Spaceborne InSAR for Monitoring and Health Assessment of Historical Architectures: The Tianjin Case Study (preprint)

Recently, interferometry synthetic aperture radar (InSAR) technology has shown its capabilities to monitor the displacement of natural processes with millimeter accuracy. Nevertheless, there is limited InSAR research on the health assessment of historical architectures. In this paper, we firstly proposed a possible methodology aiming at health assessment of historical architectures using space-borne SAR data. The proposed strategy consists of extracting building deformation from Persistent Scatterer Interferometry (PSI)results with spatial analysis between a geographical database and geocoded Persistent Scatterer (PS) and Inverse Distance Weighted (IDW) interpolation, deriving assessment parameters of both angular angle () and unequal subsidence velocity (), finally comparing them with alarm value for health assessment. This method has been applied to the Heping District of Tianjin (China), which contains many historical architectures, and two important examples (the Bohai Building and the China Theater) in the region were selected for detailed analysis, through the use of a high-resolution satellite dataset. For these two buildings, after extracting and analyzing deformation, both of the assessment parameters (and ) were acquired, and the good health conclusions were acquired in the case of values smaller than the alarm thresholds, which were validated by the similar conclusion from in situ leveling records. Finally, both the deformation mechanism of two architectures and health assessment ability with InSAR were analyzed in detail for further application.

COVID-19 and Mental Health in China: Effects of Personality and Demographics (preprint)

China was the first country affected by the COVID-19 virus and it reacted strongly in the first months of 2020. We present new evidence on the deterioration in mental health in China between 2018 and 2020. Using two waves of the China Family Panel Studies (CFPS) we can follow the same individuals pre and during the pandemic periods. We find clear evidence of a moderate level of mental health deterioration between 2018 and 2020. The prevalence of severe cases of depression, measured using an eight-item version of the common CES-D scale, increased from 6.33% in 2018 to 7.54% in 2020; quantifiable as around a 19% increase. This deterioration is higher for individuals who are subject to strict lockdowns, about 0.3 symptoms more on average, and it is stronger among those who already reported symptoms of depression in the 2018 wave of data. The effects we find are larger for individuals with more open personalities: one standard deviation of the Openness trait corresponds to 0.05 more symptoms, while more Neurotic individuals are rather surprisingly less affected. Younger cohorts and individuals with lower levels of education are more affected. Males seem slightly more affected than females, although this difference is statistically non-significant.

COVID-19 and Mental Health in China: Effects of Personality and Demographics (preprint)

China was the first country affected by the COVID-19 virus and it reacted strongly in the first months of 2020. This paper presents new evidence on the deterioration in mental health in China between 2018 and 2020. Using two waves of the China Family Panel Studies (CFPS) we can follow the same individuals pre and during the pandemic periods. We find clear evidence of a moderate level of mental health deterioration between 2018 and 2020. The prevalence of severe cases of depression, measured using an eight-item version of the common CES-D scale, increased from 6.33% in 2018 to 7.54% in 2020; quantifiable as around a 19% increase. This deterioration is higher for individuals who are subject to strict lockdowns, about 0.3 symptoms more on average, and it is stronger among those who already reported symptoms of depression in the 2018 wave of data. The effects we find are larger for individuals with more open personalities: one standard deviation of the Openness trait corresponds to 0.08 more symptoms, while more Neurotic individuals do not seem to be more affected. Younger cohorts and individuals with lower levels of education are more affected. Males seem slightly more affected than females, although this difference is statistically non-significant.

Research on the evolution of the Chinese urban biomedicine innovation network pattern: An analysis using multispatial scales

This paper addresses the spatial pattern of urban biomedicine innovation networks by separately using four scales, i.e., the national scale, interregional scale, urban agglomeration scale, and provincial scale, on the basis of Chinese biomedicine patent data from the incoPat global patent database (GPD) (2001–2020) and using the method of social network analysis (SNA). Through the research, it is found that (1) on the national scale, the Chinese biomedicine innovation network becomes denser from west to the east as its complexity continuously increases. Its spatial structure takes the form of a radial network pattern with Beijing and Shanghai as its centers. The COVID-19 pandemic has not had an obvious negative impact on this network at present. (2) On the interregional scale, the strength of interregional network ties is greater than that of intraregional network ties. The eastern, central and western biomedicine innovation networks appear to be heterogeneous networks with regional central cities as the cores. (3) At the urban agglomeration scale, the strength of intraurban-agglomeration network ties is greater than that of interurban-agglomeration network ties. The three major urban agglomerations have formed radial spatial patterns with central cities as the hubs. (4) At the provincial scale, the intraprovincial networks have poor connectivity and low internal ties strength, which manifest as core-periphery structures with the provincial capitals as centers. Our research conclusion helps to clarify the current accumulation of technology and offer guidance for the development of China's biomedicine industry.

