In addition, short-term physical activity may induce changes in neurophysiological functioning , although this evidence showed limited robustness. No meta-analytic evidence was found for positive effects on brain structure. The results underline the importance of physical activity for brain development in children.This study is the first to systematically review and quantify the effects of physical activity on brain structure and neurophysiological functioning in children. Electronic data bases were searched for relevant studies. Studies that met the following criteria were included: (1) used an RCT or cross-over design, (2) examined the effects of physical activity on brain structure and/or neurophysiological functioning, (3) included children (5–12 years old) (4) included a control group (RCTs) or control condition . A total of 26 and 20 studies were included in the systematic review and meta-analysis, respectively, representing and accompanying 973 and 782 unique children. Main analyses were separated for short-term and long-term physical activity and for effects on brain structure and neurophysiological functioning with a distinction between children from healthy and clinical populations. We found evidence for significant beneficial effects of long-term physical activity on neurophysiological functioning ( A growiThe evident lack of physical activity among children is especially worrisome in the light of existing evidence on beneficial effects of physical activity on brain development . The benFindings from fundamental neuroscience have identified several pathways through which physical activity may act on brain structure and neurophysiological functioning. A single bout of physical activity  has been shown to directly enhance cerebral blood flow  and to tIn line with this evidence, previous studies in children have revealed associations between physical fitness - which is considered as an indirect measure of long-term physical activity  - and brThe current study aims to provide an overview of all available RCTs and cross-over trials testing the causal effects of physical activity on brain structure and neurophysiological functioning in children. Earlier reviews of studies on this topic did not use a systematic approach , or conc22.1This systematic review and meta-analysis included empirical studies that: (1) used an RCT or cross-over design, (2) examined the effects of moderate to vigorous physical activity on brain structure and/or neurophysiological functioning, where moderate to vigorous physical activity was defined as physical activity that requires a moderate amount of effort and noticeably accelerates the heart rate , (3) incphysical exercise and children, and Brain Imaging or electroencephalography and their equivalents . The reference lists of all included articles were manually searched for additional relevant articles.The electronic databases PubMed, Embase, SportDiscus and Cochrane Library were searched combining search terms (MeSH and thesaurus terms) related to This systematic review and meta-analysis was performed according to PRISMA guidelines . The art2.2The following data were extracted from the included articles: (1) sample characteristics ; (2) intervention or control features ; (3) outcome measures .2.3The quality of included studies was independently assessed by two authors (AM + GV) using the Cochrane Collaboration’s tool for risk of bias in randomized trials . This to2.4Statistical analysis was performed using Comprehensive Meta-Analysis Software (CMA) - version 3 . Meta-ank = 3). Increased fMRI activation  during cognitive tasks (active-state fMRI) could be interpreted as a reflection of greater flexible processing, but decreased activation could also be interpreted as improved learning and an efficiency effect . Beneficial effects of physical activity on outcome measures  were expressed as positive effect sizes. Interpretation of neuroimaging measures is not always straightforward . Therefoy effect . The effd = 0.2−0.5), moderate (d = 0.5−0.7) and large effect sizes . The leave-one-out method was used to check the influence of single studies by iteratively removing each individual study from the calculation of the meta-analytic effect sizes. We explored whether meta-analytic effects where disproportionately driven by a single study by visual interpretation of the leave-one-out forest plots in combination with the statistical results , where all p-values below .05 are plotted on the x-axis and the percentage of studies yielding these p-values are plotted on the y-axis. According to n . The expected number was based on the estimated overall effect-size and the power to detect this effect in the individual studies. All tests of significance were two-sided with α = .05.Heterogeneity of eﬀ ;ect sizes was assessed using the ectively . As the included . Meta-an results . P-curve results . P-curveing to n  and the ing to n . Rosenthificance  was used3k = 26), followed by the meta-analytic findings (k = 20). We first distinguish between studies addressing acute and chronic effects. Further distinction is made between (1) studies focusing on brain structure and neurophysiological functioning and (2) studies in healthy and clinical samples. The main study characteristics are presented in This results section provides a narrative description of the findings of all studies . All studies in healthy children showed physical activity-induced acute effects on neurophysiological functioning. Results indicated improved neurophysiological functioning during rest  and all these studies indicated physical activity-induced beneficial effects. Results indicate greater allocation of attentional resources toward the target stimulus  described the chronic effects on brain structure in which one study included a healthy population and three studies included a clinical population . All studies used Diffusion Tensor Imaging, which is an MRI-based measure of white matter integrity (WMI). The study that assessed healthy children observed greater WMI in the genu of the corpus collosum following long-term physical activity compared to the control group . Five studies in healthy children showed physical activity-induced effects on neurophysiological functioning. Results indicated improved resting-state attention . One study investigated the chronic effects of physical activity in children with ADHD and found an improved state of alertness after long-term physical activity as measured by EEG. This result was not accompanied by improved cognitive task performance . Further distinction between children from healthy samples and clinical samples revealed no significant meta-analytic effects in these subgroups.Results of the meta-analysis are displayed in d = 0.39, p < 0.001).Analyses making a further distinction between children from healthy and clinical samples revealed a significant small effect for healthy children  and a large effect for children from clinical populations .No significant meta-analytic effects were found for the chronic effects of physical activity on brain structure. Meta-analyses of studies that observed the chronic effects of physical activity on neurophysiological function revealed a significant small-sized positive effect of physical activity . When we made a distinction between acute and chronic effects, meta-analytic effects could only be determined for acute effects, for which a significant small-sized effect was found . In further distinctions between healthy and clinical samples, meta-analytic effect sizes could only be determined for healthy samples. Meta-analyses revealed significant small-sized effect on P3 amplitude for acute effects of physical activity for healthy samples . For P3 latency, meta-analytic effects could only be determined for all studies together, acute effects of physical activity and the acute effects of physical activity for healthy children. No significant effects were observed.We estimated separate meta-analytic effects for specific outcome measures that were available in at least two studies. We found a significant small-sized effect of physical activity on P3 amplitude . The sensitivity analysis could not be executed for the effect size describing chronic effects on neurophysiological functioning in clinical populations, because the number of available studies dropped below the minimum of two studies required for meta-analysis.Lastly, we performed a sensitivity analysis to explore the possibility that our strategy to value the physical activity-induced changes in brain activation in the active-state fMRI studies as beneficial, influenced our results . We reran all analyses after excluding the results of all three active-state fMRI studies , replica3.5The heterogeneity ranged from 0 to 69%, with only high values of heterogeneity for the meta-analysis effect describing the chronic effects of physical activity on brain structure. The leave-one-out analysis revealed that none of the individual studies had an extreme influence on the meta-analytic effect sizes  for acute effects of physical activity on neurophysiological functioning , chronic effects on neurophysiological function  and acute effects on P3 amplitude . These findings indicate stability of the meta-analytic effect size estimations. For the meta-analytic effect size of acute effects of physical activity on neurophysiological functioning, it should be noted that the p-values in the leave-one-out analysis did not consistently meet conventional levels of significance (p = .004–.119). This possibly reflects heterogeneity among study outcomes underlying the effect size, and warrants caution when interpreting this result.ps < .01). P-curve analysis could not be executed for the significant chronic effects on neurophysiological function in clinical populations and for acute effects on P3 amplitude in healthy children, because the number of studies with significant effects was too low. See Appendix, Figs. A2–A5 for the p-curve plots. Analysis of Egger funnel plot asymmetry revealed no evidence for publication bias (ps = .19–.91). Fail-safe N values indicated that the reported meta-analytic effects were not robust against influence of publication bias. However, the number of positive findings is as expected from the power of the retrieved studies, reflecting no evidence of excess significance for all meta-analytic results .P-curve analysis for all significant meta-analytic effects  indicated the presence of evidential value  