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"O",
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"B-T204",
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"I-T204",
"O",
"O",
"O",
"B-T204",
"I-T204",
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"O",
"O",
... | [
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... | [
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97... | Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi - Challenge Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the "LbSapSal" vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T0), during the post-vaccination protocol (T3rd) and after early (T90) and late (T885) times following L. chagasi - challenge. Our major data indicated that immunization with " LbSapSal " is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after " LbSapSal " immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the " LbSapSal " vaccination is a potential tool to control the Leishmania chagasi infection. |
[
"O",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"B-T058",
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"I-T058",
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"O",
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"... | [
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"db_id": null,... | [
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... | Assessment of the Relationship Between Clinicophysiologic and Magnetic Resonance Imaging Findings of the Temporomandibular Disorder Patients Temporomandibular joint disorders (TMJDs) are a complex group of disorders that comprise dysfunctions of the temporomandibular joint (TMJ). In this study, we analyzed the objective and subjective findings of the TMJD patients by using Helkimo anamnesis (Ai) and clinical dysfunction (Di) indices, and tried to document a relation between these findings and magnetic resonance imaging (MRI) results.Ninety-eight patients who were admitted to our clinic were included in the study. The clinical evaluation was performed by using Ai, an 8-question-survey based on the objective symptoms of patients; Di, concluded as the score of 5 objective measurements of physical examination. The morphology of the TMJ was evaluated by MRI, and the findings were analyzed and statistically compared with respect to the Di .The most commonly seen symptoms were noise during mandibular movement (58%), pain around the joint (42.5%), and pain with mandibular movements (40%). Seventeen patients (17.3%) were Di0, 47 (48%) were DiI, 24 (24.5%) were DiII, and 10 (10.2%) were DiIII. Thirty-seven patients (37.8%) had abnormal MRI findings, whereas 61 patients (62.2%) had normal MRI. The most commonly encountered pathology was anterior disc displacement with reduction, which was reported in 15 patients. Increased TMJ Di, which points a more progressed TMJD, was found to be significantly related with the pathological MRI findings (P < 0.05). MRI is especially effective in particularly those with high Di; therefore, the results of the study may give a prospect in which types of patients does MRI give a valuable data toward diagnosis, in which stages of the TMJD should we expect pathological findings, and thereby preventing unnecessary use of MRI in patients with symptoms of TMJD. |
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"O",
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"I-T038",
"O",
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"O",
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"O",
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"db_id": "C0887944",
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... | Stochastic Subcellular Organization of Dense-Core Vesicles Revealed by Point Pattern Analysis Dense-core vesicles (DCVs) are regulated secretory organelles found in many types of neurons. In neurons of the hippocampus, their cargo includes proteins that mediate several pivotal processes, including differentiation and synaptic plasticity. Motivated by interest in DCV distribution and its impact on cargo action, we have used fluorescence microscopy and statistical analysis to develop a quantitative model of the subcellular organization of DCVs in hippocampal neurons that are spontaneously active (their most prevalent state). We also have tested the functionally motivated hypothesis that these organelles are synaptically enriched. Variance-to-mean ratio, frequency distribution, and Moran's autocorrelation analyses reveal that DCV distribution along shafts, and within synapses, follows Poisson statistics, establishing that stochastically dictated organization sustains cargo function. Occupancy in boutons exceeds that at nearby extrasynaptic axonal sites by approximately threefold, revealing significant local presynaptic enrichment. Widespread stochastic organization is consistent with the emerging functional importance of synaptically and extrasynaptically localized DCVs. Presynaptic enrichment is consistent with the established importance of protecting presynaptic sites from depletion of DCV cargo. These results enhance understanding of the link between DCV organization and mechanisms of cargo action, and they reinforce the emerging theme that randomness is a prevalent aspect of synaptic organization and composition. |
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"O",
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"O",
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"O",
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"O",
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"I-T038",
"I-T038",
"O",
"B-T038",
"I-T038",
"O",
"O",
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... | [
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9... | C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling Hexanucleotide expansion in an intron of the C9orf72 gene causes amyotrophic lateral sclerosis and frontotemporal dementia. However, beyond bioinformatics predictions that suggested structural similarity to folliculin, the Birt-Hogg-Dubé syndrome tumor suppressor, little is known about the normal functions of the C9orf72 protein. To address this problem, we used genome-editing strategies to investigate C9orf72 interactions, subcellular localization, and knockout (KO) phenotypes. We found that C9orf72 robustly interacts with SMCR8 (a protein of previously unknown function). We also observed that C9orf72 localizes to lysosomes and that such localization is negatively regulated by amino acid availability. Analysis of C9orf72 KO, SMCR8 KO, and double-KO cell lines revealed phenotypes that are consistent with a function for C9orf72 at lysosomes. These include abnormally swollen lysosomes in the absence of C9orf72 and impaired responses of mTORC1 signaling to changes in amino acid availability (a lysosome - dependent process) after depletion of either C9orf72 or SMCR8. Collectively these results identify strong physical and functional interactions between C9orf72 and SMCR8 and support a lysosomal site of action for this protein complex. |
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... | [
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... | Narcolepsy Following Yellow Fever Vaccination: A Case Report Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental factors can "trigger" narcolepsy with cataplexy in a genetically susceptible population. Here, we describe the case of a 13-year-old boy with narcolepsy following yellow fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy. Polysomnography showed rapid sleep onset with rapid eye movement (REM) latency of 47 min, significant sleep fragmentation and a mean sleep latency of 1.6 min with sleep onset REM in four out of four nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro-immunological disorder. |
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"O",
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... | Plasticity and Adult Neurogenesis in Amphibians and Reptiles: More Questions than Answers Studies of the relationship between behavioral plasticity and new cells in the adult brain in amphibians and reptiles are sparse but demonstrate that environmental and hormonal variables do have an effect on the amount of cell proliferation and/or migration. The variables that are reviewed here are: enriched environment, social stimulation, spatial area use, season, photoperiod and temperature, and testosterone. Fewer data are available for amphibians than for reptiles, but for both groups many issues are still to be resolved. It is to be hoped that the questions raised here will generate more answers in future studies. |
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"O",
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77,... | The Role of Global and Local Visual Information during Gaze - Cued Orienting of Attention Gaze direction is an important social communication tool. Global and local visual information are known to play specific roles in processing socially relevant information from a face. The current study investigated whether global visual information has a primary role during gaze - cued orienting of attention and, as such, may influence quality of interaction. Adults performed a gaze - cueing task in which a centrally presented face cued (valid or invalid) the location of a peripheral target through a gaze shift. We measured brain activity (electroencephalography) towards the cue and target and behavioral responses (manual and saccadic reaction times) towards the target. The faces contained global (i.e. lower spatial frequencies), local (i.e. higher spatial frequencies), or a selection of both global and local (i.e. mid-band spatial frequencies) visual information. We found a gaze cue - validity effect (i.e. valid versus invalid), but no interaction effects with spatial frequency content. Furthermore, behavioral responses towards the target were in all cue conditions slower when lower spatial frequencies were not present in the gaze cue. These results suggest that whereas gaze - cued orienting of attention can be driven by both global and local visual information, global visual information determines the speed of behavioral responses towards other entities appearing in the surrounding of gaze cue stimuli. |
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... | Dietary Intake and Cardiovascular Risk Factors in Icelanders Following Voluntarily a Low Carbohydrate Diet Most studies regarding low-carbohydrate diets (LCDs) have been intervention studies. The aim of the current study was to investigate dietary intake and cardiovascular risk factors among individuals who voluntarily follow a LCD. A cross-sectional study was conducted (N = 54, 20-66yrs) in Reykjavik, Iceland. Participants recorded food intake for three days. Blood samples were analyzed for cardiovascular risk factors. Nearly half of the participants were obese and around 60% had been on a LCD for ≥ 6 months. Fifty percent claimed they had lost weight during the past month. The median intake of carbohydrate, protein and fat were 8%, 22% and 68% E (hereof 25% saturated fatty acids), respectively. The consumption of bread and wholegrain cereals was very low (<5g/day), including the intake of dietary fiber (11g/day). Median fruit intake was 12 g/day. Intake of red meat and meat products was double that of the general population or ~900 g/ week. Median intake of vitamins and minerals were mostly higher than the estimated average requirements. Cardiovascular risk factors were mostly within normal range. Mean blood lipids were slightly elevated although the high density lipoprotein / total cholesterol ratio was normal. Despite poor diet quality and high prevalence of obesity, individuals who voluntarily follow a LCD have cardiovascular risk factors mostly within reference range. These individuals consume very low amounts of carbohydrates and high amounts of fat and saturated fat acids. Intake of red meat and processed meat exceeds recommended intake. Very low intake of whole grain cereals and fruits results in low intake of fiber. Long term health implications need to be examined further in longitudinal studies. |
[
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... | [
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"db_id": "C000... | [
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... | Teriparatide: benefit and safety for bone disease in CKD patients undergoing hemodialysis Teriparatide, 1-34 parathyroid hormone, is one of effective treatments for osteoporosis. Teriparatide shows an anabolic effect for bone formation, as a result, increases bone mineral density as well as prevention of fractures in the general population. On the other hand, there are a few report about the effect of teriparatide on increase of bone mineral density in maintenance hemodialysis patients. In addition to CKD-MBD, osteoporosis is also an important pathological change in ESRD patients, therefore its safety and efficacy should be discussed in more detail. |
[
"B-T103",
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"I-T038",
"I-T038",
"I-T038",
"I-T038",
"O",
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"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O... | [
{
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{
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"db_id": "C4288963",
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"db_id": "C4288963",
"db_name": "U... | [
"Polyanionic",
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0,
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55,
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71,
73
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74,
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79,
86
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87,
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97,
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... | Polyanionic carbosilane dendrimers prevent hepatitis C virus infection in cell culture Hepatitis C virus (HCV) infection is a major biomedical problem worldwide. Although new direct antiviral agents (DAAs) have been developed for the treatment of chronic HCV infection, the potential emergence of resistant virus variants and the difficulties to implement their administration worldwide make the development of novel antiviral agents an urgent need. Moreover, no effective vaccine is available against HCV and transmission of the virus still occurs particularly when prophylactic measures are not taken. We used a cell-based system to screen a battery of polyanionic carbosilane dendrimers (PCDs) to identify compounds with antiviral activity against HCV and show that they inhibit effective virus adsorption of major HCV genotypes. Interestingly, one of the PCDs irreversibly destabilized infectious virions. This compound displays additive effect in combination with a clinically relevant DAA, sofosbuvir. Our results support further characterization of these molecules as nanotools for the control of hepatitis C virus spread. |
[
"B-T033",
"I-T033",
"I-T033",
"I-T033",
"O",
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"B-T103",
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"O",
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"O",
"O",
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"I-T038",
"O",
"O",
... | [
{
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{
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{
"db_id": "C0243095",
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},
{
"db_id": null,
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{
"db_id": null,
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}... | [
"Anti",
"-",
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26,
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[
30,
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35,
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82,... | Anti-nociceptive roles of the glia -specific metabolic inhibitor fluorocitrate in paclitaxel - evoked neuropathic pain Paclitaxel (Taxol) is a powerful chemotherapy drug used in breast cancers, but it often causes neuropathic pain, leading to the early cessation of therapy and poor treatment outcomes. Approaches for the management of paclitaxel - induced neuropathic pain are urgently needed. The involvement of spinal astrocytes in the pathogenesis of paclitaxel - induced neuropathy has been reported, but little is known about the role of fluorocitrate (FC), a selective inhibitor of astrocyte activation, during neuropathic pain related to paclitaxel treatment. In this study, we investigated the effects of FC on paclitaxel - induced neuropathic pain. Glial fibrillary acidic protein (GFAP) expression was determined to assess astrocyte activation. To explore the mechanisms involved, the expression of glial glutamate transporter 1 (GLT-1) and the activation of mitogen-activated protein kinases in the spinal dorsal horn were analyzed. The results showed that paclitaxel decreased the mechanical nociceptive thresholds and increased GFAP expression, leading to spinal astrocyte activation. After paclitaxel treatment, GLT-1 was significantly down-regulated, and the phosphorylation of ERK1 / 2 and JNK were obviously up-regulated. However, paclitaxel treatment did not increase p38 phosphorylation. Additional studies showed that paclitaxel - evoked mechanical hypersensitivity was reduced by FC treatment. Moreover, FC treatment inhibited the activation of astrocytes and reversed the changes in GLT-1 expression and MAPK phosphorylation. Further study indicated that FC did not influence the antitumor effect of paclitaxel, suggesting that FC blocked paclitaxel - induced neuropathic pain without antagonizing its antitumor effect. Together, these results suggested that paclitaxel induced astrocyte-specific activation, which may contribute to mechanical allodynia and hyperalgesia, and that FC could be a potential therapeutic agent for paclitaxel - induced neuropathic pain. |
[
"B-T038",
"O",
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"I-T038",
"I-T038",
"O",
"O",
"O",
"O",
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"I-T017",
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"I-T017",
"I-T017",
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"O",
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... | [
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"db_id": "C0563212",
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{
"db_id": "C0563212",
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"db_id": null,
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}... | [
"Regeneration",
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41,
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48,
52
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53,
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57,
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... | Regeneration of mandibular ameloblastoma defect with the help of autologous dental pulp stem cells and buccal pad of fat stromal vascular fraction Ameloblastoma is benign odontogenic tumor, which is locally aggressive in behavior. Till date, the treatment of choice is resection and reconstruction using a variety of modalities. Inadequate resection may lead to many complications such as bone deformity and dysfunction. This report is about a 14- year-old male with ameloblastoma treated with autologous dental pulp stem cells (DPSCs) and stromal vascular fraction (SVF) and evidence of bone regeneration. Marsupialization was performed; tooth was extracted and sent for DPSC cultivation. On the day of surgery, SVF was processed from buccal pad of fat, and platelet-rich fibrin (PRF) was prepared from patient's peripheral blood. During the procedure, labial plate resection and curating of tumor lining were done. After which, a mesh packed with SyboGraft T-plug, prepared SVF, DPSCs, and PRF were placed over lingual cortex and pressure dressing was done. After the 1(st) month of surgery the postoperative course was uneventful, the wound shrinkage led to exposure of mesh in the intraoral region. Removal of exposed mesh was done. The correction surgery with removal of part of mesh and primary closure was achieved with SyboGraft plug, SVF and PRF. Enhanced bone formation was seen in post-operative OPG and CT Scan after 10(th) month. In this article, we propose an innovative approach to manage these cases by using a combination of autologous DPSC and buccal pad of fat SVF to regenerate a mandibular defect left by the resection of an ameloblastoma with 1.5 year follow-up. We were able to demonstrate bone regeneration using this technique with no recurrence of tumor. |
[
"O",
"O",
"O",
"O",
"O",
"B-T091",
"B-T170",
"I-T170",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T092",
"I-T092",
"I-T092",
"O",
"B-T092",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"... | [
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"db_id": "C028... | [
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... | Considering Cost-Effectiveness in Cardiology Clinical Guidelines: Progress and Prospects Since the 1980s, when the American College of Cardiology (ACC) and the American Heart Association (AHA) established a joint task force to examine the use of cardiovascular procedures and therapies, cardiologists have been leaders in the development of clinical practice guidelines. The ACC/AHA guidelines development process has evolved considerably over the last 30 or more years. Guidelines now focus on clinical conditions, such as angina, instead of procedures, such as bypass surgery. There is a formal organizational structure, with dedicated staff, a standing committee on practice guidelines, and specific panels of volunteer experts on each topic. This process tightly manages conflicts of interest and strives for evidence-based, as opposed to opinion-based, guidelines, with a clear citation of the supporting evidence. Traditional clinical guidelines consider only what is best for the individual patient, and have explicitly not considered the cost to society. Nevertheless, in many guidelines development meetings, high cost was implicitly considered: if a procedure was extremely costly, the evidence needed to be very strong. The Guidelines Committee recognized that cost considerations ought to be made more transparent, and that the evidence on economic value should be explicitly cited when available. These considerations were formalized by a recent white paper on incorporating economic considerations into ACC/AHA guidelines. In considering value, it is necessary to assess the quality of the evidence as well as to define levels of value. The next ACC/AHA guideline will incorporate value as a part of its recommendations. This will be an evidence-based process in which published economic assessments relating to key questions will be reviewed. |
[
"O",
"O",
"O",
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"I-T058",
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"B-T204",
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"I-T103",
"O",
"B-T103",
"O",
"O",
"O",
"B-T082",
"I-T082",
"O",
... | [
{
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{
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"db_id... | [
"Molecular",
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"of",
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"APRIL",
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... | [
[
0,
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30,
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37,
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43,
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47,
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51,
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[
62,
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[
71,
77
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[
78,
81
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[
82,
92
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93,
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... | Molecular Characterization of Equine APRIL and its Expression Analysis During the Adipogenic Differentiation of Equine Adipose - Derived Stem Cell In Vitro A proliferation inducing ligand (APRIL) is a member of the TNF superfamily. It shares two receptors with B-cell activating factor (BAFF), B-cell maturation antigen (BCMA), and transmembrane activator and CAML interactor (TACI). Herein, the equine APRIL was identified from equine adipose-derived stem cell (ASC), and the protein expression of APRIL and its related molecules were detected during the adipogenic differentiation of equine ASC in vitro. The equine APRIL gene was located on chromosome 11, spans 1852 base pairs (bp). Its open reading frame covers 753 bp, encoding a 250-amino acid protein with the typical TNF structure domain. During the two weeks' adipogenic differentiation of equine ASC, although the protein expression of APRIL and TACI had an insignificant change, that of BCMA increased significantly. Moreover, with the addition of recombinant protein His6-sAPRIL, a reduced differentiation of equine ASC toward adipocyte was detected. These results may provide the basis for investigating the role of APRIL in ASC adipogenic differentiation. |
[
"B-T058",
"I-T058",
"I-T058",
"O",
"O",
"O",
"B-T201",
"O",
"O",
"B-T038",
"I-T038",
"O",
"B-T201",
"I-T201",
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"B-T038",
"I-T038",
"O",
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"B-T062",
"I-T062",
"I-T062",
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"O",
"O",
"B-T058",
"I-T058",
"B-T058",
"O",
"O",
"O",
"O",
"O",
... | [
{
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},
{
"db_id": "C1446041",
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{
"db_id": "C1446041",
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{
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{
"db_id": null,
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{
"db_id": null,
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{
... | [
"Serum",
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[
0,
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6,
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11,
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[
19,
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[
29,
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[
32,
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[
34,
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[
44,
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[
47,
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53,
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58,
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77,
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8... | Serum mass profile signature as a biomarker of early lung cancer Circulating molecular biomarkers of lung cancer may allow the pre-selection of candidates for computed tomography screening or increase its efficacy. We aimed to identify features of serum mass profile distinguishing individuals with early lung cancer from healthy participants of the lung cancer screening program. Blood samples were collected during a low-dose computed tomography (LD-CT) screening program performed by one institution (Medical University of Gdansk, Poland). MALDI-ToF mass spectrometry was used to characterize the low- molecular-weight (1000-14,000Da) serum fraction. The analysis comprised 95 patients with early stage lung cancer (including 30 screen-detected cases) and a matched group of 285 healthy controls. The cases were split into two independent cohorts (discovery and validation), analyzed separately 6 months apart. Several molecular components of serum (putatively components of endogenous peptidome) discriminating patients with early lung cancer from controls were identified in a discovery cohort. This allowed building an effective cancer classifier as a model tuned to maximize negative predictive value, with an area under the curve (AUC) of 0.88, a negative predictive value of 100%, and a positive predictive value of 48%. However, the classifier performed worse in a validation cohort including independent sample sets (AUC 0.73, NPV 88% and PPV 30%). We developed a serum mass profile -based signature identifying patients with early lung cancer. Although this marker has insufficient value as a stand-alone preselecting tool for LD-CT screening, its potential clinical usefulness in evaluation of indeterminate pulmonary nodules deserves further investigation. |