Characterizing human collective behaviours of COVID-19 in Hong Kong (preprint)

People are likely to engage in collective behaviour online during extreme events, such as the COVID-19 crisis, to express their awareness, actions and concerns. Hong Kong has implemented stringent public health and social measures (PHSMs) to curb COVID-19 epidemic waves since the first COVID-19 case was confirmed on 22 January 2020. People are likely to engage in collective behaviour online during extreme events, such as the COVID-19 crisis, to express their awareness, actions and concerns. Here, we offer a framework to evaluate interactions among individuals emotions, perception, and online behaviours in Hong Kong during the first two waves (February to June 2020) and found a strong correlation between online behaviours of Google search and the real-time reproduction numbers. To validate the model output of risk perception, we conducted 10 rounds of cross-sectional telephone surveys from February 1 through June 20 in 2020 to quantify risk perception levels over time. Compared with the survey results, the estimates of the risk perception of individuals using our network-based mechanistic model capture 80% of the trend of people risk perception (individuals who worried about being infected) during the studied period. We may need to reinvigorate the public by engaging people as part of the solution to live their lives with reduced risk.

DiffDomain enables identification of structurally reorganized topologically associating domains (preprint)

Topologically associating domains (TADs) are critical structural units in three-dimensional genome organization of mammalian genome. Dynamic reorganizations of TADs between health and disease states are associated with transcription and other essential genome functions. However, computational methods that can identify reorganized TADs are still in the early stages of development. Here, we present DiffDomain, an algorithm leveraging high-dimensional random matrix theory to identify structurally reorganized TADs using chromatin contact maps. Method comparison using multiple real Hi-C datasets reveals that DiffDomain outperforms alternative methods for FPRs, TPRs, and identifying a new subtype of reorganized TADs. The robustness of DiffDomain and its biological applications are demonstrated by applying on Hi-C data from different cell types and disease states. Identified reorganized TADs are associated with structural variations and changes in CTCF binding sites and other epigenomic changes. By applying to a single-cell Hi-C data from mouse neuronal development, DiffDomain can identify reorganized TADs between cell types with reasonable reproducibility using pseudo-bulk Hi-C data from as few as 100 cells per condition. Moreover, DiffDomain reveals that TADs have clear differential cell-to-population variability and heterogeneous cell-to-cell variability. Therefore, DiffDomain is a statistically sound method for better comparative analysis of TADs using both Hi-C and single-cell Hi-C data.

SARS-CoV-2 and Plasmodium falciparum Co-Infection in a Returning Traveler

Since December 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has become a non-neglectable context for the whole healthcare system. Under the background of COVID-19, the detection and diagnosis of malaria cases are under challenge. Here, we reported a COVID-19 and malaria co-infection traveler who has a long living history in Cameroon. The case was administered with dihydroartemisinin and piperaquine tablets for malaria, Lopinavir and Ritonavir tablets, Arbidol, recombinant human interferon α-2b and Compound Maxing Yifei mixture for COVID-19, and Zolpidem Tartrate tablets, Diazepam, Paroxetine Hydrochloride tablets, Thymosin α1, and Lianhua Qinwen Jiaonang during the second hospitalization of the patient since the patient has a certain level of anxiety and insomnia with no evidence of inflammatory reactions. After being tested negative two times for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 48 h, the patient met China's COVID-19 discharge standards and was discharged with stable vital signs and mental state. Since most countries in the sub-Saharan region have a fragile health system, co-infection for both Plasmodium and SARS-CoV-2 may not be uncommon, and raise a challenge in diagnosis, treatment, and prevention for both diseases. We add to the literature on co-infection of P. falciparum malaria and COVID-19 and offer operational advice on diagnosis, prevention, and treatment for the co-infection.

