Examining liminality in professional practice, relational identities, and career prospects in resource-constrained health systems: Findings from an empirical study of medical and nurse interns in Kenya.

We examine new doctors' and nurses' experiences of transitioning from training to practising as health professionals, drawing on the concept of liminality. Liminality is a stage of 'in-betweenness', involving uncertainty and ambiguity as people leave one social context and reintegrate into a new one. Surprisingly little research has explored new health professionals' experiences of liminality during role and career transitions, particularly in precarious and resource-constrained settings. Drawing on 146 qualitative interviews and seven focus groups, involving 121 new graduate medical doctors and nurses transitioning through internship training in Kenya, we describe three aspects of liminality. First, liminal professional practice, where interns realise that best practices learned during medical and nursing schools are often impossible to implement in resource constrained health care settings; instead they learn workarounds and practical norms. Second, liminal relational identities, where interns leave behind being students and adopt the identities and responsibilities of qualified professionals within pre-existing professional hierarchies of status and expertise. We explain how these new doctors and graduate nurses negotiate their liminal status, including in relation to more experienced but less qualified professional colleagues. We also discuss how interns cope with liminality due to disappointing and inadequate supervision and role modelling from senior colleagues but then find peer support and their place within their own professions. Finally, we discuss how new doctors and nurses come to terms with the precarity of working in resource constrained health systems, abandon expectations of secure, permanent employment and careers, and accept the realities of liminal professional careers. We explain how all three forms of liminality influence professionals' developing practices, identities, and careers. We call for further studies with a specific liminality lens to explore this critical period in health workers' careers, to inform policy and practice responding to global transformations in healthcare professions and practice.

KDM1A, a potent and selective target, for the treatment of DNMT3A-deficient non-small cell lung cancer.

BACKGROUND: DNMT3A is a crucial epigenetic regulation enzyme. However, due to its heterogeneous nature and frequent mutation in various cancers, the role of DNMT3A remains controversial. Here, we determine the role of DNMT3A in non-small cell lung cancer (NSCLC) to identify potential treatment strategies. METHODS: To investigate the role of loss-of-function mutations of DNMT3A in NSCLC, CRISPR/Cas9 was used to induce DNMT3A-inactivating mutations. Epigenetic inhibitor library was screened to find the synthetic lethal partner of DNMT3A. Both pharmacological inhibitors and gene manipulation were used to evaluate the synthetic lethal efficacy of DNMT3A/KDM1A in vitro and in vivo. Lastly, MS-PCR, ChIP-qPCR, dual luciferase reporter gene assay and clinical sample analysis were applied to elucidate the regulation mechanism of synthetic lethal interaction. RESULTS: We identified DNMT3A is a tumour suppressor gene in NSCLC and KDM1A as a synthetic lethal partner of DNMT3A deletion. Both chemical KDM1A inhibitors and gene manipulation can selectively reduce the viability of DNMT3A-KO cells through inducing cell apoptosis in vitro and in vivo. We clarified that the synthetic lethality is not only limited to the death mode, but also involved into tumour metastasis. Mechanistically, DNMT3A deficiency induces KDM1A upregulation through reducing the methylation status of the KDM1A promoter and analysis of clinical samples indicated that DNMT3A expression was negatively correlated with KDM1A level. CONCLUSION: Our results provide new insight into the role of DNMT3A in NSCLC and elucidate the mechanism of synthetic lethal interaction between KDM1A and DNMT3A, which might represent a promising approach for treating patients with DNMT3A-deficient tumours.

Factors influencing the development, recruitment, integration, retention and career development of advanced practice providers in hospital health care teams: a scoping review.

