There was a threshold effect where the provision of more than 10 h of care per week for a spouse  or caring for a disabled spouse with limited ADLs  increased depression in older caregivers. There were moderating influences, including higher professional prestige before retirement  and higher annual family income , that increased depression related to the spouse’s degree of disability. It was considered that active familism measures should be formulated for older spousal caregivers, especially those with lower socioeconomic status.Using the stress process model and data from the 2011–2018 China Health and Retirement Longitudinal Study (CHARLS), this study examined the effect of spousal caregiving intensity on the depression level of older caregivers in China. The moderating role that socioeconomic status plays in the relationship between spouses was explored by constructing multilevel growth models (MGMs). The care intensity for a spouse was found to relate to significantly increased depression levels in older caregivers, while the degree of disability of the spouse being cared for (B = 0.200,  The stress of caring for older adults within the context of population aging has become a major factor affecting the health of caregivers. The average time that elders in China receive care is around 4–8 years . In EU cHowever, with the outflow of the youth labor force, a rise in the number of nuclear families, and increases in female employment rates, spouses are increasingly taking on the role of caregivers of disabled older adults within families. The theory of the deinstitutionalization of marriage argues that the meaning of marriage in contemporary times has changed from institutional to companionate marriage . StudiesSince 1970, gerontology and psychology in the West have focused on the impact of caregiving on depression in the family. The common strategy was to compare whether there was a significant difference in depression levels between caregivers and non-caregivers, but research findings have been inconsistent. On the one hand, some findings suggested that family caregiving activities contained factors that had a positive impact on mental health, such as gaining greater satisfaction and accomplishment , having Several studies focused on the impact of care intensity on depression in family caregivers from the perspectives of both the caregiver and care recipient. There were disagreements among research findings related to the effect of the time devoted to caregiving on depression levels in caregivers. Using the Patient Health Questionnaire-9 and multiple linear regression, one study in Canada showed that more hours spent on weekly caregiving were associated with more pronounced depressive symptoms . AnotherA caregiver’s reaction to stress is not always negative and indeed, could serve to mobilize their own resources to seek countermeasures to help alleviate any stress and depression. The socioeconomic status of caregivers has received some attention in the literature. For example, regarding education, a study in the U.S. found that caregivers with lower-level education experienced more stress that may be related to their lack of knowledge and access to information about health care support . One stuWhile previous studies explored the impact of caregiving on the depression levels of caregivers, the main purpose of this study was to investigate the impact of older spousal caregiving on depression. It focused on the heterogeneity of the effects of caregiving intensity, and further explored the moderating effect of socioeconomic status responsible for depression. The unique approach of this study can be seen in the following three points: first, unlike most previous studies that were based on regional and cross-sectional data, this study aimed to assess the effect of care intensity on the depression levels of older caregivers by using national tracking data and constructing multilevel growth models (MGMs); second, previous studies focused on the caregivers of people with specific medical conditions such as dementia and stroke, with little attention paid to older spousal caregivers in China; third, previous studies treated caregivers as a homogeneous group, and the intensity of caregiving stressors was usually ignored, whereas this study focused on the intensity measures of caregiving from the perspectives of both the caregiver and care recipient. The two intensity measures, duration of care and the degree of disability of the spouse being cared for, were explored and compared to determine which of them had a greater impact on the depression degree among older spousal caregivers. An answer was sought as to what heterogeneity existed in the effects of caregiving intensity on spousal caregiver depression levels and whether there was a threshold for the time devoted to caregiving and a threshold for the level of disability of the care recipient that could affect the depression degree. Finally, the moderating effects of socioeconomic status such as education, occupational prestige, and household income were comprehensively examined.The stress process model provided the theoretical foundation for this study. The stress process consists of three components: stressors, moderators, and outcomes . StressoDepression in older spousal caregivers is influenced by caregiving stressors. There is no threshold of care intensity that affects depression levels. The longer the time spent on caring for a spouse and the higher the level of disability of the spouse being cared for, then the higher the level of depression will be in the older caregivers.The theory can be developed into two hypotheses, where the first hypothesis relates to stress exposure. When individuals are exposed to different stressful situations, the impact on health outcomes varies. For example, when the stress of a social role exceeds an individual’s physical and psychological capacity, it can become a stressor that is detrimental to health. Caregivers can be subjected to chronic life stress over long periods of time, such as the 3–15 years of average caregiving responsibilities for those looking after individuals with dementia. Caregivers have to continually monitor and witness the decline in the self-care abilities of progressive dementia patients and this can lead to psychological problems . DepressThe effects of caregiving stressors on depression in spousal caregivers are moderated by the caregiver’s socioeconomic status . The higThe second hypothesis concerns stress vulnerability. When trying to cope with stress, an individual’s vulnerability due to low social status, lack of resources, and coping strategies are the main reasons for the differences in health outcomes. People with lower socioeconomic status are at a disadvantage in terms of mobilizing material and psychosocial resources, stress relief and risk perception, for instance, thus showing greater vulnerability in their responses to stress. In addition, the accumulation hypothesis suggests that the health disadvantages/advantages of individuals with a lower/higher socioeconomic status due to a lack/sufficiency of resources will accumulate with age . The impData were derived from the China Health and Retirement Longitudinal Study (CHARLS). This large-scale interdisciplinary survey project hosted by The National School of Development (NSD) at Peking University aims to collect a set of high-quality microdata representing families and individuals aged 45 and older in China. The CHARLS questionnaire included the following modules: demographics, family structure/transfer, health status, work and retirement, and income and consumption, among others. The baseline national wave of CHARLS was completed in 2011 and followed up in 2013, 2015, and 2018 and included around 17,500 individuals in 150 counties/districts and 450 villages/resident committees. CHARLS collected data covering a total of 12,400 households and 19,000 individuals by 2018. It used sampling based on multi-stage stratified probabilities proportional to size (PPS), and the development of an innovative software package called CHARLS-GIS helped to produce village sampling frames. A supervisor randomly sampled 80 households in each community/village and within those households, the family member over 45 years of age and his/her spouse were randomly selected as the main respondents.The sample in this study consisted of both partners and spouses in the household and included four waves of CHARLS from 2011–2018. This study limited the sample to older adults who were aged 60 years and older, could be matched with the sample of older spouses, and had fully answered key questions such as depression symptoms in the baseline wave and completed at least one follow-up survey. The sample sizes of the four waves finally included in this study were 1511, 1511, 1228, and 876, respectively.The dependent variable of “depression” in this study was measured using the Center for Epidemiologic Studies Depression Scale-10 (CESD-10) that was developed by Andresen et al. (1994) . The scaThe core independent variable in this study was “care intensity”, measured by the weekly caregiving duration and the degree of disability of the spouse being cared for. The two indicators reflected the caregiver’s involvement and the care recipient’s needs. Previous studies had also examined these two indicators when measuring care intensity ,44,45. T, The research report of family older care policies in OECD countries in 2011 found that care intensity was close to 20 h per week [In the time devoted to caregiving, some studies focused on a threshold of 10 h per week to distinguish between high and low levels of care ,47., Theper week , while sper week ,50. In rper week . The aveIn this study, older adults having difficulty with at least one of the ADLs (activities of daily living) were defined as disabled. The disability degree of the spouse being cared for was measured by the KATZ scale, asking older adults whether they need help with the six ADLs: bathing, dressing, eating, getting into or out of bed, using the toilet, and continence. Each item was rated as complete independence = 1, partial independence = 2, and complete dependence on others = 3. The scores were summed, and total scores ranged from 6 to 18. According to classification criteria in previous studies ,53, the The moderating variable “socioeconomic status” referred to the amount of power, resources, and opportunities that people could obtain due to their position in society and could greatly affect the resources provided to family