This commentary brings together theory, evidence and lessons from 15 years of gender and HRH analyses conducted in health systems in six WHO regions to address selected data-related aspects of WHO’s 2016 Global HRH Strategy and 2022 Working for Health Action Plan. It considers useful theoretical lenses, multi-country evidence and implications for implementation and HRH policy. Systemic, structural gender discrimination and inequality encompass widespread but often masked or invisible patterns of gendered practices, interactions, relations and the social, economic or cultural background conditions that are entrenched in the processes and structures of health systems  that can create or perpetuate disadvantage for some members of a marginalized group relative to other groups in society or organizations. Context-specific sex- and age-disaggregated and gender-descriptive data on HRH systems’ dysfunctions are needed to enable HRH policy planners and managers to anticipate bottlenecks to health workforce entry, flows and exit or retention. Multi-method approaches using ethnographic techniques reveal rich contextual detail. Accountability requires that gender and HRH analyses measure SDGs 3, 4, 5 and 8 targets and indicators. To achieve gender equality in paid work, women also need to achieve equality in unpaid work, underscoring the importance of SDG target 5.4. HRH policies based on principles of substantive equality and nondiscrimination are effective in countering gender discrimination and inequality. HRH leaders and managers can make the use of gender and HRH evidence a priority in developing transformational policy that changes the actual conditions and terms of health workers’ lives and work for the better. Knowledge translation and intersectoral coalition-building are also critical to effectiveness and accountability. These will contribute to social progress, equity and the realization of human rights, and expand the health care workforce. Global HRH strategy objectives and UHC and SDG goals will more likely be realized.The online version contains supplementary material available at 10.1186/s12960-023-00813-9. Global Strategy on Human Resources for Health (HRH) and its implementation guidance, such as the 2022 Working for Health (W4H) Action Plan [gender dynamics in health labor markets [This commentary contributes to understanding important gender-related aspects of the World Health Organization’s (WHO) 2016 ion Plan  to stren Health WH Action systemic structural gender discrimination and inequality (SSGDI) are dysfunctions that undermine gender equality, social progress and health/HRH systems’ objectives. In this commentary, we consider theoretical lenses for gender and HRH analysis, multi-country evidence of SSGDI and implications for implementation and policy. We address the following questions:What are systemic structural gender discrimination and inequality (SSGDI) in the health workforce and why are they out of the awareness of most human resources (HR) planners, managers and service providers?Why should it be a priority to collect data to make SSGDI visible in workforce systems?What are the implications for implementation and HRH policy?What are practical steps to make gender analysis results accessible to and actionable by HRH/M policy planners and managers?To achieve transformational social progress, equity and the realization of human rights, our understanding of gender equality and inequality in HRH should be informed by evidence, as must HRH policy. Both the theoretical/conceptual and evidence bases of gender and HRH should be strengthened to demonstrate the ways in which systemic structural gender discrimination and inequality and provide illustrative examples in HRH systems. See Box systemic structural gender discrimination and inequality in health education and employment systems.Theories and concepts from the sociology of gender, work and organizations describe some of the dynamics of gender discrimination and inequality in the health workforce. These can be applied as lenses through which to understand evidence generated by gender and HRH analyses, allowing policy planners and managers to connect the dots between gender dynamics and negative/dysfunctional HRH effects and consequences. Below, we highlight aspects of theory or concepts that contribute to understanding elements of Gender has been defined differently over disciplines and contexts, with some seemingly irreducible differences and some common elements [socially constructed phenomenon [Health Labour Market Analysis Guidebook refers to gender as “Socially constructed identities, attributes and roles for women and men and society’s social and cultural meaning resulting in hierarchical relationships between women and men and in the distribution of power and rights. This social positioning of women and men is affected by political, economic, cultural, social, religious, ideological and environmental factors and can be changed by culture, society and community [systemic, structural gender discrimination and inequality (SSGDI) in health systems. See Box elements , 6. One enomenon . For thienomenon . The WHOommunity , p. 167.gender order  and in organizational gender regimes . Gender is brought into social relations through interactions [ideology of domesticity [Sociological-relational theories give a central place to the small-scale behaviors and social interactions and large-scale patterned relations between women and men (and among women and among men) that constitute gender as a social structure, and which are shaped by, address, and modify this social structure . Gender ractions  that areesticity , 12, wheesticity .«gender is one of the three or four identities  that are central to the process by which people render themselves comprehensible to themselves and others in terms that are socially valid within their society…As a result, both men and women have deep cognitive interests in maintaining a clear and reasonably stable framework of gender beliefs that define “who” men and women “are” by differentiating them» [It has been observed that ng them» , 15. An ng them» . Even thng them»  over timoccupations, one of the most profound, widespread and enduring dimensions of labor market inequality, compared with segregation by race or class [delivered by women but led by men [gender regimes of health education institutions [Gender systems not only constitute people as significantly different in essence, but also as of greater or lesser value. Social relations of inequality are then organized in hierarchies on the basis of greater or lesser value , 16. Theor class . An examd by men . The defitutions . Violencitutions .glass ceiling and the glass escalator, aspects of occupational segregation in the health sector. Glass ceiling practices consist of invisible barriers to reaching top leadership and management positions, that include, for example, the initial placement of  women in relatively low-level, dead-end jobs; not offering job assignments that lead to advancement; not promoting women or greater scrutiny on women’s performance relative to men’s before being promoted; or a lack of access to informal networks and opportunities for mentoring [glass ceiling was generated  during recruitment by a criterion for a leadership and management position required the job candidate to have a medical degree to be selected—a condition to which the majority-female nurse workforce in Uganda was unable to comply [glass escalator refers to a workforce effect whereby men bring their privileged status from the wider society/culture to their entry into predominantly female occupations. Male nurses are often accepted and well-integrated in a female-dominated profession such as nursing and given fair if not preferential treatment in hiring and promotion decisions, despite their being in a minority [Other structural inequalities include the entoring . A gendeo comply . The glaminority .glass escalator and glass ceiling are linked to notions of the greater status worthiness of men  [gender-relational stereotyping and “prove it again” dynamics [glass escalator in recruitment and promotion of male nurses, which served to exclude female nurses from senior leadership roles in service delivery, research, and health policy.Both the primacy) , for exaprimacy) . This andynamics  for womesystemic structural gender discrimination and inequality in HRH systems.The foregoing examples demonstrate the processes of gender differentiation, stratification, coercion/violence and exclusion that are aspects of Box 1. Systemic structural gender discrimination and inequality in health education and employment systemssystemic, structural gender discrimination and inequality (SSGDI) covers widespread, but often masked patterns of gendered behavior, policies or practices, relations and the social, economic or cultural background conditions that are entrenched in the processes and structures of institutions  and which can create or perpetuate disadvantage for some members of a marginalized group relative to other groups in society or organizations [Is created through past/historic discrimination in gendered social orders and in institutional gender regimesIncludes direct and indirect discriminationIs the most persistent obstacle to the achievement of substantive gender equalityUnderscores the ineffectiveness of gender-blind policies that do not recognize gender and that women and other marginalized groups may continue to deal with the effects of past or historic discrimination in the present, while others may continue in the present to benefit from historic social advantage –24.The term izations –24. SSGDmasked or invisible unless concerted efforts are made to make them visible. They are masked because they are expressions of everyday behaviors and norms which are central to the smooth operation of small-scale interpersonal interactions or large-scale institutional patterns in gender systems. Often, masculine-typed behaviors are taken as the norm—either as universal or normalized. For example, an analysis of sexual harassment in Uganda’s public health sector [Gender-blind institutional policies also ignore and mask sexually harassing behaviourial norms and may contribute to maintaining class and, possibly, race and ethnic, stratification, which may also be masked in organizations [The dynamics of SSGDI are usually h sector  showed tizations .behaviors or policies that ignore gender norms, roles and relations and very often reinforce gender-based discrimination. By ignoring differences in opportunities and resource allocation for women and men, such policies are often assumed to be “fair” as they claim to treat everyone the same.» [The term «gender blindness»  describes why/how SSDGI operate out of the awareness of most HR planners, managers and service providers. It refers to «e same.» . For exablind to