BACKGROUND: Advanced practice providers (APPs), including physician assistants/associates (PAs), nurse practitioners (NPs) and other non-physician roles, have been developed largely to meet changing healthcare demand and increasing workforce shortages. First introduced in primary care in the US, APPs are prevalent in secondary care across different specialty areas in different countries around the world. In this scoping review, we aimed to summarise the factors influencing the development, recruitment, integration, retention and career development of APP roles in hospital health care teams. METHODS: We conducted a scoping review and searched Ovid MEDLINE, Ovid Embase, Ovid Global Health, Ovid PsycINFO and EBSCOhost CINAHL to obtain relevant articles published between Jan 2000 and Apr 2023 that focused on workforce management of APP roles in secondary care. Articles were screened by two reviewers independently. Data from included articles were charted and coded iteratively to summarise factors influencing APP development, recruitment, integration, retention and career development across different health system structural levels (macro-, meso- and micro-level). RESULTS: We identified and analysed 273 articles that originated mostly from high-income countries, e.g. the US (n = 115) and the UK (n = 52), and primarily focused on NP (n = 183) and PA (n = 41). At the macro-level, broader workforce supply, national/regional workforce policies such as work-hour restrictions on physicians, APP scope of practice regulations, and views of external collaborators, stakeholders and public representation of APPs influenced organisations' decisions on developing and managing APP roles. At the meso-level, organisational and departmental characteristics, organisational planning, strategy and policy, availability of resources, local experiences and evidence as well as views and perceptions of local organisational leaders, champions and other departments influenced all stages of APP role management. Lastly at the micro-level, individual APPs' backgrounds and characteristics, clinical team members' perceptions, understanding and relationship with APP roles, and patient perceptions and preferences also influenced how APPs are developed, integrated and retained. CONCLUSIONS: We summarised a wide range of factors influencing APP role development and management in secondary care teams. We highlighted the importance for organisations to develop context-specific workforce solutions and strategies with long-term investment, significant resource input and transparent processes to tackle evolving healthcare challenges.

Conducting cross-cultural, multi-lingual or multi-country scale development and validation in health care research: A 10-step framework based on a scoping review.

Background: Valid, reliable and cross-cultural equivalent scales and measurement instruments that enable comparisons across diverse populations in different countries are important for global health research and practice. We developed a 10-step framework through a scoping review of the common strategies and techniques used for scale development and validation in a cross-cultural, multi-lingual, or multi-country setting, especially in health care research. Methods: We searched MEDLINE, Embase, and PsycINFO for peer-reviewed studies that collected data from two or more countries or in two or more languages at any stages of scale development or validation and published between 2010-22. We categorised the techniques into three commonly used scale development and validation stages (item generation, scale development, and scale evaluation) as well as during the translation stage. We described the most commonly used techniques at each stage. Results: We identified 141 studies that were included in the analysis. We summarised 14 common techniques and strategies, including focus groups or interviews with diverse target populations, and involvement of measurement experts and linguists for item content validity expert panel at the item generation stage; back-and-forth translation, collaborative team approach for the translation stage; cognitive interviews and different recruitment strategies and incentives in different settings for scale development stage; and three approaches for measurement invariance (multigroup confirmatory factor analysis, differential item functioning and multiple indicator multiple causes) for scale evaluation stage. Conclusions: We provided a 10-step framework for cross-cultural, multi-lingual or multi-country scale development and validation based on these techniques and strategies. More research and synthesis are needed to make scale development more culturally competent and enable scale application to better meet local health and development needs.

Integrating interventions supported by development assistance for health into local health system: evidence from a China-World Bank-UK rural health system strengthening project (1998-2007).

INTRODUCTION: To empirically investigate sustainability of development assistance for health (DAH), we conducted a retrospective case study on the Basic Health Services Project (BHSP) for rural health system strengthening, supported by the World Bank and the UK in China between 1998 and 2007. Specifically, this study examines the integration of the BHSP interventions into China's health system. METHODS: From December 2021 to December 2022, we reviewed 64 published papers and project or policy documents, and conducted semistructured interviews with 22 key informants, ranging from managers of donor agencies and the government to township-level hospital directors. From February to March 2023, the data were analysed under an analytical framework for integration of targeted health interventions into health systems. RESULTS: Evidence of the BHSP shows that the integration outcomes can vary by the levels of integration (national or subnational), geographical coverage (project areas or both project and non-project areas) and approach to integration (policy or routinisation). The country's health system reform facilitated the integration of the interventions relevant to the reform policies, as the BHSP was one of the pilot schemes. However, interventions incompatible with this broad context were integrated to a limited extent. This integration occurred through embedding the project within the existing system, with a higher degree of embeddedness leading to smoother integration. Cross-sectoral leading groups and a technical support system heightened the project visibility and enabled contextualised local adaptation, contributing to the smooth integration of the project interventions. CONCLUSION: The DAH-supported interventions can achieve sustainability by being integrated into the local health system. This integration can take various forms to improve health outcomes, including being accepted and internalised, modified as well as innovated and expanded. The host country and development partners can promote DAH sustainability by contextually integrating these interventions within the project scope.

