Check out the papers that were recently published by Vision Cluster members:
Journal: Journal of Experimental Biology
A long-standing problem in the study of avian flight is determining how biomechanics and physiology are associated with behaviour, ecological interactions and evolution. In some avian clades, flight mechanisms are strongly linked to ecology. Hummingbirds, for example, exhibit traits that support both hovering flight and nectar foraging. In most avian clades, however, features such as wing shape are highly variable among taxa without clear relationships to biomechanics, energetics or ecology. In this Commentary, we discuss challenges to understanding associations between phenotype and performance in avian flight. A potential pitfall in studies that attempt to link trait specialization with performance is that the most relevant traits and environments are not being considered. Additionally, a large number of studies of the mechanisms of avian flight are highly phenomenological. Although observations are essential for hypothesis development, we argue that for our discipline to make progress, we will need much more integration of the observational phase with developing crucial tests of competing hypotheses. Direct comparison of alternative hypotheses can be accomplished through analytical frameworks as well as through experimentation.
Altshuler DL, Baliga VB, Lapsansky AB, Lee P, Press ER, Theriault JS. Understanding mechanisms of avian flight by integrating observations with tests of competing hypotheses. J Exp Biol. 2025 Feb 15;228(Suppl_1):JEB247992. doi: 10.1242/jeb.247992. Epub 2025 Feb 20. PMID: 39973190.
Journal: Genes
Objectives: We sought to investigate the visual function, retinal features, and genotype-phenotype correlations of an Australian cohort of RPGR carriers. Methods: In this cross-sectional study, we evaluated RPGR carriers seen in Melbourne and Perth between 2013 and 2023 and healthy women seen between 2022 and 2023 in Melbourne. Visual acuity tests, fundus-tracked microperimetry, and retinal imaging were performed. RPGR carriers were classified into four retinal phenotypes (normal, radial, focal pigmentary retinopathy, and male pattern phenotype) and compared against healthy controls. Genotype-phenotype relationships in the RPGR carriers were investigated. Results: Thirty-five female RPGR carriers and thirty healthy controls were included in this study. The median ages were 40 and 48.5 years for RPGR carriers and controls, respectively (p = 0.26). Most RPGR carriers (89%) had a genetic diagnosis. Best-corrected visual acuity (BCVA), low luminance visual acuity, retinal sensitivity, central inner retinal thickness (IRT, 1°), and photoreceptor complex (PRC) thickness across the central 1-7° of the retina differed between phenotypes of RPGR carriers. On average, RPGR carriers with ORF15 variants (n = 25 carriers) had reduced LLVA, a greater IRT at 1°, and thinner PRC thickness at 7° from the fovea (all p < 0.05) compared to those with exon 1-14 variants. Conclusions: Female RPGR carriers with severe retinal phenotypes had significantly decreased visual function and changes in retinal structure in comparison to both the controls and carriers with mild retinal disease. BCVA, LLVA, retinal sensitivity, and retinal thickness are biomarkers for detecting retinal disease in RPGR carriers. The genetic variant alone did not influence retinal phenotype; however, RPGR carriers with ORF15 variants exhibited reduced retinal and visual measurements compared to those with exon 1-14 variants.
Gocuk SA, Edwards TL, Jolly JK, Chen FK, Sousa DC, McGuinness MB, McLaren TL, Lamey TM, Thompson JA, Ayton LN. Retinal Disease Variability in Female Carriers of RPGR Variants Associated with Retinitis Pigmentosa: Clinical and Genetic Parameters. Genes (Basel). 2025 Feb 13;16(2):221. doi: 10.3390/genes16020221. PMID: 40004550; PMCID: PMC11855607.
Journal: Nurse Education Today
Background: The underrepresentation of students and professionals with disabilities in health professions is well-documented in research, emphasizing the urgent need for greater inclusivity. Institutional structures often restrict disabled individuals from sharing their specialized knowledge on navigating disability, perpetuating epistemic injustice. Research emphasizes the importance of amplifying their voices to address inequities and restore epistemic justice.
Objectives: This study explores the firsthand, experiential views of the challenges and supporting factors that disabled students and professionals face in the health professions education and practice. Participants provided advice for their disabled peers and non-disabled allies. The development of a critical disability epistemology amplifies underrepresented voices in the health field.
