Sarah Maessen and colleagues argue that identifying successful policies and practices in countries with falls in early childhood overweight can help enhance efforts and reduce within country inequities Nearly every country worldwide has experienced a steady rise in the prevalence of obesity across all age groups in recent decades.Data on trends in overweight and obesity prevalence are scarce for young children and, where available, show considerable heterogeneity between and within countries. We examined national or regionally representative data on trends in early childhood body mass index (BMI) from five countries, four of which were high income . To suppBox 1New Zealand: near universal national data from the routine age 4-5 years B4 school checkVictoria, Australia: state-wide data collected by the universal maternal and child health service, from routine clinic visits at age 3.5 yearsGermany: nationally representative data on young children attending routine medical checks collected through the CrescNet database that connects 247 paediatricians throughout the country. Data on children aged 4-6 years were summarised.England: the National Childhood Measurement Programme is a mandated annual programme of measurements in schools at ages 4-5 and 10-11 years.South Africa: national or provincial data on the prevalence of overweight in young children using differing survey designs, including the National Food Consumption Survey 1999, 2005), the South African National Health and Nutrition Examination Survey (2012), and the Provincial Dietary Intake Study (2018).99, 2005,The prevalence of overweight in preschool children fell by around 15% in New Zealand between 2010-11 and 2018-19,Although comprehensive data are lacking from lower income countries, data from South Africa,The patterns of early childhood overweight in high income countries fit the fourth, and final, stage of a conceptual model for transition in obesityBox 2—eg, space and facilities for outdoor play; infrastructure for active travel to school; density of takeaway outlets; accessibility to fresh food storesEnvironmentSocial—eg, awareness of early childhood overweight and overfeeding; maternal smoking in pregnancyPolicy—eg, provision of early years education and childcare; provision and promotion of healthy food and physical activity in early education settings; appropriate growth references for weight monitoring and parental feedbackCommercial—eg, reformulation of foods and drinks to reduce free sugars; reduction in protein content of infant milk formulasYoung children may be the first age group to show a plateau or decline in overweight because preventive efforts may be more effective when begun earlier in lifeChildcare arrangements show complex associations with overweight and obesity, with parental care typically conferring the lowest risk, especially when compared with informal non-parental care, such as by grandparents.In addition, governments have made substantial investments in formal early childhood education and care. New Zealand introduced a policy to provide 20 hours of free early childhood education a week for 3-5 year olds alongside a series of reforms throughout the 2000s increasing the number of facilities and enrolments, teachers’ qualifications, and the affordability of childcare.Maternal smoking is associated with a 1.50 higher risk of obesity at age 4,Regarding diet and nutrition, any breastfeeding and longer breastfeeding duration are both consistently associated with lower risk of childhood obesity.We may also learn about how to reduce childhood overweight from knowledge of the factors that have increased it. Several factors have been proposed to explain the increases in overweight during the covid-19 pandemic. Although increases were seen across all age groups, children were particularly affected by school and childcare closures, with greater increases in sedentary time (by around 160 min/day) than seen in adults,Road to Health booklet for postnatal care, there has been little improvement in early risk factors for overweight. South Africa has one of the lowest breastfeeding rates on the African continent and has not seen the reductions in maternal smoking reported in high income countries; indeed, the greatest uptake of tobacco use is among younger women. Furthermore, South African culture does not typically perceive childhood overweight or obesity as a concern; rather, typical attitudes prefer a chubbier baby.Levels of overweight and obesity have increased rapidly across all age groups in South Africa.Although overall levels of overweight in young children are reducing, there is significant heterogeneity between population subgroups. For example, in the UK, the prevalence of early childhood obesity increased from 12.2% to 13.6% among the most deprived decile between 2006-07 and 2021-22.To our knowledge, New Zealand is the only setting where disparities in overweight across sex, ethnicity, and affluence subgroups seem to be narrowing.Changes in the prevalence of early childhood overweight may reflect the level of influence of structural factors, including environmental, social, policy, and commercial determinants of eating patterns, diet, physical activity, and sedentary time in individual children and families. Observed plateaus or declines in Australia, Germany, New Zealand, and UK, albeit still at high levels, should provide encouragement that further structural interventions are likely to continue and hasten these declines. Proposed future policy tools include regulation of marketing of unhealthy food and drinks to young children, greater support for breastfeeding and healthy infant feeding, investment in the built environment to facilitate active children, and ensuring that schools and nurseries play a central role.Levels of overweight and obesity among preschool children are stable or declining in several high income countriesPossible contributing factors include increasing attention on early obesity prevention, changes in infant feeding, investments in early childhood education and childcare, and reduced levels of maternal smokingDespite reductions, levels of early childhood overweight remain high and have increased in some vulnerable groups and during particular periods, such as the covid-19 pandemicThese trends highlight the sensitivity of preschool overweight and obesity to structural factors and the need for further action to hasten and extend weight reductions


In conclusion, the literature on health systems internventions addressing hypertension care are limited in quantity and quality. Future studies that are adequately powered should test the effect of multi-faceted health system interventions on hypertension outcomes with a special focus on financing, leadership and governance, and service delivery interventions since these aspects were least explored.Hypertension is a significant global health problem, particularly in Sub-Saharan Africa (SSA). Despite the effectiveness of medications and lifestyle interventions in reducing blood pressure, shortfalls across health systems continue to impede progress in achieving optimal hypertension control rates. The current review explores the health system interventions on hypertension management and associated outcomes in SSA. The World Health Organization health systems framework guided the literature search and discussion of findings. We searched PubMed, CINAHL, and Embase databases for studies published between January 2010 and October 2022 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed studies for the risk of bias using the tools from the Joanna Briggs Institute. Twelve studies clustered in 8 SSA countries met the inclusion criteria. Two thirds (8/12) of the included studies had low risk of bias. Most interventions focused on health workforce factors such as providers’ knowledge and task shifting of hypertension care to unconventional health professionals (n = 10). Other health systems interventions addressed the supply and availability of medical products and technology (n = 5) and health information systems (n = 5); while fewer interventions sought to improve financing (n = 3), service delivery (n = 1), and leadership and governance (n = 1) aspects of the health systems. Health systems interventions showed varied effects on blood pressure outcomes but interventions targeting multiple aspects of health systems were likely associated with improved blood pressure outcomes. The general limitations of the overall body of literature was that studies were likely small, with short duration, and underpowered.  Hypertension remains a global health challenge, especially for low- and middle-income countries (LMICs) in Sub-Saharan Africa (SSA) . HyperteSeveral strategies have been implemented to manage hypertension in SSA. Population-based interventions such as educational campaigns to improve dietary practices by reducing salt consumption have proven cost-effective in lowering blood pressure (BP) among hypertensive patients –13. AlteMultiple guidelines exist for screening, diagnosing, and treating hypertension , 15, 16.The World Health Organization (WHO) health systems framework highlights six critical elements to target while working to improve the quality of health services . These aCollaborating with a scientific library informationist, we defined the search terms for hypertension service availability and delivery guided by the WHO health systems’ framework . We IdenThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)  guided tIn the article search and screening, we included studies (1) published in English or French between January 2010 –October 2022; (2) conducted in health facility settings  at different levels of the health system in SSA; (3) with a randomized controlled trial or quasi-experimental design; (5) exploring the impact of health systems-level interventions on any of the following hypertension outcomes: awareness, treatment initiation and adherence, systolic and diastolic BP levels, and achievement of BP control.We excluded (1) observational studies and (2) studies that explored hypertension care interventions conducted solely in the community setting without describing collaboration with health facilities, or (3) examining solely patient-level behavioral change interventions for hypertension management. Additionally, we excluded gray literature .The investigators tracked the rationale for excluding any study during the entire process following the article search.To synthesize our findings, we examined each study in view of the six WHO key building blocks of the health systems: service delivery; health workforce; medical products and technologies; information systems; financing; and leadership and governance .Service delivery. WHO defines service delivery as the activities which result in the direct provision of safe, effective, and high-quality health services to those who need them. We considered the studies to address the service delivery aspect of the health systems if the target of the intervention was to make hypertension services  more