tbuckley/cabot-search huggingface dataset:
Gut microbiota-mediated conversion of mangiferin to norathyriol alters short chain fatty acid and urate metabolism
Authors: Daan Bunt, Markus Schwalbe, Fittree Hayeeawaema, Sahar El Aidy
Journal: Gut Microbes (2025)

Mangiferin (MAN), a natural C-glycosylxanthone, is recognized for its health-promoting effects in traditional medicinal preparations. However, its poor bioavailability and limited intestinal permeability restrict its direct biological activity in vivo. Previous studies have suggested a potential bacterial breakdown of MAN into norathyriol (NOR), an aglycone with significantly higher bioavailability and absorption. Yet, the prevalence of MAN-metabolizing microbes, the presence of MAN or NOR within the gut microbial community, and their effects on the composition and metabolic activity of the gut microbiome remain unclear. In this study, fecal samples from healthy adult volunteers treated with MAN revealed its conversion to NOR, with interindividual variation attributed to the uncultured bacterial strain CAKRHR01 sp934339005. While MAN had minimal impact on microbial composition and metabolic activity, NOR treatment significantly increased pH, reduced overall bacterial cell counts, and selectively suppressed short-chain fatty acid-producing bacteria, including Faecalibacterium prausnitzii as well as urate consumers, such as Enterocloster bolteae. These findings underscore the potential of NOR to modulate gut microbial activity and highlight the importance of understanding microbiome-mediated metabolism when assessing the health implications of phytochemicals.
Treating juvenile dermatomyositis to target: Paediatric Rheumatology European Society/Childhood Arthritis and Rheumatology Research Alliance-endorsed recommendations from an international task force
Authors: Angelo Ravelli, Silvia Rosina, Jayne M MacMahon, Talia Baird, Ana Isabel Rebollo-Giménez, Claas Hinze, Liza J McCann, Ann M Reed, Lisa G Rider, Matilde Arvigo, Brigitte Bader-Meunier, Claudio Bruno, Li Caifeng, Raquel Campanilho-Marques, Sara Cuccato, Chiara Fiorillo, Nikki A Hahn, Adam M Huber, Marc Jansen, Ozgur Kasapcopur, Maria Martha Katsikas, Susan Kim, Polly Livermore, Sue Maillard, Clara Malattia, Angela Nyangore Migowa, Takako Miyamae, Ruth Murphy, Rebecca Nicolai, Charalampia Papadopoulou, Clarissa Pilkington, Helga Sanner, Sujata Sawhney, Elzbieta Smolewska, Stacey E Tarvin, Georgina Tiller, Natasa Toplak, Lucy R Wedderburn, Francesca Bovis, Alessandro Consolaro, Brian M Feldman
Journal: Annals of the Rheumatic Diseases (2025)

Despite the recent prognostic improvement, a sizeable proportion of patients with juvenile dermatomyositis (JDM) respond suboptimally to contemporary therapies. This study aimed to develop recommendations for treating JDM to target. A Steering Committee formulated a set of provisional recommendations based on evidence derived from a systematic literature review and a retrospective chart review of patients. These were discussed, amended, and voted on by an international Task Force, including 28 paediatric rheumatologists, 2 specialists in neuromuscular diseases, 1 dermatologist, 1 physical therapist, 1 research nurse, 2 patients with JDM, and 1 parent of a patient with JDM. Items that achieved at least an 80% majority vote were accepted as final recommendations. Although the literature review did not reveal trials that compared a treat-to-target strategy with a nonsteered approach, it provided indirect evidence about specific end points that could serve as targets that facilitated development of recommendations. The group reached consensus on 7 overarching principles and 12 recommendations. It was agreed that both patients/parents and treaters should share decisions in setting treatment targets and therapeutic strategies, with inactive disease as the preferred target and minimal disease activity an alternative one. Inactive disease is targeted to be achieved within 12 months after treatment start. Interim targets include minimal and moderate clinical improvement within 6 weeks and 3 months, respectively, and normalisation of muscle strength within 6 months. High-dose glucocorticoids remain fundamental in the initial management, but progressive tapering and discontinuation within 12 months through optimisation of concomitant immunomodulatory therapy was advised. A research agenda was formulated. The Task Force developed recommendations for treating JDM to target, being aware that the evidence is not strong and needs to be expanded by future research. Implementation of the recommendations in clinical practice will help to reach optimal outcomes for JDM.
