Miracle-dz/UniFAR-FTUs huggingface dataset:
GPVI modulation during platelet activation and storage: its expression levels and ectodomain shedding compared to markers of platelet storage lesion

ABSTRACT Platelet storage is associated with deleterious changes leading to the loss of platelet reactivity and response. During storage, platelets experience increased expression and shedding of P-selectin and CD40L as specific markers of platelet activation, whereas GPIbα decreases due to ectodomain shedding. As an important adhesive receptor, GPVI contributes significantly to thrombus formation while its expression and shedding levels during storage of platelet products have not been well characterized yet. This study investigated the modulation of GPVI during platelet storage. For this study, samples obtained from 10 PRP-platelet concentrates (PCs) were subjected to flow-cytometry analysis to examine the expression of platelet activation markers and GPVI on days 1, 3, and 5 post-storage. To examine the levels of etcodomain shedding of these molecules, microparticle (MP)-free supernatants were also analyzed by either ELISA or Western blot methods. According to results, the expression levels of P-selectin and CD40L as well as the amounts of their soluble forms significantly increased during storage. The expression of GPIbα and GPVI decreased whereas their shedding significantly increased post-storage. The expression and shedding levels of these two receptors were significantly correlated. Negative correlations between the expressions of GPIbα or GPVI and P-selectin have been observed whereas their shedding levels were significantly relevant together. In a control study, the use of biotinylated platelet resuspended in Tyrode’s buffer in the presence of ionophore with/without EDTA, confirmed the role of calcium in receptors shedding. In citrated PRP-PCs, recalcification of platelets also enhanced shedding levels of both GPIbα and GPVI. Intriguingly, the shedding levels of GPVI in stored PRP-PCs were much higher than those of ionophore-treated controls obtained from washed platelets. The ratios of sGPVI in stored platelet to ionophore-treated controls were also at least six times higher than those of GPIbα during storage. In conclusion, here we showed significant decreases of GPVI expression associated with its increasing levels of shedding during storage, suggesting GPVI as a valid marker of platelet storage lesion. Importantly, we found higher levels of GPVI shedding in stored platelets than those of ionophore-treated non-stored control samples. This suggests whereas platelet receptor shedding is mainly modulated by calcium-dependent signals, either platelet–surface interactions with the container walls during storage or induced shear stress under long-term agitation, might be also involved in the excessive shedding of GPVI during the storage of PCs.
nvironmental concentrations of anti-androgenic pharmaceuticals do ot impact sexual disruption in fish alone or in combination with teroid oestrogens

Sexual disruption in wild fish has been linked to the contamination of river systems with steroid oestrogens, including the pharmaceutical 17 -ethinylestradiol, originating from domestic wastewaters. As analytical chemistry has advanced, more compounds derived from the human use of pharmaceuticals have been identified in the environment and questions have arisen as to whether these additional pharmaceuticals may also impact sexual disruption in fish. Indeed, pharmaceutical anti-androgens have been shown to induce such effects under laboratory conditions. These are of particular interest since antiandrogenic biological activity has been identified in the aquatic environment and is potentially implicated in sexual disruption alone and in combination with steroid oestrogens. Consequently, predictive modelling was employed to determine the concentrations of two anti-androgenic human pharmaceuticals, bicalutamide and cyproterone acetate, in UK sewage effluents and river catchments and their combined impacts on sexual disruption were then assessed in two fish models. Crucially, fish were also exposed to the anti-androgens in combination with steroid oestrogens to determine whether they had any additional impact on oestrogen induced feminisation. Modelling predicted that the anti-androgenic pharmaceuticals were likely to be widespread in UK river catchments. However, their concentrations were not sufficient to induce significant responses in plasma vitellogenin concentrations, secondary sexual characteristics or gross indices in male fathead minnow or intersex in Japanese medaka alone or in combination with steroid oestrogens. However, environmentally relevant mixtures of oestrone, 17 -oestradiol and 17 -ethinylestradiol did induce vitellogenin and intersex, supporting their role in sexual disruption in wild fish populations. Unexpectedly, a male dominated sex ratio (100% in controls) was induced in medaka and the potential cause and implications are briefly discussed, highlighting the potential of non-chemical modes of action on this endpoint. © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license
PAX3–FOXO1 is essential for tumour initiation and maintenance but not recurrence in a human myoblast model of rhabdomyosarcoma

