Healthcare, this week...

Biomedical Research:

1.?????Nicotinamide N-methyltransferase (NNMT) explains breast cancer aggressivity:

Metastasis is responsible for over 90% of cancer-related deaths, but the molecular mechanisms behind it are not well understood.

A new study from Bentires-Alj's research team at the Department of Biomedicine, University of Basel and University Hospital Basel, identified a mechanism in basal-like breast cancer driven by the metabolic enzyme NNMT. NNMT enhances cancer cell plasticity and is associated with poor clinical outcomes in breast cancer patients. Depletion of NNMT suppresses metastasis formation in pre-clinical mouse models by increasing histone H3K9 trimethylation and DNA methylation at the promoters of PRDM5 and extracellular matrix-related genes. PRDM5 emerged as a pro-metastatic gene, inducing cancer-cell intrinsic transcription of collagens. Depletion of PRDM5 impairs metastatic colonization of the lungs. These findings reveal a critical activity of the NNMT-PRDM5-COL1A1 axis for cancer cell plasticity and metastasis in basal-like breast cancer.

Couto, J. P.,?et al.?(2023) Nicotinamide N-methyltransferase sustains a core epigenetic program that promotes metastatic colonization in breast cancer.?The EMBO Journal.?doi.org/10.15252/embj.2022112559 .

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2.?????Mirikizumab, a p-19 antibody against interleukin-23, more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis:

Mirikizumab, a p-19 antibody against interleukin-23, was effective in treating ulcerative colitis in two phase 3 trials. Patients were randomly assigned to receive mirikizumab or placebo, and those who responded to the induction therapy were assigned to the maintenance trial. The primary endpoints were clinical remission at weeks 12 and 40, and major secondary endpoints included clinical response and endoscopic remission. Mirikizumab was more effective than placebo in inducing and maintaining clinical remission, but adverse events such as nasopharyngitis and arthralgia were reported more frequently with mirikizumab. A small number of patients treated with mirikizumab had opportunistic infections or cancer.

D'Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis.?N Engl J Med. 2023;388(26):2444-2455. doi:10.1056/NEJMoa2207940

3.?????Efficacy and Safety of Tofacitinib in Patients with Polymyalgia Rheumatica (EAST PMR):

Polymyalgia rheumatica (PMR) is an inflammatory disease in elderly persons with unclear pathogenesis. Glucocorticoids are the main treatment but have side effects, so there is a need for alternative therapies. The study aimed to explore the disease's pathogenesis and assess the efficacy and safety of the Janus tyrosine kinase (JAK)-inhibitor tofacitinib in PMR patients. The study found that JAK signaling was involved in PMR's pathogenesis, and tofacitinib effectively treated patients with PMR as glucocorticoid does in a randomized, monocenter, open-label, controlled trial. Study limitations included the single-center study design with a short observation period.

Ma X, Yang F, Wu J, et al. Efficacy and Safety of Tofacitinib in Patients with Polymyalgia Rheumatica (EAST PMR): An open-label randomized controlled trial.?PLoS Med. 2023;20(6):e1004249. Published 2023 Jun 29. doi:10.1371/journal.pmed.1004249

Academia:

1.?????Transition From Mentored to Independent NIH Funding by Gender and Department:

A study led by Yale University has found that women researchers in the US are less likely to make the transition from mentored to independent research than men. The research, published in the Journal of the American Medical Association, evaluated all recipients of mentored K awards and R01-equivalent awards at US medical schools between 1997 and 2021. Women received fewer K awards than men, with only 34% of K awards granted between 2012 and 2021 being awarded to women. Women K-awardees were also less likely than male K-awardees to have a successful K-to-R transition within 10 years. The study highlights the need for more support structures for women researchers and greater transparency across academic departments.

Mytien Nguyen et al, Transition From Mentored to Independent NIH Funding by Gender and Department,?JAMA?(2023).?DOI: 10.1001/jama.2023.7693

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2.?????Real mentorship:

A college student made a mistake in a research lab by leaving enzymes at room temperature overnight, but her mentor, a postdoc named Saurja, turned the situation into a teachable moment instead of getting angry. She worked with Saurja for four years and learned important lessons, including understanding the big picture, asking questions, accepting mistakes, and sharing skills. Saurja encouraged her to ask questions and trusted her with important experimental steps, and they even published a paper together.

Weiss Z. What I owe my mentor. Science. 2023;380(6652):1398. doi:10.1126/science.adj3873

3.???Five hats of effective leaders: teacher, mentor, coach, supervisor, and sponsor :

The article discusses the distinctions, benefits, and drawbacks of teaching, mentoring, coaching, supervising, and sponsoring in leadership conversations. The authors propose a conceptual model where leaders can dynamically switch between these roles during a single conversation. They also provide examples of how leaders can use these roles to support colleagues in various contexts, such as career advancement and burnout. The authors conclude that effective leaders employ a deliberate and adaptive approach to better serve the needs of their colleagues.