A Phase 2 Trial of <scp>CPX</scp>‐351 Combined With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia
Authors: Tapan M. Kadia, Wei‐Ying Jen, Alex Bataller, Alexandre Bazinet, Gautam Borthakur, Elias Jabbour, Wei Qiao, Nicholas J. Short, Koichi Takahashi, Ghayas C. Issa, Courtney D. DiNardo, Guillermo Montalban‐Bravo, Naveen Pemmaraju, Andrew Tran, Vanthana Bharathi, Sanam Loghavi, Amin M. Alousi, Uday Popat, Naval G. Daver, Farhad Ravandi, Hagop M. Kantarjian
Journal: American Journal of Hematology (2025)

ABSTRACT Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX‐531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN. Patients aged ≥ 18 years with RR AML who were fit for intensive chemotherapy were eligible. Prior venetoclax exposure was allowed. The phase 1b portion followed a 3 + 3 design to identify the recommended phase 2 dose (RP2D) for the expansion cohort. At the starting dose level of −1, prolonged myelosuppression was observed, leading to dose level −2 (CPX‐351 dosed at daunorubicin 44 mg/m 2 on days 1,3, and 5 and venetoclax 300 mg days 2–8) being chosen as the RP2D. Thirty three patients with a median age of 58 years (range, 26–72) were treated. Patients were heavily pretreated, with 58% with prior venetoclax exposure, 44% in the second salvage or later, and 30% with prior stem cell transplant (SCT). Adverse cytogenetics were present in 51% of patients, with myelodysplasia‐related mutations in 64%, and TP53 mut in 21%. The overall response rate (ORR) was 46% (95% CI, 30–62), with a composite CR rate (CRc) of 39% (95% CI, 25–56). Patients in first salvage with wildtype TP53 had a CRc rate of 70% (95% CI, 40–89), with undetectable MRD in 71% (95% CI, 36–92) and a 2‐year OS of 49% (95% CI, 23–100). Eleven (73%) responding patients underwent SCT. The 30‐day mortality was 9%, with a 60‐day mortality of 21%. The most common adverse events were related to myelosuppression. CPX + VEN has activity in RR AML, particularly when used in first salvage and in patients who do not harbor TP53 mutations. ClinicalTrials.gov Identifier: NCT03629171
Dietary-timing-induced gut microbiota diurnal oscillations modulate inflammatory rhythms in rheumatoid arthritis
Authors: Fopei Ma, Zhuang Li, Haihua Liu, Shixian Chen, Songyuan Zheng, Junqing Zhu, Hao Shi, Haixin Ye, Zhantu Qiu, Lei Gao, Bingqi Han, Qian Yang, Xing Wang, Yang Zhang, Lifang Cheng, Huijie Fan, Shuaijun Lv, Xiaoshan Zhao, Hongwei Zhou, Juan Li, Mukeng Hong
Journal: Cell Metabolism (2025)
Nicotinic acid riboside maintains NAD+ homeostasis and ameliorates aging-associated NAD+ decline
Authors: Won-Suk Song, Xiyu Shen, Kang Du, Cuauhtemoc B. Ramirez, Sang Hee Park, Yang Cao, Johnny Le, Hosung Bae, Joohwan Kim, Yujin Chun, Nikki Joyce Khong, Marie Kim, Sunhee Jung, Wonsuk Choi, Miranda L. Lopez, Zaid Said, Zehan Song, Sang-Guk Lee, Dequina Nicholas, Yo Sasaki, Jeffrey Milbrandt, David K. Imagawa, Dorota Skowronska-Krawczyk, Danica Chen, Gina Lee, Cholsoon Jang, Qin Yang
Journal: Cell Metabolism (2025)
Estimated Current and Future Congenital Rubella Syndrome Incidence with and Without Rubella Vaccine Introduction — 19 Countries, 2019–2055
Authors: Emmaculate Lebo, Emilia Vynnycky, James P. Alexander, Matthew J. Ferrari, Amy K. Winter, Kurt Frey, Timoleon Papadopoulos, Gavin B. Grant, Patrick O’Connor, Susan E. Reef, Natasha S. Crowcroft, Laura A. Zimmerman
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Rubella is a leading cause of vaccine-preventable birth defects. Rubella virus infection during early pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of birth defects known as congenital rubella syndrome (CRS). This report describes current and future estimated CRS incidence in countries that have not yet introduced rubella-containing vaccine (RCV) into their national childhood immunization schedules and the estimated effect of implementing a recent recommendation to introduce RCV into these programs even if population coverage with measles-containing vaccine is <80%. During 2000-2022, the number of countries that introduced RCV increased from 99 (52%) of 191 in 2000 to 175 (90%) of 194 in 2022. By the end of 2023, 19 lower- and middle-income countries had not yet introduced