tbuckley/cabot-search huggingface dataset:
Underrepresentation of Hispanic women in science, technology, engineering, mathematics, and medicine
Authors: Jovanka Gencel‐Augusto, Natasha J. Minaya, Daniel E. Johnson, Jennifer R. Grandis
Journal: CA A Cancer Journal for Clinicians (2025)

Abstract Despite ongoing efforts to increase the number of women in science, technology, engineering, and mathematics (STEM) and in medicine, Hispanic women remain severely underrepresented in these fields. This disparity not only hinders scientific innovation and the delivery of culturally competent medical care but also perpetuates a systemic exclusion. Research specifically addressing the challenges faced by Hispanic women, the extent of underrepresentation in these disciplines, and strategies to mitigate these issues is sparce. The authors conducted a systematic analysis of peer‐reviewed articles to address this gap. The findings reveal a stark underrepresentation of Hispanic women across all examined fields, particularly compared with White women. In addition, the underrepresentation persists when compared with Hispanic men, although the disparity is less pronounced. The authors identify ongoing disparities in promotion, compensation, and retention rates for Hispanic women; present data for barriers to entry and retention; and highlight existing programs and strategies aimed at addressing this underrepresentation. Finally, a framework is presented for future studies and actionable initiatives, and the broader implications of these findings for the field of oncology are highlighted.
<scp>CT</scp>‐<scp>P39</scp> Compared With Reference Omalizumab in Chronic Spontaneous Urticaria: Results From a Double‐Blind, Randomized, Active‐Controlled, Phase 3 Study
Authors: Sarbjit S. Saini, Marcus Maurer, Yevgeniya Dytyatkovska, Ewa Springer, Maria Ratkova, Borislava Krusheva, Chun Wook Park, Grazyna Pulka, Marta Chełmińska, Adam Reich, Sunghyun Kim, Keumyoung Ahn, Suyoung Kim, Sewon Lee, Jieun Ka, Jongho Kim, Clive Grattan
Journal: Allergy (2025)

ABSTRACT Background This study compared the therapeutic equivalence of CT‐P39 (an omalizumab biosimilar) and EU‐approved reference omalizumab (ref‐OMA) in patients with chronic spontaneous urticaria. Methods This double‐blind, randomized, active‐controlled Phase 3 study (NCT04426890) included two 12‐week treatment periods (TPs). In TP1, patients received CT‐P39 300 mg, ref‐OMA 300 mg, CT‐P39 150 mg, or ref‐OMA 150 mg. In TP2, patients treated with ref‐OMA 300 mg were rerandomized to CT‐P39 300 mg or ref‐OMA 300 mg; patients initially randomized to CT‐P39 300 mg continued this regimen; and patients initially randomized to CT‐P39 or ref‐OMA 150 mg received 300 mg dosing with the same drug. The primary endpoint for the assessment of therapeutic equivalence of CT‐P39 300 mg and ref‐OMA 300 mg was change from baseline in weekly itch severity score (ISS7) at week 12. Results In TP1, 619 patients were randomized (CT‐P39 300 mg, n = 204; ref‐OMA 300 mg, n = 205; CT‐P39 150 mg, n = 107; ref‐OMA 150 mg, n = 103). Equivalence was demonstrated between CT‐P39 300 mg and ref‐OMA 300 mg for mean change from baseline in ISS7 at week 12; confidence intervals (CIs) were within predefined equivalence margins: global analysis: treatment difference 0.77, 95% CI –0.37 to 1.90; US analysis: treatment difference 0.70, 90% CI –0.22 to 1.63. The proportion of patients experiencing ≥ 1 treatment‐related adverse event was comparable across groups. Secondary efficacy, quality of life, pharmacokinetic, safety, and immunogenicity outcomes were comparable between groups at a given dose level, with no evident impact of switching. Conclusions Equivalent efficacy was observed between CT‐P39 and ref‐OMA, with comparable safety also evident.
Evaluating Minimal Residual Disease Negativity as a Surrogate Endpoint for Treatment Efficacy in Multiple Myeloma: A Meta‐Analysis of Randomized Controlled Trials
Authors: Ioannis Ntanasis‐Stathopoulos, Charalampos Filippatos, Anastasios Ntanasis‐Stathopoulos, Panagiotis Malandrakis, Efstathios Kastritis, Ourania E. Tsitsilonis, Meletios A. Dimopoulos, Evangelos Terpos, Maria Gavriatopoulou
Journal: American Journal of Hematology (2025)