members. The socioeconomic status of older adults can be measured primarily in terms of education level, professional prestige before retirement, and annual family income. Among these, professional prestige before retirement was based on the score obtained from Treiman’s Standard International Occupational Prestige Scale (SIOPS) . In the The covariates in this study consisted of four aspects: personal characteristics of caregivers, health behaviors, intergenerational support, and social support. Personal characteristics included age, gender, ADLs, and area; health behavioral factors included participation in social activities, smoking, and exercise; intergenerational support factors included the frequency of contact; and social support factors included pension and medical insurance participation.In the first instance, analysis of variance (ANOVA) was used to compare the differences in depression levels of older caregivers at different caregiving intensities. Secondly, the multilevel growth models (MGMs) of the hierarchical linear model (HLM) were used to study the effect of spousal caregiving intensity on the depression level of older caregivers and the moderating role of socioeconomic status in the relationship.The idea of analyzing individual tracking data through the HLM was first introduced when Huttenlocher et al. (1991) collected tracking data from children in order to study individual vocabulary growth . This stThe level-1 model studied inter-individual variability in depression in older adults, that is, the effects of time-varying variables, such as care intensity, age, ADLs, annual family income, health behavior, intergenerational support, and social support. The level-2 model studied intra-individual variability, that is, the effects of variables that do not vary over time, such as gender, education level, professional prestige before retirement, and regional factors. Multiple measures for each individual (level-1) were considered as nested within the individual (level-2).In the analysis process, a null model (Model 1) was constructed to judge the necessity of establishing an MGM that was based on the size of the intraclass correlation coefficient (ICC). The larger the ICC, the larger the variance in groups, and thus the greater the need to use MGM. In general, when ICC ≥ 0.059, it indicates that the between-group variances cannot be ignored, and the between-group effects must be considered in the MGM ; second,First, we used ANOVA to make a preliminary comparison of depression in older caregivers at different levels of caregiving intensity. As shown in p < 0.001) than the duration of care .The effects of different intensities of spousal care on depression among older caregivers were revealed by the results of the MGM . The resp > 0.05) and caring for a spouse without disability (with unlimited ADLs but limited IADLs)  on depression were not significant compared with older adults who had no care participation. Both moderate-level and high-level care participation  and caring for a disabled spouse  increased depression in caregivers. Hypothesis 1 was therefore partially confirmed.Model 4 and Model 5 further examined the results for categorical variables. The effects of low-level care participation  and the higher the annual family income , the weaker effect of the disability degree in older adults on depression. Hypothesis 2 was therefore partially confirmed.Within families, spouses are increasingly taking on the role of caring for disabled older adults. Considering the paucity of research on the relationship between the intensity of spousal caregiving and depression among older caregivers in China, and especially the lack of longitudinal data studies based on nationally representative samples, this study set out to explore this association using data from a national survey sample conducted from 2011–2018.First of all, this study found that the intensity of caring for a spouse significantly increased depression levels among older caregivers. According to the stress process model, caregivers viewed caregiving as a chronic stressor and a tedious task requiring high levels of commitment. Caregivers were vulnerable to great impacts in terms of time, physical strength, energy, and emotions and were prone to loneliness, anxiety, depression, and fatigue. As for the intensity of the effect, a key finding was that the disability degree of the spouse being cared for had a greater effect on depression than the duration of care. On the one hand, the reason for this may be that the spouse is usually the most important attachment figure for adults. Witnessing the spouse’s increasing level of disability, resulting in reduced mobility or being bedridden, could cause significant psychological stress to the spouse’s caregiver. On the other hand, some studies pointed out that the pathway of the effects of caregiving on significantly higher levels of depression involved a decrease in the caregiver’s ability to participate in the labor force and a reduction in their income . HoweverSecond, the study further discovered that moderate-level and high-level intensity caregiving, as well as caring for a disabled spouse, increased depression. In contrast, low-level intensity care, that is, providing less than 10 h of care per week and caring for a non-disabled older adult with unlimited ADLs but limited IADLs, did not significantly increase depression levels in older caregivers. This finding suggested that there was a threshold effect in the impact of both the duration of care and the disability degree of the care recipient on the depression level of the spousal caregiver. This provided a further development and refinement of previous studies that concluded that the higher the care intensity, the more pronounced the caregiver’s depressive symptoms ,28. The Third, for the moderating effect, it was found that socioeconomic status only moderated the relationship between a spouse’s disability degree and a caregiver’s depression level. It has been shown that higher professional prestige before retirement and higher annual family income were associated with weaker effects of the spouse’s disability degree on depression. The moderating effect of economic status has been confirmed by several studies ,37. BettIn the 21st century, China has experienced rapid economic development, urbanization, accelerated population mobility, and the nuclearization of the family. Family values have been challenged in many aspects. For example, the family planning policy that has lasted for more than three decades has led to a large number of one-child families in China. Also, there have been a growing number of Chinese DINK  families in recent years, and families have lost their dominant position in the construction of relationships. Spouses are playing an increasingly important role in caregiving and have become an important force in coping with the crisis of population aging. Chinese social security policies do not currently provide enough attention and support to family caregivers, which affects the welfare of the family and spousal caregivers and makes it challenging to ensure the quality of services received by older care recipients.The government and society should take positive familism measures that reinforce family caregiving functions to mitigate the increasing effect of caregiving activities on the depression levels of older spousal caregivers. Firstly, support should be given to older spousal caregivers to balance their daily leisure time with their caregiving responsibilities and provide them with adequate respite. Drawing on the experience of Australia, diversified respite services, such as in-home day respite, in-home overnight respite, host family day respite, host family overnight respite, community-based day respite, community-based overnight respite, institution respite, and respite at emergency , can be There were two main limitations in this study. First, specific information was lacking about the details of caregiving activities in the CHARLS, for example, specific details of care provided, satisfaction of the spouse being cared for, spousal relationship, and subjective perceptions of caregiving stress that limited the ability to assess the effects of spousal caregiving intensity on depression levels in older caregivers. Second, subjective personal biases may have influenced answers as the data obtained were all from the subjective responses of Chinese older adults. Although depression is a common mental illness, Chinese people have negative attitudes toward people with mental illness, and stigmatization around it still exists. As a result, the participants might have provided socially acceptable responses and underestimated their own depression levels, thus leading to certain measurement errors. Since the survey did not consider social desirability biases, whether depression scores were underestimated or not could not be confirmed. It is expected that the above limitations could be overcome in future studies.This study took the heterogeneity of care intensity into account. Using the 2011–2018 CHARLS panel data and MGM, the effects of spousal caregiving intensity on the depression level of older caregivers in China and the moderating role of socioeconomic status were examined. There were three main conclusions from this study: first, the intensity of caring for a spouse significantly increased depression levels in older caregivers, and the disability degree of the spouse being cared for had a greater effect on depression than the duration of care. Second, a key conclusion was that there was a threshold effect on the impact of the intensity of care on the depression level of the spousal caregiver, in that providing care for a spouse for more than 10 h per week or caring for a disabled spouse with limited ADLs increased depression. Third, socioeconomic status moderated the relationship between the disability degree of the spouse and depression, where higher professional prestige before retirement and higher annual family income were associated with weaker effects of the spouse’s disability degree on depression. The results showed that older spousal caregivers who took on high-level intensity caregiving in China had higher levels of depression, and their mental health status was not optimistic. Active familism measures should be developed and implemented for older spousal caregivers, especially those with low professional prestige before retirement and low family financial status, thus helping to prevent them from developing deep depression.