accessible through decentralization of care, reduction of waiting time, revision of time of services, or application of services integration delivery.Health workforce. In the health workforce aspect of the health systems, we included studies with interventions that targeted the healthcare providers who manage patients with hypertension. The interventions included strategies to improve provider density, increase provider knowledge and adherence to hypertension guidelines, address provider decision support systems, promote teamwork, and institute task sharing and/or task shifting strategies among providers who do not normally perform certain hypertension management tasks.The medical products and technologies. The interventions of interest regarding the medical products and technologies were the procurement systems to ensure the availability of anti-hypertensive medications, calibrated and validated BP measurement devices (as well as their maintenance), technologies for easier patient management and follow-up, hypertension treatment guidelines, and consumables for hypertension-related laboratory exams.Health information systems. We considered interventions to address health information systems if they studied an element of the process of patient data collection, analysis, sharing, and use to improve outcomes of patients with hypertension. We included interventions that examined the use of patient registries and patient-to-provider and provider-to-provider information sharing in patient management.Financing. The financing aspect of the health systems, as defined in the WHO building blocks, has the most significant relevance on the national macro-level health systems yet plays an impact on the micro-level health systems’ service delivery and patients’ outcomes. In the current context, we considered the interventions which evaluated the injection of money into the health systems through health insurance premiums, reduction of the patients’ out-of-pocket spending, or funding for hypertension management activities at the health facilities.Leadership and governance. Leadership and governance have direct and indirect associations with the other five building blocks of the health systems. In this review, we considered an intervention to target leadership and governance if it promoted leadership awareness of the rising burden of hypertension, used strategic planning or implementation of national strategy around hypertension management activities, explored the accountability measures at the health facility, applied regular performance appraisal and planning for improvement, integrated supportive mentorship to low health system level health facilities, instituted a patient feedback collection and response system, or studied the leadership allocation and reallocation of funds for hypertension management. We also considered interventions around leadership joining collaborations  to manage hypertension.We used the Joanna Briggs Institute (JBI) tools to assess the quality aspects of the methods and conduct of the studies included in the review . We evalAfter the data extraction, we identified the health systems factors addressed by the interventions for hypertension care. We classified the outcomes of each study into the appropriate group: hypertension awareness, systolic and diastolic BP, treatment initiation and adherence, and BP control. We tracked the reported effect(s) of interventions on hypertension outcomes and compared findings across the different countries of SSA.We identified 7,494 studies and 3,121 were duplicates . We condThe quality assessment demonstrated a low risk of bias in 67% (8/12) of the included studies . Among rThe health system factor that most interventions targeted is the health workforce, followed by interventions to address equipment and medicines, information systems, financing, service delivery, and leadership and governance . The detOnly one study conducted in Kenya and Uganda addressed the service delivery aspect of the health systems on hypertension care . The stuTen of the twelve included studies evaluated the interventions aimed toward the health workforce , 36–38. Generally, studies that included interventions for the health workforce reported improvement in hypertension outcomes. Improvement in the healthcare providers’ skills and knowledge of the correct BP measurement techniques and hypertension diagnosis and treatment, respectively, likely contributed to improved hypertension outcomes in Kenya . In its The impact of task-shifting varied across studies but bent towards positive BP outcomes. In Ghana  and CameAlmost half (5/12) of the included studies explored the availability of equipment and consumables involved in hypertension management and the associated care outcomes , 35–38. Five of the twelve studies evaluated some aspects of health information system interventions on hypertension outcomes , 34, 35.Three studies conducted in Ghana and Nigeria explored the interventions around financing to improve hypertension outcomes, 33, 34.The incentivization of clinicians who manage patients with hypertension contributed to a 66% achievement of BP control among patients even though there was no data for the control group .While leadership and governance contribute directly or indirectly to all the above health system factors, studies targeting leadership and governance were scarce. A single quasi-experimental study conducted in Sierra Leone explored one aspect of leadership and governance–the collaborations with government and non-government, local and international organizations to train the trainers of hypertension care. The consortium provided training to the providers at the referral health facilities who, in turn, trained and gave supportive mentorship to the health facilities in the lower levels of the health system . This inThe health systems interventions on hypertension targeted two or more health system components in ten of the twelve studies included. The health workforce and health information systems were the most common combination of factors targeted, followed by the health workforce and medical products. One randomized controlled trial and one quasi-experimental study which targeted a single health system factor, health workforce, and health financing, respectively, did not yield a significant improvement in hypertension outcomes. In contrast, studies which targeted multiple health system factors were likely to demonstrate significant improvements in hypertension outcomes.This systematic review assessed the health system interventions for hypertension awareness, initiation and adherence to hypertension treatment, and achievement of BP control in SSA. Our main findings are that studies to address health systems challenges of hypertension care are very limited in quality and number. The studies we identified addressed mostly the health workforce challenges, access to equipment and medicines, and health information systems. The studies addressing hypertension care delivery issues, such as decentralization of hypertension care and integration delivery, leadership and governance, and financing aspects of the health systems, were minimal. Overall, we found that interventions targeting multiple aspects of the health systems were more likely to show significant improvements in hypertension outcomes than interventions targeting solo health system components.The healthcare provider’s knowledge and adherence to hypertension treatment guidelines stood out as one of the most studied health system interventions on hypertension , 39, 40.The second health system component widely explored is the supply of essential medical products, including BP measurement devices and anti-hypertensive medications. It is intuitive to formulate the association between the availability of medical products and hypertension outcomes, yet the challenges that lead to the disruption in the supply chain of medical products are a complex issue to disentangle. The common approach addressed by the interventions was to procure the needed equipment and medications but not to fix the inherent challenges in the availability of those medical products and the supply chain–or attempt to identify loopholes in the process to recommend viable and context-specific solutions. A separate narrative synthesis has identified multiple challenges to the availability of medical products in Africa . The chaWHO defines health information systems as collecting, storing, analyzing, and utilizing patient and healthcare delivery data to improve quality, research, and inform policy . “If youThe cross-integration of hypertension services is a service delivery system-level intervention explored for managing hypertension. The advocacy for integrating hypertension and HIV care originated from the realization that many patients with HIV were presenting with hypertension and other non-communicable chronic conditions such as diabetes. HIV care outcomes , 49. SieFinancing of health systems is another critical aspect of hypertension and other health services’ accessibility and utilization. Studies in the current review have shown that addressing the cost-related barriers to care can contribute to helping patients with hypertension achieve better outcomes–the subsidization of health insurance premiums. Universal health coverage through government-subsidized insurance premiums has been advocated as a solution to prevent catastrophic spending on healthcare services and associated poor health outcomes –66. HoweWhile leadership and governance are central to the success of any endeavor to improve the quality of care, their role and impact in advancing hypertension care in SSA are not widely researched, and the few existing studies are predominantly of poor quality . ThorntoWe found that interventions addressing multiple health system factors were more likely to report better hypertension outcomes than isolated investment in a single health system component. Health systems in most SSA countries, especially rural areas, are often frail in the multiple health system factors . The invAs the burden of hypertension increases globally, the investment required by health systems to manage hypertension is rising. Hypertension is significantly associated with adverse outcomes of Coronavirus Disease 2019 (COVID-19), the ongoing pandemic ravaging the entire world’s health systems , 71. StuStandard tools for exploring the health system determinants for specific diseases are scarce in the realm of hypertension care in Africa. There is a dire need for psychometric tools to explore health system readiness to provide quality hypertension care. The availability of those tools would open doors for researchers interested in hypertension care to gather quality data on health system determinants and render the evidence to policymakers to develop policies directed at shortfalls in care delivery to improve the health outcomes of patients with hypertension.Future studies should investigate the different aspects of hypertension service delivery, especially interventions that make service