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Yanhong Deng,1,* Lishuo Shi,2,* Jianxia Li,1,* Zhipeng Jiang,3,* Chaojun Xie,4 Shuangling Luo,3 Li Ling,5 Hualiang Lin,6 Zongqiu Chen,4 Yunlong Zhao,7 Liang Kang,3 Jun Yuan,4 Weiping Wen8 1Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China; 2Clinical Research Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China; 3Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China; 4Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong Province, 510440, People’s Republic of China; 5Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 6Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 7Medical Department, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China; 8Department of Otolaryngology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiping WenDepartment of Otolaryngology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, No. 26 Yuan Cun Er Heng Road, Guangzhou, 510655, People’s Republic of ChinaTel +86-20-87333733Email wenwp@mail.sysu.edu.cnJun YuanGuangzhou Center for Disease Control and Prevention, No. 1, Qide Road of Baiyun District, Guangzhou, Guangdong Province, 510440, People’s Republic of ChinaTel +86-20-36052333-1816Email yuanjuncom@163.comBackground: The quarantine in dedicated hotels has become an inevitable safety measure due to the frequent cross-border travel since the outbreak of COVID-19. The aim of the present study was to explore the trends in the psychological status of individuals entering from high-risk areas of COVID-19 coronavirus while quarantining in dedicated hotels.Methods: A total of 591 individuals who isolated in dedicated hotels were recruited between March and June 2020. Participants self-reported mental symptoms [Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS)] every three days during the quarantine. A mixed-effects linear regression model was used to assess the trends.Results: Participants reporting anxiety and depression symptoms at least one time during quarantine accounted for 4.5% and 18.4%, respectively. Their psychological status was alleviated during some first 9 days, and then it slightly deteriorated, which was suggested by SAS and SDS scores that were negatively correlated with the days of quarantine (T) (adjusted coefficient [β] − 0.81, 95% CI − 1.00 to − 0.62; and β − 0.75, 95% CI − 0.97 to − 0.53, respectively), and were positively correlated with the square of T (β 0.04, 95% CI 0.02 to 0.06; and β 0.04, 95% CI 0.02 to 0.06, respectively). The unemployed and 18∼ 30-year-old participants were prone to greater levels of psychological distress. No significant difference in the trend of mental health was found among different subgroups.Conclusion: The mental health of the people entering Guangzhou from high-risk areas of COVID-19 coronavirus resulted positive during the early period of quarantine in dedicated hotels, after which it deteriorated. The psychological status of individuals should be closely monitored at the beginning and after more than 9 days of quarantine, especially for individuals who are unemployed and 18∼ 30-year-old ones.Keywords: quarantine, dedicated hotels, psychological distress, COVID-19

The regulation of aircraft engine NO x emissions was introduced to improve local air quality and reduce NO x emissions at altitude. Here, the authors find that greater fuel efficiency of aircrafts, and therefore lower CO2 emissions, could be preferable to reducing NO x emissions in terms of the aviation industries future climate impacts.

Jie Chen,1 Shiying Luo,1 Ning Li,1 Huimin Li,1 Jinming Han,2 Li Ling1 1Department of Neurology, Affiliated Hospital of Hebei University, Baoding, People’s Republic of China; 2Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenCorrespondence: Li LingDepartment of Neurology, Affiliated Hospital of Hebei University, Baoding, People’s Republic of ChinaEmail 592201535@qq.comJinming HanDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenEmail jinming.han@ki.seAbstract: CSF1R-related leukoencephalopathy, mainly caused by the mutation of the colony stimulating factor 1 receptor (CSF1R) gene on chromosome 5, is an underestimated neurological disease typically presenting as early-onset cognitive decline and personality changes. Currently, there is no specific treatment for CSF1R-related leukoencephalopathy. Most clinicians failed to recognize this disease during an early disease stage, leading to a high rate of misdiagnosis. Although rare, an increasing amount of CSF1R-related leukoencephalopathy cases have been reported recently. In this study, we first report a 35-year-old woman with CSF1R-related leukoencephalopathy carrying a novel missense mutation c.2463G >C (p.W821C) of CSF1R. An extensive literature research was performed in order to better understand the broader genetic and clinical characteristics of CSF1R-related leukoencephalopathy. A total of 147 patients with CSF1R-related leukoencephalopathy confirmed either by the genetic test or brain biopsy were identified. Among them, 49 patients were sporadic, and the rest of individuals had a family history originating from 46 different families. Our study indicated that the average age of CSF1R-related leukoencephalopathy onset was 41.4 years. Typical clinical symptoms of CSF1R-related leukoencephalopathy include cognitive decline, movement disorders, behavior changes and mental disorders. Genetic studies have reported 93 missense mutations, 13 splicing mutations, 6 deletion/insertion mutations, 1 code shift mutation and 1 nonsense mutation of the CSF1R gene in patients with CSF1R-related leukoencephalopathy. Early genetic detection and brain biopsy would be helpful for a confirmed diagnosis, and more translational studies are needed to combat this devastating disease.Keywords: CSF1R-related leukoencephalopathy, clinical symptoms, CSF1R

