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This episode looks at a global analysis of how city mobility shifted during the COVID-19 pandemic. Drawing on Apple’s Mobility Trends Reports from 296 cities, researchers examined how public health policies influenced walking and public transport use. They found that initiatives promoting walking, such as closing roads to cars, led to a clear rise in walking activity. The study also mapped more than 500 active transportation policies worldwide, revealing that most were introduced in high-income countries. The findings suggest that encouraging walking and other forms of active transport can strengthen public health, support sustainable cities, and improve future pandemic resilience.

Research paper:

Hunter RF, Akaraci S, Wang R, Reis R, Hallal PC, Pentland S, Millett C, Garcia L, Thompson J, Nice K, Zapata-Diomedi B, Moro E. City mobility patterns during the COVID-19 pandemic: analysis of a global natural experiment. Lancet Public Health. 2024 Nov;9(11):e896-e906

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This episode explores a groundbreaking study published inb The Lancet that identified gene expression biomarkers capable of predicting neonatal sepsis before symptoms appear. Conducted in The Gambia, researchers analysed RNA sequencing data from healthy newborns to distinguish those who later developed early- or late-onset sepsis. Using machine learning, they identified a four-gene signature — HSPH1, BORA, NCAPG2, and PRIM1 — that accurately predicted early-onset sepsis at birth. The findings also revealed that early sepsis profoundly alters immune and metabolic development in the first week of life. This research highlights how genomic tools could transform neonatal care, especially in low- and middle-income settings.

Research paper:

An AY, Acton E, Idoko OT, Shannon CP, Blimkie TM, Falsafi R,Wariri O, Imam A, Dibbasey T, Bennike TB, Smolen KK, Diray Arce J, Ben-Othman R, Montante S, Angelidou A, Odumade OA, Martino D, Tebbutt SJ, Levy O, Steen H, Kollmann TR, Kampmann B, Hancock REW, Lee AH; EPIC Consortium. Predictive gene expression signature diagnoses neonatal sepsis before clinical presentation. EBioMedicine. 2024 Dec;110:105411

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In this episode, we explore findings from the CLODIfrail trial, a Danish study published in The Lancet Healthy Longevity (2024). The trial tested whether early, comprehensive geriatric assessment (CGA) could improve outcomes for older adults hospitalised with Clostridioides difficile infection. While 90-day mortality rates were similar between groups, those receiving CGA had fewer infection recurrences, shorter hospital stays, and fewer deaths directly linked to C. difficile. Researchers suggest that earlier access to faecal microbiota transplantation may be key to these improved results.

Research paper:

Rubak T, Baunwall SMD, Gregersen M, Paaske SE, Asferg M,Barat I, Secher-Johnsen J, Riis MG, Rosenbæk JB, Hansen TK, Ørum M, Steves CJ, Veilbæk H, Hvas CL, Damsgaard EMS. Early geriatric assessment and management in older patients with Clostridioides difficile infection in Denmark (CLODIfrail):a randomised trial. Lancet Healthy Longev. 2024 Dec;5(12):100648

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Here we address the issue of “domestic helicopter research,”which occurs when well-resourced institutions conduct studies on marginalised communities or through resource limited institutions (RLIs) with minimal involvement or equitable benefit for local researchers or community members. The authors, a multidisciplinary team of health equity researchers, argue that this practice mirrors the historical concept of “helicopter research” prevalent in global health and perpetuates structural inequities by limiting RLI influence and diverting resources. The paper provides examples of this exploitative research and discusses the negative consequences, such as eroding trust and degrading the quality of scholarship. Finally, the authors propose several strategies to end domestic helicopter research, including advocating for equitable funding distribution, ensuring RLIs receive appropriate credit, and adopting models like Community-Based Participatory Research (CBPR).

Research paper:

Lambert WM, Camacho-Rivera M, Boutin-Foster C, Salifu M,Riley WJ. Ending "domestic helicopter research". Cell. 2024 Apr 11;187(8):1823-1827

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This research article investigates the mechanistic link between high iron levels and the development of colorectal cancers (CRCs), focusing on the reactivation of telomerase, an enzyme associated with cellular immortalization. The authors identify Pirin, an iron-sensing protein, as a crucial mediator that binds with oxidized iron (Fe3+) to reactivate the human telomerase reverse transcriptase (hTERT) subunit. This finding provides a molecular explanation for the known association between high dietary iron intake (such as red meat consumption) and increased CRC risk. Furthermore, the study pinpoints a small molecule, SP2509, which inhibits this process by competing with Fe3+ for binding to Pirin, suggesting a novel therapeutic approach for targeting telomerase-driven cancers, particularly those of the CMS3 subtype. The mechanism involves iron-activated Pirin stabilising the transcription factor Sp1 by repressing the E3 ubiquitin ligase FBXW7, which consequently drives hTERT expression.