Brunei Darussalam commenced its living-related renal transplant program in 2013, with subsequent attainment of independent local capacity and proficiency in 2019. The preliminary outcome from the program has already begun to shape the national nephrology landscape with a 36% increment in transplant rate and mitigation of commercialized transplantations. The blueprint for the program was first laid out in 2010 and thereupon executed in four phases. The first phase involved the gathering of evidence to support the establishment of the national program, through researches investigating feasibility, public opinion, quality of life, graft survival, and cost-effectiveness. The second phase focused on laying the foundation of the program through grooming of local expertise, implementation of legal-ethical frameworks, religious legitimization, and propagation of awareness. The third phase worked on facilitating experiential exposure and strengthening local infrastructure through the upgrading of facilities and the introduction of subsidiary services. The fourth phase was implemented in Brunei in 2013 when foreign personnel worked together with the local team to perform the transplants. Between 2013 and 2019, ten kidney transplants were performed, with two being done in 2018 and three in 2019. We hope to inspire other similar countries to develop their own self-sustainable and independent local program. Despite having the smallest population in Asia , Brunei Literature on establishing a national transplant program was scarce, especially in the settings of a small, Muslim, and Asian country. Due to the country's small population, there have always been reservations about a program's viability and sustainability due to insufficient demands and expertise retention. Funding and support from experienced international associations were less forthcoming because of the affluent economic status of the country and the presumptive conviction that existing pecuniary resolve could prevail over logistical and expertise restrictions. Small countries also have to grapple with the lack of a recognized training program and the “brain drain” phenomenon with suitable foreign-trained doctors seeking work opportunities overseas . Other sNot many clinicians have the privilege and experience to start a transplant program in a country, and the task is not helped by the paucity of data available in the literature. We would, therefore, like to share our experience of setting up a national program in a previously transplant naïve country, especially focusing on overcoming issues like the lack of expertise and facilities and religiocultural and political-legislative challenges. We will also describe a case series of our patients and present the impact of the program on our services.This case series described in detail the ten transplant cases that were performed in the country. The objectives of the study were to share our experience with phases of the establishment of a kidney transplant program and share our results of the first cases done. The duration of the study was from 2013 to the end of 2019 during which 10 kidney transplants were done. Personal patients' data were obtained through personal accounts from clinicians and recorded data in hospital computerized information system. Data collected included patient demographics and data pertaining to the operations, hospital stays, and outpatient follow-ups. Patient demographics included gender, age, the relationship between patients, year of operation, etiology, medication, blood group, crossmatch results, blood results, and radiographic findings. The operation, inpatient, and follow-up data were also collected. These results are presented in Tables 1p > 0.05), and a visual inspection of the histogram was done for age, operation time, and warm ischemia time. These data are presented in Tables Data for the country were obtained from the Brunei Dialysis and Transplant Registry  and unpuThe journey started with a vision of a universally accessible local transplant program that caters to the needs of all residents of the country. Previously all transplant patients (citizens of the country only) had the option of being sent overseas for transplantations if there was a compatible donor. The patient would typically stay abroad for 3–6 months. The absence of a local program meant that many eligible patients have forfeited transplant opportunities because they had not been able to take time away from family and work. Additionally, permanent and temporary residents of the country (which comprised 30% of the population⁵) were not entitled to have government-funded treatment. The vision of an independent program was only able to come to fruition when a local team took the initiative to instigate a pioneering project to start a local transplant program ten years ago.From the outset, the project was divided into four phases. Each phase was meticulously planned, and specific objectives and targets were established and evaluated at regular intervals. The phases are described in The team wanted to answer several key questions that were specific to the needs of the country. A study in 2010 involving 300 participants (approximately 0.1% of the country's eligible population) demonstrated that 78.7% were willing to donate their kidneys if the need arose. 59.7% wanted to have a local program in the country . AnotherPhase 2 was concerned with assembling and empowering a core local team to spearhead the project on various fronts, especially to address the multitude of nonclinical issues including ethics, law, religion, and policy.To assemble a local team, we enlisted three experienced local surgeons—a general surgeon, urologist, and vascular surgeon and deliberately fragmented the transplant surgery into different parts to cater to their existing expertise. The intentions were to have the urologist retrieving the donor's kidney and performing the ureteric anastomosis, the vascular surgeon operating the vascular anastomosis, and the general surgeon anchoring the entire procedure and preparing the transplant vascular bed. As the three surgeons were very experienced, it was felt that they could acquire the required skills with less exposure and training than a freshly trained surgeon performing an entire unfragmented procedure. Numerous studies have shown that experienced general surgeons and urologists can have safe transplant outcomes with limited training exposure –22. AddiThe team worked with the lawyers from the Attorney General Office in drafting the National Transplant Act, which primarily focused on the prohibition and penalization of organ trafficking and commercialization. Enactment of the Transplant Act is anticipated to take a few years as it required sanctioning from parliamentary offices. Interim measures through strict policy regulations with emphasis on compliance to the Istanbul Declaration of Organ Trafficking and Transplant Tourism (DOI)  were necNumerous models for international transplant partnerships were studied and scrutinized. The International Society of Nephrology and The Transplantation Society sisters transplant program created new transplant centers and developed existing kidney transplant programs in developing countries like Guatemala, Palestine, Myanmar, Tanzania, and Armenia . These cThis phase was concerned with getting the team experienced and the local infrastructure and manpower ready for the incipient program. We started sending patients with our medical team to our allied foreign center in 2002 to obtain experiential exposure in surgical, medical, and nursing training. The team stayed with the patient for the duration of the hospital stay abroad until the patient was deemed fit for discharge to Brunei.With a focus on strengthening local facilities, particular attention was given to environmental infection aversion strategies and ventilation engineering controls to prevent transmission of infections. Through guidance from our infection control team, we were able to introduce purpose-built ward facilities and procure consumables to enable the proper use of disinfectants and cleaners and maintenance of medical equipment. We also established new services to the laboratory in preparation for the program like calcineurin inhibitor assays, nuclear medicine scan, bone density scan, and new medications into our formulary. For services that we cannot implement, we sent tests to overseas laboratories in Singapore and Malaysia for crossmatching , viral assay, and everolimus assay.We took into account the varied contributions of members of the interdisciplinary team and their potential impact on transplant outcomes and enhancing living kidney donations. Special efforts were made to conciliate their roles and instill an ethos of shared program ownership. Allied healthcare professionals were given special emphasis in their training through MOH-endorsed workshops, designed to help them integrate and identify with the vision of the team and to facilitate their involvement during the workup and follow-up phases.The first transplant in Brunei was performed on 21/11/2013. A transplant team comprising a physician, a surgeon, and two nurses were flown in from Malaysia and Australia to guide and assist with the procedures. By the third transplant, we had acquired self-sufficiency in many areas and, only the Australian surgeon continued to come to the country at that point. The initial few years of the program were hampered by inadequate staffing and lukewarm interest from the public. As we progressed with a few successful stories (that we had deliberately played out in the press), the public began to register more interest. By the tenth transplant, the team was deemed to have acquired full proficiency in independently performing the transplants and running the program.Throughout the course of several transplants, we were able to gradually improve and introduce new services to the program , throughOur recipient stayed in the hospital with a mean stay of 15 days which is higher than 6–12 reported in the literature . This maThe challenges that we faced were unique and covered many nonclinical areas that were not normally encountered by established centers. We had to overcome technical, religious, cultural, political, and legislative barriers to inaugurate our national program. As stated from the outset, the core principles of the program were hinged around the ideals of equity, quality, sustainability, and morality; henceforth, the pace of the fledging program can only be determined by the slow disentanglement of existing limitations to enable the successful fulfillment of these virtues. It has been a truly enriching and gratifying journey, and we hope that our experience can inspire and benefit other new centers, especially in small and developing countries.