Jiawei Liu,1,* Yan Xu,1,* Muxin Yu,1,* Zhao Liu,1,2,* Yi Xu,3,* Ge Ma,1 Wenbin Zhou,1 Peng Kong,1 Lijun Ling,1 Shui Wang,1 Hong Pan,1 Yi Zhao1 1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Pan; Yi ZhaoDepartment of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People’s Republic of ChinaTel/Fax +86-25-83718836Email pamghong@163.com; doctorzhaoyi@sina.cnBackground: Circulating tumor cells (CTCs) intravasate into the bloodstream throughout early cancer stages, promoting metastasis. The tumor microenvironment plays a crucial role in disease progression and outcome. The aim of this prospective study was to investigate the associations of intratumoral and stromal tumor-infiltrating lymphocytes (TILs) with CTCs among patients receiving neoadjuvant chemotherapy (NAC).Methods: We analyzed CTCs in 30 patients with primary breast cancer before and after NAC. The numbers of intratumoral TILs (iTILs) and stromal TILs (sTILs) from pre-NAC formalin-fixed paraffin-embedded core biopsies and post-NAC surgical samples were analyzed. The associations of TILs with pathologic complete response (pCR) and outcome were also evaluated.Results: Of the 30 patients, pCR was achieved in nine (30.0%) patients. A total of 25 (83.3%) patients were CTC-positive before NAC, and eight (26.7%) patients were CTC-positive after NAC. Neither CTC detection before NAC nor CTC after NAC was predictive of pCR. Nevertheless, the presence of CTCs after NAC was significantly associated with early metastatic relapse (P = 0.049) and worse disease-free survival (P = 0.009). After NAC, total sTILs, CD4+ T cells, and CD8+ T cells were significantly correlated with CTC detection. Increased infiltration of sTILs and CD4+ T cells was also an unfavorable prognostic factor as measured by the rate of metastatic relapse.Conclusion: Detection of CTCs after NAC was positively associated with the metastatic relapse of breast cancer patients. Increased infiltration of sTILs after NAC was correlated with CTCs and was found to be an unfavorable prognostic factor.Keywords: circulating tumor cells, tumor infiltrating lymphocytes, neoadjuvant chemotherapy, breast cancer, metastatic relapse

Abstract This study explored relationships between students’ attitudes toward science and their preferred versus actual experience of cooperative, constructivist-oriented, or direct instruction. The sample consisted of 1334 Chinese middle school students in physics and chemistry classrooms. Results showed that students report experiencing more direct instruction, very little constructivist-oriented instruction, and a moderate amount of cooperative instruction. Attitudes toward science were positively related to cooperative teaching strategies like group work in class or developing small-group projects. There was no significant effect of constructivist-oriented instruction or of direct instruction on students’ attitudes. Whereas previous studies demonstrated positive impacts of constructivist teaching on student understanding of science concepts, student attitude toward school science appears to be more related to social interaction or cooperation. Lack of any statistically significant differential effect from constructivist-oriented instruction might also be related to the overall low incidence of such instruction experienced by our sample.

Autoreactivity to myeloperoxidase (MPO) causes autoimmune vasculitis and severe glomerulonephritis. Here, Ooi et al. show that a Staphylococcus aureus plasmid encodes a peptide that is homologous to an immunodominant MPO epitope and induces anti-MPO autoimmunity and glomerulonephritis in mice.