Design: This qualitative study was guided by a constructivist approach, with data analysis informed by reflective thematic analysis.
Methods: A series of semi-structured interviews were conducted with 56 participants (27 students and 29 professionals) in nursing, medicine, occupational therapy, physiotherapy, and social work. Participants were interviewed up to three times over the course of a year, resulting in a total of 124 interviews.
Results: Two main categories were identified. Category one, advice for disabled students and professionals, includes the themes: (1) Negotiating disclosure processes to mobilize support, (2) Recognizing personal boundaries and strengths while actively seeking mentorship, and (3) Advocating for oneself and others. Category two, advice for non-disabled allies, encompasses the themes: (4) Fostering inclusivity through thoughtful language, education, and support, and (5) Actively promoting systemic change.
Conclusion: The findings enhance the epistemic agency of disabled individuals by utilizing community resources for collective knowledge production. They offer valuable guidance for educators, institutions, and policymakers, providing a roadmap for making health education programs and workplaces more inclusive and supportive for disabled individuals.
Mayer Y, Nimmon L, Weiss A, Bulk LY, Battalova A, Krupa T, Jarus T. Promoting epistemic justice: Supporting inclusion and belonging for disabled individuals in health professions. Nurse Educ Today. 2025 Jan 21;147:106584. doi: 10.1016/j.nedt.2025.106584. Epub ahead of print. PMID: 39893898.
Journal: Leukemia & Lymphoma
Clozapine is a cornerstone treatment for schizophrenia, though long-term use has been associated with significant adverse effects, including hematologic risks. This study analyzed FDA Adverse Event Reporting System (FAERS) data from 2003 to 2024 to assess the potential link between clozapine and lymphoma. Disproportionality analyses revealed elevated reporting odds ratios (RORs) for clozapine: Hodgkin lymphoma (HL) (3.76; 95% CI: 2.84-4.97) and non-Hodgkin lymphoma (NHL) (3.62; 95% CI: 2.88-4.54), while other antipsychotics showed no significant associations. Although causality cannot be established, the results underscore the need for targeted research into clozapine-associated risks and improved monitoring strategies to protect patients reliant on this medication. Further studies are essential to refine safety protocols and understand population-specific risks.
Frey C, Etminan M. Clozapine is associated with an increased risk of Hodgkin and non-Hodgkin lymphoma. Leuk Lymphoma. 2025 Feb 12:1-3. doi: 10.1080/10428194.2025.2461663. Epub ahead of print. PMID: 39937100.
Journal: JAMA Ophthalmology
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), one of the most-prescribed classes of medications worldwide, are indicated for the treatment of diabetes or obesity. A 2024 epidemiologic study by Hathaway and colleagues1 showed that these drugs can increase the risk of nonarteritic anterior ischemic optic neuropathy (NAION) by 4-fold among patients with diabetes and by 7.6-fold among overweight patients with previous type 2 diabetes (T2D).
Etminan M, Sodhi M, Maberley D. GLP-1 RAs and Nonarteritic Anterior Ischemic Optic Neuropathy-Making Sense of the Data. JAMA Ophthalmol. 2025 Jan 30. doi: 10.1001/jamaophthalmol.2024.6181. Epub ahead of print. PMID: 39883452.
Journal: International Journal of Biological Macromolecules
This study presents the development of intelligent screen-printed labels for real-time food freshness monitoring. Using chitosan grafted with rosolic acid (RA) and immobilized on montmorillonite (MMT) through cationic exchange, a hybrid dye was synthesized and applied in screen-printing inks. The hybrid structure was characterized by XRD, TGA, and UV-vis, confirming improved thermal stability and maintained halochromic properties. SEM analysis showed consistent ink deposition on filter paper, while water contact angle (WCA) measurements demonstrated enhanced surface hydrophobicity due to the MMT. The labels exhibited clear pH-sensitive color transitions from yellow to purplish red (pH 2.0-12.0) and rapid ammonia sensitivity, with ΔE values exceeding 45.0 within 10 min. The labels also demonstrated excellent reversibility, storage stability, leaching resistance, and cytocompatibility. Practical tests on shrimp and milk confirmed the labels' ability to accurately monitor freshness through visible color changes. These findings highlight the potential of hybrid labels as effective, scalable freshness indicators for intelligent food packaging.
