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Ribosome biogenesis underpins cell growth and division. Disruptions in ribosome biogenesis and translation initiation are deleterious to development and underlie a spectrum of diseases known collectively as ribosomopathies. Here, we describe a novel zebrafish mutant, titania (tti(s450)), which harbours a recessive lethal mutation in pwp2h, a gene encoding a protein component of the small subunit processome. The biochemical impacts of this lesion are decreased production of mature 18S rRNA molecules, activation of Tp53, and impaired ribosome biogenesis. In tti(s450), the growth of the endodermal organs, eyes, brain, and craniofacial structures is severely arrested and autophagy is up-regulated, allowing intestinal epithelial cells to evade cell death. Inhibiting autophagy in tti(s450) larvae markedly reduces their lifespan. Somewhat surprisingly, autophagy induction in tti(s450) larvae is independent of the state of the Tor pathway and proceeds unabated in Tp53-mutant larvae. These data demonstrate that autophagy is a survival mechanism invoked in response to ribosomal stress. This response may be of relevance to therapeutic strategies aimed at killing cancer cells by targeting ribosome biogenesis. In certain contexts, these treatments may promote autophagy and contribute to cancer cells evading cell death.

Gut microbiota is suggested to regulate the host’s mental health via the gut-brain axis. In this study, we investigated the relationship between the microbiome and psychological pain due to social exclusion. Adult individuals with ( n  = 14) and without ( n  = 25) social exclusion experience were assessed for the psychological status using self-reported questionnaires: Beck Anxiety Inventory (BAI), Beck Depression Inventory, and the UCLA Loneliness Scale. The gut microbiota was analyzed by 16 S rRNA gene sequencing and bioinformatics. The exclusion group had a 1.70-fold higher total BAI score and 2.16-fold higher levels of anxiety-related physical symptoms ( p  < 0.05). The gut microbial profiles also differed between the two groups. The exclusion group showed higher probability of having Prevotella -enriched microbiome (odds ratio, 2.29; 95% confidence interval, 1.65–2.75; p  < 0.05), a significantly reduced Firmicutes/Bacteroidetes ratio, and decreased abundance of Faecalibacterium spp. ( p  < 0.05) which was associated with the duration and intensity of social exclusion ( p  < 0.05). Our results indicate that the psychological pain due to social exclusion is correlated with the gut microbiota composition, suggesting that targeting social exclusion-related microorganisms can be a new approach to solving psychological problems and related social issues.

Objective:MicroRNAs (miRNAs) have been shown to offer great potential in the diagnosis of cancer. We investigated whether plasma miRNAs could discriminate between patients with and without colorectal cancer (CRC).Methods:This study was divided into three phases: (1) marker discovery using real-time PCR-based miRNA profiling on plasma, corresponding cancerous and adjacent non-cancerous colonic tissues of five patients with CRC, along with plasma from five healthy individuals as controls; (2) marker selection and validation by real-time quantitative RT-PCR on a small set of plasma; and (3) independent validation on a large set of plasma from 90 patients with CRC, 20 patients with gastric cancer, 20 patients with inflammatory bowel disease (IBD) and 50 healthy controls.Results:Of the panel of 95 miRNAs analysed, five were upregulated both in plasma and tissue samples. All the five miRNAs were validated on the plasma of 25 patients with CRC and 20 healthy controls. Both miR-17-3p and miR-92 were significantly elevated in the patients with CRC (p<0.0005). The plasma levels of these markers were significantly reduced after surgery in 10 patients with CRC (p<0.05). Further validation with an independent set of plasma samples (n = 180) indicated that miR-92 differentiates CRC from gastric cancer, IBD and normal subjects. This marker yielded a receiver operating characteristic curve area of 88.5%. At a cut-off of 240 (relative expression in comparison to RNU6B snRNA), the sensitivity was 89% and the specificity was 70% in discriminating CRC from control subjects.Conclusion:MiR-92 is significantly elevated in plasma of patients with CRC and can be a potential non-invasive molecular marker for CRC screening.

