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Research led by Liverpool School of Tropical Medicine and the Malawi-Liverpool-Wellcome Programme shows that over half of hospital patients with breathlessness had died within a year of admission (51%), as opposed to just 26% of those without the symptom.

Most of these patients had more than one condition that cause breathlessness, including pneumonia, anaemia, heart failure and TB.

The findings demonstrate the importance of integrated, patient-centred care, researchers say, to tackle the burden of high mortality for people with breathlessness, particularly in low-income countries.

Dr. Stephen Spencer, Wellcome Trust Clinical PhD Fellow at Liverpool School of Tropical Medicine (LSTM) and the Malawi-Liverpool-Wellcome Programme (MLW) is lead author on the paper, he said: “Since 2020, the COVID-19 pandemic has energised healthcare communities in Africa to expand oxygen access to hospitals, which is critical for patient care. Sadly, our study shows that breathless patients in Malawi still suffer from mortality rates twice as high as in Europe, despite the younger population in Africa.

“Most of these patients live with more than one condition at the same time, which we found to be a factor linked to higher mortality, such as those with TB or pneumonia. This suggests that treating diseases in isolation is not enough, and healthcare models that have traditionally focused on single presenting conditions may overlook important concurrent diseases. Patient-centred health care interventions that can diagnose and treat multiple illnesses at the same time are urgently needed and should be evaluated to see if they can sustainably reduce mortality.”

Study

Published in Thorax, researchers tracked 751 Malawian hospital patients over 12 months, of whom 334 (44%) had breathlessness as a symptom.

Of these patients, 69% who had heart failure had died within a year, alongside 57% with anaemia, 53% with pneumonia, and 47% with TB. Most patients (63%) had multiple conditions, a factor associated with increased mortality.

Dr Ben Morton, Senior Clinical Lecturer at LSTM and senior author on the paper, said: “This is an important study as it provides robust evidence on the complexity of patients with breathlessness in Southern Africa. Whilst established vertical programmes have been important to improve the management of individual diseases like TB, this study shows that more holistic approaches are required to effectively diagnose and manage patients in this context. We also show that breathlessness is a common reason for hospital presentation with particularly poor outcomes, highlighting the urgency to develop improved programmes of care.”

While the findings from the breathlessness study are alarming and associated with poor patient outcomes, they provide the much-needed evidence and opportunity for Malawi and other resource limited settings to build respiratory support for their health systems. Availability of medical oxygen and increased capacity of healthcare professionals to diagnose and treat breathlessness and multimorbidity are essential to improving quality of care and patient outcomes.”

Dr. Felix Limbani, Co-Investigator, and Senior Research Associate at MLW

The study involved researchers from the Malawi Liverpool Wellcome Programme and Kamuzu University of Health Sciences in Malawi; Kilimanjaro Christian Medical Centre in Tanzania and Muhimbili University of Health and Allied Sciences in Tanzania; Royal United Hospitals Bath NHS Foundation Trust; Liverpool John Moores University; and the University of Manchester and the University of Edinburgh.

On Wednesday afternoon, Haifan Lin, the director of the Yale Stem Cell Center, discussed his innovative research findings in stem cell gene expression and regulation at Brown’s 2025 Mac V. Edds Lectureship.

Hosted by the Department of Molecular Biology, Cell Biology and Biochemistry, the event is held on a near-annual basis to honor Edds’s legacy. A pioneer in the field of developmental biology, Edds was the former director of medicine in Brown’s Division of Biology and Medicine. 

Lin opened his lecture by discussing the shortcomings in the conventional understanding of gene expression and regulation, which is explained through the central dogma of biology that refers to the genetic flow of information from DNA to RNA and then protein. 

Genetic regulation is controlled through a variety of mechanisms in this pathway, including changes at the transcriptional level — or the process of producing messenger RNA from DNA. These changes encompass processes like epigenetic regulation, which alters gene expression by chemically modifying DNA without changing the underlying DNA sequence, Lin said.

He explained that historically, stem cell research has focused on transcription factors, and as a result, far less is known about the role of post-transcriptional regulation. Lin acknowledged the dearth of research on gene expression of embryonic stem cells — cells found in the early stages of embryonic development and capable of differentiating into most cell types in the adult body — and discussed how his own research addressed these gaps. 

In one study, Lin explored the role of pumilio proteins in post-transcriptional control. Pumilio proteins are a family of proteins that bind to RNA to control protein production after transcription in early embryogenesis. 

