tbuckley/cabot-search huggingface dataset:
SGLT2 Inhibitors: Risks and Benefits
Authors: Iad Alhallak
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Background: Inconsistent meta-analysis results and the increased risk of co-morbid conditions in type two diabetes make it challenging to distinguish if adverse effects of Fournier’s Gangrene, acute kidney injury, ketoacidosis, genitourinary fungal infections, amputations, and bone fractures are attributed to SGLT2 inhibitors. Methods: This is a retrospective cohort study that calculates the relative risk and hazard ratio using the Food and Drug Administration Adverse Event Reporting System to compare the users of metformin and the SGLT2 inhibitors for adverse events. The Medical Expenditure Panel Survey database was used to generate total users of dapagliflozin, empagliflozin, canagliflozin, and metformin from the years 2014-2021. Results: We observed an average increased risk of Fournier’s Gangrene by 156-fold, ketoacidosis by 67-fold, genitourinary fungal infections by 185-fold, amputations by 277-fold, and bone fractures by 15-fold compared to individuals taking metformin. Canagliflozin had the highest increased risk in all categories except for Fournier’s Gangrene, and empagliflozin did not have an increased relative risk of acute kidney injury. Conclusion: We measured an increase in complications of patients on SGLT2 inhibitors, especially canagliflozin, compared to patients on metformin. We as health providers should re-evaluate our patients with increased risks of these complications and reassess if the cardiovascular benefits outweigh the possible dangerous side effects.
A new method for detecting mixed Mycobacterium tuberculosis infection and reconstructing constituent strains provides insights into transmission
Authors: Benjamin Sobkowiak, Patrick Cudahy, Melanie H. Chitwood, Taane G. Clark, Caroline Colijn, Louis Grandjean, Katharine S. Walter, Valeriu Crudu, Ted Cohen
Journal: Genome Medicine (2025)

Abstract Background Mixed infection with multiple strains of the same pathogen in a single host can present clinical and analytical challenges. Whole genome sequence (WGS) data can identify signals of multiple strains in samples, though the precision of previous methods can be improved. Here, we present MixInfect2, a new tool to accurately detect mixed samples from Mycobacterium tuberculosis short-read WGS data. We then evaluate three approaches for reconstructing the underlying mixed constituent strain sequences. This allows these samples to be included in downstream analysis to gain insights into the epidemiology and transmission of mixed infections. Methods We employed a Gaussian mixture model to cluster allele frequencies at mixed sites (hSNPs) in each sample to identify signals of multiple strains. Building upon our previous tool, MixInfect, we increased the accuracy of classifying in vitro mixed samples through multiple improvements to the bioinformatic pipeline. Major and minor proportion constituent strains were reconstructed using three approaches and assessed by comparing the estimated sequence to the known constituent strain sequence. Lastly, mixed infections in a real-world Mycobacterium tuberculosis population from Moldova were detected with MixInfect2 and clusters of recent transmission that included major and minor constituent strains were built. Results All 36/36 in vitro mixed and 12/12 non-mixed samples were correctly classified with MixInfect2, and major strain proportions were estimated with high accuracy (within 3% of the true strain proportion), outperforming previous tools. Reconstructed major strain sequences closely matched the true constituent sequence by taking the allele at the highest frequency at hSNPs, while the best-performing approach to reconstruct the minor proportion strain sequence was identifying the closest non-mixed isolate in the same population, though no approach was effective when the minor strain proportion was at 5%. Finally, fewer mixed infections were identified in Moldova than previous estimates (6.6% vs 17.4%) and we found multiple instances where the constituent strains of mixed samples were present in transmission clusters. Conclusions MixInfect2 accurately detects samples with evidence of mixed infection from short-read WGS data and provides an excellent estimate of the mixture proportions. While there are limitations in reconstructing the constituent strain sequences of mixed samples, we present recommendations for the best approach to include these isolates in further analyses.
Kdm2a inhibition in skeletal muscle improves metabolic flexibility in obesity
Authors: Yuhan Wang, Hao Xie, Qianrui Liu, Na Wang, Xi Luo, Fei Sun, Jinghan Zhu, Ruihan Dong, Yi Wang, Jia Gao, Zhichao Gao, Teng Huang, Xin Liu, Qilin Yu, Ting Wang, Yang Li, Danni Song, Shiwei Liu, Shu Zhang, Hao Yin, Wen Kong, Cong-Yi Wang
Journal: Nature Metabolism (2025)
Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis
Authors: Ali Aminian, Abdullah Aljabri, Sarah Wang, James Bena, Daniela S Allende, Hana Rosen, Eileen Arnold, Rickesha Wilson, Alex Milinovich, Rohit Loomba, Arun J Sanyal, Naim Alkhouri, Jamile Wakim-Fleming, Sobia N Laique, Srinivasan Dasarathy, Arthur J McCullough, Steven E Nissen
Journal: Nature Medicine (2025)
Retrieval of conditioned immune response in male mice is mediated by an anterior–posterior insula circuit
Authors: Haneen Kayyal, Federica Cruciani, Sailendrakumar Kolatt Chandran, Efrat Edry, Sagie Schif-Zuck, Tamar Koren, Adonis Yiannakas, Asya Rolls, Amiram Ariel, Kobi Rosenblum
Journal: Nature Neuroscience (2025)
2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association
Authors: Seth S. Martin, Aaron W. Aday, Norrina B. Allen, Zaid I. Almarzooq, Cheryl A.M. Anderson, Pankaj Arora, Christy L. Avery, Carissa M. Baker-Smith, Nisha Bansal, Andrea Z. Beaton, Yvonne Commodore-Mensah, Maria E. Currie, Mitchell S.V. Elkind, Wenjun Fan, Giuliano Generoso, Bethany Barone Gibbs, Debra G. Heard, Swapnil Hiremath, Michelle C. Johansen, Dhruv S. Kazi, Darae Ko, Michelle H. Leppert, Jared W. Magnani, Erin D. Michos, Michael E. Mussolino, Nisha I. Parikh, Sarah M. Perman, Mary Rezk-Hanna, Gregory A. Roth, Nilay S. Shah, Mellanie V. Springer, Marie-Pierre St-Onge, Evan L. Thacker, Sarah M. Urbut, Harriette G.C. Van Spall, Jenifer H. Voeks, Seamus P. Whelton, Nathan D. Wong, Sally S. Wong, Kristine Yaffe, Latha P. Palaniappan
Journal: Circulation (2025)