Background.Candida haemulonii, a yeast species that often exhibits antifungal resistance, rarely causes human infection. During 2004–2006, unusual yeast isolates with phenotypic similarity to C. haemulonii were recovered from 23 patients (8 patients with fungemia and 15 patients with chronic otitis media) in 5 hospitals in Korea. Methods.Isolates were characterized using D1/D2 domain and ITS gene sequencing, and the susceptibility of the isolates to 6 antifungal agents was tested in vitro. Results.Gene sequencing of the blood isolates confirmed C. haemulonii group I (in 1 patient) and Candida pseudohaemulonii (in 7 patients), whereas all isolates recovered from the ear were a novel species of which C. haemulonii is its closest relative. The minimum inhibitory concentration (MIC) ranges of amphotericin B, fluconazole, itraconazole, and voriconazole for all isolates were 0.5–32 µg/mL (MIC>50, 1 µg/mL), 2–128 µg/mL (MIC>50, 4 µg/mL), 0.125–4 µg/mL (MIC>50, 0.25 µg/mL), and 0.03–2 µg/mL (MIC>50, 0.06 µg/mL), respectively. All isolates were susceptible to caspofungin (MIC, 0.125–0.25 µg/mL) and micafungin (MIC, 0.03–0.06 µg/mL). All cases of fungemia occurred in patients with severe underlying diseases who had central venous catheters. Three patients developed breakthrough fungemia while receiving antifungal therapy, and amphotericin B therapeutic failure, which was associated with a high MIC of amphotericin B (32 µg/mL), was observed in 2 patients. Conclusions.Candida species that are closely related to C. haemulonii are emerging sources of infection in Korea. These species show variable patterns of susceptibility to amphotericin B and azole antifungal agents.

The Geostationary Environment Monitoring Spectrometer (GEMS) on board GEO-KOMPSAT-2B was launched in February 2020 and has been monitoring atmospheric chemical compositions over Asia. We present the first evaluation of the operational GEMS formaldehyde (HCHO) vertical column densities (VCDs) during and after the in-orbit test (IOT) period (August–October 2020) by comparing them with the products from the TROPOspheric Monitoring Instrument (TROPOMI) and Fourier-transform infrared (FTIR) and multi-axis differential optical absorption spectroscopy (MAX-DOAS) instruments. During the IOT, the GEMS HCHO VCDs reproduced the observed spatial pattern of TROPOMI VCDs over the entire domain (r= 0.62) with high biases (10 %–16 %). We found that the agreement between GEMS and TROPOMI was substantially higher in Northeast Asia (r= 0.90), encompassing the Korean Peninsula and east China. GEMS HCHO VCDs captured the seasonal variation in HCHO, primarily driven by biogenic emissions and photochemical activities, but showed larger variations than those of TROPOMI over coastal regions (Kuala Lumpur, Singapore, Shanghai, and Busan). In addition, GEMS HCHO VCDs showed consistent hourly variations with MAX-DOAS (r= 0.77) and FTIR (r= 0.86) but were 30–40 % lower than ground-based observations. Different vertical sensitivities of GEMS and ground-based instruments caused these biases. Utilizing the averaging kernel smoothing method reduces the low biases by approximately 10 % to 15 % (normalized mean bias (NMB): −47.4 % to −31.5 % and −38.6 % to −26.7 % for MAX-DOAS and FTIR, respectively). The remaining discrepancies are due to multiple factors, including spatial collocation and different instrumental sensitivities, requiring further investigation using inter-comparable datasets.

We evaluated the clinical implications of pre- and post-treatment hematological parameters as prognostic factors in patients with locally advanced cervical cancer (LACC) who received definitive concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 125 patients with LACC (FIGO stage IIB to IIIB) who received definitive CCRT. Clinical factors and hematological parameters, including neutrophil-to-lymphocyte ratio (NLR) were assessed pre- and post-CCRT. Univariate and multivariate analysis for disease-free survival (DFS) and overall survival (OS) were performed using clinicopathological and hematological parameters. Disease recurred in 46 (36.8%) patients, and 24 patients (19.2%) died. On multivariate analysis, post-treatment NLR, ΔNLR (pre-treatment NLR/post-treatment NLR) and ΔPLR (platelet-to-lymphocyte ratio) (pretreatment PLR/post-treatment PLR) were significant prognostic factors for DFS, and only post-treatment NLR was a significant prognostic factor for OS (p<0.001). However, pre-treatment hematological parameters were not associated with prognosis. Post-treatment hematological parameters, particularly NLR, may serve as a prognostic indicator in patients with LACC who received definitive CCRT.

