Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone and bone marrow disruption by endocrine‐active substances

Bone is a multifaceted dynamic tissue, involved in mobility, mineral metabolism, and mesenchymal or stromal and hematopoietic progenitor or stem cells breading. Recently, an endocrine role has been attributed to bone due to its ability to produce at least two hormones (osteocalcin and fibroblast growth factor 23) and to participate directly or indirectly in leptin, insulin, estrogens, and serotonin signaling; regulation; and action. Also, bearing in mind the enormous amounts of substances secreted by the different bone marrow cell types, it becomes understandable the contribution of bone tissue to systemic homeostasis. Besides, bone is a well‐known estrogen‐responsive tissue, reacting to environmental influences. Thus, it has been coined as a critical target of environmental xenoestrogens, known as endocrine‐disrupting chemicals (EDCs). The exposure to EDCs results to disruption or imbalance of the systemic hormonal regulation of the skeleton including bone modeling and remodeling, local hormones, and cytokine or chemokine release. The present report highlights the harmful EDCs effects on bone tissue and provides up‐to‐date information of xenoestrogen action on proliferation, maturation, and homing of bone marrow inhabitants.
Using Genetic Variants in the Targets of Lipid Lowering Therapies to Inform Drug Discovery and Development: Current and Future Treatment Options

Mendelian randomization studies and “human knock‐out” studies of rare loss‐of‐function coding variants suggest that plasma levels of low‐density lipoprotein‐cholesterol LDL‐C, triglycerides (TGs), and lipoprotein(a) (Lp(a)) are causally associated with the risk of cardiovascular disease, and, therefore, therapies directed against these targets should reduce the risk of cardiovascular events. However, several therapies directed against these targets have failed to reduce the risk of cardiovascular events in large‐scale randomized trials, thus suggesting that causality is not sufficient evidence to establish genetic target validation. Instead, the critical question that needs to be answered to improve drug discovery and development is how much a causal biomarker needs to be changed to produce a clinically meaningful benefit in a short‐term trial. This review describes how to use naturally randomized genetic evidence to accurately anticipate the results of randomized trials evaluating current and future lipid lowering therapies, inform the design of randomized trials, and transform the drug discovery and development process.
Do what you say and say what you are going to do: A preliminary meta-analysis of client change and sustain talk subtypes in motivational interviewing

Abstract Objective: This meta-analysis examines the predictive validity of client change language subtypes in motivational interviewing (MI) sessions addressing addictive behavior change. Method: A systematic review identified k = 13 primary studies, contributing 16 MI conditions (N = 1556). The pooled correlation coefficient was used to assess the significance, direction, and strength of seven language subtypes (i.e., reason, desire, need, ability, commitment, taking steps, and other) by three valences (i.e., frequency positive or change talk, frequency negative or sustain talk, and proportion change talk) and their relationship to subsequent engagement in addictive behavior. Results: For frequency measures, more sustain talk related to reason, desire, ability, and other were associated with more addictive behavior at follow up. Other change talk was associated with MI outcomes but in an unexpected direction (i.e., more addictive behavior). Proportion measures showed more proportion change talk-reason and -other statements were associated with less addictive behavior at follow up. Sensitivity analyses indicated some heterogeneity and instability of effect sizes, but no evidence of publication bias. Conclusions: This preliminary meta-analysis suggests that aggregate measures of change and sustain talk are comprised of statement subtypes that are not equally meaningful in predicting outcome following MI for addictive behavior change.
Paediatric pain management: knowledge, attitudes, barriers and facilitators among nurses – integrative review

