Perinatal mental health problems, defined as mental health problems occurring from the start of pregnancy to one year after birth, substantially affect women's and children's quality of life in low- and middle-income countries. In South Africa, despite high prevalence and documented negative impacts, most women do not receive any care.A modelling study examined the costs of perinatal mental health problems, namely depression and anxiety, for a hypothetical cohort of women and their children in South Africa over part of their life course . In sensitivity analysis, additional impacts of post-traumatic stress disorder (PTSD) and completed suicide were included. Data sources were published findings from cohort studies, as well as epidemiological and economic data from South Africa. Data from international studies were considered where no data from South Africa were available.Lifetime costs of perinatal depression and anxiety in South Africa amount to USD 2.8 billion per annual cohort of births. If the impacts of PTSD and suicide are included, costs increase to USD 2.9 billion. This includes costs linked to losses in quality of life (USD 1.8 billion), losses in income (USD 1.1 billion) and public sector costs (USD 3.5 million).Whilst important progress has been made in South Africa with regards to mental health policies and interventions that include assessment and management of perinatal mental health problems, substantial underinvestment prevents progress. Findings from this study strengthen the economic case for investing in perinatal mental health care. In Soutet al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., In addition to causing substantial human suffering for women, there are well-established adverse impacts of untreated perinatal mental health problems on pregnancy outcomes, infant growth and development, and offspring educational attainments . We included all women aged 15 to 39 years who gave birth in 2017. This is the age range when most women or girls give birth. To estimate the economic impact of perinatal mental health problems during the antenatal period, adjustments were required to include women with still-births. For simplicity, no adjustments were made to reflect multiple births (e.g. twins) since this figure is very small. In line with the UK study  were estimated from the number of children exposed to perinatal psychological distress (which overlaps with depression and anxiety) based on work by MacGinty and colleagues , which include the impact of COVID-19 on GDP for 2020. For simplicity, and to reflect an uncertain outlook for economic recovery in South Africa, we applied 2020 GDP values for subsequent years.Disability weights and unit costs (multiplied by assumed disease durations) were assigned to adverse impacts for mothers and children. Our approach follows recommendations by the WHO to include costs borne by both government and wider society WHO, . Here, gEconomic consequences linked directly to mothers are losses in quantity and quality of life (measured by DALYs) and in productivity.et al., DALYs were calculated based on the number of women with depression or anxiety, disability weights and a duration of 3 months over which the problems last , productivity losses (linked to stunting) and hospital care (linked to severe lower respiratory tract infections in the first year after birth). Effects on DALYs were calculated for the additional number of children who experience severe lower respiratory tract infections in the first year after birth, asthma, or internalising or externalising mental health problems. Disability weights were for: severe infections to reflect severe lower respiratory tract infections; partly controlled asthma to reflect asthma; a weighted average for moderate depression or anxiety to reflect internalising problems ; moderate conduct disorder to reflect child externalising problems. There is no disability weight for stunting and so we did not include this in the calculation of quantity or quality of life losses.et al., et al., et al., et al., Depending on the data, different assumptions were made about disease durations or persistence of health impacts. The impact of children's mental health problems was assumed to persist for 40 years, a figure supported by national longitudinal study data up to 10 years later (Verkuijl https://www.labourguide.co.za). The strong negative links between stunting, lost school years and earnings – and the impact of perinatal depression on these outcomes – are well established from previous studies . In keeping with global methods  suicide during the perinatal period only in sensitivity analysis, as reliable data on suicide are particularly difficult to obtain in low- and middle-income countries  and to losses in income of USD 1.1 billion (USD 0.9 billion for mothers and 0.2 billion for children). Total societal costs are USD 2818 per woman giving birth if the impacts of PTSD and completed suicide are excluded and USD 2966 if they are included. The share of total costs falling on the public  sector is comparatively small: USD 3.5 million for the cohort, linked entirely to short-term costs for hospitalisations of the infant. Over 77% of the costs of reduced quality of life are linked to the child, whilst 85% of the costs of lost income are linked to the mother. If it is assumed that costs would occur at the same rate over a 40-year period, then total costs calculated here would be equivalent to a yearly cost of USD 0.12 billion for the total population in South Africa and USD 122 per child born per cohort of women and children.each year. Costs increase further when PTSD and completed suicide impacts are considered. To our knowledge, this is the first study to assess the long-term and intergenerational costs of perinatal mental health problems in South Africa. The study established the costs in one African country, which was feasible because relevant data sources were available, including data from large, well-conducted birth cohort studies. Whilst similar prevalence and impacts are likely to occur in other African countries, a lack of data currently prevents estimating those. The methodology employed here would be applicable to other countries where the necessary data are available and would thereby help to make the case for investment.Lifetime costs linked to perinatal mental health problems in South Africa are very high. If one considers the impacts of both perinatal depression and anxiety on women (for 10 years) together with the impacts on their children (for 40 years), these costs amount to USD 2.8 billion per cohort of women giving birth et al., et al., et al., et al., Our study has several strengths. By taking a long-term and intergenerational perspective on costs, it addresses a gap that commonly occurs because studies only consider the short-term costs to individuals with the condition, a limitation that has been highlighted by the WHO  suggesting a relatively higher burden of perinatal mental problems. This is supported by evidence of the higher prevalence and more substantial health and economic impacts of mental health problems in low-and middle-income countries compared with high-income countries (Howard et al., et al., et al., Results from this study are consistent with previous findings. It has been estimated that the yearly costs of depression and anxiety among the general adult population globally amount to USD 1.15 trillion (Chisholm et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., Action is needed now to reduce the large human and economic costs of mental health problems to the population, which have been increasing as a result of the COVID-19 pandemic. This action should draw on local evidence for sustainable mental health financing strategies (Docrat This study demonstrates the substantial costs to women, their children and to society of unaddressed perinatal mental health problems in South Africa. To avert ongoing costs, sustained investment is required to address perinatal mental health problems. Future research on the return on investment of scaling evidence-based interventions would yield further valuable data for government decision making.


Skin diseases are widespread and a frequent occurrence in general practice. Providing access to medical care and high accuracy of diagnosis are important issues, specifically when it comes to distinguishing benign conditions from malignancies such as melanomas where early diagnosis and treatment increase overall survival and cure rates .Dermatologists diagnose skin lesions from dermoscopic or clinical images by performing visual inspection. To support the diagnostic process that might be slowed by an increasing workload as well as a lack of specialists in certain areas of the world, methods for computer-aided detection and computer-aided diagnosis for skin lesion image analysis have been developed . Among tThis Special Issue presents the latest advances in the use of machine learning techniques for image analysis of skin lesions. A total of six papers were selected for publication, including one review article and five papers with excellent technical contributions. All articles underwent a peer-review process with typically two rounds of review, with at least three experts in the field carefully reviewing each submitted paper.In their study titled “Uncovering and Correcting Shortcut Learning in Machine Learning Models for Skin Cancer Diagnosis”, Nauta et al.  investigIn their study titled “Integrating Domain Knowledge into Deep Learning for Skin Lesion Risk Prioritization to Support Referral in Teledermatology”, Carvalho et al.  present Chen et al. , in theiMoldovanu et al. , in theiKhan et al. , in theiKassem et al.  provide Diagnostics support team for their help in preparing and finalizing this Special Issue. We would also like to express our gratitude to all reviewers for their timely and professional comments.In this editorial, we briefly introduced the promising articles selected for this Special Issue and hope that they will inspire interested researchers to pursue future studies. Finally, we would like to thank all the authors who submitted their valuable manuscripts and the


Loneliness and social isolation are critical for health and wellbeing. Social isolation is a well-established social determinant of health, and its ill effects have been well-recognized for decades. Over the last 20 years, researchers have increasingly advocated that our health and wellbeing are not only detrimentally affected by being alone but also by feeling lonely  . LonelinThe way in which loneliness and social isolation contribute to mental health and wellbeing may be different during the COVID-19 pandemic. This was particularly evident after public health measures such as social restrictions, including national or localized lockdowns, were implemented. Furthermore, quarantine or self-isolation was also recommended for reducing infection . It is pResearch interest in this topic has accelerated, with the number of publications about “social isolation” or “loneliness” jumping significantly since 2020 . This reBentley et al.; Liu et al.; Okajima et al.; Mansour et al.; Chernova et al.; McDowell et al.; Peng et al.; Lv et al.; Luo et al.; Pilcher et al.) or “coronavirus”  in the title, and another study  tracked changes over time during the pandemic. Two papers were unrelated to the pandemic . There was a report originally submitted to this Research Topic but it was eventually published in another section of this journal .Five studies analyzed young participants aged 13–29 years old. r people , none ofLiu et al.; Lim et al.; McDowell et al.; Lv et al.), three analyzed distress  and anxiety , and two analyzed sleep or sleep problems . In addition, there were international collaborations during the pandemic . The first study examined the association between loneliness and distress in the early stage of the pandemic in eleven countries . A subset of countries (three countries) in the study also repeated the analysis 3 months later and revealed that increased loneliness over time was associated with increased psychological distress . The second study examined how social restrictions contributed to the severity of loneliness, depression, and social anxiety in participants recruited from the United Kingdom, Australia, and the United States . The authors found that as social restrictions eased, loneliness and depression reduced, but there was an increase in social anxiety. Overall, the findings of these studies highlighted how sleep problems, social anxiety, and depression are interrelated (Most studies analyzed social isolation and loneliness and their impact on mental health symptoms or related issues. Four studies analyzed depression (pandemic . Two intrrelated . HoweverThe restrictions imposed on people's lives due to COVID-19 have come as a critical reminder of how fundamental social relationships are to our mental health and wellbeing. Countries around the world observed increasing rates of mental ill health during the pandemic and responded with significant government investment and policy changes to combat it .Overall, the pandemic and its associated consequences for health and wellbeing may have highlighted the critical need for being around people and being meaningfully connected to others around us. A deeper knowledge of loneliness and social isolation is required to allow us to better understand their impact on mental health and wellbeing.HK wrote the first draft of the manuscript. ML wrote sections of the manuscript. All authors contributed to the conception, manuscript revision, read, and approved the submitted version.