Research paper:

Shanmugam R, Majee P, Shi W, Ozturk MB, Vaiyapuri TS, Idzham K, Raju A, Shin SH, Fidan K, Low JL, Chua JYH, Kong YC, Qi OY, Tan E, Chok AY, Seow-En I, Wee I, Macalinao DC, Chong DQ, Chang HY, Lee F, Leow WQ, Murata-Hori M, Xiaoqian Z, Shumei C, Tan CSH, Dasgupta R, Tan IB, Tergaonkar V. Iron (Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers. Cancer Discov. 2024 Oct 4;14(10):1940 1963.

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This academic paper explores the impact of parenting styles, specifically harsh and warm approaches, on adolescent brain architecture and subsequent mental health outcomes in early adulthood. It investigates whether these associations are dependent on the child's developmental stage, early, middle, or late childhood, rather than simply accumulating over time. The study found that psychological aggression in early childhood was linked to widespread changes in brain organisation, while later aggression affected specific emotional regulation circuits. Conversely, warm parenting during middle childhood was associated with positive changes in corticolimbic regions, which, in turn, predicted lower anxiety and depression in young adults, even during the stress of the COVID-19 pandemic. These findings highlight the importance of timing and type of parental intervention for supporting neurodevelopment and long-term well-being.

Research paper:

Michael C, Gard AM, Tillem S, Hardi FA, Dunn EC, Smith ADAC, McLoyd VC, Brooks-Gunn J, Mitchell C, Monk CS, Hyde LW. Developmental Timing of Associations Among Parenting, Brain Architecture, and Mental Health. JAMA Pediatrics. 2024 Dec 1;178(12):1326-1336.

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This article provides an overview of DNA methylation aging clocks, which are molecular tools used to measure an individual's age based on specific chemical modifications to their DNA. The authors discuss the current understanding and significant challenges in utilising these clocks, particularly in distinguishing between chronological age and biological aging. They also explore the utility of tissue- and disease-specific clocks and the importance of integrating epigenetics into large-scale longitudinal population studies to better understand aging dynamics. This paper then addresses the need for broader genome-wide analyses and the exploration of other epigenomic marks, as well as the potential and challenges of single-cell analysis to uncover cellular heterogeneity in aging. Finally, the authors emphasise the necessity of robust non-human data for mechanistic insights and the critical ethical and legal frameworks required for responsible application of these technologies.

Review paper:

Bell, C.G., Lowe, R., Adams, P.D. et al. DNA methylationaging clocks: challenges and recommendations. Genome Biol 20, 249 (2019)

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This research article investigates the long-term effects of early-life sugar intake on the development of type 2 diabetes and hypertension. Utilising a natural experiment from the end of sugar rationing in the UK in 1953, the study compares adults with varying levels of sugar exposure during their first 1000 days. The findings suggest that restricted sugar intake in early life significantly reduced the risk and delayed the onset of both conditions. This highlights the critical impact of early nutrition on lifelong metabolic health, with in-utero sugar restriction also showing a protective effect.

Review paper:

Gracner T, Boone C, Gertler PJ. Exposure to sugar rationing in the first 1000 days of life protected against chronic disease. Science. 2024 Nov 29;386(6725):1043-1048.

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This review article thoroughly examines vaccine reactogenicity, which encompasses the common, often mild, inflammatory responses individuals experience post vaccination, such as soreness or fever. The authors explore the underlying biological mechanisms that cause these reactions, detailing how the body's immune system responds to vaccine components. Furthermore, the paper investigates various factors that can influence reactogenicity, including host characteristics, vaccine composition, and administration techniques. Ultimately, the article aims to enhance understanding among healthcare professionals and the public to maintain confidence in vaccination programmes by managing expectations and mitigating anxiety related to side effects.

Review paper:

Hervé, C., Laupèze, B., Del Giudice, G. et al. The how’s and what’s of vaccine reactogenicity. npj Vaccines 4, 39 (2019).

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This research article investigates how long-term memories persist despite the turnover of brain molecules. The study reveals that a protein called KIBRA physically interacts with the enzyme PKMζ at synapses activated during learning. This KIBRA-PKMζ complex acts as a stable anchor, maintaining the synaptic changes underlying memory storage. Blocking this interaction with specific inhibitors disrupts established long-term potentiation and erases both recent and remote memories in animal models, highlighting the crucial role of this continuous molecular coupling in memory maintenance.

Review paper:

Tsokas P, Hsieh C, Flores-Obando RE, Bernabo M, Tcherepanov A, Hernández AI, Thomas C, Bergold PJ, Cottrell JE, Kremerskothen J, Shouval HZ, Nader K, Fenton AA, Sacktor TC. KIBRA anchoring the action of PKMζ maintains the persistence of memory. Sci Adv. 2024 Jun 28;10(26):eadl0030.

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