Ronte A, Chalitangkoon J, Sintoppun T, Niemhom N, Manapradit N, Munpiriyakul P, Foster EJ, Monvisade P. Advanced chitosan hybrid dye labels for dynamic monitoring of shrimp and milk freshness. Int J Biol Macromol. 2025 Apr;302:140652. doi: 10.1016/j.ijbiomac.2025.140652. Epub 2025 Feb 3. PMID: 39909265.
Journal: Materials Horizons
Achieving precise control over the composition and architecture of nanomaterial-based aerogels remains a significant challenge. Here, we introduce a droplet-templating approach to engineer ultra-lightweight aerogels via the interfacial co-assembly of nanoparticles-surfactants (NPSs) at polar/apolar liquid interfaces. This approach enables the creation of aerogels with tailored compartmentalized or welded bead architectures, exhibiting multilayer, gradient, and hybrid morphologies from a range of 1D and 2D nanomaterials. By precisely controlling evaporation and freeze-drying processes, we fabricate aerogels with customizable micro-domains, without requiring chemical binders. Our approach provides a platform for developing soft materials with tunable properties, paving a new path for applications in soft matter and aerogel engineering.
Ghasemi S, Panahi-Sarmad M, Erfanian E, Guo T, Rad V, Jalaee A, Banvillet G, Foster EJ, Tam KC, Soroush M, Jiang F, Rojas OJ, Kamkar M. Droplet-templating soft materials into structured bead-based aerogels with compartmentalized or welded configurations. Mater Horiz. 2025 Feb 28. doi: 10.1039/d4mh01896f. Epub ahead of print. PMID: 40017329.
Journal: PLOS One
Extreme temperatures associated with climate change are expected to impact the physiology and fertility of a variety of insects, including honey bees. Most previous work on this topic has focused on female honey bees (workers and queens), and comparatively little research has investigated how heat exposure affects males (drones). To address this gap, we tested body mass, viral infections, and population origin as predictors of drone survival and sperm viability in a series of heat challenge assays. We found that individual body mass was highly influential, with heavier drones being more likely to survive a heat challenge (4 h at 42°C) than smaller drones. In a separate experiment, we compared the survival of Northern California and Southern California drones in response to the same heat challenge (4 h at 42°C), and found that Southern Californian drones - which are enriched for African ancestry - were more likely to survive a heat challenge than drones originating from Northern California. To avoid survivor bias, we conducted sperm heat challenges using in vitro assays and found remarkable variation in sperm heat resilience among drones sourced from different commercial beekeeping operations, with some exhibiting no reduction in sperm viability after heat challenge and others exhibiting a 75% reduction in sperm viability. Further investigating potential causal factors for such variation, we found no association between drone mass and viability of sperm in in vitro sperm heat challenge assays, but virus inoculation (with Israeli acute paralysis virus) exacerbated the negative effect of heat on sperm viability. These experiments establish a vital framework for understanding the importance of population origin and comorbidities for drone heat sensitivity.
McAfee A, Metz BN, Connor P, Du K, Allen CW, Frausto LA, Swenson MP, Phillips KS, Julien M, Rempel Z, Currie RW, Baer B, Tarpy DR, Foster LJ. Factors affecting heat resilience of drone honey bees (Apis mellifera) and their sperm. PLoS One. 2025 Feb 7;20(2):e0317672. doi: 10.1371/journal.pone.0317672. PMID: 39919074; PMCID: PMC11805398.