Since ancient times, natural products have always been used as remedies for more or less serious pathologies. The great advantage of traditional medicine lies above all in the wealth of experience obtained “in the field” by experimenting with different natural products and different preparations to deal with specific diseases.Only recently, starting from the information of traditional medicine, an attempt has been made to apply a more “scientific” approach, trying to actually evaluate which molecules present in the natural preparation have the therapeutic effect.The awareness of being able to “take a cue” from the natural world in the process of developing new drugs has also developed from this approach, especially as these compounds are generally well tolerated and with reduced (or no) side effects.In this context, therefore, traditional medicine plays a predominant role in the discovery of new drugs based on natural products, leading to the continuous need to study new herbal matrices for pharmaceutical and nutraceutical purposes, coupled with a continuous progress of the techniques applied to the characterization of natural matrices and to the evaluation of the observed biological activities, in order to better identify the bioactive compounds.Herbal medicines contain hundreds or even thousands of primary and secondary metabolites, and it is a vital task for pharmacologists to explore which components contribute to the therapeutic effects of herbal medicines and which compounds do not. The complexity and low content of the chemical constituents of these metabolites in herbal medicines pose complex challenges. Up to now, the active components of most herbal medicines remain obscure, which hinders further pharmacological study and development of herbal medicines. In this scenario, the possibility of evaluating and characterizing herbal medicines is of great importance in order to obtain a product that is safe for human health, standardized, whose effects have been studied and evaluated from all points of view.in vivo characterization of metabolites by pharmaco-metabonomics techniques or ex vivo models focusing on the delivery, for example, in the gastrointestinal tract.In general, the absorption of these metabolites needs to be understood in order to evaluate their potential therapeutic effects. Up to now, pharmacologists have tried many methods and techniques to explore the pharmacodynamics of herbal medicines. This includes the in vivo, on new unreported biological activities or biological targets, and on new bioactive compounds as leads for the pharmaceutical industry.In this Research Topic, the main goal aims to attract innovative original contributions in the interdisciplinary area in order to understand the relative impact of different compounds/compound classes to reported pharmacological effects, but also to highlight the state of the art on profiling of metabolites’ pharmacokinetics This result can be achieved through a multidisciplinary approach that involves not only pharmacology and botany, but also disciplines such as analytical chemistry , pharmaceutical chemistry, physiology, and biochemistry.Through an integration of these disciplines and knowledge, it is possible to describe and characterize most of the observed.In the papers accepted after peer review in this Research Topic, it is also highlighted that in recent years the search for products of natural origin that can be used as they are or as lead compounds for the pharmaceutical development of new drugs is increasingly a central element of scientific research.Zeng et al., Fan et al., and Wang et al. Today these uses are being rediscovered, however, trying to follow a more scientific and systematic approach, associating what has been traditionally observed with chemical characterization and innovative techniques for evaluating biological activity in order to find a possible correlation. Han et al., Wan et al., Zheng Li et al., and Xu et al., which report approaches to proteomics, metabolomics and new strategies, respectively, amply highlight this.What we have seen so far has foundations in the traditional use of many products of plant origin, as highlighted by He et al., Gao et al., and Yang et al., focus their attention on specific markers of some native products and try to evaluate their targets and their respective biological effects.Other authors such as Jing et al., Gao et al., Hui-Yu Li et al., and Zixuan Li et al., instead closely evaluate traditional uses with respect to specific pathways involved in various pathologies.Nan et al., Xuerui Wang et al., and Su et al., instead evaluate how pills and capsules containing natural products can show therapeutic and/or preventive effects against human pathologies. Interesting the work of Pan et al., which reports how metabolomics studies carried out by hyphenated analytical approaches of LC-MS allow to evaluate and correlate the effects of EGCG on A549 cells.


A recent meta-analysis by Vaz et al. explored the vestibular function before and after cochlear implantation (CI) objectivated by cervical vestibular evoked myogenic potentials (cVEMP), the caloric test, head impulse test, and the video head impulse test (vHIT) . A speciAlterations of Vestibular Function in Cochlear Implantation.raison d'être of meta-analyses. Furthermore, Vaz et al. report the number of participants in the study of Rasmussen et al. to be 43, while the actual number being reported is 35 (Vaz et al. include data from the paper of both West et al. and Rasmussen et al. even though it is beyond doubt the same patients and preoperative outcomes that are being reported , 3. ThisVaz et al. wisely reflect on the reliability of the cVEMP following CI. However, they do not fully encapsulate the complexity of abnormal cVEMP results and by which caution they should be interpreted, despite critical evidence mounting , 5. SomeThe author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


For the past 20 years, mesenchymal stromal cells (MSCs) has become the most studied cell population in the development of adult cell therapies for disease treatment . MSCs caetc  of the cell sheets to standardize the cell sheets release criteria in GMP facilities.There is still a debate around effective delivery and use of MSCs in treating diseases, by injection, by transplantation or by using the secreted extracellular vesicles. The cheapest and fastest methodology is the injection of isolated cells. Injection of cells showed encouraging results, but the long-term effects of MSCs are unknown in terms of treating the diseases, or impairing organ function due to random anchoring of the MSCs. In addition, the survival of injected MSCs is very low , which cvivo studies cannot be explained by the number of cells that reach their target . In addition to the topics mentioned, other crucial subjects about MSCs are presented and discussed in the research topic like priming by Berglund et al., alleviation of ischemia injuries by Arjmand et al. and Chua et al., development of tendinopathy animal model for MSC treatment by Meeremans et al., discovery of new drugs to accelerate MSC differentiation into osteoblast by Wang et al., use of immortalized MSC model for hormonal by Kulebyakin et al., tissue specificity of mesangiogenic progenitors cells by Barachini et al., transcriptional characterization of MSCs by Fan et al. and the impact of MSC senescence state used in clinical trials by Alves-Paiva et al. In order to continue progressing MSC field in clinical applications, academics, clinicians, and industry partners need to continue collaborating, sharing both knowledge and best practices that help to advance this field.Due to the lack of knowledge and experience in MSC clinical applications, federal agencies had to update their guidelines, and keep improving them in parallel to increased pre-clinical and clinical experiences. Food and Drug Administration is a perfect example of how the federal agencies are updating and adding complementary guidelines in the translational field of Cellular and Gene Therapies . From 19


