A novel dsRNA virus was identified by high-throughput sequencing from tea oil trees in China
.
Its complete genome of 4714 bp contains two open reading frames (ORFs). ORF1 encodes a putative coat ...protein (CP) of 702 amino acids (aa), and ORF2 codes for an RNA-dependent RNA polymerase (RdRp) of 855 aa. The virus shares the highest aa sequence identity of 45.21% in RdRp with taro-associated totivirus L (MN_119621), a member of the genus
Totivirus
in the family
Totiviridae
. Phylogenetic analysis of the aa sequences of the RdRp places the new virus in a group with other totiviruses, suggesting that this virus, which is provisionally named "tea-oil camellia-associated totivirus 1", should be considered a member of the genus
Totivirus
.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Meta-analyses were conducted to characterize patterns of mutation incidence in non small-cell lung cancer (NSCLC).
Nine genes with the most complete published mutation coincidence data were ...evaluated. One meta-analysis generated a ‘mutMap’ to visually represent mutation coincidence by ethnicity (Western/Asian) and histology (adenocarcinoma ADC or squamous cell carcinoma). Another meta-analysis evaluated incidence of individual mutations. Extended analyses explored incidence of EGFR and KRAS mutations by ethnicity, histology, and smoking status.
Genes evaluated were TP53, EGFR, KRAS, LKB1, EML4-ALK, PTEN, BRAF, PIK3CA, and ErbB2. The mutMap highlighted mutation coincidences occurring in ≥5% of patients, including TP53 with KRAS or EGFR mutations in patients with ADC, and TP53 with LKB1 mutation in Western patients. TP53 was the most frequently mutated gene overall. Frequencies of TP53, EGFR, KRAS, LKB1, PTEN, and BRAF mutations were influenced by histology and/or ethnicity. Although EGFR mutations were most frequent in patients with ADC and never/light smokers from Asia, and KRAS mutations were most frequent in patients with ADC and ever/heavy smokers from Western countries, both were detected outside these subgroups.
Potential molecular pathology segments of NSCLC were identified. Further studies of mutations in NSCLC are warranted to facilitate more specific diagnoses and guide treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite their well-known limitations, Reynolds-Averaged Navier–Stokes (RANS) models are still the workhorse tools for turbulent flow simulations in today's engineering analysis, design and ...optimization. While the predictive capability of RANS models depends on many factors, for many practical flows the turbulence models are by far the largest source of uncertainty. As RANS models are used in the design and safety evaluation of many mission-critical systems such as airplanes and nuclear power plants, quantifying their model-form uncertainties has significant implications in enabling risk-informed decision-making. In this work we develop a data-driven, physics-informed Bayesian framework for quantifying model-form uncertainties in RANS simulations. Uncertainties are introduced directly to the Reynolds stresses and are represented with compact parameterization accounting for empirical prior knowledge and physical constraints (e.g., realizability, smoothness, and symmetry). An iterative ensemble Kalman method is used to assimilate the prior knowledge and observation data in a Bayesian framework, and to propagate them to posterior distributions of velocities and other Quantities of Interest (QoIs). We use two representative cases, the flow over periodic hills and the flow in a square duct, to evaluate the performance of the proposed framework. Both cases are challenging for standard RANS turbulence models. Simulation results suggest that, even with very sparse observations, the obtained posterior mean velocities and other QoIs have significantly better agreement with the benchmark data compared to the baseline results. At most locations the posterior distribution adequately captures the true model error within the developed model form uncertainty bounds. The framework is a major improvement over existing black-box, physics-neutral methods for model-form uncertainty quantification, where prior knowledge and details of the models are not exploited. This approach has potential implications in many fields in which the governing equations are well understood but the model uncertainty comes from unresolved physical processes.
•Proposed a physics–informed framework to quantify uncertainty in RANS simulations.•Framework incorporates physical prior knowledge and observation data.•Based on a rigorous Bayesian framework yet fully utilizes physical model.•Applicable for many complex physical systems beyond turbulent flows.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background and purpose
Restless legs syndrome (RLS) is an underestimated movement disorder in patients with end‐stage renal disease (ESRD). Several clinical and laboratory factors were inconsistently ...reported to associate with RLS. We aim to perform a large‐scale multicenter study to investigate the possible associated risk factors of RLS in patients with ESRD in Taiwan, a country with the highest incidence of uremia in the world.