[
"O",
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"O",
"B-T204",
"I-T204",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
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"O",
"O",
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"O",
"O",
"B-T204",
"I-T204",
"O",
"O",
"O",
"O",
"B-T204",
"B-T20... | [
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{
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{
"db_id": "C3849275",
"db_name": "UMLS"
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{
"db_id": "C3849275",
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83,
... | A R2R3-MYB transcription factor from Lablab purpureus induced by drought increases tolerance to abiotic stress in Arabidopsis Few regulators for drought tolerance have been identified in Lablab purpureus which is a multipurpose leguminous crop. The transcription factor MYB is involved in regulatory networks in response to abiotic and biotic stresses in plants. A novel R2R3-MYB factor in L. purpureus has been identified. An suppression subtraction hybridization (SSH) library was constructed using root tissues of L. purpureus MEIDOU 2012 from well-watered and water-stress treatments that were subjected to drought stress for 10 days. In addition, the cDNA of LpMYB1 was identified based on the SSH library. The cDNA of LpMYB1 is 858 bp and encodes a 285- amino acid protein with a calculated mass of 33.4 kDa. The LpMYB1 protein localizes to the nucleus and has transactivation activity with the activation domain in the C terminal region of the protein. In LpMYB1 overexpressed Arabidopsis, the tolerance of transgenic seedlings to drought and salt was improved, and the germination potential of transgenic seeds increase in the presence of NaCl or ABA. LpMYB1 is a drought - responsive R2R3-MYB factor that can increase the drought and salt tolerance of LpMYB1 - overexpressed Arabidopsis. |
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{
"db_id": "C3469597",
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}... | [
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... | Pharmacokinetics of Repeated Melatonin Drug Administrations Prior to and After Surgery Recent clinical studies have documented the analgesic, anti-inflammatory, antioxidative and anxiolytic effects of exogenous melatonin. The pharmacokinetic properties of melatonin have primarily been investigated in experimental studies. The aim of this study was to estimate the pharmacokinetics of melatonin in patients undergoing surgery and general anesthesia. The study was designed as a prospective, two-phase cohort study. Patients were candidates for subpectoral breast augmentation surgery, and surgical procedures were performed by a single surgeon. The perioperative treatment protocol was standardized between patients. During the study, each patient received two separate oral administrations of melatonin 10 mg. Melatonin was administered 60 min before surgery, and at 9:00 p.m. the evening after surgery. The pharmacokinetic variables absorption half-life (t ½ absorption), time to maximal plasma concentration (T max), maximal plasma concentration (C max), elimination half-life (t ½ elimination), and area under the melatonin plasma concentration-time curve from time zero to infinity (AUC ∞) were estimated for both study phases. Median (interquartile range) values of t ½ absorption and T max were significantly increased during the postoperative phase [10.8 (6.9-15.1) min; 90.0 (48.8-120.0) min] compared with perioperatively [9.5 (6.3-16.5) min; 30.0 (15.0-30.0) min] (p = 0.034; p = 0.002), respectively. C max values were significantly higher during surgery [5497.5 (2077.1-13,233.8) pg/ml] compared with postoperative values [2340.5 (1672.4-8871.4) pg/ml] (p = 0.005). Correspondingly, t ½ elimination was significantly extended during the postoperative phase [103.5 (57.8-237.8) min] compared with the perioperative phase [60.5 (47.8-83.6) min] (p = 0.015). AUC ∞ did not differ between the study phases (p > 0.05). These preliminary results indicate that postoperative melatonin dose should be augmented compared with preoperative administration if corresponding melatonin plasma levels are intended. Furthermore, postoperative administration times should be advanced compared with preoperative administration. |
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... | [
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... | Interleukin-15 as a potential new target in Sjögren's syndrome - associated inflammation IL-15 is a key regulatory cytokine that shares many biological properties with IL-2. Recently, it has been shown that IL-15 could be up-regulated in T cell -mediated inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. However, the role and expression of IL-15 in the inflammatory autoimmune disease Sjögren's syndrome (SS) has not been investigated. In the present study we evaluated the expression of IL-15 mRNA and protein in minor salivary gland (MSG) biopsy specimens and in human salivary gland epithelial cell (SGEC) cultures obtained from patients with primary SS (pSS) and compared their expression with that seen in normal healthy control subjects. IL-15 gene and protein analysis revealed that SGEC are able to produce IL-15. Results obtained demonstrated that the number of IL-15(+) cultured SGEC was significantly higher in cells derived from patients with pSS in comparison with SGEC from healthy subjects; similar results were obtained for IL-15 immunoreactivity by using immunohistochemistry that revealed a strong expression both in acinar and in ductal cells from pSS MSG. These studies could provide a rational basis to determine whether IL-15 could be a good candidate for anti-cytokine therapy in chronic inflammatory pSS diseases. |
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97,... | Hypo-Vascular Liver Metastases Treated with Transarterial chemoembolization: Assessment of Early Response by Volumetric Contrast-Enhanced and Diffusion-Weighted Magnetic Resonance Imaging To evaluate the value of anatomic and volumetric functional magnetic resonance imaging (MRI) in early assessment of response to trans-arterial chemoembolization (TACE) in hypovascular liver metastases. This retrospective study included 52 metastatic lesions (42 targeted and 10 non-targeted) in 17 patients who underwent MRI before and early after TACE. Two reviewers reported response by anatomic criteria (Response Evaluation Criteria in Solid Tumor [RECIST], modified RECIST [mRECIST], and European Association for the Study of Liver Disease [EASL]) and functional criteria (volumetric apparent diffusion coefficient and contrast enhancement). treatment endpoint was RECIST at 6 months. A 2-sample paired t test was used to compare the mean changes after intra-arterial therapy. P < .05 was considered statistically significant. Reduction in mRECIST and EASL at 1 month was significant in the whole cohort as well as in responders by RECIST at 6 months, and the changes fulfilled partial response criteria for both metrics in responders. Responders also had significant changes in volumetric apparent diffusion coefficient (P = .01 and P = .03) and contrast enhancement (P < .0001 and P < .0001) at 1 month for both readers, respectively. At 1 month post treatment, responders did not fulfill RECIST criteria but fulfilled mRECIST and EASL criteria. In addition, volumetric contrast-enhanced and diffusion-weighted MRI may be helpful in evaluating early treatment response after TACE in hypovascular liver metastases in patients who have failed to respond to initial chemotherapy. |
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... | [
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... | [
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9... | Foliar uptake of fog in coastal California shrub species Understanding plant water uptake is important in ecosystems that experience periodic drought. In many Mediterranean -type climates like coastal California, plants are subject to significant drought and wildfire disturbance. During the dry summer months, coastal shrub species are often exposed to leaf wetting from overnight fog events. This study sought to determine whether foliar uptake of fog occurs in shrub species and how this uptake affects physiology and fuel condition. In a controlled greenhouse experiment, dominant California shrub species were exposed to isotopically labeled fog water and plant responses were measured. Potted plants were covered at the base to prevent root uptake. The deuterium label was detected in the leaves of four out of five species and in the stems of two of the species. While there was a minimal effect of foliar water uptake on live fuel moisture, several species had lower xylem tension and greater photosynthetic rates after overnight fog treatments, especially Salvia leucophylla. Coastal fog may provide a moisture source for many species during the summer drought, but the utilization of this water source may vary based on foliar morphology, phenology and plant water balance. From this study, it appears that drought -deciduous species (Artemisia californica and Salvia leucophylla) benefit more from overnight fog events than evergreen species (Adenostoma fasciculatum, Baccharis pilularis and Ceanothus megacarpus). This differential response to fog exposure among California shrub species may affect species distributions and physiological tolerances under future climate scenarios. |
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69,... | AKT / GSK3β Signaling in Glioblastoma Glioblastoma (GBM) is the most aggressive of primary brain tumors. Despite the progress in understanding the biology of the pathogenesis of glioma made during the past decade, the clinical outcome of patients with GBM remains still poor. Deregulation of many signaling pathways involved in growth, survival, migration and resistance to treatment has been implicated in pathogenesis of GBM. One of these pathways is phosphatidylinositol-3 kinases (PI3K)/protein kinase B (AKT) / rapamycin-sensitive mTOR-complex (mTOR) pathway, intensively studied and widely described so far. Much less attention has been paid to the role of glycogen synthase kinase 3 β (GSK3β), a target of AKT. In this review we focus on the function of AKT / GSK3β signaling in GBM. |
[
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... | [
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... | [
"A",
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22,
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[
25,
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[
31,
33
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[
34,
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39,
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72,
... | A Whole-Body Approach to Point of Care Ultrasound Ultrasonography is an essential imaging modality in the ICU used to diagnose and guide the treatment of cardiopulmonary failure. Critical care ultrasonography requires that all image acquisition, image interpretation, and clinical applications of ultrasonography are personally performed by the critical care clinician at the point of care and that the information obtained is combined with the history, physical, and laboratory information. Point-of-care ultrasonography is often compartmentalized such that the clinician will focus on one body system while performing the critical care ultrasonography examination. We suggest a change from this compartmentalized approach to a systematic whole-body ultrasonography approach. The standard whole-body ultrasonography examination includes thoracic, cardiac, limited abdominal, and an evaluation for DVT. Other elements of ultrasonography are used when clinically indicated. Each of these elements is reviewed in this article and are accompanied by a link to pertinent cases from the Ultrasound Corner section of CHEST. |
[
"B-T062",
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"I-T038",
"I-T038",
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56,
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66,
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... | Diagnosing a rare case of desmoplastic small round cell tumour on liver biopsy A 50- year -old male of Indian descent presented with jaundice and right hypochondrium pain. Following a computed tomography (CT) scan of the abdomen, a segment 7 liver lesion was visualized, accompanied by extensive peritoneal tumour deposits. An ultrasound guided liver biopsy was performed and histology showed loose nests and sheets of tumour cells with a small blue round cell morphology. The tumour cells showed patchy strong immunopositivity for cytokeratins (AE1/3, CK7, CK19) and synaptophysin, while showing diffuse strong perinuclear positivity for desmin. Interphase fluorescence in-situ hybridization (FISH) study using EWSR1 breakapart probe was positive for EWSR1 gene rearrangement. Desmoplastic small round cell tumour is a rare but aggressive intra-abdominal mesenchymal tumour. While the primary sites of involvement are usually the peritoneum and omentum, visceral involvement can occur. We wish to highlight the importance of considering this entity when evaluating a liver biopsy especially in a less than classical clinical context. |
[
"O",
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"B-T103",
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"O",
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"O",
"O",
"O",
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"O",... | [
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{
"db_id": "C0013161",
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... | [
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[
9... | A biodistribution study of solid lipid-polyethyleneimine hybrid nanocarrier for cancer RNAi therapy Solid lipid-polymer hybrid nanocarrier (LPN) was previously reported to achieve high siRNA transfection efficiency and induce sustained RNAi -based chemosensitizing effect at cellular level. In this study, our objectives were to evaluate the in vivo biodistribution of LPNs in a prostate cancer model and determine the factors that potentially affect tumor penetration by LPNs. The LPN formulation with the highest transfection efficiency (64%) and stability was selected for the study. Mice bearing tumors of PC-3Mcells were treated with LPNs labeled with IR780 or AF647 - siRNA. Near infrared imaging showed that LPNs achieved favorable in vivo biodistribution with high tumor /low organ ratios. LPN accumulation was also observed in liver metastatic tissue. Result of extravasation study confirmed that encapsulated siRNA molecules were able to escape into the tumor tissue at the extravascular area. When LPN levels in large (volume >750mm(3)) and small (<500mm(3)) tumors were compared, no significant difference was observed. However, both docetaxel pretreatment (72hbefore LPN) and concurrent docetaxel treatment significantly enhanced the tumor LPN levels by 3.9- and 3.1-fold, respectively (both p<0.01). In conclusion, LPN is a promising carrier system to deliver RNAi therapy to solid malignancies that also receive chemotherapy. |
[
"B-T103",
"O",
"O",
"O",
"O",
"B-T103",
"O",
"B-T204",
"O",
"O",
"O",
"O",
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"B-T103",
"B-T103",
"B-T062",
"I-T062",
"O",
"O",
"O",
"O",
"B-T103",
"I-T103",
"B-T103",
"B-T103",
"O",
"O",
"O",
"O",
"O",
"B-T033",
... | [
{
"db_id": "C0003289",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
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},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0036442",
"db_name": "UMLS"
},
{
"db_id... | [
"Antidepressant",
"-",
"like",
"effects",
"of",
"scopolamine",
"in",
"mice",
"are",
"enhanced",
"by",
"the",
"group",
"II",
"mGlu",
"receptor",
"antagonist",
"LY341495",
"Clinical",
"studies",
"have",
"shown",
"that",
"the",
"muscarinic",
"receptor",
"antagonist",... | [
[
0,
14
],
[
15,
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],
[
16,
20
],
[
21,
28
],
[
29,
31
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[
32,
43
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[
44,
46
],
[
47,
51
],
[
52,
55
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[
56,
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... | Antidepressant -like effects of scopolamine in mice are enhanced by the group II mGlu receptor antagonist LY341495 Clinical studies have shown that the muscarinic receptor antagonist scopolamine induces a potent and rapid antidepressant effect relative to conventional antidepressants. However, potential undesirable effects, including memory impairment, partially limit the use of scopolamine in psychiatry. In the present study, we propose to overcome these limitations and enhance the therapeutic effects of scopolamine via administration in combination with the group II metabotropic glutamate (mGlu) receptor antagonist, LY341495. Joint administration of sub-effective doses of scopolamine (0.03 or 0.1 mg/kg, i.p.) with a sub-effective dose of LY341495 (0.1 mg/kg, i.p.) induced a profound antidepressant effect in the tail suspension test (TST) and in the forced swim test (FST) in mice. This drug combination did not impair memory, as measured using the Morris water maze (MWM), and did not influence the locomotor activity of mice. Furthermore, we found that an AMPA receptor antagonist, NBQX (10 mg/kg), completely reversed the antidepressant-like activity of a mixture of scopolamine and LY341495 in the TST. However, this effect was not influenced by para-chlorophenylalanine (PCPA) pre-treatment, indicating a lack of involvement of serotonergic system activation in the antidepressant-like effects of jointly given scopolamine and LY341495. Therefore, the combined administration of low doses of the antimuscarinic drug scopolamine and the group II mGlu receptor antagonist LY341495 might be a new, effective and safe strategy in the therapy of depression. |
[
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T058",
"I-T058",
"B-T074",
"O",
"O",
"O",
"O",
"B-T103",
"I-T103",
"O",
"O",
"O",
"B-T033",
"I-T033",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T058",
"I-T058",
"O",
"O",
"O",
"O",
"B-T0... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
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},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db... | [
"Blinking",
"Phase",
"-",
"Change",
"Nanocapsules",
"Enable",
"Background",
"-",
"Free",
"Ultrasound",
"Imaging",
"Microbubbles",
"are",
"widely",
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"as",
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"agents",
"to",
"improve",
"the",
"diagnostic",
"capability",
"of",
"conventional",
",",
"h... | [
[
0,
8
],
[
9,
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[
14,
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],
[
15,
21
],
[
22,
34
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[
35,
41
],
[
42,
52
],
[
52,
53
],
[
53,
57
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[
58,
68
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[
69,
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[
77,
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[
90,
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9... | Blinking Phase-Change Nanocapsules Enable Background-Free Ultrasound Imaging Microbubbles are widely used as contrast agents to improve the diagnostic capability of conventional, highly speckled, low-contrast ultrasound imaging. However, while microbubbles can be used for molecular imaging, these agents are limited to the vascular space due to their large size (> 1 μm). Smaller microbubbles are desired but their ultrasound visualization is limited due to lower echogenicity or higher resonant frequencies. Here we present nanometer scale, phase changing, blinking nanocapsules (BLInCs), which can be repeatedly optically triggered to provide transient contrast and enable background-free ultrasound imaging. In response to irradiation by near-infrared laser pulses, the BLInCs undergo cycles of rapid vaporization followed by recondensation into their native liquid state at body temperature. High frame rate ultrasound imaging measures the dynamic echogenicity changes associated with these controllable, periodic phase transitions. Using a newly developed image processing algorithm, the blinking particles are distinguished from tissue, providing a background-free image of the BLInCs while the underlying B-mode ultrasound image is used as an anatomical reference of the tissue. We demonstrate the function of BLInCs and the associated imaging technique in a tissue -mimicking phantom and in vivo for the identification of the sentinel lymph node. Our studies indicate that BLInCs may become a powerful tool to identify biological targets using a conventional ultrasound imaging system. |
[
"O",
"B-T058",
"O",
"B-T017",
"B-T170",
"I-T170",
"B-T082",
"O",
"O",
"B-T170",
"I-T170",
"I-T170",
"O",
"B-T038",
"B-T062",
"I-T062",
"O",
"O",
"O",
"B-T017",
"B-T017",
"B-T058",
"B-T170",
"O",
"B-T058",
"I-T058",
"I-T058",
"I-T058",
"O",
"B-T058",
"O",
... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0220825",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0006104",
"db_name": "UMLS"
},
{
"db_id": "C0925206",
"db_name": "UMLS"
},
{
"db_id": "C0925206",
"db_name": "UMLS"
}... | [
"Comparative",
"Evaluation",
"for",
"Brain",
"Structural",
"Connectivity",
"Approaches",
":",
"Towards",
"Integrative",
"Neuroinformatics",
"Tool",
"for",
"Epilepsy",
"Clinical",
"Research",
"Recent",
"advances",
"in",
"brain",
"fiber",
"tractography",
"algorithms",
"an... | [
[
0,
11
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[
12,
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],
[
23,
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[
27,
32
],
[
33,
43
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[
44,
56
],
[
57,
67
],
[
67,
68
],
[
69,
76
],
[
77,
88
],
[
89,
105
],
[
106,
110
],
[
111,
114
],
... | Comparative Evaluation for Brain Structural Connectivity Approaches: Towards Integrative Neuroinformatics Tool for Epilepsy Clinical Research Recent advances in brain fiber tractography algorithms and diffusion Magnetic Resonance Imaging (MRI) data collection techniques are providing new approaches to study brain white matter connectivity, which play an important role in complex neurological disorders such as epilepsy. Epilepsy affects approximately 50 million persons worldwide and it is often described as a disorder of the cortical network organization. There is growing recognition of the need to better understand the role of brain structural networks in the onset and propagation of seizures in epilepsy using high resolution non-invasive imaging technologies. In this paper, we perform a comparative evaluation of two techniques to compute structural connectivity, namely probabilistic fiber tractography and statistics derived from fractional anisotropy (FA), using diffusion MRI data from a patient with rare case of medically intractable insular epilepsy. The results of our evaluation demonstrate that probabilistic fiber tractography provides a more accurate map of structural connectivity and may help address inherent complexities of neural fiber layout in the brain, such as fiber crossings. This work provides an initial result towards building an integrative informatics tool for neuroscience that can be used to accurately characterize the role of fiber tract connectivity in neurological disorders such as epilepsy. |
[
"O",
"O",
"O",
"O",
"B-T058",
"I-T058",
"I-T058",
"O",
"B-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T058",
"O",
"B-T058",
"I-T058",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"O",
... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0184643",
"db_name": "UMLS"
},
{
"db_id": "C0184643",
"db_name": "UMLS"
},
{
"db_id... | [
"An",
"isolated",
"involvement",
"in",
"mental",
"health",
"care",
"-",
"experiences",
"of",
"parents",
"of",
"young",
"adults",
"To",
"explore",
"parents",
"'",
"involvement",
"in",
"the",
"informal",
"and",
"professional",
"care",
"of",
"their",
"young",
"ad... | [
[
0,
2
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[
3,
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],
[
12,
23
],
[
24,
26
],
[
27,
33
],
[
34,
40
],
[
41,
45
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[
46,
47
],
[
48,
59
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[
60,
62
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[
63,
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[
71,
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[
74,
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8... | An isolated involvement in mental health care - experiences of parents of young adults To explore parents ' involvement in the informal and professional care of their young adult child with mental illness. A further aim was to examine concepts in the caring theory of ' Involvement in the light - Involvement in the dark ' in the context of mental health care. Mental illness has increased among young people in high-income countries, and suicide is now the leading cause of death for this group. Because of their disease, these young people may have difficulty in carrying out daily, taken-for-granted, tasks. Consequently, they often become dependent on their parents, and their parents shoulder a considerable responsibility. A secondary descriptive design with a deductive content analysis was used. Ten parents who have a son or daughter with long-term mental illness (aged 18-25 years) were interviewed. The deductive analysis was based on the caring theory of ' Involvement in the light - Involvement in the dark '. The results are described using the following concepts in the theory: ' Knowing ', ' Doing ', ' Being ' and ' Attitude of the health professionals '. The result are to a great extent consistent with the ' Involvement in the dark ' metaphor, which describes an isolated involvement in which the parents were not informed, seen or acknowledged by the health professionals. Continuous support by professionals with a positive attitude was described as being of decisive importance for meaningful involvement. The theory's transferability is strengthened to the mental health care context. Parents have a considerable need for knowledge that can enable them to choose how they should act (be) and what they should do, in order to help and support their child. Since the patient, the family members and the professionals are mutually dependent, it is important to make use of each other's knowledge in a partnership to achieve a common caring strategy. |
[
"B-T062",
"I-T062",
"I-T062",
"I-T062",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T097",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T098",
... | [
{
"db_id": "C0031928",
"db_name": "UMLS"
},
{
"db_id": "C0031928",
"db_name": "UMLS"
},
{
"db_id": "C0031928",
"db_name": "UMLS"
},
{
"db_id": "C0031928",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
}... | [
"Functional",
"Neuroimaging",
"Pilot",
"Study",
"of",
"Borderline",
"Personality",
"Disorder",
"in",
"Adolescents",
"Borderline",
"personality",
"disorder",
"(",
"BPD",
")",
"is",
"being",
"increasingly",
"recognized",
"by",
"clinicians",
"working",
"with",
"adolescen... | [
[
0,
10
],
[
11,
23
],
[
24,
29
],
[
30,
35
],
[
36,
38
],
[
39,
49
],
[
50,
61
],
[
62,
70
],
[
71,
73
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[
74,
85
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[
86,
96
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[
97,
108
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[
109,
117
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[