The PAX3–FOXO1 fusion gene is generated by a 2;13 chromosomal translocation and is a characteristic feature of an aggressive subset of rhabdomyosarcoma (RMS). To dissect the mechanism of oncogene action during RMS tumourigenesis and progression, doxycycline‐inducible PAX3–FOXO1 and constitutive MYCN expression constructs were introduced into immortalized human myoblasts. Although myoblasts expressing PAX3–FOXO1 or MYCN alone were not transformed in focus formation assays, combined PAX3–FOXO1 and MYCN expression resulted in transformation. Following intramuscular injection into immunodeficient mice, myoblasts expressing PAX3–FOXO1 and MYCN formed rapidly growing RMS tumours, whereas myoblasts expressing only PAX3–FOXO1 formed tumours after a longer latency period. Doxycycline withdrawal in myoblasts expressing inducible PAX3–FOXO1 and constitutive MYCN following tumour formation in vivo or focus formation in vitro resulted in tumour regression or smaller foci associated with myogenic differentiation and cell death. Following regression, most tumours recurred in the absence of doxycycline. Analysis of recurrent tumours revealed a subset without PAX3–FOXO1 expression, and cell lines derived from these recurrent tumours showed transformation in the absence of doxycycline. The doxycycline‐independent oncogenicity in these recurrent tumour‐derived lines persisted even after PAX3–FOXO1 was inactivated with a CRISPR/Cas9 editing strategy. Whereas cell lines derived from primary tumours were dependent on PAX3–FOXO1 and differentiated following doxycycline withdrawal, recurrent tumour‐derived cells without PAX3–FOXO1 expression did not differentiate under these conditions. These findings indicate that PAX3–FOXO1 collaborates with MYCN during early RMS tumourigenesis to dysregulate proliferation and inhibit myogenic differentiation and cell death. Although most cells in the primary tumours are dependent on PAX3–FOXO1, recurrent tumours can develop by a PAX3–FOXO1‐independent mechanism, in which rare cells are postulated to acquire secondary transforming events that were activated or selected by initial PAX3–FOXO1 expression. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Replication Capacity of Viruses from Acute Infection Drives HIV-1 Disease Progression

ABSTRACT The viral genotype has been shown to play an important role in HIV pathogenesis following transmission. However, the viral phenotypic properties that contribute to disease progression remain unclear. Most studies have been limited to the evaluation of Gag function in the context of a recombinant virus backbone. Using this approach, important biological information may be lost, making the evaluation of viruses obtained during acute infection, representing the transmitted virus, a more biologically relevant model. Here, we evaluate the roles of viral infectivity and the replication capacity of viruses from acute infection in disease progression in women who seroconverted in the CAPRISA 004 tenofovir microbicide trial. We show that viral replication capacity, but not viral infectivity, correlates with the set point viral load (Spearman r = 0.346; P = 0.045) and that replication capacity (hazard ratio [HR] = 4.52; P = 0.01) can predict CD4 decline independently of the viral load (HR = 2.9; P = 0.004) or protective HLA alleles (HR = 0.61; P = 0.36). We further demonstrate that Gag-Pro is not the main driver of this association, suggesting that additional properties of the transmitted virus play a role in disease progression. Finally, we find that although viruses from the tenofovir arm were 2-fold less infectious, they replicated at rates similar to those of viruses from the placebo arm. This indicates that the use of tenofovir gel did not select for viral variants with higher replication capacity. Overall, this study supports a strong influence of the replication capacity in acute infection on disease progression, potentially driven by interaction of multiple genes rather than a dominant role of the major structural gene gag. IMPORTANCE HIV disease progression is known to differ between individuals, and defining which fraction of this variation can be attributed to the virus is important both clinically and epidemiologically. In this study, we show that the replication capacity of viruses isolated during acute infection predicts subsequent disease progression and drives CD4 decline independently of the viral load. This provides further support for the hypothesis that the replication capacity of the transmitted virus determines the initial damage to the immune system, setting the pace for later disease progression. However, we did not find evidence that the major structural gene gag drives this correlation, highlighting the importance of other genes in determining disease progression.
A cytoplasmic peptidoglycan amidase homologue controls mycobacterial cell wall synthesis