Epidemiological variations and trends in glaucoma burden in the Belt and Road countries.

BACKGROUND: Analyzing the glaucoma burden in "Belt and Road" (B&R) countries based on age, gender, and risk factors from 1990 to 2019 in order to provide evidence for future prevention strategies. METHODS: We applied global burden of disease(GBD) 2019 to compare glaucoma prevalence and Years lived with disabilities (YLDs) from 1990 to 2019 in the B&R countries. Trends of disease burden between 1990 and 2019 were evaluated using the average annual percent change and the 95% uncertainty interval (UI) were reported. RESULTS: From 1990 to 2019, most B&R countries showed a downward trend in age-standardized prevalence and YLDs (all P < 0.05). Additionally, only the age-standardized YLDs in males of Pakistan has a 0.35% increase (95%CI:0.19,0.50,P < 0.001), and most B&R countries has a decline(all P < 0.05) in age-standardized YLDs in every 5 years age group after 45 years old except for Pakistan(45-79 years and > 85 years), Malaysia(75-84 years), Brunei Darussalam(45-49 years), Afghanistan(70-79 years). Finally, in all Central Asian countries, the age-standardized YLDs due to glaucoma caused by fasting hyperglycemia demonstrated have an increase between 1990 and 2019 (all P < 0.05), but Armenia and Mongolia have a decrease between 2010 and 2019 (all P < 0.05). CONCLUSION: The prevalence of glaucoma continues to pose a significant burden across regions, ages, and genders in countries along the "B&R". It is imperative for the "B&R" nations to enhance health cooperation in order to collaboratively tackle the challenges associated with glaucoma.

Development assistance, donor-recipient dynamic, and domestic policy: a case study of two health interventions supported by World Bank-UK and Global Fund in China.

BACKGROUND: This study views sustainability after the exit of development assistance for health (DAH) as a shared responsibility between donors and recipients and sees transitioning DAH-supported interventions into domestic health policy as a pathway to this sustainability. It aims to uncover and understand the reemergent aspects of the donor-recipient dynamic in DAH and how they contribute to formulating domestic health policy and post-DAH sustainability. METHODS: We conducted a case study on two DAH-supported interventions: medical financial assistance in the Basic Health Services Project supported by the World Bank and UK (1998-2007) and civil society engagement in the HIV/AIDS Rolling Continuation Channel supported by the Global Fund (2010-2013) in China. From December 2021 to December 2022, we analyzed 129 documents and interviewed 46 key informants. Our data collection and coding were guided by a conceptual framework based on Walt and Gilson's health policy analysis model and the World Health Organization's health system building blocks. We used process tracing for analysis. RESULTS: According to the collected data, our case study identified three reemergent, interrelated aspects of donor-recipient dynamics: different preferences and compromise, partnership dialogues, and responsiveness to the changing context. In the case of medical financial assistance, the dynamic was characterized by long-term commitment to addressing local needs, on-site mutual learning and understanding, and local expertise cultivation and knowledge generation, enabling proactive responses to the changing context. In contrast, the dynamic in the case of HIV/AIDS civil society engagement marginalized genuine civil society engagement, lacked sufficient dialogue, and exhibited a passive response to the context. These differences led to varying outcomes in transnational policy diffusion and sustainability of DAH-supported interventions between the cases. CONCLUSIONS: Given the similarities in potential alternative factors observed in the two cases, we emphasize the significance of the donor-recipient dynamic in transnational policy diffusion through DAH. The study implies that achieving post-DAH sustainability requires a balance between donor priorities and recipient ownership to address local needs, partnership dialogues for mutual understanding and learning, and collaborative international-domestic expert partnerships to identify and respond to contextual enablers and barriers.

