Key Results: Three Chinese radiologists had a sensitivity of 72%, 72% and 94% and specificity of 94%, 88% and 24% in differentiating 219 COVID-19 from 205 non-COVID-19 pneumonia.  Four United States radiologists had a sensitivity of 93%, 83%, 73% and 73% and specificity of 100%, 93%, 93% and 100%.  The most discriminating features for COVID-19 pneumonia included a peripheral distribution (80% vs. 57%, p<0.001), ground-glass opacity (91% vs. 68%, p<0.001) and vascular thickening (58% vs. 22%, p<0.001). Manuscript type: original researchThe total number of words of the manuscript, including entire text from title page to tables and references: 4364 This copy is for personal use only. To order printed copies, contact reprints@rsna.org I n P r e s s Performance of radiologists in differentiating COVID-19 from viral pneumonia on chest CT Summary: Radiologists had high specificity but moderate sensitivity in differentiating COVID-19 from viral pneumonia on chest CT. Key Results:  Three Chinese radiologists had sensitivities of 72%, 72% and 94% and specificities of 94%, 88% and 24% in differentiating 219 COVID-19 from 205 non-COVID-19 pneumonia.  Four United States radiologists had sensitivities of 93%, 83%, 73% and 73% and specificities of 100%, 93%, 93% and 100%.  The most discriminating features for COVID-19 pneumonia included a peripheral distribution (80% vs. 57%, p<0.001), ground-glass opacity (91% vs. 68%, p<0.001) and vascular thickening (58% vs. 22%, p<0.001). Abstract Background: Despite its high sensitivity in diagnosing COVID-19 in a screening population, chest CT appearances of COVID 19 pneumonia are thought to be non-specific. Purpose: To assess the performance of United States (U.S.) and Chinese radiologists in differentiating COVID-19 from viral pneumonia on chest CT. Methods: A total of 219 patients with both positive COVID-19 by RT-PCR and abnormal chest CT findings were retrospectively identified from 7 Chinese hospitals in Hunan Providence, China from January 6 to February 20, 2020. A total of 205 patients with positive Respiratory Pathogen Panel for viral pneumonia and CT findings consistent with or highly suspicious for pneumonia by original radiology interpretation within 7 days of each other were identified from Rhode Island Hospital in Providence, RI. Three Chinese radiologists blindly reviewed all chest CTs (n=424) to differentiate COVID-19 from viral pneumonia. A sample of 58 age-matched cases was randomly selected and evaluated by 4 U.S. radiologists in a similar fashion. Different CT features were recorded and compared between the two groups. Results: For all chest CTs, three Chinese radiologists correctly differentiated COVID-19 from non-COVID-19 pneumonia 83% (350/424), 80% (338/424), and 60% (255/424) of the time, respectively. The seven radiologists had sensitivities of 80%, 67%, 97%, 93%, 83%, 73% and 70% and specificities of 100%, 93%, 7%, 100%, 93%, 93%, 100%. Compared to non-COVID-19 pneumonia, COVID-19 pneumonia was more likely to have a peripheral distribution (80% vs. 57%, p...

A cardinal feature of inflammation is heightened pain sensitivity at the site of the inflamed tissue. This results from the local release by immune and injured cells of nociceptor sensitizers, including prostaglandin E 2 , bradykinin, and nerve growth factor, that reduce the threshold and increase the excitability of the peripheral terminals of nociceptors so that they now respond to innocuous stimuli: the phenomenon of peripheral sensitization. We show here that the proinflammatory cytokine interleukin-1␤ (IL-1␤), in addition to producing inflammation and inducing synthesis of several nociceptor sensitizers, also rapidly and directly activates nociceptors to generate action potentials and induce pain hypersensitivity. IL-1␤ acts in a p38 mitogen-activated protein kinase (p38 MAP kinase)-dependent manner, to increase the excitability of nociceptors by relieving resting slow inactivation of tetrodotoxin-resistant voltage-gated sodium channels and also enhances persistent TTX-resistant current near threshold. By acting as an IL-1␤ sensor, nociceptors can directly signal the presence of ongoing tissue inflammation.

S-100beta and NSE are frequently increased and associated with brain injury in patients with severe sepsis and septic shock. S-100beta levels more closely reflected severe encephalopathy and type of brain lesions than NSE and the Glasgow Coma Scale.