Journal: Nucleic Acids Research
Previous studies of the 70S ribosome from Flavobacterium johnsoniae revealed a novel ribosomal protein, bL38, which interacts with uL6 on the 50S subunit. This 5.6 kDa protein is conserved across the Bacteroidia and encoded downstream of bL28 and bL33 in a three-gene operon. Here, we show that bL38 is critical for the growth of F. johnsoniae, and depletion of bL38 leads to accumulation of immature 50S particles, which lack uL6 and retain precursor rRNA sequences. Cryo-EM analysis of these particles reveals several putative assembly intermediates, all showing an absence of electron density for uL6 and the entire uL12 stalk region and additional densities corresponding to the unprocessed ends of the pre-23S rRNA. Extra copies of the uL6 gene can rescue the phenotypes caused by bL38 depletion, suggesting that bL38 facilitates uL6 incorporation during 50S subunit biogenesis. Cryo-EM analysis of 50S particles from this rescued strain reveals nearly twice as many intermediates, suggesting a broader and more robust assembly landscape. Differential scanning fluorimetry shows that uL6 of F. johnsoniae is intrinsically unstable, and bL38 increases the melting temperature of uL6 by 12°C. Collectively, these data suggest that bL38 binds and stabilizes uL6, thereby promoting 50S biogenesis in the Bacteroidia.
Alom MS, Arpin D, Zhu H, Hay BN, Foster LJ, Ortega J, Fredrick K. Protein bL38 facilitates incorporation of uL6 during assembly of the 50S subunit in Flavobacterium johnsoniae. Nucleic Acids Res. 2025 Feb 8;53(4):gkaf120. doi: 10.1093/nar/gkaf120. PMID: 39997215; PMCID: PMC11851116.
Journal: Molecular Biology and Evolution
Bats have adapted to pathogens through diverse mechanisms, including increased resistance-rapid pathogen elimination, and tolerance-limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology), several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that the elevated basal expression of innate immune genes may lead to increased resistance to infection. Here, we test whether such transcriptional patterns occur in Egyptian fruit bat tissues through single-cell and spatial transcriptomics of gut, lung, and blood cells, comparing gene expression between bat, mouse, and human. Despite numerous recent loss and expansion events of interferons in the bat genome, interferon expression and induction are remarkably similar to that of mouse. In contrast, central complement system genes are highly and uniquely expressed in key regions in bat lung and gut epithelium, unlike in human and mouse. Interestingly, the unique expression of these genes in the bat gut is strongest in the crypt, where developmental expression programs are highly conserved. The complement system genes also evolve rapidly in their coding sequences across the bat lineage. Finally, the bat complement system displays strong hemolytic activity. Together, these results indicate a distinctive transcriptional divergence of the complement system, which may be linked to bat resistance, and highlight the intricate evolutionary landscape of bat immunity.
Levinger R, Tussia-Cohen D, Friedman S, Lender Y, Nissan Y, Fraimovitch E, Gavriel Y, Tearle JLE, Kolodziejczyk AA, Moon KM, Gomes T, Kunowska N, Weinberg M, Donati G, Foster LJ, James KR, Yovel Y, Hagai T. Single-cell and Spatial Transcriptomics Illuminate Bat Immunity and Barrier Tissue Evolution. Mol Biol Evol. 2025 Feb 3;42(2):msaf017. doi: 10.1093/molbev/msaf017. PMID: 39836373; PMCID: PMC11817796.
Journal: Healthcare Managment Forum
Digital health programs continue to be implemented within Canadian health systems at a steady pace. The effectiveness of digital health initiatives has been rigorously analyzed, with both benefits and drawbacks extensively commented on. While the discussion about digital health continues, both positive and negative perspectives of it are approaching saturation in their themes. Accepting that digital health is here to stay post-pandemic, the focus should shift to strategies and supports needed to avoid the fragmentation of care through digital health implementation. This short article poses three questions which policy-makers and decision-makers should explore as part of a level-setting exercise with involved stakeholders at the outset of a digital health program's consideration. An implementation team should design the digital health program to have equity as its foundational focus, conduct value-based evaluations, and position the program in a learning health system framework to guard against the fragmentation of care.
Petrie S, McLeod S, Ho K. From fragmentation to functionality: Enhancing coherence of digital health integration in health systems. Healthc Manage Forum. 2025 Mar;38(2):120-124. doi: 10.1177/08404704241294255. Epub 2024 Oct 28. PMID: 39468822.
Journal: Physiotherapy
Objectives: This study aimed to develop best practice recommendations for physiotherapists providing telerehabilitation to First Nations people.
Design: Modified Delphi study.
