tbuckley/cabot-search huggingface dataset:
Epidemiology of Symptomatic Human Metapneumovirus Infection in the CASCADIA Community-Based Cohort — Oregon and Washington, 2022–2024
Authors: Mila Shakya, Helen Y. Chu, Janet A. Englund, Melissa Briggs-Hagen, Marco Carone, Jennifer L. Kuntz, Tina Lockwood, Claire M. Midgley, Mark A. Schmidt, Lea Starita, Ana A. Weil, Ryan E. Wiegand, Allison L. Naleway, Ian D. Plumb
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Human metapneumovirus (hMPV) is an important cause of respiratory illness. However, information about hMPV incidence, patient characteristics, and symptoms outside hospital settings is limited. During June 2022-March 2024, participants aged 6 months-49 years who were enrolled in the CASCADIA community-based cohort study submitted weekly illness surveys and nasal swabs, and completed follow-up illness surveys. Swabs collected 0-3 days before reporting new or worsening symptoms were tested for hMPV and other respiratory viruses by multiplex polymerase chain reaction. Incidence was analyzed using an exponential survival model. Among 3,549 participants, 306 had symptomatic hMPV infection, representing an average of 7.5 cases per 100 persons per year (95% CI = 6.7-8.4). Incidence was highest during January-March (adjusted hazard ratio [aHR] = 4.3; 95% CI = 3.0-6.0) compared with October-December, and among those aged 2-4 years (aHR = 5.8; 95% CI = 3.8-9.0) compared with those aged ≥40 years. The most frequently reported symptoms were cough (80.4%) and nasal congestion (71.9%). Among 252 (82.4%) participants who completed a post-illness follow-up survey, 68 (27.0%) missed work, school, or child care facility attendance. Together, these findings indicate that hMPV is a common cause of respiratory illness during late winter to spring, particularly among young children, and frequently disrupts daily activities. Understanding hMPV epidemiology can guide surveillance definitions, clinical testing, and prioritization of prevention strategies.
Response to: Demographic Differences and the Impact of Research Years for Reapplicants to Dermatology Residency Programs: A Retrospective Cohort Study
Authors: Alexis B Lyons, Henry W Lim, David M Ozog, Iltefat H Hamzavi, Indermeet Kohli, Tasneem F Mohammad
Journal: Journal of the American Academy of Dermatology (2025)
Requirement for Cyclin D1 Underlies Cell Autonomous HIF2-Dependence in Kidney Cancer
Authors: Nitin H. Shirole, Devishi Kesar, Yenarae Lee, Amy Goodale, Sudeepa Syamala, Shweta Kukreja, Rong Li, Xintao Qiu, Wenyu Yu, Seth Goldman, Paloma Cejas, Henry W. Long, Karen Adelman, John G. Doench, William R. Sellers, William G. Kaelin
Journal: Cancer Discovery (2025)

Abstract Inactivation of the VHL gene stabilizes HIF2a, which drives clear cell renal carcinoma (ccRCC). The HIF2a inhibitor belzutifan is approved for ccRCC treatment, but de novo and acquired resistance are common. HIF2a, bound to ARNT, transcriptionally activates many genes. We performed CRISPRa screens in HIF2a-dependent ccRCC lines treated with a belzutifan analog to identify HIF2a-responsive genes that confer cell-autonomous belzutifan resistance when not downregulated. Sustaining the expression of the HIF2a target gene CCND1, encoding Cyclin D1, promoted HIF2a-independence/belzutifan resistance. This activity requires Cdk4/6 activation by Cyclin D1, but is not solely due to phosphorylation of the canonical Cyclin D1 target, pRB. Indeed, ccRCC lines lacking all three pRB family members remained at least partially HIF2a-dependent. In this context, however, a kinase-defective Cyclin D1 variant partially overrode belzutifan’s antiproliferative effects, suggesting that ccRCC promotion by Cyclin D1 requires the phosphorylation of pRB paralogs and one or more kinase-independent Cyclin D1 activities.
Measurement Properties of the Comprehensive Quality-of-Life Measure for Acne (CompAQ): A Cohort Study at Three International Sites
Authors: Michael R Nock, Delaney Griffiths, Ali Shields, Karen Michael, Nuha Nasir, Jaefer Mohamad, James Choe, Delwyn Z J Lim, Alison M Layton, Jerry Tan, Hazel H Oon, John S Barbieri
Journal: British Journal of Dermatology (2025)