Regulation of cell wall assembly is essential for bacterial survival and contributes to pathogenesis and antibiotic tolerance in Mycobacterium tuberculosis (Mtb). However, little is known about how the cell wall is regulated in stress. We found that CwlM, a protein homologous to peptidoglycan amidases, coordinates peptidoglycan synthesis with nutrient availability. Surprisingly, CwlM is sequestered from peptidoglycan (PG) by localization in the cytoplasm, and its enzymatic function is not essential. Rather, CwlM is phosphorylated and associates with MurA, the first enzyme in PG precursor synthesis. Phosphorylated CwlM activates MurA ~30 fold. CwlM is dephosphorylated in starvation, resulting in lower MurA activity, decreased cell wall metabolism, and increased tolerance to multiple antibiotics. A phylogenetic analysis of cwlM implies that localization in the cytoplasm drove the evolution of this factor. We describe a system that controls cell wall metabolism in response to starvation, and show that this regulation contributes to antibiotic tolerance. DOI: http://dx.doi. org/10.7554/eLife.14590. 001
Chemotaxonomic Characterization and Chemical Similarity of Solanaceae Subfamilies Based on Ornithine Derivatives

In the present study, the database on ornithine-derived alkaloids was elaborated in order to verify the chemical profile and the chemical similarity of the subfamilies of Solanaceae. Overall, 1513 occurrences were recorded at five subfamilies. The most commonly occurring compounds were tropane alkaloids (NO=927), followed by nicotinoids (NO=353); simple pyrrolidines (NO=133), and, finally, calystegines (NO=100). The greatest number of occurrences of these substances was recorded in Solanoideae and Nicotianoideae, which together accounted for 95% of occurrences of the four groups of substances studied. Petunioideae characterized by the presence of tropane alkaloids, simple pyrrolidines and calystegines in Schizanthoideae were observed instances of simple pyrrolidines and tropane alkaloids and in the presence of only Cestroideae nicotinoids. Similarity analysis based on the Dice coefficient suggests that the chemical profile of subfamilies Solanaceae correlated with the current classification. The similarity dendrogram showed great similarity between chemical and Solanoideae Nicotianoideae and those with Petunioide. Schizanthoideae appeared somewhat similar to these subfamilies while Cestroideae appeared dissimilar to the others.
A Comparison of Nonopioid and Opioid Oral Analgesia following Pediatric Palatoplasty

Objective This article evaluates postoperative analgesia in pediatric palatoplasty patients using nonopioid oral medications. Design This study was a retrospective chart review. Setting The setting for this study was a tertiary-care children's hospital. Participants Study participants were pediatric patients who underwent palatoplasty procedures performed by a single surgeon. Interventions Interventions included nonopioid and opioid oral medications for postoperative analgesia. Main Outcome Measures The adequacy of nonopioid versus opioid oral analgesia was assessed by (1) time to discontinue IV fluid, (2) total IV morphine doses for breakthrough pain, (3) daily IV morphine doses for breakthrough pain, (4) time to discharge from the hospital, and (5) perioperative weight change. Group comparisons of outcome measures were performed using a two one-sided test. Results A total of 61 patients were identified who received three standard pain regimens: acetaminophen + ibuprofen (12), hydrocodone/acetaminophen (23), and hydrocodone/acetaminophen + ibuprofen (26). There was sufficient evidence to suggest equivalence in outcome measures for acetaminophen + ibuprofen versus hydrocodone/acetaminophen and hydrocodone/acetaminophen + ibuprofen for the following: time to discontinue IV fluid (P = .02, 90% confidence interval [CI] = –0.42 to 0.17; P = .007, 90% CI = –0.28 to 0.34), daily IV morphine doses (P = .023, 90% [CI] = –0.83 to 0.65; P = .032, 90% [CI] = –0.92 to 0.28), time to discharge from the hospital (P = .017, 90% [CI] = –0.40 to 0.27; P = .015, 90% [CI] = –0.24 to 0.39), and perioperative weight change (P = .002; 90% CI = –0.25 to 0.46; P < .0001; 90% CI = –0.34 to 0.18). There was no sufficient evidence to suggest equivalence for total IV morphine doses (P = .189, 90% CI = –1.51 to 1.78; P = .169, 90% CI = –1.51 to 0.88). Conclusions Oral acetaminophen and ibuprofen alone may provide similar analgesia to traditional regimens with reduced risks following pediatric palatoplasty.
Prevalence and causes of visual impairment amongst older adults in a rural area of North India: a cross-sectional study