the gendered nature of organizations and jobs. Common understandings of the «job» are often based on an implicit assumption that there is an abstract, disembodied universal worker who can dedicate 100% time to the job unencumbered by child-bearing/rearing, a worker  who can depend on someone else to play the gendered role of a «wife» who takes care of domestic needs, children and other family responsibilities. The conception of an abstract, disembodied universal worker in a disembodied job nevertheless operates through a gender-based division of labor and the separation between the public and the private spheres which are evident in the masked but widespread phenomenon of occupational segregation [universal worker are actual preferences for men’s expectations of paid work in the public sphere and looser relationships to procreation and labor in the private sphere  [It is not unusual to be regation . Implicidership) . Implicidership) .Gender-blind language such as «health workers» also masks the reality of a gendered relationship to public and private spheres. For example, a time-use survey comparing the public- and private-sphere workloads of female and male full-time health workers in Mali found that female health workers had more domestic responsibilities than male health workers and that these took more time , esembodied workers with the potential to procreate, among other things. At a minimum:«…All serious gender theory concerns bodies. Gender is a structure of a specific kind, built from the relationships that concern the reproductive distinctions between human bodies. Gender practice is a reflexive process of social embodiment…how a society handles sexuality, reproduction, child growth, motherhood, fatherhood, and all that is socially connected with these processes.» [cesses.» , p. 1677It should be noted that health jobs are occupied by social embodiment is typically ignored in gender-blind HR policies and practice. For example, a gender and HRH analysis in Senegal’s public health sector (which requires continuous operation) found that night duty was delegated to nurses and midwives the majority of whom were married women of reproductive age with children, separated by deployment policy from spouses in rural areas with no institutional or familial childcare support. To manage the conflicts created by tending to private-sphere responsibilities at night, these health workers were often obliged to bring their infants along with them into the public sphere where night guard duty took place. Failure to factor embodiment and public and private sphere workloads into HRH policies, job design, schedules and workloads is at the heart of the widespread problem of «work–life conflict» and attrition.That health labor market jobs involve Some managers view human reproduction as an intrusion into the workplace and respond not by proactive planning but by excluding (not hiring or promoting) women of reproductive age from good jobs in the labor market. Research demonstrates that family caregiving excludes women from health education and training , 46, 48 social closure and social closure discrimination [Social closure involves the drawing of boundaries between groups in “a process of subordination in which one group secures its advantages by closing off the opportunities of another group that it defines as inferior and ineligible”, and by maximizing rewards by restricting access to resources and opportunities to a limited circle of eligibles» [inequality generating processes [Finally, the concepts of mination  are usefmination ), the glmination . Social igibles» , 29 in mrocesses , 31. Therocesses .systemic structural gender discrimination and inequality (SSGDI) in the health workforce. Evidence in Table Inequality generating processes of gender differentiation, stratification, coercion/violence, exclusion and social closure are at work in Health Workforce Support and Safeguards List, countries which face the most pressing health workforce challenges related to Universal Health Coverage [The evidence of SSGDI in Table Coverage .Gender Discrimination and Inequality Analysis or GDIA) anticipated and addressed the need for evidence especially from low- and middle-income countries (LMICs) on the gender dimensions of the health workforce [The methodological approach taken in the multi-method analyses summarized in Table orkforce . The GDIthick description» [cross-cultural portability of some aspect of gender-related theory developed in the United States, the United Kingdom and parts of Europe where gender and workforce studies found early traction. Additional file Systemic structural discrimination and inequality in Senegal’s public health sector, discusses the meaning of GDIA data in terms of sociological-gender concepts and substantiates their cross-cultural portability.Qualitative techniques from ethnography . Among other factors, undesirable or unsafe tasks often performed during unpaid night work together suggested a category bias against nurses and midwives [male primacy in the glass ceiling and glass escalator, the devaluation or denigration of women and their competence, and the contesting of women’s authority or presence in workplaces, were underpinned by beliefs about female incompetence (Rwanda) or an ideology of domesticity , made visible by the GDIAs.midwives  in Senegsex for grades” in preservice education systems were lack of safety, student drop-out and reduced health worker pipelines . Quid pro quo and sexual coercion (Uganda) operated as “sex for employment rewards” which created hostile work climates and conflicts between supervisor and staff or between colleagues, barriers to career advancement and turnover and sometimes resulted in workforce exit and discontinuity of health services. Sexually harassing behaviors were typically normalized, silenced by victim-blaming and stigma, not reported and thus obscured in daily work interactions, though also considered an “open secret” .Sex-based harassment  or fear of sexual violence and retaliation occurred in all nine  country gender-blind HRM policy environments allowed gender bias, discrimination and inequality and social closure to operate freely. All these factors were obstacles to health workforce development, retention and expansion—and to the economic security of female health workers.The negative HRH effects and consequences summarized in Table embodied workers, then lifecycle events would more likely be planned for and staff shortages (temporary or permanent) mitigated through, for example, a pregnancy cover policy. Health service discontinuities would likely be mitigated. If enabling conditions, such as access to childcare, were routinely offered as HRM infrastructure, perhaps female health workers would less easily become targets of marginalization. Parental leave might be an incentive to sharing the burden of unpaid care and domestic work, which would promote equity and social progress, since to achieve gender equality in paid work, women need to achieve equality in unpaid work [As seen in Table aid work . Any of aid work .systemic, structural gender discrimination and inequality.To draw strong linkages between SDG5 targets and non-health Sustainable Development Goals (SDGs): gender and HRH analyses must be conceptually stronger, produce better data, and enable policy planners to connect the dots between evidence of an HRH problem and corrective policy action. All SDG 5 targets Box  are releGender and health workforce analyses provide opportunities to strengthen intersectoral linkages and impact non-health SDGs, for example, SDG 4 (Education), SDG 8 (Employment and Decent Work) and especially SDG 5 , an3.WHO Health Labour Analysis (HLMA) Guidebook provides guidance on how to analyze the invisible gender dimensions of health labor markets, suggesting gender analysis questions, variables/indicators and data sources. The mapping of gender orders and gender regimes is a major task of social science research on gender [discriminatory processes, structures and relational patterns and conditions that potentially lead to social closure and that undermine workforce attraction, retention and expansion . Most importantly, HLMA should generate evidence describing the real, gendered terms and conditions of health workers’ educational, employment and personal lives to be addressed by gender-transformative HRH policy.The 2021 n gender  and thisclosures for women in health sector is particularly important for understanding workforce flows into, in and around and out of health systems. Relevant contextual gender and HRH evidence should be available for the development of any HRH policy to demonstrate why gender-blind HRH policies would likely be ineffective in countering discrimination and correcting an uneven playing field of gender-segregated labor. Once the operation and consequences of SSGDI are visible, HRH/M policy planners would have the rationale to counter discrimination and inequality though anti-discrimination and substantive equality policies and measures to bring about changes in the real conditions of health workers’ lives and work—for the better. Gender transformative policy will then be workforce transformative. The reader is referred to readings that describe gender-transformative substantive equality and nondiscrimination principles and special measures [Gender and HRH analyses can improve policies by making the dynamics, effects and consequences of SSGDI visible as health systems dysfunctions to be addressed by proactive or corrective HRH policy. Revealing masked occupational or professional  measures –24, 41.Conducting a gender and HRH analysis is not sufficient to develop and implement effective gender- and workforce-transformative policies. New understandings of gender discrimination, inequality, equal opportunity, nondiscrimination and substantive gender equality will be necessary. To do this, systematic knowledge translation  and inteMaking the dynamics of SSGDI visible will allow HRH policy planners and managers to craft effective policy and anticipate bottlenecks to workforce entry and flows and transform the actual conditions of health workers’ work and lives for the better. There must be new understandings about systemic structural gender discrimination and inequality in HRH, investment in collecting and using context-specific, sex- and age-disaggregated, gender-descriptive data and translating knowledge into intersectoral policy action to counter their systemic, structural effects and negative consequences for the health workforce. Gender transformative policy based on nondiscrimination and substantive equality principles will be workforce transformative. Global HRH strategy and W4H Action Plan objectives and UHC and SDG goals will more likely be realized.Additional file 1. Systemic structural discrimination and inequality in Senegal’s public health sector.


