Miracle-dz/UniFAR-FTUs huggingface dataset:
AmBisome: relationship between the pharmacokinetic characteristics acquired by liposomal formulation and safety/efficacy

Abstract Amphotericin B (AMPH-B) is a polyene antifungal agent with a superior and broad fungicidal spectrum, but its administration at a dose sufficient for treatment is difficult because of dose- and duration-dependent nephrotoxicity. To solve this dilemma, a liposomal formation of AMPH-B that achieved reduction of adverse effects while maintaining the efficacy, AmBisome® (L-AMB), was developed. In L-AMB, AMPH-B molecules are stabilized by phospholipids and cholesterol in the liposomal lipid bilayer, reducing the cytotoxicity for animal cells compared with that of the free-form AMPH-B. In addition, extravascular permeation of L-AMB is limited in normal tissue because of the liposome particle size (particle diameter: 100 nm or smaller), a high blood level is maintained and the distribution in organs, including the kidney is reduced, contributing to the improvement of the safety. On the other hand, vascular permeation increases due to inflammation and damage by fungal invasion, which increases L-AMB transfer from the circulation to lesions and its antifungal activity. Furthermore, since the parameter most closely correlated with the in vivo outcome of L-AMB is Cmax/MIC, the pharmacokinetic (PK) characteristics of L-AMB, which result in a high blood level than that for the free-form AMPH-B, is advantageous for antifungal activity. Incorporation of AMPH-B into the liposomal membrane resulted in PK characteristics of L-AMB markedly different from those of AMPH-B, and the superior efficacy and safety were achieved based on these characteristics. In this review, the relationship between the PK characteristics of L-AMB and safety/efficacy is introduced.
Telepractice delivery of family-centred early intervention for children who are deaf or hard of hearing: A scoping review

Introduction The use of telepractice, a method of delivering services through telecommunications technologies that provides two-way, synchronous audio and video signals in real-time, is becoming increasingly commonplace in early childhood education and intervention for children who are deaf or hard of hearing. Although the use of telepractice has been validated in the health sector as a viable and effective alternative to in-person service provision, evidence to support its use in the delivery of family-centred early intervention is still emerging. The purpose of this scoping review was to describe the current use of telepractice in the delivery of family-centred early childhood intervention for children who are deaf or hard of hearing, and their families. Method The review followed the framework outlined by the Joanna Briggs Institute (2015), including an iterative three-step search strategy. Specific inclusion criteria and data extraction fields were outlined in advance. Results A total of 23 peer-reviewed publications were included in the review. Most publications (70%) provided anecdotal evidence of the challenges and benefits associated with telepractice. The remaining publications (30%) reported on research studies evaluating the effectiveness of early intervention delivered through telepractice. Of the 23 included papers, 18 viewed the use of telepractice positively while the remaining 5 reported mixed conclusions and the need for more data. Discussion Current evidence in the literature indicates that telepractice can be an effective model for delivering family-centred early intervention for children who are deaf or hard of hearing. However, more research is needed to substantiate the use of telepractice as a viable alternative to traditional in-person services, rather than being seen as supplemental to such services.
Facilitating Healthy Coping in Patients With Diabetes

Purpose The purpose of this study is to summarize recent literature on approaches to supporting healthy coping in diabetes in 2 specific areas: (1) the impact of different approaches to diabetes treatment on healthy coping and (2) the effectiveness of interventions specifically designed to support healthy coping. Methods A PubMed search identified 129 articles published August 1, 2006, to April 30, 2011, addressing diabetes in relation to emotion, quality of life, depression, adjustment, anxiety, coping, family therapy, behavior therapy, psychotherapy, problem solving, couples therapy, or marital therapy. Results Evidence suggests that treatment choice may significantly influence quality of life, with treatment intensification in response to poor metabolic control often improving quality of life. The recent literature provides support for a variety of healthy coping interventions in diverse populations, including diabetes self-management education, support groups, problem-solving approaches, and coping skills interventions for improving a range of outcomes; cognitive behavior therapy and collaborative care for treating depression; and family therapy for improving coping in youths. Conclusions Healthy coping in diabetes has received substantial attention in the past 5 years. A variety of approaches show positive results. Research is needed to compare the effectiveness of different approaches in different populations and determine how to overcome barriers to intervention dissemination and implementation.
Mechanisms of M3 Muscarinic Receptor Regulation by Wash-Resistant Xanomeline Binding