Abstract Background Most studies on obesity surgery have measured renal function using the estimated GFR. However, due to the reduction of muscle mass, and therefore creatinine that accompanies weight loss, such measures can falsely suggest an improvement in renal function. To balance the risks of surgery versus any potential benefits on renal function, we need to be able to determine renal function using valid and reliable methodologies. In this pilot study we aimed to measure renal function in patients with CKD undergoing obesity surgery using the gold standard 51Cr-EDTA GFR clearance methodology which is independent of measures of muscle mass. Methods Nine consecutive obese patients with CKD underwent obesity surgery. Their renal function was assessed using 51Cr-EDTA GFR, cystatin C and serum creatinine as well as using eGFR equations including MDRD CKD Epi, Cockcroft Gault and CKD Epi cystatin before and 12 months after surgery. Results Renal function using the 51Cr-EDTA measured GFR did not change significantly after surgery. Similar results were obtained when Cystatin C, CKD Epi cystatin, CKD Epi cystatin creatinine and adjusted Cockcroft Gault Creatinine clearance methods were used. In contrast there were either trends or significant improvements in renal function measured using the MDRD and CKD Epi equations. Conclusions In this pilot study using the gold standard 51Cr-EDTA method we found stabilisation in renal function after obesity surgery. Until further definitive data emerge it is critical to balance the risk and benefits of surgery, especially if renal function may not improve as often as previously suggested. Trial registration ClinicalTrials.gov NCT01507350. Registered June 2011.

Current antiviral therapy can not cure chronic hepatitis B virus (HBV) infection or eliminate the risk of hepatocellular carcinoma. The licensed epidermal growth factor receptor (EGFR) inhibitors have found to inhibit hepatitis C virus replication via downregulation of signal transducers and activators of transcription 3 (STAT3) phosphorylation. Since STAT3 is also involved in HBV replication, we further studied the anti-HBV efficacy of the EGFR inhibitors in this study. HBV-transfected HepG2.2.15 cells and HBV-infected HepG2-NTCP cells were used as cell models, and HBV replication, the syntheses of viral antigens and the magnitude of the covalently closed circular DNA (cccDNA) reservoir were used as indictors to test the anti-HBV effects of EGFR inhibitors erlotinib and gefitinib. Erlotinib inhibited HBV replication with a half-maximal inhibitory concentration of 1.05 μM. It also reduced the syntheses of viral antigens at concentrations of 2.5 μM or higher. The underlying mechanism was possibly correlated with its inhibition on STAT3 phosphorylation via up-regulation of suppressor of cytokine signaling 3. Gefitinib also inhibited HBV replication and antigen syntheses. Compared with the commonest antiviral drug entecavir, these EGFR inhibitors additionally reduced hepatitis B e antigen and erlotinib also marginally affected the cccDNA reservoir in HBV-infected HepG2-NTCP cells. Interestingly, these promising anti-HBV effects were significantly enhanced by extension of treatment duration. In conclusion, EGFR inhibitors demonstrated a comprehensive anti-HBV potential, highlighting a new strategy to cure HBV infection and suggesting animal model-related studies or clinical try in the future.

J Justin Mulvey,1,2 Eric R Littmann,3 Lilan Ling,3 Michael R McDevitt,4,5 Eric G Pamer,3,5 David A Scheinberg1,3,5 1Department of Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; 2Department of Molecular Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 4Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 5Weill Cornell Medicine, New York, NY, USA Background: Amine-modified carbon nanotubes are drug delivery platforms with great potential that have not yet been applied in human clinical trials. Although modified nanotube vectors have the ability to carry multiple effectors, targeting agents, and even wrapped RNA, reports on unmodified, insoluble carbon nanotubes have highlighted inflammation in organs, including the intestine, with disruption of its resident microbiota. Disruption of the microbiota may allow for colonization by pathogenic bacteria, such as Clostridoidies difficile, stimulate immunoinfiltrates into the lamina propria or alter the absorption of therapeutics. Most proposed nanotube drugs are soluble, modified structures that are administered parenterally, and the majority of these soluble macromolecules are renally excreted; however, some are released into the bile, gaining access to the gastrointestinal tract. Methods: Using environmentally isolated BALB/C mice in oral and intraperitoneal dosing models, high dose (3.80 or 4.25 mg/week), we administered amine-modified, soluble carbon nanotubes for 7 or 8 weeks. The general health and weight of the mice were monitored weekly, and upon killing, the diversity and content of their colonic, cecal, and ileal microbiota were assessed using shotgun 16S DNA sequencing. Results and conclusion: We show that while oral administration at suprapharmacological doses modestly altered the α- and β-diversity of the mouse microbiome, these changes did not result in observed changes in clinical end points. Intraperitoneally-dosed mice exhibited none of the toxicities assessed. Keywords: SWCNT, toxicity, 16S sequencing, nanopharmaceuticals