AIMS To identify and synthesize evidence regarding the knowledge and attitudes of nurses, and barriers and facilitators to effective pain assessment and management in infants and children. BACKGROUND Pain among children is a common experience. Relief from pain is a fundamental human right, yet hospitalized children continue to experience unrelieved pain. Provision of effective pain management is an integral part of the nurse's role. METHODS Guided by Whittemore & Knafl's five-stage framework, primary peer-reviewed studies published in English between 2000 and 2018 were searched using CINAHL, PubMed, ProQuest, PsycINFO and Scopus. The initial search yielded 292 papers. Twenty-seven papers were included in this review: quantitative (n = 18), qualitative (n = 5) and mixed-methods (n = 4). RESULTS Findings showed that nurses internationally have poor knowledge and attitudes of basic pain assessment and management principles. Barriers to effective pain management include the absence of pain education and assessment tools, parents' reluctance to report pain and insufficient prescription of analgesia by physicians. Facilitators for the effective management of pain include parental participation in care, trusting and respectful relationships between nurses and children, and adequate nurse-patient ratios. CONCLUSION The review findings suggest a need to improve education for nurses, doctors and the patients' family in relation to paediatric pain management, communication and interprofessional collaborations. There is a need to maximize facilitators and overcome barriers, such as those identified in this review, to ensure the quality of paediatric pain management. IMPLICATIONS FOR NURSING AND HEALTH POLICY Nursing and health policy should mandate the prioritization of paediatric pain management and the clinical roles and responsibilities of the interdisciplinary team members. Undergraduate, postgraduate and in-service education for nurses and other health professionals should also address paediatric pain management. In-service education on paediatric pain management should be compulsory for all health professionals caring for children.
Executive performance on the preschool executive task assessment in children with sickle cell anemia and matched controls

ABSTRACT Executive deficits are commonly reported in children with sickle cell anemia. Earlier identification of executive deficits would give more scope for intervention, but this cognitive domain has not been routinely investigated due to a lack of age-appropriate tasks normed for preschool children. In particular, information relating to patient performance on an executive task that reflects an everyday activity in the classroom could provide important insight and practical recommendations for the classroom teacher at this key developmental juncture as they enter the academic domain. The performance of 22 children with sickle cell anemia was compared to 24 matched control children on the Preschool Executive Task Assessment. Findings reveal that children with sickle cell anemia are performing poorer than their matched peers on this multi-step assessment. In particular, children with sickle cell anemia required more structured support to shift focus after a completed step, as reflected by poorer scores in the quantitative Sequencing and Completion domains. They also required more support to stay on task, as seen by poorer ratings in the qualitative Distractibility domain. Abbreviations:PETA: Preschool Executive Task Assessment; SCA: Sickle Cell Anemia; EF: Executive Functioning.
An intra‐individual surgical wound comparison shows that octenidine‐based hydrogel wound dressing ameliorates scar appearance following abdominoplasty

Hypertrophic scar formation because of surgical procedures is associated with higher levels of pain, a lower quality of life, and poor cosmetic outcome and requires more resources in follow‐up management. An octenidine‐based hydrogel has been shown to modulate immunological function in an in vitro wound model, suggesting an improved scar formation. In this prospective, randomised, observer‐blinded, and intra‐patient‐controlled study, 45 patients who underwent abdominoplasty or mastectomy with transverse rectus abdominis muscle (TRAM) flap reconstruction were given both a standard postoperative wound dressing on one wound side and an octenidine‐based hydrogel with transparent film dressing, covered with standard postoperative dressing on the other side. Four instances of hypertrophia were reported in the gel side versus 12 in the standard dressing side. Visual Analogue Scale (VAS) pain scores taken during postoperative dressing changes showed reduced scores on the gel side at all time points. Vancouver Scar Scale (VSS) scores showed improvement in the gel side at 3, 6, and 12 months postoperatively. Skin distensibility measured using a cutometer showed significantly improved measures in gel‐treated wounds, similar to measures of healthy skin. Trans‐epidermal water loss (TEWL), measured using a tewameter, showed improved values on the gel side soon after surgery, with both the control and the gel side normalising after approximately 6 months. The octenidine‐based wound dressing demonstrates improved wound healing associated with a lower incidence of hypertrophic scar formation.
Simultaneous determination of eight components in Angelica sinensis based on UHPLC-ESI-MS/MS method for quality evaluation.

