Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancing Practice Improvement by Facilitating Practitioner Interactivity: New Roles for Providers of Continuing Medical Education

&NA; Research into networking and interactivity among practitioners is providing new information that has the potential to enhance the effectiveness of practice improvement initiatives. This commentary reviews the evidence that practitioner interactivity can facilitate emergent learning and behavior change that lead to practice improvements. Insights from learning theories provide a framework for understanding emergent learning as the product of interactions between individuals in trusted relationships, such as occurs in communities of practice. This framework helps explain why some groups respond more favorably to improvement initiatives than others. Failure to take advantage of practitioner interactivity may explain in part the disappointingly low mean rates of practice improvement reported in studies of the effectiveness of practice improvement projects. Examples of improvement models in primary care settings that explicitly use relationship building and facilitation techniques to enhance practitioner interactivity are provided. Ingredients of a curriculum to teach relationship building in communities of practice and facilitation skills to enhance learning in small group education sessions are explored. Sufficient evidence exists to support the roles of relationships and interactivity in practice improvement initiatives such that we recommend the development of training programs to teach these skills to CME providers.
Flourishing of employees in a fast moving consumable goods environment

The aim of this study was to validate a scale that measures flourishing in a work and organisational context. A cross-sectional survey design was used with a stratified random sample of 779 employees in an alcoholic beverage company in South Africa. The Flourishing-at-Work Scale was administered. The results supported a three-factor model of flourishing in a work and organisational context, consisting of emotional, psychological, and social well-being. Emotional well-being includes job satisfaction, positive affect, and low negative affect. Psychological well-being comprises autonomy, competence, relatedness, engagement, purpose and meaning, and learning. Social well-being includes social acceptance, social growth, social contribution, social coherence, and social integration. The Flourishing-at-Work Scale showed configural, metric, and scalar invariance in a calibration sample. The reliabilities of the 10 subscales were highly acceptable. The highest mean frequencies on flourishing dimensions were obtained for competence and work engagement. The lowest mean frequencies were obtained for job satisfaction and meaningful work.
Learning Label-Specific Features and Class-Dependent Labels for Multi-Label Classification

Binary Relevance is a well-known framework for multi-label classification, which considers each class label as a binary classification problem. Many existing multi-label algorithms are constructed within this framework, and utilize identical data representation in the discrimination of all the class labels. In multi-label classification, however, each class label might be determined by some specific characteristics of its own. In this paper, we seek to learn label-specific data representation for each class label, which is composed of label-specific features. Our proposed method LLSF can not only be utilized for multi-label classification directly, but also be applied as a feature selection method for multi-label learning and a general strategy to improve multi-label classification algorithms comprising a number of binary classifiers. Inspired by the research works on modeling high-order label correlations, we further extend LLSF to learn class-Dependent Labels in a sparse stackingway, denoted as LLSF-DL. It incorporates both second-order- and high-order label correlations. A comparative study with the state-of-the-art approaches manifests the effectiveness and efficiency of our proposed methods.
Identification of Functionally Important Domains in the N-Terminal Region of Telomerase Reverse Transcriptase

ABSTRACT Telomerase is a ribonucleoprotein reverse transcriptase responsible for the maintenance of one strand of telomere terminal repeats. The key protein subunit of the telomerase complex, known as TERT, possesses reverse transcriptase-like motifs that presumably mediate catalysis. These motifs are located in the C-terminal region of the polypeptide. Hidden Markov model-based sequence analysis revealed in the N-terminal region of all TERTs the presence of four conserved motifs, named GQ, CP, QFP, and T. Point mutation analysis of conserved residues confirmed the functional importance of the GQ motif. In addition, the distinct phenotypes of the GQ mutants suggest that this motif may play at least two distinct functions in telomere maintenance. Deletion analysis indicates that even the most N-terminal nonconserved region of yeast TERT (N region) is required for telomerase function. This N region exhibits a nonspecific nucleic acid binding activity that probably reflects an important physiologic function. Expression studies of various portions of the yeast TERT inEscherichia coli suggest that the N region and the GQ motif together may constitute a stable domain. We propose that all TERTs may have a bipartite organization, with an N-GQ domain connected to the other motifs through a flexible linker.
Hydrodynamic advantages of swimming by salp chains

Salps are marine invertebrates comprising multiple jet-propelled swimming units during a colonial life-cycle stage. Using theory, we show that asynchronous swimming with multiple pulsed jets yields substantial hydrodynamic benefit due to the production of steady swimming velocities, which limit drag. Laboratory comparisons of swimming kinematics of aggregate salps (Salpa fusiformis and Weelia cylindrica) using high-speed video supported that asynchronous swimming by aggregates results in a smoother velocity profile and showed that this smoother velocity profile is the result of uncoordinated, asynchronous swimming by individual zooids. In situ flow visualizations of W. cylindrica swimming wakes revealed that another consequence of asynchronous swimming is that fluid interactions between jet wakes are minimized. Although the advantages of multi-jet propulsion have been mentioned elsewhere, this is the first time that the theory has been quantified and the role of asynchronous swimming verified using experimental data from the laboratory and the field.
The Nematic Phases of Bent-Core Liquid Crystals