that assessed the effects of physical activity on brain structure, that also assessed heterogeneous samples of healthy, obese and deaf children. It is unknown whether these groups respond comparably to physical activity. If sample-specific mechanisms may contribute the effects of physical activity, this may have contributed to heterogeneity in the combined effect size.The current study differentiated between acute effects resulting from a single bout of physical activity  and chronic effects resulting from longer periods of continuous physical activity . Meta-analysis revealed support for both acute and chronic effects on neurophysiological functioning, while no evidence for effects on brain structure was found. This observed discrepancy is primarily accounted for by a very limited number of studies , rather than changes in the processing time (P3 latency). This is in line with the results of a recent systematic review indicating that physical activity and cardiorespiratory fitness are associated with P3b modulation during cognitive control and attention tasks . AlthougThe current review and meta-analysis made a distinction between studies in healthy and clinical samples of children. Although we found no evidence for differences between healthy and clinical populations in the effect magnitude of physical activity, the possibility exists that the dominant mechanisms of action underlying the effects of physical activity on brain structure and neurophysiological function (partly) depend on health status and on the pathophysiology of the disorders studied . For exaWe have taken all efforts to carefully interpret the valence of meta-analytic effects, using a sequential decision chain for interpretation of the studies’ individual effect sizes. Nevertheless, the interpretation of changes in fMRI derived measures is a challenging matter . We performed a sensitivity analysis by repeating our analyses after excluding outcome measures with ambiguous interpretation (i.e. three fMRI studies). Only when the original findings were replicated by the sensitivity analysis, we also provided conclusions about the valence of the observed effects . This sensitivity analysis replicated the meta-analytic effect concerning the chronic effect of physical activity on neurophysiological functioning, indicating that the evidence for neurophysiological changes in response to physical activity indeed involve beneficial effects. Not all meta-analytic results were replicated by sensitivity analysis. The acute effects of physical activity on neurophysiological function were no longer significant without the three active state fMRI studies. The difference between results of the original analysis and the sensitivity analysis can be explained by both a loss of statistical power and a meaningful difference in the effect size. In both cases, the results concerning the acute effects of physical activity, only support that physical activity may induce changes in neurophysiological functioning. The valence of these effects remains unknown. Nevertheless, in the context of the evident benefits of physical activity for the physical health , it may The results of the systematic review provide an overview of all findings on cognitive functioning parallel to the observed changes in neural mechanisms. Almost all included studies in the systematic review reported on cognitive performance along with neuroimaging measures . Results showed that co-occurring improvement in at least one measurement of cognitive or academic performance was observed in half of the studies. More specifically, 55 % (6/11) of the studies that observed acute effects of physical activity on neurophysiological function and 42 % (5/12) of the studies that observed chronic effects on neurophysiological function reported co-occurring improvement. These percentages are in line with results of recent systematic reviews and meta-analyses concerning the effects of physical activity on cognition and academic performance in children, in which small to moderate effects were found . AnotherThis systematic review and meta-analysis has some limitations. Some meta-analytic effect sizes were based on a relatively small numbers of studies, limiting statistical power and representativeness of evidence. Despite our effort to contact authors to provide additional information for inclusion in our meta-analysis, the proportion of missing data was relatively high . It should also be noted that only five of the included studies (20 %) were preregistered trials. We used three different approaches to assess presence of and/or robustness to publication bias . The findings indicate limited robustness of the reported effect sizes, but we did not find any evidence for the influence of publication bias on the meta-analytic findings. Nevertheless, the results warrant caution in the interpretation of the obtained effect sizes. However, although evidential value could not be analyzed in two effect sizes  and some instability has been noticed in the robustness of a single meta-analytic result , comprehensive bias analysis on all other significant meta-analytic effects provided no lack of evidential value or limited robustness. Although the majority of studies (81 %) did not adopt proper procedures for blinding of intervention delivery and outcome assessment and almost half of the studies (42 %) included a sample that was not representative for the targeted population, the overall risk of bias was generally low among the included studies.The current systematic review and meta-analysis shows that long-term physical activity leads to beneficial changes in neurophysiological function. In addition, short-term physical activity may induce changes in neurophysiological functioning, although this evidence showed limited robustness. Furthermore, there is preliminary evidence indicating that physical activity could be a useful intervention to promote neurophysiological functioning (and cognitive functioning) in diverse pediatric populations. However, more research is required to gain knowledge on the effects of physical activity in such specific populations. High-quality intervention studies should include both neuroimaging techniques and behavioral outcomes. Given the signs of limited robustness of the available evidence, future studies should also consider pre-registration to limit the influence of publication bias in this field. Nevertheless, to this date, the current study presents an overview of the best available evidence regarding the causal effects of physical activity on brain structure and neurophysiological functioning in children and underlines the importance of physical activity for brain development during childhood.All authors have no conflicts of interest relevant to this article to disclose.


One of the most commonly used rodent models of acute lung inflammation and ARDS is administration of lipopolysaccharide (LPS), either into the airways  or systemically . This narrative review discusses the dynamics of important pathophysiological pathways contributing to the physiological response to LPS-induced injury. Pathophysiological pathways of LPS-induced lung injury are not only influenced by the type of the primary insult  and presence of additional stimuli , but also by time. As such, findings in animal models of LPS-induced lung injury may depend on the time point at which samples are obtained and physiological data are captured. This review summarizes the current evidence and highlights uncertainties on the molecular dynamics of LPS-induced lung injury in rodent models, encouraging researchers to take accurate timing of LPS-induced injury into account when designing experimental trials.Acute respiratory distress syndrome (ARDS) is a common disease entity in critical care medicine and is still associated with a high mortality. Because of the heterogeneous character of ARDS, animal models are an insturment to study pathology in relatively standardized conditions. Rodent models can bridge the gap from  Acute respiratory distress syndrome (ARDS) is a common but often under-recognized and under-treated disease in critical care medicine and is still associated with high morbidity and mortality . ARDS caThe purpose of animal models is to mimic human disease. An ideal animal model of ARDS should reproduce all pathophysiological features of human ARDS . HoweverLPS is a part of the outer membrane of Gram-negative bacteria and can be administered into the airways  and systemically (extra-pulmonary insult) . The timLPS-induced lung injury is one of the most commonly used rodent models for ARDS  and was Experimental evidence proposed that different pathophysiological pathways are activated during pulmonary and extra-pulmonary LPS challenge, especially during the early phase of disease progression . Direct Pathophysiological, histological, and morphological differences found in pulmonary and extra-pulmonary ARDS may influence the response to pharmacological agents, mechanical ventilation, and positioning. Some studies have reported a modulation of the inflammatory process in ARDS in response to pharmacological therapies such as dasatinib  and cortThe cellular response to LPS is initiated by binding of LPS to the extracellular binding proteins LBP (LPS binding protein), CD14 and MD-2; this facilitates the binding of LPS to its main receptor – toll-like receptor 4 (TLR-4). Intracellular adaptor proteins  bind to the TLR-4 receptor and activate various intracellular signaling cascades involving kinases like ERK1/2  and p38, which regulate the expression of cytokines with pro-inflammatory properties like TNF-α  by activation of the NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway . The comExperimental studies revealed that LPS challenge affects pulmonary expression of signaling molecules over time . For TLRThere is also evidence of differential activation of intracellular signal transduction pathways after LPS challenge. A kinetic study in mice described that pulmonary mRNA expression of the TLR-4 adaptor protein MyD88 was rapidly increased to maximal levels at 3 h after intranasal LPS challenge, followed by a decline to basal levels at 24 h . At the Further downstream in the LPS-TLR-4 signaling cascade, transnasal LPS challenge was shown to affect DNA binding activity of NFkB over time. Pulmonary NFkB binding activity increased rapidly over the first hour after LPS challenge and slowly declined over 6 h, being resolved at the end of a 24-h