a machine learning-driven tool developed using real-time EMR data for identifying patients at high risk of reaching critical conditions that may demand immediate interventions. This tool provides a pre-emptive solution that can help busy clinicians to prioritize their efforts while evaluating the individual patient risk of deterioration. The tool also provides visualized explanation of the main contributing factors to its decisions, which can guide the choice of intervention. When applied to a test cohort of 18,648 patient records, the tool achieved 100% sensitivity for prediction windows 2–8 h in advance for patients that were identified at 95%, 85% and 70% risk of deterioration.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease with a variety of symptoms such as post-exertional malaise, fatigue, and pain, but where aetiology and pathogenesis are unknown. An increasing number of studies have implicated the involvement of the immune system in ME/CFS. Furthermore, a hereditary component is suggested by the reported increased risk for disease in relatives, and genetic association studies are being performed to identify potential risk variants. We recently reported an association with the immunologically important human leucocyte antigen (HLA) genes HLA-C and HLA-DQB1 in ME/CFS. Furthermore, a genome-wide genetic association study in 42 ME/CFS patients reported significant association signals with two variants in the T cell receptor alpha (TRA) locus (P value <5 × 10−8). As the T cell receptors interact with the HLA molecules, we aimed to replicate the previously reported findings in the TRA locus using a large Norwegian ME/CFS cohort (409 cases and 810 controls) and data from the UK biobank (2105 cases and 4786 controls). We investigated numerous SNPs in the TRA locus, including the two previously ME/CFS-associated variants, rs11157573 and rs17255510. No associations were observed in the Norwegian cohort, and there was no significant association with the two previously reported SNPs in any of the cohorts. However, other SNPs showed signs of association (P value <0.05) in the UK Biobank cohort and meta-analyses of Norwegian and UK biobank cohorts, but none survived correction for multiple testing. Hence, our research did not identify any reliable associations with variants in the TRA locus.

In this article, authors attempt to provoke the need of renewed understanding and researching related to the mythologization of the Balkans in Postmodern period. In the midpoint of this article is postmodern critic of international experts for legitimacy in ‘new state democracy’ (for example Bosnia and Herzegovina). Authors will try to make distinction between what is reality on the ground and what is the desirable model of Bosnia and Herzegovina for Europe. Regardless of various processes that are ongoing in Bosnia and Herzegovina, it is not possible to move away from mythological narratives and concepts

The purpose of this article is to introduce to the literature a new extension of the Simple WISP method adapted for utilizing the triangular fuzzy numbers. This extension is proposed to allow the use of the Simple WISP method for addressing decision-making problems related to uncertainties and inaccuracies, as well as for solving problems related to predictions. In addition, this article also discusses the use of linguistic variables to collect the attitudes of the respondents, as well as their transformation into appropriate triangular fuzzy numbers. The article discusses the use of two defuzzification procedures. The first normalization procedure is easy to use, while the second procedure uses the advantages that the application of asymmetric fuzzy numbers gives in terms of analysis. The usability of the proposed extension is presented through two examples.

Background and Objectives Very poor outcome despite IV thrombolysis (IVT) and mechanical thrombectomy (MT) occurs in approximately 1 of 4 patients with ischemic stroke and is associated with a high logistic and economic burden. We aimed to develop and validate a multivariable prognostic model to identify futile recanalization therapies (FRTs) in patients undergoing those therapies. Methods Patients from a prospectively collected observational registry of a single academic stroke center treated with MT and/or IVT were included. The data set was split into a training (N = 1,808, 80%) and internal validation (N = 453, 20%) cohort. We used gradient boosted decision tree machine learning models after k-nearest neighbor imputation of 32 variables available at admission to predict FRT defined as modified Rankin scale 5–6 at 3 months. We report feature importance, ability for discrimination, calibration, and decision curve analysis. Results A total of 2,261 patients with a median (interquartile range) age of 75 years (64–83 years), 46% female, median NIH Stroke Scale 9 (4–17), 34% IVT alone, 41% MT alone, and 25% bridging were included. Overall, 539 (24%) had FRT, more often in MT alone (34%) as compared with IVT alone (11%). Feature importance identified clinical variables (stroke severity, age, active cancer, prestroke disability), laboratory values (glucose, C-reactive protein, creatinine), imaging biomarkers (white matter hyperintensities), and onset-to-admission time as the most important predictors. The final model was discriminatory for predicting 3-month FRT (area under the curve 0.87, 95% CI 0.87–0.88) and had good calibration (Brier 0.12, 0.11–0.12). Overall performance was moderate (F1-score 0.63 ± 0.004), and decision curve analyses suggested higher mean net benefit at lower thresholds of treatment (up to 0.8). Conclusions This FRT prediction model can help inform shared decision making and identify the most relevant features in the emergency setting. Although it might be particularly useful in low resource healthcare settings, incorporation of further multifaceted variables is necessary to further increase the predictive performance.

