tbuckley/cabot-search huggingface dataset:
A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy
Authors: Thomas U Marron, Jason J Luke, Brianna Hoffner, Jane Perlmutter, Connie Szczepanek, Valsamo Anagnostou, Ann W Silk, Pedro J Romero, Elizabeth Garrett-Mayer, Leisha A Emens
Journal: Journal for ImmunoTherapy of Cancer (2025)

Clinical trials of cancer immunotherapy (IO) were historically based on a drug development paradigm built for chemotherapies. The remarkable clinical activity of programmed cell death protein 1/programmed death ligand 1 blockade, chimeric antigen receptor-T cells, and T cell engagers yielded new insights into how the mechanistic underpinnings of IO are reflected in the clinic. These insights and the sheer number of novel immunotherapies currently in the pipeline have made it clear that our strategies and tools for IO drug development must adapt. Recent innovations like engineered T cells and tumor-infiltrating lymphocytes demonstrate that immune-based treatments may rely on real-time manufacturing programs rather than off-the-shelf drugs. We now recognize adoptively transferred cells as living drugs. Progression criteria have been redefined due to the unique response patterns of IO. Harnessing the power of both biomarkers and the neoadjuvant setting earlier in drug development is of broad interest. The US Food and Drug Association is increasingly impacting the design of trials with respect to dose optimization and clinical endpoints. The use of novel endpoints such as pathologic complete/major response, treatment-free survival, and minimal residual disease is becoming more common. There is growing acceptance of using patient-reported outcomes as trial endpoints to better measure the true clinical benefit and impact of novel IO agents on quality of life. New opportunities created by modern data science and artificial intelligence to inform and accelerate drug development continue to emerge. The importance of streamlining the clinical research ecosystem and enhancing clinical trial access to facilitate the enrollment of diverse patient populations is broadly recognized. Patient advocacy is critical both to drive the science of IO, and to promote patient satisfaction. To capitalize on these opportunities, the Society for Immunotherapy of Cancer (SITC) has established a goal of at least 100 new, unique IO approvals over the next 10 years. Accordingly, SITC has developed initiatives designed to integrate the viewpoints of diverse stakeholders and galvanize the field in further adapting clinical trials to the unique features of IO, moving us closer to our ultimate goal of using IO to cure and prevent cancer.
Impact of mineralocorticoid receptor antagonists on the risk of sudden cardiac death across cardio‐kidney‐metabolic diseases: A meta‐analysis of randomized clinical trials
Authors: Pedro Marques, Faiez Zannad, João Pedro Ferreira
Journal: European Journal of Heart Failure (2025)

Abstract Aims Sudden cardiac death (SCD) is a prevalent cause of mortality among patients with cardio‐kidney‐metabolic (CKM) diseases. Mineralocorticoid receptor antagonists (MRAs) reduce the risk of SCD in patients with left ventricular dysfunction, but it is unclear if similar effects are expected across different CKM risk populations irrespective of ejection fraction. Methods and results A random‐effects meta‐analysis of randomized clinical trials (RCTs) of MRA (vs. placebo) on the occurrence of SCD was performed. The number of reported SCD events were collected from the individual RCTs and the respective odds ratio (OR) and 95% confidence intervals (95% CI) calculated. Data from five major RCTs were collected including over 31 000 patients. Overall, MRAs, compared with placebo, reduced the occurrence of SCD (OR 0.79, 95% CI 0.70–0.89, p &lt; 0.001). No significant heterogeneity was found across trials ( I 2 = 0%, Q = 0.38, p = 0.98). Conclusion This meta‐analysis supports the benefit of MRAs for SCD risk reduction across CKM risk and irrespective of ejection fraction.
Final Survival Results from the Penelope-B trial investigating palbociclib vs placebo for patients with high-risk HR+/HER2- breast cancer and residual disease after neoadjuvant chemotherapy – PENELOPE-B
Authors: S Loibl, M Martin, H Bonnefoi, M Untch, S Kim, H D Bear, J A García-Sáenz, M M Olivé, N Mc Carthy, K Gelmon, C M Kelly, S-A Im, T Reimer, M-J Noelia, Z Zhang, M Toi, L Provencher, H S Rugo, M Gnant, A Makris, A A Torres, N Hirmas, J Holtschmidt, V Nekljudova, F Marmé
Journal: Annals of Oncology (2025)
Transcriptional repressor Capicua is a gatekeeper of cell-intrinsic interferon responses
Authors: Senthamizharasi Manivasagam, Julianna Han, Athmane Teghanemt, Henry Keen, Boopathi Sownthirarajan, Boyang Cheng, Abhiraj Singh, Abigail Lewis, Olivia A Vogel, Gayathri Loganathan, Lei Huang, Maryline Panis, David K Meyerholz, Benjamin tenOever, Jasmine T Perez, Santhakumar Manicassamy, Priya D Issuree, Balaji Manicassamy
Journal: Cell Host & Microbe (2025)
Excess Mortality Rate in Black Children Since 1950 in the United States: A 70-Year Population-Based Study of Racial Inequalities
Authors: Angel Paternina-Caicedo, Oscar Espinosa, Sangini S. Sheth, Nathaniel Hupert, Soroush Saghafian
Journal: Annals of Internal Medicine (2025)