period . AccordiIt has been shown that LPS elicits strong innate immune responses by activating various intracellular signaling pathways. In this regard, it is important that not all signaling molecules are being activated at the same time and not all signaling pathways are being activated for the same duration . For insIn spite of the insights gained from the kinetic studies discussed here, only specific, limited time points after LPS challenge were examined. It may be possible that the duration of molecular responses is underestimated or a secondary phase of activation remains unnoticed. Most likely, different signaling molecules will be present in lung tissue at different time points after LPS challenge. Consequently, findings in rodent models of LPS-induced lung injury may depend on the time point at which samples are obtained and corresponding physiological data are captured.In vitro studies using human alveolar epithelial cell line A549, and the human tracheobronchial epithelial cell lines BEAS-2B, showed the presence of TLRs at mRNA level, specifically TLR1–6 but not directly the TLR-4  or long period (48 h), yet is able to activate a TLR-4-dependent signaling pathway in this pulmonary epithelial cell . As prevnot CD14 . Similarnot CD14 , which cnot CD14 .Lungs of ARDS patients are not only affected by the primary disease  but also by therapeutic modalities used for supportive care . Accordingly, mechanical ventilation can be considered as a “second hit” in ARDS patients . This clin vitro studies should be performed to evaluate novel LPS-binding proteins in alveolar epithelial cells and further elucidate distinct pathways in response to LPS challenge. While the early response to LPS challenge is rather well characterized, there are few data on the late phase of LPS response.Despite advances in understanding of dynamics of LPS-induced lung injury, additional -pulmonary ARDS. Pathways of LPS-induced lung injury are not only affected by the type of the primary insult and the presence of additional stimuli but also by time. All these contributing factors should be taken into account when choosing a rodent model for developing and/or evaluating interventions that target specific pathophysiological pathways of LPS-induced lung injury. In this way, the therapeutic efficacy may be optimized and the translation of promising treatment strategies into patient care may be improved.This review describes the molecular mechanisms that contribute to lung injury in rodent models of LPS-induced organ injury mimicking either pulmonary or extraHD wrote the initial draft of the manuscript. MH composed the figures. All authors reviewed the available literature and summarized the data and reviewed and revised the final draft of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


With the advent of omics technologies, tremendous progress has been made in understanding the signaling pathways in normal and disease states across different species. Multi-omics approaches can be categorized into two groups: molecular profiling (MPro) and molecular perturbation (MPer) .WGS approaches have been extensively used to unravel the different types of genomic alterations in cancer and facilitate understanding of the mutational landscape of cancer genomes. Using WGS, Dr. Bandapalli's group identified candidate predisposing genes in families with a reported recurrence of Hodgkin-lymphoma (HL), a lymphoproliferative malignancy of B-cell origin. These variants were prioritized using an in-house pipeline “FCVPPv2.” The authors used this pipeline along with gene/variant panels based on cancer predisposing genes and variants prioritized in the largest familial HL cohort study reported to date, to identify high penetrance germline variants in the HL families. Furthermore, pathway and network analyses of these variants have provided additional molecular cues relevant to the molecular pathogenesis of HL that may aid the development of targeted therapy and the screening of individuals who are at risk of developing HL .MicroRNAs play a key role(s) in regulating gene expression via either degradation of a transcript or the inhibition of its translation. Dr. Skoblov's group presents initial insights into the complexity of human microRNA-mRNA interactions. They performed a comprehensive computational analysis on HEK293 and Huh7.5 datasets and reported interesting features of human mRNA interactome, along with more than 46,000 experimentally confirmed mRNA-miRNA duplex regions. As part of this study, they also developed a web-based tool, publicly available at Zhang et al.).In addition, Dr. Fang's group performed a comprehensive analysis of hsa-let-7i-5p miRNA in normal and pathogenic fibroblasts and studied its role ranging from controlling cellular phenotype to molecular signaling particularly TGF-β signaling .In a transcriptome study, Dr. Evelo's group performed computational analysis on transcriptomic data derived from cattle breeds with different intramuscular fat deposition to identify pathways that define marbling in beef cattle. A total of 17 pathways were significantly dysregulated between well-marbled vs. lean-marbled beef including MAPK and insulin signaling, and immune response associated pathways .Dr. Guan's group carried out a genome-wide analysis in gastric cancer and identified 548 and 2,399 differentially methylated sites and lncRNAs, respectively. The lncRNAs were able to discriminate between normal vs. cancerous samples of gastric origin .Dr. Jolly's group carried out a comprehensive and comparative analysis of methods utilizing different transcriptomics signatures to quantify the status of EMT—a cell biological process involved in cancer metastasis and chemoresistance. They showed that these methods exhibited a concordance among themselves in quantifying the extent of EMT in a given sample and that tumor cells can undergo varying degrees of EMT across tumor types. While any of the three methods can capture the generic trend in the EMT status of a given cell (or population), the multinomial logistic regression EMT scoring method has an additional advantage of being able to predict from the transcriptomic signature of a population, whether it is comprised of “pure” single hybrid E/M cells at the single-cell level, or an ensemble of E and M cell subpopulations .Another study, by Dr. Imhof's group in the context of hemolytic disorders, described a new ontology and knowledge graph “HemeKG,” which is publicly available at Lin et al.).In a study on the brain disorder Schizophrenia, Dr. Lane's group used an ensemble boosting predictive framework along with random undersampling, to assess the status of schizophrenia in the population of Taiwan by examining the levels of D-amino acid oxidase protein and its interaction partner, the D-amino acid oxidase activator, in the N-methyl-D-Aspartate receptor pathway, as well as by using melatonin levels in the tryptophan catabolic pathway. They also evaluated the performance of the ensemble boosting algorithm and compared it with other widely used machine learning algorithms, including support vector machine, and multi-layer feedforward neural networks. Notably, they showed that it performs better in distinguishing schizophrenia patients from healthy controls .Using an integrative approach, Dr. Domingo-Fernandez and his group demonstrated that the choice of pathway database could impact the results of statistical enrichment analysis and predictive modeling. They also developed an integrative pathway resource called “MPath” which showed that using multiple pathway databases or integrated resources could provide more biologically consistent results and improved prediction performances, as opposed to using equivalent pathways from different databases  strongly linked to OC. A large majority of Frizzled receptors including FZD6 and FZD8 were involved in the ß-catenin canonical signaling pathway .Dr. Zayed's group employed an integrative and systematic bioinformatics in treating ovarian cancer, and identified not only the DEGs involved in the cell cycle, but also the hub genes including core genes .In a study on the autoimmune disease SLE, Dr. Zayed's group used a high-throughput transcriptomics platform to identify dysregulated signaling pathways. They found that four genes including M. tuberculosis, Dr. Gupta's group studied Rv1915/ICL2a protein as there has been difficulty in harvesting the soluble protein. They overcome this by expression of C-terminal truncated Rv1915/ICL2a in the heterologous host E. coli BL21 (DE3) .In a study on This collective effort brings together studies covering models from prokaryotic to eukaryotic organisms using different omics approaches to delineate either signaling or molecules directly or indirectly related to signaling in cancer and/or other diseases and aberrant conditions.JS coordinated the Research Topic. MKK coordinated the editorial. JS, LB, SK, and MKK contributed to the development of the Research Topic, suggested and invited the participants, and helped with the peer review process. All authors have approved the final version of the editorial.