The diagnosis and treatment of disorders of glucose metabolism and obesity in childhood have significantly changed over the last decades. The impact of new technologies for the management of type 1 diabetes (T1D) , and theThis Research Topic includes a collection of papers on relevant topics in Pediatric Endocrinology that could help clinicians in better understanding new findings in the endocrine and diabetes fields.Casertano et al., who propose a novel comprehensive diagnostic flow chart. Diabetes mellitus ranges from T1D, an autoimmune disease requiring insulin, to monogenic diabetes, rare and not necessarily needing insulin, and to secondary diabetes, usually treated with insulin at the onset.Disorders in glucose metabolism range from hypoglycemia to diabetes mellitus. In fact, in some rare diseases, a mutation in the same gene can cause both hypoglycemia and hyperglycemia, as highlighted in the systematic review by Peng et al. show that diabetic ketoacidosis (DKA) prevalence was unchanged in a large regional center of China. The authors underline that the increasing awareness of this condition in the community and among primary care physicians could lead to earlier diagnosis, and therefore reduce the rates of DKA at presentation.A proper and early diagnosis of diabetes in the childhood and an appropriate therapeutic approach can have a relevant impact on the clinical and psychological outcomes. Chiesa and Marcovecchio report that vascular complications and the associated mortality remain a major issue for youth with T1D. Thus, it is essential the awareness about their prevalence and the importance of their early prediction and prevention in order to improve the long-term prognosis of youth with T1D. However, cardiometabolic diseases and excess adiposity are strong predictors of morbidity and mortality in children across the spectrum of glucose disorders. Chung et al. show that certain Nuclear Magnetic Resonance derived biomarkers are useful to predict the cardiometabolic risk in youth with dysglycemia.Fuchs and Hovorka underline that new technologies, such as closed-loop insulin delivery systems, are transforming diabetes management by improving glycaemic control and quality of life in children and young people. Franceschi et al. show in a systematic review of literature that, even though the new technologies have demonstrated to improve metabolic control, it is fundamental to point out to the families the peculiarities of the different devices. On one side Continuous Glucose Monitoring (CGM) allows a tighter metabolic control with less hypoglycemic events compared to intermittent scanning (isCGM); on the other side, isCGM seems to have greater benefits on psychological outcomes. Troncone et al. contribute to the scientific debate on the psychological benefits for patients and their caregivers after participating in a diabetes camp, by examining potential changes in psychological measures of youths' psychosocial adjustment and perception of diabetes, and self-efficacy in disease management.In order to prevent the cardiovascular complications of T1D, literature has given growing attention to the efficacy of technologies that allow to reach treatment targets for glucose control. Ngoc et al. and Di Iorio et al. underline that the correct genetic diagnosis improves treatment outcomes and prognosis of neonatal diabetes and Wolfram syndrome, respectively. In the latter it is shown that the clinical phenotype of Wolfram syndrome may include optic neuropathy and not only optic atrophy. Often, there is no specific relationship between the mutation and the clinical symptoms in some forms of monogenic diabetes, as stressed by Zhao et al. The authors firstly report EIF2AK3 mutations causing Wolcott-Rallison syndrome, in which diabetes is present.Over the last decades the diagnosis and management of pediatric monogenic diabetes , 5 has sMozzillo et al.. The authors underline that early diagnosis and prompt initiation of insulin therapy could have beneficial effects on clinical outcomes of patients with Cystic Fibrosis and pre-diabetes.Whether early detection and treatment of pre-diabetes may contribute to improve the clinical course of secondary diabetes, such as Cystic Fibrosis Related Diabetes, is debated in the systematic review of Gregoric et al., who describe two cases of pro-opiomelanocortin (POMC) deficiency. Focusing on idiopathic obesity, the most common type in the pediatric population, special attention deserves the association with metabolic syndrome (MS). Individuals living with MS may show hypertension, diabetes, dyslipidemia, and are at risk of cardiovascular complications. Thus, it is very important to identify those at higher risk already in the pediatric age group. Zhang et al. demonstrate that relative children's lipid accumulation product is an effective indicator for predicting MS, while Yang et al. highlight that C1q is positively associated with obesity and components of MS. In addition, Rahman et al. show an association between insulin-like growth factor binding proteins (IGFBPs) with metabolic homeostasis in adolescents, and suggest its potential use as a biomarker for obesity.Obesity is a major concern worldwide as it can dramatically affect patient's quality of life, particularly among children and adolescents. Its etiology varies from idiopathic to syndromic, up to the rarest monogenic form. Alterations in the mechanism of polyphagia prevail in the forms of obesity secondary to gene mutations, as evidenced by Klemenčič et al. suggest that a reversible bariatric surgery approach led to improvements of psychological factors in adolescents with severe obesity.Treating pediatric obesity is not always successful, and which is the most efficient approach is still discussed. Of note, severe obesity is associated not only with physical but also psychological complications, particularly in adolescence. We hope that this Research Topic will provide a valuable resource for the diagnosis and therapy of glucose metabolism disorders and the different etiologic types of obesity in pediatric age.EM, GM, VC, KD, and MM wrote manuscript and made a substantial, direct and intellectual contribution to the work. All authors have approved the submission of the final version of this manuscript for publication, and have agreed to be accountable for all aspects for the work.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 balance between exploitation and exploration essentially determines the performance of a population-based optimization algorithm, which is also a big challenge in algorithm design. Particle swarm optimization (PSO) has strong ability in exploitation, but is relatively weak in exploration, while crow search algorithm (CSA) is characterized by simplicity and more randomness. This study proposes a new crow swarm optimization algorithm coupling PSO and CSA, which provides the individuals the possibility of exploring the unknown regions under the guidance of another random individual. The proposed CSO algorithm is tested on several benchmark functions, including both unimodal and multimodal problems with different variable dimensions. The performance of the proposed CSO is evaluated by the optimization efficiency, the global search ability, and the robustness to parameter settings, all of which are improved to a great extent compared with either PSO and CSA, as the proposed CSO combines the advantages of PSO in exploitation and that of CSA in exploration, especially for complex high-dimensional problems. Bio-inspired optimization algorithms have become increasingly popular over the past decade due to their simplicity of implementation, robustness, and ability of parallel computation . AlthougParticle swarm optimization (PSO), developed by Kennedy  in 1995,Crow search algorithm (CSA), proposed by Askarzadeh  in 2016,Both PSO and CSA are population-based techniques. For optimization problems, the most critical part is to find as many local optimal solutions as possible and gradually move to the global best. Therefore, the most important thing is to give the solutions some degree of freedom during iteration while making the optimization process efficient, i.e., to balance between exploration and exploitation. It can be inferred from the previous studies that PSO is more capable in controlling exploitation by social and cognitive factors, but its ability of exploration in the unknown region is highly influenced by the current best solutions in spite of the existence of random numbers affecting the acceleration coefficients. In contrast, the individual in CSA moves completely randomly when it is aware of being tracked to get rid of the stalker. Hence, CSA performs better in exploring new regions in the search space. A few studies have proposed hybrid models combining PSO and CSA. Babu et al.  have proThe rest of the paper is organized as follows. i at the tth iteration is determined by the position vector xit and the velocity vector vit. The updating formulas for particle velocity and position are shown in Equations ::i at ther1 and r2 to avoid that the movements of the particles are completely decided by its current optimal position and the best position of the current population, it can be inferred that these two factors have great impact on the movement of particles. Thus, the initial position of the particles affects the search process greatly, and a large part of unknown regions can be hardly paid attention to. Such characteristic provides a strong capacity of exploiting the known information, while it is weaker in the exploration of new regions, which lead to premature convergence, i.e., the optimization easily converges to a local optimum.The key idea of PSO is that, under the dominant action of better particles, each particle is close to the global optimal position. Although there exist random numbers xit. During the iteration, crow i  tracks a random crow  j. If crow j is not aware of being tracked , crow i approaches the hiding place (pbjt) of crow j; while if crow j knows that crow i is chasing it, crow j fools crow  i by going to a random location in the search space to protect its hiding place from detection. The mathematical expression isrj and r3 are random