This meta-analysis examined the association between minimal residual disease (MRD) negativity and survival outcomes in 15 304 patients with multiple myeloma (MM) enrolled in randomized controlled trials published until June 2, 2024. Overall, there was a significant, negative and strong association between MRD negativity odds ratios and survival hazard ratios (β_PFS = -0.20, p < 0.001, β_OS = -0.12, p = 0.023). These associations remained significant for newly diagnosed patients (β_PFS = -0.35, p < 0.001), and they were consistent but not significant for relapsed/refractory patients (β_PFS = -0.06, p = 0.635). Sustained MRD negativity at 1 year was strongly correlated with prolonged PFS (β_PFS = -0.30, p < 0.001). In conclusion, this comprehensive meta-analysis supports MRD as a surrogate for survival in MM.
Ongoing replication stress tolerance and clonal T cell responses distinguish liver and lung recurrence and outcomes in pancreatic cancer
Authors: Jason M. Link, Jennifer R. Eng, Carl Pelz, Kevin MacPherson-Hawthorne, Patrick J. Worth, Shamaline Sivagnanam, Dove J. Keith, Sydney Owen, Ellen M. Langer, Alison Grossblatt-Wait, Gustavo Salgado-Garza, Allison L. Creason, Sara Protzek, Julian Egger, Hannah Holly, Michael B. Heskett, Koei Chin, Nell Kirchberger, Konjit Betre, Elmar Bucher, David Kilburn, Zhi Hu, Michael W. Munks, Isabel A. English, Motoyuki Tsuda, Jeremy Goecks, Emek Demir, Andrew C. Adey, Adel Kardosh, Charles D. Lopez, Brett C. Sheppard, Alex Guimaraes, Brian Brinkerhoff, Terry K. Morgan, Gordon B. Mills, Lisa M. Coussens, Jonathan R. Brody, Rosalie C. Sears
Journal: Nature Cancer (2025)
Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression
Authors: Michael Nshanian, Joshua J. Gruber, Benjamin S. Geller, Faye Chleilat, Samuel M. Lancaster, Shannon M. White, Ludmila Alexandrova, Jeannie M. Camarillo, Neil L. Kelleher, Yingming Zhao, Michael P. Snyder
Journal: Nature Metabolism (2025)

Abstract The short-chain fatty acids (SCFAs) propionate and butyrate have beneficial health effects, are produced in large amounts by microbial metabolism and have been identified as unique acyl lysine histone marks. To better understand the function of these modifications, we used chromatin immunoprecipitation followed by sequencing to map the genome-wide location of four short-chain acyl histone marks, H3K18pr, H3K18bu, H4K12pr and H4K12bu, in treated and untreated colorectal cancer (CRC) and normal cells as well as in mouse intestines in vivo. We correlate these marks with open chromatin regions and gene expression to access the function of the target regions. Our data demonstrate that propionate and butyrate bind and act as promoters of genes involved in growth, differentiation and ion transport. We propose a mechanism involving direct modification of specific genomic regions by SCFAs resulting in increased chromatin accessibility and, in the case of butyrate, opposing effects on the proliferation of normal versus CRC cells.
IRE1α–XBP1 safeguards hematopoietic stem and progenitor cells by restricting pro-leukemogenic gene programs
Authors: Brendan M. Barton, Francheska Son, Akanksha Verma, Saswat Kumar Bal, Qianzi Tang, Rui Wang, Katharine Umphred-Wilson, Rehan Khan, Josephine Trichka, Han Dong, Claudia Lentucci, Xi Chen, Yinghua Chen, Yuning Hong, Cihangir Duy, Olivier Elemento, Ari M. Melnick, Jin Cao, Xi Chen, Laurie H. Glimcher, Stanley Adoro
Journal: Nature Immunology (2025)
Implementation of guideline‐recommended therapies in heart failure with reduced ejection fraction according to heart failure duration: An analysis of 55 581 patients from the Swedish Heart Failure (<scp>SwedeHF</scp>) Registry
Authors: Angiza Shahim, Cecilia Linde, Gianluigi Savarese, Ulf Dahlström, Lars H. Lund, Camilla Hage
Journal: European Journal of Heart Failure (2025)