accessible, the role of leadership and governance, the latest methods of health information system management including the use of electronic medical records for patient follow up, as well as multi-level approaches  in the improvement of hypertension care. To improve the quality of the studies, the quality improvement projects aimed at testing the interventions in clinical settings and evaluative projects aimed at generating knowledge will have to be rigorously guided by the science of study design. Since healthcare settings are ever dynamic with many interconnected components, the appropriate design has to be carefully identified allowing the balance between controlling the allocation of the interventions with prevention of contamination and bias and the pragmatism of the project in the research setting , 75. TheThe limitation of the current review is that we conducted the literature search in English. Even though we reviewed studies published in both English and French, the English search terms, could limit our ability to identify studies published in other languages. We were unable to explore the isolated effect of individual health system factors interventions, because many system interventions were delivered in a bundled approach. However, this review offers valuable insights as the first to explore the health systems interventions on hypertension care in SSA, applied rigorous methods to critique the quality of the studies, and reviewed the interventions using the WHO health systems framework .The literature exploring health system interventions for hypertension management in SSA is limited in volume and quality. The combination of multiple health system interventions was likely to result in better hypertension outcomes. More rigorously designed studies addressing the different aspects of the health systems and their impact on hypertension outcomes, especially service delivery, health information management, and leadership and management, are needed in SSA to inform practical hypertension control efforts.S1 Checklist(DOC)Click here for additional data file.S1 Fig(TIFF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file. 25 Apr 2023Health Systems Interventions for Hypertension Management and Associated Outcomes in Sub-Saharan Africa: A Systematic ReviewPGPH-D-23-00184Dear Mr Byiringiro,We are pleased to inform you that your manuscript 'Health Systems Interventions for Hypertension Management and Associated Outcomes in Sub-Saharan Africa: A Systematic Review' has been provisionally accepted for publication in PLOS Global Public Health.Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.globalpubhealth@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Global Public Health.Best regards,Julia RobinsonExecutive EditorPLOS Global Public Health***********************************************************Reviewer Comments :Reviewer's Responses to Questions <font color="black"> Comments to the Authorpublication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented. </font> 1. Does this manuscript meet PLOS Global Public Health’s Reviewer #1: Yes********** <font color="black"> 2. Has the statistical analysis been performed appropriately and rigorously? </font> Reviewer #1: Yes********** <font color="black"> 3. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. </font> The Reviewer #1: Yes********** <font color="black"> 4. Is the manuscript presented in an intelligible fashion and written in standard English? </font> PLOS Global Public Health does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: Yes********** <font color="black"> 5. Review Comments to the Author </font> Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: The authors have summarized in exquisite detail the status of hypertension management in sub-Saharan Africa. They have found that the literature on health care interventions dealing with hypertension there is severely limited. Importantly, they outline a logical approach to addressing this deficiency in the medical literature. The manuscript provides very useful information for health care policy makers and providers in sub-Saharan Africa and low income countries worldwide. The manuscript is well written and deserves publication in its current form with a high priority.********** <font color="black"> 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.Privacy Policy. </font> For information about this choice, including consent withdrawal, please see our Reviewer #1: No**********


Dear Editor,Tuberous Sclerosis Complex (TSC) is a rare genetic neurocutaneous syndrome, with a frequency of 1/6,000‒10,000 live births, characterized by hamartomas and multiple skin manifestations.4The authors present three male patients with a prenatal diagnosis of cardiac rhabdomyomas and postnatal confirmation of TSC. Dermatologic examination of all patients revealed multiple hypopigmented macules in the trunk and scalp , more evCardiac rhabdomyomas are the most frequent childhood primary heart tumors in the general population.Fetal prognosis is dependent on effective intrauterine monitoring and an adequate birth plan. Up to 85% of the cases do not need medical or surgical treatment since most have partial or complete regression from birth to adolescence.None declared.Virginia Ruth Lopez Gamboa: Approval of the final version of the manuscript; critical literature review; data collection, analysis, and interpretation; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic management of studied cases; manuscript critical review; preparation and writing of the manuscript; study conception and planning.Mariel Giovo: Approval of the final version of the manuscript; critical literature review; data collection, analysis, and interpretation; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic management of studied cases; manuscript critical review; study conception and planning.Victor Francucci: Approval of the final version of the manuscript; data collection, analysis, and interpretation; effective participation in research orientation; manuscript critical review.None declared.


Different environmental and biological factors can originate and support different alternative life histories in different taxonomic groups. Likewise, these factors are important for the processes that assemble and structure communities. Amphibians, besides being highly susceptible to environmental conditions, have various reproductive strategies, such as the direct development of individuals. Several hypotheses have been raised about possible selective pressures related to the emergence of direct development in anurans, as well as the relationship between environmental characteristics and the occurrence of these species. Such investigations, however, have mainly focused on specific clades and/or regions. Here, we use structural equation modelling to investigate the relationships between different abiotic  and biotic  factors and the proportion of species with direct development in 766 anuran communities of the Atlantic Forest, a biome with a vast diversity of anuran species and high environmental complexity. Anuran communities with higher proportions of direct developing species were found to be mainly influenced by low potential evapotranspiration, low temperature seasonality, and high functional diversity. Phylogenetic composition and terrain slope were also found to be important in determining the occurrence of these species in Atlantic Forest communities. These results show the importance of these factors in the structuring of these communities and provide important contributions to the knowledge of direct development in anurans. As the result of a long and complex evolutionary history, the great diversity of amphibian species represents numerous morphological and behavioral varieties, an abundance of ecological relationships, and the greatest diversity of reproductive modes among tetrapods . SeventyDirect developing anurans are mostly associated with climatically stable environments, such as forests with higher levels of humidity and structural complexity –9. In thContinuously distributed along the Brazilian coast and penetrating inland regions, the Atlantic Forest has enormous environmental heterogeneity, with different forest formations, microclimatic conditions, and variations in relief ,16. Due The evolutionary and ecological relationships, different life histories, and great diversity of morphologies and reproductive modes of anurans are reflected not only in their high taxonomic diversity but also in their high phylogenetic and functional diversities in the Atlantic Forest ,22. PhylUnderstanding how biotic and abiotic factors are related to direct development in anurans is crucial, since these relationships can help to discover the conditions that are favorable or unfavorable for the occurrence of reproductive modes in distinct environments. Furthermore, based on these relationships, new insights can be gained into the evolution of terrestrial reproductive modes, such as direct development. Thus, here we employ structural equation modelling (SEM) to evaluate the relationships among environmental characteristics (climate and topography), biotic characteristics , and the proportion of direct developing anuran species in communities of the Atlantic Forest .As mentioned above, the evolution of anuran direct development can be a result of driving forces due to the actuation of abiotic factors. Thus, we expected to find higher proportions of direct developing anuran species in communities that are climatically stable and with elevated levels of humidity and rough terrain. If ecological mechanisms  are also forces related to the divergence and evolution of traits, and if these mechanisms are linked to the main hypotheses regarding the evolution of direct development in anurans, we would expect that communities that experienced high levels of these interactions in the past would currently have higher levels of functional diversity and higher proportions of direct developing anuran species. In this context, communities that historically experienced high competition and predation rates must have undergone functional divergence, with species occupying new niches. As a result, these communities should currently exhibit greater functional diversity and greater proportions of direct developing anuran species.D matrix). We then calculated the observed proportion of direct developing species in each community. Next, we generated a set of 999 null proportions through D matrix randomization and calculated the mean and standard deviation of these proportions. Finally, based on the standardized effect size metrics, we used the observed proportions and the means and standard deviations of the null proportions to calculate the proportion of direct developing species free from the composition effect for each of the communities. In total, our analyzed database comprised a comprehensive collection of 766 communities distributed along the extension of the Atlantic Forest  [https://csidotinfo.wordpress.com/2019/01/24/global-aridity-index-and-potential-evapotranspiration-climate-database-v3/) [www.earthenv.org) [To investigate the relationship among biotic and abiotic factors and the proportion of direct-developing anuran species in Atlantic Forest communities, we gathered bioclimatic and topographic data for each of the previously selected communities, utilizing their geographic coordinates. We downloaded the 19 bioclimatic variables from WorldClim 2.1 (21.html) ,36 and pase-v3/) . We consase-v3/) . Thus, senv.org) . After denv.org) , to obtaTo reduce the number of abiotic variables in our final model, we initially fitted two linear models using the proportion of direct development species in each community as the response variable and abiotic variables (temperature and precipitation) as predictors. We then selected models based on the Akaike information criterion (AIC) . The AICChiasmocleis lacrimae; Eleutherodactylus bilineatus; Boana cambui, Phrynomedusa dryade; Phyllomedusa rustica; Proceratophrys mantiqueira; Scinax melanodactylus; and Trachycephalus typhonius. We included these PUTs in the subtree by using information from the literature to define the most derived consensus clade (MDCC), which represents the most basal node containing the closest living relative [for more details see P matrix), which produces a series of eigenvectors that describe orthogonal gradients of phylogenetic structure [To consider the evolutionary history of the assemblages and to determine its role in the occurrence of direct developing species in Atlantic Forest anuran communities, we opted to incorporate phylogenetic composition in our final model. To do this, we created a phylogenetic tree of our species pool (subtree) using as a base the consensus phylogenetic hypothesis proposed by Jetz and Pyron . We usedtructure ,50. Whertructure . We usedtructure  in the Rtructure .To calculate FD, we initially compiled information about reproductive and morphological traits using data sets, articles and books to create a database containing the following seven functional traits: i) oviposition type ; ii) development type ; iii) juvenile habitat ; iv) oviposition site ; v) body length; vi) head width; and vii) tibia length . We usedDespite the effort, we were not able to collect information about head width for 139 species and tibia length for 146 species. Therefore, for species with missing data, we inferred these traits through a maximum likelihood approach using the phylogenetic tree and the Rphylopars package . This apFinally, to reduce the effect of species number on functional diversity in the Atlantic Forest amphibian communities and to allow comparisons of communities with different richness values, we calculated the standardized effect size of functional diversity (SES.FD) . These mTo calculate SES.FD we generated a distance matrix based on the first 283 phylogenetic eigenvectors (which contained 95% of data variation) previously obtained from the PVR analysis, which were later transformed into a dendrogram using the stats package . Then, bTo evaluate the relationships among biotic and abiotic variables and the proportion of direct developing species in Atlantic Forest anuran communities, as proposed in Prior to fitting the SEM model, we tested and verified the absence of spatial autocorrelation in the data. To do this, we constructed generalized least squares models (GLS) containing the abiotic and biotic variables, and the proportion of direct developing species  with expOur full dataset comprised 464 species of 19 families distributed among 766 anuran communities along the full extension of the Atlantic Forest, with species richness ranging from 2 to 49 species per community . Just over 10% (49) of the recorded species had a reproductive mode with direct development, and they were concentrated in a few lineages . About 3Together the first two PCPS eigenvectors captured 36.84% of the total variation in the phylogenetic composition data. Eigenvector 1 split communities that were formed by hylids with lower proportions of direct developing anurans from those formed by aquatic and terrestrial species (other lineages) with higher proportions of direct developing species. In turn, PCPS 2 was positively related to communities formed by terrestrial species with higher proportions of direct developing species and negatively related to communities formed by species with aquatic reproductive modes . The finding that almost all direct developers of the Atlantic Forest belong to only one clade supports the idea that South America served as a center of origin for this group of species. It also supports the idea that past environmental conditions of the coastal portion of the Atlantic Forest restricted the dispersal and occurrence of certain lineages to a suitable ecological niche [Brachycephalus and Ischnocnema, is the most represented lineage of direct developers in the Atlantic Forest. It is associated with montane forests, with a distribution restricted mainly to southern and southeastern portions of the Atlantic Forest [The clade Terrarana is a species complex, formed by four families of direct developing anurans , distributed throughout the New World  . It emeral niche ,73,74, sc Forest ,75,76. HThe effect of biotic factors on the evolution of direct development has never been effectively evaluated at the community scale, only by species-specific experiments. In this way, when functional diversity was used as a proxy of co-occurrence mechanisms, the model showed a significant positive relationship between this metric and the proportion of direct developing species in Atlantic Forest anuran communities. Thus, our results indicated that communities with higher functional diversity  were formed by a higher proportion of direct developing species, suggesting that direct development evolved as an alternative to minimize and/or avoid biotic pressures, as the main evolutionary hypotheses proposed ,11,77. FPatterns of phylogenetic and/or functional structure of communities can be identified at different scales, reflecting the actuation of distinct processes in their formation . Paz et As expected, we verified that the proportion of direct developing species in Atlantic Forest anuran communities is related to both biotic factors, namely phylogenetic composition and functional diversity, and abiotic factors, namely climate and topography. The different responses of amphibians to climatic conditions are known to be mediated by their reproductive modes . ReproduHistorically, the climatic seasonality of the coastal region of the Atlantic Forest delimited and restricted the occurrence of species with specialized reproductive modes to this portion that is climatically more stable . AmphibiAlthough terrestrial direct developers show high independence from water bodies, they remain dependent on humidity in the environment . In the Another factor that is also considered to promote reproductive diversification and specialization is the complex topography of the Atlantic Forest . High alDespite the important relationships observed among the climatic conditions, topography, biotic factors, and the proportion of direct development species in the studied Atlantic Forest anuran communities, a significant part of our data remained unexplained. In this context, other factors that we did not evaluate here could also be related to the structuring of these communities, such as micro-environmental and biogeographical factors. As noted by Lion et al. , environDirect developers have particular life history and ecological traits, such as an association with high-altitude environments, restricted distributions, and smaller clutches with larger eggs, traits that can be associated with extinction risk ,98–101. S1 FileSubset of 766 Atlantic Forest anuran communities based on Vancine et al. 2018  data.(XLSX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S3 File(XLSX)Click here for additional data file.S4 FileBiotic and abiotic factors, and the proportion of direct development species of 766 Atlantic Forest anuran communities. *Standardized data.(XLSX)Click here for additional data file.S5 FileDirect and indirect effects of predictor variables on proportion of direct developing species of Atlantic Forest anuran communities.(DOCX)Click here for additional data file.S1 Appendix(TXT)Click here for additional data file.S2 Appendix(PDF)Click here for additional data file.S3 Appendix(DOCX)Click here for additional data file.


The membrane of a cell, often compared to a dynamic city border, carries out an intricate dance of controlling entry and exit, guarding the valuable life processes occurring inside. Lipids and proteins are essential components of cell-surface membranes . The dynThe four research papers presented in this Special Issue delved into the profound yet intricate relationship between biophysics and cellular functionality, with a particular emphasis on cryopreservation of cells and the lipid behavior in cell membranes.The studies “Dimethylglycine Can Enhance the Cryopreservation of Red Blood Cells by Reducing Ice Formation and Oxidative Damage”  and “TriDelving into the microcosm of lipid rafts, the studies “Lipids in Mitochondrial Macroautophagy: Phase Behavior of Bilayers Containing Cardiolipin and Ceramide”  and “EffProviding a broader perspective, the reviews included in this Special Issue titled “The Role of Cryoprotective Agents in Liposome Stabilization and Preservation” and “Antifreeze Proteins: Novel Applications and Navigation towards Their Clinical Application in Cryobanking” highlighted how understanding the biophysical properties of cryoprotectants and anti-freeze proteins can improve the preservation of biological materials. The review on cryoprotective agents emphasized the importance of understanding the complex interactions between protectants and bilayer composition, which could lead to enhanced stability of liposomal drug delivery systems. The review on anti-freeze proteins emphasized their potential in the cryopreservation of different cells, tissues, and organs, pointing towards a promising future with less toxicity and more efficiency.In essence, this Special Issue has expanded our understanding of cellular biophysics, particularly regarding membrane dynamics and the fascinating world of cryoprotection. Yet, much more remains to be explored. A deeper comprehension of lipid rafts and their manipulation could provide a plethora of therapeutic possibilities. Moreover, the search for novel cryoprotectants and their potential applications continues to be a thrilling domain of research. We must also strive to integrate these biophysical findings with cellular biology, biochemistry, and genetics, fostering a multi-disciplinary approach.In conclusion, as the frontier of molecular and membrane biophysics continues to evolve, we look forward to more groundbreaking research that would provide insights into the delicate dance of life within the cell, ultimately leading to innovative therapeutic strategies and technological advancements in the field of cellular biology.