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background: The COVID-19 pandemic has caused considerable morbidity, mortality and disruption to people’s lives around the world. There are concerns that rates of suicide and suicidal behaviour may rise during and in its aftermath. Our living systematic review synthesises findings from emerging literature on incidence and prevalence of suicidal behaviour as well as suicide prevention efforts in relation to COVID-19, with this iteration synthesising relevant evidence up to 19th October 2020.Method:  Automated daily searches feed into a web-based database with screening and data extraction functionalities. Eligibility criteria include incidence/prevalence of suicidal behaviour, exposure-outcome relationships and effects of interventions in relation to the COVID-19 pandemic. Outcomes of interest are suicide, self-harm or attempted suicide and suicidal thoughts. No restrictions are placed on language or study type, except for single-person case reports. We exclude one-off cross-sectional studies without either pre-pandemic measures or comparisons of COVID-19 positive vs. unaffected individuals.Results: Searches identified 6,226 articles. Seventy-eight articles met our inclusion criteria. We identified a further 64 relevant cross-sectional studies that did not meet our revised inclusion criteria. Thirty-four articles were not peer-reviewed . All articles were based on observational studies. There was no consistent evidence of a rise in suicide but many studies noted adverse economic effects were evolving. There was evidence of a rise in community distress, fall in hospital presentation for suicidal behaviour and early evidence of an increased frequency of suicidal thoughts in those who had become infected with COVID-19.Conclusions:  Research evidence of the impact of COVID-19 on suicidal behaviour is accumulating rapidly. This living review provides a regular synthesis of the most up-to-date research evidence to guide public health and clinical policy to mitigate the impact of COVID-19 on suicide risk as the longer term impacts of the pandemic on suicide risk are researched. The COVID-19 pandemic is causing widespread societal disruption, morbidity and loss of life globally. By the end of December 2020 over 85 million people had been infected and over 1.8 million had died . There aThere are concerns that suicide and self-harm rates may rise during and in the aftermath of the pandemic  and TaiwThe current context is, however, very different from previous epidemics and pandemics. The 2003 SARS epidemic was restricted to relatively few countries. Furthermore, during the 100-year period since the 1918–20 influenza pandemic, global and national health systems have improved, international travel and the speed of communication of information (and disinformation) have increased, antibiotics are available to treat secondary infection, and national economies have become globally inter-dependent. The availability of the internet and technological advancement has made it far easier for people to communicate and engage in home working and home schooling. However, there are marked social inequalities in relation to access to technology and ability to stay safe and continue to work, within and between countries. Public health policies and responses, and the degree of access to technology to facilitate online clinical assessments and treatments differ greatly between countries.Key concerns in relation to suicide prevention during the pandemic include: encouraging help-seeking in those with suicidal thoughts and behaviours e.g. people who have attempted suicide may not attend hospitals because they are worried about contracting COVID-19 or being a burden on the healthcare system at this time; uncertainty regarding how best to assess and support people with suicidal thoughts and behaviours, whilst maintaining physical distancing and addressing any impacts of remote consultation; diminished access to community-based support; exposure to traumatic experiences; long term effect of infection with the virus on mental health  and dometh June 2020. This paper reports the second set of findings from the review, based on relevant articles identified up to 19th October 2020.In the context of the COVID-19 pandemic there is a rapidly expanding evidence base on its impact on suicide rates, and how best to mitigate such effects. It is therefore important that the best available knowledge is made rapidly available to policymakers, public health specialists and clinicians. To facilitate this, we are conducting a living systematic review focusing on incidence and prevention of suicide and self-harm in relation to COVID-19. Living systematic reviews are high-quality, up-to-date online summaries of research that are regularly updated, using efficient, often semi-automated, systems of production . An overview of our living review process is provided inprotocol  or attempted suicide 3.Suicidal thoughts/ideationStudies must address one of the following research questions:(i) What is the prevalence/incidence?Prevalence/incidence of each outcome during pandemic (including modelling studies)(ii) What is the comparative prevalence/incidence?Prevalence/incidence of each outcome during pandemic vs not during pandemic(iii) What are the effects of interventions?Effects of public health measures to combat COVID-19  on each outcomeEffects of changed and new approaches to clinical management of (perceived) elevated risk of self-harm or suicide risk on each outcome (any type of intervention is relevant)(iv) What are the effects of other exposures?Impact of media portrayal on each outcome and misinformation attributed to the pandemic on each outcomeImpact of bereavement from COVID-19 on each outcomeImpact of any COVID-19 related behaviour changes  on each outcomeImpact of COVID-19-related workload on crisis lines on each outcomeImpact of infection with COVID-19 (self or family member) on each outcomeImpact of changes in availability of analgesics, firearms and pesticides on each outcome Impact of COVID-19 related socio-economic exposures  on each outcomeImpact on health and social care professionals: the stigma of working with COVID-19 patients or the (perceived) risk of infection/being a ‘carrier’, as well as work-related stress on each outcomeImpact of changes in/reduced intensity of treatment for patients with mental health conditions, in particular those with severe psychiatric disorders.Impact of any other relevant exposure on our outcomes of interest.We included any qualitative research addressing perceptions or experiences around each outcome in relation to the COVID-19 pandemic ; narratives provided for precipitating factors for each outcome.No restrictions were placed on the types of study design eligible for inclusion, except for the exclusion of single-person case reports. Pre-prints will be re-assessed at the time of publication and the most current version included. There was no restriction on language of publication. We drew on a combination of internet-based translation systems and network of colleagues to translate reports in languages other than English.PubMed;Scopus;medRxiv, PsyArXiv; SocArXiv;bioRxiv;the COVID-19 Open Research Dataset (CORD-19) by Semantic Scholar and the Allen Institute for AI, which includes relevant records from Microsoft Academic, Elsevier, arXiv and PMC; and theWHO COVID-19 database. A sample search strategy (for PubMed) appears inst January 2020 to 19th October 2020. We have developed a workflow that automates daily searches of these databases, and the code supporting this process can be found athttps://github.com/mcguinlu/COVID_suicide_living). Searches are conducted daily via PubMed and Scopus application programme interface and the bioRxiv and medRxiv RSS feeds. Conversion scripts for the daily updated WHO and the weekly updated CORD-19 corpus are used to collect information from the remaining sources. The software includes a systematic search function based on regular expressions to search results retrieved from the WHO, CORD-19 and preprint repositories (search strategy available in extended data). Our review is ongoing and we continue to investigate the use of other databases and to capture articles made available prior to peer review and assess eligibility and review internally. For this update we therefore included PsyArXiv and SocArXiv repositories in our search strategy via their own open access platforms as we developed our automated system. PsycINFO searches were carried out retrospectively on 6th January 2021, using a publication date filter for 1st January 2020 to 19th October 2020.We searched the following electronic databases:A two-stage screening process was undertaken to identify studies meeting the eligibility criteria. First, two authors (either CO or EE) assessed citations from the searches and identified potentially relevant titles and abstracts. Second, either DG, AJ or RW assessed the full texts of potentially eligible studies to identify studies to be included in the review. This process was managed via a custom-built online platform . The platform allowed for data extraction via a built-in form. ((selfharm*[TIAB] OR self-harm*[TIAB] OR selfinjur*[TIAB] OR self-injur*[TIAB] OR selfmutilat*[TIAB] OR self-mutilat*[TIAB] OR suicid*[TIAB] OR parasuicid*[TIAB) OR  OR (drug overdose[TIAB] OR self?poisoning[TIAB]) OR ) OR (cutt*[TIAB] OR head?bang[TIAB] OR overdose[TIAB] OR self?immolat*[TIAB] OR self?inflict*[TIAB]))) AND ((coronavirus disease?19[TIAB] OR sars?cov?2[TIAB] OR mers?cov[TIAB]) OR (19?ncov[TIAB] OR 2019?ncov[TIAB] OR n?cov[TIAB]) OR ("severe acute respiratory syndrome coronavirus 2" [Supplementary Concept] OR "COVID-19" [Supplementary Concept] OR COVID-19 [tw] OR coronavirus [tw] OR nCoV[TIAB] OR HCoV[TIAB] OR ((virus*[Title] OR coronavirus[Title] OR nCoV[Title] OR infectious[Title] OR HCoV[Title] OR novel[Title])AND (Wuhan[Title] OR China[Title] OR Chinese[Title] OR 2019[Title] OR 19[Title] OR COVID*[Title] OR SARS-Cov-2[Title] OR NCP*[Title]) OR “Coronavirus”[MeSH]))))One author  extracted data from each included study using a piloted data extraction form, and the extracted data were checked by one other author . Disagreements were resolved through discussion, and where this failed, by referral to a third reviewer . Irrespective of study design, data source and outcome measure examined, the following basic information were extracted: citation; study aims and objectives; country/setting; characteristics of participants; methods; outcome measures ; key findings; strengths and limitations; reviewer’s notes. For articles where causal inferences are made - i.e. randomised or non-randomised studies examining the effects of interventions or aetiological epidemiological studies of the effects of specific exposures – we plan to use a suitable version of the ROBINS-I or a preliminary similar tool for exposure studies to assess risk of bias as appropriate based on the research question and study design  where relevant. Where multiple studies addressed the same research questions, we assessed whether meta-analysis was appropriate and would conduct it where suitable, following standard guidance available in the Cochrane Handbook  focused on a mix of outcomes including suicide attempts (n=2), suicide deaths (n=14) and suicidal thoughts (n=1). Of the 15 cross-sectional surveys five assessed suicidal thoughts alone, others collected data on various combinations of suicidal/self-harming behaviour or thoughts. A range of validated questionnairres were used to assess suicidal thoughts . Five suet al., 2020;et al., 2020; Syedet al., 2020;et al., 2020), patients with COVID-19 .Many reasons for COVID-19 related suicide or suicide attempts were suggested in the case series with conclusions often derived from