MrParse is a software package designed to aid decision making in molecular replacement (MR). It performs a sequence search to find search models, not only in the PDB, as would conventionally be performed, but also in the EBI AlphaFold database, and provides a series of analyses relevant to MR such as crystal pathology detection and sequence analysis. MrParse is a new pipeline to help to streamline the decision process in MR by consolidating bioinformatic predictions in one place. When reflection data are provided, MrParse can rank any experimental homologues found using eLLG, which indicates the likelihood that a given search model will work in MR. Inbuilt displays of predicted secondary structure, coiled-coil and transmembrane regions further inform the choice of MR protocol. MrParse can also identify and rank homologues in the EBI AlphaFold database, a function that will also interest other structural biologists and bioinformaticians.Crystallographers have an array of search-model options for structure solution by molecular replacement (MR). The well established options of homologous experimental structures and regular secondary-structure elements or motifs are increasingly supplemented by computational modelling. Such modelling may be carried out locally or may use pre-calculated predictions retrieved from databases such as the EBI AlphaFold database.  At the time of writing, 86% of crystal structures deposited in the Protein Data Bank . The first broadly successful algorithms in the field , which in many cases produced predictions that resembled the target as closely as a different crystal form typically would . The often high accuracy of the predictions  makes the database a very significant new source of search models for MR.As MrParse, which addresses a number of issues in MR. It will find and rank search models from both the PDB and the AFDB, providing convenient visualization of the results. It also guides choices in unconventional MR through secondary-structure prediction and predictions of regions that are relevant to MR strategy such as coiled coils  and information about the crystal pathology calculated with CTRUNCATE . As in the PDB search, information from phmmer is used to create a visualization of the search results using Pfam Domain Graphics. For the EBI AlphaFold database, these visualizations are coloured by Predicted Local Distance Difference Test (pLDDT) on an orange to blue scale, where orange indicates very low confidence in the model and blue indicates very high confidence in the model. Additional information is provided about the quality of the AF2 models, including the average pLDDT and a new measure of structural quality called the H-score.H-score can be calculated with the following equation, where N represents a list of pLDDT scores and N, B factors using an algorithm developed for phaser.voyager . Interpreting pLDDT as B factors improves the likelihood of success in MR by downweighting the less reliable regions of the model . These hits all have high sequence identity to our target  and give high eLLG scores . When eLLG is much greater than 60, structure solution by MR is likely to be straightforward  all have lower predicted reliability in this region. Any matches are downloaded from the AFDB and trimmed to match the target sequence and undergo a pLDDT to estimated B-factor conversion to improve their performance in MR. These are downloaded into the models subdirectory in the MrParse run directory.The ‘Structure predictions from the EBI AlphaFold database’ panel Fig. 1, blue pr3.2.7dry is a crystal structure of Aspergillus oryzae Rib2 deaminase experimentally determined by Zn-SAD  that only covers a 71-residue region of the target protein with 31% sequence identity . This homologue was insufficiently similar to the target protein to succeed in MR. A search of the EBI AlphaFold2 database identified a number of models that covered a larger region of the target protein and with a higher sequence identity. MR with the model of Q12362, the best hit ranked by H-score , was successfully placed by Phaser  and rebuilt with Buccaneer .PDB entry 4.MrParse is designed to bring together a range of relevant information in a single place and present it with useful visualizations and sortable tables. For most effective use, it expects both diffraction data and a target sequence, but it can run without the former. Conventional MR using homologous structures identified in the PDB is supported by the presentation of potential search models, discovered by phmmer, with graphics that illustrate their extent relative to the target and numerical data that illustrate their size and characteristics. In the future, more sensitive HHpred , can be fed directly to programs such as Phaser  methods. The potential of these methods for MR of targets with novel or divergent folds has been recognized for some time (Rigden et al., 2008et al., 2012et al., 2007et al., 2015ab initio methods has historically not always been sufficient for MR and only smaller proteins were tractable using the earliest methods. This picture has changed rapidly in recent years with first AlphaFold (Senior et al., 2020AlphaFold2 (Jumper et al., 2021ab initio structure predictions. Databases based on earlier methods such as GREMLIN (Ovchinnikov et al., 2017PconsFam (Lamb et al., 2019C-QUARK (Wang et al., 2019et al., 2019et al., 2010et al., 2015et al., 2021et al., 2022Perhaps the most exciting and forward-facing aspect of MrParse currently provides a second graphical panel devoted solely to matches in the AFDB. These can be ranked by clicking on column headings for two measures of model quality: the novel H-score described here or the percentage sequence identity between the protein of interest and the model. While the experience of the CASP structure-prediction experiment suggests that many models serve, unaltered, as successful search models, downstream editing of models after retrieval via MrParse will sometimes be necessary (McCoy et al., 2022et al., 2021et al., 2021et al., 2022et al., 2021et al., 2017et al., 2020phmmer (Eddy, 2011CCP4. Happily, the 3D-Beacons initiative (Orengo et al., 2020MrParse in facilitating access to a wide range of potential MR search models, both experimental structures and predictions, will only grow in the future. In addition, its ability to search AFDB in particular and conveniently visualize the results is likely to prove useful to bioinformaticians and cryo-EM researchers (Kryshtafovych et al., 2021et al., 2021Presently, hits are found by a


The refugee experience is associated with several potentially traumatic events that increase the risk of developing mental health consequences, including worsening of subjective wellbeing and quality of life, and risk of developing mental disorders. Here we present actions that countries hosting forcibly displaced refugees may implement to decrease exposure to potentially traumatic stressors, enhance subjective wellbeing and prevent the onset of mental disorders. A first set of actions refers to the development of reception conditions aiming to decrease exposure to post-migration stressors, and a second set of actions refers to the implementation of evidence-based psychological interventions aimed at reducing stress, preventing the development of mental disorders and enhancing subjective wellbeing. According to recent UNHCR figures, in 2 weeks over two million refugees were forcibly displaced from Ukraine to neighbouring countries UNHCR, . This poet al., The displacement and refugee experience are typically associated with loss of homes, hopes, possessions and disruption of personal, family and professional life projects. In addition, several potentially traumatic events may occur before migration, such as bombings, threats, captivity, torture, injury and witnessing death or injury of loved ones IASC, . Forciblet al., et al., et al., et al., et al., et al., et al., et al., et al., Owing to exposure to potentially traumatic events and other stressors and ongoing living difficulties, forcibly displaced refugees are at risk of developing mental health consequences, including worsening of subjective wellbeing and quality of life  has developed a number of low-intensity psychological interventions that may be scaled up as public health strategies to provide psychological support to refugee populations exposed to adversities WHO, . In addiAs the number of persons in need of protection is likely to substantially increase globally, driven by long-lasting wars as well as by new conflicts such as the Russo-Ukrainian war which broke out recently, national authorities are urged to develop reception and resettlement programs meeting the needs of vulnerable groups. Evidence-based psychological support should be an important component of such reception programs, aiming to prevent the deterioration of poor mental health towards full-blown psychiatric conditions.


Rosa canina fruit, and their use as recyclable and heterogeneous nanocatalysts for the degradation of dye pollutants in water’ by Saba Hemmati et al., RSC Adv., 2018, 8, 21020–21028.Correction for ‘Green synthesis of Pd nanoparticles supported on reduced graphene oxide, using the extract of  Samira Hossein Garakani’s name was incorrectly reproduced on the author listing of the published article; the corrected form is shown above.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


We thank Kuo et al. for their comments  on our pMediation analysis is a dynamic and evolving field. Kuo et al. raise the use of the causal steps approach, which was developed in the 1980s . In our To address the validity, we based the models on sound theoretical frameworks from the available literature ,9,11. AdWe agree with Kuo et al. that students should be trained in multiple methods of mediation analyses in order to make informed decisions about the optimal approach for analyzing their data.


COMMENTARY ON Present and future bright and dark spots for coral reefs through climate change.https://doi.org/10.1111/gcb.16083This is a commentary on Sully et al., 2022,  Coral reefs are one of the most threatened habitats on earth with up to 67% of historical global extent now lost and much of the remaining intact coral reef systems facing unprecedented risk from climate change, overfishing and pollution (Eakin et al., The outlook is and continues to be gloomy for many of our coral reefs. Work from Hughes et al.  and PandHowever, a small but significant shift being measured in coral reef trajectories may mean that coral reefs can survive these anthropogenic pressures if given enough time to recover and ongoing reduction in many of the local, direct pressures. While the recent Global Coral Reef Monitoring Network report (Souter et al., Sully et al.  add to t