Mutations of the Glu76 residue of canonical histone H2B are frequently found in cancer cells. However, it is quite mysterious how a single amino acid substitution in one of the multiple H2B genes affects cell fate. Here we found that the H2B E76K mutation, in which Glu76 is replaced by Lys (E76K), distorted the interface between H2B and H4 in the nucleosome, as revealed by the crystal structure and induced nucleosome instability in vivo and in vitro. Exogenous production of the H2B E76K mutant robustly enhanced the colony formation ability of the expressing cells, indicating that the H2B E76K mutant has the potential to promote oncogenic transformation in the presence of wild-type H2B. We found that other cancer-associated mutations of histones, H3.1 E97K and H2A.Z.1 R80C, also induced nucleosome instability. Interestingly, like the H2B E76K mutant, the H3.1 E97K mutant was minimally incorporated into chromatin in cells, but it enhanced the colony formation ability. In contrast, the H2A.Z.1 R80C mutant was incorporated into chromatin in cells, and had minor effects on the colony formation ability of the cells. These characteristics of histones with cancer-associated mutations may provide important information toward understanding how the mutations promote cancer progression.

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SummaryGenetic information encoded in chromosomal DNA is challenged by intrinsic and exogenous sources of DNA damage. DNA doublestrand breaks (DSBs) are extremely dangerous DNA lesions. RAD51 plays a central role in homologous DSB repair, by facilitating the recombination of damaged DNA with intact DNA in eukaryotes. RAD51 accumulates at sites containing DNA damage to form nuclear foci. However, the mechanism of RAD51 accumulation at sites of DNA damage is still unclear. Post-translational modifications of proteins, such as phosphorylation, acetylation and ubiquitylation play a role in the regulation of protein localization and dynamics. Recently, the covalent binding of small ubiquitin-like modifier (SUMO) proteins to target proteins, termed SUMOylation, at sites containing DNA damage has been shown to play a role in the regulation of the DNA-damage response. Here, we show that the SUMOylation E2 ligase UBC9, and E3 ligases PIAS1 and PIAS4, are required for RAD51 accretion at sites containing DNA damage in human cells. Moreover, we identified a SUMO-interacting motif (SIM) in RAD51, which is necessary for accumulation of RAD51 at sites of DNA damage. These findings suggest that the SUMO-SIM system plays an important role in DNA repair, through the regulation of RAD51 dynamics.

Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalized human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. DU possesses both a radiological (alpha particle) and a chemical (metal) component. Since DU has a low-specific activity in comparison to natural uranium, it is not considered to be a significant radiological hazard. In the current study we demonstrate that DU can generate oxidative DNA damage and can also catalyze reactions that induce hydroxyl radicals in the absence of significant alpha particle decay. Experiments were conducted under conditions in which chemical generation of hydroxyl radicals was calculated to exceed the radiolytic 6 generation by 10 -fold. The data showed that markers of oxidative DNA base damage, thymine glycol and 8-deoxyguanosine could be induced from DU-catalyzed reactions of hydrogen peroxide and ascorbate similarly to those occurring in the presence of iron catalysts. DU was 6-fold more efficient than iron at catalyzing the oxidation of ascorbate at pH 7. These data not only demonstrate that DU at pH 7 can induced oxidative DNA damage in the absence of significant alpha particle decay, but also suggest that DU can induce carcinogenic lesions, e.g. oxidative DNA lesions, through interaction with a cellular oxygen species. Published by Elsevier Science Inc. The in vivo effects of internalized DU include enhanceDesert Storm were wounded in friendly fire accidents and ment of urine mutagenicity, oncogene activation, and currently have retained large fragments (|2-20 mm) of uranium redistribution to multiple organs. A review of our depleted uranium (DU) in their bodies. The use of DU in findings is shown in Table 1 [ [3][4][5][6][7][8][9][10][11][12]. military applications worldwide could result in soldiers DU, unlike natural uranium, which is considered to be with imbedded heavy metal shrapnel. Chemically similar both a radiological and a chemical (heavy metal) hazard to natural uranium [1], DU is a low specific activity heavy[1], is not believed to be a significant radiation hazard metal, with a density |1.7-times that of lead (19 vs. 11.35 because of its low specific activity. Studies with DU in our 3 g / cm ). DU differs from natural uranium in that it has laboratory demonstrated neoplastic transformation of 235 234 been depleted of U and U. As a result, the specific human cells under conditions in which |14% of the activity of DU is significantly less than natural uranium DU-exposed cells were transformed but with less than 5% (0.44 vs. 0.7 mCi / g, respectively) [2].of the DU-exposed cells actually being traversed by an The acute and long-term health effects of exposure to alpha particle [4,8,9]. While these findings might suggest these heavy metals are unknown. Our laboratory has used that the chemical component of DU could be primarily both an in vitro human cell-model and rodent studies to responsible for the ...

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