Opioid analgesics are the mainstay of pain management. However, their acute or chronic use leads to side effects, such as respiratory depression, constipation, tolerance and opioid use disorders, representing major public health and socioeconomic issues.in vivo animal models to in vitro molecular approaches, authors provide scientifically sound evidence in the evaluation of novel opioids and potential pharmacotherapeutic tools for the treatment and prevention of opioid use disorders.In this Research Topic, “Opioids and Opioid-Use Disorders: Novel Approaches and Therapeutics,” we have compiled a Research Topic of research articles authored by leading experts in the fields of pharmacology, neuroscience, and addiction research. By harnessing a wide range of methodologies, spanning from Ou et al. measured c-fos, as a marker of neuronal activity, following administration of different doses of morphine in rats using the conditioned taste aversion (CTA) and conditioned place preference (CPP). Then, by using a correlation and network analysis strategy they revealed: 1) in the CTA procedure an association between prelimbic cortex (PrL) and  with NAc core following low doses of morphine. Notably, the authors also observed an association between PrL and IL with NAc shell following higher doses of morphine; 2) in the CPP procedure, an association between PrL and NAc core and shell at low doses of morphine. Again, the authors observed an association between IL and BLA and NAc shell with higher doses of morphine. These results suggest the recruitment of different neuronal projections between cortical and accumbal subregions and BLA after different doses of morphine and the balance between these connections may favor drug use vs. avoidance and result in continued use.Morphine and other addictive drugs may exert simultaneous reward and aversion and the tag of war between these two effects leads to drug use and misuse or avoidance, this is based on the paradoxical effect hypothesis of abused drugs. Haggerty et al. investigated in mice the impact of prenatal methadone exposure (PME) on the brain and behavioral development of neonates. The study revealed that PME altered the proteome and phosphoproteome of the primary motor cortex (M1) and other connected brain regions, including the primary somatosensory cortex (S1), dorsolateral striatum (DLS), and dorsomedial striatum (DMS). PME was found to affect glutamatergic synapses in M1, with increased glutamate synapse density and decreased glutamate receptor expression. The study suggests that the persistent neuroadaptations in M1 and connected brain regions due to prenatal opioid exposure (POE) may contribute to deficits in motor behavior function throughout the lifespan. Deciphering these changes could lead to novel treatments for mitigating the negative impact of POE on motor and other developmental features.Illenberger et al. assessed the effect of an orally administered orexin receptor antagonist, suvorexant  on intravenous escalation of oxycodone self-administration  and reinstatement elicited by a contextual/discriminative stimulus in rats. They reported that female rats self-administered oxycodone twice as much as male rats. SUV administration blocked cue-induced reinstatement of oxycodone SA in male and reduced it in female. The highest dose of SUV also reduced oxycodone SA. As the authors indicated, this class of drugs can be repurposed to treat opioid use disorder.The orexinergic system is critically involved in reward-related behavior and significantly alters stress responses. Using drug self-administration in rats, Piekielna-Ciesielska et al. described the synthesis and evaluated thirteen endomorphin 2 (EM-2) analogs with modifications in positions 1, 2, and/or 3, which displayed high affinity toward the mu opioid receptor similar to EM-2 in the calcium mobilization assay. Log p values revealed that all of the analogs had somewhat increased lipophilicity and stability compared to EM-2. All experiments were in vitro and examined affinity and activity. Using BRET, the authors showed that nearly half of the developed analogs exhibited bias toward G-protein with no preference toward beta-arrestin 2 recruitment. Considering that G-protein biased compounds could possess analgesia with limited side effects, these compounds could provide the best tools to test this possibility.Despite the recent development in pain management, opioids remain the mainstay for the treatment of moderate to severe pain. To reduce their abuse potential, attempt have been made to develop several classes of novel opioids acting at mu opioid peptide receptors (MOP) and other receptors, called bifunctional compounds have been developed, showing promise as analgesics with reduced tolerance and dependence liability. However, the effects of these novel compounds on respiratory, gastrointestinal, and cardiovascular systems have not been fully characterized. Further studies are needed to determine their impact on the brain reward circuit, as well as to assess the behavioral, neurochemical, and molecular changes following chronic use and their implications in substance use disorders. Additionally, it is essential to explore whether the addition of these novel small molecules would hinder or promote overdose and death associated with opioid use. In light of these knowledge gaps, further investigation of these bifunctional compounds is crucial to unveil their full therapeutic potential and safety profile, paving the way for improved pain management and addiction treatment strategies.Despite the recent development in the field of opioids, further research is needed to develop safer analgesics with reduced or no abuse liability or adjunct therapeutic agents, such as SUV, that reduce abuse potential of opioids.


Exploring spatiotemporal evolution features and factors affecting pollution reduction and carbon abatement on the urban agglomeration scale is helpful to better understand the interaction between ecological environment and economic development in urban agglomerations. In this study, we constructed an evaluation index system for collaborative governance of pollution reduction and carbon abatement in urban agglomerations. In addition, we employed the correlation coefficient matrix, the composite system synergy model, the Gini coefficient, and the Theil index to evaluate the level of and regional differences in collaborative governance of pollution reduction and carbon abatement in seven urban agglomerations in the Yellow River Basin from 2006 to 2020. Moreover, we explored the factors affecting collaborative governance of pollution reduction and carbon abatement in urban agglomerations in the basin. The following findings were obtained: (1) the order degree of collaborative governance of pollution reduction and carbon abatement in the seven urban agglomerations exhibited a significant growing trend, representing a spatial evolution feature of “high in the west and low in the east”; (2) the internal differences in collaborative governance synergy of pollution reduction and carbon abatement decreased in Lanzhou–Xining Urban Agglomeration, Hohhot–Baotou–Ordos–Yulin Urban Agglomeration, Central Shanxi Urban Agglomeration, Zhongyuan Urban Agglomeration, and Shandong Peninsula Urban Agglomeration, while the internal differences basically remained stable in Guanzhong Urban Agglomeration and the Urban Agglomeration along the Yellow River in Ningxia; (3) the variances in environmental regulation and industrial structure among urban agglomerations had a significant positive effect on collaborative governance of pollution reduction and carbon abatement in urban agglomerations in the basin, and the variances in economic growth had a significant inhibitory effect. In addition, the variances in energy consumption, greening construction, and opening-up had an inhibitory impact on collaborative governance of pollution reduction, but the impact was not significant. Finally, this study proposes various recommendations to improve collaborative governance for pollution reduction and carbon abatement in urban agglomerations in the basin in terms of promoting industrial structure upgrading, strengthening regional cooperation, and reducing regional differences. This paper represents an empirical reference for formulating differentiated collaborative governance strategies for pollution reduction and carbon abatement, comprehensive green and low-carbon economic and social transformation programs, and high-quality green development paths in urban agglomerations, which is of certain theoretical and practical significance. The sixth IPCC report issues the most severe warning so far: human behavior is accelerating the process of global warming at an alarming rate, and the global climate, oceans, and atmosphere are facing imminent and terrible risks [2 emitters in the world and predominant in changing the global climate [As the world economy rebounds from the COVID-19 crisis, the current trend of relying on coal to promote economic growth is continuing, and global energy related to CO climate . The rel climate , urban c climate , persona climate , regiona climate , and so 2 and air pollutants mainly originate from combustion of fossil fuels in human production and life. Because of their homology and synchronization in terms of the production process and the mutual effect of the hazard generation process, collaborative governance of pollution reduction and carbon abatement (PRCA) is theoretically feasible [2, could reduce generation of other pollutants. Thereafter, the IPCC [Both COfeasible ,9. Basedfeasible . The assthe IPCC  formallyClimate warming has attracted academic attention, and various scholars have discussed synergy effects related to relevant carbon abatement policies on reduction of atmospheric pollutants. Relevant policy research covers international climate agreements , constru2 emissions in a community in Los Angeles [2 and PM2.5, and the co-control effect