Fluorine-18 fluorodeoxyglucose (F-18 FDG) has been used to evaluate early-stage larynx cancer and metastases of thyroid cancer. However, elevated F-18 FDG uptake in laryngeal muscles may lead to misinterpretation. In this report, three patients with thyroid cancer are described who had thyroid surgery 2 months to 1 year before F-18 FDG positron emission tomographic imaging. Various degrees of moderate to intense uptake were observed in their laryngeal regions. In one patient, this was caused by laryngeal muscle uptake. To determine the origin of the increased muscle uptake in the other two patients, the authors analyzed the position and shape of the foci of high uptake in light of the patients’ clinical histories and other imaging results.
The generation of small interfering RNA (siRNAs) entails stepwise processing of single-stranded (ss) into double-stranded (ds) RNA, which is cleaved into 21–24 nt siRNA duplexes. These complicated processes involve many components, including SUPPRESSOR OF GENE SILENCING 3 (SGS3), RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) and DICER-LIKE proteins (DCLs), and how the processes are coordinated to produce siRNAs is unclear. Here, we show that SGS3 forms condensates via phase separation in vivo and in vitro. SGS3 interacts with RDR6 and drives its addition to the condensates to form siRNA bodies in the cytoplasm. This process is promoted by SGS3-targeted RNAs, especially ssRNA. Disrupting SGS3 phase separation abrogated siRNA body assembly and RDR6-dependent siRNA biogenesis. Coexpression of SGS3 and RDR6 was sufficient to induce siRNA body formation in Nicotiana benthamiana and yeast and facilitate the accumulation of endogenous siRNAs and dsRNAs, respectively. Dysfunction in translation and mRNA decay increased the number of siRNA bodies, while mutations of DCL2 and DCL4 enhanced siRNA body size, in Arabidopsis thaliana; these siRNA bodies retained abundant dsRNAs. Purification of SGS3 condensates identified numerous RNA-binding proteins and key components of siRNA processing, including RDR6, DCL2/4, AGO1 and SDE5 (silencing defective 5), indicating that SGS3 organizes siRNA body assembly and concentrates siRNA processing factors. Together, our findings reveal that SGS3 phase-separation-mediated formation of siRNA bodies is essential for siRNA production and endogenous gene silencing.
We reported imaging findings with a peculiar tau accumulation pattern in a 56 year-old woman with frontotemporal dementia caused by Q351R mutation in the microtubule-associated protein tau ( MAPT ) gene. She had a 10-year history of gradually worsening memory loss. 18 F-FDG PET demonstrated hypometabolism in medial temporal lobes, but 18 F-florbetapir PET manifested no abnormal amyloid beta deposition, which ruled out Alzheimer disease. 18 F-florzolotau PET showed tau proteins accumulated in medial temporal lobes, basal ganglia brainstem, and cerebellum. The pattern is different from other known MAPT gene mutation. Multitracer imaging can help differentiate between Alzheimer disease and frontotemporal dementia caused by MAPT mutation.
Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014
To investigate the clinical, neuropsychological, neuroimaging features and treatment of dementia with Lewy bodies (DLB).The clinical, neuropsychological, neuroimaging and therapeutic features of 33 DLB patients were retrospectively analyzed.There were 25 males and 8 females. The mean course from onset to diagnosis was 3.3 years. Sleep disorder, depression, anxiety and constipation were present at 1 - 10 years prior to DLB onset in 10 patients. Memory impairment (52%) and parkinsonism (21%) were initial symptoms. The mean duration from memory impairment to presence of parkinsonism was 17 months. Pattern of extrapyramidal signs showed bilateral, symmetry and axial muscles bias as postural instability and facial impassivity, tremor was less in DLB. Hallucination (70%), sleep disorder (63%), apathy (56%) and delusion (52%) were the major behavioral and psychological symptoms. Hallucination occurred within a mean of 15 months after presence of initial symptoms. Cognition impairment progressed rapidly in half of patients. Neuropsychological tests of mild patients revealed visuospatial dysfunction and relatively preservation of memory. Severe impairment of all domains of cognition was noticed in moderate-severe patients. MRI (magnetic resonance imaging) revealed the preservation of hippocampal structures. And PET (positron emission tomography) showed hypometabolism of occipital lobe. Cholinesterase inhibitors could improve cognitive impairment and behavioral symptoms in a large majority of patients.Neuronal dysfunction may be present at an early stage of DLB. Early presence of hallucination, a high prevalence of sleep disorders, axial rigidity and hypometabolism of occipital lobe on PET may help to distinguish DLB from other types of dementia.