Participants: Eighteen experts from four groups were selected: (a) physiotherapists who provide telerehabilitation to First Nations people, (b) Carrier Sekani Family Services leaders (CSFS, First Nations-led health organization/research partners), (c) telehealth experts from British Columbia (BC), Canada, and (d) First Nations individuals (end users) with experience in telerehabilitation.
Methods: Panelists rated recommendations on telehealth best practices in two rounds using an online questionnaire. Recommendations were synthesized from a scoping review and two qualitative studies. Each statement was rated on a four-point Likert scale indicating whether it was essential, useful, not useful, or unnecessary for inclusion in the best practices. Statements endorsed by ≥80% of panel members were considered for inclusion in the final document.
Results: Following the Delphi process, 77 recommendations covering foundational components, information technology utilization, professional expertise, therapeutic relationships, cultural safety, and the telehealth visit were validated for inclusion in the policy document. Participants also validated the methodology.
Conclusion: The recommendations offer a valuable resource for continuing education and professional development, empowering physiotherapists to enhance their skills and competencies in delivering culturally competent telerehabilitation to the First Nations population. The adoption of these best practices ensures that First Nations people are getting the best standard of care, potentially enhancing uptake and experiences with telehealth. It also enables healthcare organizations and policymakers to monitor adherence to established standards and identify areas for improvement.
Petry Moecke D, Holyk T, Campbell KL, Ho K, Camp PG. Best practice recommendations for physiotherapists providing telerehabilitation to First Nations people: a modified Delphi study. Physiotherapy. 2025 Jan 17;127:101464. doi: 10.1016/j.physio.2025.101464. Epub ahead of print. PMID: 39919644.
Journal: Canadian Journal of Emergency Medicine
Objective: Artificial intelligence (AI) offers opportunities for managing the complexities of clinical care in the emergency department (ED), and Clinical Decision Support has been identified as a priority application. However, there is a lack of published guidance on how to rigorously develop and evaluate these tools. We sought to answer the question, "What methodological standards should be applied to the development of AI-based Clinical Decision Support tools in the ED?".
Methods: We conducted an iterative consensus-establishing activity involving a subcommittee with AI expertise followed by surveys and a live facilitated discussion with participants of the 2024 Canadian Association of Emergency Physicians Research Symposium in Saskatoon. We augmented analysis of participant feedback with large language models.
Results: We established 11 recommendations AI-based Clinical Decision Support development including the selection of a relevant problem and team of experts, standards of data quality and quantity, novel AI-specific reporting guidelines, and adherence to principles of ethics and privacy. We removed the recommendation regarding model interpretability from the final list due to a lack of consensus.
Conclusion: These 11 recommendations provide guiding principles and methodological standards for emergency medicine researchers to rigorously develop AI-based Clinical Decision Support tools and for clinicians to gain knowledge and trust in using them.
Kareemi H, Li H, Rajaram A, Holodinsky JK, Hall JN, Grant L, Goel G, Hayward J, Mehta S, Ben-Yakov M, Pelletier EB, Scheuermeyer F, Ho K. Establishing methodological standards for the development of artificial intelligence-based Clinical Decision Support in emergency medicine. CJEM. 2025 Feb;27(2):87-95. doi: 10.1007/s43678-024-00826-w. Epub 2025 Feb 7. PMID: 39918783.
Journal: Canadian Journal of Emergency Medicine
No abstract available
Rajaram A, Li H, Holodinsky JK, Hall JN, Grant L, Goel G, Hayward J, Mehta S, Ben-Yakov M, Pelletier EB, Scheuermeyer F, Ho K, Kareemi H. Opening the black box: challenges and opportunities regarding interpretability of artificial intelligence in emergency medicine. CJEM. 2025 Feb;27(2):83-86. doi: 10.1007/s43678-024-00827-9. Epub 2025 Feb 17. PMID: 39962037.
Journal: Journal of Medical Internet Research
Background: Patients inevitably incur some cost for accessing health care, even in universal systems such as Canada. The COVID-19 pandemic dramatically shifted health care delivery from in-person to telehealth services, also shifting the proportion of costs offset by patients and their families by reducing the need to travel to in-person appointments.
Objective: This study aimed to develop a method for estimating the costs patients and their families incur and CO2 emissions attributed to travel needed for emergency department (ED) visits, hospitalizations, and physician appointments.