The Cancer Prevention and Control Research Network (CPCRN) is a national network focused on accelerating the translation of cancer prevention and control research evidence into practice through collaborative, multicenter projects in partnership with diverse communities. From 2003 to 2022, the CPCRN included 613 members.We: (1) characterize the extent and nature of collaborations through a bibliometric analysis of 20 years of Network publications; and (2) describe key features and functions of the CPCRN as related to organizational structure, productivity, impact, and focus on health equity, partnership development, and capacity building through analysis of 22 in-depth interviews and review of Network documentation.Searching Scopus for multicenter publications among the CPCRN members from their time of Network engagement yielded 1,074 collaborative publications involving two or more members. Both the overall number and content breadth of multicenter publications increased over time as the Network matured. Since 2004, members submitted 123 multicenter grant applications, of which 72 were funded (59%), totaling more than $77 million secured. Thematic analysis of interviews revealed that the CPCRN’s success—in terms of publication and grant productivity, as well as the breadth and depth of partnerships, subject matter expertise, and content area foci—is attributable to: (1) its people–the inclusion of members representing diverse content-area interests, multidisciplinary perspectives, and geographic contexts; (2) dedicated centralized structures and processes to enable and evaluate collaboration; and (3) focused attention to strategically adapting to change.CPCRN’s history highlights organizational, strategic, and practical lessons learned over two decades to optimize Network collaboration for enhanced collective impact in cancer prevention and control. These insights may be useful to others seeking to leverage collaborative networks to address public health problems. Cancer morbidity and mortality disparities are most pronounced among rural, minoritized, low-income and uninsured sub-populations in the United States –3. IndeeCPCRN comprises academic, public health, clinical, organizational, and community partners who collaborate to conduct partnered research in cancer prevention and control, particularly in medically underserved groups . Using aCPCRN members have worked with national, state, and local partners to reduce cancer risk, improve routine prevention and screening and timely treatment, reduce cancer death rates, enhance the value and effectiveness of cancer care, and mitigate disparities by advancing the science and practice of D&I in cancer prevention and control , 19. OurOur overarching objective in this manuscript is to clarify the ingredients of the “special sauce” of the CPCRN, that is: how has a large and complex, geographically dispersed and loosely connected network of individuals balanced a consistent mission and vision with a dynamic approach to pursuing that mission and vision over time? We attempt to resolve this question in three ways, by: (1) first, demonstrating the extent and nature of Network collaborations and expertise through a bibliometric analysis of all member publications over the past 20 years; (2) second, describing major themes that characterize the CPCRN in terms of its organization and emphasis on health equity, community partnership development, and capacity building through analysis of 22 in-depth interviews with key informants involved in the Network from inception to present; and (3) third, illustrating how strategically-developed organizational structures of the Network can meaningfully support ongoing engagement across investigators, their many institutions, and their community partners through Network policies, procedures, and norms. Our description of the longstanding the CPCRN offers lessons for population scientists across many fields who are interested in engaging with or leading formal research networks.We employed a mixed methods approach using a convergent parallel design to conduct this study. Quantitative methods were used to analyze collaborative the CPCRN publications and grants; qualitative methods were used to analyze key informant interviews and existing policies and procedures documents to better understand how Network structures, processes, strategy, and culture support its people in achieving a shared purpose. Together, these methods provide a more comprehensive picture of how CPCRN pursues its mission and vision in alignment with its strategic plan and logic model, both of which have been updated as needed over time.From two data sources—Scopus and CPCRN’s internal progress reporting system—a retrospective, longitudinal, descriptive design was used to analyze existing bibliographic and administrative data on multicenter collaborations. To assess the growth and impact of total CPCRN publications, authorship data from Scopus were collected using researchers’ first and last name or Author ID (Scopus), as well as center affiliation, for 613 CPCRN members identified through the CPCRN membership directory and archives. Searches were filtered to focus specifically on years ranging from 2003 to 2022, as the first funding cycle effectively began in October 2002, and 3 months of this calendar year would not have been enough time to publish collaboratively. Authors’ records were limited to articles published after their respective center’s start date in the Network, or, if they were an Affiliate member, the date after which they were formally approved by the Steering Committee to participate in the Network. Duplicate and false-positive records were removed. Records for Medical Subject Heading (MeSH) term extraction were searched and downloaded on 23 September 2022. To focus on the growth of collaborative efforts within the Network, we retrieved multicenter publications, defined as such if publications involved two or more CPCRN Collaborating Center authors or Affiliate members from different institutions within CPCRN. For the bibliographic analysis, each author record was assigned a center-level identifier and linked with unique article-level identifiers to construct co-authorship clusters for each year. Custom Python scripts, R, version 3.0.2, and Excel, version 16.66.1, were used to parse, process, and summarize data, and VOSviewer, version 1.6.18, was used to construct data visualizations of the clusters .The CPCRN Coordinating Center employs an online administrative reporting system to monitor and evaluate Network outputs and outcomes by collecting detailed information from Collaborating Centers annually about center-specific and multicenter publications, presentations, grant applications, trainings, reports/plans/policies, and other CPCRN-related activities . ThroughSemi-structured, key informant interviews were conducted among CPCRN leaders and members, including those currently involved in the Network and past members no longer involved. Authors SBW, RJL, ALY and RSW compiled a full list of all Principal Investigators (PIs), Project Directors (PDs), Federal Agency Partners and affiliates in leadership roles within the Network , from which the team identified a diverse group of Network members and partners, past and present, who were perceived as: instrumental in shaping and/or progressing the Network; and/or had participated over the course of many years, potentially spanning multiple funding cycles and could comment on CPCRN’s evolution over time. These individuals represented diverse professional and academic disciplines, and their roles, responsibilities, and level and duration of engagement varied. A total of 49 individuals were sent initial and follow-up recruitment emails, modifying language as needed to reflect their Network role and status of involvement . Those who expressed interest were sent additional study details, and upon providing written consent to voluntarily participate, were formally enrolled into the study. No compensation was provided.With a primary aim of gaining insight into members’ perceptions of the Network, unique experiences, best practices, lessons learned, and feedback/recommendations, the study team developed a semi-structured interview guide for use among participants. Informed by suggestions from co-authors, the guide went through several iterations before being finalized. The final draft was modified slightly to align with characteristic differences among participants, predominately relating to: Network role and respective responsibilities/contributions; center or agency with which they were or are currently affiliated; and extent of involvement, in terms of both participation duration and time elapsed since departing from or joining the Network. Over the 3-month data collection window, one team member (ALY) conducted a total of 22 one-on-one interviews averaging 45–50 min each. Characteristics of interviewees are described in Table A coding team consisting of SBW, RJL, ALY, and CE met to establish a collaborative coding approach and develop the codebook structure. They independently reviewed three different transcripts and developed an initial comprehensive collection of themes and sub-themes that emerged most prominently across the conversations. Primary themes included: (1) multidisciplinary expertise; (2) collaborative culture; (3) supportive funding; (4) Network structures and policies; (5) professional and leadership development; (6) community orientation; (7) adaptability; and (8) attention to ongoing learning and improvement. After defining and refining these codes, the codebook and all transcripts were uploaded into Dedoose qualitative data management software, Version 9.0.62 . Nine adIn addition, we conducted a comprehensive review of existing CPCRN documents, including policies, procedures, and web-based resources, to enumerate and characterize the breadth and variety of written processes and structured materials, developed and modified over time with the shared goal of orienting, supporting, and continuously guiding members within the Network.In the 20 years since CPCRN’s inception through the Special Interest Projects (SIP) mechanism of the CDC Prevention Research Center’s (PRC) Program, the Network has consisted of a cumulative total of 19 different Collaborating Centers, each of whom participated in one or more of the five cycles funded Table . The depMulticenter publications are one