... | Functional Neuroimaging Pilot Study of Borderline Personality Disorder in Adolescents Borderline personality disorder (BPD) is being increasingly recognized by clinicians working with adolescents, and the reliability and validity of the diagnosis have been established in the adolescent population. Adolescence is known to be a period of high risk for BPD development as most patients identify the onset of their symptoms to be in the adolescent period. As with other mental health disorders, personality disorder, are thought to result from the interaction between biological and environmental factors. Functional neuroimaging studies are reporting an increasing amount of data on abnormal neuronal functions in BPD adult patients. However, no functional neuroimaging studies have been conducted in adolescents with BPD .Objectives This pilot project aims to evaluate the feasibility of a functional magnetic resonance imaging (fMRI) study coupled with clinical and psychological measures in adolescent girls with a diagnosis of BPD. It also aims to identify neuronal regions of interest (ROI) for the study of BPD in adolescent girls .Method Six female adolescents meeting DSM-IV criteria for BPD and 6 female adolescents without psychiatric disorder were recruited. Both groups were evaluated for BPD symptoms, depressive symptoms, impulsivity, affective lability, and other potential psychiatric comorbidities. We used fMRI to compare patterns of regional brain activation between these two groups as they viewed 20 positive, 20 negative and 20 neutral emotion-inducing pictures, which were presented in random order .Results Participants were recruited over a period of 22 months. The protocol was well tolerated by participants. Mean age of the BPD group and control group was 15.8 ± 0.9 years-old and 15.5 ± 1.2 years-old respectively. Psychiatric comorbidity and use of medication was common among participants in the BPD group. This group showed higher impulsivity and affective lability scores. For the fMRI task, BPD patients demonstrated greater differences in activation than controls, when viewing negative pictures compared with neutral pictures, in limbic regions (amygdala and right hippocampus and parahippocampal areas) as well as in the superior frontal gyrus, right precentral gyrus and cerebellum, while control group showed greater activation in left precentral gyrus and right orbitofrontal area. Viewing positive pictures compared with neutral pictures led to increased activation of the left hippocampus and both parahippocampal regions, as well as middle cingulate cortex, superior temporal gyrus and cerebellum in the BPD group. In the control group, positive-scene viewing led to increased activity in the left superior parietal gyrus and right middle / superior temporal gyrus .Conclusion Limbic regions and areas from the prefrontal and orbitofrontal cortex are potential ROI for the study of the neurophysiology of BPD in female adolescents. The larger studies are needed to better understand the neural features found in these young patients. |
[
"B-T058",
"I-T058",
"O",
"B-T204",
"I-T204",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"B-T038",
"O",
"O",
"B-T204",
"I-T204",
"O",
"O",
"B-T033",
"I-T033",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T03... | [
{
"db_id": "C3854164",
"db_name": "UMLS"
},
{
"db_id": "C3854164",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0008888",
"db_name": "UMLS"
},
{
"db_id": "C0008888",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
}... | [
"Genomic",
"Analyses",
"of",
"Cladophialophora",
"bantiana",
",",
"a",
"Major",
"Cause",
"of",
"Cerebral",
"Phaeohyphomycosis",
"Provides",
"Insight",
"into",
"Its",
"Lifestyle",
",",
"Virulence",
"and",
"Adaption",
"in",
"Host",
"Cladophialophora",
"bantiana",
"is"... | [
[
0,
7
],
[
8,
16
],
[
17,
19
],
[
20,
36
],
[
37,
45
],
[
45,
46
],
[
47,
48
],
[
49,
54
],
[
55,
60
],
[
61,
63
],
[
64,
72
],
[
73,
90
],
[
91,
99
],
[
1... | Genomic Analyses of Cladophialophora bantiana, a Major Cause of Cerebral Phaeohyphomycosis Provides Insight into Its Lifestyle, Virulence and Adaption in Host Cladophialophora bantiana is a dematiaceous fungus with a predilection for causing central nervous system (CNS) infection manifesting as brain abscess in both immunocompetent and immunocompromised patients. In this paper, we report comprehensive genomic analyses of C. bantiana isolated from the brain abscess of an immunocompetent man, the first reported case in Malaysia and Southeast Asia. The identity of the fungus was determined using combined morphological analysis and multilocus phylogeny. The draft genome sequence of a neurotrophic fungus, C. bantiana UM 956 was generated using Illumina sequencing technology to dissect its genetic fundamental and basic biology. The assembled 37.1 Mb genome encodes 12,155 putative coding genes, of which, 1.01% are predicted transposable elements. Its genomic features support its saprophytic lifestyle, renowned for its versatility in decomposing hemicellulose and pectin components. The C. bantiana UM 956 was also found to carry some important putative genes that engaged in pathogenicity, iron uptake and homeostasis as well as adaptation to various stresses to enable the organism to survive in hostile microenvironment. This wealth of resource will further catalyse more downstream functional studies to provide better understanding on how this fungus can be a successful and persistent pathogen in human. |
[
"B-T058",
"I-T058",
"I-T058",
"I-T058",
"I-T058",
"O",
"B-T058",
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"B-T038",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T062",
"O",
"O",
"B-T062",
"B-T058",
"O",
"B-T038",
"I-T038",... | [
{
"db_id": "C0022885",
"db_name": "UMLS"
},
{
"db_id": "C0022885",
"db_name": "UMLS"
},
{
"db_id": "C0022885",
"db_name": "UMLS"
},
{
"db_id": "C0022885",
"db_name": "UMLS"
},
{
"db_id": "C0022885",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": ... | [
"Flow",
"-",
"Induced",
"Dispersion",
"Analysis",
"for",
"Probing",
"Anti",
"-",
"dsDNA",
"Antibody",
"Binding",
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"Erythematosus",
"Patients",
":",
"Toward",
"a",
"New",
"Approach",
"for",
"Diagnosis",
"and",
"Patient",
... | [
[
0,
4
],
[
4,
5
],
[
5,
12
],
[
13,
23
],
[
24,
32
],
[
33,
36
],
[
37,
44
],
[
45,
49
],
[
49,
50
],
[
50,
55
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[
56,
64
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[
65,
72
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[
73,
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[
87,... | Flow-Induced Dispersion Analysis for Probing Anti-dsDNA Antibody Binding Heterogeneity in Systemic Lupus Erythematosus Patients: Toward a New Approach for Diagnosis and Patient Stratification Detection of immune responses is important in the diagnosis of many diseases. For example, the detection of circulating autoantibodies against double-stranded DNA (dsDNA) is used in the diagnosis of Systemic Lupus Erythematosus (SLE). It is, however, difficult to reach satisfactory sensitivity, specificity, and accuracy with established assays. Also, existing methodologies for quantification of autoantibodies are challenging to transfer to a point-of-care setting. Here we present the use of flow-induced dispersion analysis (FIDA) for rapid (minutes) measurement of autoantibodies against dsDNA. The assay is based on Taylor dispersion analysis (TDA) and is fully automated with the use of standard capillary electrophoresis (CE) based equipment employing fluorescence detection. It is robust toward matrix effects as demonstrated by the direct analysis of samples composed of up to 85% plasma derived from human blood samples, and it allows for flexible exchange of the DNA sequences used to probe for the autoantibodies. Plasma samples from SLE positive patients were analyzed using the new FIDA methodology as well as by standard indirect immunofluorescence and solid-phase immunoassays. Interestingly, the patient antibodies bound DNA sequences with different affinities, suggesting pronounced heterogeneity among autoantibodies produced in SLE. The FIDA based methodology is a new approach for autoantibody detection and holds promise for being used for patient stratification and monitoring of disease activity. |
[
"O",
"O",
"O",
"B-T170",
"I-T170",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"B-T033",
"I-T033",
"B-T098",
"I-T098",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T170",
"I-T170",
"I-T170",
"O",
"B-T033",
"I-T033",
"I-T033",
"... | [
{
"db_id": null,
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},
{
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},
{
"db_id": null,
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},
{
"db_id": "C2598146",
"db_name": "UMLS"
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{
"db_id": "C2598146",
"db_name": "UMLS"
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{
"db_id": null,
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{
"db_id... | [
"Diagnostic",
"Accuracy",
"of",
"Anthropometric",
"Indicators",
"in",
"the",
"Prediction",
"of",
"Urinary",
"Incontinence",
"in",
"Physically",
"Active",
"Older",
"Women",
"Purpose",
"To",
"determine",
"the",
"diagnostic",
"accuracy",
"and",
"the",
"cutoff",
"point"... | [
[
0,
10
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[
11,
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[
20,
22
],
[
23,
37
],
[
38,
48
],
[
49,
51
],
[
52,
55
],
[
56,
66
],
[
67,
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[
70,
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[
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[
91,
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... | Diagnostic Accuracy of Anthropometric Indicators in the Prediction of Urinary Incontinence in Physically Active Older Women Purpose To determine the diagnostic accuracy and the cutoff point of the variables conicity index, waist to height ratio and fat percentage to detect urinary incontinence in physically active older women. Method A total of 152 women were analyzed. The instruments used were the International Physical Activity Questionnaire (IPAQ [Area 4]) to check the level of physical activity, and the Diagnostic Form to obtain sociodemographic data and presence of urinary incontinence. To calculate the conicity index, waist to height ratio and fat percentage, body mass, height and waist circumference were measured. Descriptive and inferential statistics were used. Cutoff points, sensitivity (S) and specificity (SP) were determined by receiver operating characteristic (ROC) curves. A 5% significance level was adopted. Results The prevalence of urinary incontinence was of 32.2%. The cutoff point with better sensitivity and specificity for the conicity index was 1.23 (S = 87.8; SP = 35.9); for the waist to height ratio, it was 0.57 (S = 79.6; SP = 45.6); and for the fat percentage, it was 39.71 (S = 89.8; SP = 42.7). The area under the ROC curve was 0.666 for the conicity index, 0.653 for the waist to height ratio, and 0.660 for the fat percentage. Conclusions The cutoff points for the anthropometric measurements conicity index, waist to height ratio and fat percentage indicate that these measures can be used to predict urinary incontinence in physically active older women. Furthermore, fat percentage seemed to be the best measure for this population. |
[
"O",
"O",
"O",
"O",
"O",
"O",
"B-T082",
"B-T037",
"I-T037",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T082",
"B-T091",
"O",
"B-T170",
"O",
"O",
"O",
"B-T170",
"I-T170",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O"... | [
{
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"db_id": "C0817096",
... | [
"When",
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"aortic",
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"in",
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... | [
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[
30,
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[
39,
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72,... | When and how should we manage thoracic aortic injuries in the modern era? A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was what are the optimum treatment modality and timing of intervention for blunt thoracic aortic injury (BTAI) in the modern era? Of the 697 papers found using the reported search, 14 (5 meta-analyses, 2 prospective and 7 retrospective studies) represented the best evidence to answer the clinical question. The author, journal, country, date of publication, patient group studied, study type, relevant outcomes, results and weakness of these papers are tabulated. All five meta-analyses reported a reduction in mortality with thoracic endovascular aortic repair (TEVAR) compared with open repair (OR), but only four found the same benefit on paraplegia rate. Similarly, the two prospective and four retrospective studies showed significantly lower mortality with TEVAR than with OR. Only one study (a meta-analysis) reported a significantly lower stroke rate with TEVAR than with OR, whereas the 13 others reported a similar or even higher stroke rate. Other complication rates were identical. Four studies demonstrated that non-operative management (NOM) as a treatment option for BTAI was associated with increased mortality, even if it has declined in recent years. One study emphasized that some cases with minimal aortic injuries (Grade I and II on CT scan) could benefit from NOM. Regarding the timing of repair, only three studies analysed outcomes of delayed repair and reported significantly lower mortality than for early repair. We conclude that with lower mortality and similar overall complications including paraplegia but higher stroke rate, TEVAR is the most suitable treatment for BTAI in the modern era, where expertise exists, especially for cases of multiple associated injuries and in the older age group. Delayed aortic repair can be proposed based on CT scan analysis, but emergent repair should still be advocated for imminent free aortic rupture. NOM remains a therapeutic option but only with selected patients. |
[
"O",
"O",
"O",
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"B-T038",
"O",
"O",
"B-T033",
"I-T033",
"B-T038",
"I-T038",
"I-T038",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"B-T01... | [
{
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85,... | A novel germline POLE mutation causes an early onset cancer prone syndrome mimicking constitutional mismatch repair deficiency In a 14-year-old boy with polyposis and rectosigmoid carcinoma, we identified a novel POLE germline mutation, p.(Val411Leu), previously found as recurrent somatic mutation in ' ultramutated ' sporadic cancers. This is the youngest reported cancer patient with polymerase proofreading -associated polyposis indicating that POLE mutation p.(Val411Leu) may confer a more severe phenotype than previously reported POLE and POLD1 germline mutations. The patient had multiple café-au-lait macules and a pilomatricoma mimicking the clinical phenotype of constitutional mismatch repair deficiency. We hypothesize that these skin features may be common to different types of constitutional DNA repair defects associated with polyposis and early-onset cancer. |
[
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"B-T033",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"B-T038",
"I-T038",
"O",
"B-T204",
"I-T204",
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"I-T204",
"I-T204",
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"O",
"B-T103",
"O"... | [
{
"db_id": "C1438918",
"db_name": "UMLS"
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{
"db_id": "C1438918",
"db_name": "UMLS"
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{
"db_id": "C1438918",
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{
"db_id": "C1438918",
"db_name": "UMLS"
},
{
"db_id": "C1438918",
"db_name": "UMLS"
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{
"db_id": "C0184511",
"db_n... | [
"Angiopoietin",
"-",
"like",
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"4",
"improves",
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"-",
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... | Angiopoietin-like protein 4 improves glucose tolerance and insulin resistance but induces liver steatosis in high-fat-diet mice Angiopoietin-like protein 4 (Angptl4) is a secreted protein predominantly expressed in liver and adipose tissues, and has been identified as an adipokine. Angptl4 is the target gene of peroxisome proliferator‑activated receptors, which are widely used as lipid‑lowering and anti‑diabetic drugs, and previous studies have demonstrated that Angptl4 is able to directly stimulate adipocyte lipolysis. The current study focused on how Angptl4 was involved in regulating lipid and glucose metabolism in high‑fat‑diet (HFD) C57 mice. In the present study, mice were divided into three groups, with standard chow mice as a normal control, adenovirus (adv)‑ injected HFD mice as a model control and adv ‑ Angptl4 ‑ injected HFD mice as the Angptl4+ group. Firstly, compared with the normal control group, mice in the model control group gained more body weight with severe liver steatosis and increased serum levels of triglyceride, total cholesterol, free fatty acids, alanine aminotransferase and aspartate aminotransferase. In the Angptl4+ group, Angptl4 reduced the weight growth rate, aggravated hepatic steatosis and further increased all the aforementioned serum indexes. Secondly, compared with the normal control, the model control group had a reduced glucose tolerance and developed insulin resistance. Angptl4 expression and the phosphorylation levels of several insulin signaling pathway‑associated genes, insulin receptor substrate 1, protein kinase B, janus kinase 2, signal transducer and activator of transcription 3 were downregulated in the liver samples. Adv ‑ Angptl4 injection was observed to improve glucose tolerance and insulin resistance. The genes measured were identified to be upregulated close to normal levels. All the results suggested that Angptl4 served an important role in lipid and glucose metabolism in HFD‑induced obese mice, and this may have a great significance for treatment of hyperlipidemia, diabetes, metabolic syndrome and other diseases. |
[
"O",
"B-T037",
"B-T037",
"I-T037",
"O",
"O",
"B-T170",
"I-T170",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T098",
"O",
"B-T058",
"I-T058",
"O",
"O",
"B-T074",
"I-T074",
"I-T074",
"I-T074",
"I-T074",
"I-T074",
"O",
"O",
"B-T103",
"O",
"O",
"B-T170",
... | [
{
"db_id": null,
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{
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{
"db_id": "C0015802",
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{
"db_id": "C0015802",
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{
"db_id": null,
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{
"db_id": null,
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... | [
"Atypical",
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"femoral",
"fracture",
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"with",
"a",
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"spanning",
"cable",
"-",
"plate",
"for",
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"bisphos... | [
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42,
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[
44,
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49,
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[
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[
66,
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[
69,
71
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[
71,
72
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7... | Atypical periprosthetic femoral fracture: a case report We report an 82-year-old woman who underwent fixation with a long-spanning cable-plate for a bisphosphonate - induced Vancouver B1 periprosthetic femoral fracture. Non-union and breakage of the plate occurred at 16 months and necessitated revision surgery using a long-stem femoral prosthesis augmented with a cable-plate construct. Bone union was achieved eventually after 10 months. |
[
"B-T082",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"B-T103",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"B-T007",
"I-T007",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O"... | [
{
"db_id": "C0014406",
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{
"db_id": null,
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"db_id": "C115... | [
"Environmental",
"fate",
"and",
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"of",
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"quorum",
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"biofilms",
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... | [
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... | Environmental fate and effects of novel quorum sensing inhibitors that can control biofilm formation The formation of bacterial biofilms can have negative impacts on industrial processes and are typically difficult to control. The increase of antibiotic resistance, in combination with the requirement for more environmentally focused approaches, has placed pressure on industry and the scientific community to reassess biofilm control strategies. The discovery of bacterial quorum sensing, as an important mechanism in biofilm formation, has led to the development of new substances (such as halogenated thiophenones) to inhibit the quorum sensing process. However, there are currently limited data regarding the biodegradability or ecotoxicity of these substances. To assess the environmental fate and effects of thiophenones capable of quorum sensing inhibition, candidate substances were first identified that have potentially high biodegradability and low ecotoxicity using quantitative structure activity relationships. Subsequent confirmatory hazard assessment of these substances, using a marine alga and a marine crustacean, indicated that these estimates were significantly under predicted with acute toxicity values more than three orders of magnitude lower than anticipated combined with limited biodegradability. Therefore, although these quorum sensing inhibitors appear a promising approach to control biofilms, they may also have environmental impacts on certain aquatic organisms. |
[
"B-T103",
"O",
"B-T038",
"O",
"O",
"O",
"B-T091",
"I-T091",
"O",
"B-T038",
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"O",
"B-T103",
"O",
"O",
"O",
"B-T038",
"B-T103",
"O",
"O",
"O",
"O",
"B-T017",
"O",
"B-T103",
"O... | [
{
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"db_id... | [
"PCSK9",
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29,
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38,
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99,... | PCSK9: Regulation and Target for Drug Development for Dyslipidemia Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted zymogen expressed primarily in the liver. PCSK9 circulates in plasma, binds to cell surface low-density lipoprotein (LDL) receptors, is internalized, and then targets the receptors to lysosomal degradation. Studies of naturally occurring PCSK9 gene variants that caused extreme plasma LDL cholesterol (LDL-C) deviations and altered atherosclerosis risk unleashed a torrent of biological and pharmacological research. Rapid progress in understanding the physiological regulation of PCSK9 was soon translated into commercially available biological inhibitors of PCSK9 that reduced LDL-C levels and likely also cardiovascular outcomes. Here we review the swift evolution of PCSK9 from novel gene to drug target, to animal and human testing, and finally to outcome trials and clinical applications. In addition, we explore how the genetics-guided path to PCSK9 inhibitor development exemplifies a new paradigm in pharmacology. Finally, we consider some potential challenges as PCSK9 inhibition becomes established in the clinic. |
[
"O",
"O",
"B-T038",
"I-T038",
"O",
"B-T038",
"I-T038",
"I-T038",
"O",
"B-T062",
"I-T062",
"I-T062",
"I-T062",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"O",
"B-T038",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",... | [
{
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{
"db_id": "C1516197",
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{
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},
{
"db_id": "C3658355",
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{
... | [
"Inactivation",
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"Cas9",
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"... | [
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33,
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[
49,
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[
50,
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[
55,
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[
64,
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69,
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[
70,
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[
77,
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[
... | Inactivation of Cancer Mutations Utilizing CRISPR/Cas9 Although whole-genome sequencing has uncovered a large number of mutations that drive tumorigenesis, functional ratification for most mutations remains sparse. Here, we present an approach to test functional relevance of tumor mutations employing CRISPR/Cas9. Combining comprehensive sgRNA design and an efficient reporter assay to nominate efficient and selective sgRNAs, we establish a pipeline to dissect roles of cancer mutations with potential applicability to personalized medicine and future therapeutic use. |
[
"O",
"O",
"B-T033",
"I-T033",
"I-T033",
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"B-T033",
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"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
... | [
{
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{
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{
"db_id": "C0877040",
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{
"db_id": "C0877040",
"db_name": "UMLS"
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{
"db_id": null,
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{
... | [
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"falling",
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... | [
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[
26,
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29,
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37,
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[
41,
51
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[
52,
58
],
[
59,
61
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[
62,
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[
70,
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],
[
75,
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[
85,
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[
... | Relationship between fear of falling and functional status in nursing home residents aged older than 65 years The present study investigated the relationship between fear of falling and functional status, and sociodemographic and health-related factors in nursing home residents aged older than 65 years. The cross-sectional study involved 100 participants who were residents of a nursing home and aged older than 65 years. Fear of falling was assessed using the Falls Efficacy Scale. Functional status was assessed by four performance-based measures. Balance was assessed by the Berg Balance Scale, mobility by the Timed Up and Go test, lower limbs muscle strength by the Chair Rising Test and participants' functional ability by the motor Functional Independence Measure. There was a significant negative correlation between the Falls Efficacy Scale and Berg Balance Scale (P < 0.001), and motor Functional Independence Measure (P < 0.001) scores; and a positive correlation with the Timed Up and Go test (P < 0.001) and Chair Rising Test (P < 0.001) values. Falls Efficacy Scale score increase is associated with age, being a widower / widow and the number of falls in the previous year. Higher fear of falling is associated with an increase in the number of falls in the previous year and with a decrease in Berg Balance Scale score. The study found a significant associations between Falls Efficacy Scale score and all of the examined parameters of functional status, the number of falls in the previous year, age and marital status of widower / widow. The major finding was that poor balance and an increase in the number of falls in the previous year are independent factors significantly associated with the fear of falling. Geriatr Gerontol Int 2016; ••: ••-••. |