Methods: We present a method to evaluate the costs associated with in-person and telehealth care appointments from the perspective of patients, their families, and the environment. We used ED locations, road distances, and duration of appointment to account for costs paid by patients (ie, lost productivity, informal caregiving, and out-of-pocket expenses) attributed to travel to receive medical care. Costs to the environment were evaluated by calculating the amount of CO2 emitted per medical visit. Using our costs calculated per visit, we apply our method to calculate total patient costs for a simulated population over 1 year.
Results: Our method estimates that patients in British Columbia pay up to $300 (2023 CAD, CAD $1=US $0.86) on average to attend an in-person ED visit, depending on where they live; $166 may be attributed to lost productivity, $83 to informal caregiving, and $50 to out-of-pocket expenses. These estimates are higher than most observed cost estimates. In addition, avoiding in-person care diverts up to 13 kg of CO2 per medical visit, depending on the distance and frequency of travel to appointments. This translates to up to $0.70 in carbon costs per visit, or cumulatively $44,120 per year in British Columbia, conventionally not included in patient cost estimates.
Conclusions: We present a novel method for estimating patient-incurred costs and CO2 emissions from accessing health care and apply it to estimate that every year, patients in British Columbia pay upwards of 30 million dollars to access health care services, primarily for medical travel. Our method adds to the economic evaluation literature by providing a more comprehensive and context-modifiable calculation of patient costs that will allow for more informed decision-making regarding health care services.
Mainer-Pearson G, Stewart K, Williams K, Pawlovich J, Graham S, Riches L, Cressman S, Ho K. Estimating Patient and Family Costs and CO2 Emissions for Telehealth and In-Person Health Care Appointments in British Columbia, Canada: Geospatial Mixed Methods Study. J Med Internet Res. 2025 Feb 19;27:e56766. doi: 10.2196/56766. PMID: 39969971.
Journal: Canadian Journal of Ophthalmology
Objective: To compare the accuracy of keratoconus-specific formulae for nontoric and toric intraocular lenses in eyes with keratoconus undergoing cataract surgery.
Design: Consecutive retrospective case series.
Participants: Patients with keratoconus who underwent cataract surgery.
Methods: A retrospective chart review was conducted on cataract surgeries performed by the Cornea Service in the Department of Ophthalmology and Visual Sciences of the University of British Columbia from 2000 to 2023. The Kane keratoconus, Kane, Barrett Universal 2, Barrett True K, SRK II, SRK/T, Hoffer Q, Holladay I, EVO, Hill RBF and Hoffer QST, and Pearl DGS formulae were calculated. The postoperative mean absolute error (MAE) and mean prediction error (MPE) were calculated for each formula.
Results: A total of 133 eyes from 88 patients were eligible for inclusion in the study, 113 from 74 patients received nontoric IOLs, and 20 from 14 patients received toric IOLs. Pearl DGS had the most myopic MPE of -0.51 ± 1.04, which was statistically significant (p < 0.001) compared to all other formulae. There were no statistically significant differences in the MPE and MAE of the Kane keratoconus, Kane, Barrett Universal 2, Barrett True K keratoconus-specific formula, SRK II, SRK/T, Hoffer Q, Holladay I, EVO, Hill RBF and Hoffer QST formulae (p > 0.05).
Conclusion: There was no difference in IOL power estimation accuracy with keratoconus-specific formulae compared to conventional formulae for cataract surgery in KC patients. The IOL power estimation in KC remains significantly less accurate compared with non-KC patients.
Kahuam-López N, Ling JY, Iovieno A, Yeung SN. Accuracy of keratoconus-specific formulae compared to standard formulae for intraocular lens power calculation in patients with keratoconus. Can J Ophthalmol. 2025 Feb 22:S0008-4182(25)00010-9. doi: 10.1016/j.jcjo.2025.01.005. Epub ahead of print. PMID: 39900112.