Black Americans have lower wealth, income, and education and higher mortality rates than White Americans, especially during childhood. To document the extent and persistence of excess infant and childhood mortality in Black Americans between 1950 and 2019. Population-based surveillance study. The United States of America. The entire population of the United States. The investigators analyzed mortality data collected by the Centers for Disease Control and Prevention and the U.S. Census Bureau from 1950 to 2019 and calculated mortality rates, life expectancy, and years of potential life lost for White and Black Americans to estimate the absolute and relative sex- and age-specific excess mortality burden among Black Americans compared with White Americans. The gaps in absolute life expectancy and age-standardized mortality between Black and White Americans decreased over the 70-year period beginning in 1950, but relative mortality in infants and children increased during this same period. The mortality rates in the 1950s for White and Black infants were 2703 and 5181 deaths per 100 000 persons, respectively, for an excess mortality ratio of 1.92 (95% CI, 1.91 to 1.93). In the 2010s, the mortality rates were 499 deaths per 100 000 persons in White infants and 1073 deaths per 100 000 persons in Black infants, for an excess mortality ratio of 2.15 (CI, 2.13 to 2.17). A total of 5.0 million excess deaths of Black Americans (including 522 617 infants) could have been avoided during these 7 decades if their mortality rates were equal to those of White Americans. The effect of health inequities was measured without inquiring about the causes of these differences. Black infants, children, and adults have experienced persistent excess mortality in the United States since the 1950s relative to the White population. None.
Reply to Currow <i>et al.</i>: Geographic Variation in Prevalence of Breathlessness: Latitude
Authors: Rajat Suri, Donald P. Tashkin, Russell G. Buhr, Igor Barjaktarevic
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"Reply to Currow et al.: Geographic Variation in Prevalence of Breathlessness: Latitude." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Morbidity After Takotsubo Syndrome: A Report From the Scottish Takotsubo Registry
Authors: Amelia E. Rudd, Graham W. Horgan, Jim McGowan, Arvind Sood, Ross McGeoch, John Irving, Jonathan Watt, Stephen J. Leslie, Mark C. Petrie, Chim C. Lang, Nicholas L. Mills, David E. Newby, Dana K. Dawson
Journal: Annals of Internal Medicine (2025)
Unlocking the Untapped Potential of Photoresponsive Dual‐Gas Nanomedicine in Glaucoma Therapy
Authors: Jiamin Liu, Yuan Liang, Yi Tian, Xinghuai Sun, Yuan Lei, Pengpeng Lei, Hongjie Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract Glaucoma, a leading cause of irreversible blindness worldwide, is characterized by optic nerve damage often associated with elevated intraocular pressure (IOP). Although gas therapies hold promise for glaucoma treatment, the limitations of single‐gas strategies constrain their therapeutic efficacy. Here, a photoresponsive dual‐gas nanomedicine is developed for targeted glaucoma therapy. The nanomedicine, PdH‐D‐S, is engineered by synthesizing mesoporous palladium hydride (meso‐PdH) with efficient hydrogen (H₂) storage capacity and abundant pore channels, followed by surface modification with DSPE‐mPEG and loading sodium nitroprusside (SNP) as a nitric oxide (NO) donor. PdH‐D‐S penetrates the cornea to reach IOP‐regulating tissues, including the trabecular meshwork and Schlemm's canal. Upon 808 nm laser excitation, PdH‐D‐S releases H₂ and NO in a controlled manner. H₂ activates the AKT/p‐AKT/eNOS/sGC signaling pathway, while NO binds to soluble guanylate cyclase (sGC), converting guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP), relaxing trabecular meshwork cells and enhancing aqueous humor outflow. This dual‐gas system demonstrates high therapeutic efficacy in lowering IOP and offers a mechanistic advancement in glaucoma treatment through synergistic gas therapy.
PROBAST+AI: an updated quality, risk of bias, and applicability assessment tool for prediction models using regression or artificial intelligence methods
Authors: Karel G M Moons, Johanna A A Damen, Tabea Kaul, Lotty Hooft, Constanza Andaur Navarro, Paula Dhiman, Andrew L Beam, Ben Van Calster, Leo Anthony Celi, Spiros Denaxas, Alastair K Denniston, Marzyeh Ghassemi, Georg Heinze, André Pascal Kengne, Lena Maier-Hein, Xiaoxuan Liu, Patricia Logullo, Melissa D McCradden, Nan Liu, Lauren Oakden-Rayner, Karandeep Singh, Daniel S Ting, Laure Wynants, Bada Yang, Johannes B Reitsma, Richard D Riley, Gary S Collins, Maarten van Smeden
Journal: BMJ (2025)