Over the last ten years, the nematic phases of liquid crystals formed from bent-core structures have provoked considerable research because of their remarkable properties. This Minireview summarises some recent measurements of the physical properties of these systems, as well as describing some new data. We concentrate on oxadiazole-based materials as exemplars of this class of nematogens, but also describe some other bent-core systems. The influence of molecular structure on the stability of the nematic phase is described, together with progress in reducing the nematic transition temperatures by modifications to the molecular structure. The physical properties of bent-core nematic materials have proven difficult to study, but patterns are emerging regarding their optical and dielectric properties. Recent breakthroughs in understanding the elastic and flexoelectric behaviour are summarised. Finally, some exemplars of unusual electric field behaviour are described.
Optimized Methods to Explore the Mechanistic and Biomarker Potential of Hepatocyte-Derived Exosomes in Drug-Induced Liver Injury

Recent evidence supports that alterations in hepatocyte-derived exosomes (HDE) may play a role in the pathogenesis of drug-induced liver injury (DILI). HDE-based biomarkers also hold promise to improve the sensitivity of existing in vitro assays for predicting DILI liability. Primary human hepatocytes (PHH) provide a physiologically relevant in vitro model to explore the mechanistic and biomarker potential of HDE in DILI. However, optimal methods to study exosomes in this culture system have not been defined. Here we use HepG2 and HepaRG cells along with PHH to optimize methods for in vitro HDE research. We compared the quantity and purity of HDE enriched from HepG2 cell culture medium by 3 widely used methods: ultracentrifugation (UC), OptiPrep density gradient ultracentrifugation (ODG), and ExoQuick (EQ)-a commercially available exosome precipitation reagent. Although EQ resulted in the highest number of particles, UC resulted in more exosomes as indicated by the relative abundance of exosomal CD63 to cellular prohibitin-1 as well as the comparative absence of contaminating extravesicular material. To determine culture conditions that best supported exosome release, we also assessed the effect of Matrigel matrix overlay at concentrations ranging from 0 to 0.25 mg/ml in HepaRG cells and compared exosome release from fresh and cryopreserved PHH from same donor. Sandwich culture did not impair exosome release, and freshly prepared PHH yielded a higher number of HDE overall. Taken together, our data support the use of UC-based enrichment from fresh preparations of sandwich-cultured PHH for future studies of HDE in DILI.
Complement and cytokine response in acute Thrombotic Thrombocytopenic Purpura

Complement dysregulation is key in the pathogenesis of atypical Haemolytic Uraemic Syndrome (aHUS), but no clear role for complement has been identified in Thrombotic Thrombocytopenic Purpura (TTP). We aimed to assess complement activation and cytokine response in acute antibody‐mediated TTP. Complement C3a and C5a and cytokines (interleukin (IL)‐2, IL‐4, IL‐6, IL‐10, tumour necrosis factor, interferon‐γ and IL‐17a) were measured in 20 acute TTP patients and 49 remission cases. Anti‐ADAMTS13 immunoglobulin G (IgG) subtypes were measured in acute patients in order to study the association with complement activation. In acute TTP, median C3a and C5a were significantly elevated compared to remission, C3a 63·9 ng/ml vs. 38·2 ng/ml (P < 0·001) and C5a 16·4 ng/ml vs. 9·29 ng/ml (P < 0·001), respectively. Median IL‐6 and IL‐10 levels were significantly higher in the acute vs. remission groups, IL‐6: 8 pg/ml vs. 2 pg/ml (P = 0·003), IL‐10: 6 pg/ml vs. 2 pg/ml (P < 0·001). C3a levels correlated with both anti‐ADAMTS13 IgG (rs = 0·604, P = 0·017) and IL‐10 (rs = 0·692, P = 0·006). No anti‐ADAMTS13 IgG subtype was associated with higher complement activation, but patients with the highest C3a levels had 3 or 4 IgG subtypes present. These results suggest complement anaphylatoxin levels are higher in acute TTP cases than in remission, and the complement response seen acutely may relate to anti‐ADAMTS13 IgG antibody and IL‐10 levels.
Biofilm Producing Salmonella Typhi: Chronic Colonization and Development of Gallbladder Cancer

Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention.
Inclusion of Multiple Fragment Types in the Site Identification by Ligand Competitive Saturation (SILCS) Approach