[
"O",
"O",
"B-T058",
"I-T058",
"I-T058",
"I-T058",
"I-T058",
"O",
"O",
"O",
"B-T103",
"I-T103",
"I-T103",
"O",
"B-T058",
"B-T058",
"O",
"O",
"O",
"O",
"O",
"B-T058",
"I-T058",
"I-T058",
"I-T058",
"I-T058",
"I-T058",
"O",
"B-T058",
"O",
"O",
"B-T033",
"I... | [
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{
"db_id": "C4055114",
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{
"db_id": "C4055114",
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{
"db_id": "C4055114",
"db_name": "UMLS"
},
{
"db_id": "C4055114",
"db_name": "UMLS"
}... | [
"Utility",
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... | [
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6... | Utility of dual-energy spectral CT and low- iodine contrast medium in DIEP angiography To evaluate the utility of dual-energy spectral computed tomography (CT) and low-iodine intake in CT angiography (CTA) of deep inferior epigastric perforator (DIEP) flaps. In this prospective study, 40 patients with a BMI <28.0 kg/m(2) underwent CTA examination for breast reconstruction and were randomly assigned into two groups (n=20 for each group) as follows: Group A was submitted to dual-energy spectral CT and iodixanol (270 mg I/mL) and Group B was submitted to conventional high iodine contrast agent iohexol (350 mg I/mL). The volume CT dose index (CTDIvol) and dose length product were recorded and the effective dose (ED) was calculated. The best mono-spectrum images of Group A were selected according to the optimal contrast to noise ratio (CNR). Both mono-spectrum images of Group A and polychromatic images of Group B were used to reconstruct maximum intensity projection (MIP) and volume rendering (VR) images of the perforating artery, respectively. Two radiologists evaluated subjective image quality using a 4-point score. The diameter of the perforating artery, CT value and SD value for the common femoral artery were measured and the CNR was calculated. The total iodine intake and radiation doses of the two groups were calculated and compared. The best mono-spectrum energy with the optimal CNR of the perforating artery was 63 keV. The CT value of common femoral artery in Group A (380.96±42.75HU) was 7.40% higher than in Group B (354.71±42.01 HU) but with no statistical significance (P>.05). The CNR of the common femoral artery in Group A (23.84±6.73) was 6.88% lower than in Group B (25.60±6.20), with no significant difference (P>.05). The diameters of the perforator vessels were 2.44±0.15 and 2.49±0.14 mm, respectively, with no significant difference (P>.05). Subjective image qualities for the two groups were both good for diagnostics, and the scores for Group A and Group B were (3.88±0.28) and (3.93±0.18), respectively. The scores of the two radiologists were consistent (kappa=0.634). The effective radiation dose in Group A (9.09±0 mSv) was 10.62% lower than in Group B (10.17±1.91 mSv). The total iodine intake in Group A (27 000 mg) was 22.86% lower than in Group B (35 000 mg). The combination of dual-energy spectral CT and low-iodine intake in CTA of DIEP flap examination with the optimal CNR technology can meet the requirements of clinical diagnostics, with a 22.86% reduction in total iodine intake and an 11.01% reduction in radiation dose. |
[
"O",
"O",
"O",
"B-T103",
"I-T103",
"O",
"O",
"B-T038",
"I-T038",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",... | [
{
"db_id": null,
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{
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{
"db_id": "C0003009",
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{
"db_id... | [
"Gut",
"Microbiota",
"Promote",
"Angiotensin",
"II",
"-",
"Induced",
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"Hypertension",
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[
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[
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[
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9... | Gut Microbiota Promote Angiotensin II - Induced Arterial Hypertension and Vascular Dysfunction The gut microbiome is essential for physiological host responses and development of immune functions. The impact of gut microbiota on blood pressure and systemic vascular function, processes that are determined by immune cell function, is unknown. Unchallenged germ-free mice (GF) had a dampened systemic T helper cell type 1 skewing compared to conventionally raised (CONV-R) mice. Colonization of GF mice with regular gut microbiota induced lymphoid mRNA transcription of T-box expression in T cells and resulted in mild endothelial dysfunction. Compared to CONV-R mice, angiotensin II (AngII; 1 mg/kg per day for 7 days) infused GF mice showed reduced reactive oxygen species formation in the vasculature, attenuated vascular mRNA expression of monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS) and NADPH oxidase subunit Nox2, as well as a reduced upregulation of retinoic-acid receptor-related orphan receptor gamma t (Rorγt), the signature transcription factor for interleukin (IL)-17 synthesis. This resulted in an attenuated vascular leukocyte adhesion, less infiltration of Ly6G(+) neutrophils and Ly6C(+) monocytes into the aortic vessel wall, protection from kidney inflammation, as well as endothelial dysfunction and attenuation of blood pressure increase in response to AngII. Importantly, cardiac inflammation, fibrosis and systolic dysfunction were attenuated in GF mice, indicating systemic protection from cardiovascular inflammatory stress induced by AngII. Gut microbiota facilitate AngII - induced vascular dysfunction and hypertension, at least in part, by supporting an MCP-1 / IL-17 driven vascular immune cell infiltration and inflammation. |
[
"B-T103",
"O",
"B-T017",
"I-T017",
"I-T017",
"B-T038",
"O",
"B-T103",
"I-T103",
"O",
"O",
"B-T017",
"O",
"B-T103",
"I-T103",
"O",
"B-T103",
"O",
"O",
"O",
"B-T038",
"B-T038",
"I-T038",
"B-T038",
"O",
"B-T038",
"I-T038",
"O",
"B-T038",
"O",
"O",
"O",
"O... | [
{
"db_id": "C0001443",
"db_name": "UMLS"
},
{
"db_id": null,
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},
{
"db_id": "C1512505",
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{
"db_id": "C1512505",
"db_name": "UMLS"
},
{
"db_id": "C1512505",
"db_name": "UMLS"
},
{
"db_id": "C0007608",
"db_name": "U... | [
"Adenosine",
"arrests",
"breast",
"cancer",
"cell",
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[
61,
72
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[
73,
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[
76,
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[
87,
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... | Adenosine arrests breast cancer cell motility by A3 receptor stimulation In neutrophils, adenosine triphosphate (ATP) release and autocrine purinergic signaling regulate coordinated cell motility during chemotaxis. Here, we studied whether similar mechanisms regulate the motility of breast cancer cells. While neutrophils and benign human mammary epithelial cells (HMEC) form a single leading edge, MDA-MB-231 breast cancer cells possess multiple leading edges enriched with A3 adenosine receptors. Compared to HMEC, MDA-MB-231 cells overexpress the ectonucleotidases ENPP1 and CD73, which convert extracellular ATP released by the cells to adenosine that stimulates A3 receptors and promotes cell migration with frequent directional changes. However, exogenous adenosine added to breast cancer cells or the A3 receptor agonist IB-MECA dose - dependently arrested cell motility by simultaneous stimulation of multiple leading edges, doubling cell surface areas and significantly reducing migration velocity by up to 75 %. We conclude that MDA-MB-231 cells, HMEC, and neutrophils differ in the purinergic signaling mechanisms that regulate their motility patterns and that the subcellular distribution of A3 adenosine receptors in MDA-MB-231 breast cancer cells contributes to dysfunctional cell motility. These findings imply that purinergic signaling mechanisms may be potential therapeutic targets to interfere with the motility of breast cancer cells in order to reduce the spread of cancer cells and the risk of metastasis. |
[
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T031",
"B-T103",
"O",
"O",
"B-T058",
"O",
"B-T103",
"O",
"O",
"B-T103",
"I-T103",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T082",
"O",
... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
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{
"db_id": null,
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"db_id": null,
"db... | [
"Severity",
"of",
"Gastric",
"Mucosal",
"Atrophy",
"Is",
"the",
"Major",
"Determinant",
"of",
"Plasma",
"Ghrelin",
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"an",
"orexigenic",
"hormone",
",",
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"includin... | [
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0,
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36,
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39,
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43,
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[
49,
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61,
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64,
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71,
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79,
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8... | Severity of Gastric Mucosal Atrophy Is the Major Determinant of Plasma Ghrelin Level in Hemodialysis Patients Ghrelin, an orexigenic hormone, has multiple favorable functions including protein anabolism enhancement, anti-inflammatory actions, and cardiovascular protection. A low plasma ghrelin level is associated with increased mortality in patients treated with hemodialysis (HD). However, it is unclear whether the plasma ghrelin level in HD patients correlates with the severity of gastric mucosal atrophy and Helicobacter pylori status. Seventy-eight maintenance HD patients and 51 non-dialysis patients with chronic kidney disease were evaluated for severity of gastric mucosal atrophy by gastroduodenoscopy and for H. pylori status using an anti-H. pylori-antibody and rapid urease test. Plasma acyl and des-acyl ghrelin levels were measured and their associations with relevant clinical parameters were investigated. Des-acyl ghrelin level in HD patients was significantly higher than that in patients with kidney function preserved. Although acyl and des-acyl ghrelin levels were similar between current H. pylori positive and negative HD patients, both levels decreased significantly with the progress of endoscopic gastric mucosal atrophy in HD patients. Serum pepsinogen (PG) I level and PG I / II ratio decreased significantly according to the severity of atrophy in HD patients and positively significantly correlated with both ghrelin levels. Multiple regression analysis showed significant positive correlations between acyl ghrelin and PG I levels (β = 0.738, p < 0.001) and significant negative correlations between ghrelin and age, albumin, and creatinine levels. Gastric atrophy is the major determinant of ghrelin level in HD patients. Management practices, such as H. pylori eradication, before advanced atrophy may be required to prevent the decrease of ghrelin levels and improve the prognosis of HD patients. |
[
"O",
"O",
"O",
"O",
"O",
"B-T033",
"I-T033",
"I-T033",
"O",
"B-T007",
"I-T007",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"B-T058",
"I-T058",
"O",
"B-T058",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T033",
"I-T033",
"I-T033",
"I-T033",
"O",
"O",
"... | [
{
"db_id": null,
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{
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{
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{
"db_id": "C0449426",
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{
"db_id": "C044... | [
"The",
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30,
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33,
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9... | The Heater Cooler as a Source of Infection from Nontuberculous Mycobacteria Nosocomial infections acquired during the course of cardiac surgery and hospitalization can have devastating patient consequences. The source of these infections is often difficult to determine which complicates eradication efforts. Recently it has become apparent that the heater-cooler devices used in conjunction with cardiopulmonary bypass may become contaminated with bacteria that are normally found in hospital water sources. The culprit organisms are nontuberculous mycobacteria which coat the intrinsic surfaces found within the circuits of the heater-coolers. Aerosolization of the bacteria occurs during normal heater-cooler operation which can disperse the organisms throughout the operating room. The bacteria are slow-growing and may not present for months, or years, following exposure which makes epidemiological determination a challenge. The ensuing report summarizes a recent outbreak in these infections that have been reported both in Europe and the United States, along with efforts to reduce the risk for patient infection. |
[
"B-T103",
"I-T103",
"B-T038",
"O",
"O",
"O",
"B-T082",
"B-T082",
"B-T103",
"O",
"B-T103",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"I-T038",
"O",
"O",
"B-T058",
"I-T058",
"I-T058",
"I-T058",
"I-T058",
"I-T058",
"O",
"O",
"O",
"O",
"B-T062",
"O... | [
{
"db_id": "C1739039",
"db_name": "UMLS"
},
{
"db_id": "C1739039",
"db_name": "UMLS"
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{
"db_id": "C1171362",
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{
"db_id": null,
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{
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{
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{
... | [
"EGFR",
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[
13,
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[
24,
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[
30,
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[
32,
40
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[
41,
54
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[
55,
61
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[
62,
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[
71,
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[
75,
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80,
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[
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9... | EGFR protein expression using a specific intracellular domain antibody and PTEN and clinical outcomes in squamous cell lung cancer patients with EGFR-tyrosine kinase inhibitor therapy The aim of this research was to examine the molecular and clinical features that are related with EGFR-tyrosine kinase inhibitor (EGFR-TKI) efficacy in previously treated patients with squamous cell carcinoma of the lung (SCCL). This retrospective study included 67 SCCL patients with obtainable lung cancer tissue and records on EGFR-TKI treatment response and survival. EGFR protein expression in lung cancer tissue was measured by immunohistochemistry with a specific antibody that recognizes the intracellular domain (ID) of EGFR. PTEN expression in lung cancer tissue was also evaluated with immunohistochemistry. PI3KCA gene amplification was detected by quantitative real-time polymerase chain reaction, and FGFR1 amplification was assessed by fluorescent in situ hybridization. EGFR ID expression (hazard ratio [HR] 0.53, P=0.022) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) (HR 0.43, P=0.022) were significantly related with progression - free survival following EGFR-TKIs treatment. PTEN expression (HR 0.52, P=0.025) was significantly related to overall survival. The group of EGFR - positive or PTEN - positive patients with ECOG PS of 0 or 1 had better clinical outcomes than patients who were EGFR - negative and PTEN - negative or who had poor ECOG PS with longer median progression - free survival (2.1 vs 1.0 months, P=0.05) and overall survival (6.2 vs 2.1 months, P=0.05). EGFR expression using an ID -specific antibody and PTEN protein expression may be used to identify SCCL patients who might benefit from EGFR-TKI treatment. |
[
"B-T017",
"O",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"B-T038",
"I-T038",
"I-T038",
"O",
"O",
"O",
"B-T017",
"O",
"O",
"B-T082",
"O",
"O",
"B-T017",
"I-T017",
"O",
"O",
"B-T017",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"O",
"O"... | [
{
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{
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{
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"db_id": "C0003507",
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{
"db_id": "C0003507",
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{
... | [
"MicroRNA",
"Expression",
"Signature",
"in",
"Degenerative",
"Aortic",
"Stenosis",
"Degenerative",
"aortic",
"stenosis",
",",
"characterized",
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"left",
"ventricle",
"of",
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"heart",
",",
"has",
"become",
"... | [
[
0,
8
],
[
9,
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],
[
20,
29
],
[
30,
32
],
[
33,
45
],
[
46,
52
],
[
53,
61
],
[
62,
74
],
[
75,
81
],
[
82,
90
],
[
90,
91
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[
92,
105
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[
106,
108
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[
... | MicroRNA Expression Signature in Degenerative Aortic Stenosis Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease. |
[
"B-T082",
"O",
"B-T017",
"B-T033",
"O",
"O",
"O",
"O",
"B-T033",
"O",
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"B-T058",
"I-T058",
"I-T058",
"O",
"B-T058",
"I-T058",
"B-T062",
"O",
"B-T033",
"B-T033",
"I-T033",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
... | [
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... | [
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8... | Patterns of coronary plaque progression: phasic versus gradual. A combined optical coherence tomography and intravascular ultrasound study Some plaques grow slowly in a linear manner, whereas others undergo a rapid phasic progression. However, the detailed in-vivo relationship between plaque characteristics and plaque progression pattern has not been reported. The current study aimed to investigate the plaque progression patterns with serial intravascular ultrasound (IVUS) examinations, and to correlate baseline plaque characteristics assessed by optical coherence tomography and IVUS with plaque progression patterns. A total of 248 coronary lesions from 157 patients were identified and imaged by both optical coherence tomography and IVUS at baseline. IVUS examination was repeated at 6 and 12 months. Plaque progression was defined as greater than or equal to 5% increase in percent atheroma volume by IVUS. The progression patterns were divided into three groups: no progression, rapid phasic progression, and gradual progression. Among 248 lesions, 190 (77%) showed no progression. Among 58 lesions with progression, 20 (34%) showed gradual progression, whereas 38 (66%) showed rapid phasic progression. Multivariate analysis indicated that thin-cap fibroatheroma [odds ratio (OR)=5.24, 95% confidence interval (CI) 2.04-13.4; P=0.001], microvessel (OR =2.20, 95% CI 1.10-4.79; P=0.045), and positive remodeling (OR =2.64, 95% CI 1.19-5.81; P=0.016) were associated independently with rapid phasic progression. Three-quarters of coronary plaques did not progress over time with contemporary medical treatment. Among the lesions with progression, one-third showed a gradual pattern and two-thirds showed a rapid phasic pattern. The presence of thin-cap fibroatheroma, microvessel, and positive remodeling were the independent predictors for rapid phasic pattern progression of coronary atherosclerotic plaques. |
[
"O",
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"O",
"B-T082",
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... | [
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... | Prevalence and risk factors of anxiety and depression in patients with systemic lupus erythematosus in Southwest China Systemic lupus erythematosus (SLE) patients have high risk for anxiety and depression. We aimed to investigate the prevalence and risk factors of anxiety and depression in SLE patients in Southwest China. Participants were recruited by convenience sampling from Rheumatic Outpatient Clinic of West China Hospital Sichuan University between August and October 2014. The prevalence of anxiety and depression was evaluated using Hospital Anxiety and Depression Scale (HADS). Risk factors were explored by multiple logistic regression analyses. A total of 352 participants were enrolled, of who 64 (18.2 %) met the HADS criteria for anxiety and 82 (23.3 %) for depression. In multivariable analysis, higher levels of pain (OR = 1.17, P = 0.02) and fatigue (OR = 1.19, P < 0.01) predicted a higher risk of anxiety. Similarly, a higher level of fatigue (OR = 1.2, P < 0.01) was associated with a higher risk of depression. The results suggest that anxiety and depression are common in patients with SLE in Southwest China. Health care providers and SLE patients should take some measures to cope with them as early as possible. Strengthening management of pain and fatigue may be useful. But further studies are needed to verify these findings. |
[
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
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"I-T092",
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"I-T092",
"O",
"O",
"B-T092",
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... | [
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75,... | Use of Six Sigma Methodology to Reduce Appointment Lead-Time in Obstetrics Outpatient Department This paper focuses on the issue of longer appointment lead-time in the obstetrics outpatient department of a maternal-child hospital in Colombia. Because of extended appointment lead-time, women with high-risk pregnancy could develop severe complications in their health status and put their babies at risk. This problem was detected through a project selection process explained in this article and to solve it, Six Sigma methodology has been used. First, the process was defined through a SIPOC diagram to identify its input and output variables. Second, six sigma performance indicators were calculated to establish the process baseline. Then, a fishbone diagram was used to determine the possible causes of the problem. These causes were validated with the aid of correlation analysis and other statistical tools. Later, improvement strategies were designed to reduce appointment lead-time in this department. Project results evidenced that average appointment lead-time reduced from 6,89 days to 4,08 days and the deviation standard dropped from 1,57 days to 1,24 days. In this way, the hospital will serve pregnant women faster, which represents a risk reduction of perinatal and maternal mortality. |
[
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"db_id": "C1537736",
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... | Disulfiram and Diphenhydramine Hydrochloride Upregulate miR-30a to Suppress IL-17-Associated Autoimmune Inflammation T-helper 17 (Th17) cells play an important role in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease that affects the CNS. In the present study, MicroRNA sequencing (miRNA-seq) was performed in mouse Th0 and Th17 cells to determine the critical miRNAs that are related to Th17 differentiation. We found that miR-30a was significantly downregulated during mouse Th17 differentiation. In addition, the level of miR-30a in CD4(+) T cells from peripheral blood of MS patients and experimental autoimmune encephalomyelitis (EAE) animal models was also decreased and inversely correlated with the expression of interleukin 17a, the canonical cytokine of Th17 cells. Moreover, overexpression of miR-30a inhibited Th17 differentiation and prevented the full development of EAE, whereas interference of miR-30a promoted Th17 differentiation. Mechanism studies showed that miR-30a reduced IRF4 expression by specifically binding with the 3'-untranslated region. Through screening of 640 different Food and Drug Administration (FDA)-approved drugs, we found that disulfiram and diphenhydramine hydrochloride were effective candidates for inhibiting Th17 differentiation and ameliorating EAE development through upregulating miR-30a. To our knowledge, the present work is not only the first miRNA-seq study focusing on Th17 differentiation, but also the first chemical screening for FDA-approved drugs that inhibit Th17 differentiation through regulating miRNA expression. The present work is the first miRNA sequencing (miRNA-seq) study focusing on T-helper 17 (Th17) differentiation. By miRNA deep sequencing, we found that miR-30a was downregulated during Th17 differentiation. miR-30a was also decreased in CD4(+) T cells from multiple sclerosis patients and experimental autoimmune encephalomyelitis (EAE) mice. miR-30a reduced IRF4 expression by specific binding with the 3'-untranslated region and thus suppressed Th17 differentiation and prevented the full development of EAE. Interestingly, by performing a chemical screen with Food and Drug Administration-approved small-molecule drugs, we found that disulfiram and diphenhydramine upregulated miR-30a and suppressed Th17 - associated autoimmune demyelination. |
[
"O",
"O",
"B-T103",
"O",
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"I-T017",
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"I-T103",
"O",
"B-T103",
"O",
"O",
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"O",
"O",
"O",
"O",
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"I-T038",
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"O",
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... | [
"Modulation",
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... | Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol d-chiroinositol (DCI) is a inositolphosphoglycan (IPG) involved in several cellular functions that control the glucose metabolism. DCI functions as second messenger in the insulin signaling pathway and it is considered an insulin sensitizer since deficiency in tissue availability of DCI were shown to cause insulin resistance (IR). Polycystic ovary syndrome (PCOS) is a pathological condition that is often accompanied with insulin resistance. DCI can positively affects several aspect of PCOS etiology decreasing the total and free testosterone, lowering blood pressure, improving the glucose metabolism and increasing the ovulation frequency. The purpose of this study was to evaluate the effects of DCI and insulin combined with gonadotrophins namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on key steroidogenic enzymes genes regulation, cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and cytochrome P450 side-chain cleavage (P450scc) in primary cultures of human granulosa cells (hGCs). We also investigated whether DCI, being an insulin-sensitizer would be able to counteract the expected stimulator activity of insulin on human granulosa cells (hGCs). The study was conducted on primary cultures of hGCs. Gene expression was evaluated by RT-qPCR method. Statistical analysis was performed applying student t-test, as appropriate (P < 0.05) set for statistical significance. DCI is able to reduce the gene expression of CYP19A1, P450scc and insulin-like growth factor 1 receptor (IGF-1R) in dose-response manner. The presence of DCI impaired the increased expression of steroidogenic enzyme genes generated by the insulin treatment in gonadotrophin - stimulated hGCs. Insulin acts as co-gonadotrophin increasing the expression of steroidogenic enzymes genes in gonadotrophin - stimulated granulosa cells. DCI is an insulin-sensitizer that counteracts this action by reducing the expression of the genes CYP19A1, P450scc and IGF-1R. The ability of DCI to modulate in vitro ovarian activity of insulin could in part explain its beneficial effect when used as treatment for conditions associated to insulin resistance. |