of decreasing carbon discharge and air pollution was remarkable [Environmental governance studies demonstrate that reducing discharge of air pollutants, solid waste, and wastewater pollutants is a good way to attain environmental governance, and reducing emissions of pollutants can bring about such synergistic effects as carbon emission reduction and climate change. Okorn et al. verified synergy of pollutant emission reduction by simultaneously monitoring air pollutant emissions and CO Angeles . Peng We Angeles . Wang etmarkable .2 concentration across different agricultural forms of production, showing that productive application of green infrastructure was as beneficial as nonproductive applications in reducing ozone, nitrogen dioxide, and CO2 concentration [In recent years, most scholars have introduced multiple indicators to discuss the synergistic effect of PRCA, and measures to improve PRCA fall into three categories: technical improvement , structuntration . By compntration .Urban agglomerations are the chief drivers of regional economic development and the places with the highest concentrations of carbon discharge and air pollution . With inThe main contributions of this paper are as follows: first, regarding investigation of level of inter-regional PRCA collaborative governance, the existing studies are mainly conducted from a single dimension, while this study establishes the assessment index system of PRCA collaborative governance in four dimensions. Second, the paper reveals the spatiotemporal evolution features of PRCA collaborative governance level on urban agglomeration scale, measures PRCA collaborative governance degree of urban agglomerations using the correlation coefficient matrix and composite system synergy degree, and analyzes regional differences in PRCA collaborative governance of urban agglomerations by combining the Gini coefficient and Thiel index. Finally, this paper discusses the factors that affect PRCA collaborative governance in the basin’s urban agglomerations and explores the impact of different factors in urban agglomerations on PRCA collaborative governance.The remaining sections are arranged as follows. 2 emission intensity, which account for the emphasis on energy conservation and carbon reduction [The Yellow River Basin covers nine provinces, which contains three mature urban agglomerations and four emerging urban agglomerations, forming a “3 + 4” spatial organization pattern  Environmental pollution. In full consideration of the comprehensiveness and complexity of environmental pollution, we selected five indicators as order variables to gauge atmospheric and water pollution: discharge of industrial wastewater, discharge of industrial sulfur dioxide (SO), total discharge of smoke (dust), CO(2) Environmental governance. Environmental governance is the core component of urban sustainable development. Representative indicators were chosen from the angles of water, solid waste, and garbage treatment, and rate of industrial solid waste integrated processing, centralized processing rate of sewage treatment plants, rate of innoxious disposal of urban garbage, and disposal rate of urban domestic sewage were used to reflect the emission control levels of various environmental pollutants.(3) Resource utilization. In addition to economic growth, intensive use of resources is also a great concern. Total energy consumption was introduced to reflect energy use, coal consumption was used to reflect energy consumption structure, and total water supply was used to reflect the control level of regional water resource utilization in the study.(4) Economic development. Economic development is substantially manifested in economic aggregate expansion and improvement of developmental quality. In this study, regional GDP was adopted to reflect total economic output, GDP growth rate was applied to assess quality of urban wealth creation, per capita disposable income and social consumable total retail sales were used to reflect national consumption capacity, direction of economic development was evaluated by amount of regional social fixed assets investment, and added value ratio of tertiary industry in GDP was employed to represent the optimized structure of the urban economic structure.The correlation coefficient matrix was introduced to measure weight so as to avoid the influence of subjective factors . SupposiThe order parameter of PRCA collaborative governance is  formula ,46:(3)Uwequation :(4)UwF=β∑wThe Gini coefficient (Gini) and Theil index (TB) were employed to analyze the PRCA composite system synergy difference of the urban agglomerations, which were calculated using the following equations :(6)Gini= follows :(8)TB=TBCHINA CITY STATISTICAL YEAR BOOK, CHINA INDUSTRY STATISTICAL YEAR BOOK, CHINA STATISTICAL YEARBOOK OF THE TERITARY INDUSTRY, CHINA STATISTICAL YEARBOOK ON ENVIRONMENT, and CHINA ENERGY YEARBOOK. In addition, the relevant data on carbon emissions were obtained from China Emission Accounts and Datasets.The study selected relevant data concerning urban agglomerations in the Yellow River Basin from 2006 to 2020. Most of the data were selected from According to the mode and characteristics of PRCA collaborative governance in the urban agglomerations, in order to better reflect the order parameters and overall degree of order of the subsystems, we assessed the weight of each order parameter using the correlation coefficient matrix. Considering the different dimensions of each order parameter, the original data were processed in a dimensionless manner and introduced into Formula (3) to obtain the order degree of each order parameter. Then, the index weight determined by the correlation coefficient matrix method was applied in Formula (4) to obtain the order degree of PRCA governance system of the seven urban agglomerations from 2006 to 2020 , we obtained the PRCA collaborative governance synergy of the urban agglomerations from 2007–2020 , PRCA synergy degree (SD) expresses the variables explained in this study. When selecting explanatory variables, taking the existing literature into consideration, we extracted six indicators to probe the factors that affect PRCA synergy degree (as shown in (1) Industrial structure variance. Industry is an essential driving force for economic and social development in the basin’s urban agglomerations and represents the main source of local air pollutants and carbon emissions. At present, the industrial structure of the basin’s urban agglomerations is composed of the heavy chemical and energy industries, which causes obvious problems, such as extensive industrial development and a low proportion of technology-intensive industries. Therefore, the proportion of secondary industry to GDP was employed to reflect the industrial structure, and the relative dispersion of the ratio of secondary industry to GDP was used to express regional differences in terms of industrial structure in this paper.(2) Environmental regulation variance. From the perspective of public economics, as a public product with strong positive externality, environment is essentially a public service provided by the government. Environmental governance investment comes from government subsidies, enterprise self-financing, and bank loans, but it is ultimately affected by work of local governments. However, gravity of environmental pollution in the basin’s urban agglomerations is disproportionate to environmental protection investment. Moreover, there is a certain deviation that makes environmental governance investment fail to function as it should, i.e., to improve the environment. Therefore, this paper uses environmental governance investment to characterize environmental regulation and introduces relative dispersion of environmental governance investment to reflect the variances in environmental regulation between regions.(3) Economic growth variance. Improvement in economic development tends to impact regional industrial structure, consumption structure, and other aspects. On the one hand, residents in areas with low economic development are more willing to trade environment for growth. On the other hand, in order to gain political support, local governments interfere in implementation of environmental policies in exchange for local economic growth. Accordingly, variance in economic development can affect the regional synergy of environmental governance. Therefore, in this paper, GDP per capita is employed to represent economic growth degree, and relative dispersion of GDP per capita is applied to reflect variances in economic growth between regions.(4) Energy consumption variance. Generally, in regions where energy is produced from fossil fuels, high economic growth means more energy consumption, which is liable to generate more air pollution and carbon discharge. To reach the target of PRCA collaborative governance, the basin’s urban agglomerations need to control total energy consumption and reduce lagging capacity as increase in energy consumption variances between regions has an impact on PRCA collaborative governance. Therefore, this paper uses energy consumption intensity to express energy consumption and uses relative dispersion of energy consumption intensity to reflect variances in energy consumption among regions.(5) Greening construction variance. A higher green coverage rate is more conducive to air purification and tends to promote the PRCA effect. Urban agglomerations in the Yellow River Basin should guarantee that the eco-environmental area will not decrease and strengthen eco-space protection. The increase in regional variances in greening construction have an impact on PRCA collaborative governance.