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BACKGROUND This study assesses the value of image fusion using 18F-fluoro-L-DOPA (18F-DOPA) positron emission tomography (PET) and magnetic resonance imaging (MRI) for examining patients with neuroendocrine tumors (NETs) and a suspicion of metastasis of the liver. METHODS Eleven patients (five women and six men aged between 20 and 81, with a mean age of 54.6 years) were included in the study. All patients underwent whole-body 18F-DOPA PET examinations and contrast-enhanced MRI with diffusion-weighted sequences (DWS). Image fusion was performed using a semiautomatic voxel-based algorithm. Images obtained using PET and MRI were assessed separately. Side-by-side evaluations of fused PET/MRI images were also performed. RESULTS In total, 55 liver lesions (52 liver metastases and 3 benign lesions) were detected in the 11 patients. Sensitivity detection for liver lesions was higher when using PET/CT than when using contrast-enhanced MRI without DWSs and lower than using MRI with DWSs. The sensitivity of PET/MRI image fusion in the detection of liver metastasis was significantly higher than that of MRI with DWSs (P  less then  0.05). CONCLUSION Images of the liver obtained using PET and MRI in patients with NETs exhibited characteristic features. These findings suggest that an appropriate combination of available imaging modalities can optimize patient evaluations.BACKGROUND A BRAF V600E mutation is found as driver oncogene in patients with non-small cell lung cancer. Although combined treatment with dabrafenib and trametinib is highly effective, the efficacy of reduced doses of the drugs in combination therapy has not yet been reported. CASE PRESENTATION A Japanese man in his mid-sixties was diagnosed with unresectable lung adenocarcinoma and was unresponsive to cytotoxic chemotherapy and immune checkpoint inhibitors. The BRAF V600E mutation was detected by next generation sequencing, and the patient was subjected to treatment with dabrafenib and trametinib in combination. Although the treatment reduced the tumor size, he experienced myalgia and muscle weakness with elevated serum creatine kinase and was diagnosed with rhabdomyolysis induced by dabrafenib and trametinib. After the patient recovered from rhabdomyolysis, the treatment doses of dabrafenib and trametinib were reduced, which prevented further rhabdomyolysis and maintained tumor shrinkage. CONCLUSION The reduction of the doses of dabrafenib and trametinib was effective in the treatment of BRAF V600E-mutant NSCLC, and also prevented the incidence of rhabdomyolysis.BACKGROUND Studies report serious adherence problems among youth (individuals age 15-24 years of age) in Uganda. Recent growth in mobile phone ownership has highlighted the potential of using text-based interventions to improve antiretroviral treatment (ART) adherence among Ugandan youth. We piloted a randomized controlled trial of a text-based intervention providing weekly real-time antiretroviral adherence feedback, based on information from a smart pill box, to HIV-positive Ugandan youth. In this paper, we report the acceptability, feasibility, and preliminary impact of the intervention. METHODS We randomized participants to a control group, or to receive messages with information on either their own adherence levels (Treatment 1 - T1), or their own adherence and peer adherence levels (Treatment 2 - T2). We conducted six focus groups from December 2016 to March 2017 with providers and youth ages 15-24, double coded 130 excerpts, and achieved a pooled Cohen's Kappa of 0.79 and 0.80 based on 34 randomly sele's own adherence information alone appears to have less potential. TRIAL REGISTRATION NCT02514356 07/30/2015.BACKGROUND Lung adenocarcinoma (LAC) is composed of lepidic, papillary, mucinous, micropapillary and solid components in its parenchyma. Complex responses to therapeutics result from intratumoral heterogeneity. However, it remains confused that what components in a mixed LAC tumor are responsible to the heterogeneous EGFR mutation and PD-L1 expression. METHODS We investigated EGFR status via laser microdissection to capture spatially separated cancer cell subpopulations and digital droplet PCR to determine the abundance of EGFR sensitizing mutation and naïve T790M. Whilst, PD-L1 expression level via tumor proportion score (TPS) was evaluated by Ventana immunohistochemistry using SP263 antibody. PD-L1 expression levels were tiered in  0.05). CONCLUSION Intratumoral genetic heterogeneity of LACs was demonstrated associated with histological patterns. Heterogeneous PD-L1 expression in higher level usually occurred in solid component both in EGFR mutated and EGFR wild-typed LACs. EGFR mutated LACs heterogeneously had sensitizing and resistant mutation and was accompanied with PD-L1 expression, but discordant among histological constituents. Immune checkpoint inhibitor combined with third generation EGFR tyrosine kinase inhibitor should be more effective to these LACs.BACKGROUND Migraine is recognized as the second leading cause of disability globally. Lasmiditan is a novel, selective serotonin 5-HT1F receptor agonist developed for acute treatment of migraine. Here we analyzed effects of lasmiditan on migraine disability assessed with the Migraine Disability Assessment (MIDAS) scale for interim data from a long-term safety study. METHODS Completers of two single-attack parent studies were offered participation in the 1 year GLADIATOR study, that randomized participants to treatment with lasmiditan 100 mg or 200 mg taken as needed for migraine attacks of at least moderate severity. Changes in MIDAS were modeled using a mixed model repeated measures analysis. RESULTS The sample included 1978 patients who received ≥1 lasmiditan dose and were followed for a median of 288 days. Baseline mean MIDAS scores for