[
"O",
"O",
"O",
"B-T038",
"O",
"B-T082",
"O",
"B-T038",
"O",
"B-T038",
"O",
"O",
"O",
"O",
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"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T082",
... | [
{
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"db_id... | [
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8... | The fatter are happier in Indonesia Although obesity and happiness are known to be negatively related in the developed world, little attention has been paid to this relationship in the developing world. We thus investigated the relationship in Indonesia and attempted to explain the underlying rationale. We considered about 12,000 respondents aged 15+ for each gender obtained from the Indonesian Family Life Survey 2007 by relating a measure of happiness to weight - related measures in ordered probit models. The relationship between obesity and happiness was positive in Indonesia, and this relationship was robust. Our evidence suggests that the contrasting results for the two worlds result from affordability of obesity. That is, while even low socioeconomic status (SES) individuals in the developed world can afford to be obese, only high SES individuals in the developing world can do. Our findings imply that obesity prevention in the developing world requires different measures than those used in the developed world. |
[
"B-T058",
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"I-T007",
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"I-T007",
"O",
"O",
"O",
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"B-T103",
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"B-T038",
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... | [
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... | [
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... | [
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... | Live imaging of the genetically intractable obligate intracellular bacteria Orientia tsutsugamushi using a panel of fluorescent dyes Our understanding of the molecular mechanisms of bacterial infection and pathogenesis are disproportionally derived from a small number of well-characterised species and strains. One reason for this is the enormous time and resources required to develop a new organism into experimental system that can be interrogated at the molecular level, in particular with regards to the development of genetic tools. Live cell imaging by fluorescence microscopy is a powerful technique to study biological processes such as bacterial motility, host cell invasion, and bacterial growth and division. In the absence of genetic tools that enable exogenous expression of fluorescent proteins, fluorescent chemical probes can be used to label and track living cells. A large number of fluorescent chemical probes are commercially available, but these have overwhelmingly been applied to the study of eukaryotic cell systems. Here, we present a methodical analysis of four different classes of probes, which can be used to delineate the cytoplasm, nucleic acids, cell membrane or peptidoglycan of living bacterial cells. We have tested these in the context of the important but neglected human pathogen Orientia tsutsugamushi but expect that the methodology would be broadly applicable to other bacterial species. |
[
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"db_id": "C0872076",
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[
... | Improved hematopoietic differentiation of human pluripotent stem cells via estrogen receptor signaling pathway Aside from its importance in reproduction, estrogen (E2) is known to regulate the proliferation and differentiation of hematopoietic stem cells in rodents. However, the regulatory role of E2 in human hematopoietic system has not been investigated. The purpose of this study is to investigate the effect of E2 on hematopoietic differentiation using human pluripotent stem cells (hPSCs). E2 improved hematopoietic differentiation of hPSCs via estrogen receptor alpha (ER-α)-dependent pathway. During hematopoietic differentiation of hPSCs, ER-α is persistently maintained and hematopoietic phenotypes (CD34 and CD45) were exclusively detected in ER-α positive cells. Interestingly, continuous E2 signaling is required to promote hematopoietic output from hPSCs. Supplementation of E2 or an ER-α selective agonist significantly increased the number of hemangioblasts and hematopoietic progenitors, and subsequent erythropoiesis, whereas ER-β selective agonist did not. Furthermore, ICI 182,780 (ER antagonist) completely abrogated the E2 -induced hematopoietic augmentation. Not only from hPSCs but also from human umbilical cord bloods, does E2 signaling potentiate hematopoietic development, suggesting universal function of E2 on hematopoiesis. Our study identifies E2 as positive regulator of human hematopoiesis and suggests that endocrine factors such as E2 influence the behavior of hematopoietic stem cells in various physiological conditions. |
[
"O",
"O",
"O",
"O",
"B-T062",
"I-T062",
"I-T062",
"I-T062",
"I-T062",
"I-T062",
"O",
"O",
"O",
"O",
"B-T033",
"O",
"B-T033",
"B-T038",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"O",
"B-T098",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T06... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
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},
{
"db_id": null,
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},
{
"db_id": null,
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{
"db_id": "C1709846",
"db_name": "UMLS"
},
{
"db_id": "C1709846",
"db_name": "UMLS"
},
{
"db_id... | [
"Establishment",
"of",
"a",
"Flexible",
"Real",
"-",
"Time",
"Polymerase",
"Chain",
"Reaction",
"-",
"Based",
"Platform",
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"Prevalent",
"Deafness",
"Mutations",
"Associated",
"with",
"Variable",
"Degree",
"of",
"Sensorineural",
"Hearing",
"Loss",
... | [
[
0,
13
],
[
14,
16
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[
17,
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],
[
19,
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[
28,
32
],
[
32,
33
],
[
33,
37
],
[
38,
48
],
[
49,
54
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[
55,
63
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[
64,
65
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[
65,
70
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[
71,
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... | Establishment of a Flexible Real-Time Polymerase Chain Reaction -Based Platform for Detecting Prevalent Deafness Mutations Associated with Variable Degree of Sensorineural Hearing Loss in Koreans Many cutting-edge technologies based on next-generation sequencing (NGS) have been employed to identify candidate variants responsible for sensorineural hearing loss (SNHL). However, these methods have limitations preventing their wide clinical use for primary screening, in that they remain costly and it is not always suitable to analyze massive amounts of data. Several different DNA chips have been developed for screening prevalent mutations at a lower cost. However, most of these platforms do not offer the flexibility to add or remove target mutations, thereby limiting their wider use in a field that requires frequent updates. Therefore, we aimed to establish a simpler and more flexible molecular diagnostic platform based on ethnicity -specific mutation spectrums of SNHL, which would enable bypassing unnecessary filtering steps in a substantial portion of cases. In addition, we expanded the screening platform to cover varying degrees of SNHL. With this aim, we selected 11 variants of 5 genes (GJB2, SLC26A4, MTRNR1, TMPRSS3, and CDH23) showing high prevalence with varying degrees in Koreans and developed the U-TOP™ HL Genotyping Kit, a real-time PCR -based method using the MeltingArray technique and peptide nucleic acid probes. The results of 271 DNA samples with wild type sequences or mutations in homo- or heterozygote form were compared between the U-TOP™ HL Genotyping Kit and Sanger sequencing. The positive and negative predictive values were 100%, and this method showed perfect agreement with Sanger sequencing, with a Kappa value of 1.00. The U-TOP™ HL Genotyping Kit showed excellent performance in detecting varying degrees and phenotypes of SNHL mutations in both homozygote and heterozygote forms, which are highly prevalent in the Korean population. This platform will serve as a useful and cost-effective first-line screening tool for varying degrees of genetic SNHL and facilitate genome -based personalized hearing rehabilitation for the Korean population. |
[
"B-T170",
"O",
"B-T062",
"I-T062",
"O",
"O",
"B-T082",
"O",
"B-T082",
"O",
"B-T074",
"I-T074",
"O",
"O",
"B-T058",
"O",
"B-T058",
"I-T058",
"O",
"O",
"B-T017",
"O",
"B-T017",
"O",
"O",
"B-T017",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T082",
"... | [
{
"db_id": "C0887962",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0870071",
"db_name": "UMLS"
},
{
"db_id": "C0870071",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
... | [
"Physical",
"and",
"virtual",
"modelling",
"of",
"the",
"head",
"and",
"neck",
"for",
"surgical",
"simulation",
"and",
"training",
"Investigation",
"and",
"surgical",
"manipulation",
"of",
"the",
"larynx",
",",
"pharynx",
",",
"and",
"oesophagus",
"suffer",
"fro... | [
[
0,
8
],
[
9,
12
],
[
13,
20
],
[
21,
30
],
[
31,
33
],
[
34,
37
],
[
38,
42
],
[
43,
46
],
[
47,
51
],
[
52,
55
],
[
56,
64
],
[
65,
75
],
[
76,
79
],
[
8... | Physical and virtual modelling of the head and neck for surgical simulation and training Investigation and surgical manipulation of the larynx, pharynx, and oesophagus suffer from inherent challenges with access to the sites of interest. To reduce trauma and external scarring, visualization and minimally invasive interventions by the transnasal or transoral routes have become more prevalent. This article discusses engineering methods used to understand and overcome the mechanical constraints inside the airway and upper gastrointestinal tract, and examines the role that robotics and engineering are beginning to play in modelling of surgical interventions in this region. Although robotic solutions to minimally invasive surgery of the airway and upper gastrointestinal tract already exist, there is still scope for increasing the breadth of their use. Physical and virtual models of these organs are used to investigate the capability and limitations of manual and robotic surgical interventions in this region. Understanding the tissue mechanics and tool capabilities is central to improving outcomes in the clinical setting. Both physical and virtual modelling modalities are used in training surgeons for both manual - assisted and robot-assisted surgeries. Minimally invasive surgical interventions via the transnasal and the transoral route are strong candidates for overcoming access issues to the airway. They are likely to become more robotically driven as the demand for higher dexterity and accuracy increases for fine manipulation. Physical and virtual organ models are required to enable surgical training for these procedures. |
[
"O",
"O",
"O",
"O",
"O",
"B-T062",
"O",
"B-T058",
"B-T062",
"O",
"O",
"O",
"O",
"O",
"B-T017",
"O",
"B-T082",
"O",
"O",
"O",
"B-T091",
"I-T091",
"I-T091",
"I-T091",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T058",
"I-T058",
"I-T058",
"O",
"O",
"O",
"O",... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C1516769",
"db_name": "UMLS"
},
{
"db_id": null,... | [
"Evolution",
"of",
"Cardiac",
"Biomodels",
"from",
"Computational",
"to",
"Therapeutics",
"Biomodeling",
"the",
"human",
"anatomy",
"in",
"exact",
"structure",
"and",
"size",
"is",
"an",
"exciting",
"field",
"of",
"medical",
"science",
".",
"Utilizing",
"medical",... | [
[
0,
9
],
[
10,
12
],
[
13,
20
],
[
21,
30
],
[
31,
35
],
[
36,
49
],
[
50,
52
],
[
53,
65
],
[
66,
77
],
[
78,
81
],
[
82,
87
],
[
88,
95
],
[
96,
98
],
[
... | Evolution of Cardiac Biomodels from Computational to Therapeutics Biomodeling the human anatomy in exact structure and size is an exciting field of medical science. Utilizing medical data from various medical imaging topography, the data of an anatomical structure can be extracted and converted into a three-dimensional virtual biomodel; thereafter a physical biomodel can be generated utilizing rapid prototyping machines. Here, we have reviewed the utilization of this technology and have provided some guidelines to develop biomodels of cardiac structures. Cardiac biomodels provide insights for cardiothoracic surgeons, cardiologists, and patients alike. Additionally, the technology may have future usability for tissue engineering, robotic surgery, or routine hospital usage as a diagnostic and therapeutic tool for cardiovascular diseases (CVD). Given the broad areas of application of cardiac biomodels, attention should be given to further research and development of their potential. |
[
"B-T037",
"B-T058",
"O",
"B-T058",
"I-T058",
"O",
"B-T082",
"O",
"B-T058",
"I-T058",
"O",
"O",
"O",
"B-T058",
"O",
"O",
"O",
"B-T058",
"I-T058",
"O",
"O",
"O",
"B-T033",
"I-T033",
"I-T033",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"I-T038",
"O",
"O",
... | [
{
"db_id": "C0015333",
"db_name": "UMLS"
},
{
"db_id": "C0086930",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0281182",
"db_name": "UMLS"
},
{
"db_id": "C0281182",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
}... | [
"Radiation",
"risk",
"of",
"breast",
"screening",
"in",
"England",
"with",
"digital",
"mammography",
"To",
"estimate",
"the",
"risks",
"and",
"benefits",
"of",
"breast",
"screening",
"in",
"terms",
"of",
"number",
"of",
"deaths",
"due",
"to",
"radiation",
"-",... | [
[
0,
9
],
[
10,
14
],
[
15,
17
],
[
18,
24
],
[
25,
34
],
[
35,
37
],
[
38,
45
],
[
46,
50
],
[
51,
58
],
[
59,
70
],
[
71,
73
],
[
74,
82
],
[
83,
86
],
[
... | Radiation risk of breast screening in England with digital mammography To estimate the risks and benefits of breast screening in terms of number of deaths due to radiation-induced cancers and the number of lives saved owing to modern screening in the National Health Service Breast Screening Programme (NHSBSP) in England. Radiation risk model, patient dose data and data from national screening statistics were used to estimate the number of deaths due to radiation-induced breast cancers in the NHSBSP in England. Dose and dose effectiveness factors (DDREFs) equal to one and two were assumed. The breast cancer mortality reduction in the invited population due to screening and the percentage of females diagnosed with symptomatic breast cancer, who die from breast cancer, were collated from the literature. The number of lives saved owing to screening was calculated. Assuming, a total of 1,770,436 females between the ages of 50-70 years were screened each year, and a breast cancer mortality reduction of 20% due to screening in the invited population, the number of screen-detected cancers were 14,872 annually, resulting in 1071 lives saved. Conversely, for the same mortality reduction, the number of radiation-induced cancer s was 36 and 18 for DDREFs of 1 and 2, respectively. This resulted in seven and three deaths due to radiation-induced cancers annually for DDREFs of 1 and 2, respectively. The ratios of lives saved owing to screening to radiation-induced cancers were 30: 1 and 60: 1 for DDREFs of 1 and 2. The ratios of lives saved owing to screening to deaths due to radiation-induced cancer s were 156: 1 and 312: 1 for DDREFs of 1 and 2. For the 1.8% of the screening population with very thick breasts, the latter ratios decrease to 94: 1 and 187: 1 for DDREFs of 1 and 2. The breast cancer mortality reduction due to screening greatly outweighs the risk of death due to radiation-induced cancer s. Advances in knowledge: Estimation of the radiation risk for modern breast screening in England using digital mammography. |
[
"O",
"O",
"B-T098",
"B-T091",
"O",
"O",
"O",
"B-T082",
"I-T082",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T091",
"O",
"O",
"O",
"O",
"B-T058",
"B-T204",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T082",
"I-T082",
"O",
"O",
"O",
"B-T0... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0450049",
"db_name": "UMLS"
},
{
"db_id": "C0600169",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id... | [
"Analysis",
"of",
"occupant",
"kinematics",
"and",
"dynamics",
"in",
"nearside",
"oblique",
"impacts",
"The",
"objective",
"of",
"this",
"article",
"is",
"to",
"analyze",
"the",
"kinematics",
"and",
"dynamics",
"of",
"restrained",
"postmortem",
"human",
"surrogate... | [
[
0,
8
],
[
9,
11
],
[
12,
20
],
[
21,
31
],
[
32,
35
],
[
36,
44
],
[
45,
47
],
[
48,
56
],
[
57,
64
],
[
65,
72
],
[
73,
76
],
[
77,
86
],
[
87,
89
],
[
9... | Analysis of occupant kinematics and dynamics in nearside oblique impacts The objective of this article is to analyze the kinematics and dynamics of restrained postmortem human surrogates (PMHS) exposed to a nearside oblique impact and the injuries that were found after the tests. Three male PMHS of similar age (64 ± 4 years) and anthropometry (weight: 61 ± 9.6 kg; stature: 172 ± 2.7 cm) were exposed to a 30° nearside oblique impact at 34 km/h. The test fixture approximated the seating position of a front seat occupant. A rigid seat was designed to match the pelvic displacement in a vehicle seat. Surrogates were restrained by a 3-point seat belt consisting of a 2 kN pretensioner (PT), 4.5 kN force-limiting shoulder belt, and a 3.5 kN PT lap belt. The shoulder belt PT was not fired in one of the tests. Trajectories of the head, shoulder, and hip joint (bilaterally) were recorded at 1,000 Hz by a 3D motion capture system. The 3D acceleration and angular rate of the head, T1, and pelvis, and the 3D acceleration of selected spinal locations was measured at 10,000 Hz. Seat belt load cells measured the belt tension at 4 locations. PMHS donation and handling were performed with the approval of the relevant regional ethics review board. Activation of the shoulder PT reduced substantially the peak forward excursion of the head but did not influence the lateral displacement of the head center of gravity (CG). In all 3 subjects, the lateral excursion of the head CG (291.1, 290, 292.1 mm) was greater than the forward displacement (271.4, 216.7, 171.5 mm). The hip joint excursion of the PMHS that was not exposed to the shoulder PT seat belt was twice the magnitude observed for the other 2 subjects. The 3 PMHS sustained clavicle fractures on the shoulder loaded by the seat belt and 2 of them were diagnosed atlantoaxial subluxation in the radiologist examination. Avulsion fractures of the right lamina of T1, T2, T3, and T4 were found when the PT was not used. The 3 PMHS received multiple fractures spread over both aspects of the rib cage and involving the posterior aspect of it. In this study of nearside oblique impact loading, the PMHS exhibited kinematics characterized by reduced torso pitching and increased lateral head excursion as compared to previous frontal impact results. These kinematics resulted in potential cervical and thoracic spinal injuries and in complete, displaced fractures of the lateral and posterior aspects of the rib cage. Though this is a limited number of subjects, it shows the necessity of further understanding of the kinematics of occupants exposed to this loading mode. |
[
"B-T103",
"I-T103",
"O",
"B-T103",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"O",
"B-T103",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T033",
"O",
"O",
"B-T038",
"O",
"... | [
{
"db_id": "C0002520",
"db_name": "UMLS"
},
{
"db_id": "C0002520",
"db_name": "UMLS"
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{
"db_id": null,
"db_name": null
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{
"db_id": "C3888046",
"db_name": "UMLS"
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{
"db_id": null,
"db_name": null
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{
"db_id": null,
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{
... | [
"Amino",
"Acids",
"Regulate",
"mTORC1",
"by",
"an",
"Obligate",
"Two",
"-",
"step",
"Mechanism",
"The",
"mechanistic",
"target",
"of",
"rapamycin",
"complex",
"1",
"(",
"mTORC1",
")",
"coordinates",
"cell",
"growth",
"with",
"its",
"nutritional",
",",
"hormona... | [
[
0,
5
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[
6,
11
],
[
12,
20
],
[
21,
27
],
[
28,
30
],
[
31,
33
],
[
34,
42
],
[
43,
46
],
[
46,
47
],
[
47,
51
],
[
52,
61
],
[
62,
65
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[
66,
77
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[
7... | Amino Acids Regulate mTORC1 by an Obligate Two-step Mechanism The mechanistic target of rapamycin complex 1 (mTORC1) coordinates cell growth with its nutritional, hormonal, energy, and stress status. Amino acids are critical regulators of mTORC1 that permit other inputs to mTORC1 activity. However, the roles of individual amino acids and their interactions in mTORC1 activation are not well understood. Here we demonstrate that activation of mTORC1 by amino acids includes two discrete and separable steps: priming and activation. Sensitizing mTORC1 activation by priming amino acids is a prerequisite for subsequent stimulation of mTORC1 by activating amino acids. Priming is achieved by a group of amino acids that includes l-asparagine, l-glutamine, l-threonine, l-arginine, l-glycine, l-proline, l-serine, l-alanine, and l-glutamic acid. The group of activating amino acids is dominated by l-leucine but also includes l-methionine, l-isoleucine, and l-valine. l-Cysteine predominantly inhibits priming but not the activating step. Priming and activating steps differ in their requirements for amino acid concentration and duration of treatment. Priming and activating amino acids use mechanisms that are distinct both from each other and from growth factor signaling. Neither step requires intact tuberous sclerosis complex of proteins to activate mTORC1. Concerted action of priming and activating amino acids is required to localize mTORC1 to lysosomes and achieve its activation. |
[
"B-T201",
"I-T201",
"O",
"B-T058",
"I-T058",
"I-T058",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"B-T091",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"B-T038",
"O",
"O",
"O",
"O",
"B-T033",
"I-T033",
"O",
"O",
"O",
"O",
"O"... | [
{
"db_id": "C0521982",
"db_name": "UMLS"
},
{
"db_id": "C0521982",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0020431",
"db_name": "UMLS"
},
{
"db_id": "C0020431",
"db_name": "UMLS"
},
{
"db_id": "C0020431",
"db_name": "U... | [
"Successful",
"treatment",
"with",
"hyperbaric",
"oxygen",
"therapy",
"for",
"severe",
"brain",
"edema",
"characterized",
"by",
"radiological",
"appearance",
"of",
"pseudosubarachnoid",
"hemorrhage",
"in",
"a",
"child",
"Pseudosubarachnoid",
"hemorrhage",
"(",
"PSAH",
... | [
[
0,
10
],
[
11,
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],
[
21,
25
],
[
26,
36
],
[
37,
43
],
[
44,
51
],
[
52,
55
],
[
56,
62
],
[
63,
68
],
[
69,
74
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[
75,
88
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[
89,
91
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[
92,
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[
... | Successful treatment with hyperbaric oxygen therapy for severe brain edema characterized by radiological appearance of pseudosubarachnoid hemorrhage in a child Pseudosubarachnoid hemorrhage (PSAH) is a rare neuroradiological finding, particularly in pediatric patients. The appearance of PSAH is commonly associated with poor clinical outcome due to refractory cerebral edema. Recent clinical trials have favored hyperbaric oxygen therapy (HBOT) as a promising therapeutic strategy for adult patients with severe head injuries. The present report describes a pediatric case of diffuse brain edema characterized by the radiological appearance of PSAH successfully treated with HBOT. An adolescent boy collapsed unconscious following convulsion for 3-5 min with fever and headache for 2 days. A brain computed tomography (CT) scan provided an image compatible with subarachnoid hemorrhage (SAH). Lumbar puncture was conducted on admission to hospital and showed no evidence of SAH. The CT scan was again considered and eventually interpreted as PSAH. The patient received drug treatment including acyclovir and mannitol, but the condition deteriorated rapidly. HBOT was administered at 72 h post admission and the condition was clearly improved following the initial therapy. The patient was discharged with 20 sessions of HBOT and recovered completely after 1 year. The appearance of PSAH indicates severe cerebral edema refractory to treatment with conventional internal medicine. HBOT maybe an effective therapeutic strategy for this condition. |
[
"O",
"B-T038",
"O",
"B-T204",
"I-T204",
"O",
"B-T005",
"I-T005",
"I-T005",
"O",
"O",
"O",
"O",
"O",
"B-T103",
"I-T103",
"O",
"B-T038",
"I-T038",
"B-T038",
"I-T038",
"B-T005",
"I-T005",
"I-T005",
"O",
"B-T005",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0520989",
"db_name": "UMLS"
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{
"db_id": null,
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{
"db_id": "C0330922",
"db_name": "UMLS"
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"db_id": "C0330922",
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... | [
"The",
"resistance",
"of",
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"orange",
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"tristeza",
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"... | [
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33,
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40,
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7... | The resistance of sour orange to Citrus tristeza virus is mediated by both the salicylic acid and RNA silencing defence pathways Citrus tristeza virus (CTV) induces in the field the decline and death of citrus varieties grafted on sour orange (SO) rootstock, which has forced the use of alternative decline - tolerant rootstocks in affected countries, despite the highly desirable agronomic features of the SO rootstock. Declining citrus plants display phloem necrosis below the bud union. In addition, SO is minimally susceptible to CTV compared with other citrus varieties, suggesting partial resistance of SO to CTV. Here, by silencing different citrus genes with a Citrus leaf blotch virus -based vector, we have examined the implication of the RNA silencing and salicylic acid (SA) defence pathways in the resistance of SO to CTV. Silencing of the genes RDR1, NPR1 and DCL2 / DCL4, associated with these defence pathways, enhanced virus spread and accumulation in SO plants in comparison with non-silenced controls, whereas silencing of the genes NPR3 / NPR4, associated with the hypersensitive response, produced a slight decrease in CTV accumulation and reduced stunting of SO grafted on CTV - infected rough lemon plants. We also found that the CTV RNA silencing suppressors p20 and p23 also suppress the SA signalling defence, with the suppressor activity being higher in the most virulent isolates. |
[
"O",
"O",
"O",
"O",
"O",
"O",
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"O",
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"B-T103",
"O",
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"O",
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"O",
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... | [