(6) Opening-up variance. With adjustments in regional cooperation of the global value chain, the regions and provinces in the basin are likely to become the key locations in which China participates in international cooperation and receives direct foreign investment in the future. It is unclear whether the pollution haven effect or pollution halo effect influence variances in degree of regional opening-up in PRCA collaborative governance. Therefore, this paper uses the scale of actual foreign capital utilization to characterize opening-up and uses the relative dispersion degree of the actual foreign capital utilization scale to reflect opening-up variances between regions.xtscc were used for estimation (as shown in According to Formula (9), the study employed Stata16 software to carry out regression analysis on the influencing factors of synergy degree of PRCA in the urban agglomerations in the Yellow River Basin. To guarantee that the model specification is objective, we first verified the variance expansion coefficient (VIF) for each explanatory variable. The values were all lower than 10, so it can be determined that there was not any multicollinearity among the explanatory variables. Second, the Hausman test was applied and the original hypothesis, i.e., in support of the stochastic effect model, was rejected. Thus, the regression model for the fixed effect panel was selected. Finally, the modified heteroscedasticity and autocorrelation The estimated coefficient of industrial structure variance was significantly positive on the level of 1%, which, to some extent, shows that the variance in industrial structure was conducive to PRCA collaborative governance. For a long time, heavy chemical industries have dominated the Yellow River Basin, such as the petroleum processing industry, the nonferrous metal smelting industry, and the mining industry. Certain cities in SX have been manipulated by resource-intensive industries; thus, strategic emerging industries and modern service industries have developed relatively slowly, and industrial development and economic growth have negatively impacted the ecological environment. However, the more concentrated the polluting industries are in intensive industrial clusters, the more cautious the implementation of strict environmental management policies. Thus, maintaining industrial structure variance in urban agglomerations tends to positively influence PRCA collaborative governance.The estimated coefficient for variance in environmental regulation was significantly positive on the 1% and 5% levels. Considering that current environmental governance investment has different effects on environmental improvement in various regions, certain regions have invested more in environmental governance, but the effects are not obvious. Each urban agglomeration should actively guide a shift in governance investment structure according to its own characteristics, adopt differentiated investment modes, further strengthen targeted governance of pollution sources, improve the investment effect of industrial pollution source governance, and strive for industrial transformation.The estimated coefficient of variance in economic growth was significantly negative on the 1% and 5% levels, which demonstrates that variance in economic growth significantly restrains synergy of regional PRCA governance. This shows that, the greater the variance in per capita GDP among regions, the more unfavorable it is for PRCA collaborative governance. In other words, the greater the variance in per capita GDP among regions, the more difficult it is for PRCA collaborative governance.The negative coefficient of estimation of energy consumption variance shows that energy consumption does not significantly inhibit PRCA collaborative governance synergy. Although the basin’s urban agglomerations currently prefer diversified development strategies based on efficiency and clean energy, the industrial structures of most cities in the basin are still in the order of secondary–primary–tertiary industries, in which traditional high-energy consumption industries occupy a large part and prevent the industrial structure from being effectively adjusted. Therefore, advantages and benefits of optimization and upgrading the energy structure for regional PRCA may not be effectively observed in the short term, so actively adjusting the industrial structure, eliminating outdated production capacities and processes, and optimizing industrial layout and process structures are particularly important to improve PRCA collaborative governance.The estimated coefficient of variance in greening construction was negative, which did not significantly inhibit PRCA collaborative governance synergy. The better the degree of urban agglomeration greening construction, the greater the improvement in urban air environment quality and the better residents’ physical and mental health. In order to achieve efficient cooperation as regards PRCA among the basin’s urban agglomerations, the differences in social growth dimensions, such as regional greening construction, need to be constantly narrowed.The estimated coefficient of variance in opening-up was negative, which did not significantly inhibit PRCA collaborative governance synergy. Moreover, the possible existence of a pollution haven or pollution halo could not be confirmed nor could its potential effects be assessed. The opening-up economic growth in the basin was extremely uneven, with a large gap in overall level of opening-up. In addition, the transportation conditions on the Yellow River are limited, and the overall economic ties between cities in the basin are very weak, so there is little close regional economic and trade coordination. For the sake of attracting foreign capital, local governments tend to use loosening environmental regulations as bait, which may generate a “Race to the Bottom” effect as regards environmental regulation. This also shows that there is still some room for improvement in the structure and efficiency of domestic and foreign investment in the Yellow River Basin.Considering that the factors affecting PRCA collaborative governance synergy degree have a certain lag, a robustness test was conducted on the explanatory variables with a one-period lag  The urban agglomerations in the basin should accelerate industrial structure upgrading and formulate differentiated collaborative strategies for PRCA. In accordance with their developmental stages, natural conditions, and resource endowment structures, each urban agglomeration should increase proportion of tertiary industry, actively advance high-tech industries , appropriately reduce proportion of secondary industries based on coal, petroleum, chemicals, and promote green and low-carbon transformation of the aforementioned key industries. They should increase pollution reduction and carbon abatement intensity and focus on energy structure adjustment, energy efficiency improvement, industrial structure transformation and upgrading, and multipollutant coordinated control.(2) The urban agglomerations in the basin should strengthen regional cooperation to achieve PRCA collaborative governance among cities and industries. PRCA is a shared responsibility and regional cooperation is an important path to promote PRCA collaborative governance. They should use industrial developmental status and regional advantages of each urban agglomeration to promote industrial transfer and technology flow from developed regions to underdeveloped regions so as to attain industrial layout optimization among regions and PRCA collaborative governance. They should push development of urban regional integration, accelerate interconnection between urban infrastructure and spatial design of urban agglomerations, economic circles, and metropolitan areas, reduce administrative barriers and transaction costs, and further facilitate free flow of market elements. While increasing investment in environmental regulation in urban agglomerations, they should avoid the “Race to the Bottom” effect caused by excessive variances in environmental regulation intensity and attempt to establish a cross-regional market-oriented platform for pollution control. Furthermore, they should strengthen enthusiasm and commonality in terms of participating in PRCA collaborative governance so that they can improve the environmental governance capacity and cooperation performance in the basin.(3) The urban agglomerations in the basin should comply with the trend of regional coordinated development and aim to constantly reduce regional differences. Taking the opportunity to construct a unified market, they should promote a new development pattern that is dominated by large-scale domestic circulation and is mutually promoted by domestic and international circulation. First, they should strengthen green technology by opening-up and adopt multiple paths, such as technology introduction, imitation, and learning, and independent innovation. Second, they should take the initiative to apply certain carbon abatement measures, such as volunteer domestic industrial structure transformation and energy system change, and encourage carbon abatement in terminal sectors, with the view of advancing the domestic eco-environment and raising the environmental threshold for foreign investment. Finally, they should accelerate implementation of environmental tax policies, formulate strict technology- and industry-access mechanisms, curb excessive supply of high-energy-consumption- and highly polluting technologies by foreign-funded enterprises, and effectively promote environmental technology spillover as a result of direct foreign investment.Although we have conducted much work on the research subject, there is still room for improvement in future research. This paper only discusses spatiotemporal evolution features and factors that affect PRCA collaborative governance in the basin’s urban agglomerations. In the future, we will consider measuring the urban agglomeration’s green productivity in the Yellow River Basin under the constraint of PRCA. In addition, we will use the partial differential method of the spatial regression model to test and decompose the factors and spillover effect of green productivity in the urban agglomerations.