indicator used to gauge the level of collaborative impact within the Network. Across the 20 years of CPCRN (2003–2022), CPCRN members have produced 22,781 total publications , of which 1,074 are multicenter publications with at least two authors from different CPCRN institutions. In 2003, the Network produced eight multicenter publications; in contrast, by 2021, the last full year for which data are available, the number of multicenter publications produced in a single year grew to almost 100 publications  the University of Arizona establishing an academic-community partnership with Mariposa Community Health Center (MCHC) to improve the health and reduce morbidity among border-dwelling Hispanic cancer survivors; (2) the University of Iowa College of Public Health launching the Health Equity Advancement Lab (HEAL) in 2012 to support researchers and non-academic community partners interested in tackling persistent health inequities through a community-based participatory research approach; and (3) the University of North Carolina partnering with four federally qualified health centers and health departments to increase implementation of colorectal cancer screening, lung cancer screening, HPV vaccination, and HPV/Pap co-testing.CPCRN began collecting grants data in 2004. Since that time, CPCRN members have received a total of 682 grants in support of research efforts to advance the adoption and implementation of evidence-based cancer prevention and control. Of the 123 multicenter collaborative grant applications submitted since 2004, 72 ~ 59%) have been funded, resulting in over $77.1 million in funding support for collaborative CPCRN-related research  dedicated, centralized structures and processes designed to promote healthy collaboration and the ability to meaningfully evaluate those efforts; and (3) focused attention around strategic adaptation in response to rapidly-changing evidence and to meet the dynamic, contextually specific needs and interests of community partners.A total of 22 key informants were interviewed over a 3-month window in July–September 2022, representing a diverse group of CPCRN members whose duration of involvement in the Network ranged from three to all 20 years. PIs, PDs, Federal Agency Partners, and community partners were included. In-depth content analyses of these data revealed eight prominent themes of the Network that have significantly contributed to the success and impact of CPCRN: Multidisciplinary expertise; Collaborative culture; Supportive funding; Network structures and policies; Professional and leadership development; Community orientation; Adaptability; and Ongoing learning and improvement. These eight themes can be grouped into three overarching meta-themes: (1) inclusion of Each of the eight themes and corresponding sub themes are summarized below. A comprehensive breakdown of the full codebook, along with de-identified, illustrative quotations drawn from the discussions to further describe the codes in context, is described in Table The breadth of expertise that comprises the Network has become increasingly diverse over time. The current composition of members reflects an extensive range of expertise across content areas , disciplines  and partnerships/settings  across a variety of organizations and representing broad geographic regions and diverse institutions, including minority serving institutions, NCI-designated cancer centers, and more.The nature by which CPCRN members engage with one another within their own Centers and across the Network, and the types of relationships that stem from those engagements, are seen as inherently collaborative, welcoming, and accessible. Key subthemes related to collaborative culture include: shared motivations and values; longevity of the Network; culture of collegiality; democratic decision processes; and CPCRN being a network of friends and “family.”The sustained and flexible funding from CDC available to Collaborating Centers to support CPCRN efforts, according to key informant interviewees, has been crucial to maintaining and growing operations over time and has allowed academic centers and individual investigators to support early career scholars, community partners, and bold scientific research efforts directly in ways that may not have been possible otherwise. The flexibility of CPCRN funding relates to its focus on building a collaborative research infrastructure where cross-center projects can emerge organically over time as researcher and partner interests align. As a result, the Network can be nimbler to quickly pivot to pursue new topics of shared interest. Key subthemes related to funding include: award amount ; allocation expectations ; funding mechanism and its role in Federal Agency Partner accessibility ; and additional grant applications and awards pursued by Network members .The organizational structure, operating processes and practices, and day-to-day functioning of the CPCRN reflect an intentional shared leadership model bolstered by collaborative guidance documents and procedures developed by the Coordinating Center with input from the Steering Committee. The structure of the CPCRN–consisting of eight funded Collaborating Centers, one funded Coordinating Center, Federal Agency Partners from the CDC and the NCI, an active Steering Committee that meets monthly, and multiple priority Workgroups and Interest Groups–has enhanced its capability to conduct work efficiently and effectively. The CPCRN Steering Committee consists of the Coordinating Center PI, PIs from all funded Collaborating Centers, Federal Agency Partners from the CDC and NCI, and all Workgroup and Interest Group leaders. Each year, two Collaborating Center PIs serve as Steering Committee co-chairs. Collaborating Center PIs work closely with their local communities and bring feedback from their community partners to the Steering Committee. Key subthemes related to Network structure include: its engaged key personnel consisting of PIs, PDs, Co-Investigators (Co-I), Federal Agency Partners, Affiliates, intra-Network entities and community partners; the structure of Center-specific (Core) and multicenter (Workgroup and Interest Group) Projects; the development of strong guidance documents written, maintained, and updated over time; strength of Network leadership; development of an Affiliate membership process and inclusive orientation; use of a robust progress reporting structure; and strong Network communications structures.Network members often attribute their noteworthy professional achievements attained, opportunities seized, milestones reached, and their evolution into leaders in the Network and in their respective fields, in large part, to their involvement in the CPCRN. Key subthemes related to professional and leadership development include: a strong commitment to mentorship across the Network; member and community partner engagement and collaborations beyond the Network; and the development and growth of the CPCRN Scholars Program to formalize training activities for the next generation.The CPCRN has always been community-connected-oriented—a network of networks strengthened by community advisors’ input within each Collaborating Center—with an explicit focus on recognizing and addressing social and environmental determinants of health at the community level, building capacity for knowledge translation and adaptation in diverse settings, and improving public health outcomes, especially for the most marginalized communities. Key subthemes related to community orientation include: emphasis on community-based participatory research and engaged research; focus on capacity-building activities; active dissemination of research products; and production of evidence-based interventions.Adaptability reflects the degree to which the CPCRN recognizes and is receptive to the need for change, makes informed, joint decisions about the best course of action, and sustains changes over time, as needed, to align with the forces driving for change and in the best interests of the Network. An open, continuous-learning mindset allows the CPCRN to adapt more quickly to new challenges  and to be responsive to opportunities for synergy . Key subthemes related to adaptability include responding to: the social and political environment; priorities and needs in the field; expectations of the funders and Network members; and the CPCRN funding cycle fluctuations and transitions.Being attentive to lessons learned and being open to, and responding directly, to critical feedback are core principles that guide the CPCRN functions. This theme reflects lessons learned through involvement in the Network, as well as constructive criticisms, identification of opportunities for improvement, and suggestions for modifying existing practices/adopting new ones to ensure that the Network maintains forward momentum and continues to grow and have impact in years to come. Opportunities for improvement noted in the interviews were: increasing the representation of underrepresented investigators in the CPCRN; continuing to embed health equity principles in all network functions; identifying more ways to support the rapid growth in numbers of unfunded Affiliates and scholars; creating more mechanisms for community partner input; and ensuring that the network can sustain its work and momentum across funding cycle transitions.When assessed altogether, the policies and procedures documents, Network progress reporting and Workgroup charter templates, and other miscellaneous resources were collectively effective in painting a complete and comprehensible picture of the CPCRN document infrastructure, including the breakdown of roles, intra-Network dynamics, and functions and processes integral to, and increasingly characteristic of the CPCRN. The CPCRN Coordinating Center has developed guidance resources, communication infrastructures, and efficient processes for supporting integration and logistics among Network members and continues to create new materials to improve productivity, visibility, and impact as needed. Network structures and processes have helped clarify roles, functions and expectations of the CPCRN members. This includes establishing productivity norms, deliverables, timelines, and metrics up front when orienting new Collaborating Centers and Affiliate members, chartering a Workgroup/Interest Group, and monitoring leadership and dynamics at regular intervals. Among