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2025 AHA Statistical Update is the product of a full year’s worth of effort in 2024 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. This year’s edition includes a continued focus on health equity across several key domains and enhanced global data that reflect improved methods and incorporation of ≈3000 new data sources since last year’s Statistical Update. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
sMAdCAM‐1 is decreased after allo‐HCT, along with gut microbiota dysbiosis, and is associated with hematopoietic recovery
Authors: Karen Fadel, Lama Siblany, Razan Mohty, Nicolas Stocker, Ludovic Suner, Eolia Brissot, Anne Banet, Simona Sestili, Rémy Duléry, Zoé Van de Wyngaert, Laure Ricard, Ramdane Belhocine, Agnès Bonnin, Antoine Capes, Tounes Ledraa, Frederic De Vassoigne, Harry Sokol, Mohamad Mohty, Béatrice Gaugler, Florent Malard
Journal: HemaSphere (2025)
Limited stage mantle cell lymphoma: A real‐world study of primary treatment and prognosis in Sweden 2006–2018
Authors: Alexandra Albertsson‐Lindblad, Sara Ekberg, Ingrid Glimelius, Fredrik Ellin, Kristina Sonnevi, Catharina Lewerin, Lena Brandefors, Karin E. Smedby, Mats Jerkeman
Journal: HemaSphere (2025)
From X‐ To J‐Aggregation: Subtly Managing Intermolecular Interactions for Superior Phototheranostics with Precise 1064 nm Excitation
Authors: Jun Tang, Leilei Si, Yigang Wang, Guomin Xia, Hongming Wang
Journal: Advanced Healthcare Materials (2025)