a journalist’s report of the death. Contributory factors reported included fear of contracting the disease or of passing it on to others, reactive psychoses, financial or economic issues, loneliness and isolation due to quarantine, stress among health professionals, the uncertainty around when the pandemic would end, misinterpretation of fever as COVID-19, contracting COVID-19, an inability for migrants to return home, frustration and the stigma of a (possibly perceived) positive result, which resulted in harassment or victimisation by others in the community. In the largest case series from India (n=72 suicide deaths),In the USA, four case reports described stressors for adolescents which include inability to see friends, arguments with parents, unresolvable misunderstandings over social media, academic stress, and feelings of isolation  from 11 universities, with predominantly female respondents. No statistical evidence of a rise in suicidal thoughts or self-injury was found over a number of waves of data collection. Surveys were targeted at specific populations in a further three studies  reported a 54.8% decrease in overall psychiatric emergency consultations and a 42.6% decrease in self-harm/suicide attempts during the first 4 weeks of the lockdown in France compared with the same period in 2019. Likewise, Gonçalves-Pinhoet al. (2020) identified a 55.6% decrease in presentations of “suicide and intentional self-inflicted injury” to a metropolitan psychiatric emergency department in Portugal in the period 19th March to 2nd May between 2019 and 2020.PignonIn contrast, whilstet al., 2020) showed that the number of general mental health calls declined after the onset of the pandemic in that city, while calls relating to suicides in progress remained relatively stable over the 4 year period. Calls involving suicide threats declined inversely to the increase in COVID-19 infections, although the authors noted some ‘hotspots’ within the city for both infection rates and suicide threats. A study of 31 prisons in the UK found that after lockdown there were fewer implementations of Assessment, Care in Custody and Teamwork (ACCT) processes to initiate care- plans for prisoners considered at risk of self-harm or suicide  have been published  – these report either no change or a fall in suicide deaths in the early months of the pandemic, although in keeping withet al. (2020) report a rise in suicides in Japan since July associated with increased unemployment . In keeping with concerns from Nepal, data from Thailand’s Department of Mental Health indicate suicide numbers have risen during the pandemic  of increases in suicidal/self-harm thoughts in the general population during the pandemic compared with pre-pandemic levels. Two robustly sampled general population, nationally representative cross-sectional surveys with pre pandemic baseline data from 2017/18 reported a three to four fold increase in suicide risk  which reiterate and extend these findings. Jollantet al. (2020) report a 8.5% decrease in hospitalisation for self-harm, greater in females than males, in France in January to August 2020 compared with the same period in 2019. There was also an increase in use of some more lethal methods (firearms / jumping/ drowning) as well as a rise in in-hospital deaths and ITU admissions. Carret al. (2020) report a 30% fall in consultations for self-harm in April to June 2020 in primary care and secondary care in the UK, the former a setting not explored in currently included studies. They highlight that the treatment gap for depression and anxiety was greater in working age adults, for practice populations in deprived areas, and for self-harm. A limitation of all studies based on hospital presentations is that they may not reflect community prevalence of suicidal thoughts and behaviours. This may be a particular issue if people were deterred from presenting to hospital because of fears of either over-burdening already stretched healthcare systems or of contracting the virus in these settings themselves. That said, those who present to services may be able to give some insight into whether COVID-19-related concerns are important. In one UK study, ‘stay-at-home’ related issues contributed to around half of cases, more so in males than females. The most frequent COVID-related factors were mental health issues, including new and worsening disorders, cessation, reduction or transformation of services (including absence of face-to-face support), isolation and loneliness, reduced contact with key individuals, disruption to normal routine, and entrapment (The review included 20 service utilisation studies (compared with only three in the previous update), the majority of which identified a drop in frequency of emergency department contacts for suicidal thoughts, behaviours and self-harm. An increase in contacts to a mental health digital platform was identified in one study  between social media reports and behavioural change in the context of suicide needs to be better understood. Insights derived from such approaches may help deepen our understanding of the mental health challenges of the pandemic and how these may change over time. Future research could usefully try to segment the posts by individuals and sociodemographics to explore changes in sub-groups. Another potentially useful approach to assessing the impact on COVID-19 on population mental health and suicide risk is analysis of Google trends data  network analysis of symptoms of anxiety and depression in young people highlighted an increasing connection between ‘too much worry’ and suicidal thoughts. It is challenging to assess how generalisable these findings from China are to other countries and other phases of the pandemic. If generalisable, it could point to some treatment targets that are more central to suicide risk, but this is not yet clear.Only 14% (11/78) included studies specifically focussed on children and young people. An early report (data up to May 2020) provided some reassurance about the impact of public health measures/school closures on suicide rates in children (<20 years) in Japan  based on news reports of six or eight nurses deaths . Factors reported as associated with deaths included: fear they had become infected; positive test result; being in quarantine; fearful of becoming infected; and “ extreme stress and mental disturbance”. The third, a case control study, reported that the prevalence of suicidal thoughts was no higher in medical staff who were in direct contact with COVID-19 patients, compared to those who had no direct contact  we identified a further 4156 potentially eligible studies. While most of the published evidence that we identified in this update had important limitations there was a marked improvement in study quality compared with our last update. Importantly, a large volume of the literature remains not peer reviewed; some reports are pre-prints, so this may change, but a number are research letters. All included studies remain observational in design and thus potentially prone to multiple sources of bias .The literature exploring COVID-19 and suicide deaths, suicidal behaviours, self-harm and suicidal thoughts is expanding rapidly. Since our last review end-date , economic disruption and COVID-19 infection rates in the any population at the time data are collected. A final limitation of the review is that, due to resource limitations, we excluded grey literature e.g.There is thus far no clear evidence of an increase in suicidal behaviour or self-harm associated with the pandemic, nor with the measures taken to curb the spread of COVID-19, although signals from some repeated population surveys and suicide trend data from Nepal and Japan are concerning. There are suggestions of increased risk in people who have been infected with COVID-19, in line with findings from studies showing increased risk of mental health problems in survivors of COVID-19 . There aOur living review provides a regular synthesis of the most up-to-date research evidence to guide public health and clinical policy to mitigate the impact of COVID-19 on risk of suicidality. However, the rapid growth of research in this area necessarily makes the reporting of the large volume of included studies brief. Therefore in the future we plan to publish timely updates focussed on specific topics like suicide rates, for instance, or in specific populations such as children and adolescents, those with confirmed COVID-19 or healthcare workers. Our future updates will also focus on studies investigating suicide deaths, suicide attempts and self-harm. We will no longer include studies: with suicidal thoughts and “suicide risk” as outcomes; modelling studies (since these have been superseded by studies based on suicide deaths) and those based on social media posts (because of the lack of evidence for diagnoses and self-selecting biases in respect of who contributes to these).available. All further data are publicly available via our Harvard Dataverse repository including all results of the continuous evidence surveillance and screening. Findings from the review will be widely disseminated through conference presentations, policy briefings, peer-reviewed publications, a project website (https://covid19-suicide-lsr.info/), and traditional and social media outlets.This living review, along with further updates, will be published via F1000Research. This review was registered on PROSPERO, with ID CRD42020183326. The protocol isWe are currently searching and screening on a daily basis.Since this is a systematic review, ethical approval is not required.https://doi.org/10.7910/DVN/7WZXZK Harvard Dataverse: Full review data for: "The impact of the COVID-19 pandemic on self-harm and suicidal behaviour: update of living systematic review".This project contains the following underlying data:- Screening_snapshot.csv (Screening progress for literature published before June 7th)https://doi.org/10.7910/DVN/7WZXZK Harvard Dataverse: Full review data for: "The impact of the COVID-19 pandemic on self-harm and suicidal behaviour: update of living systematic review".This project contains the following extended data:LSR update tables and figures.docx (Tables and figures from this publication)PRISMA.docData regarding the Protocol are available via our Harvard Dataverse repository for the protocolhttps://doi.org/10.7910/DVN/9JYHLS Data extraction sheet/ study reportPrisma.pdf (the PRISMA-P statement)Prospero