Abstract Aims Guidelines recommend immediate initiation of all four class I guideline‐directed medical therapies, renin–angiotensin system inhibitors (RASI) or angiotensin receptor–neprilysin inhibitors (ARNI), beta‐blockers, mineralocorticoid receptor antagonists (MRA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) following the diagnosis of heart failure (HF) with reduced ejection fraction (HFrEF). The extent to which this occurs in new‐onset HFrEF is unclear. We assessed guideline‐recommended therapies during the first year following a HFrEF diagnosis. Methods and results The Swedish HF Registry was linked to additional national registries. In patients with HFrEF (ejection fraction &lt;40%), clinical characteristics and HF treatment from when they were available and recommended in guidelines were assessed according to time from HF diagnosis (&lt;3, 3 to &lt;6, 6–12 and &gt;12 months). Of 55 581 patients with HFrEF enrolled between 2000 and 2021, 54%, 5.8%, 4.8% and 36% had an HF duration of &lt;3, 3 to &lt;6, 6–12 and &gt;12 months, respectively. Patients with shorter HF duration were younger, had lower New York Heart Association class and had fewer cardiovascular comorbidities. Within 3 months, 3 to &lt;6 months, 6–12 months and &gt;12 months from HF diagnosis, 93%, 92%, 90% and 89% were on RASI or ARNI, 9.8%, 17%, 19% and 22% on ARNI alone, 35%, 43%, 44% and 46% on MRA, 92%, 92%, 92% and 91% on beta‐blockers, and 26%, 30%, 19% and 28% on SGLT2i, respectively. Additionally, 18% received cardiac resynchronization therapy/implantable cardioverter‐defibrillator &gt;12 months after diagnosis. Conclusions Most patients received RASI and beta‐blockers in the first months following HFrEF diagnosis. Use of ARNI, MRA and SGLT2i was limited, both in the early and later time periods. Our findings suggest that strategies to improve guideline‐directed use of HFrEF therapies remain urgently needed.
Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma
Authors: Tejas Jammihal, Renee Maria Saliby, Chris Labaki, Hanna Soulati, Juan Gallegos, Arnau Peris, Dustin McCurry, Chunlei Yu, Valisha Shah, Deepak Poduval, Talal El Zarif, Nourhan El Ahmar, Yasmin Nabil Laimon, Marc Eid, Aseman Bagheri Sheshdeh, Katherine M. Krajewski, Florian A. Büttner, Matthias Schwab, Daniel Heng, Rafael C. Casellas, Kunal Rai, Niki M. Zacharias Millward, Pavlos Msaouel, Jose Karam, Sabina Signoretti, Eliezer Van Allen, Toni K. Choueiri, David A. Braun, Sachet A. Shukla
Journal: Nature Cancer (2025)
Low-avidity T cells drive endogenous tumor immunity in mice and humans
Authors: Summit Singhaviranon, Joseph P. Dempsey, Adam T. Hagymasi, Ion I. Mandoiu, Pramod K. Srivastava
Journal: Nature Immunology (2025)