Significant advances have been recently made in the development of the genetic and genomic platforms. This has greatly contributed to a better understanding of gene expression and regulation machinery. Consequently, this led to considerable progress in unraveling evidence of the genotype-phenotype correlation between normal/abnormal embryonic development and human disease complexity. For example, advanced genomic tools such as next-generation sequencing, and microarray-based CGH have substantially helped in the identification of gene and copy number variants associated with diseases as well as in the discovery of causal gene mutations. In addition, bioinformatic analysis tools of genome annotation and comparison have greatly aided in data analysis for the interpretation of the genetic variants at the individual level. This has unlocked potential possibilities for real advances toward new therapies in personalized medicine for the targeted treatment of human diseases. However, each of these genomic and bioinformatics tools has its limitations and hence further efforts are required to implement novel approaches to overcome these limitations. It could be possible that the use of more than one platform for genotype-phenotype deep analysis is an effective approach to disentangling the cause and treatment of the disease complexities. Our research topic aimed at deciphering these complexities by shedding some light on the recent applications of the basic and advanced genetic/genomic and bioinformatics approaches. These include studying gene-gene, protein-protein, and gene-environment interactions. We, in addition, aimed at a better understanding of the link between normal/abnormal embryonic development and the cause of human disease induction. These included 26 original research articles, 3 case reports, 1 brief research report, 1 systematic review, and 1 opinion article (The current Research Topic (RT) was aimed at deciphering the molecular signaling pathways’ interactions that orchestrate the complexity of embryonic development and human disease. Understanding these pathways should aid in developing targeted therapies. Several reports showed that many genes and/or microRNAs have a dual functional role during normal embryonic development and in human disease conditions . Hence,  article . The finin vitro experimental model. In a consortium study, Rieke and his colleagues Rieke et al., showed that SLC20A1 is involved in urinary tract and urorectal development. The study used morpholino to manipulate SLC20A1 function in the zebrafish embryo and the gene was analyzed in patients. The study showed that SLC20A1 was associated with bladder exstrophy-epispadias complex . Another research group in the RT used mouse embryonic retinal cells as their model and RNA-seq analysis to study perinatal glucose deprivation during early embryonic development and showed changes in gene expression during retinal neurogenesis. The study concluded that abnormal embryonic programming during retinogenesis could lead to retinopathy in patients with diabetes Özgümüs et al. Mice blastocysts transfected with lentivirus aiming at establishing placenta-specific knockdown or overexpression mouse model were used to study the role of Osteoprotegerin (OPG) in gestational diabetes mellitus (GDM). The study showed that OPG regulates glucose homeostasis during pregnancy through a negative feedback mechanism Huang et al. Polycystic ovary syndrome (PCOS) is another important disease studied in the RT using mitochondrial sequencing of patient oocytes. Transcriptomic dynamics analysis at the single-cell level using the weighted gene co-expression network analysis (WGCNA) approach was applied to show that abnormal mitochondrial function may contribute to a deteriorated oocyte quality in patients diagnosed with polycystic ovary syndrome (PCOS). The authors concluded that the oocyte quality might be affected by mitochondrial function Qi et al. Sall4 is a developmental gene that plays a crucial role in the pluripotency of embryonic stem cells  derived from the bone marrow of osteoarthritis (OA) patients were used to show that the expression of several chemokines, and pro- and anti-inflammatory factors were upregulated. The authors concluded that BM-MSCs could be used for cartilage differentiation and repair Jafri et al. Another study showed that Thymoquinone natural product has anti-inflammatory properties in BM-MSCs derived from OA patients suggesting a therapeutic potential of this natural product Kalamegam et al. Moreover, Wharton’s Jelly stem cell secretion was used in vitro to suppress human leukemia cells through cell cycle arrest and apoptosis induction Huwaikem et al.Human stem cells are an In summary, the research theme discussed above showed that analyzing gene expression and regulation during embryonic development could give clues to human disease induction and progression. Several developmental genes have a functional dual role in development and disease including SLC20A1, Osteoprotegerin, and SALL4. Stem cell-based therapies or regenerative medicine represent a highly promising alternative route for disease cure.A considerable number of articles in the RT aimed at using a wide range of genomic/genetic and/or bioinformatics tools to decode the biological complexity and identify causal genes in human diseases were published . These aJung et al. and Rieke et al., genome-wide association Bensenor et al., and whole exome-sequencing Naseer et al., Haque et al., and Ouyang et al. There was a tendency in several studies for using a combination of more than one genomic tool to critically discover the gene/marker/factor associated with the disease. For example, BHMT2 was identified as a new regulator for lipid metabolism in metabolic-associated fatty liver disease by combining RNA-seq analysis of the expression profile both in a mouse model and human patients Ma et al. In another study, RNA-seq was combined with the eQTL analysis to show the association of causal genes in Crohn’s disease Jung et al. Moreover, a combined exome and mitochondrial sequencing were successfully used for the rapid diagnosis of suspected pediatric mitochondrial disorders Ouyang et al. Next-generation sequencing (NGS) combined with simple short tandem repeat (STR) marker haplotypes were both used to identify a mutation in the adenomatous polyposis coli (APC) of Chinese kindred diagnosed with familial adenomatous polyposis (FAP) Zhan et al.Authors of articles published in this RT applied several advanced genomic tools including RNA-sequencing Lv et al. Additionally, several studies identified novel genetic variants associated with many disorders and/or diseases such as developmental disorders Naseer et al., acute myocardial infarction Han et al., urolithiasis Chen et al., and endophenotypes in gestational diabetes Firneisz et al. Other RT studies identified copy number variants (CNVs) Zhou et al., gene mutations Krämer et al. and Zhan et al., and gene deletions Chelbi et al. and Song et al., with all, were shown to be associated with different human diseases.Targeted exome sequence (TES) was recommended in one of the RT studies as an effective approach for the genetic skeletal dysplasias (GSD) diagnosis Luo et al. This with no doubt gives hope to follow this approach for treatment in humans for Hemophilia A or any other mutation associated with other diseases.An interesting RT study used a genomic CRISPR/Cas9 mutation repair approach and showed for the first time successful treatment of Hemophilia A in a mouse model Bahlas et al., and to identify therapeutic targets for pulmonary arterial hypertension Li et al. Other tools such as Gene Expression Omnibus (GEO), Gene ontology (GO), Kyoto Encyclopedia of Gene, Genome (KEGG) enriched pathways, and STRING online database were applied to identify the functional interactions of the differentially expressed genes (DEGs) associated with the progression of stomach adenocarcinoma Yang et al.There have been significant advances in the use of bioinformatics tools and datasets available online that could be used for deciphering the complexity of human disease . In our In summary, the research theme described above focused on identifying causal genes, gene variants, copy number variants, mutations, or deletions associated with human diseases. A wide range of advanced bioinformatics tools was used to analyze the genomic data. Combined genomic/genetic/bioinformatics tools and model systems were applied to decipher the mechanistic complexity of the disease.Guo et al. Feng and his team used Cox regression analysis and LASSO algorithm on a considerable number of DNA replication-related genes to stratify the postoperative tumor-free margin (R0) treated pancreatic ductal adenocarcinoma (PDAC) patients with different recurrence risks. This study resulted in identifying novel DNA replication-related gene signatures Feng et al. A combined approach using NGS data, karyotyping, mutation detection analysis, and flow cytometry was shown to be a better protocol for targeted therapy of acute myeloid leukemia (AML) patients El Omri et al. In summary, this research theme showed that data collected from genomic and bioinformatics analysis were effectively used to evaluate the prognostic value of biomarkers in cancer.Gene ontology (GO), gene analysis using Kyoto Encyclopedia, genomes (KEGG) analysis, and gene enrichment analysis (GSEA) were all used to show that STEAP1 is a potential prognostic biomarker for lung adenocarcinoma (LAUD) We had two aims with this RT: the first was to study genes and/or microRNAs that play a dual function in embryonic development and disease and to deliver an update about the applications of the genomics and bioinformatics advanced tools for understanding the complexity of the disease. To a large extent, these aims were met and achieved in the RT. All accepted articles were divided into 3 categories. The results published in the first category of the RT supported the notion of previous reports showing that many genes function in a dual role manner in development and disease . Other rJafri et al., Kalamegam et al., and Huwaikem et al. In addition, stem cells can be also used for cell transplantation methods to cure diseases. For example, in this RT, Luo et al., showed successful CRISPR-mediated targeting of a Hemophilia A mutation, which may eventually one day be offered in the clinic as a treatment option.Stem cell medical research aiming at developing therapies has been recently the promise for chronic disease treatment . The curNaseer et al., Naseer et al., Haque et al., Jung et al., Krämer et al., Zhan et al., Luo et al., Lv et al., Ma et al., Ouyang et al., and Özgümüs et al.For the second aim/category of the RT, a considerable number of published studies applied a wide range of genomic tools to unravel the causal gene(s) in disease Jafri et al., Kalamegam et al., and Huwaikem et al. In several studies, there was a good use of the freely available gene expression datasets for disease analysis Chen et al., Firneisz et al., Guo et al., Li et al., Qi et al., Yang et al., Feng et al., Yang et al., and Bahlas et al. However, the use of these data presents many ethical challenges (There was, in addition, substantial use in these studies of many advanced bioinformatics tools aimed at analyzing the involved molecular signaling pathways controlling the disease induction and progression allenges . For theOur Research Topic aimed at expanding our knowledge of the use of advanced genomic and bioinformatics tools. Results from several articles showed that genes could play a dual functional role in embryonic development and human disease. Stem cell-based therapy and CRISPR/cas9 mutation repair approaches are promising strategies for therapy. Several combined genomic approaches were successfully used to decipher disease induction mechanisms. Advances made in genomic and bioinformatic applications for understanding the complexities of human disease should be of great help to clinicians in personalized therapy.


IUCrJ, 9, 728–734Urzhumtsev & Lunin (2022). ] proposing a new method for the analytic modelling of inhomogeneous resolution in electrostatic potential volumes and electron density maps for improved real-space refinement.Commentary is given on a paper [ IUCrJ, Urzhumtsev & Lunin (2022Our experimental knowledge of structure in atomic detail is derived from the electron density or electrostatic potential map interpreted as an atomic model. Conversely, we calculate the theoretical map from our model and comparison of both sources is used to refine (Urzhumtsev & Lunin, 2019unin 2022 revisit et al., 2022et al., 2020The last decade has seen an expansion of powerful experimental structural techniques, the ‘resolution revolution’ in cryoEM (Kühlbrandt, 2014In the absence of an analytic expression of the convolution between the Gaussian function accounting for displacement and the interference function limiting resolution, the latter has been recast into a shell decomposition allowing the calculation, in a closed analytical form, of the atomic model map distorted by restricted resolution and positional disorder.The particular implementation and large-scale refinement tests on real data remain to be explored for each envisaged application, and it is anticipated that such development will soon follow. Nevertheless, the present work provides proof of principle of the superior effect of accounting for Fourier ripples with synthetic data calculated for a protein model and establishes the computational advantages.et al., 2021et al., 2021et al., 2020et al., 2022The availability of accurate predicted models for protein components of macromolecular complexes (Jumper This development will enable real-space refinement in a more appropriate way and thus be welcomed by the community once implementations tailored to each envisaged application are available in refinement software. In the meantime, this theoretical proposal stirring discussion on how to best connect model and experiment for a critical and accurate assessment is timely, and is a development that will make ripples in the structural sciences.