Objectives To determine the prevalence, causes and associated factors for visual impairment (VI) in rural population of Jhajjar district, Haryana, north India. Methods A community-based, cross-sectional study was conducted in two blocks of Jhajjar district. A total of 34 villages were selected using probability proportionate to size sampling method. Adults aged 50 years and above were selected using compact segment cluster sampling approach. Presenting visual acuity using LogMAR E chart was measured along with collection of other demographic details as part of the house-to-house survey. Subjective refraction and torch light examination were performed at a clinic site within the village to ascertain VI and its cause. VI was considered when presenting visual acuity was less than 6/18 in the better eye. Common causes of VI viz uncorrected refractive errors, cataract, central corneal opacity and others were noted by optometrists. Descriptive analysis was undertaken. Multivariate logistic regression analysis was performed for determining associated factors with VI. Results Out of 2025 enumerated adults, 1690 (83.5%) were examined at the household level and 1575 (78%) completed all study procedures. The prevalence of VI was found to be 24.5% (95% CI 21.1 to 26.3) and blindness was 5% (95% CI 3.9 to 6.1). The most common causes of VI were uncorrected refractive errors (50%) and cataract (37%). The VI in study participants was found to be associated with age, gender, marital and educational status. Conclusions VI is still a public health problem in rural population of Jhajjar district, Haryana. Provision of spectacles and cataract surgical services are simple interventions to address this issue.
A Review of Randomized Controlled Trials in Cleft and Craniofacial Surgery

Abstract This study presents a systematic review of randomized controlled trials (RCTs) in cleft and craniofacial surgery. All studies reporting on RCTs in cleft and craniofacial surgery were identified on PubMed using the search terms “cleft,” “velopharyngeal insufficiency,” “velopharyngeal dysfunction,” “nasoalveolar molding,” “gingivoperiosteoplasty,” “Pierre Robin sequence,” “craniofacial,” “craniosynostosis,” “craniofacial microsomia,” “hemifacial microsomia,” “hypertelorism,” “Le Fort,” “monobloc,” “distraction osteogenesis,” “Treacher Collins,” and “Goldenhar. ” Studies were excluded if they were not randomized, did not focus primarily on topics related to cleft or craniofacial surgery, included repeat publications of data, or were unavailable in English. Studies were evaluated on demographic and bibliometric data, study size, specific area of focus, and findings reported. Four hundred forty-seven unique studies were identified. One hundred eighty-three papers met inclusion criteria (115 cleft lip and palate, 65 craniofacial, and 3 spanning both disciplines). Sixty-six (36%) were dedicated to topics related to surgical techniques. There were no studies comparing current cleft lip or soft palate repair techniques and no studies on cleft rhinoplasty. The most frequently reported surgical topic was cleft palate. There were several studies on orthognathic techniques which compared distraction osteogenesis to traditional advancement. Most craniofacial operations, such as cranial vault remodeling and frontofacial advancement/distraction, were not represented. Several standard operations in cleft and craniofacial surgery are not supported by Level I evidence from randomized controlled trials. Our community should consider methods by which more RCTs can be performed, or redefine the acceptable standards of evidence to guide our clinical decisions.
Early determinants of women in the IT workforce: a model of girls' career choices

Purpose – To develop a testable model for girls' career choices in technology fields based on past research and hypotheses about the future of the information technology (IT) workforce.Design/methodology/approach – Review and assimilation of literature from education, psychology, sociology, computer science, IT, and business in a model that identifies factors that can potentially influence a girl's choice towards or against IT careers. The factors are categorized into social factors (family, peers, and media), structural factors (computer use, teacher/counselor influence, same sex versus coeducational schools), and individual differences. The impact of culture on these various factors is also explored.Findings – The model indicates that parents, particularly fathers, are the key influencers of girls' choice of IT careers. Teachers and counselors provide little or no career direction. Hypotheses propose that early access to computers may reduce intimidation with technology and that same‐sex education may s.
Metabolic syndrome in people with a psychotic illness: is cannabis protective?