Winters RC, Chan TM, Barth BE. Five hats of effective leaders: teacher, mentor, coach, supervisor and sponsor.BMJ Leader Published Online First: 21 June 2023. doi: 10.1136/leader-2022-000733

Clinical Practice:

1.???Acanthocytosis: a key feature for the diagnosis of abetalipoproteinemia

A baby girl with feeding difficulties and severe failure to thrive was diagnosed with abetalipoproteinemia at 7 weeks of age. A biallelic MTTP mutation causes this rare inherited disorder and results in fat and fat-soluble vitamins malabsorption, leading to hypolipidemia. Patients typically manifest with gastrointestinal symptoms and failure to thrive in infancy and can develop serious neurological and ophthalmological complications if left untreated. Hematological features include acanthocytosis and hemolytic anemia. Early diagnosis and high-dose vitamin supplementation are crucial for preventing severe complications and improving prognosis. This case highlights the importance of microscopic blood smear evaluation for patients with undiagnosed diseases.

Lausch E, Yoshimi A. Acanthocytosis: a key feature for the diagnosis of?abetalipoproteinemia. Blood. 2023;141(26):3231.doi:10.1182/blood.202302026

2.???The therapeutic potential of natural killer cells in neuropathic pain:

Scientists are exploring natural killer (NK) cells as a potential treatment for neuropathic pain, which is caused by nerve damage and can be chronic. NK cells have been found to prune damaged nerve cells and could potentially resolve pain symptoms. Current therapies such as opioids and antidepressants have risks and side effects and do not treat the underlying cause of pain. While NK cells have shown promise in experiments with mice, further research is needed to understand their mechanisms and potential side effects before they can be developed into a realistic therapy.

Hyoung Woo Kim, Shuaiwei Wang, Alexander J. Davies, Seog Bae Oh.?The therapeutic potential of natural killer cells in neuropathic pain.?Trends in Neurosciences, 2023; DOI:?10.1016/j.tins.2023.05.008

3.???New advances in Small-cell lung Cancer:

Vienna's Department of Thoracic Surgery has made significant contributions to the understanding and treatment of small-cell lung cancer (SCLC). They have categorized SCLC into subgroups with varying clinical behaviors and potential therapeutic strategies and found that certain drug combinations are promising for patients with specific molecular SCLC profiles. Their research has been published in CA: A Cancer Journal for Clinicians, the highest-ranked international scientific journal. The team aims to develop personalized therapeutic approaches for SCLC, which has a high mortality rate and affects around 15% of lung cancer patients.

Megyesfalvi, Z,?Gay, CM,?Popper, H, et al.?Clinical insights into small cell lung cancer: tumor heterogeneity, diagnosis, therapy, and future directions.?CA Cancer J Clin.?2023;?1-?33. doi:10.3322/caac.21785

Emerging Technologies In Healthcare:

1.??POF Smart Pants: a fully portable optical fiber-integrated smart textile for remote monitoring of lower limb biomechanics:

Researchers from the Federal University of Espirito Santo, Vitoria, Brazil, have developed a smart textile integrated with optical fiber sensors for biomechanical and activity recognition. The sensors are based on the multiplexed intensity variation technique and are integrated into pants, with 60 sensors in total. Tests with volunteers performing daily activities showed the device's suitability for assessing biomechanics and spatio-temporal parameters of human movement and activity recognition with 100% accuracy using a neural network. Principal components analysis indicated a threefold reduction in the number of sensors with an accuracy of 99%. The proposed POF Smart Pants is a low-cost and highly reliable sensor system for remote monitoring of patients, with the possibility of customization.

?Leticia Avellar, Anselmo Frizera, and Arnaldo Leal-Junior, "POF Smart Pants: a fully portable optical fiber-integrated smart textile for remote monitoring of lower limb biomechanics," Biomed. Opt. Express?14, 3689-3704 (2023). DOI:?https://doi.org/10.1364/BOE.492796

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2.?????Bubble-Based Microrobots with Rapid Circular Motions for Epithelial Pinning and Drug Delivery.?

Microrobots powered remotely are being developed for drug delivery, but most swim in straight lines and struggle to stick to soft tissues, limiting their effectiveness. However, new bubble-based microrobots with complex geometries can swim in non-linear patterns in mouse bladders, attach to the epithelium, and gradually release therapeutic drugs. The robots have asymmetric fins that induce rapid rotational motion, allowing them to stick to the bladder even during urination. The robots can also release dexamethasone, a drug used for inflammatory diseases, over several days, reducing inflammation more effectively than free drug controls. This technology could be used to navigate large volumes and release drugs over time for various diseases.

Lee, J. G.,?Raj, R. R.,?Thome, C. P.,?Day, N. B.,?Martinez, P.,?Bottenus, N.,?Gupta, A.,?Wyatt Shields, C.,?Bubble-Based Microrobots with Rapid Circular Motions for Epithelial Pinning and Drug Delivery.?Small?2023,2300409.? https://doi.org/10.1002/smll.202300409

3.???Artificial Intelligence in Molecular Medicine:

New methods like genomic sequencing and mass spectrometry have led to an increase in molecular data available for refined diagnoses and therapeutic precision. High-dimensional measurement of proteins and metabolites is also increasing. Analytic tools have improved to match this data's volume, velocity, and variety, with machine learning being especially valuable. Deep learning is a powerful subset of machine learning that has had high-profile applications in various fields and is now being applied in medicine for clinically directive information. This article briefly describes the methods used to generate high-dimensional molecular data and focuses on the key role of machine learning in its clinical application.

Gomes B, Ashley EA. Artificial Intelligence in Molecular Medicine.?N Engl J Med. 2023;388(26):2456-2465. doi:10.1056/NEJMra2204787

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