Background/Aims: Xanomeline has been shown to bind in a unique manner at M1 and M3 muscarinic receptors, with interactions at both the orthosteric site and an allosteric site. We have previously shown that brief exposure of Chinese hamster ovary cells that express the M3 receptor to xanomeline followed by removal of free agonist results in a delayed decrease in radioligand binding and receptor response to agonists. In the current study, we were interested in determining the mechanisms of this effect. Methods: Cells were treated with carbachol, pilocarpine or xanomeline for 1 h followed by washing and either used immediately or after waiting for 23 h. Control groups included cells that were not exposed to agonists and cells that were treated with agonists for 24 h. Radioligand binding and functional assays were conducted to determine the effects of agonist treatments. Results: The above treatment protocol with xanomeline resulted in similar effects of the binding of [3H]NMS and [3H]QNB. When receptor function is blocked using a variety of methods, the long-term effects of xanomeline binding were absent. Conclusion: Our data indicate that xanomeline wash-resistant binding at the receptor allosteric site leads to receptor downregulation and that receptor activation is necessary for these effects.
Laser treatment of congenital melanocytic naevi: a systematic review

Recent studies on congenital melanocytic naevi (CMN) indicate a lower risk of melanoma than has been previously assumed. As a result, the treatment paradigm in CMN has shifted from complete removal to cosmetically acceptable, less invasive treatment options, such as laser treatment. Our objective was to review systematically the efficacy and safety of laser therapy for CMN. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and PubMed. We rated the quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twenty‐four eligible studies (three nonrandomized controlled studies; 21 case series) with 434 patients were included; the majority were of poor quality). Twenty different laser modalities or combinations were evaluated. Overall, the Q‐switched laser was used most frequently, although large or giant CMN were generally treated with an ablative laser. Owing to heterogeneity between studies, comparison between laser modalities was hampered and statistical analysis was precluded. Lasers in CMN showed rather good results (albeit with very low‐quality evidence) for clearing of hyperpigmentation in the short term. Outcome measures varied widely, patient satisfaction was rarely measured and high incidences of scarring, repigmentation and complications were reported. No malignant change was seen. While most studies report short‐term improvement of CMN after laser therapy, there is no high‐quality evidence for the efficacy and safety of laser modalities in CMN in the long term. Future research should focus on well‐conducted and well‐reported prospective studies on different laser modalities for CMN, with the use of recognized and validated outcome measures.
Individual variation in urinary sodium excretion among adolescent girls on a fixed intake

Background: According to traditional understanding of sodium homeostasis, nearly all of daily sodium intake is excreted in urine, with intraindividual variability attributed to variability in dietary sodium intake and urine collection errors. Objective: To analyze the variability of urinary sodium in excretion from a balance study with fixed sodium intakes. Methods: Daily 24-h urine collections were assessed for sodium, potassium, and creatinine in 22 black and 13 white adolescent girls (11–15 year, BMI 15–29 kg/m2) in a randomized, crossover design with controlled diets containing either low (57 mmol/day) or high (167 mmol/day) sodium, each fed for 3 weeks. Results: Coefficient of variation analysis indicated higher variation in urinary sodium excretion about the mean on low (vs high) sodium (40 vs 32%, P = 0.02) and in black (vs white) girls (42 vs 30%, P < 0.001). A mixed model showed no sodium intake × race interaction. Urinary sodium excretion was not correlated with urinary potassium or creatinine excretion. Excretion of 65 mmol/day (adequate intake) or less was documented on 16% on the days during the high-sodium diet. Reliability of the mean of several urine sodium samples varied from 23% for one sample to 75% for 10 samples for the high-sodium diet. Conclusion: The high intraindividual variability in urinary sodium excretion on a fixed diet highlights the potential for substantial error in (a) using a single 24-h urine collection to estimate an individual's usual sodium intake and (b) relating sodium excretion from a single 24-h collection with outcomes. Further research is warranted to understand the causes of such variation.
Evidence of Stage Shift in Women Diagnosed With Ovarian Cancer During Phase II of the United Kingdom Familial Ovarian Cancer Screening Study

Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC). Patients and Methods Women whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO. Results Between June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at RRSO). No symptomatic interval cancers occurred. Ten (52.6%) of the total 19 diagnoses were stage I to II OC/FTC (CI, 28.9% to 75.6%). Of the 13 screen-detected cancers, five (38.5%) were stage I to II (CI, 13.9% to 68.4%). Of the six occult cancers, five (83.3%) were stage I to II (CI, 35.9% to 99.6%). Modeled sensitivity, positive predictive value, and negative predictive value for OC/FTC detection within 1 year were 94.7% (CI, 74.0% to 99.9%), 10.8% (6.5% to 16.5%), and 100% (CI, 100% to 100%), respectively. Seven (36.8%) of the 19 cancers diagnosed < 1 year after prior screen were stage IIIb to IV (CI, 16.3% to 61.6%) compared with 17 (94.4%) of 18 cancers diagnosed > 1 year after screening ended (CI, 72.7% to 99.9%; P < .001). Eighteen (94.8%) of 19 cancers diagnosed < 1 year after prior screen had zero residual disease (with lower surgical complexity, P = .16) (CI, 74.0% to 99.9%) compared with 13 (72.2%) of 18 cancers subsequently diagnosed (CI, 46.5% to 90.3%; P = .09). Conclusion ROCA-based screening is an option for women at high risk of OC/FTC who defer or decline RRSO, given its high sensitivity and significant stage shift. However, it remains unknown whether this strategy would improve survival in screened high-risk women.
Influence of Mixing Procedure on Robustness of Self-Consolidating Concrete