The Prediction model Risk Of Bias ASsessment Tool (PROBAST) is used to assess the quality, risk of bias, and applicability of prediction models or algorithms and of prediction model/algorithm studies. Since PROBAST's introduction in 2019, much progress has been made in the methodology for prediction modelling and in the use of artificial intelligence, including machine learning, techniques. An update to PROBAST-2019 is thus needed. This article describes the development of PROBAST+AI. PROBAST+AI consists of two distinctive parts: model development and model evaluation. For model development, PROBAST+AI users assess quality and applicability using 16 targeted signalling questions. For model evaluation, PROBAST+AI users assess the risk of bias and applicability using 18 targeted signalling questions. Both parts contain four domains: participants and data sources, predictors, outcome, and analysis. Applicability of the prediction model is rated for the participants and data sources, predictors, and outcome domains. PROBAST+AI may replace the original PROBAST tool and allows all key stakeholders (eg, model developers, AI companies, researchers, editors, reviewers, healthcare professionals, guideline developers, and policy organisations) to examine the quality, risk of bias, and applicability of any type of prediction model in the healthcare sector, irrespective of whether regression modelling or AI techniques are used.
Porous Fe/Cu Nanoreactor with Dual Insurance Design for Precision Chemotherapy and Chemodynamic Therapy
Authors: Xianyu Zhu, Lingli Gao, Yanbo Zheng, Peng Fei Zhao, Hanrui Wei, Ruixue Liu, Liping Zhao, Junyi Zhang, Qi Sun, Lingling Zheng, Han Lv, JiGang Yang, Jianhua Gong, Zhenchang Wang
Journal: Advanced Healthcare Materials (2025)

Abstract Poor prognosis and chemotherapy response stem from difficulties in precise targeting and the lack of effective synergistic treatments. Nanozymes show promising potential in tumor chemodynamic therapy (CDT) by catalyzing hydrogen peroxide (H₂O₂) decomposition and glutathione depletion in the tumor microenvironment (TME). However, integrating precise chemotherapy targeting with CDT remains challenging. In this study, a porous Fe/Cu bimetallic nanozyme carrier (FeCuNPs) is developed for co‐loading with the humanized 3F8 anti‐GD2 disialoganglioside antibody (3F8) and the novel pyridazinone‐based chemotherapeutic agent (IMB), forming a nanoreactor (3F8@FeCuNPs@IMB) for targeted chemotherapy and CDT. The nanoreactor responds specifically to the acidic TME as a primary insurance, allowing for the controlled release of IMB at the tumor site. The targeting antibody 3F8 coating on the surface of the nanozyme carrier acts as a secondary insurance, minimizing chemotherapy drug leakage during the delivery process and ensuring precise targeting for effective chemotherapy. Furthermore, FeCuNPs act as peroxidase‐like (POD) and glutathione oxidase‐like (GSHOX) enzymes, catalyzing hydroxyl radical (•OH) generation and depleting excess GSH, enhancing CDT. The results in vitro and in vivo indicate that the dual insurance designed 3F8@FeCuNPs@IMB offers a promising prospect for a targeted, precise, and effective combination of chemotherapy and CDT against melanoma.
Changes in the quality of life of adults with sickle cell disease following allogeneic stem cell transplantation: A mixed‐methods, prospective cohort study
Authors: Elisabeth Dovern, Sterre J. A. M. Nijland, Annemarie M. J. Braamse, Maud M. van Muilekom, Elisabeth M. J. Suijk, Gerianne M. Hoogendoorn, Charlotte F. J. van Tuijn, Michael R. DeBaun, Bart J. Biemond, Lotte Haverman, Erfan Nur
Journal: HemaSphere (2025)