Background Rates of the metabolic syndrome in people with psychotic illness are high. Emerging evidence suggests that cannabis use may have a positive impact on cardiometabolic risk factors in the general population, but little is known about its impact for people with psychotic illness. Our aim was to investigate whether the rate of the metabolic syndrome in people with psychotic illness was associated with frequency of cannabis use. Method The 2010 Australian psychosis survey used a two-phase design to randomly select a nationally representative sample of 1825 adults with psychotic illness for interview and physical assessment. This study is based on 1813 participants who provided data on cannabis use. Multiple logistic regression was used to model the influence of frequency of cannabis use on the metabolic syndrome, adjusting for potential covariates including antipsychotic medication use, smoking, alcohol use and cognitive function. Results One-third (33.0%) of participants had used cannabis in the past year. The proportion of non-users, occasional users and frequent users with the metabolic syndrome was 63.0, 51.7 and 43.5%, respectively (p < 0.001). In unadjusted analyses, both occasional use and frequent cannabis use were associated with significantly lower odds of the metabolic syndrome. In the adjusted analyses, the association between the metabolic syndrome and frequent cannabis use remained significant [odds ratio = 0.56, 95% confidence interval (CI) 0.39–0.80], but not the association with occasional use (odds ratio = 0.75, 95% CI 0.49–1.13). Conclusions While cannabis use may be detrimental for mental health, these data suggest that it may also have a cardiometabolic protective effect. Further investigation is required to understand the mechanism underlying this paradoxical finding.
Topological index‐calculation of DAEs in circuit simulation

In electric circuit simulation we are confronted with highly nonlinear DAEs with low smoothness properties. They may have index 2 but they do not belong to the class of Hessenberg form systems that are well understood. The classic and the charge‐oriented modified analysis are shown to lead to the same DAE‐index if the circuit models satisfy some natural assumptions.
Differential permethrin susceptibility of head lice sampled in the United States and Borneo.

BACKGROUND Pediculiasis is treated aggressively in the United States, mainly with permethrin- and pyrethrin-containing pediculicides. Increasingly frequent anecdotal reports of treatment failure suggest the emergence of insecticidal resistance by these lice. OBJECTIVE To confirm or refute the susceptibility of head lice sampled in the United States to permethrin. DESIGN Survey. Head lice were removed from children residing where pediculicides are readily available and where such products are essentially unknown. Their survival was compared following exposure to residues of graded doses of permethrin in an in vitro bioassay. SETTING School children from Massachusetts, Idaho, and Sabah (Malaysian Borneo). SUBJECTS In the United States, 75 children aged 5 to 8 years. In Sabah, 59 boys aged 6 to 13 years. Virtually all sampled US children had previously been treated with pediculicides containing pyrethrins or permethrin; none of the Sabahan children were so exposed. MAIN OUTCOME MEASURE Survival of head lice exposed to permethrin. RESULTS Permethrin did not affect head lice sampled from chronically infested US children who had previously been treated for pediculiasis. The slope of the dose-response regression line for these lice did not differ significantly from zero (P = .66). This pediculicide immobilized lice sampled in Sabah. Mortality correlated closely with permethrin concentration (P = .008). CONCLUSIONS Head lice in the United States are less susceptible to permethrin than are those in Sabah. The pyrethroid susceptibility of the general population of head lice in the United States, however, remains poorly defined. Accordingly, these relatively safe over-the-counter preparations may remain the pediculicides of choice for newly recognized louse infestations.
Exact relation between spatial mean enstrophy and dissipation in confined incompressible flows

An exact non‐trivial relation between spatial mean enstrophy and dissipation in closed incompressible flows is derived analytically, which also applies to unbounded fluid domains when the velocity decays to zero sufficiently rapidly at infinity. The quantity 〈ω2−σ2〉 is shown to depend only on the boundary conditions, and it is pointed out that in many confined flows, the equality 〈ω2〉=〈σ2〉 is not satisfied.