RCV. In 2019, an estimated 24,000 CRS cases occurred in these countries, representing 75% of the estimated 32,000 cases worldwide. In a modeling study estimating the effect of RCV introduction in these countries during 2025-2055, an estimated 1.03 million CRS cases are projected to occur without RCV. In contrast, fewer than 60,000 cases are estimated if RCV is introduced with catch-up and follow-up supplementary immunization activities, averting more than an estimated 986,000 CRS cases over 30 years. Based in part on these estimates, in September 2024, the World Health Organization Strategic Advisory Group of Experts on Immunization recommended removing the ≥80% coverage threshold and instituting universal RCV introduction in these countries. RCV introduction in these 19 countries during 2025-2030 could rapidly accelerate progress toward rubella and CRS elimination worldwide.
<i>Notes from the Field</i>: HeatRisk Forecasts and Emergency Department Visits for Heat-Related Illness — New York, May–September 2024
Authors: Neil A. Muscatiello, Wanhsiang Hsu, Heather Aydin-Ghormoz, Charlene Weng, Vajeera Dorabawila, Kathleen F. Bush, Ambarish Vaidyanathan
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
Elevated Blood Lead Levels in a Pregnant Woman and her Family from Traditional <i>Kansa</i> (Bronze) and <i>Pital</i> (Brass) Metalware — New York City, 2024
Authors: Paromita Hore, Kolapo Alex-Oni, Slavenka Sedlar, Nevila Bardhi, Jacqueline Ehrlich
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Lead exposure, even at low levels, can cause detrimental health effects across all ages. The New York City (NYC) Department of Health and Mental Hygiene receives blood lead results for NYC residents who are tested for lead and routinely conducts investigations to determine sources of lead exposure. In July 2024, blood lead surveillance activities in NYC revealed high levels of lead in traditional kansa (bronze) and pital (brass) metalware from Nepal. Use of these metalware items for preparing and serving food and drinks was associated with blood lead levels above the Council of State and Territorial Epidemiologists' blood lead reference value of 3.5 μg/dL in a pregnant woman, her spouse, and their child (range = 6-18.7 μg/dL). Clinicians and public health professionals should be aware that traditional metalware from around the world can contain high levels of lead, and when used to prepare or serve food and drinks, can be communal sources of lead exposure.
Pyrophosphate‐Containing Calcium Phosphates Negatively Impact Heterotopic Bone Quality
Authors: Martina Jolic, Isabella Åberg, Omar Omar, Håkan Engqvist, Thomas Engstrand, Anders Palmquist, Peter Thomsen, Furqan A. Shah
Journal: Advanced Healthcare Materials (2025)

Abstract In bone, critical size defects pose substantial challenge in maxillofacial and orthopedic reconstructions as they are incapable of spontaneous regeneration. In such cases, autografts, allografts, and bone graft substitutes are used. Calcium phosphates (CaP) are widely used bone graft substitutes due to their biocompatibility, osteoconductive properties, and potential for osteoinductivity. CaP materials containing monetite, beta‐tricalcium phosphate (β‐TCP), and a small amount of calcium pyrophosphate (Ca‐PP) possess both osteoconductive and osteoinductive properties. However, the role of Ca‐PP in osteoinduction and material degradation remains unexplored. This study investigates heterotopic bone formation in response to five CaP compositions, maintaining a constant monetite to β‐TCP ratio, with varying amounts of Ca‐PP (0–12.5%). Twelve adult female sheep ( Ovis aries ) are subcutaneously implanted with constructs made of six CaP tiles interconnected by a Ti6Al4V frame and a control implant. Histological analysis, backscattered electron scanning electron microscopy, and Raman spectroscopy of samples retrieved at 12‐ and 52 weeks reveal that Ca‐PP does not hinder heterotopic bone formation and minimally impacts CaP degradation. While monetite and β‐TCP transform into apatite, the Ca‐PP phase remains unchanged. The addition of Ca‐PP to the CaP influences heterotopic bone quality and inflammatory response during tissue regeneration.
