Dear Editor, The rapid emergence of COVID-19 in Wuhan city, Hubei Province, China, has resulted in thousands of deaths . Many infected patients, however, presented mild flu-like symptoms and quickly recover . To effectively prioritize resources for patients with the highest risk, we identified clinical predictors of mild and severe patient outcomes.Using the database of Jin Yin-tan Hospital and Tongji Hospital, we conducted a retrospective multicenter study of 68 death cases (68/150, 45%) and 82 discharged cases (82/150, 55%) with laboratory-confirmed infection of SARS-CoV-2. Patients met the discharge criteria if they had no fever for at least 3 days, significantly improved respiratory function, and had negative SARS-CoV-2 laboratory test results twice in succession. Case data included demographics, clinical characteristics, laboratory results, treatment options and outcomes. For statistical analysis, we represented continuous measurements as means (SDs) or as medians (IQRs) which compared with Student's t test or the Mann-Whitney-Wilcoxon test. Categorical variables were expressed as numbers (%) and compared by the χ 2 test or Fisher's exact test.The distribution of the enrolled patients' age is shown in Fig. 1a. There was a significant difference in age between the death group and the discharge group (p < 0.001) but no difference in the sex ratio (p = 0.43). A total of 63% (43/68) of patients in the death group and 41% (34/82) in the discharge group had underlying diseases (p = 0.0069). It should be noted that patients with cardiovascular diseases have a significantly increased risk of death when they are infected with SARS-CoV-2 (p < 0.001). A total of 16% (11/68) of the patients in the death group had secondary infections, and 1% (1/82) of the patients in the discharge group had secondary infections (p = 0.0018). Laboratory results showed that there were significant differences in white blood cell counts, absolute values of lymphocytes, platelets, albumin, total bilirubin, blood urea nitrogen, blood creatinine, myoglobin, cardiac troponin, C-reactive protein (CRP) and interleukin-6 (IL-6) between the two groups ( Fig. 1b and Supplementary Table 1).The survival times of the enrolled patients in the death group were analyzed. The distribution of survival time from disease onset to death showed two peaks, with the first one at approximately 14 days (22 cases) and the second one at approximately 22 days (17 cases) (Fig. 1c). An analysis of the cause of death was performed. Among the 68 fatal cases, 36 patients (53%) died of respiratory failure, five patients (7%) with myocardial damage died of circulatory failure, 22 patients (33%) died of both, and five remaining died of an unknown cause (Fig. 1d). Based on the analysis of the clinical data, we confirmed that some patients died of fulminant myocarditis. In this study, we first reported that the infection of SARS-CoV-2 may cause fulminant myocarditis. Given that fulminant myocarditis is characterized by a rapid progress and a severe state of illness , o...
Nearly a century after the significance of the human complement system was recognized we have come to realize that its versatile functions extend far beyond the elimination of microbes. Indeed, complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses, and sending `danger' signals, complement contributes substantially to homeostasis, but it may also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure, and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its dual role in homeostasis and disease.
At strong magnetic fields double-layer two-dimensional-electron-gas systems can form an unusual broken symmetry state with spontaneous interlayer phase coherence. In this paper we explore the rich variety of quantum and finite-temperature phase transitions associated with this broken symmetry. We describe the system using a pseudospin language in which the layer degree-of-freedom is mapped to a fictional spin 1/2 degree-of-freedom. With this mapping the spontaneous symmetry breaking is equivalent to that of a spin 1/2 easy-plane ferromagnet. In this language spin-textures can carry a charge. In particular, vortices carry ±e/2 electrical charge and vortexantivortex pairs can be neutral or carry charge ±e. We derive an effective low-energy action and use it to discuss the charged and collective neutral excitations of the system. We have obtained the parameters of the LandauGinzburg functional from first-principles estimates and from finite-size exact diagonalization studies. We use these results to estimate the dependence of the critical temperature for the Kosterlitz-Thouless phase transition on layer separation.
Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral encephalitis in western countries. Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority of HSV-1-infected individuals. Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in the intracellular protein UNC-93B, resulting in impaired cellular interferon-alpha/beta and -lambda antiviral responses. HSE can result from a single-gene immunodeficiency that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Other severe infectious diseases may also reflect monogenic disorders of immunity.