numbers with uniform distribution between 0 and 1, fl is the length of a crow's flight, AP is the perceptual probability of crow j, and pbjt is the location where the current crow j stores food, which is equivalent to the historical optimal solution the current crow j has found.CSA is a new search algorithm inspired by the behavior of crows hiding and stealing food. It is nongreedy and can increase the variety of generated solutions. The principles of CSA are listed as follows: (1) crows live in the form of flock, (2) each crow can memorize the position of their hiding places and steal food from other crows, and (3) with a certain probability, the crow can be aware of being stalked and then protect its food from being stolen by flying randomly. The position of each crow represents a solution fl and perceived probability AP), which in turn makes it very attractive for different engineering applications. In CSA, the parameters of perceived probability are directly used to control the diversity of the algorithm. Compared with genetic algorithm (GA), PSO, and harmony search algorithm (HS), CSA has fewer parameters to adjust and is easier to implement. Moreover, the individual in CSA has the possibility of reaching a total random position, and thus, it has stronger ability of exploring newly unknown regions. However, CSA has lack of the criterion for choosing the destination and the selection is done randomly between crows; besides, the flight length is a constant value. Such characteristics of CSA lead to a weaker ability of exploitation of current information compared with PSO, resulting in low search precision, high possibility of getting into the local optimum, and premature convergence, especially for multidimensional optimization problems.CSA is a population-based optimization algorithm that is fairly simple with only two adjustable parameters . The movement of particles in CSO is influenced by the best position found so far by the particle itself and the best position identified so far by the whole swarm, as in PSO. Meanwhile, the particle keeps an eye on each other, i.e., there exists a possibility that its movement is determined by the best position identified by the whole swarm and the best solution found so far by another particle; in CSA, it tracks the position where another crow hides the food. The formula updating the flying velocity of crows in CSO isvit+1=ωvirj ≥ AP, the individual i decided to track individual j, and the velocity of individual i is affected by inertia velocity, global optimal solution, and current optimal solution of individual j. Otherwise, the velocity of individual  i is composed of inertia velocity, global optimal solution, and local optimal solution of individual i. When the velocity of individual i is obtained, the position of individual i in the next iteration is calculated by equation  and multimodal functions (such as Ackely and Griewank). Unimodal functions with one global optimum and no local optima are used to investigate the exploitation level and the convergence rate of the algorithms, while multimodal benchmark functions with multiple local optima are used to test the ability of algorithms to avoid entrapment in local optima and explore new unknown regions.In addition, a parameter representing the improvement efficiency is introduced to evaluate the progress of CSO compared with standard PSO or CSA:−23, while those from CSA and PSO rise to 102 and 10−3, respectively. Moreover, CSO also has the shortest error bars, which represent the stability of the algorithm. η of CSO is as high as 0.96 and 0.26 compared with CSA and PSO, respectively. The improvement made by CSO on the multimodal problems varies with different problems. For Ackley function, fl = 2, the optimal value of AP is concentrated between 0 and 0.2 . fl and vmax play the similar role in the optimization process as they both restrict the updating velocity of the solution, the parameter vmax  in CSO is taken as fl. As can be explored from D = 96.Optimization algorithm is often used in the optimal operation of reservoir. This section describes the ability of the CSO algorithm to solve real-world problem. It is a short-term scheduling of a hydrothermal power system described in CEC 2011 competition. The optimal goal is to meet the load demand and reduce the cost in accordance with the various constraints put on the hydraulic systems and the power system networks. Hourly discharge management for four hydro units requires 96 variables, i.e., The objective function for this problem is to minimize the cost of thermal power plant. The operation is subjected to several limitations, including demand constraints, thermal generator constraints, hydro generator constraints, storage capacity constraints, and reservoir limit constraints. These constraints are added in the fitness function as penalty term. The detailed description and data could be found in .Each algorithm was run for 25 times, and the average value of the optimal solution for each run was calculated to get the results, as shown in fl and AP than CSA, which was regarded a major drawback of CSA previously. Although the proposed algorithm performs better than traditional PSO and CSO, it does sometimes become inferior to other algorithms. CSO, in this paper, is based on original PSO, but it could be applied in other modified version of PSO instead of traditional ones for possible further improvements. It is impossible for this algorithm to beat all the other algorithms, but it can be improved further, such as setting adaptive parameters, including subswarms. In addition to above algorithms, many other representative computational intelligence algorithms can be used to solve the problems, such as Harris hawks optimization (HHO) [The balance between exploitation and exploration essentially determines the performance of a population-based optimization algorithm, which is also a big challenge in algorithm design. PSO is a popular bio-inspired optimization algorithm with strong ability in exploiting the existing information, i.e., every movement of the particles is under a certain guidance resulting from the previous knowledge, which leads to the weakening of the ability of exploring. CSA is a recent proposed algorithm with characteristics of simplicity, less parameters, and more randomness. The probability of flying totally randomly makes CSA has stronger ability of exploring new regions in the search space, while also results in a large computational cost and low search precision. This study proposes a new crow swarm optimization algorithm coupling PSO and CSA, which provides the individuals the possibility of exploring the unknown regions under the guidance of another random individual. The proposed CSO algorithm is tested on several benchmark functions, including both unimodal and multimodal problems with different variable dimensions. An example of its application in hydrothermal scheduling problem is also presented. The performance of the proposed CSO, the standard PSO, and CSA is evaluated by the optimization efficiency, the global search abilities, and the robustness to parameter settings. The results verify that the proposed CSO has better optimization ability compared with PSO and CSA, and it is less likely to fall into the local optimal solution than PSO algorithm and more efficient than CSA algorithm, i.e., CSO is good at approaching the global optimum quickly while maintaining a certain diversity of solutions during iteration. It can be concluded that the proposed PSO combines the advantages of PSO in exploitation and that of CSA in exploration. In addition, CSO has stronger robustness to the parameter on (HHO) , which a


Ethnic minorities in countries such as the UK are at increased risk of dementia or minor cognitive impairment. Despite this, cognitive tests used to provide a timely diagnosis for these conditions demonstrate performance bias in these groups, because of cultural context. They require adaptation that accounts for language and culture beyond translation. The Montreal Cognitive Assessment (MoCA) is one such test that has been adapted for multiple cultures.We followed previously used methodology for culturally adapting cognitive tests to develop guidelines for translating and culturally adapting the MoCA.We conducted a scoping review of publications on different versions of the MoCA. We extracted their translation and cultural adaptation procedures. We also distributed questionnaires to adaptors of the MoCA for data on the procedures they undertook to culturally adapt their respective versions.Our scoping review found 52 publications and highlighted seven steps for translating the MoCA. We received 17 responses from adaptors on their cultural adaptation procedures, with rationale justifying them. We combined data from the scoping review and the adaptors’ feedback to form the guidelines that state how each question of the MoCA has been previously adapted for different cultural contexts and the reasoning behind it.This paper details our development of cultural adaptation guidelines for the MoCA that future adaptors can use to adapt the MoCA for their own languages or cultures. It also replicates methods previously used and demonstrates how these methods can be used for the cultural adaptation of other cognitive tests. Currently, there are an estimated 88 languages other than English spoken in the UK, with over 8% of the population not having English as a first language, and over 864 000 people struggling or unable to speak it.8Because of the impact of globalisation, many Western countries, including the UK, have formed significant ethnic minority populations; currently 14% of the UK population identify as an ethnic minority,10 Whereas previously many ethnic minorities would return to their home country as they grew older, many people from minority backgrounds who migrated in between the 1950s and 1970s as young adults are now choosing to permanently reside in the UK in their old age.11In countries such as the UK, there is also a growing ageing ethnic minority population.12 They are highly susceptible to risk factors known to increase the likelihood of dementia, showing higher prevalence for diseases and conditions