Research shows persistent ethnic inequities in mental health experiences and outcomes, with a higher incidence of illnesses among minoritised ethnic groups. People with psychosis have an increased risk of multiple long-term conditions . However, there is limited research regarding ethnic inequities in multimorbidity in people with psychosis. This study investigates ethnic inequities in physical health multimorbidity in a cohort of people with psychosis.In this retrospective cohort study, using the Clinical Records Interactive Search (CRIS) system, we identified service-users of the South London and Maudsley NHS Trust with a schizophrenia spectrum disorder, and then additional diagnoses of diabetes, hypertension, low blood pressure, overweight or obesity and rheumatoid arthritis. Logistic and multinomial logistic regressions were used to investigate ethnic inequities in odds of multimorbidity , and multimorbidity severity , compared with no additional health conditions (no multimorbidity), respectively. The regression models adjusted for age and duration of care and investigated the influence of gender and area-level deprivation.On a sample of 20 800 service-users with psychosis, aged 13–65, ethnic differences were observed in the odds for multimorbidity. Controlling for sociodemographic factors and duration of care, compared to White British people, higher odds of multimorbidity were found for people of Black African , Black Caribbean  and Black British  ethnicity. Reduced odds were observed among people of Chinese  and Other ethnic  backgrounds. Increased odds of severe multimorbidity  were also observed for people of any Black background.Ethnic inequities are observed for multimorbidity among people with psychosis. Further research is needed to understand the aetiology and impact of these inequities. These findings support the provision of integrated health care interventions and public health preventive policies and actions. SLaM's catchment area comprises four ethnically diverse London boroughs  covering 1.3 million people. Access to clinical records was obtained via the Clinical Record Interactive Search (CRIS) system  algorithms, which eliminate the need for researchers to read and code large volumes of text (Perera SLaM service-users who meet the following inclusion criteria: (i) had a schizophrenia spectrum disorder .The results from the logistic regression analyses  showed tet al., et al., et al., et al., We investigated ethnic inequities in risks of multimorbidity in people with psychosis, using data from the electronic health records of South London and Maudsley NHS Trust. Black African, Black Caribbean and Black British people with psychosis have around 1.5 greater odds for multimorbidity, and around twice the odds for severe multimorbidity . People of Chinese ethnicity and Other ethnicity had reduced odds for multimorbidity. This is the first study that investigates potential ethnic inequities in multimorbidity among a cohort of people with psychosis. These findings are partly in line with a study that observed a greater risk of the development of diabetes among minoritised ethnic people within the first year of treatment for psychosis  that have a simple genetic basis, studies have failed to provide sound biological explanations for the ethnic inequities observed , to service-related factors  (De Hert et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., This study used data from one of the UK's largest secondary mental health facilities, serving an ethnically diverse community. The cohort of the study is representative of South London and Maudsley NHS Trust catchment, and the findings should be generalisable to other ethnically dense urban areas in the United Kingdom. Indeed, most ethnic minorities live in urban areas. Ethnicity was self-defined, within NHS categories; however we could not include other relevant factors that can be related to inequities in health, most importantly migration, which could be associated with potential related barriers in the use of health services and under-detection of health conditions, but also an investigation of the healthy migrant paradox (Helgesson et al., et al., et al., This study shows that Black people with psychosis are at higher risk of multimorbidity. Although this study is not focused on aetiology, the findings are consistent with adversity-related onset of disease, where marginalised ethnic groups face higher rates of psychosis and other health conditions when living with this severe mental illness (Dubath


In their article, Liu et al  investigIn our recent study , althougIn any event, I agree with the conclusions of Liu et al  that add


Autoimmune encephalitides—including the paraneoplastic disorders associated with malignancy —have come to be recognized as major and surprisingly common causes of potentially treatable neurological disease. The disorders, first thought to be rare autoimmune complications of cancer, are now recognized to occur in individuals with and without cancer and to involve antibodies directed against antigens found either at the neuronal cell surface or present in the neuronal cytoplasm or nucleus. Today, we know that conditions associated with antibodies to cell surface antigens may be paraneoplastic or non-paraneoplastic, are usually associated with non-lethal neuronal dysfunction, and are frequently treatable. In contrast, conditions associated with antibodies to intracellular neuronal proteins are usually found in patients with underlying systemic cancer, are characterized by neuronal death, and tend to respond poorly to treatment. At present, over 50 separate antineuronal antibodies have been associated with these disorders, with additional potentially clinically relevant autoantibodies being described every year.Greenlee et al.), discussion by Fredrich et al. and Ruiz-Garcia et al. of antibody testing in the diagnosis of these conditions in clinical practice; an intriguing case report by Bartley et al. regarding the use of phage display library in identifying anti-Yo antibody not detectable by immunofluorescence; characterization of antibody-mediated neurological syndromes by Garza and Piquet, Totland et al., and Liu et al.; articles concerning the use of biomarkers in studying these conditions as well as neuromyelitis spectrum disorders by Li Q. et al., Kammeyer et al., Mizenko et al., Chen et al., and Li Y. et al.; and a review by Zoccarato et al. of the important but less-studied area of paraneoplastic neuropathies. Each of these articles makes a valuable contribution the field.This Research Topic in Frontiers in Neurology addresses several aspects of autoimmune and paraneoplastic encephalitides as understood at this point in time. These include a review of pathogenesis . Although elegant work by Chefdeville et al. and Small et al. has analyzed expression of NMDAR and CDR2/CDR2L antigens in tumors of patients with anti-NMDAR and anti-Yo antibody responses . This is important because recent work strongly suggests that the pathogenic antigen involved in anti-Yo antibody response is not CDR2, as has long been assumed, but, rather, the related protein, CDR2L . An unanswered—and significant—question is how T lymphocytes might target neurons, given that normal adult neurons do not express the MHC class I molecules needed to allow recognition by cytotoxic T cells . The spectrum of immune mediated neuropathies has greatly expanded over the past decade and now includes neuronal surface antibodies such as CASPR2 . Some an et al.; , 16].ClinicalTrials.gov: NCT04372615) involving the CD19-specific monoclonal, inebilizumab, in NMDAR encephalitis represents an exciting and important step forward. Badly needed—for patients with antibodies to neuronal surface antigens as well as patients with antibodies to intracellular neuronal antigens—are actual studies, using standardized protocols involving the agents currently in use, such as corticosteroids, IVIG, PLEX, or rituximab singly or in combination. Such studies would be difficult to fund but could conceivably be carried out over time on a less formal multi-institutional basis and, like use of pre-clinical animal models, could provide invaluable information regarding treatment. Future studies also need to explore and validate more robust clinical outcomes measures beyond the modified Rankin scale, which is heavily weighted toward motor deficits and does not encompass cognitive impairment and psychiatric/behavioral sequelae seen in frequently seen in patients with autoimmune encephalitis. These future scoring systems could even help identify patients who may benefit from more aggressive/longer duration immunotherapy or more meaningful outcomes such as resumption of gainful employment or schooling.The final—and clinically most important—area has to do with treatment of affected patients. Although several authors such as Graus et al. and Abboud et al. have published excellent clinical guidelines for provisionally diagnosing these disorders and initiating immunomodulatory therapies , 17, treThe decade ahead promises to be fascinating in terms of advancement of knowledge and development of new diagnostic and therapeutic approaches for this important group of disorders.JG, NC, SC, and CV conceived and wrote the initial draft of this manuscript. JA and IH contributed to the final revision as submitted. All authors contributed to the article and approved the submitted version.This work was supported by a Merit Review Award from the United States Department of Veterans Affairs (JG) awards from the Western Institute for Biomedical Research (JG and SC) and by grants from Helse Vest (CV).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Perspectives are discussed on future directions for the field of marginal ice zone (MIZ) dynamics, based on the extraordinary progress made over the past decade in its theory, modelling and observations. Research themes are proposed that would shift the field’s focus towards the broader implications of MIZ dynamics in the climate system. In particular, pathways are recommended for research that highlights the impacts of trends in the MIZ on the responses of Arctic and Antarctic sea ice to climate change.This article is part of the theme issue ‘Theory, modelling and observations of marginal ice zone dynamics: multidisciplinary perspectives and outlooks’. A notable example is the wave–ice interaction model (WIM) proposed by Dumont et al.  and Will [et al. ,3, in wh [et al.  has also [et al. –3 emanatean, and   sixth assessment report (AR6). The IPCC provides the most authoritative scientific information on climate change for influencing high-level environmental and societal policies. In terms of MIZ science, the headline findings in the ce Basis  and the  Climate  are on t Climate  and CMIP Climate ), focus the importance of changing wave activity on sea ice is unclear due to limited process understanding [The sea ice and climate communities are showing increasing recognition of the MIZ as a crucial component of the ice-covered ocean ,25, and standing –32 is thet al.’s [holy grail for MIZ research by Squire [et al. [The last comment should be heeded by the MIZ community, as it expresses the opinion that there is not yet sufficient confidence in understanding of the MIZ and its trends for it to influence policy. In fact, there are very few studies that connect the MIZ to climate-scale behaviours of either the Arctic or Antarctic ice covers, with the most notable exception being by Kohout et al.’s  correlaty Squire , and they Squire ,11. Howe [et al. , who sho [et al. , who use. 4Squire  describe


Prescribing for older patients presents several challenges. Older people often suffer from two or more chronic diseases (multimorbidity) and therefore use a greater number of medications compared to other age groups. As a result, they are more susceptible polypharmacy, and associated drug-related problems, including potentially inappropriate medication (PIM), drug ineffectiveness, drug interactions, and adverse drug events . ConsequMany studies  point ouAmbrož et al.; Candeias et al.; Chen et al.; Kardas et al.; Kurczewska-Michalak et al.; Machado-Duque et al.; Perpétuo et al.; Schneider et al.; Bobrova et al.) studied PIM and polypharmacy in older adults. Four of them  estimate the prevalence of PIM or polypharmacy in older adults.This Research Topic included 23 articles and nine of them  published in this Research Topic mapped available interventions and more complex strategies to prevent and manage polypharmacy in the older adults and discussed their potential implementation. The authors concluded that the development of strategies for the detection and prevention of drug-related problems is important to guide and support clinical decision-making and strengthen research into drug safety. This is an essential condition for achieving wide-ranging improvements in the management of older patients. Whilst different approaches have been identified to avoid drug-related problems in older patients, there is still insufficient information about their clinical importance or their public health impact. The authors also suggested that guidance on polypharmacy management in older adults is still limited. Initiatives to understand and conceptualize healthcare professional’s barriers and enablers can be used to increase knowledge translation and strengthen capacity for appropriate interventions in routine clinical practice . This is important as there were concerns with excessive bleeding in the elderly when dabigatran, the first non-vitamin K antagonist oral anticoagulants (NOAC) was first launched  estimated the efficacy of propofol in adult or older patients with different conditions. Two systematics reviews  studied the efficacy and safety of drug use in secondary care. Gao et al. conducted a network meta-analysis to summarize all available evidence about relative effectiveness of different pharmacotherapy of macular edema secondary to retinal vein occlusion. Yu et al. conducted a cross-sectional study, analyzing the trends in the topical prescription’s treatment of old patients with dry eye disease.Studies that analyzed the safety and efficacy of medications in other common problems in older patients were also included in this Research Topic. Two studies (Optimizing the use of medications is increasingly recognized as an important pillar in the health care of older people. Collectively, this Research Topic highlights pertinent concerns related to the safe use of medications in this age group and promotes awareness of optimizing older adults’ medication regimens. The results demonstrate that improving the quality of medication use and medication safety are still important challenges for healthcare professionals who care for older patients. Other initiatives are required for this field to reach its full potential of optimizing drug use in older patient to improve their health care outcomes within available resources.


