Miracle-dz/UniFAR-FTUs huggingface dataset:
BRAF in the cross-hairs

ABSTRACT Introduction: Hairy cell leukemia (HCL) is a rare, chronic B-cell lymphoproliferative disorder characterized by distinctive morphologic features and an indolent clinical course. The discovery of a recurrent activating mutation in BRAF (BRAF V600E) as a disease-defining genetic event in HCL has substantial diagnostic and therapeutic implications. Areas covered: Herein the authors review the role of BRAF V600E and RAF-MEK-ERK signaling in the pathogenesis of HCL, anecdotal clinical reports of BRAF inhibitor monotherapy in management of relapsed or refractory HCL, larger phase 2 trials investigating efficacy of BRAF inhibitor therapy for HCL, adverse effects commonly associated with BRAF inhibitor therapy, including cutaneous toxicity, and mechanisms of therapeutic resistance. Expert opinion: Ongoing and planned studies will help to optimize the use of BRAF inhibitor therapy for HCL by determining the efficacy of BRAF inhibition in combination with other antigen targeted or molecularly targeted therapies, and more broadly, to determine how hematologists can best utilize and sequence emerging diagnostic and therapeutic modalities in the care of patients with newly diagnosed and relapsed or refractory HCL.
Genetic and epigenetic alteration of the programmed cell death 1 in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease where both genetics and epigenetics are contributing factors. In order to discover genetic and epigenetic associations with RA and its phenotypes, we analysed RNA expression, DNA variations and DNA methylation of programmed cell death 1 (PDCD1) in a cohort of RA patients and healthy controls.
NOX5: Molecular biology and pathophysiology

What is the topic of this review? This review provides a comprehensive overview of Nox5 from basic biology to human disease and highlights unique features of this Nox isoform What advances does it highlight? Major advances in Nox5 biology relate to crystallization of the molecule and new insights into the pathophysiological role of Nox5. Recent discoveries have unravelled the crystal structure of Nox5, the first Nox isoform to be crystalized. This provides new opportunities to develop drugs or small molecules targeted to Nox5 in an isoform‐specific manner, possibly for therapeutic use. Moreover genome wide association studies (GWAS) identified Nox5 as a new blood pressure‐associated gene and studies in mice expressing human Nox5 in a cell‐specific manner have provided new information about the (patho) physiological role of Nox5 in the cardiovascular system and kidneys. Nox5 seems to be important in the regulation of vascular contraction and kidney function. In cardiovascular disease and diabetic nephropathy, Nox5 activity is increased and this is associated with increased production of reactive oxygen species and oxidative stress implicated in tissue damage.
NAPPFAST: An Internet System for the Weather-Based Mapping of Plant Pathogens.

In recent years, the number of exotic pest introductions has increased rapidly as a result of increased volume of trade (22). The serious and sometimes irreparable ecological and economic damage of exotic pathogens, such as Cryphonectria parasitica, Ophiostoma novo-ulmi, and Phytophthora ramorum, the causal agents of chestnut blight, Dutch elm disease, and Sudden Oak Death, respectively, are amply documented (1,6,42). An estimate of annual losses for exotic plant pathogens is $21 billion dollars (32). The Plant Protection and Quarantine (PPQ) (Sidebar 1) division within the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (USDA-APHIS) has the goal of safeguarding agriculture and natural resources from the risks associated with the entry, establishment, and spread of exotic pathogens. Two important components of the APHIS-PPQ mission are risk analysis and pest detection. A key goal of the risk analysis program is to identify exotic pest pathways and to assess the risks these exotic pests pose to plants and plant products as well as to the environment. Three types of risk assessments that evaluate the probability of the introduction and establishment of exotic plant pests are pathway analysis, organism pest risk assessment, and commodity risk assessment. The PPQ pest detection program and its state cooperators provide a continuum of pest surveillance, from offshore preclearance programs through port inspections, to surveys in rural and urban sites across the United States. The Center for Plant Health Science and Technology (CPHST) and the Cooperative Agricultural Pest Survey (CAPS) programs are instrumental in APHIS-PPQ’s pest detection programs. CAPS is responsible for supplying a means of detection, documentation, and rapid dissemination of information regarding the survey of regulated significant plant pests and weeds in the United States. The survey information gathered by CAPS is entered into a central database known as National Agricultural Pest Information System (NAPIS). CPHST, headquartered in Raleigh, NC, is a multi-program scientific support organization for PPQ. One way CPHST scientists help facilitate the APHIS-PPQ activities of risk analysis and pest detection is by mapping the potential introduction and establishment of exotic pathogens in the United States. These maps are the result of pathogen-specific information analyses, including climate, pathogen distribution, host distribution, and trade. Given its influence on pest phenology, reproduction, dispersion, and overwintering survival, climate is a critical component for the geographic assessment of potential pathogen distribution. A large number of climate-based risk mapping systems, such as CLIMEX, BIOCLIM, and GARP, have been used for pest risk analysis (3,10,38,44). Literature typically focuses on the development and/or evaluation of the best modeling techniques (10); however, often the quality of the inputs, including biological parameters, weather
Novel cutaneous mediators of chemical allergy