Journal: BMJ Case Reports
We present a case of an acute dystonic reaction (ADR) following the two-injection start of aripiprazole once-monthly (AOM) in a patient who previously tolerated equivalent doses of oral aripiprazole (20 mg daily). The ADR occurred two times within 3 weeks of the two-injection start and was effectively treated with benztropine each time. The patient tolerated maintenance treatments of AOM 400 mg without recurrent ADR. A key risk factor in this patient was a prior ADR to a different antipsychotic. We also speculate on the potential roles of strenuous physical activity and infection in increasing the sensitivity to the two-injection initiation regimen compared with the conventional one-injection start. The two-injection start of AOM has been approved by regulatory bodies on the basis of population pharmacokinetic modelling. Our case may, therefore, identify a new safety concern with this alternative initiation option that was not captured in the modelling.
Levit A, Procyshyn RM, Keramatian K. Acute dystonia following the two-injection start of aripiprazole once-monthly. BMJ Case Rep. 2025 Feb 13;18(2):e263842. doi: 10.1136/bcr-2024-263842. PMID: 39947725.
Journal: Alzheimers & Dementia: Diagnosis, Assessment & Disease Monitoring
Introduction: Neighborhood disadvantage may be an important determinant of cardiometabolic health and cognitive aging. However, less is known about relationships among individuals with mild cognitive impairment (MCI).
Methods: The objective of this study is to investigate the relationship between neighborhood disadvantage measured by national Area Deprivation Index (ADI) rank with measures of cardiometabolic health and cognition among Wake Forest (WF) Alzheimer's Disease Research Center (ADRC) participants, with and without MCI.
Results: ADI was positively associated with blood pressure and cardiometabolic index (CMI), and negatively associated with global and Preclinical Alzheimer's Cognitive Composite (PACC5) scores, in cognitively unimpaired (CU) individuals. ADI was only positively associated with hemoglobin A1c (HbA1c) in MCI.
Discussion: Neighborhood disadvantage is associated more strongly with measures of cardiometabolic health and cognition among CU individuals rather than MCI. These findings demonstrate a need for structural solutions to address social determinants of health in an attempt to reduce cardiometabolic and cognitive risks.
Krishnamurthy S, Lu L, Johnson CJ, Baker LD, Leng X, Gaussoin SA, Hughes TM, Ma D, Caban-Holt A, Byrd GS, Craft S, Lockhart SN, Bateman JR. Impact of neighborhood disadvantage on cardiometabolic health and cognition in a community-dwelling cohort. Alzheimers Dement (Amst). 2024 Dec 6;16(4):e70021. doi: 10.1002/dad2.70021. PMID: 39780773; PMCID: PMC11709415.
Journal: Neuro-Oncology Advances
Background: Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM).
Methods: We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and females using known predictors of GBM overall survival (OS) as covariates. A sex-specific composite score of predisposing and protective factors was constructed using the relative importance of each metric in GBM OS.
Results: Higher skeletal muscle volume and lower skeletal muscle fat fraction were associated with better OS in the entire dataset. A robust and independent effect on GBM OS was seen specifically for fraction of inter/intramuscular adipose tissue to total adipose tissue after correction for known survival predictors and comorbidities. Worse OS was observed with increased abdominal aortic calcification volume in both sexes. There was a significant difference in GBM OS among participants stratified into quartiles based on sex-specific composite predisposing and protective scores.
Conclusion: The relationship between body composition and GBM OS provides an actionable advancement toward precision medicine in GBM management, as lifestyle and dietary regimens can alter body composition and metabolism and from there GBM survival.
Rahmani F, Camps G, Mironchuk O, Atagu N, Ballard DH, Benzinger TLS, Chow VTY, Dahiya S, Evans J, Jaswal S, Hosseinzadeh Kassani S, Ma D, Naeem M, Popuri K, Raji CA, Siegel MJ, Xu Y, Liu J, Beg MF, Chicoine MR, Ippolito JE. Abdominal myosteatosis measured with computed tomography predicts poor outcomes in patients with glioblastoma. Neurooncol Adv. 2024 Nov 28;7(1):vdae209. doi: 10.1093/noajnl/vdae209. PMID: 39791017; PMCID: PMC11713020.