Abstract The stacking mode in aggregate state results from a delicate balance of supramolecular interactions, which closely affects the optoelectronic properties of organic π‐conjugated systems. Then, managing these interactions is crucial for advancing phototheranostics, yet remains challenging. A subtle strategy involving peripheral phenyl groups is debuted herein to transform X‐aggregated SQ‐H into J‐aggregated SQ‐Ph, reorienting intermolecular dipole interactions while rationally modulating π–π interactions. Co‐assembled with liposomes (DSPE‐PEG2000), SQ‐Ph nanoparticles (NPs) exhibit low toxicity, superior biocompatibility, and a bathochromic shift to the 1064 nm match‐excited NIR‐II region, with a fluorescence brightness (ε 1064 nm Φ NIR‐II ) of 4129 M −1 cm −1 and a photothermal conversion efficiency (PCE) of 48.3%. Preliminary in vivo experiments demonstrate that SQ‐Ph NPs achieve a signal‐to‐background ratio (SBR) of up to 14.29 in NIR‐II fluorescence imaging (FLI), enabling highly efficient photothermal therapy (PTT) of tumors guided by combined photoacoustic imaging (PAI). This study not only enriches the J‐aggregation library but also provides a paradigm for optimizing photosensitizers at the supramolecular level.
Pro‐inflammatory dietary pattern and the risk of female gout: sex‐specific findings from three prospective cohort studies
Authors: Sharan K. Rai, Hyon K. Choi, Na Lu, Chio Yokose, Kehuan Lin, Dong Hoon Lee, Fred K. Tabung, Natalie McCormick
Journal: Arthritis & Rheumatology (2025)

Objective We aimed to determine whether a pro‐inflammatory dietary pattern (mechanism‐based diet) is associated with incident female gout among two large cohorts of US women. Methods We prospectively followed 79,104 women from Nurses’ Health Study (NHS; 1984‐2016) and 93,454 women from NHSII (1991‐2017); 45,445 men from Health Professionals Follow‐up Study (1986‐2016) served as a comparison cohort. Validated food frequency questionnaires were used to calculate Empirical Dietary Inflammatory Pattern (EDIP; food‐based index predictive of circulating inflammatory biomarkers) scores every 4‐years. Cox proportional hazards models were used to evaluate multivariable associations between EDIP and incident, physician‐diagnosed gout. We further tested whether these associations were independent of key guideline‐based healthy eating patterns that previously showed beneficial associations with gout (i.e., Dietary Approaches to Stop Hypertension [DASH], Alternative Health Eating Index [AHEI]). Results We documented 5,425 incident female gout cases over 4,372,320 person‐years. EDIP was positively associated with female gout risk; hazard ratio (HR; 95% confidence interval [CI]) for the most vs. least pro‐inflammatory quintile was 2.02 (1.83, 2.22). Additional adjustment for BMI attenuated this association (HR=1.71 [1.55, 1.88]). Reversing the EDIP score, women in the most anti‐inflammatory EDIP quintile had largest magnitude of protective association for gout (HR=0.58 [0.53, 0.65]) compared to HRs for healthiest DASH (0.80 [0.73, 0.87]) and AHEI quintiles (0.81 [0.74, 0.89]). The magnitude of association between EDIP and male gout was substantially smaller (HR=1.24 [1.13, 1.37]; P‐heterogeneity &lt;0.0001). Conclusion These findings support a pivotal role of inflammation as a potential modulator between diet and gout onset, particularly among women.
Systemic Sclerosis: a multisystem disease, time to think beyond scleroderma
Authors: Yannick Allanore, Shervin Assassi
Journal: Arthritis & Rheumatology (2025)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Efficacy, Safety, Pharmacokinetics, and Immunogenicity of <scp>ABBV</scp>‐154 in Adults With Glucocorticoid‐Dependent Polymyalgia Rheumatica: A Phase 2, Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Robert F. Spiera, Valerie Devauchelle‐Pensec, Claire E. Owen, Federico Díaz‐González, Tsutomu Takeuchi, Edit Drescher, Jaclyn Anderson, Dilek Arikan, Ronilda D'Cunha, Julie Parmentier, Denise T. Kruzikas, Weihan Zhao, Yang Yang, Karen Stellpflug, Frank Buttgereit
Journal: Arthritis & Rheumatology (2025)