Abstract Chemical allergy can manifest into allergic contact dermatitis and asthma and the importance of skin sensitization in both of these diseases is increasingly being recognized. Given the unique characteristics of chemical allergy, coupled with the distinct immunological microenvironment of the skin research is still unraveling the mechanisms through which sensitization and elicitation occur. This review first describes the features of chemical sensitization and the known steps that must occur to develop a chemical allergy. Next, the unique immunological properties of the skin - which may influence chemical sensitization - are highlighted. Additionally, mediators involved with the development of allergy are reviewed, starting with early ones - including the properties of haptens, skin integrity, the microbiome, the inflammasome, and toll-like receptors (TLR). Novel cellular mediators of chemical sensitization are highlighted, including innate lymphoid cells, mast cells, T-helper (TH) cell subsets, and skin intrinsic populations including γδ T-cells and resident memory T-cells. Finally, this review discusses two epigenetic mechanisms that can influence chemical sensitization, microRNAs and DNA methylation. Overall, this review highlights recent research investigating novel mediators of chemical allergy that are present in the skin. It also emphasizes the need to further explore these mediators to gain a better understanding of what makes a chemical an allergen, and how best to prevent the development of chemical-induced allergic diseases.
On the Limits of the Precautionary Principle

The precautionary principle (PP) is an influential principle of risk management. It has been widely introduced into environmental legislation, and it plays an important role in most international environmental agreements. Yet, there is little consensus on precisely how to understand and formulate the principle. In this article I prove some impossibility results for two plausible formulations of the PP as a decision‐rule. These results illustrate the difficulty in making the PP consistent with the acceptance of any tradeoffs between catastrophic risks and more ordinary goods. How one interprets these results will, however, depend on one's views and commitments. For instance, those who are convinced that the conditions in the impossibility results are requirements of rationality may see these results as undermining the rationality of the PP. But others may simply take these results to identify a set of purported rationality conditions that defenders of the PP should not accept, or to illustrate types of situations in which the principle should not be applied.
A methodological comparison of risk scores versus decision trees for predicting drug-resistant infections: A case study using extended-spectrum beta-lactamase (ESBL) bacteremia

Abstract Background: Timely identification of multidrug-resistant gram-negative infections remains an epidemiological challenge. Statistical models for predicting drug resistance can offer utility where rapid diagnostics are unavailable or resource-impractical. Logistic regression–derived risk scores are common in the healthcare epidemiology literature. Machine learning–derived decision trees are an alternative approach for developing decision support tools. Our group previously reported on a decision tree for predicting ESBL bloodstream infections. Our objective in the current study was to develop a risk score from the same ESBL dataset to compare these 2 methods and to offer general guiding principles for using each approach. Methods: Using a dataset of 1,288 patients with Escherichia coli or Klebsiella spp bacteremia, we generated a risk score to predict the likelihood that a bacteremic patient was infected with an ESBL-producer. We evaluated discrimination (original and cross-validated models) using receiver operating characteristic curves and C statistics. We compared risk score and decision tree performance, and we reviewed their practical and methodological attributes. Results: In total, 194 patients (15%) were infected with ESBL-producing bacteremia. The clinical risk score included 14 variables, compared to the 5 decision-tree variables. The positive and negative predictive values of the risk score and decision tree were similar (>90%), but the C statistic of the risk score (0.87) was 10% higher. Conclusions: A decision tree and risk score performed similarly for predicting ESBL infection. The decision tree was more user-friendly, with fewer variables for the end user, whereas the risk score offered higher discrimination and greater flexibility for adjusting sensitivity and specificity.
Fine Cellulosic Materials Produced from Chemical Pulp: the Combined Effect of Morphology and Rate of Addition on Paper Properties

