Cancer plasticity: Investigating the causes for this agility.

Cancer is not a hard-wired phenomenon but an evolutionary disease. From the onset of carcinogenesis, cancer cells continuously adapt and evolve to satiate their ever-growing proliferation demands. This results in the formation of multiple subtypes of cancer cells with different phenotypes, cellular compositions, and consequently displaying varying degrees of tumorigenic identity and function. This phenomenon is referred to as cancer plasticity, during which the cancer cells exist in a plethora of cellular states having distinct phenotypes. With the advent of modern technologies equipped with enhanced resolution and depth, for example, single-cell RNA-sequencing and advanced computational tools, unbiased cancer profiling at a single-cell resolution are leading the way in understanding cancer cell rewiring both spatially and temporally. In this review, the processes and mechanisms that give rise to cancer plasticity include both intrinsic genetic factors such as epigenetic changes, differential expression due to changes in DNA, RNA, or protein content within the cancer cell, as well as extrinsic environmental factors such as tissue perfusion, extracellular milieu are detailed and their influence on key cancer plasticity hallmarks such as epithelial-mesenchymal transition (EMT) and cancer cell stemness (CSCs) are discussed. Due to therapy evasion and drug resistance, tumor heterogeneity caused by cancer plasticity has major therapeutic ramifications. Hence, it is crucial to comprehend all the cellular and molecular mechanisms that control cellular plasticity. How this process evades therapy, and the therapeutic avenue of targeting cancer plasticity must be diligently investigated.

Drivers of stunting reduction in Nepal: a country case study.

BACKGROUND: Chronic child malnutrition represents a serious global health concern. Over the last several decades, Nepal has seen a significant decline in linear growth stunting - a physical manifestation of chronic malnutrition - despite only modest economic growth and significant political instability. OBJECTIVE: This study aimed to conduct an in-depth assessment of the determinants of stunting reduction in Nepal from 1996 to 2016, with specific attention paid to national-, community-, household-, and individual-level factors, as well as relevant nutrition-specific and -sensitive initiatives rolled out within the country. METHODS: Using a mixed-methods approach, 4 types of inquiry were employed: 1) a systematic review of published peer-reviewed and gray literature; 2) retrospective quantitative data analyses using Demographic and Health Surveys from 1996 to 2016; 3) a review of key nutrition-specific and -sensitive policies and programs; and 4) retrospective qualitative data collection and analyses. RESULTS: Mean height-for-age z-scores (HAZ) improved by 0.94 SDs from 1996 to 2016. Subnational variation and socioeconomic inequalities in stunting outcomes persisted, with the latter widening over time. Decomposition analysis for children aged under 5 y explained 90.9% of the predicted change in HAZ, with key factors including parental education (24.7%), maternal nutrition (19.3%), reduced open defecation (12.3%), maternal and newborn health care (11.5%), and economic improvement (9.0%). Key initiatives focused on decentralizing the health system and mobilizing community health workers to increase accessibility; long-standing nationwide provision of basic health interventions; targeted efforts to improve maternal and child health; and the prioritization of nutrition-sensitive initiatives by both government and donors. National and community stakeholders and mothers at village level highlighted a mixture of poverty reduction, access to health services, improved education, and increased access to water, sanitation, and hygiene as drivers of stunting reduction. CONCLUSIONS: Improvements in both nutrition-specific and nutrition-sensitive sectors have been critical to Nepal's stunting decline, particularly in the areas of poverty reduction, health, education, and sanitation.