Abstract Background Comprehensive Quality-of-Life Measure for Acne (CompAQ) is a patient reported outcome measure (PROM) assessing health-related quality of life (HRQoL) among patients with acne. The measure is one of two acne-specific PROMs which had the strongest evidence to support its use in a recent COSMIN systematic review. Objective To build on prior validation studies of CompAQ by confirming several of its known measurement properties in a cohort of patients with acne at three international sites; and, to establish the responsiveness of the measure during acne treatment. Methods Adults being seen for routine acne treatment at dermatology clinics in Canada, the United States, and Singapore were recruited between July 2022 and September 2024 to participate in this cohort study. At each visit, participants completed CompAQ, which consists of twenty items representing five domains (i.e., emotions, social judgement, social interaction, treatment, and symptoms domains), and several other relevant measures. Structural validity was assessed by confirmatory factor analysis, internal consistency by calculating Cronbach alpha values, and construct validity by known groups and convergent validity hypothesis testing. We further evaluated for differential item functioning (DIF) across study site, sex, and age. In addition, we assessed responsiveness by change-score validity hypothesis testing and calculating standardized response means (SRM). Results Our study included 315 participants (mean [SD] age, 25.2 years [6.1 years]; 219 females [69.8%]), and data was collected from a total of 588 visits. CompAQ was found to have sufficient structural validity, internal consistency, and construct validity among patients at each study site and in the combined cohort. In addition, no statistically significant uniform or non-uniform DIF was flagged for most items when analyzing DIF by site, sex, and age. Based on SRM estimates, the emotions (SRM = 0.927) and symptoms (0.914) domains had the largest responsiveness while the social judgement (0.606), social interaction (0.522), and treatment (0.787) domains had more moderate responsiveness. Conclusions CompAQ represents a useful and responsive PROM to evaluate HRQoL among those with acne in clinical trials and clinical practice. Future studies are needed to evaluate the interpretability of the measure (i.e., identifying severity strata and minimally important differences).
How to behave with paediatric myocarditis: imaging methods and clinical considerations
Authors: Rosalba De Sarro, Nunzia Borrelli, Giulia Pelaia, Alessia Mendicino, Sara Moscatelli, Isabella Leo, Giulia La Vecchia, Giuseppe Mazza, Lucy Castaldo, Antonio Strangio, Martina Avesani, Salvatore De Rosa, Daniele Torella, Giovanni Di Salvo, Jolanda Sabatino
Journal:  (2025)

Abstract Paediatric myocarditis is a challenging and heterogeneous condition, with varied clinical presentations ranging from mild symptoms to life-threatening complications such as heart failure, arrhythmias, and sudden cardiac death. Effective management hinges on early diagnosis, appropriate treatment, and ongoing monitoring, which can be significantly enhanced through multimodal imaging techniques. This review emphasizes the crucial role of advanced imaging in the diagnosis, prognostication, and management of paediatric myocarditis. While traditional echocardiography remains the first-line imaging tool, it is often insufficient in detecting subtle myocardial changes and it does not allow the identification of myocardial inflammation and fibrosis, particularly in cases with preserved left ventricular function. Recent advancements, including speckle-tracking echocardiography, provide enhanced sensitivity for detecting early signs of myocardial dysfunction, even in the absence of overt abnormalities. Cardiovascular magnetic resonance (CMR) has emerged as a cornerstone in the non-invasive evaluation of myocarditis, offering unparalleled tissue characterization. Indeed, CMR provides critical insights into myocardial oedema, necrosis, and fibrosis, which are essential for confirming the diagnosis, stratifying prognosis, and guiding therapy. Parametric mapping techniques allow for highly accurate detection of myocardial fibrosis (native T1 mapping) and inflammation (T2 mapping), even in the absence of gadolinium contrast, making it particularly valuable in paediatric patients. In conclusion, multimodality imaging, integrating echocardiography and CMR, allows for a comprehensive understanding of disease severity, guiding treatment decisions and optimizing long-term outcomes. This review underscores the importance of a tailored, imaging-driven approach to managing paediatric myocarditis, ensuring the best possible care for this special population.
Functional characterization of luciferase in a brittle star indicates parallel evolution influenced by genomic availability of haloalkane dehalogenase
Authors: Emily S Lau, Marika Majerova, Nicholai M Hensley, Arnab Mukherjee, Michal Vasina, Daniel Pluskal, Jiri Damborsky, Zbynek Prokop, Jérôme Delroisse, Wendy-Shirley Bayaert, Elise Parey, Paola Oliveri, Ferdinand Marletaz, Martin Marek, Todd H Oakley
Journal: Molecular Biology and Evolution (2025)