Clustering Based on Continuous Hopfield Network

Clustering aims to group n data samples into k clusters. In this paper, we reformulate the clustering problem into an integer optimization problem and propose a recurrent neural network with n×k neurons to solve it. We prove the stability and convergence of the proposed recurrent neural network theoretically. Moreover, clustering experiments demonstrate that the proposed clustering algorithm based on the recurrent neural network can achieve the better clustering performance than existing clustering algorithms.

Long-Term Outcomes of COVID-19 Survivors and an Exploratory Analysis of Factors Associated with Sequela-Free Survival of Patients Treated at Leishenshan Hospital in Wuhan, China (preprint)

Objective: To determine key factors associated with sequela-free survival of patients with COVID-19.Design: Retrospective–prospective observational study.Setting: Leishenshan Hospital in Wuhan, China.Participants: Patients with COVID-19 admitted at Leishenshan Hospital in Wuhan, China between 15 February 2020 and 1 April 2020 and discharged.Main Outcomes: MeasuresSequela-free survival is defined as having none of the long-term sequelae measured with the Activity of Daily Living (ADL) Scale, Modified Medical Research Council (mMRC) Dyspnoea Scale, New York Heart Association (NYHA) classification, Self-rating Depression Scale (SDS), Carcinologic Handicap Index (CHI) and Modified Telephone Interview for Cognitive Status (TICS-M). Multivariable logistic regression was used to examine the key factors of sequela-free survival.ResultsThe follow-up period for the 464 patients was 10 August to 30 September 2020. Of these, 424 patients completed the assessment of all scales. 30.2% (128 of 424) were categorised as sequela-free at follow-up. The most common sequelae were psychosocial problems (254 [57.7%]), respiratory function abnormality (149 [32.6%]) and cardiac function abnormality (98 [21.5%]). Risk factors associated with COVID-19 sequelae were anaemia on admission, longer duration from the onset of symptoms to admission and advanced age, whereas anti-anaemia treatment was a protective factor against sequelae. A haemoglobin level of <113 g/l for female patients or <92 g/l for male patients at admission discriminated a higher risk of any COVID-19 sequelae.Conclusions: Only one third COVID-19 survivors were sequela-free. Anaemia on admission, longer duration from the onset of symptoms to admission and advanced age were the risk factors of any long-term sequela. Anti-anaemia treatment was associated with beneficial outcomes in COVID-19 survivors.Funding: This study was funded by grants to DSS from the National Natural Science Foundation of China (Nos.81771133, 81970995) (DSD grants), Shanghai Shenkang Hospital Development Center Founding (SHDC12017X11), Renji Hospital Clinical Innovation Foundation (PYMDT-007), Shanghai municipal Education Commission-Gaofeng Clinical Medicine Support (20191903), State Key Laboratory of Neuroscience(SKLN－201803), the National Natural Science Foundation of China (No.81701358) (DH grants), the Shanghai Municipal Commission of Health and Family Planning Funding (20184Y0205) (CYC grants) and Renji Hospital founding (RJZZ18-019) (LLH grants).Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Institutional Research Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiaotong University (ethics committee approval No. KY2020-34).

Inflammatory indexes and T lymphocyte subsets in patients with severe coronavirus disease 2019 pneumonia

Objective: To analyze inflammatory indicators and T lymphocyte subsets in severe patients with coronavirus disease-19 (COVID-19).

Long-Term Outcomes and Sequelae for 464 COVID-19 Patients Discharged from Leishenshan Hospital in Wuhan, China (preprint)