T cells recognize neoepitope peptide-major histocompatibility complex class I on cancer cells. The strength (or avidity) of the T cell receptor–peptide-major histocompatibility complex class I interaction is a critical variable in immune control of cancers. Here, we analyze neoepitope-specific CD8 cells of distinct avidities and show that low-avidity T cells are the sole mediators of cancer control in mice and are solely responsive to checkpoint blockade in mice and humans. High-avidity T cells are ineffective and immune-suppressive. The mechanistic basis of these differences lies in the higher exhaustion status of high-avidity cells. High-avidity T cells have a distinct transcriptomic profile that is used here to calculate an 'avidity score', which we then use for in silico identification of low-avidity and high-avidity T cells in mice and humans. Surprisingly, CD8+ T cells with identical T cell receptors exhibit wide variation in avidities, suggesting an additional level of regulation of T cell activity. Aside from providing a better understanding of endogenous T cell responses to cancer, these findings might instruct future immunotherapy strategies. Here the authors show that, in mouse tumors, CD8+ T cells with a low-avidity TCR are the mediators of antitumor and immunotherapy responses, in part because T cells with a high-avidity TCR are more exhausted.
Time‐varying analyses of survival and outcomes in patients with <scp>HeartMate</scp> 3 left ventricular assist devices
Authors: Aaron J. Weiss, Jean‐Luc A. Maigrot, Michael Z.Y. Tong, Lucy Thuita, Nicholas G. Smedira, Shinya Unai, Pavan Bhat, Maria Mountis, Eugene H. Blackstone, Randall C. Starling, Edward G. Soltesz
Journal: European Journal of Heart Failure (2025)
A scalable variational inference approach for increased mixed-model association power
Authors: Hrushikesh Loya, Georgios Kalantzis, Fergus Cooper, Pier Francesco Palamara
Journal: Nature Genetics (2025)

Abstract The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing the benefits of large-scale data collection efforts. We developed Quickdraws, a method that increases association power in quantitative and binary traits without sacrificing computational efficiency, leveraging a spike-and-slab prior on variant effects, stochastic variational inference and graphics processing unit acceleration. We applied Quickdraws to 79 quantitative and 50 binary traits in 405,088 UK Biobank samples, identifying 4.97% and 3.25% more associations than REGENIE and 22.71% and 7.07% more than FastGWA. Quickdraws had costs comparable to REGENIE, FastGWA and SAIGE on the UK Biobank Research Analysis Platform service, while being substantially faster than BOLT-LMM. These results highlight the promise of leveraging machine learning techniques for scalable GWASs without sacrificing power or robustness.
Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via <i>Akkermansia muciniphila</i>
Authors: Miaomiao Pan, Chenglang Qian, Shaoye Huo, Yuchen Wu, Xinyi Zhao, Yueming Ying, Boyu Wang, Hao Yang, Anaguli Yeerken, Tongyao Wang, Mengwei Fu, Lihong Wang, Yuhuan Wei, Yunhua Zhao, Chunhai Shao, Huijing Wang, Chao Zhao
Journal: Gut Microbes (2025)

The gut microbiota plays a pivotal role in anxiety regulation through pathways involving neurotransmitter production, immune signaling, and metabolic interactions. Among these, gut-derived serotonin (5-hydroxytryptamine, 5-HT), synthesized from tryptophan metabolism, has been identified as a key mediator. However, it remains unclear whether specific microbial factors regulate tryptophan metabolism to influence 5-HT production and anxiety regulation. In this study, we analyzed 110 athletes undergoing closed training and found that fecal lactate levels were significantly associated with anxiety indicators. We observed a significant negative correlation between Akkermansia abundance and anxiety levels in athletes. Co-supplementation with lactate and Akkermansia muciniphila (A. muciniphila) modulated tryptophan metabolism by increasing key enzyme TPH1 and reducing IDO1, thus shifting metabolism from kynurenine (Kyn) to 5-HT. In addition, lactate enhanced the propionate production capacity of A. muciniphila, potentially contributing to anxiety reduction in mice. Taken together, these findings suggest that enteric lactate and A. muciniphila collaboratively restore the imbalance in tryptophan metabolism, leading to increased 5-HT activity and alleviating anxiety phenotypes. This study highlights the intricate interplay between gut metabolites and anxiety regulation, offering potential avenues for microbiota-targeted therapeutic strategies for anxiety.
Unleashing the champion mindset among Melaka’s para athletes of the Malaysia Games
Authors: Ahmad Fadhly Arham, Nor Sabrena Norizan, Rani Diana Othman
Journal: British Journal of Sports Medicine (2025)

