DNMT3A loss drives a HIF-1-dependent synthetic lethality to HDAC6 inhibition in non-small cell lung cancer.

encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed -defective NSCLC cells.

Public perception of the physician associate profession in the UK: a systematic review.

Background: The physician associate (PA) role within the NHS is currently under scrutiny due to recent legislative changes and concerns about their scope of practice within primary and secondary healthcare. There is currently limited knowledge of public understanding of PAs and their levels of satisfaction with PAs. This review synthesises the evidence relating to patients' and potential patients' understanding of and satisfaction with the PA profession in the UK.

Public service motivation, public sector preference and employment of Kenyan medical doctor interns: a cross-sectional and prospective study.

Background: Kenya grapples with a paradox; severe public sector workforce shortages co-exist with rising unemployment among healthcare professionals. Medical schools have increased trainee outputs, but only 45% of newly qualified/registered doctors were absorbed by the public sector during 2015-2018. In such a context, we explore what influences doctors' career choices at labour market entry, specifically understanding the role of public service motivation (PSM).

Financing health in sub-Saharan Africa 1990-2050: Donor dependence and expected domestic health spending.

In 2021, global life expectancy at birth was 74 years whereas in sub-Saharan Africa it was 66 years. Yet in that same year, $92 per person was spent on health in sub- Saharan Africa, which is roughly one fifth of what the next lowest geographic region-North Africa and Middle East-spent ($379). The challenges to healthy lives in sub-Saharan Africa are many while health spending remains low.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

'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.

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.

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.

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.

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 .

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. 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.

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.

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.

Development assistance for human resources for health, 1990-2020.

Background: Investing in the health workforce is key to achieving the health-related Sustainable Development Goals. However, achieving these Goals requires addressing a projected global shortage of 18 million health workers (mostly in low- and middle-income countries). Within that context, in 2016, the World Health Assembly adopted the WHO Global Strategy on Human Resources for Health: Workforce 2030.