tbuckley/cabot-search huggingface dataset:
Reporting of concomitant and rescue topical therapies in atopic dermatitis randomised controlled trials evaluating a systemic treatment: a scoping review
Authors: Sophie Leducq, Wei Chern Gavin Fong, Hywel C Williams, Lucy Bradshaw, Kim S Thomas
Journal: British Journal of Dermatology (2025)

Abstract Background Randomised controlled trials (RCTs) evaluating new systemic treatments for atopic dermatitis (AD) have increased dramatically over the last decade. These trials often incorporate topical therapies either as permitted concomitant or rescue treatments. Differential use of these topicals post-randomisation introduces potential bias as they may nullify or exaggerate treatment responses. Objectives To determine the proportion of RCTs that clearly report the allowance or prohibition of concomitant and rescue topical treatments. Secondary outcomes involved examining the reporting of specific key parameters for these topicals. Methods We included AD systemic medication RCTs included in the living systematic review of Drucker et al (updated in March 2023, available at the time of this review). Inclusion criteria were published RCTs evaluating systemic immunomodulatory treatments in AD. Only anti-inflammatory topical therapies were included therapies in this review; emollients were not considered. Results We screened 83 AD trials and included 67 RCTs, published between 1991 and 2023. The majority adequately reported the allowance or prohibition of concomitant topical treatments (95.5%, N=64/67), but this clarity was less prevalent regarding rescue topicals (73.1%, N=49/67). All trials permitting concomitant therapies consistently reported the type, though details on potency (88.6%, N=31/35), duration (54.3%, N=19/35), application frequency (34.3%, N=12/35), and quantity (5.7%, N=2/35) were less frequently reported. Similarly, trials allowing rescue treatments often specified the type (91.2%, N=31/34) but provided limited information on potency (52.9%, N=18/34), duration (8.8%, N=3/34), application frequency (5.9%, N=2/34), and quantity (0%, N=0/34). Notably, only 23.5% (N=8/34) clearly reported the criteria for using rescue topical treatments, with the phrase "at investigator’s discretion" being used in most cases (61.8%, N=21/34). In the multivariable logistic regression analysis including impact factor, journal’s policy on adhering to CONSORT guidelines, publication year, funding, number of patients randomised and blinding status, only the publication year (≥ 2020) was associated with having better reporting for rescue topical treatments (aOR 9.55, 95% CI 1.76–39.8). Conclusions While most AD clinical trials of systemic treatments report concomitant topical treatments, reporting practices for rescue topicals were less consistent and inadequate. A standardized approach to reporting topical therapy in AD trials is needed to enhance transparency and interpretability.
Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma
Authors: Kang Sun, Xiaozhen Zhang, Jiatao Shi, Jinyan Huang, Sicheng Wang, Xiang Li, Haixiang Lin, Danyang Zhao, Mao Ye, Sirui Zhang, Li Qiu, Minqi Yang, Chuyang Liao, Lihong He, Mengyi Lao, Jinyuan Song, Na Lu, Yongtao Ji, Hanshen Yang, Lingyue Liu, Xinyuan Liu, Yan Chen, Shicheng Yao, Qianhe Xu, Jieru Lin, Yan Mao, Jingxin Zhou, Xiao Zhi, Ke Sun, Xiongbin Lu, Xueli Bai, Tingbo Liang
Journal: Journal of Clinical Investigation (2025)

Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME. Analysis of 18F-FDG uptake in patients showed that increased global protein lactylation in PDAC correlates with worse clinical outcomes in immunotherapy. Inhibition of lactate production in pancreatic tumors via glycolysis or mutant-KRAS inhibition reshaped the TME, thereby increasing their sensitivity to immune checkpoint blockade (ICB) therapy. In pancreatic tumor cells, lactate induces K63 lactylation of Endosulfine alpha (ENSA-K63la), a crucial step that triggers STAT3-CCL2 signaling. Consequently, elevated CCL2 secreted by tumor cells facilitates tumor-associated macrophage (TAM) recruitment to the TME. High levels of lactate also drive transcriptional reprogramming in TAMs via ENSA-STAT3 signaling, promoting an immunosuppressive environment. Targeting ENSA-K63la or CCL2 enhances the efficacy of ICB therapy in murine and humanized pancreatic tumor models. In conclusion, elevated lactylation reshapes the TME and promotes immunotherapy resistance in PDAC. Therapeutic approach targeting ENSA-K63la or CCL2 has shown promise in sensitizing pancreatic cancer immunotherapy.
KidneyintelX.dkd
Authors: Steven G. Coca, Girish N. Nadkarni
Journal: Journal of the American Society of Nephrology (2025)

1Barbara T Murphy Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA 2Division of Digital and Data Driven Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA 3The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA aCorresponding Authors: Dr. Steven Coca and Dr. Girish Nadkarni, Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1243, New York, NY 10029, Tel: (212) 241-6633, E-mail Address: [email protected] or [email protected]
Monocytes and interstitial macrophages contribute to hypoxic pulmonary hypertension
Authors: Rahul Kumar, Kevin Nolan, Biruk Kassa, Neha Chanana, Tsering Palmo, Kavita Sharma, Kanika Singh, Claudia Mickael, Dara Fonseca Balladares, Julia Nilsson, Amit Prabhakar, Aastha Mishra, Michael H. Lee, Linda Sanders, Sushil Kumar, Ari B. Molofsky, Kurt R. Stenmark, Dean Sheppard, Rubin M. Tuder, Mohit D. Gupta, Tashi Thinlas, Qadar Pasha, Brian B. Graham
Journal: Journal of Clinical Investigation (2025)