Adapting national data systems for donor transition: comparative analysis of experience from Georgia and China.

Health management information systems (HMISs) are essential in programme planning, budgeting, monitoring and evidence-informed decision-making. This paper focuses on donor transitions in two upper-middle-income countries, China and Georgia, and explores how national HMIS adaptations were made and what facilitated or limited successful and sustainable transitions. This comparative analytical case study uses a policy triangle framework and a mixed-methods approach to explore how and why adaptations in the HMIS occurred under the Gavi Alliance and the Global Fund-supported programmes in China and Georgia. A review of published and grey literature, key informant interviews and administrative data analysis informed the study findings. Contextual factors such as the global and country context, and health system and programme needs drove HMIS developments. Other factors included accountability on a national and international level; improvements in HMIS governance by establishing national regulations for clear mandates of data collection and reporting rules and creating institutional spaces for data use; investing in hardware, software and human resources to ensure regular and reliable data generation; and capacitating national players to use data in evidence-based decision-making for programme and transition planning, budgeting and outcome monitoring. Not all the HMIS initiatives supported by donors were sustained and transitioned. For the successful adaptation and sustainable transition, five interlinked and closely coordinated support areas need to be considered: (1) coupling programme design with a good understanding of the country context while considering domestic and external demands for information, (2) regulating appropriate governance and management arrangements enhancing country ownership, (3) avoiding silo HMIS solutions and taking integrative approach, (4) ensuring the transition of funding onto domestic budget and enforcing fulfilment of the government's financial commitments and finally (5) investing in technologies and skilled human resources for the HMIS throughout all levels of the health system. Neglecting any of these elements risks not delivering sustainable outcomes.

External technical assistance and its contribution to donor transition and long-term sustainability: experience from China and Georgia.

External technical assistance has played a vital role in facilitating the transitions of donor-supported health projects/programmes (or their key components) to domestic health systems in China and Georgia. Despite large differences in size and socio-political systems, these two upper-middle-income countries have both undergone similar trajectories of 'graduating' from external assistance for health and gradually established strong national ownership in programme financing and policymaking over the recent decades. Although there have been many documented challenges in achieving effective and sustainable technical assistance, the legacy of technical assistance practices in China and Georgia provides many important lessons for improving technical assistance outcomes and achieving more successful donor transitions with long-term sustainability. In this innovation and practice report, we have selected five projects/programmes in China and Georgia supported by the following external health partners: the World Bank and the UK Department for International Development, Gavi Alliance and the Global Fund to Fight AIDS, Tuberculosis and Malaria. These five projects/programmes covered different health focus areas, ranging from rural health system strengthening to opioid substitution therapy. We discuss three innovative practices of technical assistance identified by the cross-country research teams: (1) talent cultivation for key decision-makers and other important stakeholders in the health system; (2) long-term partnerships between external and domestic experts; and (3) evidence-based policy advocacy nurtured by local experiences. However, the main challenge of implementation is insufficient domestic budgets for capacity building during and post-transition. We further identify two enablers for these practices to facilitate donor transition: (1) a project/programme governance structure integrated into the national health system and (2) a donor-recipient dynamic that enabled deep and far-reaching engagements with external and domestic stakeholders. Our findings shed light on the practices of technical assistance that strengthen long-term post-transition sustainability across multiple settings, particularly in middle-income countries.

'We were treated like we are nobody': a mixed-methods study of medical doctors' internship experiences in Kenya and Uganda.