the lasmiditan 100-mg and 200-mg groups were 29.4 and 28.9, respectively, indicating severe migraine-related disability. Relative to baseline, MIDAS total scores were signiresponses in completers and those who dropped out suggests that selective attrition does not account for the improvements. Benefits were significant at 3 months and maintained through 12 months. TRIAL REGISTRATION clinicaltrials.govNCT02565186; first posted October 1, 2015.BACKGROUND Congenital mydriasis and retinal arteriolar tortuosity are associated with the life-threatening multisystemic smooth muscle dysfunction syndrome (MSMDS) due to mutations in the gene, ACTA2, which encodes alpha-smooth muscle actin (α-SMA). Previous reports attributed MSMDS-related congenital mydriasis to the absence of iris sphincter muscle. Similarly, it has been hypothesized that abnormal proliferation of the vascular smooth muscle cells causes the marked tortuosity of retinal arterioles in MSMDS. In this report, high-resolution ocular imaging reveals unexpected findings that reject previous hypotheses. CASE PRESENTATION The proband is a 37-year-old female with a history of neonatal patent ductus arteriosus (PDA) ligation, left-sided choreiform movements at the age of 11 and a transient aphasia with right-sided weakness at the age of 30. Her older sister also had PDA ligation and congenital mydriasis but no neurological deficit up to age 41. Magnetic resonance angiogram demonstrated cerebrovascula within the cerebrovascular smooth muscle cell. MSMDS-related congenital mydriasis is due to reduced iris sphincter contractility rather than its absence. Retinal arteriolar tortuosity might be due to longitudinal proliferation of arteriolar smooth muscle cells. The described cerebrovascular and ocular signs are consistent with predicted effects of the novel Asn117Lys substitution in ACTA2.BACKGROUND To assess the association of sleep duration and quality with the risk of preterm birth. METHODS Relevant studies were retrieved from the PubMed and Web of Science databases up to September 30, 2018. The reference lists of the retrieved articles were reviewed. Random effects models were applied to estimate summarized relative risks (RRs) and 95% confidence intervals (CIs). RESULTS Ten identified studies (nine cohort studies and one case-controlled study) examined the associations of sleep duration and quality with the risk of preterm birth. As compared with women with the longest sleep duration, the summary RR was 1.23 (95% CI = 1.01-1.50) for women with the shortest sleep duration, with moderate between-study heterogeneity (I2 = 57.4%). Additionally, as compared with women with good sleep quality, the summary RR was 1.54 (95% CI = 1.18-2.01) for women with poor sleep quality (Pittsburgh Sleep Quality Index > 5), with high between-study heterogeneity (I2 = 76.7%). Funnel plots as well as the Egger's and Begg's tests revealed no evidence of publication bias. CONCLUSIONS This systematic review and meta-analysis revealed that short sleep duration and poor sleep quality may be associated with an increased risk of preterm birth. Further subgroup analyses are warranted to test the robustness of these findings as well as to identify potential sources of heterogeneity.BACKGROUND Lifelong healthy habits developed during childhood may prevent chronic diseases in adulthood. Interventions to promote these habits must begin early. The BONES (Beat Osteoporosis - Nourish and Exercise Skeletons) project assessed whether early elementary school children participating in a multifaceted health behavior change, after-school based intervention would improve bone quality and muscular strength and engage in more bone-strengthening behaviors. METHODS The 2-year BONES (B) intervention included bone-strengthening physical activity (85 min/week), educational materials (2 days/week), and daily calcium-rich snacks (380 mg calcium/day) delivered by after-school program leaders. BONES plus Parent (B + P) included an additional parent education component. From 1999 to 2004, n = 83 after-school programs (N = 1434 children aged 6-9 years) in Massachusetts and Rhode Island participated in a group randomized trial with two intervention arms (B only, n = 25 programs; B + P, n = 33) and a control arm (LUSION After-school programs, coupled with parental engagement, serving early elementary school children are a potentially feasible platform to deliver bone-strengthening behaviors to prevent osteoporosis in adulthood, with some encouraging bone and physical activity outcomes. TRIAL REGISTRATION ClinicalTrials.gov NCT00065247. Retrospectively registered. First posted July 22, 2003.BACKGROUND Sporobolomyces pararoseus is regarded as an oleaginous red yeast, which synthesizes numerous valuable compounds with wide industrial usages. This species hold biotechnological interests in biodiesel, food and cosmetics industries. Moreover, the ballistospores-shooting promotes the colonizing of S. pararoseus in most terrestrial and marine ecosystems. However, very little is known about the basic genomic features of S. pararoseus. To assess the biotechnological potential and ballistospores-shooting mechanism of S. pararoseus on genome-scale, the whole genome sequencing was performed by next-generation sequencing technology. RESULTS Here, we used Illumina Hiseq platform to firstly assemble S. pararoseus genome into 20.9 Mb containing 54 scaffolds and 5963 predicted genes with a N50 length of 2,038,020 bp and GC content of 47.59%. Genome completeness (BUSCO alignment 95.4%) and RNA-seq analysis (expressed genes 98.68%) indicated the high-quality features of the current genome. Through the annotation information of the genome, we screened many key genes involved in carotenoids, lipids, carbohydrate metabolism and signal transduction pathways.

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