registrationhttps://doi.org/10.7910/DVN/7WZXZK Harvard Dataverse: PRISMA checklist for ‘The impact of the COVID-19 pandemic on self-harm and suicidal behaviour: a living systematic review’Creative Commons Attribution 4.0 International license (CC-BY 4.0).Data are available under the terms of thehttps://github.com/mcguinlu/COVID_suicide_living.The development version of the software for automated searching is available from Github:http://doi.org/10.5281/zenodo.3871366 Archived source code at time of publication:MITLicense: This manuscript is a great scientific contribution. The main strength of the manuscript (that it builds on a remarkable effort -- their living systematic review) goes hand in hand with the most important limitation (the period included in the particular iteration that is under consideration for publication). I would like to thank the authors for such a great addition to science (the living systematic review) and express my admiration. Next, I expand on these observations.https://www.businessinsider.com/gun-sales-boom-2020-background-checks-hit-record-highs-2021-1). Methods are sound. Results are concise and informative. The tables are particularly interesting and we congratulate the authors on the table including modelling studies as it conveys the most important information easily. The discussion also reads well and adjusts well to the findings. The introduction is right on target and reads well. A reference to recent increases in gun purchases in the US  have become public in the meantime, some adding to the evidence reviewed here without notably changing the overarching results but enhancing their reliability  and, more importantly, some creating groundbreaking evidence that may change the conclusion of this review .  See some key recent key additions to the literature as an example:https://www.nature.com/articles/s41562-020-01042-zhttps://www.medrxiv.org/content/10.1101/2020.11.13.20231571v1https://www.medrxiv.org/content/10.1101/2020.10.06.20207530v5https://www.medrxiv.org/content/10.1101/2020.10.21.20187419v1https://www.medrxiv.org/content/10.1101/2020.10.20.20215343v1 The impact of this profound and sound review is somewhat limited by the period included: readers should resort to the authors’ ongoing live review.Are the rationale for, and objectives of, the Systematic Review clearly stated?YesIs the statistical analysis and its interpretation appropriate?Not applicableAre sufficient details of the methods and analysis provided to allow replication by others?YesAre the conclusions drawn adequately supported by the results presented in the review?YesReviewer Expertise:Psychiatric epidemiology.I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. This article provides a review of empirical studies on suicide ideation, behavior, and deaths as related to the COVID-19 pandemic (up to June 2020). Given prior data linking disasters and crises more generally, and pandemics specifically, to changes in suicide rates, describing any changes in suicide rates  due to the COVID-19 pandemic could contribute to suicide prevention science and promote public health efforts to save lives. A key strength of this paper is its design as a ‘living review’ that will be updated every six months as more data is available. Another strength is the transparent reporting on search methods and strategies. A limitation of the paper is inadequate attention to study quality in the analysis and interpretation of findings. I will give several examples. First, the authors report that they used a formal tool to assess the risk of bias for epidemiological or clinical trial design studies, but do not report findings from these assessments; given that many papers included in the review were not peer reviewed, it seems especially useful for the authors to use such assessments of study quality to guide their review and to ‘weight’ findings from these studies in their analysis. Second, the degree of methodological rigor could be assessed for all studies, not just those with epidemiology/clinical trial designs and the authors should consider doing so. Third, the authors indicate in the primary table that letters to the editor were ‘probably not peer reviewed.’ Given that this information could be verified by contacting the journals, this would be a useful strategy to bolster findings from this review. Fourth, when the authors describe the findings, they do not differentiate between findings that appear methodologically-sound versus those that may not be, thus negating one of the most useful features of review papers for readers. Another limitation of the paper is that it provides relatively little synthesis or conclusions, which is a key function of review papers, as opposed to a database that contains a listing of available studies. The discussion section includes more of a summary of what studies examined (and did not examine) as opposed to a synthesis of findings. The authors do not provide a nuanced discussion of the fact that these studies come from numerous countries around the world and what addressing this issue could potentially tell us about possible variability in suicide rates around the world. They do not discuss limitations with sampling that appeared across studies . In the discussion section, the authors conclude that “a marked improvement in the quality of design, methods, and reporting in future studies is needed.” This may be accurate, but I do not think it is an especially useful statement to guide the field. A more useful set of statements might involve a synthesis of methodological strengths and weaknesses as well as a discussion on strategies that can be taken going forward to address these weaknesses. The authors do not posit further implications; this may be accurate—that nothing else can be concluded right now—but in that case, perhaps the paper is premature. The authors should provide additional details on the methods used for the review process to construct Tables 1-4. In particular, for the column labeled ‘Conclusions,’ presumably, this refers to conclusions made by the authors of the original papers? This should be stated explicitly. Did the authors of this review include all conclusions made by the authors of the original studies in the table or did they select ones deemed most useful?  How did the authors of this review select the limitations and comments included in the final column? Some of the comments included in that final column appear opinion-based and are not supported by data from the papers . For future updates, the authors should consider providing dates for data collection in their tables given that the timing of when studies are conducted may moderate findings, given the variability in length of physical distancing, amount of economic disruption, and the number of deaths due to COVID-19.Are the rationale for, and objectives of, the Systematic Review clearly stated?YesIs the statistical analysis and its interpretation appropriate?Not applicableAre sufficient details of the methods and analysis provided to allow replication by others?NoAre the conclusions drawn adequately supported by the results presented in the review?PartlyReviewer Expertise:Suicide preventionI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. This is a much needed study during the pandemic which is constantly evolving with many ramifications.In the category of what are the effects of other exposures, suicide by railways can be added. In fact there a likely reduction of railway suicides. The other addition could be the impact of working from home, change in workplace etc.The authors have righty pointed out that the studies are from newspaper reports, non-representative samples and cross-sectional, hence the generalizability of these findings are limited.One is not sure of when studies using proxy data like newspaper data are included, and why Google trend studies are not included.The paper is a call for more robust well-designed studies to understand the association between the pandemic and suicidal behaviour.Are the rationale for, and objectives of, the Systematic Review clearly stated?YesIs the statistical analysis and its interpretation appropriate?YesAre sufficient details of the methods and analysis provided to allow replication by others?YesAre the conclusions drawn adequately supported by the results presented in the review?YesReviewer Expertise:suicide researchI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


In the last decade, unceasing interest in atom transfer radical polymerization (ATRP) has been noted, especially in aqueous dispersion systems. Emulsion or miniemulsion is a preferred environment for industrial polymerization due to easier heat dissipation and lower production costs associated with the use of water as a dispersant. The main purpose of this review is to summarize ATRP methods used in emulsion media with different variants of initiating systems. A comparison of a dual over single catalytic approache by interfacial and ion pair catalysis is presented. In addition, future development directions for these methods are suggested for better use in biomedical and electronics industries. The CuIIBr2/DOD-BPED* catalytic system proved to be extremely useful in miniemulsion ARGET ATRP, maintaining control over the polymerization of n-butyl methacrylate (nBMA) at concentrations of catalyst as low as 50 ppm .,43.IIBr2Sono-ATRP provides polymerization of well-defined polymers with preservation of chain-end functionality and a narrow molecular weight distribution by using an external stimulus. Moreover, temporal control in miniemulsion sono-ATRP is also possible by turning on/off the ultrasonication without having an adverse influence on the precisely-defined, receiving polymers with low dispersity and preserved chain-end fidelity. Considering the “green chemistry” aspect, as well as the results of experiments and the simplicity of scaling reaction setup, this procedure constitutes a simple and eco-friendly approach to obtain functional polymeric materials . Table 4nBA and poly(methyl methacrylates) (PMMA) homopolymers and copolymers was successfully conducted, and products with narrow molecular weight distribution were obtained. The polymerization of PMMA initiated by ethyl α-bromophenylacetate (EBPA) gave polymers with wider distribution (Đ = 1.6) Although 100% conversion has not been achieved in any reaction, this method is promising for industrial applications due to its easy scalability and reduced amount of reagents. However, it requires further optimization to increase conversion and reduce the response time while maintaining well-defined final products. The ultrasonication-mediated system based on the ion-pair and interfacial catalysis without the application of additional reducing agent can be considered an interesting and promising possibility in the field of ATRP [The application of anionic surfactant (SDS) with the presence of catalyst copper(II) bromide/tris(2-pyridylmethyl) amine provided a single catalyst system. The series of syntheses of P of ATRP .eATRP , ARGET ATRP , photo-ATRP (100–800 ppm) and sono-ATRP (585–717 ppm). All of the mentioned ATRP techniques enable the use of a low quantity of catalyst accompanied by a good control over the polymerization and the preparation of well-defined final products with a narrow molecular weight distribution. In this context, the proper development path will be the complete elimination of the catalytic complex from the reaction system. This type of concept was implemented in the metal-free approach according to the Pickering emulsion [Over the past decade there has been significant progress in ATRP techniques. The lower catalytic complex quantities in aqueous dispersed media wereaccomplished, especially beneficial in microelectronic and biomedical applications. These methods in water dispersed media were conducted using (ultra)low ppm catalyst loading: emulsion ; howeveremulsion . The pol