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... | [
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"... | [
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68,
... | One-hour post-load hyperglycemia combined with HbA1c identifies pre-diabetic individuals with a higher cardio-metabolic risk burden Evidence suggests that combining 1-hour plasma glucose ≥155 mg/dl during an oral glucose tolerance test (OGTT) with glycosylated hemoglobin (HbA1c) significantly increases their predictive power for incident diabetes, while their individual and joint associations with cardio-metabolic risk factors remain undefined. Herein, we evaluated whether 1-hour post-load plasma glucose ≥155 mg/dl combined with HbA1c may identify pre-diabetic individuals with a higher cardio-metabolic risk. Anthropometric and metabolic characteristics, insulin sensitivity and insulin secretion assessed by OGTT -derived indexes, carotid intima-media thickness (IMT), pulse pressure, and rate pressure product were evaluated in 1495 individuals. As compared with subjects with 1-hour post-load glucose <155 mg/dl, individuals with 1-hour post-load glucose ≥155 mg/dl exhibited a significantly worse cardio metabolic profile, both in the group with HbA1c <5.7%, and in the group with prediabetes (HbA1c 5.7-6.4%). Specifically, in both groups, subjects with 1-hour post-load glucose ≥155 mg/dl had higher fasting and 2-h post-load glucose (p < 0.0001 for all in both group s), higher HOMA-IR (p < 0.0001 in both groups), and carotid IMT (p = 0.05 in the group with HbA1c <5.7% and p = 0.03 in the group HbA1c 5.7-6.4%), as well as lower Matsuda index, insulinogenic index and disposition index (p < 0.0001 in both groups), and lower insulin - stimulated glucose disposal (p < 0.0001 in the group with HbA1c <5.7% and p = 0.03 in the group HbA1c 5.7-6.4%). Hyperglycemia at 1-hour during an OGTT may be a useful tool to identify a subset of individuals within HbA1c -defined glycemic categories at higher risk of developing type 2 diabetes and cardiovascular disease. |
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"O",
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"O... | [
{
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... | [
"Ruscogenin",
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61,
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... | Ruscogenin Attenuates Cerebral Ischemia -Induced Blood-Brain Barrier Dysfunction by Suppressing TXNIP / NLRP3 Inflammasome Activation and the MAPK Pathway Ruscogenin, an important steroid sapogenin derived from Ophiopogon japonicus, has been shown to inhibit cerebral ischemic injury. However, its potential molecular action on blood-brain barrier (BBB) dysfunction after stroke remains unclear. This study aimed to investigate the effects of ruscogenin on BBB dysfunction and the underlying mechanisms in middle cerebral artery occlusion / reperfusion (MCAO / R)- injured mice and oxygen-glucose deprivation / reoxygenation (OGD / R)- injured mouse brain microvascular endothelial cells (bEnd.3). The results demonstrated that administration of ruscogenin (10 mg/kg) decreased the brain infarction and edema, improved neurological deficits, increased cerebral brain flow (CBF), ameliorated histopathological damage, reduced evans blue (EB) leakage and upregulated the expression of tight junctions (TJs) in MCAO / R - injured mice. Meanwhile, ruscogenin (0.1-10 µM) treatment increased cell viability and trans-endothelial electrical resistance (TEER) value, decreased sodium fluorescein leakage, and modulated the TJs expression in OGD / R -induced bEnd.3 cells. Moreover, ruscogenin also inhibited the expression of interleukin-1β (IL-1β) and caspase-1, and markedly suppressed the expression of Nucleotide-binding domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) and thiredoxin-interactive protein (TXNIP) in vivo and in vitro. Furthermore, ruscogenin decreased reactive oxygen species (ROS) generation and inhibited the mitogen-activated protein kinase (MAPK) pathway in OGD / R -induced bEnd.3 cells. Our findings provide some new insights into its potential application for the prevention and treatment of ischemic stroke. |
[
"O",
"O",
"B-T062",
"O",
"B-T204",
"B-T170",
"I-T170",
"I-T170",
"O",
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"O",
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"O",
"O",
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"O",
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"O",
"O",
"O",
"O",
"O",
"O",
"B-T062",
"O",
"B-T201",
"O",
"O",
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"O",
"O... | [
{
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{
"db_id": "C0936012",
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{
"db_id": "C0086418",
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{
"db_id": "C0598139",
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{
... | [
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"and",
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"synthetic",
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"libraries",
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[
0,
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11,
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24,
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27,
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33,
42
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[
43,
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[
52,
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[
62,
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66,
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72,
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84,
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... | Generation and analyses of human synthetic antibody libraries and their application for protein microarrays Antibody -based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities of these antibodies were analyzed in a variety of immunochemical assays and a subset was further evaluated for functionality in protein microarray applications. This high-throughput approach demonstrates the ability to rapidly generate a wealth of reagents not only for proteome research, but potentially also for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen - binding sites, synthetic libraries offer increased understanding of how different diversity contributes to antibody binding reactivity and stability, thereby providing the key to future library optimization. |
[
"O",
"O",
"O",
"O",
"B-T103",
"O",
"B-T038",
"B-T038",
"O",
"O",
"O",
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"I-T103",
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"B-T091",
"O",
"O",
"O",
"O",
"O",
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"O",
"O",
"O",
"B-T103",
"I-T103",
"O",
"O",
"O",
"O",
"B-T058",
"O",
"O",
"O",
"O",... | [
{
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"db_id": "C0013161",
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"db_id": "C002... | [
"A",
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80,
... | A pH - Sensitive Nanocarrier for Tumor Targeting: Delivery of Ruthenium Complex for Tumor Theranostic by pH - Sensitive Nanocapsule Ruthenium complex is a potentially theranostic agent for cancer imaging and therapy, however its application is limited due to poor water-solubility and lack of tumor selectivity. To overcome the above drawbacks, pH - sensitive nanocapsule as a novel targeting carrier was designed to deliver ruthenium complex for treating xenograft tumor of mice. The core / shell structured nanocapsule with ruthenium complex tris(1,10-phenanthroline) ruthenium(II) complex (3P-Ru) as the core and a pH - sensitive polymeric material poly (2-diisopropylaminoethyl methacrylate)-block poly(2-aminoethyl methacrylate hydrochloride) (PbPS) as the shell was synthesized and characterized. Meanwhile, the nanocapsule was used to investigate cell viability and evaluate tissue distribution as well as preventing tumor growth efficacy in U251 stem cells tumor -bearing mouse model. The nanocapsule had a size of 103.1 ± 11.3 nm, zeta potential of -40 ± 5.3 mV, EE of 76.7 ± 0.9%, LE of 25.4 ± 0.6% and it could control drug release under different pH conditions. The results of cell uptake showed that the fluorescent 3P-Ru loaded in the nanocapsule could be delivered into cells with high efficiency, and then significantly inhibited U251 proliferation in a concentration - dependent manner. After U251 stem cells were transplanted subcutaneously into mice, the 3P-Ru / PbPS nanocapsule (PbPS - Ru - NC) via intravenous administration could concentrate in tumor area and obviously prevent tumor growth. The pH - sensitive nanocapsule as a antitumor agent carrier was able to effectively deliver 3P-Ru into gliomas cells, and cell growth was significantly inhibited both in vitro and in vivo. Such pH - sensitive nanocapsule for ruthenium complex delivery would have great potential application in tumor theranostics. |
[
"B-T103",
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"I-T038",
"I-T038",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
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"O",
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"B-T017",
"I-T017",
"O",
"B-T017",
"O",
"O",
"O",
"B-T103",
"B-T103",
"O",
"O",
"O",
"O",
"O"... | [
{
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{
"db_id": "C0058698",
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{
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{
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{
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{
... | [
"Dopamine",
"D2",
"Receptors",
"Enhance",
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12,
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22,
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30,
40
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41,
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[
50,
52
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[
53,
60
],
[
61,
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[
72,
79
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80,
86
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87,
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96,
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... | Dopamine D2 Receptors Enhance Population Dynamics in Primate Prefrontal Working Memory Circuits Working memory is associated with persistent activity in the prefrontal cortex (PFC). The neuromodulator dopamine, which is released by midbrain neurons projecting into the frontal lobe, influences PFC neurons and networks via the dopamine D1 (D1R) and the D2 receptor (D2R) families. Although behavioral, clinical and computational evidence suggest an involvement of D2Rs in working memory, a neuronal explanation is missing. We report an enhancement of persistent working memory responses of PFC neurons after iontophoretically stimulating D2Rs in monkeys memorizing the number of items in a display. D2R activation improved working memory representation at the population level and increased population dynamics during the transition from visual to mnemonic representations. Computational modeling suggests that D2Rs act by modulating interneuron-to-pyramidal signaling. By increasing the population's response dynamics, D2Rs might put PFC networks in a more flexible state and enhance the neurons ' working memory coding, thereby controlling dynamic cognitive control. |
[
"O",
"B-T017",
"I-T017",
"I-T017",
"I-T017",
"I-T017",
"O",
"O",
"B-T103",
"O",
"B-T005",
"B-T103",
"I-T103",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"B-T204",
"B-T005",
"O",
"B-T005",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O"... | [
{
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{
"db_id": "C0039215",
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{
"db_id": "C0039215",
"db_name": "UMLS"
},
{
"db_id": "C0039215",
"db_name": "UMLS"
},
{
"db_id": "C0039215",
"db_name": "UMLS"
},
{
"db_id": "C0039215",
"db_name": "U... | [
"Circulating",
"Memory",
"CD4",
"+",
"T",
"Cells",
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"Capsid",
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"Humans",
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"(",
"RV",
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[
0,
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12,
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19,
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22,
23
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24,
25
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[
26,
31
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[
32,
38
],
[
39,
48
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[
49,
57
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[
58,
60
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61,
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72,
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... | Circulating Memory CD4+ T Cells Target Conserved Epitopes of Rhinovirus Capsid Proteins and Respond Rapidly to Experimental Infection in Humans Rhinovirus (RV) is a major cause of common cold and an important trigger of acute episodes of chronic lung diseases. Antigenic variation across the numerous RV strains results in frequent infections and a lack of durable cross-protection. Because the nature of human CD4(+) T cells that target RV is largely unknown, T cell epitopes of RV capsid proteins were analyzed, and cognate T cells were characterized in healthy subjects and those infected by intranasal challenge. Peptide epitopes of the RV-A16 capsid proteins VP1 and VP2 were identified by peptide / MHC class II tetramer-guided epitope mapping, validated by direct ex vivo enumeration, and interrogated using a variety of in silico methods. Among noninfected subjects, those circulating RV-A16 -specific CD4(+) T cells detected at the highest frequencies targeted 10 unique epitopes that bound to diverse HLA-DR molecules. T cell epitopes localized to conserved molecular regions of biological significance to the virus were enriched for HLA class I and II binding motifs, and constituted both species -specific (RV-A) and pan-species (RV-A, - B, and - C) varieties. Circulating epitope -specific T cells comprised both memory Th1 and T follicular helper cells, and were rapidly expanded and activated after intranasal challenge with RV-A16. Cross-reactivity was evidenced by identification of a common *0401- restricted epitope for RV-A16 and RV-A39 by tetramer-guided epitope mapping and the ability for RV-A16 -specific Th1 cells to proliferate in response to their RV-A39 peptide counterpart. The preferential persistence of high-frequency RV -specific memory Th1 cells that recognize a limited set of conserved epitopes likely arises from iterative priming by previous exposures to different RV strains. |
[
"B-T038",
"O",
"O",
"O",
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"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
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"I-T038",
"O",
"O",
"O",
"O",
"O",
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"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T098",
"O",
"O... | [
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"db_id": null,... | [
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7... | Sitting Time and Mortality in Older Adults With Disability: A National Cohort Study The progressive aging of the population has increased the number of older adults with disabilities. Regular physical activity has shown to improve health among these individuals, but the effects of sedentary behavior are mostly unknown. Thus, this study examined the association between sitting time and mortality in older adults with disability. Prospective cohort of 2470 people aged ≥60 years. In 2000-2011, the study participants reported their sitting time and physical activity levels and were subsequently followed up through 2011 to ascertain mortality. During an average follow-up of 8.7 years, 982 deaths occurred. Compared with people who spent seated <4 hours/d, the hazard ratio (95% confidence interval) of mortality was 1.27 (1.07-1.51) in those seated during 4-6 hours/d and 1.55 (1.29-1.87) in those seated for >6 hours/d. Each increment of 1 hour/day in sitting time was linked to a 7% increase in mortality. Compared with active individuals who spent seated <4 hours/day, those who were inactive and spent seated >6 hours/d showed the highest mortality (hazard ratio 1.82, 95% confidence interval 1.37-2.42). Sitting time is associated with higher mortality in older people with disability. Interventions combining the reduction of sedentary behavior with increased physical activity should be developed and evaluated in this group of population. |
[
"B-T103",
"O",
"B-T017",
"B-T038",
"O",
"O",
"O",
"B-T103",
"I-T103",
"I-T103",
"O",
"O",
"B-T103",
"I-T103",
"I-T103",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"B-T038",
"I-T038",
"I-T038",
"I-T038",
"I-T038",
"I-T038",
"O",
"B-T038",
"O",
"O",
"O",
"O",... | [
{
"db_id": "C1529556",
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{
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{
"db_id": "C0024109",
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{
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{
"db_id": null,
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{
"db_id": null,
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{
... | [
"TFAP2C",
"promotes",
"lung",
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"and",
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... | [
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7... | TFAP2C promotes lung tumorigenesis and aggressiveness through miR-183 - and miR-33a -mediated cell cycle regulation Non-small cell lung cancer (NSCLC) remains one of the leading causes of death worldwide, and thus new molecular targets need to be identified to improve treatment efficacy. Although epidermal growth factor receptor (EGFR)/ KRAS mutation -driven lung tumorigenesis is well understood, the mechanism of EGFR / KRAS -independent signal activation remains elusive. Enhanced TFAP2C (transcription factor activating enhancer-binding protein 2C) expression is associated with poor prognosis in some types of cancer patients, but little is known of its relation with the pathogenesis of lung cancer. In the present study, we found that TFAP2C overexpression was associated with cell cycle activation and NSCLC cell tumorigenesis. Interestingly, TFAP2C blocked AKAP12 -mediated cyclin D1 inhibition by inducing the overexpression of oncogenic microRNA (miRNA)-183 and simultaneously activated cyclin-dependent kinase 6 -mediated cell cycle progression by downregulating tumor-suppressive miRNA-33a. In a mouse xenograft model, TFAP2C promoted lung tumorigenesis and disease aggressiveness via the miR-183 and miR-33a pathways. The study provides a mechanism of mitogenic and oncogenic signaling via two functionally opposed miRNAs and suggests that TFAP2C -induced cell cycle hyperactivation contributes to lung tumorigenesis. |
[
"O",
"O",
"O",
"O",
"B-T005",
"I-T005",
"I-T005",
"I-T005",
"O",
"B-T005",
"I-T005",
"I-T005",
"B-T058",
"B-T005",
"I-T005",
"I-T005",
"O",
"B-T005",
"O",
"O",
"O",
"O",
"B-T005",
"I-T005",
"I-T005",
"O",
"B-T005",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
... | [
{
"db_id": null,
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{
"db_id": null,
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{
"db_id": null,
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{
"db_id": "C0011220",
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{
"db_id": "C0011220",
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{
"db_id... | [
"Recognizing",
"the",
"impact",
"of",
"endemic",
"hepatitis",
"D",
"virus",
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"hepatitis",
"B",
"virus",
"eradication",
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"B",
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... | [
[
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44,
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46,
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67,
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... | Recognizing the impact of endemic hepatitis D virus on hepatitis B virus eradication Hepatitis delta virus (HDV) in conjunction with hepatitis B virus (HBV) increases adult morbidity and mortality. A number of studies have performed cost-benefit analyses for HBV interventions, but they have ignored the impact of HDV on these outcomes. Using a mathematical model of HBV - HDV epidemiology, we compare health benefits and cost outcomes of four interventions: testing with HBV adult vaccination (diagnosis), diagnosis with antiviral treatment for HBV infections (mono - infections), diagnosis with antiviral treatment for HBV - HDV infections (dual - infections), and awareness programs. The relationship between optimal levels and outcomes of each of these interventions and HDV prevalence in HBV infected individuals ranging from 0 to 50% is determined. Over a 50 year period under no intervention, HBV prevalence, per capita total cost and death toll increase by 2.25%, -$11 and 2.6-fold respectively in moderate HDV endemic regions compared to mono - infected regions; the corresponding values for high HDV endemic regions are 4.2%, -$21 and 3.9-fold. Optimal interventions can be strategized similarly in mono and dually endemic regions. Only implementation of all four interventions achieves a very low HBV prevalence of around 1.5% in a moderate HDV endemic region such as China, with 2.8 million fewer deaths compared to no intervention. Although the policy of implementation of all four interventions costs additional $382 billion compared to no intervention, it still remains cost - effective with an incremental cost - effectiveness ratio of $1400/ QALY. Very high efficacy awareness programs achieve less prevalence with fewer deaths at a lower cost compared to treatment and/or vaccination programs. HDV substantially affects the performance of any HBV - related intervention. Its exclusion results in over-estimation of the effectiveness of HBV interventions. |
[
"O",
"O",
"O",
"O",
"B-T058",
"O",
"O",
"O",
"B-T038",
"O",
"O",
"O",
"O",
"O",
"B-T082",
"O",
"B-T062",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"B-T058",
"O",
"O",
"O",
"O",
"O",
"B-T082",
"O",
"O",
"B-T058",
"B-T038",
"O",
... | [
{
"db_id": null,
"db_name": null
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{
"db_id": null,
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},
{
"db_id": null,
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{
"db_id": null,
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{
"db_id": "C1710032",
"db_name": "UMLS"
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{
"db_id": null,
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"db_id": null,... | [
"Factors",
"associated",
"with",
"delayed",
"screening",
"of",
"contacts",
"of",
"tuberculosis",
"cases",
"in",
"the",
"Somme",
",",
"France",
"To",
"analyze",
"the",
"factors",
"associated",
"with",
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"time",
"to",
"initiating",
"tuberculosis",
"contact",
... | [
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42,
44
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54,
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[
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8... | Factors associated with delayed screening of contacts of tuberculosis cases in the Somme, France To analyze the factors associated with the time to initiating tuberculosis contact investigations in the Somme department, France. All reported tuberculosis cases and all their contacts screened between 2007 and 2011 were retrospectively included. Univariate and multivariate analyses were conducted to determine the factors associated with a "system delay "≤1 month and a " contact delay "≤0 days. The mean time between the mandatory notification of a case of tuberculosis and the date set for the contact 's screening (system delay) was 35.3 days and the average time between that date and when the contact was actually screened (contact delay) was 12.5 days. In multivariate analysis, a smear-positive sputum sample (OR: 3.68; 95% CI: 1.63-8.30) and a diagnosis at the university hospital (OR: 2.61; 95% CI: 1.14-5.96) were significantly associated with a system delay ≤1 month. A smear-positive sputum sample (OR: 1.35; 95% CI: 1.08-1.69), male gender (OR: 1.21; 95% CI: 1.01-1.49), being born in a foreign country (OR: 1.31; 95% CI: 1.02-1.69), being a family member (OR: 1.37; 95% CI: 1.05-1.77), or being another type of close contact of the case (OR: 2.47; 95% CI: 1.81-3.36) were significantly associated with a contact delay ≤0 days. System and contact delays were longer than recommended, and the factors associated with the lengthening of these delays need to be taken into account. |
[
"B-T017",
"I-T017",
"I-T017",
"O",
"B-T038",
"I-T038",
"I-T038",
"O",
"O",
"O",
"O",
"B-T092",
"O",
"O",
"B-T098",
"I-T098",
"I-T098",
"B-T038",
"I-T038",
"B-T058",
"O",
"B-T038",
"I-T038",
"I-T038",
"B-T062",
"O",
"B-T033",
"I-T033",
"I-T033",
"O",
"B-T03... | [
{
"db_id": "C3850017",
"db_name": "UMLS"
},
{
"db_id": "C3850017",
"db_name": "UMLS"
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{
"db_id": "C3850017",
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{
"db_id": null,
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},
{
"db_id": "C2827469",
"db_name": "UMLS"
},
{
"db_id": "C2827469",
"db_name": "U... | [
"Circulating",
"progenitor",
"cells",
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"dysfunction",
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... | Circulating progenitor cells and coronary microvascular dysfunction: Results from the NHLBI -sponsored Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD) Ischemia stimulates a reparative response resulting in mobilization of circulating progenitor cells (CPCs). We hypothesized that women with chronic myocardial ischemia from coronary microvascular disease (CMD) will mobilize CPCs. In 123 women with ischemic symptoms and signs but no obstructive coronary artery disease (CAD) enrolled in the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD), we measured coronary flow reserve (CFR) in response to intracoronary adenosine. Peripheral blood CPCs were measured using flow cytometry for expression of CD34, CD133, CXCR4, and VEGFR2. Subjects were 53 ± 11 years, BMI 30 ± 8; 44% hypertensive, 11% diabetic, 23% hyperlipidemic and 7% smokers. Lower CFR correlated inversely with higher levels of hematopoietic -enriched CD34+ (r = -0.23, p = 0.011), CD34+ / CD133+ (r = -0.24, p = 0.008), and CD34+ / CXCR4+ (r = -0.19, p = 0.036) cells. In multivariable regression analyses, after adjusting for traditional cardiovascular risk factors, lower CFR remained significantly associated with elevated levels of CD34+ (β -0.18, p = 0.042), CD34+ / CD133+ (β -0.24, p = 0.036), and CD34+ / CXCR4+ (β -0.22, p = 0.050) cells. We found no association between CFR and CD34+ / VEGFR2+ cells. In women with non-obstructive CAD, impaired CFR is associated with higher levels of CPCs, suggesting that chronic myocardial ischemia from CMD stimulates CPC mobilization. The functional significance of elevated CPCs in these subjects requires further investigation as a potential biomarker and treatment target. |
[
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"B-T058",
"I-T058",
"O",
"O",
"B-T103",
"B-T033",
"O",
"O",
"B-T204",
"B-T038",
"B-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T058",
"I-T058",
"O",
"B-T204",
"I-T204",
"O",
"O"... | [
{
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{
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{
"db_id": "C0017393",
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{
"db_id": "C0017393",
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"db_id... | [