Among bio-based reinforcement additives for paper existing on the market, microfibrillated cellulose (MFC) turned out to be a promising material, showing outstanding potential in composites science. Its relevance in papermaking as a new family of paper components was suggested more recently. There remains a number of constraints limiting the promotion of their use in papermaking, mostly related to their high cost and effect on dewatering resistance. Also, contrasting results reported in the literature suggest that the effect of fibrillation rate and quantity of such cellulosic additives in a furnish on the technological paper properties needs further research. The purpose of this study is to produce and characterize different MFC-like fine fibrous materials of varying particle size and degree of fibrillation from the same batch of pulp through mechanical treatment or fractionation. The effect of the thus obtained fine fibrous materials on paper properties is evaluated with respect to their concentration within a fiber furnish. We compared: (i) a mixture of primary and secondary fines isolated from the pulp by means of a purpose-built laboratory pressure screen; (ii) MFC-like fine fibrous materials of increasingly fibrillar character obtained by refining and subsequent steps of high-pressure homogenization. The morphology of the different materials was first characterized using flow cell based and microscopic techniques. The thus obtained materials were then applied in handsheet forming in blends of different proportions to evaluate their influence on paper properties. The results of these experiments indicate that all these products lead to a substantial decrease in air permeability and to improved mechanical properties already at low concentration, independent of the type and morphological character of the added fine cellulosic material. At higher addition rates, only highly fibrillated materials allowed a further considerable increase in tensile and z-strength. These observations should help to allow a more targeted application of this new generation of materials in papermaking, depending on the desired application.
Elevated homocysteine level and prognosis in patients with acute coronary syndrome: a meta-analysis

Abstract Objective: Controversial results exist with respect to the association between elevated homocysteine level and adverse prognosis in acute coronary syndrome (ACS) patients. We performed a meta-analysis to evaluate the prognostic value of homocysteine level on ACS patients. Materials and methods: A comprehensive literature search of PubMed and Embase databases was conducted prior to August 2018. Prospective observational studies reporting the association of baseline homocysteine level with major adverse cardiovascular events (MACE), cardiovascular or all-cause mortality in ACS patients were selected. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CI) were calculated for the highest versus the lowest homocysteine level. Results: Ten studies including 4120 ACS patients were identified. ACS patients with the highest homocysteine level had an increased risk of MACE (RR 2.01; 95% CI 1.53–2.64) and all-cause mortality (RR 2.05; 95% CI 1.50–2.79) after controlling confounding factors. However, the association between elevated homocysteine level and cardiovascular mortality (RR 1.08; 95% CI 0.83–1.39) was not statistically significant. Conclusions: Elevated homocysteine level was associated with an increased risk of MACE and all-cause mortality among ACS patients. However, the association of elevated homocysteine level with cardiovascular mortality in ACS patients should be further confirmed in future studies.
Association of Ethnic Identity with Oral Health Knowledge, Attitudes, Behavior, and Outcomes on the Navajo Nation

Abstract:American Indians and Alaska Natives (AI/ANs) experience poor oral health. Children and adults living on the Navajo Nation have a particularly high rate of dental decay. The literature suggests that health outcomes are often associated with the strength of one's ethnic identity. We investigated the association of ethnic identity among Native parents with oral health knowledge, attitudes, behavior, and outcomes. Analyses used baseline data from a randomized controlled trial designed to reduce dental decay among AI/AN preschoolers enrolled in the Navajo Nation Head Start Program. Greater perceived importance of ethnic identity was associated with better oral health knowledge and attitudes but was unassociated with oral health behavior and was linked to worse oral health status. Parents who were better able to speak their tribal language had greater confidence in their ability to manage their children's oral health, engaged in better oral health behavior, and reported better parental oral health status.
Femininity, masculinity, and body image in a community-based sample of lesbian and bisexual women

ABSTRACT This study expands the literature on body image among lesbian and bisexual women by examining the relationship between self-perceived gendered personality traits and expressions (i.e., sense of self in relation to cultural constructions of femininity and masculinity) and body satisfaction, a key body image construct. We used data from Wave 3 (2010–2012) of the Chicago Health and Life Experiences of Women (CHLEW) study. The CHLEW includes a novel measure of gender expression, with masculinity and femininity as distinct but overlapping constructs. In the large analytic sample (N = 553), we found both similarities and differences in the association between femininity/masculinity and body image in lesbian and bisexual women. Bisexual women reported significantly lower body satisfaction than lesbian women. Higher masculinity was associated with greater body satisfaction in the full sample, but the association was stronger for bisexual than lesbian women. Femininity was positively associated with body satisfaction only for bisexual women. These findings suggest that masculinity and femininity play different roles in body satisfaction for lesbian and bisexual women and highlight the importance of disaggregating sexual identity in studies of sexual minority women’s health. Clinicians should routinely ask about sexual identity and gender expression, especially when presenting concerns involve body image or disordered eating.
Assessing speech perception in children with language difficulties: Effects of background noise and phonetic contrast