Recurrent Events Analysis of MASTER DAPT: Total Ischemic and Bleeding Events After Abbreviated vs Prolonged DAPT in HBR Patient
Authors: Dario Bongiovanni, Antonio Landi, Enrico Frigoli, Dik Heg, Konstantina Chalkou, Jozef Bartunek, Laurent Delorme, Willem Dewilde, David Hildick-Smith, Gregor Leibundgut, Sergio Leonardi, Maciej Lesiak, Petr Kala, Sasko Kedev, Marco Roffi, Goran Stankovic, Pim A L Tonino, Vasil Velchev, Pascal Vranckx, Stephan Windecker, Pieter C Smits, Marco Valgimigli
Journal: Journal of the American College of Cardiology (2025)
CellLENS enables cross-domain information fusion for enhanced cell population delineation in single-cell spatial omics data
Authors: Bokai Zhu, Sheng Gao, Shuxiao Chen, Yuchen Wang, Jason Yeung, Yunhao Bai, Amy Y Huang, Yao Yu Yeo, Guanrui Liao, Shulin Mao, Zhenghui G Jiang, Scott J Rodig, Ka-Chun Wong, Alex K Shalek, Garry P Nolan, Sizun Jiang, Zongming Ma
Journal: Nature Immunology (2025)
Microglia activation orchestrates CXCL10-mediated CD8+ T cell recruitment to promote aging-related white matter degeneration
Authors: Janos Groh, Ruoqing Feng, Xidi Yuan, Lu Liu, Dennis Klein, Gladis Hutahaean, Elisabeth Butz, Zhen Wang, Lisa Steinbrecher, Jonas Neher, Rudolf Martini, Mikael Simons
Journal: Nature Neuroscience (2025)

Abstract Aging is the major risk factor for neurodegeneration and is associated with structural and functional alterations in white matter. Myelin is particularly vulnerable to aging, resulting in white matter-associated microglia activation. Here we used pharmacological and genetic approaches to investigate microglial functions related to aging-associated changes in myelinated axons of mice. Our results reveal that maladaptive microglia activation promotes the accumulation of harmful CD8 + T cells, leading to the degeneration of myelinated axons and subsequent impairment of brain function and behavior. We characterize glial heterogeneity and aging-related changes in white matter by single-cell and spatial transcriptomics and reveal elaborate glial–immune interactions. Mechanistically, we show that the CXCL10–CXCR3 axis is crucial for the recruitment and retention of CD8 + T cells in aged white matter, where they exert pathogenic effects. Our results indicate that myelin-related microglia dysfunction promotes adaptive immune reactions in aging and identify putative targets to mitigate their detrimental impact.