Methods
From October 2009 to October 2011, we constitutively recruited 1130 patients with ESRD from 17 hemodialysis centers. Demographic, laboratory data, presence and severity of RLS were collected. Odds ratios (ORs) were estimated by logistic regression models.
Results
We found the prevalence of RLS to be 25.3% in patients with ESRD. Having type 2 diabetes OR = 3.61 (2.27–5.77), P < 0.01, low serum transferrin saturation OR = 1.42 (1.01–2.03), P < 0.05 and duration of dialysis OR = 1.09 (1.03–1.14), P < 0.01 were associated with RLS. In contrast, high serum hemoglobin level was inversely associated with RLS OR = 0.61 (0.40–0.89), P < 0.05. RLS has a significant impact on sleep quality in dialysis patients. Among patients with RLS, history of type 2 diabetes OR = 4.04 (1.65–10.79), P < 0.05, low serum hemoglobin level OR = 5.41 (2.43–13.12), P < 0.01 and duration of dialysis OR = 1.01 (1.01–1.02), P < 0.01 were associated with increased severity of RLS.
Conclusions
Our findings demonstrated that RLS is common in Taiwanese dialysis patients. Clinicians should have a high suspicion for the presence of RLS symptoms in patients with ESRD, especially those with type 2 diabetes, anemia, low serum iron status and long duration of dialysis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Osteoarthritis (OA) is a family of degenerative diseases affecting multiple joint tissues. Despite the diverse etiology and pathogenesis of OA, increasing evidence suggests that macrophages can play ...a significant role in modulating joint inflammation, and thus OA severity, via various secreted mediators. Recent advances in next-generation sequencing technologies coupled with proteomic and epigenetic tools have greatly facilitated research to elucidate the embryonic origin of macrophages in various tissues including joint synovium. Furthermore, scientists have now begun to appreciate that macrophage polarization can span beyond the conventionally recognized binary states (i.e., pro-inflammatory M1-like vs anti-inflammatory M2-like) and may encompass a broad spectrum of phenotypes. Although the presence of these cells has been shown in multiple joint tissues, additional mechanistic studies are required to provide a comprehensive understanding of the precise role of these diverse macrophage populations in OA onset and progression. New approaches that can modulate macrophages into desired functional phenotypes may provide novel therapeutic strategies for preventing OA or enhancing cartilage repair and regeneration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Head and neck cancer is one of the most prevalent cancers around the world. Head and neck squamous cell carcinoma (HNSCC) accounts for nearly 90% of head and neck cancer. In recent years, significant ...advances have been made in immunotherapy for HNSCC. Although some clinical trials targeting immune checkpoints have shown success, the molecular mechanism for regulation of programmed death 1 (PD-1) and its ligand (PD-L1) is partially understood. In an effort to explore the effect of activation of signal transducers and activators of transcriptions (STAT3) on PD-1/PD-L1, the expression and correlation between phosphorylation of STAT3 and PD-1/PD-L1 were determined with immunostaining of human and mouse HNSCC tissue sections. PD-1/PD-L1 overexpression was found to be significantly associated with p-STAT3 in human and mouse HNSCC. Targeting STAT3 by a small molecule effectively inhibited the expression of PD-L1 in the CAL27 cell line. Furthermore, we found that blockade of STAT3 signaling downregulated PD-1/PD-L1 in a Tgfbr1/Pten 2cKO HNSCC mouse model. These findings suggest that STAT3 signaling plays an important role in PD-1/PD-L1 regulation and the antitumor immune response of HNSCC.
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CMK, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
In a randomized trial involving patients with non–small-cell lung cancer with mutant EGFR (T790M) in whom a tyrosine kinase inhibitor had failed, osimertinib was associated with significantly longer ...progression-free survival than platinum therapy plus pemetrexed.