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7... | Mining for Candidate Genes in an Introgression Line by Using RNA Sequencing: The Anthocyanin Overaccumulation Phenotype in Brassica Introgression breeding is a widely used method for the genetic improvement of crop plants; however, the mechanism underlying candidate gene flow patterns during hybridization is poorly understood. In this study, we used a powerful pipeline to investigate a Chinese cabbage (Brassica rapa L. ssp. pekinensis) introgression line with the anthocyanin overaccumulation phenotype. Our purpose was to analyze the gene flow patterns during hybridization and elucidate the genetic factors responsible for the accumulation of this important pigment compound. We performed RNA-seq analysis by using two pipelines, one with and one without a reference sequence, to obtain transcriptome data. We identified 930 significantly differentially expressed genes (DEGs) between the purple - leaf introgression line and B. rapa green cultivar, namely, 389 up-regulated and 541 down-regulated DEGs that mapped to the B. rapa reference genome. Since only one anthocyanin pathway regulatory gene was identified, i.e., Bra037887 (bHLH), we mined unmapped reads, revealing 2031 de novo assembled unigenes, including c3563g1i2. Phylogenetic analysis suggested that c3563g1i2, which was transferred from the Brassica B genome of the donor parental line Brassica juncea, may represent an R2R3-MYB transcription factor that participates in the ternary transcriptional activation complex responsible for the anthocyanin overaccumulation phenotype of the B. rapa introgression line. We also identified genes involved in cold and light reaction pathways that were highly upregulated in the introgression line, as confirmed using quantitative real-time PCR analysis. The results of this study shed light on the mechanisms underlying the purple leaf trait in Brassica plants and may facilitate the use of introgressive hybridization for many traits of interest. |
[
"O",
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"I-T103",
"O",
"B-T204",
"O",
"O",
"O",
"O",
"B-T017",
"I-T017",
"O",
"O",
"O",
"B-T038",
"O",
"O",
"O",
"B-T103",
"O",
"B-T103",
"O",
"O",
"B-T103",
"I-T103",
"O",
"O",
"O",
"B-T038",
"O",
"B-T204",
"I-T204",
"O",
"O",
"O",
"O",
... | [
{
"db_id": null,
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},
{
"db_id": "C0597298",
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{
"db_id": "C0597298",
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{
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{
"db_id": "C0012120",
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{
"db_id": null,
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{
... | [
"The",
"C",
"Isoform",
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97,... | The C Isoform of Dictyostelium Tetraspanins Localizes to the Contractile Vacuole and Contributes to Resistance against Osmotic Stress Tetraspanins (Tsps) are membrane proteins that are widely expressed in eukaryotic organisms. Only recently, Tsps have started to acquire relevance as potential new drug targets as they contribute, via protein-protein interactions, to numerous pathophysiological processes including infectious diseases and cancer. However, due to a high number of isoforms and functional redundancy, knowledge on specific functions of most Tsps is still scarce. We set out to characterize five previously annotated Tsps, TspA-E, from Dictyostelium discoideum, a model for studying proteins that have human orthologues. Using reverse transcriptase PCRs, we found mRNAs for TspA-E in the multicellular slug stage, whereas vegetative cells expressed only TspA, TspC and, to a lesser extent, TspD. We raised antibodies against TspA, TspC and TspD and detected endogenous TspA, as well as heterologously expressed TspA and TspC by Western blot. N-deglycosylation assays and mutational analyses showed glycosylation of TspA and TspC in vivo. GFP -tagged Tsps co-localized with the proton pump on the contractile vacuole network. Deletion strains of TspC and TspD exibited unaltered growth, adhesion, random motility and development. Yet, tspC- cells showed a defect in coping with hypo-osmotic stress, due to accumulation of contractile vacuoles, but heterologous expression of TspC rescued their phenotype. In conclusion, our data fill a gap in Dictyostelium research and open up the possibility that Tsps in contractile vacuoles of e.g. Trypanosoma may one day constitute a valuable drug target for treating sleeping sickness, one of the most threatening tropical diseases. |
[
"B-T103",
"O",
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"I-T017",
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"B-T038",
"O",
"B-T103",
"O",
"O",
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"I-T038",
"O",
"O",
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"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
... | [
{
"db_id": "C0028040",
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{
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{
"db_id": "C0229565",
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{
"db_id": "C0229565",
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},
{
"db_id": "C0290758",
"db_name": "UMLS"
},
{
"db_id": "C1171362",
"db_name": "U... | [
"Nicotine",
"Suppressed",
"Fetal",
"Adrenal",
"StAR",
"Expression",
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... | [
[
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34,
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50,
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... | Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated- Histone Deacetylation Modification Mechanism Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine -mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine - treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1 -medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression. |
[
"B-T017",
"I-T017",
"I-T017",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"O",
"O",
"O",
"B-T033",
"I-T033",
"I-T033",
"O",
"O",
"B-T062",
"I-T062",
"I-T062",
"I-T062",
"O",
"O",
"O",
"O",
"B-T062",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T017"... | [
{
"db_id": "C0010271",
"db_name": "UMLS"
},
{
"db_id": "C0010271",
"db_name": "UMLS"
},
{
"db_id": "C0010271",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
... | [
"Dural",
"Venous",
"Sinus",
"Diameters",
"in",
"Children",
"with",
"Sickle",
"Cell",
"Disease",
":",
"Correlation",
"with",
"History",
"of",
"Stroke",
"in",
"a",
"Case",
"-",
"Control",
"Study",
"The",
"purpose",
"of",
"this",
"study",
"was",
"to",
"compare"... | [
[
0,
5
],
[
6,
12
],
[
13,
18
],
[
19,
28
],
[
29,
31
],
[
32,
40
],
[
41,
45
],
[
46,
52
],
[
53,
57
],
[
58,
65
],
[
65,
66
],
[
67,
78
],
[
79,
83
],
[
8... | Dural Venous Sinus Diameters in Children with Sickle Cell Disease: Correlation with History of Stroke in a Case-Control Study The purpose of this study was to compare the diameters of the dural venous sinuses (DVSs) in children with sickle cell disease (SCD) with healthy controls and determine whether the size has any correlation to history of cerebral infarct among children with SCD. A retrospective review compared demographics, medical history and magnetic resonance venography (MRV) findings in children with SCD with those in controls. Venous sinus diameters were measured on MRV in all subjects by the authors, who were blinded to the children's clinical history. The study cohort included 38 MRVs in children with SCD and 38 control subjects. Statistical comparison showed children with SCD had significantly (P < 0.05) larger DVS diameters than controls. Among children with SCD with a history of stroke or silent infarct, DVS diameters were not significantly different. Children with SCD had larger DVS diameters than did controls, regardless of the former group's history of cerebral infarct. The difference in size of venous sinuses is important to be aware of during the interpretation of neuroimaging studies to avoid unneeded additional imaging or referral. |
[
"B-T204",
"I-T204",
"O",
"O",
"O",
"O",
"O",
"B-T033",
"I-T033",
"O",
"B-T038",
"O",
"O",
"B-T005",
"I-T005",
"O",
"B-T082",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T005",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T005",
"I-T005",
"O",
"B-T005",
"O",
"O",
"O",... | [
{
"db_id": "C0322806",
"db_name": "UMLS"
},
{
"db_id": "C0322806",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id... | [
"Culex",
"quinquefasciatus",
"from",
"Rio",
"de",
"Janeiro",
"Is",
"Not",
"Competent",
"to",
"Transmit",
"the",
"Local",
"Zika",
"Virus",
"The",
"Americas",
"have",
"suffered",
"a",
"dramatic",
"epidemic",
"of",
"Zika",
"since",
"May",
"in",
"2015",
",",
"wh... | [
[
0,
5
],
[
6,
22
],
[
23,
27
],
[
28,
31
],
[
32,
34
],
[
35,
42
],
[
43,
45
],
[
46,
49
],
[
50,
59
],
[
60,
62
],
[
63,
71
],
[
72,
75
],
[
76,
81
],
[
8... | Culex quinquefasciatus from Rio de Janeiro Is Not Competent to Transmit the Local Zika Virus The Americas have suffered a dramatic epidemic of Zika since May in 2015, when Zika virus (ZIKV) was first detected in Brazil. Mosquitoes belonging to subgenus Stegomyia of Aedes, particularly Aedes aegypti, are considered the primary vectors of ZIKV. However, the rapid spread of the virus across the continent raised several concerns about the transmission dynamics, especially about potential mosquito vectors. The purpose of this work was to assess the vector competence of the house mosquito Culex quinquefasciatus from an epidemic Zika area, Rio de Janeiro, Brazil, for local circulating ZIKV isolates. Culex quinquefasciatus and Ae. aegypti (positive control of ZIKV infection) from Rio de Janeiro were orally exposed to two ZIKV strains isolated from human cases from Rio de Janeiro (Rio-U1 and Rio-S1). Fully engorged mosquitoes were held in incubators at 26 ± 1°C, 12 h:12 h light:dark cycle and 70 ± 10% humidity. For each combination mosquito population- ZIKV strain, 30 specimens were examined for infection, dissemination and transmission rates, at 7, 14 and 21 days after virus exposure by analyzing body (thorax plus abdomen), head and saliva respectively. Infection rates were minimal to completely absent in all Cx. quinquefasciatus - virus combinations and were significantly high for Ae. aegypti. Moreover, dissemination and transmission were not detected in any Cx. quinquefasciatus mosquitoes whatever the incubation period and the ZIKV isolate. In contrast, Ae. aegypti ensured high viral dissemination and moderate to very high transmission. The southern house mosquito Cx. quinquefasciatus from Rio de Janeiro was not competent to transmit local strains of ZIKV. Thus, there is no experimental evidence that Cx. quinquefasciatus likely plays a role in the ZIKV transmission. Consequently, at least in Rio, mosquito control to reduce ZIKV transmission should remain focused on Ae. aegypti. |
[
"O",
"O",
"O",
"B-T204",
"O",
"O",
"O",
"B-T103",
"I-T103",
"I-T103",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"O",
"B-T170",
"B-T204",
"O",
"B-T170",
"O",
"B-T204",
"I-T204",
"O",
"O",
"B-T038",
"O",
"B-T038",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0016832",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,... | [
"Detrimental",
"Effect",
"of",
"Fungal",
"60",
"-",
"kDa",
"Heat",
"Shock",
"Protein",
"on",
"Experimental",
"Paracoccidioides",
"brasiliensis",
"Infection",
"The",
"genus",
"Paracoccidioides",
"comprises",
"species",
"of",
"dimorphic",
"fungi",
"that",
"cause",
"pa... | [
[
0,
11
],
[
12,
18
],
[
19,
21
],
[
22,
28
],
[
29,
31
],
[
31,
32
],
[
32,
35
],
[
36,
40
],
[
41,
46
],
[
47,
54
],
[
55,
57
],
[
58,
70
],
[
71,
87
],
[
... | Detrimental Effect of Fungal 60-kDa Heat Shock Protein on Experimental Paracoccidioides brasiliensis Infection The genus Paracoccidioides comprises species of dimorphic fungi that cause paracoccidioidomycosis (PCM), a systemic disease prevalent in Latin America. Here, we investigated whether administration of native 60-kDa heat shock protein of P. brasiliensis (nPbHsp60) or its recombinant counterpart (rPbHsp60) affected the course of experimental PCM. Mice were subcutaneously injected with nPbHsp60 or rPbHsp60 emulsified in complete's Freund Adjuvant (CFA) at three weeks after intravenous injection of P. brasiliensis yeasts. Infected control mice were injected with CFA or isotonic saline solution alone. Thirty days after the nPbHsp60 or rPbHsp60 administration, mice showed remarkably increased fungal load, tissue inflammation, and granulomas in the lungs, liver, and spleen compared with control mice. Further, rPbHsp60 treatment (i) decreased the known protective effect of CFA against PCM and (ii) increased the concentrations of IL-17, TNF-α, IL-12, IFN-γ, IL-4, IL-10, and TGF-β in the lungs. Together, our results indicated that PbHsp60 induced a harmful immune response, exacerbated inflammation, and promoted fungal dissemination. Therefore, we propose that PbHsp60 contributes to the fungal pathogenesis. |
[
"O",
"O",
"O",
"O",
"B-T058",
"I-T058",
"O",
"B-T058",
"O",
"B-T103",
"O",
"B-T103",
"O",
"B-T017",
"I-T017",
"O",
"B-T058",
"I-T058",
"I-T058",
"I-T058",
"I-T058",
"B-T103",
"O",
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"O",
"O",
"B-T103",
"O",
"B-T103",... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0079595",
"db_name": "UMLS"
},
{
"db_id": "C0079595",
"db_name": "UMLS"
},
{
"db_id... | [
"A",
"Single",
"Nanoprobe",
"for",
"Ratiometric",
"Imaging",
"and",
"Biosensing",
"of",
"Hypochlorite",
"and",
"Glutathione",
"in",
"Live",
"Cells",
"Using",
"Surface",
"-",
"Enhanced",
"Raman",
"Scattering",
"Hypochlorite",
"(",
"ClO",
"(",
"-",
")",
")",
"an... | [
[
0,
1
],
[
2,
8
],
[
9,
18
],
[
19,
22
],
[
23,
34
],
[
35,
42
],
[
43,
46
],
[
47,
57
],
[
58,
60
],
[
61,
73
],
[
74,
77
],
[
78,
89
],
[
90,
92
],
[
93,... | A Single Nanoprobe for Ratiometric Imaging and Biosensing of Hypochlorite and Glutathione in Live Cells Using Surface-Enhanced Raman Scattering Hypochlorite (ClO(-)) and glutathione (GSH) have been reported to closely correlate with oxidative stress and related diseases; however, a clear mechanism is still unknown, mainly owing to a lack of accurate analytical methods for live cells. Herein we create a novel surface-enhanced Raman scattering (SERS) nanoprobe, 4-mercaptophenol (4-MP)-functionalized gold flowers (AuF / MP), for imaging and biosensing of ClO(-) and GSH in RAW 264.7 macrophage cells upon oxidative stress. The SERS spectra of AuF / MP change with the reaction between ClO(-) and 4-MP on AuFs within 1 min and then recover after reaction with GSH, resulting in the ratiometric detection of ClO(-) and GSH with high accuracy. The single SERS probe also shows high selectivity for ClO(-) and GSH detection against other reactive oxygen species and amino acids which may exist in biological systems, as well as remarkable sensitivity ascribed to a larger amount of hot spots on AuFs. The significant analytical performance of the developed nanoprobe, together with good biocompatibility and high cell-permeability, enables the present SERS probe imaging and real-time detection of ClO(-) and GSH in live cells upon oxidative stress. |
[
"B-T058",
"O",
"B-T103",
"O",
"O",
"B-T103",
"B-T103",
"O",
"O",
"O",
"B-T103",
"I-T103",
"B-T103",
"I-T103",
"O",
"O",
"B-T103",
"I-T103",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"O",
"B-T103",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T... | [
{
"db_id": "C1511790",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0006463",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0033684",
"db_name": "UMLS"
},
{
... | [
"Detection",
"of",
"busulfan",
"adducts",
"on",
"proteins",
"Busulfan",
"is",
"a",
"bifunctional",
"alkyl",
"sulfonate",
"antineoplastic",
"drug",
".",
"This",
"alkylating",
"agent",
"was",
"described",
"as",
"forming",
"covalent",
"adducts",
"on",
"proteins",
"."... | [
[
0,
9
],
[
10,
12
],
[
13,
21
],
[
22,
29
],
[
30,
32
],
[
33,
41
],
[
42,
50
],
[
51,
53
],
[
54,
55
],
[
56,
68
],
[
69,
74
],
[
75,
84
],
[
85,
99
],
[
... | Detection of busulfan adducts on proteins Busulfan is a bifunctional alkyl sulfonate antineoplastic drug. This alkylating agent was described as forming covalent adducts on proteins. However, only limited data are available regarding the interaction of busulfan with proteins. Mass spectrometry and bioinformatics were used to identify busulfan adducts on human serum albumin and hemoglobin. Albumin and hemoglobin were incubated with busulfan or control compounds, digested with trypsin and analyzed by LC-MS / MS on a Thermo Fisher LTQ Orbitrap Velos Pro. MS data were used to generate spectral libraries of non-modified peptides and an open modification search was performed to identify potential adduct mass shifts and possible modification sites. Results were confirmed by a second database search including identified mass shifts and by visual inspection of annotated tandem mass spectra of adduct -carrying peptides. Five structures of busulfan adducts were detected and a chemical structure could be attributed to four of them. Two were primary adducts corresponding to busulfan monoalkylation and alkylation of two amino acid residues by a single busulfan molecule. Two others corresponded to secondary adducts generated during sample processing. Adducts were mainly detected on Asp, Glu, and His residues. These findings were confirmed by subsequent database searches and experiments with synthetic peptides. The combination of in vitro incubation of proteins with the drug of interest or control compounds, high-resolution mass spectrometry, and open modification search allowed confirming direct interaction of busulfan with proteins and characterizing resulting adducts. Our results also showed that careful analysis of the data is required to detect experimental artifacts. |
[
"B-T103",
"O",
"B-T017",
"I-T017",
"B-T037",
"I-T037",
"I-T037",
"I-T037",
"O",
"O",
"B-T103",
"I-T103",
"I-T103",
"B-T103",
"O",
"O",
"O",
"O",
"B-T103",
"I-T103",
"O",
"O",
"B-T103",
"O",
"O",
"O",
"B-T017",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-... | [
{
"db_id": "C0036581",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0031119",
"db_name": "UMLS"
},
{
"db_id": "C0031119",
"db_name": "UMLS"
},
{
"db_id": "C0349419",
"db_name": "UMLS"
},
{
"db_id": "C0349419",
"db_name": "U... | [
"Selenium",
"Ameliorate",
"Peripheral",
"Nerve",
"Ischemic",
"-",
"Reperfusion",
"Injury",
"via",
"Decreased",
"TNF",
"-",
"α",
"Selenium",
"is",
"considered",
"as",
"a",
"trace",
"element",
"that",
"plays",
"antioxidant",
"role",
"in",
"the",
"body",
".",
"So... | [
[
0,
8
],
[
9,
19
],
[
20,
30
],
[
31,
36
],
[
37,
45
],
[
45,
46
],
[
46,
57
],
[
58,
64
],
[
65,
68
],
[
69,
78
],
[
79,
82
],
[
82,
83
],
[
83,
84
],
[
8... | Selenium Ameliorate Peripheral Nerve Ischemic-Reperfusion Injury via Decreased TNF-α Selenium is considered as a trace element that plays antioxidant role in the body. So, the aim of this study was to evaluate the effect of selenium on ameliorating of sciatic nerve ischemia-reperfusion injury. Eighty (80) adult male Wistar rats weighing 250-300 g were used. They were divided into 10 groups (n = 8). Then, femoral vessels were obstructed by using 4/0 silk and splitknot techniques. After 3-h ischemia for all the groups, reperfusion was applied for different periods: 3, 7, 14, and 28 days. In half of each experimental group, 0.2 mg/kg selenium was injected intraperitoneally, coinciding with ischemia. After reperfusion, according to the grouping, rats were killed by using high dose of anesthetic drug and then sciatic nerve was removed and fixed. Then, tissue samples were processed and subsequently stained with hematoxylin-eosin, apoptosis, and immunohistochemistry stains. On the third day of reperfusion, the amount of TNF-α as an inflammatory marker of ischemia - reperfusion acute phase increased. On the seventh day of reperfusion, the amount of NF-кB as an apoptotic index and infiltration of mast cells increased in the tissue as a result of development of inflammation. But, on the 14th day of reperfusion, the amount of NF-кB as an apoptotic index decreased to the lowest amount. On the 28th day of reperfusion, the amount of TNF-α as an inflammatory marker decreased to its lowest level. Prescription of selenium concurrent with development of ischemia can reduce the damage caused by sciatic nerve ischemia-reperfusion. |
[
"O",
"O",
"B-T037",
"I-T037",
"O",
"O",
"O",
"B-T062",
"I-T062",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"B-T038",
"I-T038",
"I-T038",
"I-T038",
"I-T038",
"O",
"B-T098",
"I-T098",
"I-T098",
"O",
"B-T037",
"I-T037",
"I-T037",
"O",
"B-T037",
"I-T037",
"I-T037",... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0000932",
"db_name": "UMLS"
},
{
"db_id": "C0000932",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id... | [
"Methodology",
"of",
"AA",
"CRASH",
":",
"a",
"prospective",
"observational",
"study",
"evaluating",
"the",
"incidence",
"and",
"pathogenesis",
"of",
"adverse",
"post",
"-",
"traumatic",
"sequelae",
"in",
"African",
"-",
"Americans",
"experiencing",
"motor",
"vehi... | [
[
0,
11
],
[
12,
14
],
[
15,
17
],
[
18,
23
],
[
23,
24
],
[
25,
26
],
[
27,
38
],
[
39,
52
],
[
53,
58
],
[
59,
69
],
[
70,
73
],
[
74,
83
],
[
84,
87
],
[
... | Methodology of AA CRASH: a prospective observational study evaluating the incidence and pathogenesis of adverse post-traumatic sequelae in African-Americans experiencing motor vehicle collision A motor vehicle collision (MVC) is one of the most common life-threatening events experienced by individuals living in the USA. While most individuals recover following MVC, a significant proportion of individuals develop adverse post-traumatic sequelae such as post-traumatic stress disorder or persistent musculoskeletal pain. Adverse post-traumatic sequelae are common, morbid and costly public health problems in the USA and other industrialised countries. The pathogenesis of these disorders following MVC remains poorly understood. In the USA, available data suggest that African-Americans experience an increased burden of adverse post-traumatic sequelae after MVC compared to European Americans, but to date no studies examining the pathogenesis of these disorders among African-Americans experiencing MVC have been performed. The African-American CRASH (AA CRASH) study is an NIH - funded, multicentre, prospective study that enrols African-Americans (n=900) who present to the emergency department (ED) within 24 hours of MVC. Participants are enrolled at 13 ED sites in the USA. Individuals who are admitted to the hospital or who report a fracture or tissue injury are excluded. Participants complete a detailed ED interview that includes an assessment of crash history, current post-traumatic symptoms and health status prior to the MVC. Blood samples are also collected in the ED using PAXgene DNA and PAXgene RNA tubes. Serial mixed-mode assessments 6 weeks, 6 months and 1 year after MVC include an assessment of adverse sequelae, general health status and health service utilisation. The results from this study will provide insights into the incidence and pathogenesis of persistent pain and other post-traumatic sequelae in African-Americans experiencing MVC. AA CRASH has ethics approval in the USA, and the results will be published in a peer-reviewed journal. |
[
"B-T038",
"I-T038",
"O",
"O",
"B-T103",
"O",
"O",
"B-T038",
"O",
"B-T017",
"I-T017",
"O",
"O",
"O",
"O",
"B-T103",
"O",
"O",
"B-T038",
"O",
"B-T062",
"O",
"O",
"B-T103",
"I-T103",
"I-T103",
"O",
"B-T103",
"O",
"O",
"O",
"O",
"O",
"B-T103",
"I-T103"... | [
{
"db_id": "C3537153",
"db_name": "UMLS"
},
{
"db_id": "C3537153",
"db_name": "UMLS"
},
{
"db_id": null,
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},
{
"db_id": null,
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},
{
"db_id": "C0672708",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
... | [
"Molecular",
"mechanism",
"leading",
"to",
"SAHA",
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"induced",
"autophagy",
"in",
"tumor",
"cells",
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"p53",
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"dependent",
"pathway",
"Recent",
"studies",
"indicated",
"that",
"histone",
"deacetylase",
"inhibitors",
"(",
"HDACi... | [
[
0,
9
],
[
10,
19
],
[
20,
27
],
[
28,
30
],
[
31,
35
],
[
36,
37
],
[
38,
45
],
[
46,
55
],
[
56,
58
],
[
59,
64
],
[
65,
70
],
[
70,
71
],
[
72,
80
],
[
... | Molecular mechanism leading to SAHA - induced autophagy in tumor cells: evidence for a p53 -dependent pathway Recent studies indicated that histone deacetylase inhibitors (HDACi), a class of anticancer agents, are in addition to their ability of apoptosis induction also capable of provoking autophagy. Promoted by the treatment of malignant uterine sarcoma cells with the HDACi suberoylanilide hydroxamic acid (SAHA), we previously demonstrated predominant dose-dependent activation of autophagy in ESS-1 cells, but prevalent induction of apoptosis in MES-SA cells. In order to extend our previous studies, SAHA - treated ESS-1 and MES-SA cells were monitored for protein expression to reveal differences in known markers of apoptosis explaining the different cytotoxic responses. Further analysis of the identified candidate protein included cell rescue experiments by gene transfer followed by subsequent screening of cells for induction of apoptosis and autophagy by immunoblotting, caspase activity as well as LC3 and MDC / PI staining. LDH release assays were performed to assess the amount of cell -mediated cytotoxicity. In our search for responsible autophagic regulatory genes upstream of mammalian target of rapamycin (mTOR), we now discovered that, in contrast to MES-SA cells, a TP53-637C>T nonsense mutation located in the transactivating domain of the oncogenic suppressor p53 causes loss of its protein and consequently reduced PUMA induction in ESS-1 cells. Upon re-introduction of wild-type TP53, SAHA - treated ESS-1 cells underwent immediate apoptotic cell death as supported by upregulation of PUMA and caspase-9 as well as by activation of caspases-3 and - 7 and PARP-1 cleavage. Concurrent downregulation of autophagy was noticed by upregulated mTor and phospho-mTOR expression as well as monitoring autophagosome formation employing LC3 and MDC staining. Previously, cytoplasmic master regulatory activities of the oncogenic suppressor p53 in inhibiting autophagy and triggering apoptosis were unravelled. Accordingly, p53 - deficiency could explain both, the previously documented apoptosis resistance and prevailing SAHA - induced autophagy in ESS-1 cells. Using MES-SA cells with RNAi-silenced p53 expression and several p53 - deficient tumor cell lines undergoing SAHA - induced autophagy, we could generally validate our finding suggesting an inhibitory role for p53 in the autophagic pathway in response to SAHA treatment. Conclusively, these results could identify cytoplasmic p53 protein as a molecular switch that directly mediates the cytotoxic response of SAHA and thus open new therapeutic avenues. |
[
"O",
"B-T204",
"B-T204",
"I-T204",
"O",
"O",
"O",
"O",
"O",
"B-T103",
"O",
"B-T038",
"I-T038",
"I-T038",
"B-T204",
"O",
"O",
"B-T098",
"O",
"O",
"B-T204",
"I-T204",
"O",
"B-T204",
"O",
"B-T204",
"O",
"B-T204",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038"... | [
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... | [
"The",
"cnidarian",
"Hydractinia",
"echinata",
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"... | [