A method employing ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for determination of eight components including ferulic acid, senkyunolide A, butylphthalide, ligustilide, butylidenephalide, senkyunolide I, senkyunolide H and levistolide A in Angelica sinensis was established. The separation was carried out using a Waters ACQUITY UHPLC BEH C18 column with gradient elution with 0.1% formic acid aqueous and acetonitrile at a flow rate of 0.4 mL/min. Good linearity was attained with R2 of 0.9983-0.9998 in wide concentration ranges. The method had limit of detection (LOD) and quantitation (LOQ) in the range of 0.42-6.98 ng/mL and 1.39-23.28 ng/mL, respectively. Intra- and inter-day precisions varied with relative standard deviations (RSDs) from 0.33% to 0.88% and 0.37% to 1.04%, respectively. Moreover, the average recoveries were in a satisfactory range of 92.7%-102.1% with RSDs of less than 3.60%. Finally, the method was successfully applied to analyze 19 batches of A. sinensis samples grown in Min County, Gansu province, China, as well as that collected in other regions. The findings indicated that the established method is reliable and may thus be applied as a powerful tool for qualitative and quantitative analysis of components in A. sinensis, which has its implications in quality control of A. sinensis.
Development and psychometric properties of the Self-efficacy for Mindfulness Meditation Practice scale

This study aimed to develop a self-efficacy measure for mindfulness meditation practice (Self-efficacy for Mindfulness Meditation Practice scale). The scale was developed through a process of expert consensus, cognitive interviewing, and evaluation among 199 mindfulness meditation practitioners who completed an online survey. The 9-item Self-efficacy for Mindfulness Meditation Practice scale was unidimensional with three subconstructs of attention, compassion, and emotion. The omega hierarchical coefficient for the total scale was 0.78, and test–retest reliability was intraclass correlation coefficient = 0.85 (95% confidence interval: 0.80, 0.89). This study provides preliminary evidence that Self-Efficacy for Mindfulness Meditation Practice scale is a reliable and valid measure of self-efficacy for mindfulness meditation practice.
Getting to the heart of myofibroblast differentiation: implications for scleraxis in ECM remodeling and therapeutic targeting.

Myoﬁbroblasts are major contributors to cardiac remodeling after injury. These cells derive partly from the differentiation of resident cardiac ﬁbroblasts, express a more tensile pheno-type, and exhibit very high levels of extracellular matrix (ECM) synthesis. The ECM is a dynamic, acellular scaffold of structural proteins (such as collagen, ﬁbronectin, integrins, and cadherins) maintained by ﬁbrocytes (quiescent, immo-tile, low ECM-modifying) and ﬁbroblasts (proliferative, motile, high ECM-modifying) within the interstitial space. The essential ECM regulates cell migration, cardiomyocyte alignment, and maintains proper chamber morphology and mechanical function (9). In the infarcted heart, ECM pro-duced by ﬁbroblasts and differentiated myoﬁbroblasts re-places necrotic cardiomyocytes. Cell death and progressive cardiomyocyte loss weaken the structural integrity of the ventricular wall, making it prone to hemorrhagic rupture and sudden cardiac death. As cardiomyocytes possess little re-generative capacity in the adult heart, increased ECM deposition in the form of a ﬁbrotic scar is essential to maintain ventricular wall integrity and function after myocardial infarction. Although ﬁbrotic remodeling plays an important role in adaptive repair, excess ECM synthesis and matrix type can become maladaptive. In the peri-infarct zone, cardiomyocytes struggle to survive and adapt to the increased hemodynamic load brought on by the loss of contractile cells. Progressive mechanical stretch due to cell death, protracted inﬂammation, and hemodynamic stress stimulate extensive interstitial ﬁbrosis in the
Yra1-bound RNA–DNA hybrids cause orientation-independent transcription–replication collisions and telomere instability

Here, Garcia-Rubio et al. show that Yra1, an abundant RNA-binding factor conserved from yeast to humans and required for mRNA export, binds RNA–DNA hybrids in vitro and, when artificially overexpressed, can be recruited to chromatin in an RNA–DNA hybrid-dependent manner, stabilizing R loops and converting them into replication obstacles in vivo, suggesting that RNA–DNA hybrids form transiently in cells regardless of replication and, after stabilization by excess Yra1, compromise genome integrity.
Mutational screening of newly diagnosed multiple myeloma patients by deep targeted sequencing