Abstract Determining why convergent traits use distinct versus shared genetic components is crucial for understanding how evolutionary processes generate and sustain biodiversity. However, the factors dictating the genetic underpinnings of convergent traits remain incompletely understood. Here, we use heterologous protein expression, biochemical assays, and phylogenetic analyses to confirm the origin of a luciferase gene from haloalkane dehalogenases in the brittle star Amphiura filiformis. Through database searches and gene tree analyses, we also show a complex pattern of the presence and absence of haloalkane dehalogenases across organismal genomes. These results first confirm parallel evolution across a vast phylogenetic distance, because octocorals like Renilla also use luciferase derived from haloalkane dehalogenases. This parallel evolution is surprising, even though previously hypothesized, because many organisms that also use coelenterazine as the bioluminescence substrate evolved completely distinct luciferases. The inability to detect haloalkane dehalogenases in the genomes of several bioluminescent groups suggests that the distribution of this gene family influences its recruitment as a luciferase. Together, our findings highlight how biochemical function and genomic availability help determine whether distinct or shared genetic components are used during the convergent evolution of traits like bioluminescence.
Cell-type-specific subtyping of epigenomes improves prognostic stratification of cancer
Authors: Qi Luo, Andrew E Teschendorff
Journal: Genome Medicine (2025)

Most molecular classifications of cancer are based on bulk-tissue profiles that measure an average over many distinct cell types. As such, cancer subtypes inferred from transcriptomic or epigenetic data are strongly influenced by cell-type composition and do not necessarily reflect subtypes defined by cell-type-specific cancer-associated alterations, which could lead to suboptimal cancer classifications. To address this problem, we here propose the novel concept of cell-type-specific combinatorial clustering (CELTYC), which aims to group cancer samples by the molecular alterations they display in specific cell types. We illustrate this concept in the context of DNA methylation data of liver and kidney cancer, deriving in each case novel cancer subtypes and assessing their prognostic relevance against current state-of-the-art prognostic models. In both liver and kidney cancer, we reveal improved cell-type-specific prognostic models, not discoverable using standard methods. In the case of kidney cancer, we show how combinatorial indexing of epithelial and immune-cell clusters define improved prognostic models driven by synergy of high mitotic age and altered cytokine signaling. We validate the improved prognostic models in independent datasets and identify underlying cytokine-immune-cell signatures driving poor outcome. In summary, cell-type-specific combinatorial clustering is a valuable strategy to help dissect and improve current prognostic classifications of cancer in terms of the underlying cell-type-specific epigenetic and transcriptomic alterations.
Nootropic foods in neurodegenerative diseases: mechanisms, challenges, and future
Authors: Le Anh Minh Nguyen, Courtney Wayne Simons, Raymond Thomas
Journal: Translational Neurodegeneration (2025)

Neurodegenerative diseases (NDDs) such as Alzheimer's and Parkinson's disease are increasing globally and represent a significant cause of age-related death in the population. Recent studies emphasize the strong association between environmental stressors, particularly dietary factors, and brain health and neurodegeneration unsatisfactory outcomes. Despite ongoing efforts, the efficiency of current treatments for NDDs remains wanting. Considering this, nootropic foods with neuroprotective effects are of high interest as part of a possible long-term therapeutic strategy to improve brain health and alleviate NDDs. However, since it is a new and emerging area in food and neuroscience, there is limited information on mechanisms and challenges to consider for this to be a successful intervention. Here, we seek to address these gaps by presenting a comprehensive review of possible pathways or mechanisms including mutual interactions governing nootropic food metabolism, linkages of the pathways with NDDs, intake, and neuroprotective properties of nootropic foods. We also discuss in-depth intervention with nootropic compounds and dietary patterns in NDDs, providing a detailed exploration of their mechanisms of action. Additionally, we analyze the demand, challenges, and future directions for successful development of nootropic foods targeting NDDs.
VEN in combination with 10-day DEC in newly diagnosed elderly or relapsed/refractory acute myeloid leukemia, and high-risk myelodysplastic syndrome: long term follow-up of a phase 2 trial
Authors: Mahesh Swaminathan, Courtney D DiNardo, Abhishek Maiti, Naveen Pemmaraju, Maro Ohanian, Navel G Daver, Guillermo Garcia-Manero, Ghayas C Issa, Gautam Borthakur, Farhad Ravandi, Guillermo Montalban-Bravo, Tapan M Kadia, Yesid Alvarado, Elias J Jabbour, Nicholas J Short, William G Wierda, Nitin Jain, Steven M Kornblau, Lucia Masarova, Sherry A Pierce, Wei Qiao, Jing Ning, Hagop Kantarjian, Marina Y Konopleva
Journal: Blood Cancer Journal (2025)
Real-time surveillance system for patient deterioration: a pragmatic cluster-randomized controlled trial
Authors: Sarah C Rossetti, Patricia C Dykes, Chris Knaplund, Sandy Cho, Jennifer Withall, Graham Lowenthal, David Albers, Rachel Y Lee, Haomiao Jia, Suzanne Bakken, Min-Jeoung Kang, Frank Y Chang, Li Zhou, David W Bates, Temiloluwa Daramola, Fang Liu, Jessica Schwartz-Dillard, Mai Tran, Syed Mohtashim Abbas Bokhari, Jennifer Thate, Kenrick D Cato
Journal: Nature Medicine (2025)
Packaging of Cannabis Edibles, Health Warning Recall, and Perceptions Among Young Adults
Authors: Michael Cooper, Yuyan Shi
Journal: JAMA Network Open (2025)