Sukan Para Malaysia (Para Sukma) is a multisport event for disabled athletes in Malaysia, established in 1982.Initially called the National Games for Disabled Members of Malaysia, it became the Malaysian Paralympic Games in 1998 and was renamed Sukan Para Malaysia in 2018.The event now occurs biennially, alongside the Malaysian Games, in the same host state.In 2024, Melaka will participate with 83 contingents, including 63 athletes and 20 officials, competing in various sports such as archery, swimming, tenpin bowling, chess, badminton, table tennis, powerlifting, athletics, boccia and lawn bowls.Athletes represent diverse disabilities, including physical, intellectual and visual impairments.Based on previous achievements, Melaka aims to secure nine gold medals this year.Table 1 provides the breakdown of the Melaka's Para Contingent 2024.
Impact of Heart Transplant Allocation Changes on Waitlist Mortality and Clinical Practice in Pediatric and Adult Patients With Congenital Heart Disease and Cardiomyopathy
Authors: Luke Wooster, Matthew J. O’Connor, Xuemei Zhang, Constantine D. Mavroudis, Katsuhide Maeda, Humera Ahmed, Jonathan Edwards, Kimberly Y. Lin, Carol Wittlieb-Weber, Joseph Rossano, Jonathan B. Edelson
Journal: Circulation (2025)

BACKGROUND: The United Network of Organ Sharing made changes to the priority for allocation of hearts for transplantation (HT) in 2016 for pediatric patients and 2018 for adult patients. Although recent work has evaluated the impact of the revised allocation systems on mechanical circulatory support practices and waitlist outcomes, there are limited data that focus more specifically on the impact of the allocation changes on patients with congenital heart disease (CHD) or cardiomyopathy and how these relationships might differ in pediatric and adult patients. METHODS: The United Network of Organ Sharing database was queried for pediatric (&lt;18 years of age) and adult (18–50 years of age) patients with a CHD or cardiomyopathy diagnosis listed for HT. Cohorts were grouped into preallocation and postallocation change eras: pediatric patients from January 1, 2011, to March 21, 2016, and January 1, 2017, to December 31, 2021; and adult patients from January 1, 2015, to October 17, 2018, and January 1, 2019, to December 31, 2021. Differences in era for survival or waitlist removal because of clinical deterioration from the time of HT listing were compared using competing risk models. RESULTS: We identified 11 637 patients listed for HT during the study period, including 2882 pediatric patients with CHD, 594 adults with CHD, 2348 pediatric patients with cardiomyopathy, and 5813 adults with cardiomyopathy. In a competing risk model adjusting for demographic and clinical factors, allocation changes were significantly associated with lower death or waitlist removal within 1 year of HT listing in infants with CHD (HR, 0.75 [0.57–0.99]; P =0.04), children with CHD (HR, 0.61 [0.43–0.86]; P =0.005), and adults with cardiomyopathy (HR, 0.60 [0.44–0.81]; P =0.001), but not in infants with cardiomyopathy, children with cardiomyopathy, or adults with CHD. CONCLUSIONS: The recent allocation changes of the Organ Procurement and Transplantation Network associations with waitlist duration and outcome were not uniform across pediatric and adult cohorts with CHD or those with cardiomyopathy. Children with cardiomyopathy and adults with CHD did not experience the mortality benefits experienced by adults with cardiomyopathy and children with CHD. Future iterations of the allocation systems should consider differential access to mechanical circulatory support options for children and adults, patient sensitization status, and whether having separate systems for adults and children is the most appropriate method to allocate organs.
Induction of macrophage efferocytosis in pancreatic cancer via PI3Kγ inhibition and radiotherapy promotes tumour control
Authors: Shannon Nicole Russell, Constantinos Demetriou, Giampiero Valenzano, Alice Evans, Simei Go, Tess Stanly, Ahmet Hazini, Frances Willenbrock, Alex Nicolas Gordon-Weeks, Somnath Mukherjee, Matthias Tesson, Jennifer P Morton, Eric O'Neill, Keaton Ian Jones
Journal: Gut (2025)