Early and intense epidemic of respiratory syncytial virus (RSV) in Denmark, August to December 2022’ by Munkstrup et al., a publication error caused some of the citations to be incorrectly numbered. This was corrected on 26 January 2023, and we apologise for any inconvenience this error may have caused.In the article ‘


Projects that seek to address Code implementation need to understand the current landscape of corporate marketing activities in the government and health care settings and mobilize stakeholders from the government to the community when implementing these projects. Reinsma et al.See related article by ,Unethical marketing of commercial milk formulas remains a global challenge.GHSP, Reinsma et al.In a recent issue of ,While some of the challenges are due to limited resources, many complexities Reinsma et al.Systematic efforts to undermine breastfeeding by companies remain the norm, rather than the exception.,As described in detail by Baker et al.,The activities mentioned here are just a selection of corporate political activities undertaken in the Philippines. In light of this history, it is not surprising that coordinating with the government proved challenging. Political will is necessary to succeed in fully implementing and enforcing laws. Unfortunately, corporate actors play an enormous role in undermining them. Of course, such practices are hardly unique across settings.Reinsma et al.It's essential to listen to local communities' preferences for how they wish to be engaged in Code implementation efforts.


To the Editor: We read with great interest the recent article by Anzinger et al. (Anzinger et al.’s results reinforce the findings of Sharp et al. (The introduction of chikungunya in the Americas has brought greater complexity to surveillance in the region, which includes some low-resource countries. It is essential to establish active and viable surveillance tools and, perhaps, new case definitions in order to better assess the population burden of this disease and the complications of acute and chronic cases.


Migraine in developmental age is a common pathology. It is estimated that more than 10% of children at the age of 10 suffer from it around the world. In recent years, this disorder has attracted attention for its peculiarities, which often differentiate it from that which occurs in adulthood.The purpose of this collection is to focus on the different characteristics present in the child and its most common and rarest forms.Vincenzo Raieli et al.  discuss Ilaria Frattale et al. , in theiThe gastroenterological episodic syndromes share a common pathogenetic mechanism with migraine due to the same embryologic origin of both enteric and central nervous tissues, which can exert direct effects on each other. In the trigger mechanisms of migraine, a crucial role is played by CGRP  and PACAP (pituitary adenylate cyclase-activating peptide), that mediate vasodilation, and serotonin, that mediates sensitization of the trigeminal neurons.Giovanni Prezioso et al.  created Luigi Francesco Iannone et al.  reviewedGenizi et al.  in a newThis Special Issue emphasizes the importance and heavy burden that migraine has in the pediatric population. Pediatric migraine has a great impact on school activities, family life and parents’ work. Thus, appropriate resources should be dedicated to educating and treating children and adolescents with migraine.


In this setting, the aim of this Research Topic is to address the main topics about skin cancer from a multidisciplinary point of view. Cutaneous melanoma is certainly a hot issue, and this Research Topic includes articles about new classification, histological diagnosis, in-vivo technologies, new therapies. Umano et al., evaluated the value of Preferentially expressed Antigen in Melanoma (PRAME) for differential diagnosis of spitzoid melanocytic lesions in pediatric patients. Pediatric melanoma is also the topic of a retrospective study by Ryan et al., which provided clinical and prognostic information about this rare neoplasm in a challenging patient group. Ferrara and Argenziano., revised the WHO 2018 classification of cutaneous melanocytic neoplasms, with particular emphasis on intermediate melanocytic tumors and immunohistochemical and molecular algorithms needed to address the morphological ambiguous cases to a correct clinical management.Skin cancer is an extremely heterogenous group of neoplasms, including tumors of the epidermis , tumors of the dermal adnexa , tumors of melanocytes (cutaneous melanoma), tumors of soft tissue (angiosarcoma and other sarcomas) and tumors of neuroendocrine cells (Merkel cell carcinoma). Despite the better knowledge of its pathological and molecular features, actually skin cancer is a clinical challenge with relevant consequences in terms of morbidity and mortality. Indeed, skin cancer, including cutaneous melanoma and non-melanoma skin cancer, is the most common cancer worldwide. It has been calculated that 1 in 5 subjects will develop skin cancer by the age of 70 in the U.S., and more than 2 subjects die of skin cancer in the U.S. every hour  in the diagnosis of skin cancer, while Broggi et al., focused on the correlation between in vivo reflectance confocal microscopy and horizontal histopathology.In the last decades, the development of new technologies has dramatically changed the diagnosis of skin cancer, mainly cutaneous melanoma, and it is to be expected that technologies will acquire an ever-greater role in the next future . In the Zhang et al., immunotherapy is confirmed as a hot issue in cutaneous melanoma research. Palmieri et al., examine the potential role of molecular alterations linked to genetic instability in cutaneous melanoma as predictive biomarkers for response to immunotherapy. Zheng et al. examine current evidence about the effectiveness of immune checkpoint inhibitors therapy in advanced acral melanoma. Melanoma metastases of unknown primary is a relatively common clinical challenge and the recent improvements about clinical management, therapy and prognostic factors are evaluated by the retrospective study by Del Fiore et al.With regards to the management, immunotherapy is certainly one of the most important novelty in the therapy of skin cancer in the last years, but the effectiveness of immunotherapy in advanced melanoma cannot be predicted . In the Pampena et al., define the clinical-dermoscopic findings of aggressive subtypes of basal cell carcinoma, while Russo et al., provide evidence that the expression of Carbonic Anhydrase IX may be used as a prognostic marker in basal cell carcinoma and has a potential therapeutic role for target therapy in advanced cases. Data about the use of sonidegib for the treatment of advanced basal cell carcinoma are detailed by Brancaccio et al. Hashimoto et al., analyze the impact of mucosal involvement and surgical treatment on the survival of patients with extramammary Paget’s disease. Bi et al., examine the different therapeutic chances for cutaneous angiosarcoma, while Feng et al., describe a case of recurrent Merkel cell carcinoma responding to Tyrosine Kinase Inhibitor Apatinib.Although most non-melanoma skin cancer is easily healed with surgery alone, some neoplasms are extremely relevant in terms of morbidity and mortality. This Research Topic includes several articles about the therapy and the prognostic evaluation of these neoplasms. Czepczynski et al.,Venanzi Rullo et al., describe the peculiar findings of non-melanoma skin cancer in patients affected by HIV. Immunodepression influences not only the epidemiology and the biology of skin cancer, but mainly the clinical management of the patients. Interestingly, Crisafulli et al. systematically review the cutaneous malignancy risk in patients treated for chronic inflammatory cutaneous diseases.Lastly, the general clinical context always plays an important role in the management of patients affected by skin cancer. A possible misinterpretation of PET/CT images caused by the recent COVID-19 vaccination is described in the case report by Altogether, the different contributions to this Research Topic offer a comprehensive analysis of improvements in diagnosis and therapy of skin cancer, highlighting the importance of a multidisciplinary approach to this heterogeneous group of neoplasms.All authors equally contributed to the manuscript. All authors read and approved the final 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The result is a well-balanced collection of research articles and comprehensive reviews that tackle fundamental questions about the formation, migration and multi-organ contributions of neural crest cells in diverse model organisms, while also reflecting the growing interest for applying these discoveries to understand and treat neurocristopathies in humans. These articles can be subdivided into four groups based on their links with:  syndrome in mice, Beauchamp et al. [The second group contains four articles that focus on the contribution of cranial and cardiac subpopulations of neural crest cells to craniofacial ,5, eye , and heap et al.  not onlyp et al.  add to tp et al.  review tIn the third group of articles, one focusses on lower urinary tract innervation  while thLast but not least, Mohamad et al. remind us that the abnormal development of neural crest cells can not only lead to congenital malformations, but also cancer, as reviewed here for malignant peripheral nerve sheath tumors that arise from neural crest-derived Schwann cells .