The site identification by ligand competitive saturation (SILCS) method identifies the location and approximate affinities of small molecular fragments on a target macromolecular surface by performing molecular dynamics (MD) simulations of the target in an aqueous solution of small molecules representative of different chemical functional groups. In this study, we introduce a set of small molecules to map potential interactions made by neutral hydrogen bond donors and acceptors and charged donor and acceptor fragments in addition to nonpolar fragments. The affinity pattern is obtained in the form of discretized probability or, equivalently, free energy maps, called FragMaps, which can be visualized with the target surface. We performed SILCS simulations for four proteins for which structural and thermodynamic data is available for multiple diverse ligands. Good overlap is shown between high affinity regions identified by the FragMaps and the crystallographic positions of ligand functional groups with similar chemical functionality, thus demonstrating the validity of the qualitative information obtained from the simulations. To test the ability of FragMaps in providing quantitative predictions, we calculate the previously introduced ligand grid free energy (LGFE) metric and observe its correspondence with experimentally measured binding affinity. LGFE is computed for different conformational ensembles and improvement in prediction is shown with increasing ligand conformational sampling. Ensemble generation includes a Monte Carlo sampling approach that uses the GFE FragMaps directly as the energy function. The results show that some but not all experimental trends are predicted and warrant improvements in the scoring methodology. In addition, the potential utility of atom-based free energy contributions to the LGFE scores and the use of multiple ligands in SILCS to identify displaceable water molecules during ligand design are discussed.
Being Present: Focusing on the Present Predicts Improvements in Life Satisfaction But Not Happiness

Mindfulness theorists suggest that people spend most of their time focusing on the past or future rather than the present. Despite the prevalence of this assumption, no research that we are aware of has evaluated whether it is true or what the implications of focusing on the present are for subjective well-being. We addressed this issue by using experience sampling to examine how frequently people focus on the present throughout the day over the course of a week and whether focusing on the present predicts improvements in the 2 components of subjective well-being over time—how people feel and how satisfied they are with their lives. Results indicated that participants were present-focused the majority of the time (66%). Moreover, focusing on the present predicted improvements in life satisfaction (but not happiness) over time by reducing negative rumination. These findings advance our understanding of how temporal orientation and well-being relate.
Frontal networks in adults with autism spectrum disorder

Autism spectrum disorder (ASD) is proposed to reflect atypical connectivity between higher-order association areas. Using diffusion imaging, Catani et al. reveal associations between ASD and white matter abnormalities of the frontal lobe, and suggest that the condition is linked to aberrant developmental trajectories of frontal networks that persist in adulthood.
Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans

The 18kDa Translocator Protein (TSPO) is the most commonly used tissue-specific marker of inflammation in positron emission tomography (PET) studies. It is expressed in myeloid cells such as microglia and macrophages, and in rodent myeloid cells expression increases with cellular activation. We assessed the effect of myeloid cell activation on TSPO gene expression in both primary human and rodent microglia and macrophages in vitro, and also measured TSPO radioligand binding with 3H-PBR28 in primary human macrophages. As observed previously, we found that TSPO expression increases (∼9-fold) in rodent-derived macrophages and microglia upon pro-inflammatory stimulation. However, TSPO expression does not increase with classical pro-inflammatory activation in primary human microglia (fold change 0.85 [95% CI 0.58–1.12], p = 0.47). In contrast, pro-inflammatory activation of human monocyte-derived macrophages is associated with a reduction of both TSPO gene expression (fold change 0.60 [95% CI 0.45–0.74], p = 0.02) and TSPO binding site abundance (fold change 0.61 [95% CI 0.49–0.73], p < 0.0001). These findings have important implications for understanding the biology of TSPO in activated macrophages and microglia in humans. They are also clinically relevant for the interpretation of PET studies using TSPO targeting radioligands, as they suggest changes in TSPO expression may reflect microglial and macrophage density rather than activation phenotype.
Robust Detection of EGFR Copy Number Changes and EGFR Variant III: Technical Aspects and Relevance for Glioma Diagnostics

Epidermal growth factor receptor (EGFR) is commonly affected in cancer, generally in the form of an increase in DNA copy number and/or as mutation variants [e.g., EGFR variant III (EGFRvIII), an in‐frame deletion of exons 2–7]. While detection of EGFR aberrations can be expected to be relevant for glioma patients, such analysis has not yet been implemented in a routine setting, also because feasible and robust assays were lacking.
Left-Ventricular Structure in the Southall And Brent REvisited (SABRE) Study: Explaining Ethnic Differences