Cannabis edibles have increased in popularity, particularly among young adults and in states with recreational cannabis legalization. Little is known about the association of cannabis packaging regulations with health warning recall and perceptions. To evaluate whether features of packaging are associated with ability to recall health warnings as well as perceptions of cannabis edible products among young adults. This cross-sectional study was conducted from October 6 to 18, 2023, in 23 states and Washington, DC, that legalized recreational cannabis. Participants included young adults aged 18 to 29 years, including cannabis users and nonusers. In the between-individual 3 (packaging styles) × 3 (health claims) × 7 (health warning themes) full-factorial randomized online experiment, participants viewed an image of the packaging of cannabis edible products with random variations in package styles (plain, normal branded, and youth-appealing packaging), health claims (none, pain relief, and sleep aid), and health warning themes (long-lasting effects, pregnancy-related harms, driving impairment, mental health problems, harms to youths, harms of high potency products, and delayed effects). Five self-reported outcomes, including warning recall (ability to correctly recall the warning label shown), product appeal rating, relative harm, adult-oriented appearance, and target age group. Participants comprised 4500 young adults aged 18 to 29 years, including 3000 cannabis users and 1500 nonusers. These participants included 2287 men (50.8%); 1095 participants (24.3%) were aged 18 to 20 years, and 1905 (42.3%) were aged 21 to 25 years. Compared with normal branded packaging, plain packaging was associated with increased odds of correct warning recall (correct rate, 52.9%; odds ratio [OR], 1.47 [95% CI, 1.27-1.70]), decreased appeal ratings (mean appeal rating, 5.2 of 10; OR, 0.70 [95% CI, 0.61-0.80]), and increased perceived relative harm (mean harm rating, 2.6 of 5; OR, 1.48 [95% CI, 1.27-1.74]). Compared with normal branded packaging, youth-appealing packaging was associated with increased appeal ratings (OR, 1.40 [95% CI, 1.20-1.64]), particularly among younger adults aged 18 to 20 years. Compared with no health claims, the pain relief and sleep aid claims were associated with increased appeal ratings (pain relief: OR, 1.31 [95% CI, 1.17-1.46]; sleep aid: OR, 1.36 [95% CI, 1.24-1.50]), particularly among past-year nonusers. Results of this cross-sectional study of the features of cannabis edible packaging suggested that requiring plain packaging, prohibiting youth-appealing features, and regulating unsubstantiated health claims may improve warning recall and accurate harm perceptions among young adults. Future observational studies evaluating the effects of these regulations are recommended.
Medicare Beneficiary Receipt of Methadone by Drive Time to Opioid Treatment Programs
Authors: Jonathan Cantor, Helin G. Hernandez, Aaron Kofner, Julie Lai, Denis Agniel, Kosali I. Simon, Bradley D. Stein, Erin A. Taylor
Journal: JAMA Network Open (2025)