Objective An unmet need exists for glucocorticoid‐sparing treatments for patients with polymyalgia rheumatica (PMR). The antibody‐drug conjugate ABBV‐154 comprises adalimumab conjugated to a glucocorticoid receptor modulator. We evaluated ABBV‐154 versus placebo in patients with glucocorticoid‐dependent PMR. Methods In this phase 2, randomized, double‐blind, placebo‐controlled, dose‐ranging study, eligible patients had confirmed PMR, glucocorticoid response and ≥2 unequivocal PMR flares while tapering glucocorticoids and still on ≥ 5 mg daily prednisone equivalent. Randomized patients received subcutaneous placebo or ABBV‐154 40, 150, or 340 mg once every other week. The primary efficacy endpoint was time to flare. The sponsor voluntarily terminated the study early. Results Overall, 181 patients were randomized (placebo, n = 50; ABBV‐154: 40 mg, n = 42; 150 mg, n = 45; 340 mg, n = 44) and 67.4% completed study drug at week 24 Time to flare was longer for patients receiving ABBV‐154 than those receiving placebo, with Kaplan‐Meier estimate of 24‐week flare‐free rate being lower for placebo. The hazard ratios of ABBV‐154 vs placebo (95% confidence interval) were 0.49 (0.27, 0.88), P = 0.017 for 40 mg; 0.44 [0.25, 0.79], P = 0.006 for 150 mg; 0.20 [0.09, 0.42], P &lt; 0.001 for 340 mg. Incidences of treatment‐emergent adverse events were similar between groups, and the most common across ABBV‐154 cohorts was COVID‐19 (16.0%). Conclusion Treatment effects were observed for ABBV‐154 cohorts compared with placebo for time to flare. ABBV‐154 was generally well tolerated. Due to early study termination, results should be interpreted with caution. ClinicalTrials.gov identifier: NCT04972968
International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma
Authors: Luciano J. Costa, Rahul Banerjee, Hira Mian, Katja Weisel, Susan Bal, Benjamin A. Derman, Maung M. Htut, Chandramouli Nagarajan, Cesar Rodriguez, Joshua Richter, Matthew J. Frigault, Jing C. Ye, Niels W. C. J. van de Donk, Peter M. Voorhees, Benjamin Puliafito, Nizar Bahlis, Rakesh Popat, Wee Joo Chng, P. Joy Ho, Gurbakhash Kaur, Prashant Kapoor, Juan Du, Fredrik Schjesvold, Jesus Berdeja, Hermann Einsele, Adam D. Cohen, Joseph Mikhael, Yelak Biru, S. Vincent Rajkumar, Yi Lin, Thomas G. Martin, Ajai Chari
Journal: Leukemia (2025)

Abstract T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein–coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies. The International Myeloma Working Group conveyed panel of experts to review patient and disease-related factors affecting efficacy and safety of immunotherapy, summarize existing information on sequencing therapy and provide a series of core recommendations.
Effective eradication of acute myeloid leukemia stem cells with FLT3-directed antibody-drug conjugates
Authors: Marina Able, Marc-André Kasper, Binje Vick, Jonathan Schwach, Xiang Gao, Saskia Schmitt, Belay Tizazu, Amrei Fischer, Sarah Künzl, Marit Leilich, Isabelle Mai, Philipp Ochtrop, Andreas Stengl, Mark A. R. de Geus, Michael von Bergwelt-Baildon, Dominik Schumacher, Jonas Helma, Christian P. R. Hackenberger, Katharina S. Götze, Irmela Jeremias, Heinrich Leonhardt, Michaela Feuring, Karsten Spiekermann
Journal: Leukemia (2025)

Abstract Refractory disease and relapse are major challenges in acute myeloid leukemia (AML) therapy attributed to survival of leukemic stem cells (LSC). To target LSCs, antibody-drug conjugates (ADCs) provide an elegant solution, combining the specificity of antibodies with highly potent payloads. We aimed to investigate if FLT3-20D9h3-ADCs delivering either the DNA-alkylator duocarmycin (DUBA) or the microtubule-toxin monomethyl auristatin F (MMAF) can eradicate quiescent LSCs. We show here that DUBA more potently kills cell-cycle arrested AML cells compared to microtubule-targeting auristatins. Due to limited stability of 20D9h3-DUBA ADC in vivo, we analyzed both ADCs in advanced in vitro stem cell assays. 20D9h3-DUBA successfully eliminated leukemic progenitors in vitro in colony-forming unit and long-term culture initiating cell assays, both in patient cells and in patient-derived xenograft (PDX) cells. Further, it completely prevented engraftment of AML PDX leukemia-initiating cells in NSG mice. 20D9h3-MMAF had a similar effect in engraftment assays, but a less prominent effect in colony assays. Both ADCs did not affect healthy stem and progenitor cells at comparable doses providing the rationale for FLT3 as therapeutic LSC target. Collectively, we show that FLT3-directed ADCs with DUBA or MMAF have potent activity against AML LSCs and represent promising candidates for further clinical development.
Advances in Electrochemical Nitrite Reduction toward Nitric Oxide Synthesis for Biomedical Applications
Authors: Xun He, Chang Zou, Limei Zhang, Peilin Wu, Yongchao Yao, Kai Dong, Yuchun Ren, Wenchuang (Walter) Hu, Yi Li, Han Luo, Binwu Ying, Fengming Luo, Xuping Sun
Journal: Advanced Healthcare Materials (2025)