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9... | The cnidarian Hydractinia echinata employs canonical and highly adapted histones to pack its DNA Cnidarians are a group of early branching animals including corals, jellyfish and hydroids that are renowned for their high regenerative ability, growth plasticity and longevity. Because cnidarian genomes are conventional in terms of protein-coding genes, their remarkable features are likely a consequence of epigenetic regulation. To facilitate epigenetics research in cnidarians, we analysed the histone complement of the cnidarian model organism Hydractinia echinata using phylogenomics, proteomics, transcriptomics and mRNA in situ hybridisations. We find that the Hydractinia genome encodes 19 histones and analyse their spatial expression patterns, genomic loci and replication -dependency. Alongside core and other replication - independent histone variants, we find several histone replication -dependent variants, including a rare replication -dependent H3.3, a female germ cell - specific H2A.X and an unusual set of five H2B variants, four of which are male germ cell - specific. We further confirm the absence of protamines in Hydractinia. Since no protamines are found in hydroids, we suggest that the novel H2B variants are pivotal for sperm DNA packaging in this class of Cnidaria. This study adds to the limited number of full histone gene complements available in animals and sets a comprehensive framework for future studies on the role of histones and their post-translational modifications in cnidarian epigenetics. Finally, it provides insight into the evolution of spermatogenesis. |
[
"O",
"B-T082",
"O",
"B-T082",
"I-T082",
"I-T082",
"O",
"B-T103",
"O",
"O",
"O",
"O",
"O",
"B-T017",
"I-T017",
"O",
"O",
"O",
"B-T038",
"I-T038",
"I-T038",
"I-T038",
"I-T038",
"O",
"O",
"O",
"B-T033",
"O",
"O",
"O",
"B-T038",
"O",
"O",
"O",
"O",
"... | [
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"db_id": "C1708690",
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{
"db_id": "C1708690",
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}... | [
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... | Distinctive pattern of let-7 family microRNAs in aggressive carcinoma of the oral tongue in young patients Oral cavity squamous cell carcinoma may be more aggressive at presentation and recurrence in young patients compared with older patients. Dysregulation of microRNAs (miRNAs or miRs) has been associated with the development and prognosis of oral cavity cancer. The present study investigated miRNA expression in carcinoma of the oral tongue in young patients. miRNA expression profiles were evaluated in formalin-fixed, paraffin-embedded samples of tumor and normal mucosa from 12 patients aged <30 years old with squamous cell carcinoma of the tongue. The levels of let-7f-5p, miR-30b-5p and let-7e-5p were upregulated in tumors (P<0.05). The expression of let-7f-5p was upregulated in non-aggressive tumors, while the expression of let-7e-5p was upregulated in aggressive tumors, compared with the corresponding normal tissue. Aggressive tumors had higher levels of let-7c, miR-130a-3p, miR-361-5p, miR-99a-5p, miR-29c-3p and let-7d-5p than non-aggressive tumors (P<0.05). The findings remained significant for let-7c upon false-discovery rate correction. An excellent correlation was noticed on validation of NanoString counts by quantitative polymerase chain reaction. The comparison with published findings in adults demonstrated a unique miRNA signature in young patients with aggressive disease. Aggressive oral cavity cancer in patients <30 years old is associated with a distinctive expression pattern of the let-7 family. Larger studies including direct comparison with older patients are warranted. |
[
"B-T058",
"I-T058",
"I-T058",
"I-T058",
"I-T058",
"O",
"B-T058",
"I-T058",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"B-T062",
"I-T062",
"I-T062",
"O",
"B-T062",
"I-T062",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"B-T058",
"O",
"B-T038",
"I-T038",
"O... | [
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"db_id": "C1271494",
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"db_id": "C1271494",
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{
"db_id": "C1271494",
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"db_id": null,
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"Early",
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... | [
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8... | Early goal-directed treatment versus standard care in management of early septic shock: Meta-analysis of randomized trials Since the incorporation of the early hemodynamic resuscitation in septic shock according to the early goal-directed therapy (EGDT) protocol among the 6- hour resuscitation bundle of the Surviving Sepsis Campaign guidelines, a great debate has been raised about the issue. The present meta-analysis aims to determine whether the resuscitative phase really takes advantages by being performed with EGDT. A systematic review with meta-analysis of randomized controlled trials (RCTs) of EGDT versus usual care in patients with early septic shock was performed. Four high- quality RCTs have been included with 4,464 patients (1990 in EGDT and 2013 in usual care arm). ICU admission and cardiovascular support necessity increased in the EGDT group (OR = 2.00, 95% CI 1.55-2.57 and OR = 1.33, 95% CI 1.08-1.64, respectively). EGDT has no significant effect on mortality (90 days, 60 days, 28 days, and mortality by the time of hospital discharge). EGDT has no significant effect in reducing the length of hospital stay, the necessity of respiratory and renal function support, and the duration of respiratory and cardiocirculatory support. EGDT seems to increase the resource demand in terms of ICU admissions and cardiocirculatory support necessity without reducing mortality, renal and respiratory organ support necessity, respiratory and cardiocirculatory support duration, and length of hospital stay. Systematic review, level I. |
[
"B-T103",
"O",
"B-T033",
"O",
"O",
"O",
"B-T033",
"I-T033",
"I-T033",
"O",
"O",
"O",
"B-T103",
"O",
"B-T168",
"I-T168",
"I-T168",
"I-T168",
"I-T168",
"I-T168",
"I-T168",
"B-T168",
"B-T168",
"O",
"O",
"O",
"B-T082",
"O",
"O",
"O",
"B-T103",
"O",
"O",
... | [
{
"db_id": "C1510464",
"db_name": "UMLS"
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{
"db_id": null,
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{
"db_id": "C0243095",
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"db_id... | [
"Structural",
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"Wheat",
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... | [
[
0,
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10,
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20,
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22,
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34,
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38,
42
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[
42,
43
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[
43,
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[
55,
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... | Structural, Culinary, Nutritional and Anti-Nutritional Properties of High Protein, Gluten Free, 100% Legume Pasta Wheat pasta has a compact structure built by a gluten network entrapping starch granules resulting in a low glycemic index, but is nevertheless unsuitable for gluten - intolerant people. High protein gluten-free legume flours, rich in fibers, resistant starch and minerals are thus a good alternative for gluten-free pasta production. In this study, gluten-free pasta was produced exclusively from faba, lentil or black-gram flours. The relationship between their structure, their cooking and Rheological properties and their in-vitro starch digestion was analyzed and compared to cereal gluten-free commercial pasta. Trypsin inhibitory activity, phytic acid and α-galactosides were determined in flours and in cooked pasta. All legume pasta were rich in protein, resistant starch and fibers. They had a thick but weak protein network, which is built during the pasta cooking step. This particular structure altered pasta springiness and increased cooking losses. Black-gram pasta, which is especially rich in soluble fibers, differed from faba and lentil pasta, with high springiness (0.85 vs. 0.75) and less loss during cooking. In comparison to a commercial cereal gluten-free pasta, all the legume pasta lost less material during cooking but was less cohesive and springy. Interestingly, due to their particular composition and structure, lentil and faba pasta released their starch more slowly than the commercial gluten-free pasta during the in-vitro digestion process. Anti-nutritional factors in legumes, such as trypsin inhibitory activity and α-galactosides were reduced by up to 82% and 73%, respectively, by pasta processing and cooking. However, these processing steps had a minor effect on phytic acid. This study demonstrates the advantages of using legumes for the production of gluten-free pasta with a low glycemic index and high nutritional quality. |
[
"O",
"O",
"O",
"B-T082",
"B-T017",
"O",
"O",
"B-T017",
"O",
"O",
"O",
"B-T017",
"O",
"B-T017",
"I-T017",
"O",
"O",
"O",
"O",
"B-T017",
"I-T017",
"I-T017",
"O",
"O",
"B-T017",
"I-T017",
"O",
"O",
"O",
"B-T017",
"I-T017",
"I-T017",
"O",
"O",
"O",
"... | [
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"db_id... | [
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"in",
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"Obturator",
"Vasculature",
"During",
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86,
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... | Variation in the Obturator Vasculature During Routine Anatomy Dissection of a Cadaver The obturator artery normally originates from the internal iliac artery while the obturator vein drains into the internal iliac vein. During a routine gross anatomy dissection class for undergraduate students at the All India Institute of Medical Sciences, New Delhi, India, in 2016, a rare unilateral variation in the obturator vasculature was found in a female cadaver of approximately 55 years of age. In this case, the left obturator artery originated from the superior gluteal artery and the left obturator vein drained into the external iliac vein. Knowledge of such variations is necessary during hernia procedures, ligation of the internal iliac artery and muscle graft surgeries. |
[
"O",
"O",
"O",
"O",
"O",
"O",
"B-T062",
"O",
"B-T058",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T062",
"B-T062",
"O",
"O",
"O",
"O",
"B-T062",
"B-T170",
"O",
"O",
"O",
"O",
"B-T170",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"... | [
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{
"db_id": "C0004939",
... | [
"Trends",
"in",
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"-",
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[
0,
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[
7,
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18,
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46,
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79... | Trends in Behavior-Analytic Gambling Research and Treatment The purpose of the present review was to analyze research outcomes for all gambling studies reported in the behavior analysis literature. We used the search term " gambling " to identify articles that were published in behaviorally oriented journals between the years 1992 and 2012 and categorized the content of each article as empirical or conceptual. Next, we examined and categorized the empirical articles by inclusion of an experimental manipulation and treatment to alleviate at least some aspect of pathological gambling, participant population used, type of gambling task employed in the research, whether the participants in the study actually gambled, and the behavioral phenomena of interest. The results show that the rate of publication of gambling research has increased in the last 6 years, and a vast majority of articles are empirical. Of the empirical articles, examinations of treatment techniques or methods are scarce; slot machine play is the most represented form of gambling, and slightly greater than half of the research included compensation based on gambling outcomes within experiments. We discuss implications and future directions based on these observations of the published literature. |
[
"B-T038",
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"O",
"B-T058",
"O",
"O",
"O",
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"O",
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"O",
"O",
"O",
"O",
"O",
"B-T058",
"O",
"B-T058",
"O",
... | [
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8... | Juvenile dermatomyositis with anti-signal recognition particle antibodies: a case report Serologic investigation has been explored in inflammatory myopathies in order to define subgroups that can help us predict clinical course, treatment and prognosis. The level of similarity between juvenile and adult myopathies regarding the presence of myositis - specific autoantibodies has not been fully elucidated. We report the case of a 8-year-old girl who presented with a rapid progression of muscle weakness and cutaneous signs consistent with the diagnosis of juvenile dermatomyositis and whose serologic testing revealed the presence of anti-signal recognition particle (SRP) antibodies. So far these antibodies have been described mostly in adult subsets, frequently associated with poorer outcomes and rarely related to cutaneous manifestations. The knowledge of the degree of overlap between paediatric and adult SRP positive myopathies may improve the medical care we provide to these children. |
[
"B-T097",
"O",
"O",
"O",
"O",
"B-T038",
"O",
"O",
"O",
"O",
"O",
"O",
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"O",
"O",
"O",
"O",
"B-T038",
"O",
"O",
"O",
"O",
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"O",
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"B-T092",
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"O",
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"O",
"B-T058",
"I-T058",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
... | [
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"db_id": "C0004271",
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30,
39
],
[
40,
45
],
[
46,
53
],
[
54,
60
],
[
61,
69
],
[
69,
70
],
[
71,
77
],
[
78,
80
],
[
81,... | Nurses ' Perceived Skills and Attitudes About Updated Safety Concepts: Impact on Medication Administration Errors and Practices Approximately a quarter of medication errors in the hospital occur at the a dministration phase, which is solely under the purview of the bedside nurse. The purpose of this study was to assess bedside nurses ' perceived skills and attitudes about updated safety concepts and examine their impact on medication administration errors and adherence to safe medication administration practices. Findings support the premise that medication administration errors result from an interplay among system -, unit -, and nurse -level factors. |
[
"B-T058",
"I-T058",
"O",
"B-T058",
"I-T058",
"I-T058",
"I-T058",
"I-T058",
"O",
"O",
"O",
"O",
"B-T062",
"B-T062",
"I-T062",
"O",
"O",
"B-T092",
"I-T092",
"I-T092",
"O",
"B-T082",
"O",
"O",
"O",
"O",
"B-T062",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O"... | [
{
"db_id": "C0338237",
"db_name": "UMLS"
},
{
"db_id": "C0338237",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0039548",
"db_name": "UMLS"
},
{
"db_id": "C0039548",
"db_name": "UMLS"
},
{
"db_id": "C0039548",
"db_name": "U... | [
"Antibiotic",
"Treatment",
"in",
"End",
"-",
"of",
"-",
"Life",
"Cancer",
"Patients",
"-",
"A",
"Retrospective",
"Observational",
"Study",
"at",
"a",
"Palliative",
"Care",
"Center",
"in",
"Sweden",
"The",
"aim",
"of",
"this",
"study",
"was",
"to",
"elucidate... | [
[
0,
10
],
[
11,
20
],
[
21,
23
],
[
24,
27
],
[
27,
28
],
[
28,
30
],
[
30,
31
],
[
31,
35
],
[
36,
42
],
[
43,
51
],
[
52,
53
],
[
53,
54
],
[
55,
68
],
[
... | Antibiotic Treatment in End-of-Life Cancer Patients -A Retrospective Observational Study at a Palliative Care Center in Sweden The aim of this study was to elucidate whether palliative cancer patients benefit from antibiotic treatment in the last two weeks of life when an infection is suspected. We reviewed medical records from 160 deceased palliative cancer patients that had been included in previous studies on vitamin D and infections. Patients treated with antibiotics during the last two weeks of life were identified and net effects of treatment (symptom relief) and possible adverse events were extracted from medical records. Seventy-nine patients (49%) had been treated with antibiotics during the last two weeks in life. In 37% (n = 29), the treatment resulted in evident symptom relief and among these 50% had a positive bacterial culture, 43% had a negative culture and in 7% no culture was taken. Among the patients with no or unknown effect of antibiotics, 50% had a positive culture. When the indication for antibiotic treatment was to avoid or treat sepsis, symptom relief was achieved in 50% of the patients (n = 19). Only 4% (n = 3) of the patients experienced adverse events of the treatment (diarrhea, nausea). Treating infections with antibiotics in the last weeks of life may improve the quality of life for palliative cancer patients, especially if sepsis is suspected or confirmed. According to our results, the beneficial effects outweigh the potentially negative outcomes. |
[
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"B-T204",
"B-T038",
"I-T038",
"B-T038",
"O",
"O",
"B-T033",
"O",
"B-T091",
"I-T091",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db... | [
"A",
"Bayesian",
"Network",
"-",
"Based",
"Approach",
"to",
"Selection",
"of",
"Intervention",
"Points",
"in",
"the",
"Mitogen",
"-",
"Activated",
"Protein",
"Kinase",
"Plant",
"Defense",
"Response",
"Pathway",
"An",
"important",
"problem",
"in",
"computational",
... | [
[
0,
1
],
[
2,
10
],
[
11,
18
],
[
18,
19
],
[
19,
24
],
[
25,
33
],
[
34,
36
],
[
37,
46
],
[
47,
49
],
[
50,
62
],
[
63,
69
],
[
70,
72
],
[
73,
76
],
[
7... | A Bayesian Network-Based Approach to Selection of Intervention Points in the Mitogen-Activated Protein Kinase Plant Defense Response Pathway An important problem in computational biology is the identification of potential points of intervention that can lead to modified network behavior in a genetic regulatory network. We consider the problem of deducing the effect of individual genes on the behavior of the network in a statistical framework. In this article, we make use of biological information from the literature to develop a Bayesian network and introduce a method to estimate parameters of this network using data that are relevant to the biological phenomena under study. Then, we give a novel approach to select significant nodes in the network using a decision-theoretic approach. The proposed method is applied to the analysis of the mitogen-activated protein kinase pathway in the plant defense response to pathogens. Results from applying the method to experimental data show that the proposed approach is effective in selecting genes that play crucial roles in the biological phenomenon being studied. |
[
"O",
"O",
"O",
"B-T201",
"I-T201",
"O",
"B-T098",
"O",
"B-T098",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"B-T062",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T201",
"O",
"B-T038",
"I-T038",
"O",
"O",
"B-T092",
"I-T092",
"I-T092",
"O",
"B-T092",
"... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C1514474",
"db_name": "UMLS"
},
{
"db_id": "C1514474",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id... | [
"The",
"clinicopathological",
"and",
"prognostic",
"features",
"of",
"Chinese",
"and",
"Japanese",
"inpatients",
"with",
"lung",
"cancer",
"Here",
",",
"we",
"retrospectively",
"compared",
"the",
"differences",
"in",
"clinicopathological",
"behaviors",
"and",
"prognos... | [
[
0,
3
],
[
4,
23
],
[
24,
27
],
[
28,
38
],
[
39,
47
],
[
48,
50
],
[
51,
58
],
[
59,
62
],
[
63,
71
],
[
72,
82
],
[
83,
87
],
[
88,
92
],
[
93,
99
],
[
1... | The clinicopathological and prognostic features of Chinese and Japanese inpatients with lung cancer Here, we retrospectively compared the differences in clinicopathological behaviors and prognosis of lung cancer from the First Affiliated Hospital (CMU1, n=513), Shengjing Hospital (CMUS, n=1021), Tumor Hospital (CMUT, n=5378) of China Medical University, the First Affiliated Hospital of Dalian (DMU, n=2251) and Jinzhou (JMU, n=630) Medical University, Takaoka Kouseiren Hospital (Takaoka, n=163) of Japan. Japanese lung cancer patients showed smaller tumor size, lower TNM staging, lower ratio of squamous cell carcinoma and higher ratio of small and large cell carcinomas than Chinese patients (p<0.05). Survival analysis showed that tumor size was employed as a prognostic factor for the Japanese and Chinese cancer patients (p<0.05). In DMU and CMUS, the ratio s of female patients or adenocarcinoma were higher than other hospitals (p<0.05), while the patients from CMUT and CMU1 were younger than the others (p<0.05). The ratio s of squamous cell carcinoma from CMUT, CMU1 and JMU were higher than the others, while it was the same for the ratio of large and small cell carcinoma in Takaoka and CMU1 (p<0.05). TNM staging was higher in CMUT than JMU and Takaoka (p<0.05). The female patients of lung cancer showed young prone, large tumor size, a high ratio of adenocarcinoma and advanced TNM staging in comparison to the counterpart (p<0.05). The younger patients of lung cancer displayed smaller tumor size, higher ratio of adenocarcinoma, lower TNM staging than the elder in Takaoka (p<0.05). There were more aggressive behaviors and shorter survival time for Chinese than Japanese lung cancer patients. The prevention of lung cancer should be strengthened by establishing a systematic and effective screening strategy, especially for the young and female patients. |
[
"O",
"O",
"O",
"B-T062",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
"O",
"O",
"B-T038",
"I-T038",
"O",
"B-T038",
"O",
"O",
"O",
"B-T062",
"B-T082",
"O",
"O",
"O",
"O",
"B-T062",
"O",
"O",
"B-T017",
"I-T017",
"O",
"O",
"B-T038",... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0870071",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,... | [
"Rate",
"-",
"equation",
"modelling",
"and",
"ensemble",
"approach",
"to",
"extraction",
"of",
"parameters",
"for",
"viral",
"infection",
"-",
"induced",
"cell",
"apoptosis",
"and",
"necrosis",
"We",
"develop",
"a",
"theoretical",
"approach",
"that",
"uses",
"ph... | [
[
0,
4
],
[
5,
6
],
[
7,
15
],
[
16,
25
],
[
26,
29
],
[
30,
38
],
[
39,
47
],
[
48,
50
],
[
51,
61
],
[
62,
64
],
[
65,
75
],
[
76,
79
],
[
80,
85
],
[
86,... | Rate - equation modelling and ensemble approach to extraction of parameters for viral infection - induced cell apoptosis and necrosis We develop a theoretical approach that uses physiochemical kinetics modelling to describe cell population dynamics upon progression of viral infection in cell culture, which results in cell apoptosis (programmed cell death) and necrosis (direct cell death). Several model parameters necessary for computer simulation were determined by reviewing and analyzing available published experimental data. By comparing experimental data to computer modelling results, we identify the parameters that are the most sensitive to the measured system properties and allow for the best data fitting. Our model allows extraction of parameters from experimental data and also has predictive power. Using the model we describe interesting time - dependent quantities that were not directly measured in the experiment and identify correlations among the fitted parameter values. Numerical simulation of viral infection progression is done by a rate - equation approach resulting in a system of "stiff" equations, which are solved by using a novel variant of the stochastic ensemble modelling approach. The latter was originally developed for coupled chemical reactions. |
[
"B-T082",
"I-T082",
"I-T082",
"O",
"O",
"O",
"O",
"B-T005",
"I-T005",
"I-T005",
"I-T005",
"O",
"B-T005",
"I-T005",
"I-T005",
"I-T005",
"I-T005",
"I-T005",
"O",
"O",
"O",
"B-T005",
"O",
"O",
"B-T204",
"I-T204",
"B-T204",
"O",
"B-T204",
"I-T204",
"O",
"O",... | [
{
"db_id": "C2348746",
"db_name": "UMLS"
},
{
"db_id": "C2348746",
"db_name": "UMLS"
},
{
"db_id": "C2348746",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
... | [
"Complete",
"Genome",
"Sequence",
"of",
"the",
"Largest",
"Known",
"Flavi",
"-",
"Like",
"Virus",
",",
"Diaphorina",
"citri",
"flavi",
"-",
"like",
"virus",
",",
"a",
"Novel",
"Virus",
"of",
"the",
"Asian",
"Citrus",
"Psyllid",
",",
"Diaphorina",
"citri",
... | [
[
0,
8
],
[
9,
15
],
[
16,
24
],
[
25,
27
],
[
28,
31
],
[
32,
39
],
[
40,
45
],
[
46,
51
],
[
51,
52
],
[
52,
56
],
[
57,
62
],
[
62,
63
],
[
64,
74
],
[
7... | Complete Genome Sequence of the Largest Known Flavi-Like Virus, Diaphorina citri flavi-like virus, a Novel Virus of the Asian Citrus Psyllid, Diaphorina citri A novel flavi-like virus tentatively named Diaphorina citri flavi-like virus (DcFLV) was identified in field populations of Diaphorina citri through small RNA and transcriptome sequencing followed by reverse transcription (RT)-PCR. We report here the complete nucleotide sequence and genome organization of DcFLV, the largest flavi-like virus identified to date. |
[
"B-T082",
"O",
"O",
"B-T204",
"O",
"B-T038",
"O",
"B-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"I-T103",
"B-T082",
"O",
"O",
"B-T204",
"O",
"B-T038",
"O",
"B-T103"... | [
{
"db_id": "C0521387",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0025929",
"db_name": "UMLS"
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C1171362",
"db_name": "UMLS"
},
{
... | [
"Myometrial",
"relaxation",
"of",
"mice",
"via",
"expression",
"of",
"two",
"pore",
"domain",
"acid",
"sensitive",
"K",
"(",
"+",
")",
"(",
"TASK",
"-",
"2",
")",
"channels",
"Myometrial",
"relaxation",
"of",
"mouse",
"via",
"expression",
"of",
"two",
"-",... | [
[
0,
10
],
[
11,
21
],
[
22,
24
],
[
25,
29
],
[
30,
33
],
[
34,
44
],
[
45,
47
],
[
48,
51
],
[
52,
56
],
[
57,
63
],
[
64,
68
],
[
69,
78
],
[
79,
80
],
[
... | Myometrial relaxation of mice via expression of two pore domain acid sensitive K(+) (TASK-2) channels Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing K(+) channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward K(+) current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing K(+) channels (TASK-2). NIOK in the presence of K(+) channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery. |
[
"O",
"O",
"O",
"B-T103",
"B-T103",
"I-T103",
"I-T103",
"O",
"B-T058",
"O",
"B-T038",
"I-T038",
"O",
"O",
"B-T058",
"O",
"O",
"O",
"B-T103",
"O",
"B-T103",
"I-T103",
"O",
"O",
"B-T058",
"O",
"B-T038",
"I-T038",
"O",
"O",
"O",
"O",
"B-T038",
"I-T038",
... | [
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": null,
"db_name": null
},
{
"db_id": "C0010467",
"db_name": "UMLS"
},
{
"db_id": "C0042264",
"db_name": "UMLS"
},
{
"db_id": "C0042264",
"db_name": "UMLS"
},
{
... | [
"Development",
"of",
"a",
"Curcumin",
"Bioadhesive",
"Monolithic",
"Tablet",
"for",
"Treatment",
"of",
"Vaginal",
"Candidiasis",
"The",
"present",
"investigation",
"was",
"designed",
"to",
"formulate",
"a",
"natural",
"tablet",
"for",
"the",
"treatment",
"of",
"va... | [
[
0,
11
],
[
12,
14
],
[
15,
16
],
[
17,
25
],
[
26,
37
],
[
38,
48
],
[
49,
55
],
[
56,
59
],
[
60,
69
],
[
70,
72
],
[
73,
80
],
[
81,
92
],
[
93,
96
],
[
... | Development of a Curcumin Bioadhesive Monolithic Tablet for Treatment of Vaginal Candidiasis The present investigation was designed to formulate a natural tablet for the treatment of vaginal candidiasis in order to eliminate side effects that are caused by existing antifungal drugs. Curcumin has promising antifungal activity in comparison with the existing azole antifungal drugs. Bioadhesive curcumin vaginal tablets were prepared by direct compression with different ratios of biadhesive polymers like xanthan gum, guar gum and HPMC. Curcumin tablets were characterized by studies of friability, hardness, hydration, DSC, mucoadhesion, In-vitro release and antifungal activity. DSC and FT-IR data indicate there was no interaction between the drug and the excipients and also polymer concentration has some effects on melting point of curcumin. Formulation F3 showed the best results in terms of swelling and mucoadhesion together with prolonged drug release. The antifungal activity of the Curcumin tablet has demonstrated a significant effect against Candida albicans. Hence, the study indicates the possible and effective use of curcumin bioadhesive monolithic vaginal tablet for vaginal candidiasis as a promising natural antifungal treatment. |
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