Among patients with advanced non–small-cell lung cancer with a mutant epidermal growth factor receptor (EGFR), EGFR tyrosine kinase inhibitors (TKIs) are the standard first-line therapy.
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Despite high tumor response rates with first-line EGFR-TKIs, disease progresses in a majority of patients after 9 to 13 months of treatment.
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At the time of progression, approximately 60% of patients (regardless of race or ethnic background) are found to have a p.Thr790Met point mutation (T790M) in the gene encoding EGFR.
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The presence of the T790M variant reduces binding of first-generation or second-generation EGFR-TKIs to the ATP-binding pocket of EGFR, thereby reducing . . .
Background
Previous studies comparing early laparoscopic cholecystectomy (ELC) with delayed laparoscopic cholecystectomy (DLC) for acute cholecystitis were incomplete. A meta‐analysis was undertaken ...to compare the cost‐effectiveness, quality of life, safety and effectiveness of ELC versus DLC.
Methods
PubMed, Embase, the Cochrane Library and Web of Science were searched for randomized clinical trials (RCTs) that compared ELC (performed within 7 days of symptom onset) with DLC (undertaken at least 1 week after symptoms had subsided) for acute cholecystitis.
Results
Sixteen studies reporting on 15 RCTs comprising 1625 patients were included. Compared with DLC, ELC was associated with lower hospital costs, fewer work days lost (mean difference (MD) –11·07 (95 per cent c.i. –16·21 to −5·94) days; P < 0·001), higher patient satisfaction and quality of life, lower risk of wound infection (relative risk 0·65, 95 per cent c.i. 0·47 to 0·91; P = 0·01) and shorter hospital stay (MD −3·38 (−4·23 to −2·52) days; P < 0·001), but a longer duration of operation (MD 11·12 (4·57 to 17·67) min; P < 0·001). There were no significant differences between the two groups in mortality, bile duct injury, bile leakage, conversion to open cholecystectomy or overall complications.
Conclusion
For patients with acute cholecystitis, ELC appears as safe and effective as DLC. ELC might be associated with lower hospital costs, fewer work days lost, and greater patient satisfaction.
The sooner the better
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Following the 15 January 2022 Hunga Tonga‐Hunga Ha'apai eruption, several trace gases measured by the Aura Microwave Limb Sounder (MLS) displayed anomalous stratospheric values. Trajectories and ...radiance simulations confirm that the H2O, SO2, and HCl enhancements were injected by the eruption. In comparison with those from previous eruptions, the SO2 and HCl mass injections were unexceptional, although they reached higher altitudes. In contrast, the H2O injection was unprecedented in both magnitude (far exceeding any previous values in the 17‐year MLS record) and altitude (penetrating into the mesosphere). We estimate the mass of H2O injected into the stratosphere to be 146 ± 5 Tg, or ∼10% of the stratospheric burden. It may take several years for the H2O plume to dissipate. This eruption could impact climate not through surface cooling due to sulfate aerosols, but rather through surface warming due to the radiative forcing from the excess stratospheric H2O.
Plain Language Summary
The violent Hunga Tonga‐Hunga Ha'apai eruption on 15 January 2022 not only injected ash into the stratosphere but also large amounts of water vapor, breaking all records for direct injection of water vapor, by a volcano or otherwise, in the satellite era. This is not surprising since the Hunga Tonga‐Hunga Ha'apai caldera was formerly situated 150 m below sea level. The massive blast injected water vapor up to altitudes as high as 53 km. Using measurements from the Microwave Limb Sounder on NASA's Aura satellite, we estimate that the excess water vapor is equivalent to around 10% of the amount of water vapor typically residing in the stratosphere. Unlike previous strong eruptions, this event may not cool the surface, but rather it could potentially warm the surface due to the excess water vapor.
Key Points
Following the Hunga Tonga‐Hunga Ha'apai eruption, the Aura Microwave Limb Sounder measured enhancements of stratospheric H2O, SO2, and HCl
The mass of SO2 and HCl injected is comparable to that from prior eruptions, whereas the magnitude of the H2O injection is unprecedented
Excess stratospheric H2O will persist for years, could affect stratospheric chemistry and dynamics, and may lead to surface warming
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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