Nitric oxide (NO) is an essential molecule in biomedicine, recognized for its antibacterial properties, neuronal modulation, and use in inhalation therapies. The effectiveness of NO-based treatments relies on precise control of NO concentrations tailored to specific therapeutic needs. Electrochemical generation of NO (E-NOgen) via nitrite (NO2 -) reduction offers a scalable and efficient route for controlled NO production, while also addressing environmental concerns by reducing NO2 - pollution and maintaining nitrogen cycle balance. Recent developments in catalysts and E-NOgen devices have propelled NO2 - conversion, enabling on-demand NO production. This review provides an overview of NO2 - reduction pathways, with a focus on cutting-edge Fe/Cu-based E-NOgen catalysts, and explores the development of E-NOgen devices for biomedical use. Challenges and future directions for advancing E-NOgen technologies are also discussed.
Selective In Situ Analysis of Hepatogenic Exosomal microRNAs via Virus‐Mimicking Multifunctional Magnetic Vesicles
Authors: Lingchang Meng, Lulu Wang, Zhiting Sun, Genglin Mu, Zhiyang Li, Jing Wu
Journal: Advanced Healthcare Materials (2025)

Abstract Drug‐induced liver injury (DILI) is a common clinical problem with urgent respect to demanding early diagnosis. Exosomal miRNAs are reliable and noninvasive biomarkers for the early diagnosis of DILI. However, accurate and feasible detection of exosomal miRNAs is often hampered by the low abundance of miRNAs, inefficient exosome separation techniques, and the requirement for RNA extraction from large sample volumes. Here, the multifunctional magnetic vesicles are constructed by loading a multiple signal amplification detection system and magnetic nanoparticles into virus‐mimicking engineered vesicles to achieve in situ analysis of hepatogenic exosomal miRNAs, which do not require miRNA extraction or target amplification. Virus‐mimicking engineered vesicles carrying large surface proteins of hepatitis B virus are designed to achieve the specific identity and fusion of hepatogenic exosomes, and the multiple signal amplification detection system assembled by catalytic hairpin assembly technology and CRISPR/Cas13a technology can achieve highly sensitive in situ detection of miRNAs in exosomes with a low limit of detection (LOD) of 1.25 × 10 2 particles·µL −1 . This novel nanoplatforms open a promising avenue for the early clinical diagnosis of DILI.
Probability of remission with reinduction with 7+3 versus high-dose cytarabine: analysis of SWOG trial S1203
Authors: Megan Othus, Guillermo Garcia-Manero, Frederick R Appelbaum, Harry P Erba, Eliana Dietrich, Suravi Raychaudhuri, Jacob Appelbaum, Elihu Estey, Mary-Elizabeth Percival
Journal: Leukemia (2025)
A systematic review of portable technologies for the early assessment of motor development in infants
Authors: Weiyang Deng, Megan K. O’Brien, Rachel A. Andersen, Richa Rai, Erin Jones, Arun Jayaraman
Journal: npj Digital Medicine (2025)

Early screening and evaluation of infant motor development are crucial for detecting motor deficits and enabling timely interventions. Traditional clinical assessments are often subjective, without fully capturing infants' "real-world" behavior. This has sparked interest in portable, low-cost technologies to objectively and precisely measure infant motion at home, with a goal of enhancing ecological validity. In this systematic review, we explored the current landscape of portable, technology-based solutions to assess early motor development (within the first year), outlining the prevailing challenges and future directions. We reviewed 66 publications, which utilized video, sensors, or a combination of technologies. There were three key applications of these technologies: (1) automating clinical assessments, (2) illuminating new measures of motor development, and (3) predicting developmental outcomes. There was a promising trend toward earlier and more accurate detection using portable technologies. Additional research and demographic diversity are needed to develop fully automated, robust, and user-friendly tools. Registration & Protocol OSF Registries https://doi.org/10.17605/OSF.IO/R6JAE .