OBJECTIVE: Medical interns are an important workforce providing first-line healthcare services in hospitals. The internship year is important for doctors as they transition from theoretical learning with minimal hands-on work under supervision to clinical practice roles with considerable responsibility. However, this transition is considered stressful and commonly leads to burn-out due to challenging working conditions and an ongoing need for learning and assessment, which is worse in countries with resource constraints. In this study, we provide an overview of medical doctors' internship experiences in Kenya and Uganda. METHODS: Using a convergent mixed-methods approach, we collected data from a survey of 854 medical interns and junior doctors and semistructured interviews with 54 junior doctors and 14 consultants. Data collection and analysis were guided by major themes identified from a previous global scoping review (well-being, educational environment and working environment and condition), using descriptive analysis and thematic analysis respectively for quantitative and qualitative data. FINDINGS: Most medical interns are satisfied with their job but many reported suffering from stress, depression and burn-out, and working unreasonable hours due to staff shortages. They are also being affected by the challenging working environment characterised by a lack of adequate resources and a poor safety climate. Although the survey data suggested that most interns were satisfied with the supervision received, interviews revealed nuances where many interns faced challenging scenarios, for example, poor supervision, insufficient support due to consultants not being available or being 'treated like we are nobody'. CONCLUSION: We highlight challenges experienced by Kenyan and Ugandan medical interns spanning from burn-out, stress, challenging working environment, inadequate support and poor quality of supervision. We recommend that regulators, educators and hospital administrators should improve the resource availability and capacity of internship hospitals, prioritise individual doctors' well-being and provide standardised supervision, support systems and conducive learning environments.

Development and validation of a new measurement instrument to assess internship experience of medical doctors in low-income and middle-income countries.

Routine surveys are used to understand the training quality and experiences of junior doctors but there are lack of tools designed to evaluate the training experiences of interns in low-income and middle-income countries (LMICs) where working conditions and resource constraints are challenging. We describe our process developing and validating a 'medical internship experience scale' to address this gap, work involving nine LMICs that varied in geographical locations, income-level and internship training models. We used a scoping review of existing tools, content validity discussions with target populations and an expert panel, back-and-forth translations into four language versions and cognitive interviews to develop and test the tool. Using data collected from 1646 interns and junior medical doctors, we assessed factor structure and assessed its reliability and validity. Fifty items about experiences of medical internship were retained from an initial pool of 102 items. These 50 items represent 6 major factors (constructs): (1) clinical learning and supervision, (2) patient safety, (3) job satisfaction, (4) stress and burnout, (5) mental well-being, and (6) fairness and discrimination. We reflect on the process of multicountry scale development and highlight some considerations for others who may use our scale, using preliminary analyses of the 1646 responses to illustrate that the tool may produce useful data to identify priorities for action. We suggest this tool could enable LMICs to assess key metrics regarding intern straining and initial work experiences and possibly allow comparison across countries and over time, to inform better internship planning and management.

The influence of internship training experience on Kenyan and Ugandan doctors' career intentions and decisions: a qualitative study.

BACKGROUND: Medical internship is a key period for doctors' individual career planning and also a transition period for the broader labour market. OBJECTIVES: We aimed to understand the complex set of factors influencing the career intentions and decisions of junior doctors, post-internship in Kenya and Uganda. METHODS: We conducted semi-structured interviews with 54 junior medical officers and 14 consultants to understand doctors' internship experiences and subsequent employment experiences. We analysed the data using a mix of a direct content approach, informed by an internship experience and career intentions framework developed primarily from high-income country literature, alongside a more inductive thematic analysis. RESULTS: Echoing the internship experience and career intentions framework, we found that clinical exposure during internship, work-life balance, aspects of workplace culture such as relationships with consultants and other team members, and concerns over future job security and professional development all influenced Kenyan and Ugandan doctors' career preferences. Additionally, we added a new category to the framework to reflect our finding that interns might want to 'fill a health system gap' when they choose their future careers, based on what they witness as interns. However, often career intentions did not match career and employment decisions due to specific contextual factors, most importantly a shortage of job opportunities. CONCLUSION: We have shown how internship experiences shape medical doctors' career intentions in Kenya and Uganda and highlighted the importance of job availability and context in influencing doctors' career choices.

Examining the absorption of post-internship medical officers into the public sector at county-level in devolved Kenya: a qualitative case study.