This theme issue presents collaborative research by anthropologists, linguists, archaeologists, geneticists, historians and biogeographers, who work across disciplinary boundaries to investigate the Amazonian past. Amazonia is a fertile ground in which to develop such multidisciplinary approaches because its relative paucity of documentary records makes other sources of evidence regarding the past more important; because multidisciplinary approaches are well suited to address important unanswered questions in Amazonian history; and because a recent and dramatic reappraisal of the region's past make this an exciting time to conduct this sort of research. The papers in this theme issue feature different combinations of academic disciplines, and they address different geographical regions and historical periods, but all of them show how combining insights from different fields can help illuminate aspects of the Amazonian past that would otherwise remain obscure to them all. Interface Focus brings together the work of researchers who investigate the Amazonian past from a range of disciplinary perspectives. The issue grew out of a workshop held during the 2021 conference of the Society for the Anthropology of Lowland South America (SALSA), hosted by the University of Virginia, which featured collaborations among anthropologists, linguists, archaeologists, geneticists, historians and biogeographers. The challenge that these contributors have sought to address is a familiar one in the contemporary research landscape: each of those disciplines has made great strides in illuminating their respective aspects of the Amazonian past, but the increasing specialization and technical sophistication of the disciplines, and the volume of empirical data that they generate, has made it more difficult than ever to work across the disciplines to build an integrated historical picture. In light of this challenge, each of the contributions to this theme issue attempts the hard work of bringing together the data, methods, or theories of more than one discipline to clarify a specific aspect of the Amazonian past. The complexity of this endeavour is reflected in the long list of authors who have contributed their diverse disciplinary expertise to these papers.This theme issue of The papers address various geographical regions of Amazonia, which is a fertile ground in which to develop such multidisciplinary approaches. For one, Amazonia is characterized by a relative paucity of documentary records, which makes other sources of evidence regarding the past more important. Furthermore, South America remains today the historically ‘least known continent’ —the Amazet al. [et al. [et al. [et al. [et al. [et al. [et al.'s [et al. [The papers in this theme issue vary in their geographical and temporal focus (though there is considerable overlap among them). Two papers examine the historical dynamics of the linguistically diverse Northwest Amazonian region around the Upper Rio Negro in Colombia and Brazil , while  [et al.  take a b [et al.  examine  [et al.  focuses  [et al. , Cayón & [et al. , Arias e [et al. ) take a  [et al. . Michaelet al.'s  study of [et al.  do not m [et al. , with es [et al.  to about [et al. .et al. [et al. [The paper by van Gijn et al.  asks wha [et al.  set out The second paper in the theme issue, by Cayón & Chacon , also exet al. [The third paper, by Arias et al. , zooms iet al. [et al. [The fourth paper, by Michael et al. , also exet al. , it brin [et al.  thus proet al. [Finally, like the previous paper, Zariquiey et al.  also focWithin the pages of this theme issue, the many contributing authors have reached beyond their own disciplinary expertise and attempted to reconcile their own data and analyses with those of their co-authors. These collaborations have required not only immersion in the technical aspects of other research fields, but also engagement with the markedly different perspectives and assumptions about human experience that underlie each one. Joint progress in such a context is hard-won, but the papers in this theme issue show how combining insights from different disciplines can help illuminate aspects of the Amazonian past that would otherwise remain obscure to them all.


We further emphasized in our concluding remarks that ‘knowledge gaps still exist regarding the impact of administration of antibiotics in different compartments of dual-chamber bags and the stability and compatibility data of antifungal agents and narrow-spectrum antibiotics targeting specific species’ and that ‘future research is required in this area’ .et al. [We agree with Ling et al.  that an


Misfolded Proteins, paragraph 1 of the paper. The sentence previously stated:In the published article, there was an error. We stated that recent research had identified preeclampsia as a proteinopathy disease because misfolded proteins were found in urine and serum. We cited Cheng et al., 2021 with that statement. However, Cheng et al., 2021 found misfolded proteins in serum and did not study urine. We did not include Buhimschi et al., 2014, who made the finding in urine in the specified place in this paragraph. This statement, as mistakenly written, misrepresents the work of Cheng et al., 2021 and does not properly cite Buhimschi et al., 2014. As such, a correction has been made to “Recent research has identified preeclampsia as a proteinopathy disease due to detectable misfolded proteins being found in the urine and serum of preeclampsia patients .”The corrected sentence appears below:“Recent research has identified preeclampsia as a proteinopathy disease due to detectable misfolded proteins being found in the urine  and serum of preeclampsia patients .”The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.


Intermolecular forces, determined by the critical balance of interacting components having physical and chemical natures, control most of the static and dynamic properties of matter such as their existence in solid, liquid and gaseous phases, with their relative stability, and their chemical reactivity. In particular, they form simple interacting systems that represent the weakly bound precursor states of myriad phenomena. In some cases, such states promote the following nucleation, leading to the formation of large clusters and nanostructures, and in others, they open the passage to specific configurations of the reaction transition state of elementary reactions. Therefore, the characterization of intermolecular forces at a high level of detail is a question of crucial interest in several advanced research fields and represents a challenge for both experimentalists and theoreticians that will open new avenues in the study of systems of increasing complexity and of applied interest.The core of this Special Issue is on the building up process that controls the transition from simple no covalent adducts to complex chemical structures. This Research Topic aims to underline the relationship between forces established among the particles of the system and other properties across different scales, i.e., from molecules, simple aggregates or small clusters to nanostructures and other types of matter at the mesoscale.The Special Issue has 13 papers written by 50 authors from different countries with theoretical or experimental contributions (or both) in this research area. The work of González-Veloso et al. [3 reaction, which is based on high-level ab initio calculations. The authors performed rigorous tests to analyze the quality and accuracy of the PES, from the Quasi-Classical Trajectory (QCT) calculations, and the results were compared with available experimental data. In turn, Raczyński et al. [The paper from Espinosa-Garcia and co-workers  presentsL) by Borocci et al. [LAr to the L-ArBeO complexes. In another methodological contribution, Vázquez and collaborators [The role of i et al. . These aborators  have pro+ with helium has been investigated at the atomic level by Bartolomei et al. [NCa+ is The importance of the solvent effect in nonpolar solvents for the pyridone–hydroxy–pyridine tautomeric equilibrium and the dissociation of alkali metal halides have been studied by Shenderovich and Denisov . Specifii et al.  in a coma et al.  have als8The importance of intermolecular forces in the ionic polymerization process on large clusters of acetylene molecules to form polyaromatic hydrocarbons (PAHs) has been studied by Molina and Stein . They emn et al. .The formation of complex supramolecular structures via self-assembly of small molecules is a phenomenon also conducted by intermolecular forces. An example is the competition between hydrogen bonding and aromatic-rings stacking, which may lead to a dramatic change in the structure of biological systems. By using supersonic jet expansions, Zimmermann et al.  have preFernández et al.  have appThus, as we have seen, these papers covered different aspects of the research presently carried out on intermolecular forces and showcase the diversity of methodologies employed by theoreticians and experimentalists, making this Special Issue an interesting contribution to this field of knowledge.