The receptors for interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma activate components of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, leading to the formation of at least two transcription factor complexes. STAT1 interacts with STAT2 and p48/IRF-9 to form the transcription factor IFN-stimulated gene factor 3 (ISGF3). STAT1 dimers form gamma-activated factor (GAF). ISGF3 is induced mainly by IFN-alpha/beta, and GAF by IFN-gamma, although both factors can be activated by both types of IFN. Individuals with mutations in either chain of the IFN-gamma receptor (IFN-gammaR) are susceptible to infection with mycobacteria. A heterozygous STAT1 mutation that impairs GAF but not ISGF3 activation has been found in other individuals with mycobacterial disease. No individuals with deleterious mutations in the IFN-alpha/beta signaling pathway have been described. We report here two unrelated infants homozygous with respect to mutated STAT1 alleles. Neither IFN-alpha/beta nor IFN-gamma activated STAT1-containing transcription factors. Like individuals with IFN-gammaR deficiency, both infants suffered from mycobacterial disease, but unlike individuals with IFN-gammaR deficiency, both died of viral disease. Viral multiplication was not inhibited by recombinant IFN-alpha/beta in cell lines from the two individuals. Inherited impairment of the STAT1-dependent response to human IFN-alpha/beta thus results in susceptibility to viral disease.
Purpose-To prospectively identify markers of response to therapy and outcome in an organsparing trial for advanced oropharyngeal cancer.Patients and Methods-Pretreatment biopsies were examined for expression of epidermal growth factor receptor (EGFR), p16, Bcl-xL, and p53 as well as for p53 mutation. These markers Authors' Disclosures of Potential Conflicts of Interest:Although all authors completed the disclosure declaration, the following author (s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure were assessed for association with high-risk human papillomavirus (HPV), response to therapy, and survival. Patient variables included smoking history, sex, age, primary site, tumor stage, and nodal status.Results-EGFR expression was inversely associated with response to induction chemotherapy (IC) (P = .01), chemotherapy/radiotherapy (CRT; P = .055), overall survival (OS; P = .001), and diseasespecific survival (DSS; P = .002) and was directly associated with current smoking (P = .04), female sex (P = .053), and lower HPV titer (P = .03). HPV titer was significantly associated with p16 expression (P < .0001); p16 was significantly associated with response to IC (P = .008), CRT (P = . 009), OS (P = .001), and DSS (P = .003). As combined markers, lower HPV titer and high EGFR expression were associated with worse OS (ρ EGFR = 0.008; ρ HPV = 0.03) and DSS (ρ EGFR = 0.01; ρ HPV = 0.016). In 36 of 42 biopsies, p53 was wild-type, and only one HPV-positive tumor had mutant p53. The combination of low p53 and high Bcl-xL expression was associated with poor OS (P = . 005) and DSS (P = .002).Conclusion-Low EGFR and high p16 (or higher HPV titer) expression are markers of good response to organ-sparing therapy and outcome, whereas high EGFR expression, combined low p53/ high Bcl-xL expression, female sex, and smoking are associated with a poor outcome. Smoking cessation and strategies to target EGFR and Bcl-xL are important adjuncts to the treatment of oropharyngeal cancer.
The unfolded protein response (UPR) is a transcriptional and translational intracellular signaling pathway activated by the accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER). We have used C. elegans as a genetic model system to dissect UPR signaling in a multicellular organism. C. elegans requires ire-1-mediated splicing of xbp-1 mRNA for UPR gene transcription and survival upon ER stress. In addition, ire-1/xbp-1 acts with pek-1, a protein kinase that mediates translation attenuation, in complementary pathways that are essential for worm development and survival. We propose that UPR transcriptional activation by ire-1 as well as translational attenuation by pek-1 maintain ER homeostasis. The results demonstrate that the UPR and ER homeostasis are essential for metazoan development.
Carbon nanomaterials are novel manufactured materials, having widespread potential applications. Adsorption of hydrophobic organic compounds (HOCs) by carbon nanomaterials may enhance their toxicity and affect the fate, transformation, and transport of HOCs in the environment. In this research, adsorption of naphthalene, phenanthrene, and pyrene onto six carbon nanomaterials, including fullerenes, single-walled carbon nanotubes, and multiwalled carbon nanotubes was investigated, which is the first systematic study on polycyclic aromatic hydrocarbons (PAHs) sorption by various carbon nanomaterials. All adsorption isotherms were nonlinear and were fitted well by the Polanyi-Manes model (PMM). Through both isotherm modeling and constructing "characteristic curve", Polanyi theory was useful to describe the adsorption process of PAHs by the carbon nanomaterials. The three fitted parameters (Q0, a, and b) of PMM depended on both PAH properties and the nature of carbon nanomaterials. For different PAHs, adsorption seems to relate with their molecular size, i.e., the larger the molecular size, the lower the adsorbed volume capacity (Q0), but higher a and b values. For different carbon nanomaterials, adsorption seems to relate with their surface area, micropore volume, and the volume ratios of mesopore to micropore. Quantitative relationships between these sorbent properties and the estimated parameters of PMM were obtained. These relationships may represent a first fundamental step toward establishing empirical equations for quantitative prediction of PAH adsorption by carbon nanomaterials and possibly other forms of carbonaceous (geo-) sorbents, and for evaluating their environmental impact. In addition, high adsorption capacity of PAHs by carbon nanotubes may add to their high environmental risks once released to the environment, and result in potential alteration of PAHs fate and bioavailability in the environment.
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