Background: While coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, millions of COVID-19 patients have recovered and returned to their families and work, although the long-term outcomes remain unknown.Methods: This retrospective–prospective study analysed data for COVID-19 patients discharged from Leishenshan Hospital in Wuhan, China. Long-term outcomes were measured by Activity of Daily Living (ADL) Scale, Modified Medical Research Council (mMRC) Dyspnoea Scale, New York Heart Association (NYHA) classification, Self-rating Depression Scale (SDS), Carcinologic Handicap Index (CHI), and Modified Telephone Interview for Cognitive Status (TICS-M). Multivariable logistic regression was used to examine the risk factors of long-term outcomes.Findings: The follow-up period for the 464 patients was August 10–September 30, 2020. The most common sequelae were psychosocial problems (254 [57·7%]), respiratory function abnormality (149 [32·6%]), and cardiac function abnormality (98 [21·5%]). Rare sequelae were ADL disability (61 [13·3%]); pain (55 [12·5%]); feeding difficulties (54 [12·2%]); dysphonia (46 [10·4%]); and hyposmia (27 [6·1%]), as well as impairment in hearing (40 [9·1%]), vison (37 [8·4%]), swallowing (30 [6·8%]), and gustation (18 [4·1%]). Almost all patients (98·2%) had normal cognitive function. Risk factors associated with ADL disability were advanced age, intensive care unit (ICU) stay, and cancer, which were also associated with respiratory function abnormality. Risk factors associated with cardiac function abnormality were long hospital stay, cancer, and respiratory diseases. Advanced age, ICU stay, and nonischemic heart diseases were associated with psychosocial problems. Compared with female patients, male patients had decreased odds of declined respiratory, cardiac function, depression and anxiety, and pain.Interpretation: Nearly normal ADL, moderate cardiopulmonary function and psychosocial issues, and minor sensory abnormalities were observed in COVID-19 survivors. Advanced age, ICU stay, cancer, and female sex were adverse risk factors in long-term sequelae. These data provide a generalisable estimate of long-term outcomes for COVID-19.Trial Registration: This study was registered in the ClinicalTrial.gov database (NCT04508712).Funding: National Natural Science Foundation of China, Shanghai Shenkang Hospital Development Center, Shanghai municipal Education Commission, State Key Laboratoy of Neuroscience, and Renji Hospital.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: This study was approved by the Institutional Research Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiaotong University (Ethical Committee approval number: KY2020-34). Oral consent was acquired from patients or from their immediate family members in cases of communication disorder or death.

Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate (preprint)

The ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8- to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.

COVID-19 risk haplogroups differ between populations, deviate from Neanderthal haplotypes and compromise risk assessment in non-Europeans (preprint)

Recent genome wide association studies (GWAS) have identified genetic risk factors for developing severe COVID-19 symptoms. The studies reported a 1bp insertion rs11385942 on chromosome 3 and furthermore two single nucleotide variants (SNVs) rs35044562 and rs67959919, all three correlated with each other. Zeberg and Paabo subsequently traced them back to Neanderthal origin. They found that a 49.4 kb genomic region including the risk allele of rs35044562 is inherited from Neanderthals of Vindija in Croatia. Here we add a differently focused evaluation of this major genetic risk factor to these recent analyses. We show that (i) COVID-19-related genetic factors of Neanderthals deviate from those of modern humans and that (ii) they differ among world-wide human populations, which compromises risk prediction in non-Europeans. Currently, caution is thus advised in the genetic risk assessment of non-Europeans during this world-wide COVID-19 pandemic.

Computational prediction of SARS-CoV-2 encoded miRNAs and their putative host targets (preprint)

Background: Over the past two decades, there has been a continued research on the role of small non-coding RNAs including microRNAs (miRNAs) in various diseases. Studies have shown that viruses modulate the host cellular machinery and hijack its metabolic and immune signaling pathways by miRNA mediated gene silencing. Given the immensity of coronavirus disease 19 (COVID-19) pandemic and the strong association of viral encoded miRNAs with their pathogenesis, it is important to study Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) miRNAs. Results: To address this unexplored area, we identified 8 putative novel miRNAs from SARS-CoV-2 genome and explored their possible human gene targets. A significant proportion of these targets populated key immune and metabolic pathways such as MAPK signaling pathway, maturity-onset diabetes of the young, Insulin signaling pathway, endocytosis, RNA transport, TGF-{beta} signaling pathway, to name a few. The data from this work is backed up by recently reported high-throughput transcriptomics datasets obtains from SARS-CoV-2 infected samples. Analysis of these datasets reveal that a significant proportion of the target human genes were down-regulated upon SARS-CoV-2 infection. Conclusions: The current study brings to light probable host metabolic and immune pathways susceptible to viral miRNA mediated silencing in a SARS-CoV-2 infection, and discusses its effects on the host pathophysiology.