Tumor antigens preferentially derive from unmutated genomic sequences in melanoma and non-small cell lung cancer
Authors: Anca Apavaloaei, Qingchuan Zhao, Leslie Hesnard, Maxime Cahuzac, Chantal Durette, Jean-David Larouche, Marie-Pierre Hardy, Krystel Vincent, Sylvie Brochu, Jean-Philippe Laverdure, Joël Lanoix, Mathieu Courcelles, Patrick Gendron, Mathieu Lajoie, Maria Virginia Ruiz Cuevas, Eralda Kina, Julie Perrault, Juliette Humeau, Grégory Ehx, Sébastien Lemieux, Ian R Watson, Daniel E Speiser, Michal Bassani-Sternberg, Pierre Thibault, Claude Perreault
Journal: Nature Cancer (2025)

Melanoma and non-small cell lung cancer (NSCLC) display exceptionally high mutational burdens. Hence, immune targeting in these cancers has primarily focused on tumor antigens (TAs) predicted to derive from nonsynonymous mutations. Using comprehensive proteogenomic analyses, we identified 589 TAs in cutaneous melanoma (n = 505) and NSCLC (n = 90). Of these, only 1% were derived from mutated sequences, which was explained by a low RNA expression of most nonsynonymous mutations and their localization outside genomic regions proficient for major histocompatibility complex (MHC) class I-associated peptide generation. By contrast, 99% of TAs originated from unmutated genomic sequences specific to cancer (aberrantly expressed tumor-specific antigens (aeTSAs), n = 220), overexpressed in cancer (tumor-associated antigens (TAAs), n = 165) or specific to the cell lineage of origin (lineage-specific antigens (LSAs), n = 198). Expression of aeTSAs was epigenetically regulated, and most were encoded by noncanonical genomic sequences. aeTSAs were shared among tumor samples, were immunogenic and could contribute to the response to immune checkpoint blockade observed in previous studies, supporting their immune targeting across cancers.
Inequality in infrastructure access and its association with health disparities
Authors: Ying Tu, Bin Chen, Chuan Liao, Shengbiao Wu, Jiafu An, Chen Lin, Peng Gong, Bin Chen, Hong Wei, Bing Xu
Journal: Nature Human Behaviour (2025)

Abstract Economic, social and environmental infrastructure forms a fundamental pillar of societal development. Ensuring equitable access to infrastructure for all residents is crucial for achieving the Sustainable Development Goals, yet knowledge gaps remain in infrastructure accessibility and inequality and their associations with human health. Here we generate gridded maps of economic, social and environmental infrastructure distribution and apply population-weighted exposure models and mixed-effects regressions to investigate differences in population access to infrastructure and their health implications across 166 countries. The results reveal contrasting inequalities in infrastructure access across regions and infrastructure types. Global South countries experience only 50–80% of the infrastructure access of Global North countries, whereas their associated inequality levels are 9–44% higher. Both infrastructure access and inequality are linked to health outcomes, with this relationship being especially pronounced in economic infrastructure. These findings underscore the necessity of informed decision-making to rectify infrastructure disparities for promoting human well-being.
Mechanics Mediated Semi‐Convertible Hydrogel Enabled Sustained Drug Release
Authors: Hongyue Jiang, Xing Lu, Tianshi Bu, Xuhao Yang, Xiang Li, Xue Ren, Xinyi Xu, Chengcheng Fan, Jingxuan He, Xiaopeng Zhang, Wenlong Song, Wenjing Tian, Bin Xu
Journal: Advanced Healthcare Materials (2025)

Abstract The dynamic mechanic environment surrounding the wound may retard wound healing, and even lead to an exacerbation of inflammation and scar. How to actively promote wound healing under a dynamic mechanical environment during human motion is still a long‐standing challenge. Therefore, a mechanics mediated semi‐convertible hydrogel (M ech SCH) loaded with drug is proposed in this study employing the synergistic interaction between mechanics mediated supramolecular non‐covalent networks and polyvinyl alcohol/Gelatin polymer networks for enhancing dynamic wound healing. The formed M ech SCH exhibits a partial gel‐sol transition even under a shear stress of ≈9.04 Pa that is satisfied with most tissues or organs' stress. The sustained release of encapsulated drugs would be efficiently compared with the mechanics of non‐sensitive polyvinyl alcohol/Gelatin hydrogel. The loaded platelet‐derived growth factor (PDGF) of the M ech SCH exhibited a rapid onset of therapeutic effect in a mice dorsal full‐thickness dermal wound model, which demonstrated sustaining drug release through mechanics of skin tension at the wound site, along with alleviating the inflammation and promoting rapid vascular regeneration. This mechanics mediated semi‐convertible hydrogel presents potential clinical applications for the dynamic management of chronic wounds.