Micro-bolometers based on VO2and carbon nanocoils are developed in this work. The photoresponse of the micro-bolometer is greatly enhanced by the helical structure of the device.
The aim of this study was to describe brain metabolic changing patterns demonstrated by serial brain FDG PET/CT scans and their relationship with the clinical course in patients with anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE).Eighteen serial PET scans of 8 patients with ANMDARE were reviewed. All the 18 PET scans were divided into 4 groups according to studies timing in different clinical course: group A, the acute and subacute phase; group B, early recovery phase; group C, recovery phase; and group D, relapsing phase. Antibody levels of ANMDARE of all these patients were tested at the same time. The PET images of each group were analyzed visually and also compared with 10 age- and sex-matched normal controls using voxel-wise statistical parametric mapping analysis (SPM5).Variable brain metabolic patterns and its association with the clinical course and the levels of NMDA antibody were demonstrated by FDG PET images. First, severe hypometabolism in bilateral occipital lobes and relatively mild hypermetabolism in the partial frontal and basal ganglia in acute and subacute phase, the level of antibody was high. Second, in early recovery phase when the symptoms was partially improved, extensive cortical hypometabolism was observed, and the level of antibody was low. Third, the patients in the recovery phase have no obvious neurological and psychiatric symptoms; PET images were nearly normal, and the antibodies tests were all negative, correspondingly. Fourth, 3 scans of relapsing phase presented heterogeneous brain metabolic abnormalities.There existed a specific serial brain metabolic changing pattern that correlated with the clinical course and antibody level in ANMDARE.
African swine fever virus (ASFV) can cause highly lethal disease in pigs and is becoming a global threat. ASFV DNA Polymerase X (AsfvPolX) is the most distinctive DNA polymerase identified to date; it lacks two DNA-binding domains (the thumb domain and 8-KD domain) conserved in the homologous proteins. AsfvPolX catalyzes the gap-filling reaction during the DNA repair process of the ASFV virus genome; it is highly error prone and plays an important role during the strategic mutagenesis of the viral genome. The structural basis underlying the natural substrate binding and the most frequent dG:dGTP misincorporation of AsfvPolX remain poorly understood. Here, we report eight AsfvPolX complex structures; our structures demonstrate that AsfvPolX has one unique 5′-phosphate (5′-P) binding pocket, which can favor the productive catalytic complex assembly and enhance the dGTP misincorporation efficiency. In combination with mutagenesis and in vitro catalytic assays, our study also reveals the functional roles of the platform His115-Arg127 and the hydrophobic residues Val120 and Leu123 in dG:dGTP misincorporation and can provide information for rational drug design to help combat ASFV in the future.
Motivation: Medical images in different modalities (MR\PET\CT) can provide different information, which can help to fully understand a patient's condition and assist physicians in making accurate diagnoses and treatment plans. Goal(s): Using the diffusion model to generate multiple modal images from a single modality. Approach: We propose the conditional latent diffusion model (CLDM) guided by category information to address the challenge of completing the target modal image within the same body. Results: Compared to images generated by GANs, our model produces higher quality images with enhanced capabilities, particularly in capturing intricate details. Impact: Our study offers bright future for diffusion models in the complementary field of medical imaging modalities.
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