Antiviral activity of plant juices and green tea against SARS-CoV-2 and influenza virus in vitro (preprint)

Respiratory viruses initially infect the naso- and oropharyngeal regions, where they amplify, cause symptoms and may also be transmitted to new hosts. Preventing initial infection or reducing viral loads upon infection might soothe symptoms, prevent dissemination into the lower airways, or transmission to the next individual. We here analyzed the potential of plant derived products to inactivate SARS-CoV-2 and influenza virus. We found that black chokeberry (Aronia melanocarpa) juice, pomegranate (Punica granatum) juice, and green tea (Camellia sinensis) have virucidal activity against both viruses, suggesting that oral rinsing may reduce viral loads in the oral cavity thereby lowering virus transmission.

Potential Opportunity Of Antisense Therapy Of COVID-19 on an in vitro model (preprint)

Data on potential effectiveness and prospects of treatment of new coronavirus infection of COVID-19 caused by virus SARS-CoV-2 with the help of antisense oligonucleotides acting against RNA of virus on an in vitro model are given. The ability of antisense oligonucleotides to suppress viral replication in diseases caused by coronaviruses using the example of SARS and MERS is shown. The identity of the initial regulatory section of RNA of various coronaviruses was found within 50 - 100 nucleotides from the 5'-end, which allows using antisense suppression of this RNA fragment. A new RNA fragment of the virus present in all samples of coronovirus SARS-CoV-2 has been identified, the suppression of which with the help of an antisense oligonucleotide can be effective in the treatment of COVID-19. The study of the synthesized antisense oligonucleotide 5`-AGCCGAGTGACAGCC ACACAG, complementary to the selected virus RNA sequence, was carried out. The low toxicity of the preparations of this group in the cell culture study and the ability to reduce viral load at high doses according to real time-PCR data are shown. The cytopathogenic dose exceeds 2 mg/ml. At a dosage of 1 mg/ml, viral replication is reduced by 5 - 13 times. Conclusions are made about the prospects of this direction and the feasibility of using the inhalation way of drug administration into the body.

Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design (preprint)

Having claimed over 1 million lives worldwide to date, the ongoing COVID-19 pandemic has created one of the biggest challenges to develop an effective drug to treat infected patients. Among all the proteins expressed by the virus, RNA helicase is a fundamental protein for viral replication, and it is highly conserved among the coronaviridae family. To date, there is no high-resolution structure of helicase bound with ATP and RNA. We present here structural insights and molecular dynamics (MD) simulation results of the SARS-CoV-2 RNA helicase both in its apo form and in complex with its natural substrates. Our structural information of the catalytically competent helicase complex provides valuable insights for the mechanism and function of this enzyme at the atomic level, a key to develop specific inhibitors for this potential COVID-19 drug target.

A High-Coverage SARS-CoV-2 Genome Sequence Acquired by Target Capture Sequencing (preprint)

This manuscript is based on the method we developed urgently to deal with the research requirement in the conflict between achieving a complete genome sequence for the evolutionary history of SARS-CoV-2 study and the low viral RNA concentration. Here, in this manuscript, we developed a set of SARS-CoV-2 enrichment probes to increase the sensitivity of sequence-based virus detection and characterization via obtaining the comprehensive genome sequence. Following the CDC health and safety guidelines, we test the concept using the culturing supernatant contain SARS-CoV-2 particles, and its full-length sequence was used for further analysis. The fraction of SARS-CoV-2 endogenous DNA was 93.47% with Cluster Factor about 1.1, which demonstrate that the numbers of mapped reads to SARS-CoV-2 reference sequence significantly increased, compared to metagenomic sequencing technology, following SARS-CoV-2 probe enrichment. Moreover, based on the high-quality sequence, we discussed the heterozygosity and viral expression during replication of coronavirus, and its phylogenetic relationship with other selected high-quality samples from The Genome Variation Map (GVM) (on 2020/03/22). We believe this manuscript is valuable for all the researchers who are interested in using clinical warp samples to obtain the high coverage of SARS-CoV-2 genome sequence with a relatively low concentration of viral particles. This would allow the clinician to correlate the diagnostic data with molecular monitoring in viral evolutional, the most importantly, to track the functional mutation of SARS-CoV-2.