Journal: Statistics in Medicine
Brain imaging data is one of the primary predictors for assessing the risk of Alzheimer's disease (AD). This study aims to extract image-based features associated with the possibly right-censored time-to-event outcomes and to improve predictive performance. While the functional proportional hazards model is well-studied in the literature, these studies often do not consider the existence of patients who have a very low risk and are approximately insusceptible to AD. We introduce a functional mixture cure rate model that extends the proportional hazards model by allowing a proportion of event-free patients. We propose a novel supervised functional principal component analysis (sFPCA) method to extract image features associated with AD risk while accounting for the complexity arising from right censoring. The proposed method accommodates the irregular boundary issue inherent in brain images with bivariate splines over triangulations. We demonstrate the advantages of the proposed method through extensive simulation studies and provide an application to the Alzheimer's Disease Neuroimaging Initiative (ADNI) study.
Feng J, Shi H, Ma D, Faisal Beg M, Cao J. Supervised Functional Principal Component Analysis Under the Mixture Cure Rate Model: An Application to Alzheimer'S Disease. Stat Med. 2025 Feb 10;44(3-4):e10324. doi: 10.1002/sim.10324. PMID: 39853780; PMCID: PMC11760660.
Joanne Matsubara: TDP-43 as a potential retinal biomarker for neurodegenerative diseases
Journal: Frontiers in Neuroscience
TDP-43 proteinopathies are a spectrum of neurodegenerative diseases (NDDs) characterized by the pathological cytoplasmic aggregation of the TDP-43 protein. These include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), and others. TDP-43 in the eye shows promise as a biomarker for these NDDs. Several studies have identified cytoplasmic TDP-43 inclusions in retinal layers of donors with ALS, FTLD, AD, CTE, and other conditions using immunohistochemistry. Our findings suggest that pathological aggregates of TDP-43 in the human retina are most prevalent in FTLD-TDP, ALS, and CTE, suggesting these diseases may provide the most reliable context for studying the potential of TDP-43 as a retinal biomarker. Animal model studies have been pivotal in exploring TDP-43's roles in the retina, including its nuclear and cytoplasmic localization, RNA binding properties, and interactions with other proteins. Despite these advances, more research is needed to develop therapeutic strategies. A major limitation of human autopsy studies is the lack of corresponding brain pathology assessments to confirm TDP-43 proteinopathy diagnosis and staging. Other limitations include small sample sizes, lack of antemortem eye pathology and clinical histories, and limited comparisons across multiple NDDs. Future directions for the TDP-43 as a retinal biomarker for NDDs include retinal tracers, hyperspectral imaging, oculomics, and machine learning development.
Glashutter M, Wijesinghe P, Matsubara JA. TDP-43 as a potential retinal biomarker for neurodegenerative diseases. Front Neurosci. 2025 Feb 12;19:1533045. doi: 10.3389/fnins.2025.1533045. PMID: 40012679; PMCID: PMC11861351.
Journal: Nature Communications Biology
The skin, the body's largest organ, has a heterogeneous structure with various cell types and tissue layers. In vivo noninvasive 3D volumetric imaging with multi-contrast, high resolution, a large field-of-view (FOV), and no-motion artifacts is crucial for studying skin biology and diagnosing/evaluating diseases. Traditionally high-resolution in vivo skin microscopy methods capture images in the en-face (xy) plane parallel to the skin surface but are affected by involuntary motion, particularly during large-area volumetric data acquisition using xy-z mosaicking. In this work, we developed an xz-y imaging method that acquires images in the vertical (xz) plane and extends the FOV by moving the skin laterally along the y-direction. This approach is conceived based on our observation that involuntary skin movements are mostly along the vertical direction. Combined with a unique motion correction method, it enables 3D image reconstruction with subcellular resolution and an extended FOV close to a centimeter (8 mm). A multimodality microscopy system using this method provides simultaneous reflectance confocal, two-photon excited fluorescence, and second harmonic generation imaging, enabling multi-contrast capabilities. Using this system, we captured histology-like features of normal skin, vitiligo, and melanoma, demonstrating its potential for in vivo skin biology studies, clinical diagnosis, treatment planning and monitoring.
Wu Z, Tian Y, Zhao J, Huang Y, Lui H, Kalia S, Zeng H. Motion-tolerant 3D volumetric multimodality microscopy imaging of human skin with subcellular resolution and extended field-of-view. Commun Biol. 2025 Feb 5;8(1):186. doi: 10.1038/s42003-025-07614-x. PMID: 39910179; PMCID: PMC11799432.