Self-Consolidating Concrete (SCC) is, in the fresh state, more sensitive to small variations in the constituent elements and the mixing procedure compared to Conventional Vibrated Concrete. Several studies have been performed recently to identify robustness of SCC and to develop solutions to increase the robustness of SCC. Ghent University obtained a major research project from the Research Foundation in Flanders (FWO) to investigate fundamentally robustness of SCC and to identify potential solutions in the form of alternative materials to enhance robustness. In the present research project, Missouri University of Science and Technology (Missouri S&T) extended the research at Ghent University by investigating the influence of the mixing procedure on the robustness of SCC. The project was split into four tasks. In a first task, the sequence of adding the constituent elements and mixing was investigated by measuring the rheological properties of cement pastes. In a second task, the combined influence of the most significant mix design and mixing procedure parameters were investigated, with particular attention to the mix design parameters which influence the robustness of the cement paste to a change in time of addition of the superplasticizer. In the third task, the results obtained on cement pastes were validated on concrete scale, with focus on the adding sequence of the aggregates and their initial moisture content. In the fourth task, the robustness of thixotropy and loss of workability was investigated on cement paste and concrete scale. To enhance the application of SCC for the construction and repair of transportation infrastructure, two key concepts are of importance: quality control and consistency. The consistency refers to the mixing operations and transportation of SCC. It is recommended to keep the mixing procedure constant for every SCC produced. This includes the addition sequence of the materials, the mixing time, the mixing speed and the concrete volume (parameter not tested, but it is reflected in mixing energy). The quality control is not only necessary to determine the moisture content of the aggregates, but also for any of the other constituent elements used.
Condensins promote chromosome individualization and segregation during mitosis, meiosis, and amitosis in Tetrahymena thermophila

In Tetrahymena, different condensins are required to segregate chromosomes in the germline versus the somatic nuclei. Germline condensins promote condensation and individualization of chromosomes. In the polyploid somatic nucleus, condensin acts as an insulator, preventing the multiple copies of each chromosome from clustering.
Long-term trends of liver cancer mortality by gender in urban and rural areas in China: an age-period-cohort analysis

Objectives To provide an up-to-date overview of long-term trends of liver cancer mortality and evaluate the effects attributable to age, period and cohort in Chinese population stratified by gender and urban/rural areas. Methods Population and liver cancer mortality data were obtained based on the Disease Surveillance Points in China from 1991 to 2014. To examine the time trends of liver cancer mortality by gender in urban and rural areas in China, Joinpoint analysis was used to estimate the annual per cent change. The intrinsic estimator, a method of age-period-cohort analysis to estimate age, period and cohort effects simultaneously, was used to analyse the underlying mechanisms for liver cancer mortality trends in the aforementioned four groups. Results We observed a significant decline in liver cancer mortality for urban men (average annual per cent change (AAPC)=−1.1%, P<0.05) and urban women (AAPC=−1.4%, P<0.05), while the liver cancer mortality remained stable for rural men (AAPC=−0.1%, P>0.05) and rural women (AAPC=−0.9%, P>0.05). Compared with the 15–19 age group, the liver cancer mortality risk of the 85 and above age group increased 65 and 42 times for urban and rural men, and 102 and 70 times for urban and rural women. From the 1990–1994 period to the 2005–2009 period, the risk increased 56% and 92% for urban and rural men, and 30% and 74% for urban and rural women. Compared with period and cohort effects, age effects were the most influential factor in liver cancer mortality. Conclusions As the status of ageing population in China gets worse, the burden caused by liver cancer mortality could still be a great challenge for China in the future. The disparity of liver cancer mortality trends between urban and rural residents can be attributed to period effects, referring to the unequal medical levels and resources between urban and rural areas.
Impact on smoking of England's 2012 partial tobacco point of sale display ban: a repeated cross-sectional national study