The Geostationary Environment Monitoring Spectrometer (GEMS) is scheduled for launch in February 2020 to monitor air quality (AQ) at an unprecedented spatial and temporal resolution from a geostationary Earth orbit (GEO) for the first time. With the development of UV–visible spectrometers at sub-nm spectral resolution and sophisticated retrieval algorithms, estimates of the column amounts of atmospheric pollutants (O₃, NO₂, SO₂, HCHO, CHOCHO, and aerosols) can be obtained. To date, all the UV–visible satellite missions monitoring air quality have been in low Earth orbit (LEO), allowing one to two observations per day. With UV–visible instruments on GEO platforms, the diurnal variations of these pollutants can now be determined. Details of the GEMS mission are presented, including instrumentation, scientific algorithms, predicted performance, and applications for air quality forecasts through data assimilation. GEMS will be on board the Geostationary Korea Multi-Purpose Satellite 2 (GEO-KOMPSAT-2) satellite series, which also hosts the Advanced Meteorological Imager (AMI) and Geostationary Ocean Color Imager 2 (GOCI-2). These three instruments will provide synergistic science products to better understand air quality, meteorology, the long-range transport of air pollutants, emission source distributions, and chemical processes. Faster sampling rates at higher spatial resolution will increase the probability of finding cloud-free pixels, leading to more observations of aerosols and trace gases than is possible from LEO. GEMS will be joined by NASA’s Tropospheric Emissions: Monitoring of Pollution (TEMPO) and ESA’s Sentinel-4 to form a GEO AQ satellite constellation in early 2020s, coordinated by the Committee on Earth Observation Satellites (CEOS).

BackgroundPhysician online ratings are ubiquitous and influential, but they also have their detractors. Given the lack of scientific survey methodology used in online ratings, some health systems have begun to publish their own internal patient-submitted ratings of physicians.ObjectiveThe purpose of this study was to compare online physician ratings with internal ratings from a large healthcare system.DesignRetrospective cohort study comparing online ratings with internal ratings from a large healthcare system.SettingKaiser Permanente, a large integrated healthcare delivery system.ParticipantsPhysicians in the Southern California region of Kaiser Permanente, including all specialties with ambulatory clinic visits.Main MeasuresThe primary outcome measure was correlation between online physician ratings and internal ratings from the integrated healthcare delivery system.ResultsOf 5438 physicians who met inclusion and exclusion criteria, 4191 (77.1%) were rated both online and internally. The online ratings were based on a mean of 3.5 patient reviews, while the internal ratings were based on a mean of 119 survey returns. The overall correlation between the online and internal ratings was weak (Spearman’s rho .23), but increased with the number of reviews used to formulate each online rating.ConclusionsPhysician online ratings did not correlate well with internal ratings from a large integrated healthcare delivery system, although the correlation increased with the number of reviews used to formulate each online rating. Given that many consumers are not aware of the statistical issues associated with small sample sizes, we would recommend that online rating websites refrain from displaying a physician’s rating until the sample size is sufficiently large (for example, at least 15 patient reviews). However, hospitals and health systems may be able to provide better information for patients by publishing the internal ratings of their physicians.

Alzheimer’s disease (AD) is characterized by neuronal loss in several regions of the brain. Recent studies have suggested that stem cell transplantation could serve as a potential therapeutic strategy to halt or ameliorate the inexorable disease progression. However, the optimal stage of the disease for stem cell transplantation to have a therapeutic effect has yet to be determined. Here, we demonstrated that transplantation of neural stem cells into 12-month-old Tg2576 brains markedly improved both cognitive impairments and neuropathological features by reducing β -amyloid processing and upregulating clearance of β -amyloid, secretion of anti-inflammatory cytokines, endogenous neurogenesis, as well as synapse formation. In contrast, the stem cell transplantation did not recover cognitive dysfunction and β -amyloid neuropathology in Tg2576 mice aged 15 months when the memory loss is manifest. Overall, this study underscores that stem cell therapy at optimal time frame is crucial to obtain maximal therapeutic effects that can restore functional deficits or stop the progression of AD.