Abstract Deficits in speech perception are reported for some children with language impairments. This deficit is more marked when listening against background noise. This study investigated the speech perception skills of young children with and without language difficulties. A speech discrimination task, using non-word minimal pairs in an XAB paradigm, was presented to 20 5–7-year-old children with language difficulties and 33 typically-developing (TD) children aged between 4– to 7-years. Stimuli were presented in quiet and in background noise (babble), and stimuli varied in phonetic contrasts, differing in either place of articulation or presence/absence of voicing. Children with language difficulties performed less well than TD children in all conditions. There was an interaction between group and noise condition, such that children with language difficulties were more affected by the presence of noise. Both groups of children made more errors with one voicing contrast /s z/ and there was some indication that children with language difficulties had proportionately greater difficulty with this contrast. Speech discrimination scores were significantly correlated with language scores for children with language difficulties. Issues in developing material for assessment of speech discrimination in children with LI are discussed.
Compliance with OIE animal welfare standards in slaughterhouses in Tehran Province, Iran: An introductory survey

ABSTRACT World Organization for Animal Health (OIE) recommends member countries to comply with global standards of animal welfare. The present study was conducted to reveal the compliance of animal welfare standards in slaughterhouses in Tehran province (Iran). The following three major parameters were evaluated through direct observation, study of plant records, and interviewing slaughterhouse staff across all 14 operative animal slaughterhouses in Tehran province: (1) employing trained and committed workers; (2) appropriate environment and proper design parameter; and (3) proper construction, equipment, and tools. Only 30% of modern slaughterhouses employed trained personnel for handling livestock in an appropriate way, which reaches zero for traditional slaughterhouses. Regarding electrical stunning application for sheep, animal welfare quality was significantly greater in modern slaughterhouses than in the traditional ones (P < 0.05). Out of nine slaughterhouses with unloading platforms and animal lairage, 55% and 35.7% were found to comply with standards, respectively. Concerning lairage parameters and entrance hall, modern plants stood higher compared to traditional slaughterhouses (P > 0.05). It is recommended training courses for involved veterinarians and slaughterhouse staff along with upgrading slaughterhouse construction.
Global Typhoid Fever Incidence: A Systematic Review and Meta-analysis

Abstract Background Contemporary incidence estimates of typhoid fever are needed to guide policy decisions and control measures and to improve future epidemiological studies. Methods We systematically reviewed 3 databases (Ovid Medline, PubMed, and Scopus) without restriction on age, country, language, or time for studies reporting the incidence of blood culture–confirmed typhoid fever. Outbreak, travel-associated, and passive government surveillance reports were excluded. We performed a meta-analysis using a random-effects model to calculate estimates of pooled incidence, stratifying by studies that reported the incidence of typhoid fever and those that estimated incidence by using multipliers. Results Thirty-three studies were included in the analysis. There were 26 study sites from 16 countries reporting typhoid cases from population-based incidence studies, and 17 sites in 9 countries used multipliers to account for underascertainment in sentinel surveillance data. We identified Africa and Asia as regions with studies showing high typhoid incidence while noting considerable variation of typhoid incidence in time and place, including in consecutive years at the same location. Overall, more recent studies reported lower typhoid incidence compared to years prior to 2000. We identified variation in the criteria for collecting a blood culture, and among multiplier studies we identified a lack of a standardization for the types of multipliers being used to estimate incidence. Conclusions Typhoid fever incidence remains high at many sites. Additional and more accurate typhoid incidence studies are needed to support country decisions about typhoid conjugate vaccine adoption. Standardization of multiplier types applied in multiplier studies is recommended.
Accordance of Adolescent and Parental Ratings of Internet Gaming Disorder and Their Associations with Psychosocial Aspects

In 2013, Internet gaming disorder (IGD) was incorporated in the DSM-5. In 2018, the World Health Organization (WHO) confirmed the inclusion of the new diagnosis "Gaming disorder" in the ICD-11. Both IGD and Gaming disorder refer to a problematic use of video games. Yet, IGD has thus far only been assessed by self-ratings, while external ratings have not been available. We adapted a frequently used screening tool for IGD (Internet Gaming Disorder Scale, IGDS) to a parental rating (Parental version of the Internet Gaming Disorder Scale, PIGDS) and evaluated its psychometric properties. Data were collected in 1,970 face-to-face interviews (with 985 parents and 985 related adolescents) using a standardized questionnaire measuring adolescent IGD by self- and parental ratings and frequency of gaming, psychopathological burden, hyperactivity/inattention, family functioning, and school performance. Furthermore, we determined the accordance of adolescent and parental ratings for IGD. We conducted a confirmatory factor analysis, correlation analyses, and have determined reliability and concordance. We observed a one-dimensional factor structure of the PIGDS and its internal consistency was 0.86. We found very first indications of criterion validity for the PIGDS. The correlation between IGDS and PIGDS was 0.78 and we observed kappa coefficients between both ratings of 0.62 and 0.61 (based on the most suitable cutoff points for the PIGDS). Both adolescent and parental ratings of IGD were consistently associated with higher psychopathological burden, stronger hyperactivity/inattention, poorer family functioning, and poorer school performance. According to the results, a parental assessment of IGD in adolescence seems to be a promising new approach and it opens a new perspective in the exploration of IGD.