KK2845, a PBD dimer-containing antibody-drug conjugate targeting TIM-3-expressing AML
Authors: Jian Zou, Haruka Kinosada, Shin-Ichiro Takayanagi, Toshihiko Ishii, Toru Amano, Kaito Nihira, Shohei Kanie, Maiko Adachi, Harunobu Tahara, Teppei Sakoda, Yoshikane Kikushige, Koichi Akashi, Hidetaka Satou
Journal: Leukemia (2025)

Acute myeloid leukemia (AML) is a common hematopoietic malignancy with high recurrence rates, and there is an urgent need for new therapeutic agents. T-cell immunoglobulin mucin-3 (TIM-3) is expressed on the surface of both LSCs and blasts in most AML patients, but not in normal hematopoietic stem cells (HSCs). We have developed KK2845, an antibody drug conjugate (ADC) that consists of an anti-TIM-3 fully human IgG1 antibody, a valine-alanine linker and a highly potent DNA cross-linking pyrrolobenzodiazepine (PBD) dimer SG3199. KK2845 exhibited potent cytotoxicity against AML cells both in vitro and in vivo. The cytotoxicity against AML cells was almost comparable between KK2845 and CD33-ADC, an anti-CD33 antibody conjugated with PBD dimer that has shown high remission rates in clinical studies. In addition to the cytotoxicity depending on PBD dimer, KK2845 also showed potent antibody-dependent cell cytotoxicity (ADCC) activity against AML cells. KK2845 showed less cytotoxicity against human normal bone marrow cells than CD33-ADC. The pharmacokinetics of KK2845 in cynomolgus monkey after intravenous infusion demonstrated a favorable profile. Taken together, these data suggest that KK2845 could be a novel ADC therapeutic in AML.
Impact of optical coherence tomography-based post-PCI physiology assessment to predict clinical outcomes: an ILUMIEN-IV substudy
Authors: Thomas W Johnson, Brian A Bergmark, Kevin Croce, Dario Pellegrini, Akiko Maehara, Tommaso Gori, Natalia Pinilla-Echeverri, Jason Wollmuth, Nieves Gonzalo, Hsien-Li Kao, Giulio Guagliumi, Kanitha Phalakornkule, Divine Ediebah, JoAnna McNutt, Wei-Che Chiu, Jorn Op den Buijs, Jana Buccola, Ulf Landmesser, Ziad Ali, Gregg W Stone, Allen Jeremias
Journal: Journal of the American College of Cardiology (2025)

A novel optical coherence tomography (OCT)-based physiology assessment technique, virtual flow reserve (VFR), has been demonstrated to perform as a reliable surrogate for invasive physiology. We sought to examine the performance of post-PCI VFR as a predictor of 2-year clinical outcomes independent from the OCT-based minimal stent area (MSA). The ILUMIEN-IV trial prospectively recruited 2487 patients with diabetes or high-risk coronary lesions randomizing to OCT- versus angiography-guided drug-eluting stent implantation. All patients with single lesion treatment, who had a final OCT imaging available, underwent retrospective post-PCI VFR analysis offline. Of 2128 eligible patients, VFR analysis was successfully performed in 2057 (96.6%). Independent OCT predictors for the primary endpoint of 2-year target vessel failure (TVF), a composite of cardiac death, target-vessel myocardial infarction and ischemia-driven target vessel revascularization, were evaluated by multivariable analysis. The median [25th percentile, 75% percentile] post-PCI VFR was 0.90 [0.86, 0.92], with a significant difference in VFR observed between the angiography- and OCT-guided groups (0.89 [0.86, 0.92] vs 0.90 [0.87, 0.92], p<0.001). By multivariable analysis both MSA (per 1mm2) and VFR (per 0.1 mmHg/mmHg) were independent predictors of 2-year TVF. Overall, MSA, proximal edge dissection and VFR independently predicted both TVF and target lesion failure. Post-PCI OCT-based VFR assessment is predictive of 2-year clinical outcomes independent of MSA. Online VFR analysis can provide operators with an immediate assessment of post-PCI physiology in addition to OCT anatomy, providing incremental value in assessing procedural success and informing on clinical prognosis.