Nutrition influences health throughout the life course. Good nutrition increases the probability of good pregnancy outcomes, proper childhood development, and healthy aging, and it lowers the probability of developing common diet-related chronic diseases, including obesity, cardiovascular disease, cancer, and type 2 diabetes. Despite the importance of diet and health, studying these exposures is among the most challenging in population sciences research. US and global food supplies are complex; eating patterns have shifted such that half of meals are eaten away from home, and there are thousands of food ingredients with myriad combinations. These complexities make dietary assessment and links to health challenging both for population sciences research and for public health policy and practice. Furthermore, most studies evaluating nutrition and health usually rely on self-report instruments prone to random and systematic measurement error. Scientific advances involve developing nutritional biomarkers and then applying these biomarkers as stand-alone nutritional exposures or for calibrating self-reports using specialized statistics. Adoption and maintenance of a healthy diet are among the most important and modifiable factors for ensuring healthy pregnancies , promotiMuch of the recent progress in understanding etiologic relationships between diet and health has been led by nutritional epidemiology research , 64, 90.The strength of the evidence to improve both population and individual health is only as good as the strength of the underlying science. Herein lies an important problem. Most of the recent nutrition-related population and clinical recommendations noted above are based on self-reported diet, primarily from observational studies, and accumulating evidence supports that self-reported dietary data that do not correct for measurement error are distorted by systematic and random measurement error , 75, 80.The goal of this article is to describe the challenges of dietary assessment in population sciences research, including addressing the important problem of systematic bias and demonstrating the potential that nutritional biomarkers offer to improve the validity of dietary assessment and its application to studies of diet and chronic disease risk. We explain first the challenges of self-report dietary assessment, the strengths and limitations of standard dietary assessment methods that have been in use for decades, and the potential for nutritional biomarkers combined with novel statistical modeling to advance the field of nutritional epidemiology.The United States is at a critical juncture in the health of the nation, where the heavy burden of morbidity, mortality, and health care expenditures imposed by diet-related poor health must be reduced . The fou2 or older age] have features that differ from other persons in the study population; these characteristics influence dietary reporting, a phenomenon known as systematic bias , food diary or record (FR), and 24-h dietary recall (24HR). The roots of these tools stem from Burke’s  seminal FFQs are food lists with options for respondents to mark foods and food combinations, frequency of consumption, and approximate portion size typically consumed over a period of time, which may range from “in the past month” to “in the past year.” Being self-administered on a mark sense print format or online, FFQs are a cost-effective and low-burden method for capturing a respondent’s usual or average dietary intake over the specified time period. FFQs are popular for reporting dietary intake in large population sciences research studies.Designing FFQs requires careful attention to the characteristics of the population under study , includiThe WHI, conducted nationally in 40 clinical centers across the United States , offers The terms food diary and food record are functionally synonymous, so here we use the term food record (FR). FRs are designed to capture short-term intake of foods and portion sizes actually consumed. The number of days reported for FRs depends on whether individual or group intakes are being assessed, the nutrients of interest, and the frequency and types of foods , althoug24HRs capture an individual’s intake over a 24-h period. Similar to FRs, 24HRs capture short-term dietary intake of foods and portion sizes actually consumed. The number of days recalled depends on whether variation within individual intake is in question, in which case multiple days are needed to calculate intraclass correlations, or group means are in question, in which case a single 24HR from the group or select subset group is needed ’s five-step multiple-pass system  to definDietary self-report, like many other research data collection activities, are going or have gone paperless. Examples include online Automated Self-Administered 24-Hour Dietary Recall (ASA-24)  and sevea) the USDA National Nutrient Database for Standard Reference, Legacy Release , which has data on 150 output variables from nearly 7,800 foods commonly consumed in the United States; and (b) the NDSR® Food and Nutrient Database (http://www.ncc.umn.edu/ndsr-database-page/), which includes 178 output variables from 19,500 foods. Food composition databases should include fresh raw ingredients, ready-to-eat foods, and restaurant foods.All dietary assessment instruments must be analyzed with high-quality food and nutrient databases. The processing of the raw food consumption data is linked with food composition databases to yield an output of the average daily intake of more than 150 nutrients , food components , plant compounds , and food group serving counts . Comprehensive research-grade food and nutrient databases must be used, as most foods have been subjected to chemical analysis to derive nutrient composition. In the United States, these include  . Random a) exposure biomarkers, (b) susceptibility markers, and (c) outcome biomarkers  has also expanded to include food-component biomarkers (nutritive and non-nutritive), biomarkers of food intake, and dietary pattern biomarkers, while recognizing that some markers may be used for characterizing a variety of diet exposures . For exaThese studies of recovery-based nutritional biomarkers raise important questions: Is the paucity of established biomarkers that can be used quantitatively as recovery biomarkers a necessity, or can additional biomarkers be identified by also considering new measures in blood or other body fluids and by bringing in higher-dimensional data sources, such as serum and urine metabolomics profiles? Trying to answer these questions about nutritional biomarker discovery and their application to population sciences research has been the aim of considerable recent research . FurtherThe extent to which the properties of intake biomarkers depend on participant characteristics are transportable to other populations is also an important concern. At this stage of biomarker development, it seems advisable for cohort-based research groups to incorporate biomarker development studies for their populations, at least if the research includes a substantial focus on nutritional exposures and their associations with chronic disease risk. The reasoning is that the participant characteristics associated with systematic bias in dietary self-report will vary in each study population. In addition, it will typically not be practical to measure established or novel dietary biomarkers for all members of large epidemiologic cohorts owing to the extensive costs and logistics involved. Rather, such biomarkers may be measured in nutritional biomarker substudies in large cohorts and used to develop calibration equations for use in calculating biomarker-calibrated intakes for participants in the entire cohort for use in disease association analyses. This raises the question of which properties should be required for calibrated intakes, a topic of ongoing research , 72.Metabolomics, the high-throughput study of substrates and products of metabolism in a biological system, is a promising application for nutritional biomarker development , 92. It In these WHI ancillary studies, efforts to identify and apply objective dietary biomarkers to strengthen the evidence of diet–disease associations using biomarker-calibrated intake have expanded from using established nutrient recovery biomarkers , 74, 78 2 (CV-R2) of ≥36% was selected as a criterion for acceptable intake biomarkers in the NPAAS-FS. The rationale is that new biomarkers should have a rigorous correlational criterion that approximates the criterion observed for gold standard DLW and UN biomarkers. Investigators have developed a pipeline to apply the biomarkers to calibration of self-reported intake within the WHI cohort. As part of this pipeline, log-transformed metabolite signatures meeting the cross-validation R2 were advanced to the next step of regressing linearly on corresponding log-transformed FFQ intake values and personal characteristics to produce calibration equations for these variables. These equations were then used to calculate calibrated intake values in the WHI cohorts and associate these with disease risk in the WHI cohorts  methods for variable selection , were ru cohorts , 79, 110Larger initiatives have also contributed substantially to dietary biomarker discovery using metabolomics. From 2014 to 2018, the Joint Programming Initiative A Healthy Diet for a Healthy Life Food Biomarker Alliance (FoodBAll) a consortium of 24 partners from 13 countries, carried out a systematic exploration and assessment of metabolomics-based biomarkers of food intake . With thAs part of the FoodBAll program, researchers established guidelines for conducting literature searches on food biomarkers so as to identify existing candidate biomarkers for a specific food or food group and to provide available evidence for the subsequent systematic evaluation of the quality of such compounds as biomarkers . A recenhttps://dietarybiomarkerconsortium.org/), comprising three clinical centers and a data coordinating center, to expand the available metabolite signatures for foods within the USDA MyPlate food groups (https://www.choosemyplate.gov/). MyPlate operationalizes the US Dietary Guidelines for Americans to help consumers choose fruits, vegetables, grains, protein foods, and dairy as part of their overall dietary pattern. Multidisciplinary teams within the DBDC provide the necessary expertise and experience in dietary intervention and dietary assessment, metabolomics, and bioinformatics for exploring metabolomics-based dietary biomarkers and biostatistical analysis of dietary biomarker data. The clinical centers