BACKGROUND: After Kenya's decentralization and constitutional changes in 2013, 47 devolved county governments are responsible for workforce planning and recruitment including for doctors/medical officers (MO). Data from the Ministry of Health suggested that less than half of these MOs are being absorbed by the public sector between 2015 and 2018. We aimed to examine how post-internship MOs are absorbed into the public sector at the county-level, as part of a broader project focusing on Kenya's human resources for health. METHODS: We employed a qualitative case study design informed by a simplified health labour market framework. Data included interviews with 30 MOs who finished their internship after 2018, 10 consultants who have supervised MOs, and 51 county/sub-county-level managers who are involved in MOs' planning and recruitment. A thematic analysis approach was used to examine recruitment processes, outcomes as well as perceived demand and supply. RESULTS: We found that Kenya has a large mismatch between supply and demand for MOs. An increasing number of medical schools are offering training in medicine while the demand for MOs in the county-level public sector has not been increasing at the same pace due to fiscal resource constraints and preference for other workforce cadres. The local Department of Health put in requests and participate in interviews but do not lead the recruitment process and respondents suggested that it can be subject to political interference and corruption. The imbalance of supply and demand is leading to unemployment, underemployment and migration of post-internship MOs with further impacts on MOs' wages and contract conditions, especially in the private sector. CONCLUSION: The mismatched supply and demand of MO accompanied by problematic recruitment processes led to many MOs not being absorbed by the public sector and subsequent unemployment and underemployment. Although Kenya has ambitious workforce norms, it may need to take a more pragmatic approach and initiate constructive policy dialogue with stakeholders spanning the education, public and private health sectors to better align MO training, recruitment and management.

Understanding and Targeting the Epigenetic Regulation to Overcome EGFR-TKIs Resistance in Human Cancer.

BACKGROUND: The occurrence and progression of cancer are the results of the dysregulation of genetics and epigenetics. Epigenetic regulation can reversibly affect gene transcription activity without changing DNA structure. Covalent modification of histones is crucial in the epigenetic regulation of gene expression. Furthermore, epidermal growth factor receptor (EGFR) significantly affects cell tumorigenesis, proliferation, antitumor drug resistance, etc. Overexpression of EGFR promotes cancer development. Therefore, EGFR-targeted drugs have become the focus of tumor therapy. With the advent of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), EGFR-TKIs resistance, which occurs about half a year to a year, has become an obstacle in cancer treatment. OBJECTIVE: The objective of this study is to discuss the ways to overcome EGFR-TKIs resistance in a variety of tumors. METHODS: The combination therapy of epigenetic drugs and other drugs is used. RESULTS: The combination of the two drugs can overcome the resistance of EGFR-TKIs and prolong the survival of patients. CONCLUSION: This article depicts the concepts of epigenetics and the mechanism of EGFR-TKIs resistance and then illustrates the relationship between epigenetic mechanisms and EGFR-TKIs resistance. Finally, it discusses the clinical research and the latest patents for using epigenetic drugs to reverse EGFR-TKIs resistance in human cancer. In the future, more novel targets may be discovered for overcoming resistance to EGFR-TKIs, not just on histone deacetylases (HDACs). The dosing course and mode of administration of the combination therapy containing epigenetic drugs need further study. This review provides new ideas for using epigenetic agents to overcome EGFR-TKIs resistance.

How do foundation year and internship experience shape doctors' career intentions and decisions? A meta-ethnography.

PURPOSE: Foundation years or internships are an important period for junior doctors to apply their knowledge and gain clinical competency. Experiences gained during the foundation years or internships are likely to inform newly qualified doctors' opinions about how they want to continue their career. We aimed to understand how medical doctors' internship experiences influence their career intention/decision. METHODS: We conducted qualitative evidence synthesis using meta-ethnography. We searched six electronic bibliographic databases for papers published between 2000-2020 and included papers exploring how foundation years or internship experiences shape doctors' career intention/decisions, including in relation to migration, public/private/dual practice preference, rural/urban preference, and specialty choice. We used the GRADE-CERQual framework to rate confidence in review findings. RESULTS: We examined 23 papers out of 6085 citations screened. We abstracted three high-level inter-related themes across 14 conceptual categories: (1) Deciding the personal best fit both clinically and in general (which option is 'more me'?) through hands-on and real-life experiences (2) Exploring, experiencing and witnessing workplace norms; and (3) Worrying about the future in terms of job market policies, future training and professional development opportunities. Confidence in findings varied but was rated high in 8 conceptual categories. CONCLUSIONS: Our meta-ethnographic review revealed a range of ways in which internship experience shapes medical doctors' career intentions/decisions allowing us to produce a broad conceptual model of this phenomenon. The results highlight the importance of ensuring sufficient, positive and inspiring clinical exposure, improving workplace environment, relationship and culture, refraining from undermining specific specialities and communicating contractual and job market policies early on to young doctors, in order to attract doctors to less popular specialties or work locations where they are most needed. We propose our conceptual model should be further tested in new research across a range of contexts.