Three global chemistry-transport models (CTM) are used to quantify the radiative forcing (RF) from aviation NOx emissions, and the resultant reductions in RF from coupling NOx to aerosols via heterogeneous chemistry. One of the models calculates the changes due to aviation black carbon (BC) and sulphate aerosols and their direct RF, as well as the BC indirect effect on cirrus cloudiness. The surface area density of sulphate aerosols is then passed to the other models to compare the resulting photochemical perturbations on NOx through heterogeneous chemical reactions. The perturbation on O3 and CH4 (via OH) is finally evaluated, considering both short- and long-term O3 responses. Ozone RF is calculated using the monthly averaged output of the three CTMs in two independent radiative transfer codes. According to the models, column ozone and CH4 lifetime changes due to coupled NOx/aerosol emissions are, on average, +0.56 Dobson Units (DU) and −1.1 months, respectively, for atmospheric conditions and aviation emissions representative of the year 2006, with an RF of +16.4 and −10.2 mW/m2 for O3 and CH4, respectively. Sulphate aerosol induced changes on ozone column and CH4 lifetime account for −0.028 DU and +0.04 months, respectively, with corresponding RFs of −0.63 and +0.36 mW/m2. Soot-cirrus forcing is calculated to be 4.9 mW/m2.

Surface ocean phosphate is commonly below the standard analytical detection limits, leading to an incomplete picture of the global variation and biogeochemical role of phosphate. A global compilation of phosphate measured using high-sensitivity methods revealed several previously unrecognized low-phosphate areas and clear regional differences. Both observational climatologies and Earth system models (ESMs) systematically overestimated surface phosphate. Furthermore, ESMs misrepresented the relationships between phosphate, phytoplankton biomass, and primary productivity. Atmospheric iron input and nitrogen fixation are known important controls on surface phosphate, but model simulations showed that differences in the iron-to-macronutrient ratio in the vertical nutrient supply and surface lateral transport are additional drivers of phosphate concentrations. Our study demonstrates the importance of accurately quantifying nutrients for understanding the regulation of ocean ecosystems and biogeochemistry now and under future climate conditions.

This study explored relationships between students' attitudes toward science and their preferred versus actual experience of cooperative, constructivist-oriented, or direct instruction. The sample consisted of 1334 Chinese middle school students in physics and chemistry classrooms. Results showed that students report experiencing more direct instruction, very little constructivist-oriented instruction, and a moderate amount of cooperative instruction. Attitudes toward science were positively related to cooperative teaching strategies like group work in class or developing small-group projects. There was no significant effect of constructivist-oriented instruction or of direct instruction on students' attitudes. Whereas previous studies demonstrated positive impacts of constructivist teaching on student understanding of science concepts, student attitude toward school science appears to be more related to social interaction or cooperation. Lack of any statistically significant differential effect from constructivist-oriented instruction might also be related to the overall low incidence of such instruction experienced by our sample.

BACKGROUND In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti--neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels. METHODS In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%). RESULTS Live birth at 32 weeks' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks' gestation or later and one fetus before fetal loss at 22 weeks and 5 days' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity. CONCLUSIONS Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.) [ABSTRACT FROM AUTHOR]

The activity patterns of grid cells form distinctively regular triangular lattices over the explored spatial environment and are largely invariant to visual stimuli, animal movement, and environment geometry. These neurons present numerous fascinating challenges to the curious (neuro)scientist: What are the circuit mechanisms responsible for creating spatially periodic activity patterns from the monotonic input-output responses of single neurons? How and why does the brain encode a local, nonperiodic variable—the allocentric position of the animal—with a periodic, nonlocal code? And, are grid cells truly specialized for spatial computations? Otherwise, what is their role in general cognition more broadly? We review efforts in uncovering the mechanisms and functional properties of grid cells, highlighting recent progress in the experimental validation of mechanistic grid cell models, and discuss the coding properties and functional advantages of the grid code as suggested by continuous attractor network models of grid cells. [ABSTRACT FROM AUTHOR]