MHPSS is increasingly seen as a critical component to effective and responsible humanitarian programming. This review examines the extent to which MHPSS research generated since 2010 has contributed to the public health evidence base and how this has influenced and impacted programming and policy in humanitarian settings.n = 50) and a consultation process with qualitative key informant interviews (n = 19) and online survey responses (n = 52) to identify the facilitating and inhibiting factors for the two areas of inquiry and to understand the broader context in which knowledge is generated and taken up. The interviews were thematically analysed and the survey responses were descriptively analysed.This mixed-method study included a scoping literature review (The review identified a rapidly growing evidence base that has evaluated a range of MHPSS interventions. However, few studies examined long-term impacts of interventions, there was limited direct evidence on outcomes for children and adolescents and whole family approaches, and there were minimal replications of the same approach that could test efficacy across settings and population groups. A general shift was identified in the consultation process away from a focus on disorder towards the more positive aspects of wellbeing. However, there remained a mismatch in many studies included in the literature review, whereby the interventions were broad, community-based but the outcome measures used still focused on changes in symptoms of mental disorders.The evidence base for MHPSS has grown significantly over the last 10 years. However, several knowledge gaps remain, as does the divide between research and practice. Moving forward, MHPSS intervention research needs to be more responsive to the needs on the ground. As noted in the introduction, in reality most MHPSS programmes do not target people with a diagnosable mental disorder. We wanted to understand the scope and range of research on MHPSS interventions that do not set out to treat mental disorders – e.g., those interventions that are used more in practice.Selection criteria included studies published between January 2010 and April 2020 that described the testing, trialling or evaluation of MHPSS interventions delivered in humanitarian settings that were Studies were included on interventions that targeted non-specific psychological distress or wellbeing and other related psychosocial outcomes as their primary outcome measures . In addition, studies were included on interventions that were explicit in not targeting people meeting criteria for a mental disorder, even if scales for mental disorders were included as outcome measures, as long as the study was not looking for clinical change on these measures.Interventions included those integrated into basic humanitarian service provision, activities focused on community and family support, and psychological or social activities, provided in order to achieve MHPSS-related outcomes. Studies had to be based in lower-income countries or lower-middle income countries, in the context of a humanitarian response by governmental or non-governmental organisations (NGOs) to address the immediate impacts, aftermath or consequences of an emergency, including war, conflict, natural disaster and epidemic. The MHPSS interventions identified in the study targeted adults, children and/or adolescents. Inclusion and exclusion criteria are shown in Intervention outcome studies and studies focusing on participant experiences  were included. Where a purely quantitative design was used to measure outcomes, including experimental, quasi-experimental and prospective cohort studies, only controlled designs were included. Comparison groups could be those with no intervention, on a waiting list, other active interventions or usual care. Qualitative and mixed-methods studies were included even where the quantitative component had no pre-test or control group.et al., The following international databases were searched: PsycINFO (peer-reviewed), Medline, Web of Science, the Cochrane Library and Google Scholar. The search terms, as set out in et al., The grey literature search included the resources or publications section of the websites of 27 organisations and agencies working on MHPSS in emergencies  with the aim of capturing a cross-section of these two participant groups. The final sample included 19 key informant interview participants, which took place between May and June 2020 (two key informants requested to be interviewed together), and 52 survey respondents , and a second taking detailed notes of the interview content . Questions and answers were transcribed during the interview, cross-referenced with the sound recording to ensure clarity and annotated with comments and analysis.The quantitative survey data were analysed using descriptive statistics on Excel software. Thematic analysis was used for the qualitative data. A coding scheme was developed based on the broad themes of the topic guide and from the initial hand coding of the interview data. This involved systematically sorting through the data, labelling ideas and phenomena as they appeared and reappeared. The researchers trialled the coding scheme to isolate discrepancies and revised the scheme accordingly. All interview data were coded and analysed, with the coded transcripts being reviewed by a second researcher. The trends that emerged were critically analysed according to the study's aims.All procedures were approved by the Research Ethics Board of the London School of Economics (#2090). Informed consent was obtained from key informants and survey respondents, including the consent to use anonymised quotes in reporting and publications.et al., et al., A total of 11062 references were generated from the searches. After excluding duplicates and screening from title and abstract, the full-text reports of 737 remaining citations were retained and screened. A total of 50 research studies were included in the final review, of which one contributed to two study reports from two different data pools   How has knowledge on MHPSS interventions researched in humanitarian settings advanced in the past 10 years? And (2) How has MHPSS intervention research been taken up in policy and practice at various levels of the humanitarian system? To answer these questions within the frame of the data collected, the results are structured around seven core themes that emerged from the literature and the consultation process. The core themes that emerged to answer question one include (1) an unbalanced evidence base, (2) a broadening in scope, but with mismatched outcome measures and (3) the influence of the RCT. The core themes that emerged to answer question two include (4) some progress in policy and practice, (5) a geographic divide between decision-making and locally perceived needs, (6) a disconnection of country-level MHPSS practitioners and (7) hindrances to uptake.et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., There was a geographic emphasis in the literature towards East, West and Central Africa, where two-thirds of the studies reported were located  stated,et al., et al., et al., et al., et al., et al., et al., et al., et al., The influence of the RCTHowever, a disconnect was identified in many of the studies reviewed, whereby the interventions were broad, community-based and geared towards positive outcomes, but the outcome measures used focused only on changes in symptoms of mental disorder. In several cases, there was a mismatch between the stated intervention aims and the focus of the research (including selected outcome measures). For example, in 12 studies Having RCTs that demonstrate the effectiveness of MHPSS interventions was seen by key informants as advancing the field: ‘everyone loves an RCT, it adds an extra level of credibility to interventions’ (Pr 1). Indeed, amongst the new interventions that have been adopted into MHPSS practice (see below), many have been researched through RCTs, indicating the influence of these research designs. The limitations of this research design were also acknowledged by key informants, for example, being less readily applied to community-focused interventions that address difficult-to-measure changes and complex social dynamics. The literature review confirmed that person-focused psychological interventions have been disproportionately studied through RCTs, whereas community-focused interventions, including reintegration programmes, reconciliation and healing interventions, community-led support and community support groups, were less likely to have a controlled design. A risk associated with this was noted by one global coordinator:Some progress in policy and practiceAlthough key informants agreed that RCTs are important to demonstrate effectiveness, given the controlled conditions required for an RCT, many felt that other types of research design are required to understand how an intervention works in real-world programme implementation. MHPSS evidence generated more recently was acknowledged to include ‘a greater range of methods’, and key informants also concluded that the global MHPSS community was increasingly placing greater ‘legitimacy’ and value on qualitative research. The literature review was able to capture this broader range of designs, including controlled before-and-after studies, mixed-methods and qualitative designs.et al., et al., et al., The consultation process indicated that MHPSS intervention research conducted over the last 10 years has influenced programmatic changes and uptake for several interventions, particularly scalable psychological interventions and a smaller number of broader, community-based interventions. Although not all intervention research has led to continued change or new programming, the following examples identified in the literature review and by key informants have been instrumental: (1) contextual refinement and implementation of newly developed scalable psychological interventions  sold to professionals in the South’ (NaGov 2). The survey asked researchers for the single most important reason behind their choice of current/most recent MHPSS intervention research topic out of five options and found that 40%  with global research and research generated in country settings beyond their own, and none had heard of the 2010 MHPSS research priorities. This extended into a wider theme of ‘fragile knowledge’ and the disconnection of country-level based MHPSS practitioners from formal MHPSS intervention research findings. Country-level based MHPSS practitioners felt particularly disconnected from certain types of research, for example, research published primarily in academic journals: ‘Another thing – who has access to journals? Field-based practitioners don't have access’ (Co1). Although this lack of access to journals may be true for many country-based practitioners, headquarter-based key informants still reported that practice has been impacted by research, and this was further supported by survey findings.n = 8) of practitioners surveyed who were based in Europe and North America rated their familiarity with MHPSS intervention research from the past 10 years as either four or five out of five, but only 36% (n = 2) of practitioners based outside of Europe and North America did so. When asked how easy it is to access MHPSS research, 60% (n = 6) of practitioners in Europe and North America reported a four or five out of five, compared to only 27% (n = 6) of those based outside Europe and North America. Ninety-four per cent (n = 30) of all practitioners agreed somewhat or very much that information is expensive or in difficult-to-access closed communities or portals. The findings indicated that the pathway that research travels through organisations and into practice is multi-layered involving several different actors at different levels, each likely engaged in their own preferred channels.Hindrances to uptakeThe survey results demonstrated that 80% A further limit to the knowledge brokering process was that practitioners and policymakers lacked the time to access and become familiar with research. Ninety-four per cent of the practitioners surveyed agreed somewhat or very much that they lacked time to search for and engage in research learnings. As noted by one policymaker who was interviewed, this can present a ‘Catch-22’:‘How research findings can be digested in a way that is easy to understand and see how it related… How evidence can lead to higher quality, more effective programming.’ (Co3)‘Key challenges with research projects and findings is the communication of them and that often they are not targeted to who needs to receive them.’ (DoG1)‘We need to simplify the information. One-page policy brief, giving infographics if there is a need for that.’ (NaGo2)The step of actively transforming and translating evidence from knowledge to practice was raised across all the stakeholder groups interviewed as being critical to the knowledge brokering process. The majority suggested that evidence products should be digestible, practical and focused on the end user, without losing the nuance of the findings. The following quotes are representative of the different stakeholder groups engaged.not focused on mental disorders which allowed for a broader perspective more likely to capture interventions commonly implemented in MHPSS programming.This study sought to answer how MHPSS interventions researched in humanitarian settings have advanced in the past 10 years and how the evidence has been adopted into policy and practice at various levels of the humanitarian system. The study was unique in that it focused on MHPSS interventions delivered in humanitarian settings that were et al.  found minimal or no change on these outcomes . Supporting and tracking change should be the responsibility of all parties involved in generating and using evidence-based interventions; this especially pertains to the resources allocated by donors. Adequate time and funds are needed for uptake activities on research projects, and for monitoring and evaluation of these activities against specified outcomes, to ensure tangible change and demonstrable impacts for people and communities.Researchers may find it challenging to isolate the changes which result from their research projects in emergency environments and monitoring the results of knowledge uptake is not a routine part of many research project or funding cycles. Supporting and tracking change should be the responsibility of all parties involved in generating and using evidence-based interventions; this especially pertains to the resources allocated by donors. Adequate time and funds are needed for uptake activities on research projects, and for monitoring and evaluation of these activities against specified outcomes, to ensure tangible change and demonstrable impacts for people and communities.et al., et al., et al.  mutual learning for all parties involved, (2) improved quality of research through the insights of partners, (3) buy-in for the intervention from key stakeholders and (4) more direct avenues for programme and policy change.Greater investment in collaborative research by funders, researchers, practitioners and their organisations, policy makers and people with lived experience would build the capacity and competencies of those involved, increase the likelihood of sustained buy-in from key stakeholders, and generate direct avenues to influence programming and policy change.v. (‘stress’ AND ‘reduction’) might have yielded different results.The literature review was a scoping review rather than a systematic review, and in its balance of rigour and realism some relevant studies may not have been captured. By including only English language studies, relevant studies from non-Anglophone settings may have been omitted. Also, studies that focus on mental disorders were not included, but defining whether or not research is ‘disorder-focused’ is complex. Despite the robust rationale and rigorous selection process, another research team may have yielded different results. Using the search term ‘evaluation’ and ‘stress reduction’ Due to constraints from the COVID-19 pandemic, interviews were conducted remotely. As a number of potential key informants from national governments were engaged in their emergency response capacity, only two were interviewed. Fortunately, other key informants provided data on their interactions with national government actors, particularly senior practitioners and coordinators who work closely with this cohort. The same problem may have limited the number of respondents to the survey. The response to the survey was positive considering these circumstances; however, it was too small to disaggregate findings to a very granular level, e.g. comparing answers of community-based organisation staff with those working for international NGOs. The sample size was not large enough to provide statistically significant findings but was adequate for its intended purpose of triangulation with the qualitative interview data and considering the depth and detail of the form, the number of responses was judged to be satisfactory.