other noteworthy takeaways from the documents analysis was a recurring emphasis—explicitly stated or clearly illustrated—regarding the critical importance of promoting new and bolstering existing multidisciplinary collaborations within and across Network centers  Table .Table 5Thttps://www.cpcrn.org/about-areas-of-expertise). Current cycle data indicate that CPCRN5 (2019–2024) members represent diverse disciplines, including epidemiology, health behavior, health services research, health economics, nutrition, nursing, medicine, and pharmacy and possess a broad range of research methods expertise, including program evaluation, survey development, simulation and systems science, community engagement and community-based participatory research (CBPR), capacity building, training and training evaluation, providing technical assistance, economic evaluation, health and risk communication, dissemination, implementation science, de-implementation, social network analyses, intervention development and testing, measures/measures development, qualitative methods/configurational comparative methods, large database analytics, systematic review/meta-analysis, human-centered design/design thinking/innovation techniques, comparative effectiveness, mHealth/eHealth, and spatial analysis/GIS and mapping.The CPCRN Coordinating Center has tracked self-reported disciplinary strengths and methods expertise of its members for the past two cycles of funding. These data have been used to create network cluster diagrams in Kumu, which are available on our website for investigators, Federal Agency Partners and others to use to help identify collaborators, subject matter experts, or to understand network members’ research expertise prioritization of activities –35. Specraison d’etre for the Network, the CPCRN employs an inclusive engagement process to invite and support new collaborative ideas and opportunities, aided and vetted by the Steering Committee, which evaluates whether new collaborative ideas reflect the objectives and priorities of the CPCRN, as well as the expertise and skills of participating member institutions and individual investigators and Affiliate members. This process allows new Workgroups to emerge organically, to adapt strategically, and then dissolve, if appropriate, when their work is complete.Large, complex research networks with competing values and demands need effective coordination, communication, and facilitation to ensure that the work of investigators, collaborating partners, and Affiliate members occurs smoothly, is completed in a timely manner, and meets Network goals, which is facilitated by well-organized structures and processes centralized within the Coordinating Center. The introduction of new Collaborating Center institutions over time—a process that occurs in 5-year funding cycles with the PRC Program and engagement of new community, and clinical partners and individual investigators on an ongoing basis—can bring a fresh perspective and different strengths to existing the CPCRN partnerships. On the other hand, turnover can sometimes introduce uncertainty and confusion since new members are not as familiar with the culture and norms of the Network. The Policies and Procedures guidance document and other resources help to orient new members to the Network and engage them quickly in Network activities. Because multicenter collaboration is the This shared ownership and decision-making process was viewed by key informants as helpful in keeping members connected and productive over time. The Network has clearly grown in terms of its membership and publication productivity from its 10-year anniversary bibliometric analysis—249 collaborative the CPCRN publications were reported out of 6,534 total articles among 309 unique the CPCRN researchers at 11 centers—to its 20-year anniversary—1,074 collaborative publications were reported out of 22,781 total articles among more than 600 unique the CPCRN researchers at 17 centers . In addiSome limitations accompany this work. First, for the bibliometric analysis, we chose to define center-level identifiers as the individual institutions with which each author was affiliated at the time that they entered the Network. Some authors were affiliated with two or more institutions during their respective years of involvement. As such, this decision may have resulted in a small number of publications being incorrectly attributed to authors’ original centers; however, because the focus of the Network is on multicenter collaborations rather than tracking individual authors’ professional trajectories, this was felt to be a reasonable approach. Second, for the interviews, key informants whose involvement was limited to early years of the CPCRN were less likely to respond to our invitations to participate (due to retirements or other reasons), which may have biased our analysis towards the inclusion of more recent observations. Third, it is, of course, possible that respondents who chose to participate in interviews had more positive experiences and/or perceptions of the CPCRN than non-respondents. Similarly, social desirability bias may have also prompted them to be more complimentary when interviewed by our research assistant. In an effort to account for and minimize risk of collecting socially desirable response data, we invited a broad range of the CPCRN members from multiple institutions and roles over time, using a single research assistant interviewer, de-identifying all data, and assuring privacy and confidentiality. As noted in Theme 8, several opportunities for improvement and future work were noted by interviewees, which suggested that interviewees felt comfortable sharing strengths and weaknesses of the CPCRN. The latter have already been incorporated into network strategic planning and prioritization.people from diverse disciplines, backgrounds and geographic settings and sharing the decision making and priority setting with these individuals—invites meaningful input and continued commitment over time. Developing and adapting infrastructure  to support collaboration provides the structure to incorporate new members and guide Network functioning and operations. And finally, being willing to embrace change and balance competing values helps ensure responsiveness, relevance, and longevity of the Network over time. These ingredients help to ensure that the CPCRN will have a lasting impact on the science and practice of cancer prevention and control for many years to come.Our analysis offers some important insights to guide other thematic population health-focused research networks, particularly those in cancer prevention and control, seeking to build scientific synergy and promote community-academic collaboration in a rapidly changing environment. Other networks may seek to adopt similar collaborative values, organizational structures and processes to support remote and multicenter cooperation while facing competing and potentially contradictory demands. Our findings suggest that the special sauce of the CPCRN is made up of three key ingredients: people; processes and structure; and adaptability. Investing in and focusing on the professional development and inclusion of


To investigate the effect of an enhanced recovery after surgery (ERAS) programme following liver transplantation and to further clarify the safety and clinical application value of an ERAS programme.A retrospective analysis of 250 patients who underwent liver transplant at Beijing You’an Hospital affiliated to Capital Medical University between March 2019 and December 2021 was conducted. According to different perioperative management methods, patients were divided into a control group (120 cases) and an ERAS group (130 cases). Postoperative safety indicators, efficacy indicators and economic indicators were compared between the two groups.There was no significant difference in the safety indicators between the two groups. The ERAS group showed significantly lower results compared with the control group in terms of ventilator-associated pneumonia, urinary tract infection, pressure injury of oral and nasal mucosa, postoperative pain score 5 days after surgery and the incidence of delirium, whereas the Barthel score 10 days after surgery was significantly higher. There was no significant difference between the two groups in skin pressure injury or the Subjective Global Assessment grade 10 days after surgery. The length of intensive care unit stay, the total length of stay after surgery and the 10-day medical expenses after surgery were significantly lower in the ERAS group than in the control group.The application of an ERAS programme after liver transplantation can effectively promote the postoperative recovery of patients and reduce medical costs. Studies have shown that the ERAS programme has important application value in improving the postoperative quality of life and reducing the economic burden of patients after liver transplantation. This programme provides a new concept for related clinical improvement and application. In 2001, the enhanced recovery after surgery (ERAS) research association was established in Europe and formally proposed the concept of ERAS . Since tLiver transplantation is an effective treatment for advanced liver diseases such as liver cancer, liver failure and cirrhosis. Compared with other surgical operations, liver transplantation is a difficult operation, involving a long surgery time, a high degree of trauma and a high incidence of postoperative complications. Coupled with the use of immunosuppressants, the perioperative management of liver transplantation is complicated. It is crucial to optimise the perioperative management strategy for patients undergoing liver transplant, accelerate the recovery of patients and improve the postoperative survival rate. There is currently no accepted standard protocol for ERAS after liver transplantation. Many previous studies on ERAS after liver transplantation have focused on a specific problem in the recovery process of patients, such as the early removal of tracheal intubation, early enteral nutrition, analgesia and sedation, or fluid management, but they have not adopted a comprehensive approach. Some domestic transplant centres have begun to explore the bundled ERAS scheme after liver transplantation and have achieved positive results, but the evaluation system is not perfect, and indicators, such as