Background A partial tobacco point of sale (PoS) display ban was introduced in large shops (>280 m2 floor area) in England on 6 April 2012. The aim of this study was to assess the medium-term effects of the partial tobacco PoS display ban on smoking in England. Methods Data were used from 129 957 respondents participating in monthly, cross-sectional household surveys of representative samples of the English adult population aged 18+ years from January 2009 to February 2015. Interrupted-time series regression models assessed step changes in the level of current smoking and cigarette consumption in smokers and changes in the trends postban compared with preban. Models were adjusted for sociodemographic variables and e-cigarette use, seasonality and autocorrelation. Potential confounding by cigarette price was accounted for by time, as price was almost perfectly correlated with time. Results Following the display ban, there was no immediate step level change in smoking (−3.69% change, 95% CI −7.94 to 0.75, p=0.102) or in cigarette consumption (β −0.183, 95% CI −0.602 to 0.236). There was a significantly steeper decline in smoking post display ban (−0.46% change, 95% CI −0.72 to −0.20, p=0.001). This effect was demonstrated by respondents in manual occupations (−0.62% change, 95% CI −0.72 to −0.20, p=0.001), but not for those in non-manual occupations (−0.42, 95% CI −0.90 to 0.06, p=0.084). Cigarette consumption declined preban period (β −0.486, 95% CI −0.633 to −0.339, p<0.001), but no significant change in cigarette consumption trend was observed (β 0.019, 95% CI −0.006 to 0.042, p=0.131). Conclusions The partial tobacco PoS display ban introduced in England in April 2012 did not lead to an immediate decline in smoking, but was followed by a decline in the trend of smoking prevalence that could not be accounted for by seasonal factors, e-cigarette use or price changes.
Neonatal neural networks predict children behavioral profiles later in life

This study aimed to examine heterogeneity of neonatal brain network and its prediction to child behaviors at 24 and 48 months of age. Diffusion tensor imaging (DTI) tractography was employed to construct brain anatomical network for 120 neonates. Clustering coefficients of individual structures were computed and used to classify neonates with similar brain anatomical networks into one group. Internalizing and externalizing behavioral problems were assessed using maternal reports of the Child Behavior Checklist (CBCL) at 24 and 48 months of age. The profile of CBCL externalizing and internalizing behaviors was then examined in the groups identified based on the neonatal brain network. Finally, support vector machine and canonical correlation analysis were used to identify brain structures whose clustering coefficients together significantly contribute the variation of the behaviors at 24 and 48 months of age. Four meaningful groups were revealed based on the brain anatomical networks at birth. Moreover, the clustering coefficients of the brain regions that most contributed to this grouping of neonates were significantly associated with childhood internalizing and externalizing behaviors assessed at 24 and 48 months of age. Specially, the clustering coefficient of the right amygdala was associated with both internalizing and externalizing behaviors at 24 months of age, while the clustering coefficients of the right inferior frontal cortex and insula were associated with externalizing behaviors at 48 months of age. Our findings suggested that neural organization established during fetal development could to some extent predict individual differences in behavioral‐emotional problems in early childhood. Hum Brain Mapp 38:1362–1373, 2017. © 2016 Wiley Periodicals, Inc.
BioMuta and BioXpress: mutation and expression knowledgebases for cancer biomarker discovery

Abstract Single-nucleotide variation and gene expression of disease samples represent important resources for biomarker discovery. Many databases have been built to host and make available such data to the community, but these databases are frequently limited in scope and/or content. BioMuta, a database of cancer-associated single-nucleotide variations, and BioXpress, a database of cancer-associated differentially expressed genes and microRNAs, differ from other disease-associated variation and expression databases primarily through the aggregation of data across many studies into a single source with a unified representation and annotation of functional attributes. Early versions of these resources were initiated by pilot funding for specific research applications, but newly awarded funds have enabled hardening of these databases to production-level quality and will allow for sustained development of these resources for the next few years. Because both resources were developed using a similar methodology of integration, curation, unification, and annotation, we present BioMuta and BioXpress as allied databases that will facilitate a more comprehensive view of gene associations in cancer. BioMuta and BioXpress are hosted on the High-performance Integrated Virtual Environment (HIVE) server at the George Washington University at https://hive.biochemistry. gwu.edu/biomuta and https://hive.biochemistry. gwu.edu/bioxpress, respectively.
An Annular Rotating-Die Technique in Extrusion Process: Effect of Mandrel Rotating Speed on Extrudate Swell Behavior of HDPE Parison

Abstract This work aims to propose an annular rotating-die technique which is specifically designed and constructed in order for the mandrel to rotate in the stationary barrel during extrusion. The annular rotating-die was employed to study the effect of the mandrel rotating speeds on the extrudate swell behavior of HDPE parison in single screw extruder at a test temperature of 210°C. The results of experiment found that rotation of mandrel caused significant change in dimension of HDPE parison after it flowed out from the annular rotating-die. It was also found that at the same apparent shear rate, the diameter swell decreased with increasing mandrel rotating speed whereas the thickness swell yielded opposite results. These results could be explained by the change of flow direction during the flow of HDPE melt in the annular rotating-die. Furthermore, the annular rotating-die technique proposed in this research could be applied in adjusting size of diameter and thickness and in predicting thickness of HDPE parison during extrusion with no need to change any production parameter in the polymer extruder.