such as diabetes, heart disease, hypertension and obesity.15 Furthermore, ethnic minorities are more likely to come from low socioeconomic backgrounds, which is associated with their likelihood of developing dementia.17These older ethnic minorities are at particularly high risk for receiving a diagnosis of dementia.18 However, a key limitation of cognitive tests available to us is that they are designed for people from European cultures, fluent in the English language.20For an early and accurate diagnosis of dementia, the use of cognitive tests in the diagnostic process is vital.24Therefore, when administering cognitive tests to ethnic minorities, there is reduced sensitivity and specificity; we see higher instances of false positive scores  and false negative scores (where a person's dementia or MCI is not detected by the test) within ethnic minorities compared with their English-speaking European counterparts.23 Therefore, when assessing for dementia, cultural bias can significantly affect the validity of these cognitive tests.26To overcome this issues, cognitive tests are often translated into target languages. However, translation alone does not address these increased rates of false positive and false negative scores that may also arise from cultural differences. Ethnic minorities may not be familiar with Western concepts such as questions about the Western calendar, Western names or Western historical and general knowledge, which are used for assessing cognitive domains such as orientation, language and memory tasks.27 explored this in their research on the five dimensions of cross-cultural equivalence that can be used to minimise cultural bias and measurement errors in cross-cultural testing.27 These dimensions are content, conceptual, criterion, semantic and technical equivalence, and should be maintained by tests when they are adapted for different language and culture backgrounds.27Flaherty et al27In the context of cognitive tests for dementia and MCI technical equivalence  and semantic equivalence  are retained through simply translating the cognitive test into a target language.27However, without accounting for cultural differences as well, there is still a loss of three of the five dimensions. These are content equivalence , criterion equivalence  and conceptual equivalence .29 However, this has still been shown to reduce the sensitivity and specificity.29 With developing and piloting new cognitive tests not being the most feasible solution, adapting existing cognitive tests for different languages and cultures has been proposed.30To ensure that all five dimensions of cross-cultural equivalence are maintained, solutions such as altering cut-off scores of cognitive tests for different ethnic minorities and non-English-speaking groups has been suggested.31 This tool was developed by Nasreddine et al,31 and is currently used to aid physicians primarily in detecting MCI, a state that can progress to dementia. The test lasts 10 minutes and is given a score out of 30. There are 13 questions that assess the cognitive domains attention, fluency, memory, language, orientation, visuospatial abilities and executive functioning  is a cognitive test, developed to screen and assess for dementia and MCI.ning see .Table 131 Since its inception, the MoCA has been used to assess for several variations of dementia and associated diseases such as Parkinson's disease, vascular dementia and Huntington's disease.34A validation study conducted in 2005 found that the MoCA is a better substitute for the assessment of MCI and dementia than the Mini-Mental State Examination (MMSE).35 The review reported a wide range of cut-off scores cross-culturally (both across countries and within regions), making it difficult to identify cut-off scores to differentiate between cognitively healthy individuals and those with MCI, as scores could be considered either cognitively healthy or indicative of MCI depending on which cut-offs are used. Furthermore, the review indicates very few studies having conducted validation studies on their adapted measures, meaning sensitivity and high false positive rates. Thus, the review highlights how it can be difficult to identify recommended adjusted cut-offs according to culture, age and education level.35A recent systematic review of cross-cultural applicability of the MoCA investigated the effect language and cultural diversity have on assessing for MCI, using this cognitive screening tool.35 Yet, despite there being literature present that highlights the various adaptations of the MoCA and their development, using methods such as the use of global guidelines or the involvement of experts, there is no consensus on which questions must be culturally adapted and why.37 There is also a lack of standard steps and procedures that can be undertaken to translate and culturally adapt the MoCA.Therefore, as suggested, culturally adapting the existing MoCA would be the best approach to make it suitable for different languages and cultural contexts. In fact, the MoCA is currently widespread in use across over 50 different language and cultural versions.38 proposed that every cognitive test should have its own set of specific guidelines on culturally adapting each of its questions. These would be developed through an incorporation of previous literature and feedback from those who have previously adapted it.38Waheed et al38 These are for the Addenbrooke's Cognitive Examination Version III (ACE-III), a gold standard for the diagnostic accuracy of cognitive impairment and dementia.40 These guidelines were developed through a multi-stage qualitative study combining findings from a systematic review on the translation and cultural adaptations of the ACE-III with feedback received via questionnaires from previous adaptors of the ACE-III.41At present, there are only one set of guidelines that have been developed for the cultural adaptation of a specific cognitive test.38 As a demonstration of their applicability, these guidelines were then implemented, with input from focus groups, to develop an Urdu version of the ACE-III.38The findings identified how adaptors of the ACE-III had adapted each test question for their culture, and their rationale for how they applied changes to test questions based on cultural differences. Through these findings, steps were identified for the cultural adaptation of each ACE-III test question, and these were formatted into a set of guidelines that stated which questions of the ACE-III required cultural adaptation and how they had been adapted, with justification for the adaptation process.41 Waheed et al38 determined that when translating and culturally adapting a test, particularly cognitive tests that are heavily reliant on language and culture, developing cultural adaptation guidelines for the test, implementing them to create a culturally appropriate version of the test and culturally validating the test are all steps that should precede a psychometric validation of the new version of the test.38This Urdu version of the ACE-III was then culturally validated by administering it to 25 cognitively health Urdu speakers, who were then interviewed to determine if the test questions matched their language and cultural context.In this paper, we will describe undertaking the initial portion of this methodology to develop guidelines, this time specifically for translating and culturally adapting the MoCA. Because of the widespread availability of its existing adapted versions, it was a suitable cognitive test to develop guidelines for. The research team also consisted of two of the original developers of the ACE-III guidelines (N.M. and W.W.).27We developed the guidelines for culturally adapting the MoCA through a scoping review of the literature, using a systematic search strategy and utilising feedback from those who had adapted the MoCA for their respective cultures and languages. By developing these guidelines, we endeavoured to provide a series of evidence-based instructions that future adaptors of the MoCA can incorporate into their culturally adapted protocols, with evidence to allow for the maintaining of content, criterion and conceptual equivalence.A multi-stage qualitative approach was undertaken to develop guidelines for translating and culturally adapting the MoCA. Step 1 was a scoping review of publications on translated and culturally adapted versions of the MoCA. Step 2 involved collecting feedback from previous MoCA adaptors. Finally, in step 3, data was collated from steps 1 and 2 to form the guidelines.It is important to note that steps 1 and 2 are mutually exclusive, and can be conducted independently. However, both steps must be complete to allow for step 3, the collation of their findings. This research took place at the Centre for Primary Care and Health Services Research, The University of Manchester.36We conducted a scoping review with a systematic search of all primary publications of translations and cultural adaptations of the MoCA. The methods of this review followed a similar systematic review of the ACE-III conducted by Mirza et al.31 In addition, we utilised Web of Science and Scopus to see if there were any publications that cited the original paper by Nasreddine et al.31Because of the nature of the review, the search was conducted with healthcare-based electronic databases EMBASE, Medline and PsycINFO. The search terms were ‘Montreal cognitive assessment OR MoCA’ AND ‘dementia’ OR ‘Alzheimer*’ OR ‘cognitive’. A broad search was conducted to yield the maximum number of papers. Furthermore, a filter was applied to restrict the search period from April 2005 (as that was when the first paper on the MoCA was published) to July 2020.Papers that mentioned a translated and/or culturally adapted version of the MoCA and were the original paper to have reported that adaptation were included. This included but were not limited to validation studies.Papers that did not mention a translated or culturally adapted version of the MoCA were excluded.https://endnote.com/downloads) and duplicates were removed. The selection of studies was conducted in two steps. First, the titles and abstracts were screened, and following this, the full texts of