To combat the ongoing opioid crisis, policy makers and public health officials are developing novel policies to increase the availability of medications for opioid use disorder (OUD). An important question is to what extent geographic availability of opioid treatment programs (OTPs) is associated with treatment receipt. Understanding this association may help with developing additional policies to increase medication for OUD dispensing and improve population health outcomes. To quantify trends in dispensing methadone to Medicare beneficiaries based on proximity to an OTP. This cross-sectional study analyzed 2020 Medicare fee-for-service claims for methadone for beneficiaries with a recent diagnosis of OUD merged with drive times to OTP locations. Medicare beneficiaries enrolled in a Part D prescription plan and diagnosed with OUD in any of the 3 quarters before and during the 2020 quarter of interest were examined. Drive time between the centroid of a beneficiary's zip code and the closest OTP. Quarterly methadone receipt among Medicare beneficiaries with a recent OUD diagnosis was assessed using logistic regression models. In 2020, there were 640 706 Medicare beneficiaries with a recent OUD diagnosis (mean [SD] age, 62.5 [13.5] years; 55.6% female; 65.5% residing in an urban locality at the time of diagnosis). Of these beneficiaries, 9.6% lacked an OTP within a 60-minute drive time. The probability of a beneficiary receiving methadone decreased as the drive time from an OTP increased. Specifically, in urban areas, the likelihood of methadone receipt decreased by a relative 54% from a mean of 5.29% (national interval, 4.27%-6.52%) for beneficiaries who lived within a 5-minute drive of an OTP to 2.39% (national interval, 1.92%-2.98%) for those who lived within a 15-minute drive from an OTP. For rural beneficiaries, the likelihood of methadone receipt decreased by a relative 27% from a mean of 3.42% (national interval, 2.73%-4.28%) for a 5-minute drive time to 2.39% (national interval, 1.92%-2.98%) for a 15-minute drive time. Evidence of a threshold effect at a drive time of 20 minutes was observed for methadone receipt, after which the rate slowed and was similar between urban and rural beneficiaries. These findings suggest that the likelihood of methadone receipt may vary based on proximity to OTP facilities. Where OTPs are located may be a contributor to whether an individual receives methadone treatment.
HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy
Authors: Maša Zrimšek, Kristina Draganić, Anna Malzer, Verena Doblmayr, Katarina Mišura, Rafael de Freitas E Silva, Jamie D Matthews, Fabio Iannelli, Sabrina Wohlhaupter, Carlos Uziel Pérez Malla, Heinz Fischer, Helga Schachner, Ana-Iris Schiefer, Raheleh Sheibani-Tezerji, Roberto Chiarle, Suzanne Dawn Turner, Wilfried Ellmeier, Christian Seiser, Gerda Egger
Journal: Leukemia (2025)
Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study
Authors: Carlyn Rose Tan, Sireesha Asoori, Chiung-Yu Huang, Larissa Brunaldi, Rakesh Popat, Efstathios Kastritis, Joaquin Martinez-Lopez, Radhika Bansal, Andre De Menezes Silva Corraes, Saurabh Chhabra, Ricardo Parrondo, Sikander Ailawadhi, Despina Fotiou, Meletios A Dimopoulos, Kwee Yong, Catriona Mactier, Chris Lau, Magdalena Corona, Adolfo Jesús Sáez Marin, Hira Mian, Brian Gm Durie, Saad Z Usmani, Thomas G Martin, Yi Lin
Journal: Blood Cancer Journal (2025)

Teclistamab, a BCMAxCD3-directed bispecific antibody, has shown high response rates and durable remissions in triple-class-exposed patients with relapsed/refractory multiple myeloma. We performed a retrospective study evaluating the efficacy and safety of teclistamab in 210 patients treated at 9 academic centers from five countries within the IMWG Immunotherapy Working Group Committee. Patients were heavily pretreated, with 83% having triple-class refractory disease and 44% with prior BCMA-targeted therapy. With a median follow-up of 5.3 months, the overall response rate (ORR) was 67% in 188 response-evaluable patients, including 55% with a very good partial response or better. The 6-month progression-free survival (PFS) and overall survival rates were 53% (95% CI, 46-61%) and 73% (67-80%), respectively. Patients who received prior BCMA-directed therapy compared to BCMA-treatment-naïve patients had a lower ORR (58.3 vs 74.0%; P = 0.03) and PFS (6-month PFS 43% [95% CI, 33-55%] vs 63% [54-73%]; logrank P = 0.004). Step-up dosing occurred in an outpatient setting for 23% of patients. CRS occurred in 54% of patients, and infections were reported in 56.2% of patients, with 22% having grade ≥3 infections. In this multicenter real-world study, we found that teclistamab can lead to rapid responses in heavily pretreated myeloma patients with comparable efficacy and safety profiles, as demonstrated in MajesTEC-1.