are generating initial sets of metabolite signatures for selected foods in the context of controlled feeding in small groups of study participants. Properties of the identified metabolites, such as pharmacokinetic profiles and half-lives, as well as initial performance of the signatures will be evaluated in this phase. In follow-up studies, biomarker signatures will be evaluated further for predicting recent and habitual consumption of more complex mixed meal diets and dietary patterns fed as part of controlled feeding studies. The performance of the biomarkers will also be compared with the current benchmark predictive markers . Robust validated markers will ultimately be tested for their ability to predict both recent and habitual consumption of dietary components in independent cohorts along with 24HRs and FRs and other benchmark biomarkers.In 2021, the National Institutes of Health (NIH) and the USDA’s National Institute of Food and Agriculture established the Dietary Biomarker Development Consortium  criteria can be applied essentially independently relative to statistical properties of the resulting biomarker-calibrated intakes. Under pertinent modeling assumptions, the set of calibrated dietary intakes, along with potential confounding factors, can be inserted into standard outcome analyses, such as Cox regression, for time to clinical outcomes in cohort settings, with some refinement needed for variance estimators to acknowledge random variation in calibration equation coefficient estimates (2 criteria ensure a certain closeness between estimated and actual intakes, it is also important to consider possible influential sources of reduced sensitivity or specificity for both biomarkers and calibrated intakes, even if evaluation of sensitivity and specificity can be done only informally in specific applications.Despite the promise for nutritional biomarkers to improve dietary assessment in population studies, it is neither practical nor financially feasible to assess biomarkers in cohorts with tens of thousands of participants. Related to these financial and logistical limitations is the complication that the DLW energy intake biomarker requires an expensive protocol and cannot be measured from biospecimens in biorepositories owing to the need to ingest the stable isotopes and collect timed urine samples over a course of several days to two weeks. For these reasons, cohort substudies may be the most practical way to implement nutritional biomarker assessments. In our work in the NPAAS, the biomarkers together with the participant characteristics are used to develop a calibration equation where participants without biomarker values are given a predicted energy intake value representing true energy intake, given a participant’s age, BMI, race/ethnicity, and other characteristics . In thisR2 value , 77, 109stimates , 73. FinThese analytic approaches using statistical calibration have revealed an important role for total energy intake in CVD, cancer, and diabetes incidence and mortality analyses  because,


Intracycle velocity variation is a swimming relevant research topic, focusing on understanding the interaction between hydrodynamic propulsive and drag forces. We have performed a systematic scoping review to map the main concepts, sources and types of evidence accomplished. Searches were conducted in the PubMed, Scopus and Web of Science databases, as well as the Biomechanics and Medicine in Swimming Symposia Proceedings Book, with manual searches, snowballing citation tracking, and external experts consultation. The eligibility criteria included competitive swimmers’ intracycle velocity variation assessment of any sex, distance, pace, swimming technique and protocol. Studies’ characteristics were summarized and expressed in an evidence gap map, and the risk of bias was judged using RoBANS. A total of 76 studies, corresponding to 68 trials involving 1440 swimmers , were included, with only 20 (29.4%) presenting an overall low risk of bias. The front crawl was the most studied swimming technique and intracycle velocity variation was assessed and quantified in several ways, leading to extremely divergent results. Researchers related intracycle velocity variation to coordination, energy cost, fatigue, technical proficiency, velocity, swimming techniques variants and force. Future studies should focus on studying backstroke, breaststroke and butterfly at high intensities, in young, youth and world-class swimmers, as well as in IVV quantification. Intracycle velocity variation (IVV) is a biomechanical variable that reflects the velocity fluctuation within a swimming cycle and was one of the first swimming-related research topics ,2 aimingAfterwards, the natograph was improved ,5,6,7, wMethods dealing with the centre of mass motion have the abovementioned problems but are even more time-consuming and complex. Nowadays, depending on the aims of IVV investigation, researchers are divided between using an anatomical fixed point or the centre of mass ,16,17. CDespite the above-referenced methodological concerns, the association between swimming IVV and performance continues to be investigated even though the findings are quite divergent. Increases in velocity were associated with lower ,21, stabConsidering the IVV research background and its significance to assess biomechanical development in swimming, the aim of the current study wa to accomplish a systematic scoping review of IVV in competitive swimming regarding the four conventional techniques, assessment and quantification methods, participants’ information , protocols, and association with swimming economy and hydrodynamic drag. The closest work to a review about IVV is a book chapter  addressihttps://osf.io/m43pj, accessed on 23 December 2022).The current systematic scoping review protocol was designed according to PRISMA 2020  and PrisOriginal peer-reviewed articles and texts from the Proceedings Book of the Biomechanics and Medicine in Swimming, published in any language or date, were included in the current study. Letters, editorials, meetings abstracts, commentaries, and reviews were excluded. The eligibility criteria were defined by the Population, Exposition, Comparator, Outcomes and Study (PECOS) design model, in accordance with PRISMA guidelines: (i) population ; (ii) exposure ; (iii) comparison (not mandatory if intervention was performed); (iv) outcome  and (v) study design (no limitations for the study strategy).Searches were conducted until 6 July 2022, in the PubMed, Scopus and Web of Science literature databases, as well as in the Proceedings Books of the Biomechanics and Medicine in Swimming Symposia (no filters were applied). After the automated searches, the reference lists of the included studies were screened and prospective snowballing citation tracking was performed in PubMed, Scopus and Web of Science databases. Two external experts (holding a PhD in Sport Sciences and having considerable published research on the topic) were consulted to provide further suggestions of potentially relevant studies. Included studies’ errata, corrections, corrigenda and retractions were sought .https://www.iat.uni-leipzig.de/datenbanken/iks/bms/ accessed on 6 July 2022), as sought and valuable as some of the available studies published in high-impact, peer-reviewed journals. All submissions go through a peer review process, leading to a collection of peer-reviewed scientific papers, serving as a valuable resource for all who are interested in keeping up to date with aquatic research. Relevant pioneering works were published in the 13 editions of the Symposium, adding relevant information to the current review. The International Symposia for Biomechanics and Medicine in Swimming have been held every four years since 1970 and are considered the most prestigious international aquatic-oriented scientific congresses. These meetings have provided the swimming science community with some of the most outstanding contributions books and collections , but manual duplicate removal was required.Two authors (AF and JA) independently screened all the database records and performed the manual searches, as well as snowballing citation tracking, with disagreements decided by a third author (RJF). Automated removal of duplicates was performed using EndNoteTwo authors (AF and BM) independently collected data, and, in the case of disagreements, a third author (RJF) provided arbitrage. No automation tools were used, and a specifically tailored Excel worksheet was created for the extraction of raw data.The current study’s primary outcome was IVV assessment in the four conventional swimming techniques (according to the above-referred defined eligibility criteria). Velocity assessment methodologies, IVV quantification, participant and protocol information, and associations with swimming economy or hydrodynamic drag were the secondary outcomes. Velocity can be assessed by mechanical, image-based and mixed methods, and IVV can be quantified by the (i) difference between maximal and minimum instantaneous velocity (dv); (ii) ratio of the mean velocity/difference between the maximal and minimum instantaneous velocity; (iii) ratio of the minimum and maximum velocities/intracycle mean velocity (dv/v); (iv) coefficient of variation (CV); and (v) other. Regarding participants’ characteristics, we have included studies with samples of female, male or both sexes and young (<14), youth (between 15–16), junior (between 17–18), senior (>19) or master (>25 years) swimmers (following the World of Aquatics stratification). Aiming for a homogeneous classification of competitive level, two authors (AF and JA) applied the Participant Caliber Framework  using trRisk of bias in individual studies was judged using Cochrane’s Risk of Bias Assessment for Non-randomized studies , evaluaIVV mean ± SD or median ± IQR values were calculated, and, when needed, two authors (AF and BM) independently extracted data from graphs using the WebPlotDigitizer v4.5  .A narrative synthesis of the main findings was performed and supplemented with an interactive evidence gap map . This map can be accessed online, providing interactive ways to visualize the current review’s included studies  and the primary and secondary outcomes.The initial search identified 227 potentially relevant articles, with 126 being duplicates, which were consequently removed . FollowiSixty-eight trials were considered for judging risk of bias, with 20 ,102,103 Considering that no data were provided concerning the validity and reliability of the software used or whether the process was fully automated in the different studies