Finally, 11 ALOS-2 PALSAR-2 and 82 Sentinel-1 SAR images are analyzed to derive post-disaster annual deformation rate and long time series displacements of the Sunkoshi landslide. The results illustrated that the upper part of the landslide were still in active deformation with the largest LOS displacement velocity exceeding − 100 mm/year.A catastrophic landslide disaster happened on 2 August 2014 on the right bank of Sunkoshi River in Nepal, resulting in enormous casualties and severe damages of the Araniko highway. We collected multi-source synthetic aperture radar (SAR) data to investigate the evolution life cycle of the Sunkoshi landslide. Firstly, Distributed Scatterers SAR Interferometry (DS-InSAR) technology is applied to analyze 20 ALOS PALSAR images to retrieve pre-disaster time-series deformation. The results show that the upper part, especially the top of the landslide, has long been active before collapse, with the largest annual LOS deformation rate more than − 30 mm/year. Time series deformations measured illustrate that rainfall might be a key driving factor. Next, two pairs of TerraSAR-X/TanDEM-X bistatic data are processed to identify the landslide affected area by intensity change detection, and to generate pre- and post-disaster DSMs. Surface height change map showed maximum values of − 150.47 m at the source region and 55.65 m in the deposit region, leading to a debris volume of 5.4785 ± 0.6687 million m Many landslides show characteristics of large scale, complex mechanism and catastrophic losses. It has become a great challenge for scientists and engineers of geotechnical engineering to understand and mitigate landslide hazards in mountainous areas. For this purpose, the spatial–temporal evolution pattern of deformation field for a certain landslide during its life cycle should be well known. Unfortunately, such information is usually difficult to obtain using traditional ground-based measurements that are only available at sparse points. As a modern geodetic technology, synthetic aperture radar interferometry (InSAR) can be utilized to solve above problem and has been successfully applied in landslide monitoring5. However, most landslide investigations focus on a specific stage only, such as pre-disaster deformation signal extraction10, quantification of mass wasting volume12 and post-failure displacement monitoring14, while there has been few application of InSAR to comprehensively characterize a collapsed landslide during its pre-, co- and post-disaster stages.Landslide disasters along highway in mountainous area are increasing progressively to constitute a majority of highway disaster eventsThe Sunkoshi landslide is located at the northern half of the Araniko highway. The road was built in 1960s with the assistance of China, with the total span of about 115 km from the Zhangmu Port on the border between China and Nepal to Kathmandu, the capital of Nepal  and destroyed the highway of about 700 m. As a result, the operation of the Araniko highway has been suspended for a long period, which brought great difficulties to goods transportation and economic communication along the line, and also hampered the vigorous development of the golden tourism route between China and Nepal. The Sunkoshi River flowing through the slope toe was blocked by slipped rocks, forming a dam of about 56 m high and a large volume barrier lake. Supplementary Fig. 25, while very few scientific investigations of this landslide stability analysis has been carried out, which may be primarily due to its remote location and low accessibility.Although the collapse of Sunkoshi landslide had a strong impact on the Sino-Nepal transportation and the Nepal social-economic development, more attentions have been paid to the safety of dam and barrier lake formed by the landslideIn this study, the evolution life cycle of the Sunkoshi landslide during different periods  is characterized using various InSAR techniques with multi-source SAR data. The deformation pattern and possible driving factors in the pre-disaster stage are explored, the sliding area is determined with the collapse volume estimated, and the post-disaster stability of the landslide is evaluated. Such kinds of information should be of significance to help decision making for post-disaster treatment and risk management.The Sunkoshi landslide is located in the northern mountainous area of Nepal with steep topography, complex geologic background and dense vegetation. With a long wavelength, ALOS PALSAR data can maintain high coherence and achieve deep penetration into vegetation. 20 scenes of ALOS PALSAR images are analyzed to inverse the LOS surface deformation. The SRTM DEM of 3 arc-second resolution is used for the estimation and removal of flat-earth and topographic phase components. Both Distributed Scatterer SAR Interferometry (DS-InSAR) and Small Baseline Subset SAR Interferometry (SBAS-InSAR) techniques are applied to retrieve time-series displacements. The SBAS-InSAR functionality was fully implemented in the StaMPS software package, while the DS-InSAR processing chain was established in a mixed way by self-developing the preprocessing steps and adopting the spatial–temporal 3D phase unwrapping procedure embedded in StaMPS.Firstly, annual mean LOS deformation rates of Sunkoshi landslide during pre-disaster stage derived by SBAS-InSAR and DS-InSAR separately are shown in Fig. The climate of Nepal belongs to a typical monsoon climate type. In its northern mountainous area characterized by humid with mist clouds, and the precipitation is abundant in rainy season. We used the archived precipitation data over this area acquired by the NASA Tropical Rainfall Measuring Mission (TRMM) to verify whether the historic deformations of the Sunkoshi landslide were correlated with seasonal rainfall. The time series mean cumulative displacements of MPs within the deforming region (the top part of the landslide) as well as the precipitation data are plotted in Fig. We can see that the annual precipitation was mainly concentrated in summer from June to September. The deformation shows an overall linear trend with seasonal variations that might be related to rainfall. The maximum cumulative deformation in four years was more than − 100 mm. During the months of heavy rainfall, acceleration of the deformation tended to show up. Moreover, the landslide disaster occurred on 2 August 2014, hence it is reasonable to identify rainfall as an important factor that can deeply affect the landslide stability. However, more information on the geological structure and deformation mechanism of the landslide are needed to further validate if precipitation is the main cause of the 2014 collapse event.After the landslide disaster happened, the surface underwent dramatic changes due to collapse and sliding, leading to serious decorrelation. Two pairs of TerraSAR-X/TanDEM-X (TSX/TDX) bistatic SAR data acquired before and after the 2014 Sunkoshi landslide event were processed to generate pre- and post-disaster DSMs to further quantify the slope surface changes. Landslide-affected area can be identified by intensity change detection, and the debris volume can be estimated through surface height change mapping.In this section, the approach of intensity differencing between pre- and post-disaster SAR images is employed to identify the failure-affected area. Firstly, SAR amplitude images showing radar backscatter intensity are multi-looked to suppress the speckles. Then subpixel level geometric alignment of multitemporal SAR images is carried out to facilitate change detection.Figure The mean intensities of 20 ALOS PALSAR images and 11 ALOS-2 PALSAR-2 images are also produced and rendered in Supplementary Fig. The difference of intensity reflects the temporal alteration of backscattering characteristics of the ground surface, which can be applied to identify the landslide affected area, but it cannot quantify the actual variation of the surface landscape.In order to quantitatively assess the surface damage caused by the collapse, the height change map is generated by differentiating the pre- and post-disaster DSMs, as shown in Fig. 26, and a theoretically synthetic uncertainty of 5.6569 m can be produced in height differences between pre- and post-disaster DSMs. By multiplying the vertical uncertainty with the area of depletion zone, we can roughly assess the uncertainty of mass volume estimation. As the result, the total debris volume of the Sunkoshi landslide was estimated as 5.4785 ± 0.6687 million m3.A large volume of mass wasting destroyed the road and diverted the river to form a huge barrier lake. The mass volume collapsed from the depletion zone is estimated from the height difference map  with repeat-pass satellite SAR observations can be employed as powerful geodetic tools as they are capable of measuring land surface displacements that range from millimeters to meters. In particular, traditional two-pass DInSAR and Stacking InSAR techniques are usually first applied