Background The immune suppression mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unknown, but preclinical studies have implicated macrophage-mediated immune tolerance. Hence, pathways that regulate macrophage phenotype are of strategic interest, with reprogramming strategies focusing on inhibitors of phosphoinositide 3-kinase-gamma (PI3Kγ) due to restricted immune cell expression. Inhibition of PI3Kγ alone is ineffective in PDAC, despite increased infiltration of CD8+ T cells. Objective We hypothesised that the immune stimulatory effects of radiation, and its ability to boost tumour antigen availability could synergise with PI3Kγ inhibition to augment antitumour immunity. Design We used orthoptic and genetically engineered mouse models of pancreatic cancer (LSL-Kras G12D/+ ;Trp53 R172H/+ ;Pdx1-Cre). Stereotactic radiotherapy was delivered using contrast CT imaging, and PI3Kγ inhibitors by oral administration. Changes in the tumour microenvironment were quantified by flow cytometry, multiplex immunohistochemistry and RNA sequencing. Tumour-educated macrophages were used to investigate efferocytosis, antigen presentation and CD8+ T cell activation. Single-cell RNA sequencing data and fresh tumour samples with autologous macrophages to validate our findings. Results Tumour-associated macrophages that employ efferocytosis to eradicate apoptotic cells can be redirected to present tumour antigens, stimulate CD8+ T cell responses and increase local tumour control. Specifically, we demonstrate how PI3Kγ signalling restricts inflammatory macrophages and that inhibition supports MERTK-dependent efferocytosis. We further find that the combination of PI3Kγ inhibition with targeted radiotherapy stimulates inflammatory macrophages to invoke a pathogen-induced like efferocytosis that switches from immune tolerant to antigen presenting. Conclusions Our data supports a new immunotherapeutic approach and a translational rationale to improve survival in PDAC.
Multifunctional Hydrogel with Photothermal ROS Scavenging and Antibacterial Activity Accelerates Diabetic Wound Healing
Authors: Yijia Xue, Fan Yang, Yunjiao He, Feilong Wang, Dandan Xia, Yunsong Liu
Journal: Advanced Healthcare Materials (2025)

Abstract Poor diabetic wound healing poses a critical threat to human health. Excessive oxidative stress and increased susceptibility to bacterial infection are key issues that impede diabetic wound healing. Cerium oxide nanoparticles (CeO 2 NPs) have attracted increasing attention because of their unique antioxidant and antimicrobial properties. Here, this work designs a near‐infrared (NIR) light‐responsive gelatin methacryloyl (GelMA)/CeO 2 /polydopamine (PDA) hydrogel with antibacterial and antioxidant effects. The hydrogel exhibits a stable, efficient, and controllable photothermal conversion capacity under NIR stimulation. The hydrogel can be used to construct a local microenvironment conducive to chronic diabetic wound healing. Significant antibacterial effects of the NIR‐responsive GelMA/CeO 2 /PDA hydrogel on both Escherichia coli (E.coli) and methicillin‐resistant Staphylococcus aureus (MRSA) are demonstrated by counting colony‐forming units (CFUs) and in bacterial live/dead staining experiments. The strong antioxidant activity of hydrogels is demonstrated by measuring the level of reactive oxygen species (ROS). The effect of the NIR‐responsive GelMA/CeO 2 /PDA hydrogel in terms of promoting diabetic wound healing is validated in full‐thickness cutaneous wounds of diabetic rat models. Additionally, this work describes the mechanism by which the NIR‐responsive GelMA/CeO 2 /PDA hydrogel promotes diabetic wound healing; the hydrogel inhibits the interleukin (IL)‐17 signaling pathway. This NIR‐responsive, multifunctional hydrogel dressing provides a targeted approach to diabetic wound healing.