Lin helped discover that Pum1 proteins — a subset of pumilio proteins — play a crucial role in the differentiation of stem cells, while Pum2 proteins promote properties that allow stem cells to replicate themselves. Through regulating over a thousand types of mRNAs, these proteins can enhance or repress protein synthesis. 

In the second half of the talk, Lin discussed his discovery of a novel group of small noncoding RNA molecules called PIWI-interacting RNAs, or piRNAs. The journal Science included Lin’s discovery in their list of 2006’s 10 most important scientific breakthroughs. 

Lin’s studies found that piRNAs derived from certain DNA segments are capable of degrading mRNA and other non-coding forms of RNA. 

“We were euphoric about these findings,” Lin said during the lecture. “If you liken the genome to the world, the traditional genes are like the old world, and suddenly, we found ourselves landed in a completely new world.” 

Jien Li GS, a second-year graduate student studying aging biology, shared his surprise at the novelty of these findings and the existing limitations in the field.  

“It shows how much more there is to discover,” Li said. These findings, he added, “are important enough that we should have a better understanding of (them) by now, but we don’t.”

Patients with type 1 or type 2 diabetes are at a higher risk of developing uveitis compared to healthy individuals, and the risk is increased with coexisting diabetic retinopathy (DR) and advancing stages of DR, according to a real-world data analysis from the Case Western Reserve University School of Medicine.¹

DR is among the most prevalent complications of diabetes, affecting almost 1 in 3 patients with diabetes globally. It is also a leading cause of blindness, given the irreversible damage it inflicts on the retina. Despite effective therapies such as anti-VEGF injections and photocoagulation, limitations such as drug resistance, partial therapeutic responses, and low patient compliance resulting from a reliance on intravitreal injections are consistently unresolved.²

In addition to DR, diabetes mellitus can also negatively impact the course and outcome of uveitis. Preexisting diabetes has long been associated with a greater inflammatory response during uveitis episodes, which translates to a higher degree of complications. Poor glycemic control, frequently caused by side effects of medication used to treat uveitis, can also be linked to more severe inflammation.³

The retrospective cohort study utilized data from the TriNetX Global Collaborative Network. Included patients had to have a diagnosis of type 1 diabetes (T1D) or type 2 diabetes (T2D); investigators included both insulin users and non-insulin users among those with T2D, with and without DR. The team also employed 1:1 propensity score matching, adjusting for demographic variables and relevant medical conditions, to ensure compatibility between cohorts.¹

Ultimately, investigators saw a substantially greater risk of uveitis in patients with T2DM, irrespective of DR, compared to the control group (adjusted hazard ratio [HR], 6.054; 95% CI, 5.484-6.683 and 1.381; 95% CI, 1.254-1.521). The risk remained high at 5- and 10-year follow-ups. In patients with T1D and DR, the HR increased compared to control from years 1 to 10 (HR at 1 year, 2.274; 95% CI, 1.137-4.547). Additionally, patients with T2D and non-proliferative DR saw a reduced uveitis risk versus those with T2D and proliferative DR at years 1-10 (HR at 1 year, 0.339; 95% CI, 0.302-0.380).¹

Ultimately, investigators concluded that patients with T2D have a higher risk of uveitis, which increases with coexisting DR. Patients with T1D are also at an increased risk, albeit a lesser one.¹

“These findings emphasize the critical need for vigilant monitoring and targeted interventions to manage ocular health complications in diabetic populations,” wrote Darren Jindal, PhD, a researcher at Columbia University Irving Medical Center, and colleagues.¹

References

1. Jindal, D. A., Alshammari, N., Dihan, Q., Chauhan, M. Z., Gupta, V., Soliman, M. K., & Sallam, A. B. (2025). The Association of Diabetes Mellitus with Uveitis: A Real-World Data Analysis. Ocular Immunology and Inflammation, 1–9. https://doi.org/10.1080/09273948.2025.2548333

2. Seo H, Park SJ, Song M. Diabetic Retinopathy (DR): Mechanisms, Current Therapies, and Emerging Strategies. Cells. 2025;14(5):376. Published 2025 Mar 4. doi:10.3390/cells14050376

3. Mohapatra A, Sudharshan S, Majumder PD, Sreenivasan J, Raman R. Clinical Profile and Ocular Morbidities in Patients with Both Diabetic Retinopathy and Uveitis. Ophthalmol Sci. 2024;4(6):100511. Published 2024 Mar 7. doi:10.1016/j.xops.2024.100511