to carry out preliminary detection of potential landslides across wide areas. However, there might be big uncertainty in their results due to decorrelations and atmospheric disturbances.Methods of time series InSAR analysis including PSI, SBAS-InSAR, and DS-InSAR, etc., need a long stack of repeat-pass SAR data as input. They can be used to not only derive more accurate results of landslide detection than DInSAR, but also perform regular monitoring of long-term landslide surface displacements. Generally speaking, the conventional PSI method is much less applicable than SBAS-InSAR and DS-InSAR in mountainous areas of Nepal.29.Two fundamental products can be derived by time series InSAR analyses. One is the mean LOS displacement rate map showing the spatial pattern of deformations. The other is the time series displacements of MPs that can reveal temporal evolution of deformations. Dramatic accelerations in time series displacements might be taken as a kind of precursory signal of possible forthcoming slope failures to facilitate landslide disaster early warning, which has been demonstrated by several studies using long time series Sentinel-1 datasetsAn additional lesson we can learn from the case study of the Sunkoshi landslide is that it is necessary to evaluate post-disaster slope stability by continuing deformation monitoring after the collapse, because the remaining part of the slope as well as the accumulated debris might be still in high risk of secondary failure subject to triggering factors such as earthquakes and intensive rainfall. The measurements of post-disaster deformation can support decision making on disaster relief and following treatments to avoid further damages and losses.Multi-source SAR datasets are used in the case study of the Sunkoshi landslide. X-band high-resolution TerraSAR-X/TanDEM-X bistatic data pairs are specifically used to reconstruct pre- and post-disaster slope topography for quantitative identification of slope surface changes as well as estimation of collapsed mass volume. Archived L-band ALOS PALSAR data (2007–2011), L-band ALOS-2 PALSAR-2 data (2014–2017) and C-band Sentinel-1 data (2017–2019) are analyzed by DS-InSAR, Stacking InSAR and SBAS-InSAR techniques respectively to retrieve landslide surface displacements during the pre- and post-disaster stages. Comparisons among their results suggested that L-band data with longer wavelength and higher resolution outperforms C-band data in characterizing spatial pattern of deformation, while C-band data of much higher acquisition frequency shows advantage of revealing more detailed temporal evolution pattern of deformations.Due to the limitation of SAR data availability and revisit period, most landslide monitoring investigations are focusing on a specific stage and cannot reveal the whole evolution process of the landslides. Therefore, the primary objective of this study is to make full use of archived and in orbit satellite data and employ various InSAR techniques to characterize the life cycle of the Sunkoshi landslide, i.e. including exploration of deformation pattern and possible driving factors in the pre-disaster stage, identification of the sliding area as well as estimation of the collapsed mass volume, and evaluation of the post-disaster slope stability. The results can provide important information to support deformation mechanism analysis of the Sunkoshi landslide and enable secondary disaster prevention.As a typical example of catastrophic landslide disasters along the Araniko highway in north Nepal, little detail on the historic evolution of the Sunkoshi landslide has been known till now due to its remote location and absence of ground measurement. In this study, we analyzed multi-source satellite SAR datasets to characterize the evolution life cycle of this landslide. Our major findings are summarized as follows.First, according to the results of time series InSAR analyses with ALOS PALSAR data, the upper part of the landslide has long become unstable before collapse, with the maximum mean LOS displacement rate of about − 30 mm/year. Joint analysis of time series displacements retrieved and monthly cumulative precipitation records suggested that rainfall was the predominant impact factor for the landslide stability, and the 2014 failure event might be triggered by intensive rainfall in the summer monsoon season.3.Second, by differencing pre- and post-disaster DSMs generated from two pairs of bistatic mode TerraSAR-X/TanDEM-X data over the Sunkoshi landslide, we quantified the slope surface height changes induced by the collapse event and estimated the collapsed mass volume. The results show that the maximum surface height changes reached − 150.47 m at the depletion zone and 55.65 m in the accumulation zone, leading to a debris volume of 5.4785 ± 0.6687 million mThirdly, we evaluated the post-disaster slope stability of the Sunkoshi landslide with InSAR analyses of ALOS-2 PALSAR-2 and Sentinel-1 data. The results clearly indicated that the upper part of the landslide was still in active deformation since late 2014 and thus the potential risk of catastrophic failure in the future cannot be ignored. Furthermore, intermittent accelerations of displacement can be observed, which might be induced by the 2015 Gorkha earthquake and heavy rainfall of summer monsoon. Therefore, regular monitoring of the slope stability with operational SAR data acquisitions should be carried out to facilitate landslide risk management and disaster early warning.30. Aiming at this problem, DS-InSAR is applied to ensure high spatial density of MPs extracted from the ALOS PALSAR data stack, and to solve the difficult problem of mapping landslide surface deformation in mountainous areas. Two key processing steps for DS-InSAR analysis are DS target identification and optimal phase estimation.The Sunkoshi landslide is located at a high-altitude area with dense vegetation and complicated topography. Traditional InSAR technologies cannot identify sufficient measurement points and the low spatial density of detectable coherent points generally results in phase unwrapping errors and consequently big uncertainties in the deformation measurements31, and they behave as statistically homogenous pixels (SHP). K-S test is usually used to calculate and select the appropriate DS by testing if the amplitude time series of two pixels follow the same probability distribution function32, which can be intrinsically formulated as a nonparametric goodness-of-fit test33. In this study, those pixels centered at a window of fixed size 25 × 25 with more than 20 SHPs are selected as DS candidates. The resultant SHP map for the landslide region outlined in Supplementary Fig. DS is the coherent ensemble of radar echo signals from all small scatterers within the same resolution cell, among which none of these scatterers is dominantP, the sample coherence matrix can be estimated by32:H indicates Hermitian conjugation and For the identified SHP of pixel 34:k is the iteration step and the starting point of the iteration was assumed as the phase of the vector The optimal phase series 37. The processing flowchart is shown in Supplementary Fig. The DS candidates identified are then combined together with PS candidates to establish the observation network, upon which the standard PS-InSAR algorithm implemented in the StaMPS software package is applied to estimate the deformation time series of each MP38 with multitemporal SAR images acquired over the same area. In consideration of dissimilar imaging geometries adopted by SAR observations of multiple epochs, geometric correction and image registration are needed before performing change detection.After landslide disaster, the slope surface will undergo dramatic changes, leading to serious decorrelations. We make use of SAR intensity information to detect the landslide affected area39. For this purpose, two pairs of TSX/TDX bistatic SAR data were processed to generate pre- and post-disaster DSMs representing the surface topography before and after the collapse. Then a DSM change map was created to evaluate the mass volume of debris accumulated.Surface height changes can be deduced by differencing two digital surface models (DSMs) acquired at two different datesA limited number of 11 ALOS-2 PALSAR-2 images acquired after the collapse event were collected. It is usually difficult to apply time-series InSAR methods to achieve reliable results from such a small and temporarily sparse group of SAR observations. Therefore, stacking InSAR technique is adopted to retrieve post-disaster deformation during period I.n interferograms with good coherence generated from N SAR images are unwrapped after proper corrections of phase ramp, baseline errors and residual height errors. With the assumptions of almost linear deformation pattern and random atmospheric disturbances, the deformation rate of the study area can be estimated as below according to the stacking InSAR technique40:ith interferogram, and tbi is the corresponding temporal baseline.In this study, the post-disaster DSM derived from TSX/TDX bi-static data pair was utilized to remove flat-earth and topographic phase components from eighteen high-quality interferograms generated with ALOS-2 data pairs. Then all selected 41 to evaluate the landslide stability with 82 Sentinel-1 SAR images. 240 differential interferograms were generated following the criteria of small spatial and temporal baselines . The quantitative relationship between the unknown mean phase velocity δφ can be expressed as:M interferograms generated from N + 1 SAR images acquired at epochs t0 to tN. B is the coefficient matrix of size M × N recording temporal baselines for these interferograms. The unknown parameters of deformation velocities as well as time series deformations can be derived by singular value decomposition (SVD) and least squares estimation41.In consideration of the strong temporal decorrelation for C-band InSAR in vegetated area and the high computational cost of the DS-InSAR method, we employed the SBAS-InSAR techniqueWe acquired 20 scenes of ALOS PALSAR images from January 2007 to January 2011, 11 scenes of ALOS-2 PALSAR-2 images from September 2014 to October 2017, 82 scenes of Sentinel-1 SAR images from 4 January 2017 to 21 October 2019, and two pairs of TerraSAR-X/TanDEM-X (TSX/TDX) bistatic SAR data acquired before and after the 2014 Sunkoshi landslide event. Supplementary Table Supplementary information.