Next-generation sequencing has substantially improved our understanding of the genomic landscape of multiple myeloma; however, the application of this technology has been confined mostly to research studies. Here, we report on a customized panel to characterize the mutational profile of 79 newly diagnosed patients with multiple myeloma, older than 65 years and who were not transplant candidates, applying the highest read depth to date that has been used for equivalent studies in multiple myeloma. Overall, we identified 53 genes mutated in 85% of patients, including KRAS, NRAS, BRAF, DIS3 and TP53, and found a complex subclonal structure. In addition, the total number of mutations, as well as mutations in TP53 and the Cereblon pathway, were negatively associated with survival. The latter result is particularly noteworthy as patients enrolled in this phase II clinical trial were treated with lenalidomide, which targets this pathway. Our next-generation sequencing strategy not only identified a group of patients with poor outcome, but also provided an extensive genetic profile that should prove useful in the search for new biomarkers and therapeutic targets in multiple myeloma, at an affordable price and with a small amount of sample, which are indispensable features for translating personalized medicine protocols to clinical practice.
Cesium emissions from laboratory fires

ABSTRACT If a radiological incident such as a nuclear power plant accident, a radiological dispersal device, or detonation of an improvised nuclear device occurs, significant areas may be contaminated. Initial cleanup priorities would likely focus on populated areas, leaving the forested areas to pass several seasons where the overhead canopy materials would fall to the forest floor. In the event of a wildfire in a radionuclide-contaminated forest, some radionuclides would be emitted in the air while the rest would remain in the ash. This paper reports on a laboratory simulation study that examines the partitioning of cesium-133 (a nonradioactive isotope of cesium) between airborne particulate matter and residual nonentrained ash when pine needles and peat are doped with cesium. Only 1–2.5% of the doped cesium in pine needles was emitted as particulate matter, and most of the cesium was concentrated in the particulate fraction greater than 10 µm in aerodynamic diameter. For peat fires, virtually all of the cesium remained in the ash. The results from this study will be used for modeling efforts to assess potential exposure risks to firefighters and the surrounding public. Implications: There is a potential for emissions of radionuclides such as cesium-137 from a wildfire over a radionuclide-contaminated forest. This paper reports on a laboratory simulation study of a wildfire with two types of biomass doped with nonradioactive cesium. This simulation suggests that only 1–2.5% of the cesium in the biomass will be emitted from the wildfire, while the rest will reside in the residual ash. In this study, pine needles were the only contributor to the air emissions of cesium; duff was not a source of cesium emissions. In this study, cesium emitted from the simulated wildfire was concentrated in the particle sizes larger than 10 µm.
Increased fMRI activity correlations in autobiographical memory versus resting states

Autobiographical memory retrieval is associated with activity of a distributed network that is similar to the default‐mode network (DMN) identified via activity correlations measured during rest. We tested whether activity correlations could be used to identify the autobiographical network during extended bouts of retrieval. Global‐correlativity analysis identified regions with activity correlation differences between autobiographical‐retrieval and resting states. Increased correlations were identified for retrieval versus resting states within a distributed network that included regions prototypical for autobiographical memory. This network segregated into two subnetworks comprised of regions related to memory versus cognitive control, suggesting greater functional segregation during autobiographical retrieval than rest. DMN regions were important drivers of these effects, with increased correlations between DMN and non‐DMN regions and segregation of the DMN into distinct subnetworks during retrieval. Thus, the autobiographical network can be robustly identified via activity correlations and retrieval is associated with network functional organization distinct from rest.
Preeclampsia and the challenge of early prediction: reality or utopia? State of art and critical review of literature