Peste des petits ruminants (PPR) is an acute disease of small ruminants caused by a morbillivirus. Clinical observation of the disease in the field revealed that several species of small ruminants are affected to varying degrees. This difference in disease-related effects could depend either on the host or on the virulence of the virus strain. A previous study highlighted the difference in virulence between two strains of PPRV used to infect Saanen goats. For this breed, PPRV Morocco 2008 strain (MA08) was highly virulent while PPRV Côte d’Ivoire 1989 (IC89) strain induced mild disease. Experimental studies generally based on healthy and young animals do not permit exploration of the natural variability of the host susceptibility to PPRV. Therefore, building on the previous study on Saanen goats, the current study focussed on this breed of goat and used commercially available animals with an unknown history of infection with other pathogens. Results confirmed the previous disease pattern for PPRV IC89 and MA08 strains. Viral RNA detection, macroscopic and histological lesions were stronger for the highly virulent MA08 strain. We show here for the first time that viral RNA can be detected in the tissues of vaccinated animals. Viral RNA was also detected for the first time in serum samples, which is in agreement with the role of circulating immune cells in transporting the virus into host target organs. Thus, this study provides insight into the pathogenesis of strains of different virulence of PPRV and will help to better understand the onset of the disease.

BACKGROUND: Stenosis of the carotid arteries, as a consequence of atherosclerosis is the most common cause of cerebrovascular insult (CVI). Severe (>70%) contralateral stenosis or occlusion (SCSO) of the carotid artery may represent an additional pre-operative risk factor  for neurologic incidents.             AIM: The aim of this study was to confirm and compare early perioperative results (0-30 days) of carotid endarterectomy (CEA) in patients with and without SCSO.                 PATIENT AND METHODS: In our retrospective-prospective study, we analysed the results of 273 CEA, divided into two groups based on the presence of significant contralateral stenosis or occlusion (non-SCSO and SCSO groups)             RESULTS: 273 CEA’s were performed, divided into two groups: SCSO groups 40 (14.7%) and non-SCSO group 233 (85.3%). Between the two groups, a statistically significant difference between patients was found (54.1% compared to 87.5%; p<0.0005), CEA with patch angioplasty (25.3% compared to 52.5%; p=0.001),  and CEA with the use of a shunt (3.9% compared to 35%; p<0.0005) in favour of the SCSO group. There was no statistically significant difference (SCSO was not identified as a risk factor) for any type of stroke or mortality. Logistically regression confirmed SCSO to be an independent predictor of 30-day mortality (OR 21.58; 95% CI  1.27-36.3; p= 0.033) and any type of stroke or mortality (OR 9.27; 95% CI  1.61-53.22; p= 0.012). SCSO was not a predictor of any type of stroke within 30 days. Predictors of any type of stroke was dyslipidemia (OR 0.12, 95% CI  0.02-0.76; p= 0.024).             CONCLUSIONS: There was no statistically significant difference in the incidence of early (30 day) perioperative complications between the analysed groups. The percentage of perioperative complications remains within the accepted parameters, and thus, SCSO should not be qualified as a significant risk factor for CEA. We are of the opinion that CEA remains a safe and acceptable options for patients with SCSO, and SCSO should not be a reason for preferential use of carotid stenting.

In recent years, it has been shown that gastrointestinal microflora has a substantial impact on the development of a large number of chronic diseases. The imbalance in the number or type of microbes in the gastrointestinal tract can lead to diseases and conditions, including autism spectrum disorder, celiac disease, Crohn’s disease, diabetes, and small bowel cancers. This can occur as a result of genetics, alcohol, tobacco, chemotherapeutics, cytostatics, as well as antibiotic overuse. Due to this, essential taxa can be lost, and the host’s metabolism can be severely affected. A less known condition called small intestine bacterial overgrowth (SIBO) can be seen in patients who suffer from hypochlorhydria and small intestine cancers. It is characterized as a state in which the bacterial population in the small intestine exceeds 105–106 organisms/mL. The latest examination methods such as double-balloon enteroscopy and wireless capsule endoscopy have the potential to increase the accuracy and precision of diagnosis and provide better patient care. This review paper aims to summarize the effect of the gastrointestinal environment on chronic disease severity and the development of cancers.

A graph is locally irregular if the degrees of the end-vertices of every edge are distinct. An edge coloring of a graph G is locally irregular if every color induces a locally irregular subgraph of G. A colorable graph G is any graph which admits a locally irregular edge coloring. The locally irregular chromatic index X'irr(G) of a colorable graph G is the smallest number of colors required by a locally irregular edge coloring of G. The Local Irregularity Conjecture claims that all colorable graphs require at most 3 colors for a locally irregular edge coloring. Recently, it has been observed that the conjecture does not hold for the bow-tie graph B, since B is colorable and requires at least 4 colors for a locally irregular edge coloring. Since B is a cactus graph and all non-colorable graphs are also cacti, this seems to be a relevant class of graphs for the Local Irregularity Conjecture. In this paper we establish that X'irr(G)<= 4 for all colorable cactus graphs.