Tracking development assistance for health from India to low- and middle-income countries, 2009-2020.

BACKGROUND: Development assistance for health (DAH) is an important source of financing for health for many low-income and some middle-income countries. Most DAH has predominantly been contributed by high-income countries. However, in the context of economic progress and changing global priorities, DAH contributions from countries of the Global South such as India have gained importance. In this paper, we estimate DAH contributed by India between 2009 and 2020. METHODS: We leveraged data from budgetary documents, databases, and financial reports of the Ministry of External Affairs and multilateral organizations to estimate DAH contributions. The proportions of development assistance that go towards health in major recipient countries were estimated and reported by recipient country and year. RESULTS: Between 2009 and 2020, DAH contributed by India to bilateral and multilateral partners totaled $206.0 million. South Asian countries including Bangladesh, Bhutan, Nepal, Sri Lanka, and Myanmar received the most DAH from India. DAH contributed relative to DAH received ranged from 1.42% in 2009 to 5.26% in 2018, the latest year with country-level data. Health focus areas prioritized by India included technical training and innovation, health care infrastructure support, and supply of medications and medical equipment. CONCLUSION: India is an important development partner to many countries-particularly to those in the South Asian region. India's DAH allocation strategy prioritizes contributions toward neighboring countries in the South Asia region in several health focus areas. Detailed project-level data are needed to estimate DAH contributions from India with greater precision and accuracy.

7,8-Dihydroxyflavone Simultaneously Provides Neuroprotection of Retinal Explants and Proangiogenesis of Human Umbilical Vein Endothelial Cells via the Tropomyosin-Related Kinase Receptor B Signaling Pathway In Vitro.

Purpose: This study aimed to investigate the simultaneous neuroprotective and proangiogenic effects of 7,8-dihydroxyflavone (7,8-DHF) and explore the potential underlying molecular mechanisms. Methods: A coculture system of rat retinal explants and human umbilical vein endothelial cells (HUVECs) was established to determine the optimal concentration of 7,8-DHF, promoting neurite regeneration and HUVEC proliferation. Subsequently, the neuroprotective effect, proangiogenesis properties, and action mechanism of 7,8-DHF at an optimal concentration were investigated. Results: The cell proliferation, survival, migration, tube formation and p-tropomyosin-related kinase receptor B (TrkB)/TrkB levels in HUVECs were significantly promoted by 5 µM 7,8-DHF. The ganglion cell layer neuron survival, neurite regeneration, and p-TrkB/TrkB levels in retinal explants were also significantly promoted by 5 µM 7,8-DHF. All of these pharmacological actions of 7,8-DHF were blocked by N-[2-[(2-oxoazepan-3-yl)carbamoyl]phenyl]-1-benzothiophene-2-carboxamide. Conclusions: 7,8-DHF yields neuroprotection of retinal explants and proangiogenesis of HUVECs through the TrkB signaling pathway in vitro.

The emerging therapeutic target of dynamic and reversible N6-methyladenosine modification during cancer development.

As a reversible and dynamic epigenetic modification, N6-methyladenosine (m6A) modification is ubiquitous in eukaryotic cells. m6A methylation is prevalent in almost all RNA metabolism processes that affect the fate of cells, including cancer development. As indicated by the available evidence, targeting m6A regulators may play a crucial role in tumor therapy and multidrug resistance. Currently, many questions remain uncovered. Here, we review recent studies on m6A modification in various aspects of tumor progression, tumor immunity, multidrug resistance, and therapeutic targets to provide new insight into the m6A methylation process.