Abstract Advances in conditioning regimens have made non‐myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) a viable curative option for adults with sickle cell disease (SCD). However, prospective studies comparing pre‐ and post‐transplant patient‐reported health outcomes are scarce. Therefore, in a prospective, mixed‐methods cohort study in adults with SCD undergoing HSCT, we tested the hypothesis that physical, mental, and social health improves after HSCT relative to baseline. We compared 9 Patient‐Reported Outcomes Measurement Information System (PROMIS®) measures at 6, 12, and 18 months post‐transplant to baseline and general population values. Semi‐structured interviews were conducted pre‐ and post‐transplant that were thematically analyzed (MAXQDA). Seventeen patients (7 females, 10 males; median age 26 years) underwent matched sibling (9) or haploidentical donor (8) transplantation. Compared to baseline, pain interference ( p = 0.008), physical function ( p &lt; 0.001), fatigue ( p = 0.001), anxiety ( p = 0.016), anger ( p = 0.037), and the ability to ( p &lt; 0.001) and satisfaction with ( p &lt; 0.001) social roles and activities improved at 18 months. Compared to reference values, physical function, sleep disturbance, fatigue, anxiety, and the ability to and satisfaction with social roles and activities T ‐scores were significantly worse at baseline but comparable or better after 18 months. Thematic analysis of the interviews revealed high satisfaction with improved physical and social abilities alongside complex mental health challenges, including processing the psychological aftermath of SCD, dealing with transplant‐related toxicity, adjustment challenges, and identity conflicts. In conclusion, while physical, mental, and social health improves after HSCT, the effects on mental health can be complex and warrant psychosocial support early in the process of curative therapies.
Scaling up clinical research capacity in Africa requires more non-communicable disease studies
Authors: Gabriel Seidman, Roger Chenn, Sophia David, Matthew Lee, Josh Leffler, Magdalena Moore, Sophia Stumpf, Giridhar Viswanathan, Muhammad Ali Pate, Michel Sidibé, Tariro Makadzange, Romina Mariano, Kyle Daniels, Megan Akodu, Shan Soe-Lin
Journal: The Lancet (2025)
Estimation of Proximal Tubular Function by Stimulation of Organic Anion and Cation Transporters
Authors: Magdalena Madero, Ana Karen Fernández-Yepez, Aldo Arturo Reséndiz-Albor, José Alberto Rivera Chávez, Jesse C. Seegmiller, Bernardo Rodriguez-Iturbe
Journal: Journal of the American Society of Nephrology (2025)

Tubular pathophysiology plays a critical role in the progression of chronic kidney disease (CKD). Exogenous stimulation of proximal tubule organic anion (OAT) and cation (OCT) transporters may be used to evaluate their responses independently of glomerular filtration rate (GFR) and their relation with clearance of protein-bound solutes and other biomarkers of tubular function. A proof of principle study was conducted in nine healthy volunteers and 22 patients with CKD classified by their GFR in KDIGO stages. They were studied hourly during 4 hours with water-induced diuresis, after the ingestion of 5g of creatinine and intravenous injection of 1-1.5mg/kg of furosemide, as means to stimulate OCTs and OATs, respectively. GFR determination (iohexol urinary clearance) was done in hours 2 to 3 and 3 to 4 of the study. Indoxyl sulfate, pCresol sulfate and urinary biomarkers of tubular function were studied in the first hour. GFR was stable during the study. Maximal values of tubular secretion of creatinine (TScr) and furosemide (TSfuro) were obtained in the first hour. The KDIGO categories of GFR were widely distributed throughout the range of tubular secretory responses. One-hour stimulated response of organic anion transporters was negatively correlated with serum levels of Indoxyl sulfate (r=-0.59, p=0.005) and pCresol sulfate (r=-0.59, p=0.004). Urinary epidermal growth factor, ammonium, alpha 1 microglobulin, and uromodulin correlated with the increment of TScr and TSfuro. The urinary excretion rate of creatinine in the first hour after the ingestion of 5g of creatinine was strongly correlated with the TScr (r=0.836, p<0.001). The functions of OATs and OCTs of the proximal tubule varied considerably between patients with similar GFRs and their impaired response was associated with retention of protein-bound uremic solutes and urine biomarkers of tubular dysfunction. The response of OCTs may be estimated by the urinary excretion of creatinine 1-hour after the ingestion of 5g of creatinine.
Ototoxicity and Cognitive Outcomes among Very Young Children Treated for Brain Tumors: Findings from a Multisite, Prospective, Longitudinal Trial
Authors: Heather M Conklin, Nicole A Salman, Johnnie K Bass, Jie Huang, Arzu Onar-Thomas, Jason M Ashford, Jennifer Harman, Jeanelle S Ali, Michelle A Swain, Lana L Harder, Bonnie L Carlson-Green, Jonathan M Miller, Joanna Wallace, Ryan J Kaner, Thomas E Merchant, Giles W Robinson, Amar Gajjar
Journal: Neuro-Oncology (2025)