mortality, organ failure, hospital stay or cost, have been too macroscopic –12.In response to the above two problems, the team has constructed a new bundled ERAS treatment and management programme after liver transplantation using standardised evidence-based medicine and evidence-based nursing methods, involving respiratory therapy, nutritional therapy, and mental and psychological treatment; by also including treatments from other disciplines, such as anaesthetic pain treatment and critical care, a comprehensive ERAS programme for patients has been created. This study retrospectively analysed the clinical data of 250 recipients of liver transplant who were admitted to Beijing You’an Hospital affiliated with Beijing University of Science and Technology between March 2019 and December 2021 and explored the effectiveness and safety of an ERAS bundled management programme after liver transplantation.This is a retrospective cohort study. The clinical data of 250 patients who underwent liver transplantation in our hospital between March 2019 and December 2021 were retrospectively analysed. All 250 patients received deceased donor liver transplantation. According to different perioperative treatments, they were randomly divided into a control group (120 cases) and an ERAS group (130 cases). Using the methods of evidence-based medicine and evidence-based nursing, our team constructed a bundled ERAS treatment and nursing programme after liver transplantation and applied it to the ERAS group. The control group received conventional perioperative management protocols. The detailed protocol is provided in Table The inclusion criteria for recipients were the following: (1) complete clinical data, preoperative diagnosis with clear indications for liver transplantation and approval by the hospital transplant ethics committee; (2) elective allogeneic orthotopic liver transplantation; and (3) voluntary participation in the study and signed informed consent. The exclusion criteria were as follows: (1) patients undergoing emergency liver transplantation, (2) patients undergoing re-liver transplantation, (3) patients undergoing combined liver and kidney transplantation or liver transplantation combined with other operations, (4) patients who died during the operation, (5) patients who were automatically discharged or moved to another hospital, and (6) critically ill patients with postoperative primary graft failure or delayed graft recovery, postoperative severe bleeding, acute renal failure, acute respiratory distress syndrome or acute dysfunction of other organs.General information: sex, age, body mass index (BMI), diagnosis, model of end-stage liver disease (MELD) score , cirrhosSafety indicators: The incidence of postoperative complications .Efficacy indicators: Incidence of ventilator-associated pneumonia, incidence of urinary tract infection, incidence of skin pressure injury, incidence of pressure injury of oral and nasal mucosa, SGA grading 10 days after surgery, activities of daily living scale score 10 days after surgery (Barthel index) , postopeEconomic indicators: Intensive care unit (ICU) length of stay, total postoperative hospital stay, hospitalisation costs and readmissions within 90 days.t-test or rank combined analysis was used. Enumeration data were expressed as cases (%), and the χ2 test was used for comparison between groups. A score of p < 0.05 was considered statistically significant.Statistical analysis was performed using SPSS 19.0 software . Measurement data were expressed as mean ± standard deviation ; there were 130 patients in the ERAS group, with a male to female ratio of 41:24 and an average age of 49 years (range 22–63 years). There was no significant difference between the two groups in sex ratio, age, BMI, MELD index, Child score, preoperative SGA grade, operation time, intraoperative blood loss or anhepatic phase . The Barthel score in the ERAS group 10 days after surgery was 71, which was significantly higher than that in the control group. The pain score in the ERAS group 5 days after surgery was 3.5, and delirium was observed in 10 patients, both of which were significantly lower than in the control group. Three patients in the ERAS group and two patients in the control group had low arterial flow within 2 weeks of surgery, but no definite findings of arterial thrombosis or anastomotic stenosis were found. All five patients received active anticoagulant therapy but did not receive thrombolysis, arterial catheter intervention or surgical treatment. None of the 250 patients had portal vein stenosis, portal embolus, bile duct stenosis or biliary fistula within 90 days of surgery.The above results are shown in Table Comparing the ICU length of stay, total postoperative hospital stay and 10-day postoperative medical expenses between the two groups, the results for the ERAS group were lower than those of the control group, and the differences were statistically significant. There was no significant difference between the ERAS group and the control group in terms of readmission at 90 days after surgery. The above results are shown in Table p = 0.131).In all 250 patients who underwent liver transplantation, the operation was completed successfully (completion rate 100%). The 250 patients were followed up for 12 months; of the 130 patients in the ERAS group, 9 patients died, whereas out of the 120 patients in the control group, 15 patients died. The survival analysis curve is shown in Fig. In this study, using standardised evidence-based medicine and evidence-based nursing methods, a new bundled ERAS treatment and management programme after liver transplantation were constructed, involving respiratory therapy, nutritional therapy, psychotherapy, anaesthetic pain treatment, critical care and other disciplines. This study revealed that there were no significant differences in the safety indicators between the two groups, but the ERAS group exhibited significantly better results than the control group in terms of ventilator-associated pneumonia, urinary tract infection, pressure injury of the oral and nasal mucosa and malnutrition. The length of stay in the ICU, the total length of hospital stay after surgery and the 10-day medical expenses after surgery were lower in the ERAS group, which effectively reduced medical costs.Previous studies have shown that an ERAS programme can be effective, and this is closely related to the patient’s baseline state. A study published by Wang et al. in 2018 showed that during the application of an ERAS programme after hepatectomy, poor liver function and intraoperative bleeding were the risk factors most likely to result in failure of the postoperative ERAS programme . HepatecSafety during diagnosis and treatment is the primary issue for the implementation of ERAS programmes; however, many studies have placed equal importance on the safety and efficacy of ERAS treatments –23. In tProlonged mechanical ventilation, prolonged immobilisation in bed, prolonged parenteral nutrition and prolonged retention of gastric and urinary catheters after liver transplantation can lead to a series of complications , includiThe final part of this study compared the differences in ICU stay time, total postoperative hospital stay and 10-day postoperative hospitalisation cost between the two groups, and the results suggested that ERAS measures resulted in a significant economic advantage. The reason is that, in the ERAS group, the incidence of complications was greatly reduced by optimising the postoperative invasive treatment time of liver transplant patients, rationally applying analgesic drugs and actively giving patients rehabilitative treatment. This is an effective solution to improve rehabilitation efficiency and reduce medical expenditure, which is consistent with the research results of other transplant centres in China –11. HoweOur results preliminarily confirm that the ERAS programme can improve the recovery of patients following liver transplant. However, since this study is a single-centre retrospective study, the sample size is limited and the patients involved are from one hospital; therefore, the generalisability of the research results needs to be further verified. To better evaluate generalisability, large-scale multi-centre prospective studies should be conducted to expand the sample size and case type. In this way, the efficacy of the ERAS programme in different liver transplantation centres and patients with different types of liver transplantation can be observed. In this study, the formulation of the ERAS programme itself was based on evidence-based nursing. The author speculates that the ERAS programme is also applicable in different transplant centres and to a wider population, but this needs to be assessed; if future multi-centre studies also confirm that the ERAS programme can improve patient outcomes, the generalisation of our single-centre study results will be supported. At present, this study can only be used as a preliminary investigation to provide a reference for subsequent research.The post-liver transplantation bundled ERAS scheme proposed in this study was developed by team members through the systematic and standardised retrieval, evaluation, evidence grading, review and finalisation of evidence-based medicine and evidence-based nursing literature and is highly comprehensive and scientific. During the implementation of the research, tasks were divided among the team members, who cooperated and implemented the diagnosis and treatment nursing measures in strict accordance with the bundled ERAS plan; the results are therefore objective and accurate.In conclusion, the application of the ERAS programme can shorten the ICU and hospitalisation time of patients, reduce the incidence of postoperative complications and reduce the cost of postoperative hospitalisation. Our results demonstrate that the ERAS programme, which can also effectively reduce the postoperative burden of patients and improve survival outcomes, has a high clinical application value, and it provides reliable research evidence for the promotion of the ERAS programme in the field of liver transplantation. However, in view of the retrospective nature of this study and the limitation of the small sample size, prospective studies with larger samples should be conducted in the future to further clarify the impact of the ERAS programme on long-term follow-up after liver transplantation.