selected papers were accessed and compared against the eligibility criteria.The results of the searches in each database were exported to Endnote .The reported translation procedures of each paper were broken down into mutually exclusive steps. The translation steps of all papers were then merged, and duplicates were removed, to create a list of all potential steps on translating the MoCA.The reported cultural adaptation procedures of each paper were reviewed to identify which questions of the MoCA had been culturally adapted and how. The cultural adaptation procedures for each question across papers were merged and duplicates were removed. This created a list of mutually exclusive steps for each question of the MoCA on how to culturally adapt it, along with the accompanying rationale.38 These scales help display which papers reported their translation and cultural adaptation procedures in sufficient detail to be replicated by future adaptors.Two authors (G.K. and N.M.) assessed the quality of the reported translation and cultural adaptation procedures of the papers by using the Manchester Translation Reporting Questionnaire (MTRQ) and the Manchester Cultural Adaptation Reporting Questionnaire (MCAR) see . These sEach questionnaire is a seven-point rating scale that quantifies the quality of the reporting of the translation and cultural adaptation of a health measure, particularly cognitive tests. A score of 0 means that translation or cultural adaptation was not mentioned; 1 means that it was mentioned but with no details of the process; 2a or 2b means that a description of translation or cultural adaptation was mentioned either in the paper or referring to another paper, respectively, but the description was in insufficient detail for replication; 3 means that the translation or cultural adaptation described according to pre-existing guidelines, with a reference provided; and 4a or 4b means that a description of translation or cultural adaptation was mentioned either in the paper or referring to another paper, respectively, and the description was in sufficient detail for replication.It is important to note that the MTRQ and MCAR do not assess the quality of the actual translation and cultural adaptation, as papers may not always report in detail what procedures they undertook. Instead, rating is based on the extent to which translation and cultural adaptation can be replicated from the information reported.We aimed to gather a description of the cultural adaptation procedures and associated rationale from previous adaptors of the MoCA, who had translated and culturally adapted it for their respective language and culture.42Previous adaptors of the MoCA were identified as those who had made their version available on the MoCA website.https://translate.google.co.uk/), we translated the MoCA versions to English.43 We checked which questions had been directly translated and which questions had been culturally adapted beyond a change in language.We downloaded all adaptations of the MoCA from the website, which currently hosts the MoCA and all its versions, currently providing 62 translations and cultural adaptations of the test, across 54 languages. This included one English version for Singapore and six Chinese versions, highlighting the impact of culture beyond language differences. Using the online translation application Google Translate .These questionnaires asked participants to first mention if their version of the MoCA was mentioned in any publications, and to list them. Following this, it presented them with the MoCA questions they had culturally adapted along with the question's original counterpart. For each of these questions, it enquired why cultural changes were needed, and the rationale behind how they changed it from the original to their version (see Supplementary Appendix 1 available at Questionnaires for 45 of the 62 versions were developed (72.6%). For the remaining 17 versions, we could not make questionnaires as we were unable to create back translations of the test in English. This was because of a lack of resources in terms of electronic translation applications and translators available. These were the Bengali, Kannada, Lithuanian, Malayalam, Marathi, Myanmar, Persian, Russian, Sinhalese, Slovak, Slovenian, Swahili, Tamil, Telugu, Thai, Ukrainian and Vietnamese versions. Therefore, they have been excluded from the analysis (27.4%).Contact information for the adaptors of the MoCA was tracked down by first checking the MoCA version, followed by contacting the MoCA website. If a name was identified, we searched PubMed, ResearchGate and LinkedIn for an active email address. We also searched respective publications on those versions of the MoCA to see if one of the authors was also the initial adaptor and could be contacted through the journal or via the corresponding author.These questionnaires were then sent out to the adaptors via email, along with a request to check our English translation of their version. If the adaptors responded and agreed to complete the questionnaire, we sent a reminder email after 2 weeks. If the adaptors did not respond after another 2 weeks, the email request was re-sent. If no further reply was received after this, no further contact was made.Overall, the contact information for six adaptors could not be identified . Questionnaires for the remaining 39 versions were sent out. Of these, 17 were returned fully completed, including after follow-up emails .To develop guidelines for translating and culturally adapting the MoCA, we combined data on cultural adaptation and rationale behind the adaptation from our scoping review and questionnaire feedback from MoCA adaptors.The questionnaires sent to adaptors were already organised by question and we were able to merge all adaptors’ feedback on the cultural adaptation procedures for each question. We again removed duplicating information so that each question of the MoCA had independent steps that could be undertaken to adapt it, along with the rationale.For each question of the MoCA, its respective data on the cultural adaption steps and rationale behind cultural adaptation from the both the scoping review and questionnaire feedback were merged. Where we saw repetition , the duplicate information was removed.This resulted in a final list of mutually exclusive cultural adaptation steps for each question of the MoCA, along with rationale and guidance on how to conduct those steps. The respective papers and adapted versions of the MoCA were cited, resulting in a question-by-question set of guidelines.Our search identified 19 768 papers on the MoCA  participated. After completion of the BM [Bahasa Malaysia] MoCA, participants were asked to comment on whether any parts of the test were difficult to comprehend or complete.’46Expert recommendations: Individuals with specialist knowledge on translation, target languages or subject matters related to the test, provide information or advice that may affect how the translated test is developed, e.g. ‘The resulting revision was reviewed and amended by a translation committee, which consisted of 3 Korean psychiatrists and 2 psychologists.’47Revisions based on step-by-step feedback: Changes and adaptations are made to the translated test based on suggestions that have been proposed and approved, e.g. ‘Wording was adjusted where necessary, and the process was repeated until the final MoCA-ChLA [Chinese-Language Los Angeles] was considered by the two bilingual psychologists (ELT and PL) to be linguistically and semantically equivalent to the original MoCA, unambiguous, and easily comprehensible.’31 e.g. ‘The original author (ZSN) reviewed and approved the back-translated MoCA-B [MoCA-Basic] version.’48Involvement of the original authors: Authors of the original test provide information or advice that may affect how the translated test is developed; in this instance, authors of the original paper by Nasreddine et al,45Pilot study: A small scale preliminary study is implemented in which the translated version of the test is administered and evaluated to see whether it is viable and suitable for the proposed users, e.g. ‘A pilot study was conducted to establish whether the new BM [Bahasa Malaysia] version of the MoCA could be understood and completed by stroke patients in Malaysia.’The scoping review identified and considered seven discrete steps that can be undertaken in any order when translating the MoCA:Across the 52 papers in our scoping review, a total of 30 different languages were used, with Chinese being the most widely reported; eight papers were included that looked into the translation and cultural adaptation of the MoCA into a Chinese version. This was followed by five papers for the Turkish version, four papers for the Czech version, four papers for the Cantonese version, three papers for the Arabic version, two papers for the Finnish version, two papers for the Indonesian version, two papers for the Malay version and two papers for the Polish version. There was one paper each for the following MoCA versions; Brazilian, Chinese (Changsha), Dutch, English, Filipino, French, Georgian, German, Greek, Hebrew, Hiligaynon, Hungarian, Italian, Japanese, Kazakh, Korean, Malayalam, Persian, Portuguese, Sinhala, Slovenian and Swahili.52 two were for the Chinese version54 and two were for the Czech version;56 there was one paper each for the Singaporean,57 Slovenian,58 Malay,59 Italian,60 Indonesian,61 Hungarian,62 Hebrew63 and Greek versions.64Out of 52 papers, 16 mentioned a translation process taking place but did not provide enough detail with regards to specific steps. Consequently, a score of 1 was given to these papers on the MTRQ scale. Of these, four papers were for the Turkish version,44 Freitas et al,90 Husein et al84 and Sahathevan et al45) reported using all of the translation steps. The remaining 32 reported to have undertaken some translation steps, in various combinations.Excluding the aforementioned papers, All of the papers reported simple translation, 25 papers undertook back translation, 21 involved the use of expert recommendations, 15 involved original authors, 14 made revisions based on step-by-step feedback, 14 directed pilot studies and