Cardiometabolic risk is elevated in South Asians and African Caribbeans compared with Europeans, yet whether this is associated with ethnic differences in left-ventricular structure is unclear. Conventional M-mode or 2-dimensional echocardiography may be misleading, because they calculate left-ventricular mass and remodeling using geometric assumptions. Left-ventricular structure was compared in a triethnic population-based cohort using conventional and 3-dimensional echocardiography on 895 individuals (aged 55–85 years; 427 European, 325 South Asian, 143 African Caribbean). Left-ventricular mass was indexed, and left-ventricle remodeling index and relative wall thickness were calculated. Anthropometry, blood pressure, and fasting bloods were measured. Three-dimensional left-ventricular mass index did not differ between Europeans (mean±SE, 29.8±0.3 g/m2.7) and African Caribbeans (29.9±0.5 g/m2.7; P=0.9), but it was significantly lower in South Asians (28.1±0.4 g/m2.7; P<0.0001) compared with Europeans. These findings persisted on multivariate adjustment. In contrast, conventional left-ventricle mass index was significantly higher in African Caribbeans (46.4±0.9 g/m2.7) than in Europeans (41.9±0.5 g/m2.7; P<0.0001). Left-ventricle remodeling index was the highest in African Caribbeans and the lowest in South Asians. Relative wall thickness was also higher in African Caribbeans, but no different in South Asians, compared with Europeans. Differences in left-ventricle remodeling index were attenuated by adjustment for cardiometabolic factors between African Caribbeans and Europeans only. In conclusion, left-ventricular mass is lower in South Asians and equivalent in African Caribbeans compared with Europeans, even when cardiometabolic risk factors are accounted for. Left-ventricular remodeling rather than hypertrophy may explain the increased risk of heart failure in people of African Caribbean origin.
Using Tree Diagrams without Numerical Values in Addition to Relative Numbers Improves Students’ Numeracy Skills

Background. Physicians and medical students may lack sufficient numeracy skills to make treatment decisions, interpret test results, and practice evidence-based medicine. We evaluated whether the use of a tree diagram without numerical values as an aid for numerical processing might improve students’ test results when dealing with percentages. Methods. A prospective randomized study was carried out with 102 third-year students. Participants received 3 diagnostic test problems and were asked to determine positive predictive values. The information in these tests was expressed either in (1) natural frequencies, (2) conditional probabilities, or (3) conditional probabilities with a tree diagram without numbers. Results. Ninety-eight (96.1%) complete data sets could be obtained. The group working with natural frequencies achieved significantly higher test results (n = 29, mean score: 1.1, P = 0.045) than the group working with conditional probabilities (n = 34, mean score: 0.56). The students who were given a tree diagram in addition to conditional probabilities (n = 35, mean score: 1.26) also achieved significantly better scores than the group with conditional probabilities alone (P = 0.008). The difference between the group who had received natural frequencies and the group working with conditional probabilities and the tree diagram was not significant. Conclusions. We suggest the use of a tree diagram as a visual aid when dealing with diagnostic tests expressed in conditional probabilities.
Hardware Transactional Memory Supporting I/O Operations within Transactions

I/O operation within transactions is one of the challenges for hardware transactional memory. This paper analyses the problem of I/O operations within transactions, and proposes a hardware transactional memory system architecture based on multi-core processor and current cache coherent mechanisms. The system supports execution of transactions by adding transactional buffer and related hardware and software. I/O operations within transactions are implemented by partial commit based on commit-lock, and blocking / waking-up of transactional threads. The solution solves or avoids the problems that I/O operations within transactions faced, including rollback, transaction migration and transactional buffer overflow. The system has been implemented by simulation. Its performance is evaluated by five benchmark applications. Simulation results show that the transactional programs executed in our system outperformed traditional lock-based programs.
Human platelet antigen 1 (HPA 1) genotyping with 5′ nuclease assay and sequence‐specific primers reveals a single nucleotide deletion in intron 2 of the HPA 1a allele of platelet glycoprotein IIIa

Summary. We have established a 5′ nuclease assay (5′ NA) for human platelet antigen (HPA) 1a/b allelic discrimination. The assay is based on the simultaneous amplification and detection of the two targets in a one‐tube system. The results are read optically, immediately after termination of the polymerase chain reaction (PCR), and no post‐PCR processing is necessary. This genotyping procedure is less time‐consuming and cheaper than our conventional sequence‐specific primer PCR (SSP‐PCR), which is run as a two‐tube test, with verification of the results after electrophoresis in agarose gel. The reduction of analytical steps, simplification of the procedure and potential for automation were important advantages for our choice of system. This test system is more suitable for large‐scale testing and fits better for our screening programme for HPA 1bb determination. DNA from 1093 individuals were tested in parallel with the SSP‐PCR and the 5′ NA. One thousand and ninety‐one samples gave identical results in SSP‐PCR and 5′ NA. Upon repeated testing, two samples consistently came out as HPA 1bb in SSP‐PCR and HPA 1ab in 5′ NA. DNA sequencing revealed a defect located in an intronic area that corresponds to the consensus primer used for the SSP‐PCR HPA 1a typing.