Abstract Purpose: The challenge to obtain improved predictive tools, able to identify women destined to develop preeclampsia (PE), is raising the interest of researchers for the attractive chance to allow for timely initiation of prophylactic therapy, appropriate antenatal surveillance, and better-targeted research into preventive interventions. We aimed to gather all the evidence reported up to now in scientific literature relating to all prediction tests for PE. Materials and methods: We searched articles on conventional literature platforms from January 1952 to August 2016, using the terms “preeclampsia,” “gestational preeclampsia,” and “gestational hypertensive disorders” combined with “predictive test” and “risk assessment. ” Abstracts/titles identified by the search were screened by three investigators. Results: The search identified 203 citations, of which 154 potentially relevant after the initial evaluation. Among these studies, 20 full articles were excluded, therefore, 134 primary studies met the criteria for inclusion and were analyzed. Conclusions: Current evidence suggests that a combination of several features may provide the best predictive accuracy for the identification of PE. Large-scale, multicenter, multiethnic, prospective trials are required to propose an ideal combination of markers for routine screening.
Chlamydiales Bacterial Sequences in Lesional and Healthy Skin of Patients with Parapsoriasis.

1https://www.medicaljournals. se/acta/content/abstract/10.2340/00015555-2999 Chlamydia-related bacteria represent a diverse group of bacteria within the order Chlamydiales that have been detected ubiquitously in various environmental samples, such as soil and water, in animals, and also in humans (1–6). We recently demonstrated the presence of Chlamydiales DNA in human skin (7). Chlamydiales DNA could be detected in > 50% of all the skin biopsies studied, but the prevalence was higher and the type range was wider in biopsies from individuals with a suspected tick-related skin condition, compared with biopsies from healthy skin (8). Parapsoriasis is part of the continuum of cutaneous lymphoproliferative disorders of unknown aetiology and is clinically classified into small-plaque parapsoriasis (SPP) and large-plaque parapsoriasis (LPP) (9). This study examined the prevalence, distribution and relative abundance of Chlamydiales DNA in skin biopsies and skin swab samples, both from lesional and contralateral healthy skin, from 13 patients with parapsoriasis (6 SPP, 7 LPP; see Appendix S11). The clinical characteristics and skin microbiome data for these patients have been reported earlier (10).
Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients

Objectives: To investigate whether diabetes and glucose dysregulation (hyperglycemia and/or hypoglycemia) are associated with ICU delirium. Design: Prospective cohort study. Setting: Thirty-two–bed mixed intensive care in a tertiary care center. Patients: Critically ill patients admitted to the ICU with transitions of mental status from awake and nondelirious to delirious or remaining awake and nondelirious on the next day. Patients admitted because of a neurologic illness were excluded. Interventions: None. Measurements and Main Results: The study population consisted of 2,745 patients with 1,720 transitions from awake and nondelirious to delirious and 11,421 nontransitions remaining awake and nondelirious. Generalized mixed effects models with logit link function were performed to study the association between diabetes mellitus, glucose dysregulation, and delirium, adjusting for potential confounders. Diabetes was not associated with delirium (odds ratio adjusted, 0.93; 95% CI, 0.73–1.18). In all patients, the occurrence of hyperglycemia (odds ratio adjusted, 1.35; 95% CI, 1.15–1.59) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.65; 95% CI, 1.12–2.28) compared with normoglycemia were associated with transition to delirium. Hypoglycemia was not associated with transition to delirium (odds ratio adjusted, 1.86; 95% CI, 0.73–3.71). In patients without diabetes, the occurrence of hyperglycemia (odds ratio adjusted, 1.41; 95% CI, 1.16–1.68) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.87; 95% CI, 1.07–2.89) were associated with transition to delirium. In patients with diabetes, glucose dysregulation was not associated with ICU delirium. Conclusions: Diabetes mellitus was not associated with the development of ICU delirium. For hypoglycemia, only a nonsignificant odds ratio for ICU delirium could be noted. Hyperglycemia and the occurrence of hyperglycemia and hypoglycemia on the same day were associated with ICU delirium but only in patients without diabetes. Our study supports the institution of measures to prevent glucose dysregulation in nondiabetic ICU patients and contributes to the understanding of the determinants of delirium.