eight reported users in co-production.49 Bezdicek et al,55 Memoria et al,68 Nortunen et al,78 Potocnik et al,58 Puustinen et al,79 Reban,56 Thissen et al,76 Tsoy et al85 and Volosin et al62) did not mention any cultural adaptation that may have taken place, resulting in a score of 0 on the MCAR scale. Ten papers  mentioned that a cultural adaptation process took place but did not describe it, scoring 1 on the MCAR.Out of the 52 papers, ten .20 The current breadth of cognitive tests are susceptible to cultural bias and require an extensive cultural adaptation beyond a translation verbatim.30The diagnosis of dementia and MCI within elderly ethnic minority populations is currently compromised because of the lack of cognitive tests that account for the language and culture of individuals from these populations.38 We aimed to replicate these methods for the MoCA, a popular cognitive test used to screen and diagnose for dementia and MCI. Through the combination of a scoping review and questionnaire feedback from adaptors of the MoCA, we were able to successfully develop guidelines on translating and culturally adapting the MoCA.One solution to this is to produce individual guidelines for the cultural adaptation of various cognitive tests, as has been previously done for the ACE-III.The scoping review was able to list all papers on existing translations and cultural adaptation of the MoCA and through the MTRQ and MCAR ratings, highlight which papers provide the most replicable data on translating and culturally adapting the MoCA for future adaptors to consider.94 A native speaker is not necessarily someone qualified or informed about the nuances of cognitive tests, thus an additional expert in this field of study would be desirable to help form a cultural adaptation or accurate translation.Through our review, a full list of independent translation steps that can be undertaken by future adaptors was identified along with the frequency of their occurrence. This allows future adaptors to make judgement calls regarding which steps they may endeavour to undertake, based on what previous adaptors followed. Naturally, some approaches such as simply having a native speaker back-translate a measure would be problematic from a clinical or psychometric standpoint.84 whereas in the other only one step was.61 This would suggest that translation steps were undertaken on the basis of convenience and resources, as opposed to the best fit for different language and cultural groups.We can see that direct translation was the most common step, undertaken by all of the publications, followed by back translation, expert recommendations, the involvement of original authors, revisions based on step-by-step feedback, pilot studies and finally, users in co-production. Across the same language versions, although there is some overlap of translation steps undertaken, there is no consistency. For example, in one Indonesian version all of the translation steps were undertaken,We also identified which cognitive domains and their respective questions were considered to be dependent on culture and therefore most likely to be culturally adapted. Question 10 for language, which focused on verbal fluency, was culturally adapted the most, followed by further questions for language and memory. On the other hand, questions for attention based on numbers  and visuospatial abilities had not been reportedly culturally adapted as much in any of the papers.Thus, we have identified which possible domains of the MoCA display significant cultural reliance. It is important to note that although cognitive domains such as attention and visuospatial abilities were not frequently adapted in our findings, this does not necessarily mean that they cannot be influenced by culture in other cases.Through our questionnaires we were able to acquire additional and far richer data on the cultural adaptation of the MoCA, including rationale behind changes made. As with our scoping review, this feedback from adaptors showed which questions were most likely to require cultural adaptation, indicating their cultural dependence.Findings from the questionnaires mirrored those from our review: question 10 for language was once again the most culturally adapted, followed by the same questions for language and memory. Similarly, questions for attention based on numbers, executive functioning and visuospatial abilities received little to no cultural adaptation by adaptors.The previous systematic review of adaptations of the ACE-III reported similar findings across cognitive domains and their questions. Reasoning behind these findings in both our scoping review and across questionnaires is that executive functioning, visuospatial abilities and number-based tasks are not associated with culture. This indicates to future adaptors which questions should be prioritised for cultural adaptation.Across the same language versions there was little overlap, suggesting that different cultures may have different needs with regards to cultural adaptation, even if they share a language. Interestingly, however, within the Cantonese and Chinese versions there was consistency across the versions in requiring cultural adaptation for question 1 for executive functioning and question 7 for attention – questions that typically do not require adaptation. This is because they rely specifically on the alphabet, in contrast to Cantonese and Chinese characters. In this instance, language and culture played a dual role and required the cultural adaptation of these questions for these specific language versions, irrespective of which country the version was for.Our scoping review was restricted in several ways that prevented the incorporation of some language and cultures. First, it was restricted by what was reported in the papers. Further and additional adaptation procedures that may have been undertaken by adaptors but were not mentioned in their respective papers still resulted in scores of 1 and 0 on the MTRQ and MCAR. The scales also cannot guarantee the quality of those processes, and whether they resulted in robustly adapted versions of the MoCA.Second, regarding our questionnaires sent to adaptors, we were limited by resources and translators available to us, and therefore unable to produce and distribute questionnaires for all 62 versions of the MoCA. The relatively poor return rate of 17 out of 62 questionnaires reduced the amount of additional information we could have included in the guidelines.This highlights the significance of conducting the scoping review and questionnaires in tandem, and combining the findings to allow for the incorporation of as much information as possible. The guidelines are not restricted to information available in published literature, and incorporate primary experiences of cultural adaptation by existing adaptors of the MoCA, which accounted for adaptations that may not have had corresponding papers.Additionally, the adaptations reported were culturally skewed favouring primarily MoCA versions from Asia (mainly China) and Europe. However, the guidelines are designed in such a way that they can be used to culturally adapt the MoCA in countries such as those from Africa or South America.If a language in these countries is not letter-based but character-based, then it may be more appropriate to use a category fluency task rather than a letter fluency task, as it has been shown to be just as effective. Similarly, if the images of animals that have to be recognised are not animals familiar in certain countries, native animals knowledgeable to older groups should be selected. Words that have to be remembered should not just be directly translated into the corresponding language; a word that represents the same concept but also has the same fluency in the target language and, ideally, the same number of syllables should be used instead.Examples and associated rationale like this within the guidelines can help support and guide adaptors who want to adapt the MoCA for their respective language and culture, regardless of where they are from.38 the guidelines for the MoCA compiled data for 32 languages across 38 countries. Additionally, the ACE-III review found 32 papers and only six completed questionnaires from adaptors of the ACE-III were received.36 In comparison, the MoCA guidelines are composed of far richer and extensive data.Overall, we replicated a novel approach that has only previously been done once before. However, unlike the ACE-III guidelines, for the MoCA we were able to gain more data as the MoCA originated earlier, with far more translated and culturally adapted versions. Although the ACE-III guidelines compiled data from 22 languages and cultural contexts,The implications of this methodology, and the findings regarding questions pertaining to specific cognitive domains, can be replicated further to develop guidelines in the same manner for other cognitive tests. Furthermore, these particular methods allow for familiarity with a chosen test.However, although we have demonstrated that these set of guidelines can assist future adaptors in creating their own version of the MoCA, it does not obviate the need to conduct a formal cultural and psychometric validation within a target population. These are essential steps that should follow the development and utilisation of guidelines to produce a culturally adapted version of a test.Naturally, other factors beyond culture, such as age and education level, can also influence sensitivity. Therefore, it may also be appropriate to use cut-offs and point adjustments for these factors once translation and cultural adaptation has occurred for a test, and future researchers should endeavour to establish what these might be during psychometric validation in large clinical populations.Overall, these guidelines can act as a starting point for future adaptors of the MoCA, and have been designed so that necessary updates and further information on cultural adaptation can continue to be added to them. The next step would be to implement these guidelines to develop an adaptation of the MoCA for a particular language and cultural context, as was done for the ACE-III, to demonstrate usability and cultural validity.