Abstract Background Brain tumor treatment can result in sensorineural hearing loss (SNHL) that is associated with cognitive declines in school-age children. Young children treated for brain tumors are at heightened cognitive risk. This study examines the unique contribution of treatment-related ototoxicity to cognitive outcomes in young children treated for brain tumors. Methods 135 young children (mean age= 1.7 years) with a newly diagnosed malignant brain tumor were treated with chemotherapy, with or without focal proton or photon radiation therapy. Serial audiology and neurocognitive assessments were conducted for five years as part of a prospective, multisite, longitudinal trial (SJYC07; NCT00602667). SNHL was dichotomized as present versus not present (Chang grade ≥1a vs. 0). Neurocognitive assessments included intellectual functioning and parent ratings of adaptive functioning and attention. Results 67% of patients experienced mild-to-severe SNHL, which was associated with younger age at diagnosis (p&amp;lt;. 001) but not sex, treatment, or study risk arm (p&amp;gt; .10). Pre-treatment, higher IQ was associated with older age and higher socioeconomic status (p&amp;lt; .01), with a negative change in IQ trajectory after SNHL that was worse for children with supratentorial tumors. Pre-treatment, higher adaptive functioning was associated with older age (p= .0001), with a negative change in adaptive functioning trajectory after SNHL that was worse for those treated at a younger age. Attention problems increased after SNHL for the entire group (p= .0099). Conclusions SNHL is associated with IQ decline and worsening adaptive functioning and attention in young children treated for brain tumors. These findings have important implications for treatment modifications, interventions, and caregiver education.
Protein‐Interference‐Free and Kidney‐Targeting NIR Fluorophores for Accurate in Vivo Imaging of H<sub>2</sub>S<sub>2</sub> during Kidney Ferroptosis
Authors: Zhangkang Lv, Jing Wang, Jinyuan Xu, Xiaoshan Chen, Dongxue Lu, Jingting Huang, Xing‐Can Shen, Hua Chen
Journal: Advanced Healthcare Materials (2025)

High-fidelity kidney function imaging is important for assessing the nephrotoxicity of drugs and diagnosing renal diseases. However, the current challenges in achieving accurate kidney imaging include unspecific signal enhancement due to albumin binding and relatively low distribution of imaging agents in kidneys. Here, for the first time, a side-chain engineering strategy that incorporates hydrophilic six-membered heterocycles into aza-hemicyanine for generating high-performance kidney imaging agents with protein-interference-free and kidney-targeting features is proposed. Based on these unique aza-hemicyanine dyes, the first kidney-targeting and albumin-insensitive H2S2 near-infrared (NIR) fluorescent probe NA-H2S2 is designed, which demonstrates effective kidney distribution following intravenous injection and is specifically activated by H2S2. The designed probe presents a highly rapid, selective and sensitive response to H2S2 with a detection limit as low as 24.21 nm. Additionally, it successfully achieves real-time in vivo NIR fluorescence imaging of H2S2 during erastin/cisplatin induced renal ferroptosis. Moreover, it also enables rapid detection of H2S2 through in vitro optical urinalysis, offering significant diagnostic value for renal ferroptosis. Overall, this study not only presents a practical kidney-targeting H2S2 fluorescent probe NA-H2S2 with increased imaging accuracy but also provides promising kidney-targeting and albumin-insensitive aza-hemicyanine dyes for further development of kidney disease-related probes.
Steroid Refractory Acute <scp>GVHD</scp>: The Hope for a Better Tomorrow
Authors: Portia Smallbone, Rohtesh S. Mehta, Amin Alousi
Journal: American Journal of Hematology (2025)

Steroid-refractory acute graft-versus-host disease (SR-AGVHD) presents a significant barrier to successful outcomes following allogeneic hematopoietic cell transplantation (HCT), despite advancements in GVHD prophylaxis and management. While ruxolitinib therapy has shown improved response rates, survival benefits remain elusive. This review explores the definitions and proposed distinct pathophysiology and treatment landscape of SR-AGVHD. Emerging therapies offer potential, yet further research is critical to better define steroid-refractory populations, improve treatment precision with biomarkers, and overcome resistance, particularly in ruxolitinib-refractory cases.