analysed, exposure measurement was judged unclear for 63% of the trials. High risk was evaluated for 6% of the trials with specific measurement issues; in particular, (i) the electrical resistance variation method had not been previously validated, with authors not providing proof of its reliability ; (ii) thMany trials 74%) did not mention outcome assessment blinding and it was unclear if video analysis was fully automated (probably interfering with the measurements). High risk was attributed to 7% of the trials due to no blinding and to the inexistence of data concerning the reliability of the automated process % did not,116,124.The included trials’ main characteristics are presented in IVV was not the primary outcome in 31 trials but was included in a larger analysis, being described  and analThe evaluation of the evidence gap map and trials’ risk of bias can be accessed through the Image- (47 and 53% in two and three dimensions) and mechanical-based methods were used , with speedometers being mostly selected (82%). Velocity was calculated using an anatomical fixed point as a reference, most of the time with the hip chosen (and only twice selecting the head/neck) rather than the centre of mass . The coefficient of variation was preferred regarding IVV quantification versus the difference between the maximum and minimum instantaneous velocity , the ratio maximum and minimum instantaneous velocity difference/intracycle mean velocity , the ratio of the mean velocity/difference between the maximal and minimum instantaneous velocity (3%) and other methods . Twenty-five trials reported variables associated with swimming economy (such stroke length and stroke index) and only two reported hydrodynamic drag related variables.Front-crawl-related trials almost covered all secondary outcomes, even though gaps were identified for the four conventional swimming techniques. No trials were conducted with world-class swimmers focused on extreme, heavy, moderate and low intensities; used accelerometers; or quantified IVV with overall methods. Young swimmers were not used as samples in trials that were conducted at extreme and low swimming intensities, accelerometers were employed, and, when characterizing these age group IVV, its quantification was performed using only three methods. Master swimmers were not called to participate in protocols with extreme intensity and were not evaluated using accelerometers, while IVV quantification in this population was conducted only through the coefficient of variation. Trials using youth/junior, world-class, elite, highly trained and trained swimmers did not have associated IVV and hydrodynamic drag.Higher-level swimmers presented superior mean velocities for the same swimming intensity, but IVV was not related to swimming competitive levels or to the mean velocities regarding the four swimming techniques . Except In breaststroke, IVV is usually quantified by dv/v (m/s), as presented in Equation (1), with vmax,LL as the maximum centre of mass’s velocity achieved at the end of lower limb propulsion; vmin,LL as the first minimum peak of the centre of mass’s velocity following upper and lower limbs recovery (corresponding to the beginning of lower limb propulsion); vmax,UL as the maximum centre of mass’s velocity at the end of the upper limb propulsion; and vmin,T as the minimum centre of mass’s velocity during the transition between upper and lower limb propulsion (corresponding to the centre of mass’s velocity during gliding).Some trials showed periodic velocity fluctuations related to the upper limbs’ actions and the rate and the number of peaks per cycle, with a higher IVV range in lower- than in higher-level swimmers ,118,127.IVV was directly related to swimming economy in the four swimming techniques ,123,126 Methodological trials mainly assessed the relationship between the hip and the centre-of-mass kinematics to provide simpler methods to quantify IVV in swimming. It seems consensual that the hip does not adequately represent the centre of mass in intracycle variation in butterfly, breaststroke and front crawl. Some authors clearly state that this anatomic point should not be used in this kind of assessment ,19,20 beThe current systematic scoping review focused on the IVV assessment in swimming that is retrospectively available for almost a century. The IVV-related trials’ main interest is in the interactions between the cyclical propulsive and drag forces, which help understand the cyclic effectiveness of the upper and lower limbs while swimming and, consequently, swimmers’ technical efficiency. In the first studies on IVV, breaststroke was the most studied swimming technique due to the simultaneity between the movements of the upper and lower limbs  ,118. TheFrom the analysed trials, we could observe that male swimmers were the most studied even though mixed groups were also used due to the interest in checking differences between female and male swimmers , displaying larger amplitude of velocity ,124. HowThe quality of the trials included in the current study can be questioned due to the lack of detailed information and uncertainty of the evidence provided (being indeterminate whether it would result in a high or low risk of bias). Disregarding the already mentioned factors that influenced a high risk of bias, most variables were unclear because it the validity and reliability of the exposure measurement were not mentioned, nor were the blinding of the outcome assessment or even the information about whether swimmers belonged to a larger sample. In the scope of swimming, experimental protocols aim to replicate swimmers’ performance and are not usually registered in databases. Furthermore, the current scoping review included trials since 1971 that were not as concerned about the studies’ quality as is dictated today.The number of included trials highlighted the importance and utility of performing a systematic scoping review in swimming IVV. We believe that including the Proceedings Books of the Biomechanics and Medicine in Swimming Symposia strengthened our work, since this book series contains several important documents that added relevant information to the current review. This research aimed to provide an overall representation of the IVV scope of competitive swimming, but we recognize that considering IVV calculations in conditions such as using snorkelling or swimming with/without breathing could affect its interpretation. For sake of the clarity, those studies were properly identified.The current study compiles the studies available on the topic of the swimming IVV in the most respected and well-known literature databases. We have described the literature gaps and the most interesting IVV-related topics within almost the past century. IVV was often used in front-crawl-related studies, involving mixed samples and senior swimmers that performed at sprint intensity in swimming pools and were evaluated with cable speedometer using an anatomical fixed point as a reference and that quantified IVV using the coefficient of variation. There is a clear need for investigating backstroke, breaststroke and butterfly swimming techniques performed at heavy, severe and extreme intensities. Since these paces correspond to the characteristics of the official competitive events, it would be imperative to assess them more often. Young and youth swimmers were less studied, even though their performance development in swimming is important in their training process throughout their careers. It would be very helpful to evaluate world-class swimmers as well to acknowledge the top-level performers’ behaviour. Although there is no proof that the coefficient of variation is the best measure to assess IVV, researchers generally agreed that it best reflects the velocity fluctuations in swimming.Future investigations should cover the gaps found in the current study to allow for meaningful results and possible comparisons. IVV measurements should be revised, and a new approach that accounts for hydrodynamic characteristics is welcome to standardize results according to these factors. Future research should strive to reduce the risk of bias by (i) attending to a balance between female and male swimmers, looking for better sample homogeneity; (ii) providing important personal characteristics; (iii) controlling the evaluation conditions; (iv) providing the software validity and reliability; (v) blinding the outcome evaluators; (vi) providing data on the inter-evaluator reliability of outcome measurement or measures of error for the methodologies used (when applicable); (vii) providing information about whether swimmers are part of larger samples; and (viii) pre-registering the research protocols.


Lactoferrin (Lf), a naturally occurring glycoprotein involved in innate immunity, was first discovered in bovine milk  and lateThis Special Issue, entitled “Lactoferrin, the Moonlighting Protein of Innate Immunity”, consists of five articles selected for publication.Bukowska-Ośko and colleagues reviewed the most recent studies about Lf’s ability to defend the host from DNA damage induced by chemical and biological agents . Such chAs an ancestral guardian, the primary defense activities of Lf against pathogens and their sequelae have been dissected in different studies in the present Special Issue. Li and colleagues have investigated the beneficial effect of Lf administration in a model of lipopolysaccharide (LPS)-induced intestinal immune barrier damage . The innD value relative to RBD–ACE2 complex formation [The antiviral activity of Lf has been widely recognized ,20, and ormation .+ patients can experience HIV-associated neurocognitive disorders [−, thus highlighting the utmost importance of considering Lf iron saturation when applied to clinical therapies, as it can dramatically influence the success or failure of the treatment itself [The protective role of Lf against pathogenic processes related to the expression of the sole viral proteins was also reported in the study by Ianiro and colleagues, where iron saturation rate was found to drive bLf effects on oxidative stress and neurotoxicity induced via HIV-1 Tat . Despiteisorders , mainly isorders ,31. BLf t itself . In this framework, the role of iron in driving Lf activities was also remarked in the study by Lian and colleagues in which, as a natural defense agent in ocular wellness ,33, Lf wThis Special Issue was effective in bringing together new and promising studies in the lactoferrin field, emphasizing the potential application of this natural product in current and future research as an effective alternative or complement to standard therapy.