Hypoxia is a major cause of pulmonary hypertension (PH) worldwide, and it is likely that interstitial pulmonary macrophages contribute to this vascular pathology. We observed in hypoxia-exposed mice an increase in resident interstitial macrophages, which expanded through proliferation and expressed the monocyte recruitment ligand CCL2. We also observed an increase in CCR2+ macrophages through recruitment, which express the protein thrombospondin-1 that functionally activates TGF-beta to cause vascular disease. Blockade of monocyte recruitment with either CCL2 neutralizing antibody treatment or CCR2 deficiency in the bone marrow compartment suppressed hypoxic PH. These data were supported by analysis of plasma samples from humans who travelled from low (225m) to high (3500m) elevation, revealing an increase in thrombospondin-1 and TGF-beta expression following ascent, which was blocked by dexamethasone prophylaxis. In the hypoxic mouse model, dexamethasone prophylaxis recapitulated these findings by mechanistically suppressing CCL2 expression and CCR2+ monocyte recruitment. These data suggest a pathologic cross-talk between two discrete interstitial macrophage populations, which can be therapeutically targeted.
Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential
Authors: Zachary A. Kohutek, Heather L. Caslin, Daniel J. Fehrenbach, J. Brett Heimlich, Jonathan D. Brown, Meena S. Madhur, P. Brent Ferrell, Amanda C. Doran
Journal: Circulation Research (2025)

Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating hematopoiesis. Under normal conditions, this niche ensures a return to immune homeostasis after acute stress. However, in the setting of inflammatory conditions such as those seen in cardiometabolic diseases, it becomes dysregulated, leading to enhanced myelopoiesis and immune activation. This review explores the reciprocal relationship between the bone marrow niche and cardiometabolic diseases, highlighting how alterations in the niche contribute to disease development and progression. The niche regulates HSCs through complex interactions with stromal cells, endothelial cells, and signaling molecules. However, in the setting of chronic diseases such as hypertension, atherosclerosis, and diabetes, inflammatory signals disrupt the balance between HSC self-renewal and differentiation, promoting the excessive production of proinflammatory myeloid cells that exacerbate the disease. Key mechanisms discussed include the effects of hyperlipidemia, hyperglycemia, and sympathetic nervous system activation on HSC proliferation and differentiation. Furthermore, the review emphasizes the role of epigenetic modifications and metabolic reprogramming in creating trained immunity, a phenomenon whereby HSCs acquire long-term proinflammatory characteristics that sustain disease states. Finally, we explore therapeutic strategies aimed at targeting the bone marrow niche to mitigate chronic inflammation and its sequelae. Novel interventions that modulate hematopoiesis and restore niche homeostasis hold promise for the treatment of cardiometabolic diseases. By interrupting the vicious cycle of inflammation and marrow dysregulation, such therapies may offer new avenues for reducing cardiovascular risk and improving patient outcomes.
Results From First-in-Human Phase I Study of a Novel CD19-1XX Chimeric Antigen Receptor With Calibrated Signaling in Large B-Cell Lymphoma
Authors: Jae H. Park, M. Lia Palomba, Karlo Perica, Sean M. Devlin, Gunjan Shah, Parastoo B. Dahi, Richard J. Lin, Gilles Salles, Michael Scordo, Karthik Nath, Yannis K. Valtis, Alec Lynch, Elizabeth Cathcart, Honglei Zhang, Heiko Schoder, Doris Leithner, Kelly Liotta, Alina Yu, Kelsey Stocker, Jia Li, Agnish Dey, Leopold Sellner, Reshma Singh, Varsha Sundaresan, Xin Tong, Faye Zhao, Jorge Mansilla-Soto, Changhao He, Joel Meyerson, Kinga Hosszu, Devin McAvoy, Xiuyan Wang, Isabelle Rivière, Michel Sadelain
Journal: Journal of Clinical Oncology (2025)

PURPOSE We designed a CD19-targeted chimeric antigen receptor (CAR) comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3ζ and 4-1BB/CD3ζ CARs. Preclinical data demonstrated that 1XX CARs generated potent effector function without undermining T-cell persistence. We hypothesized that 1XX CAR T cells may be effective at low doses and elicit minimal toxicities. METHODS In this first-in-human, phase I, dose escalation and expansion clinical trial, patients with relapsed or refractory large B-cell lymphoma received 19(T2)28z-1XX CAR T cells at four dose levels (DLs), ranging from 25 to 200 × 10 6 . RESULTS Twenty-eight patients underwent apheresis and received CAR T cells. Sixteen and 12 patients were treated in the dose escalation and expansion cohorts, respectively. The overall response rate (ORR) was 82% and complete response (CR) rate was 71% in the entire cohort. The lowest dose of 25 × 10 6 was selected for dose expansion. In 16 patients treated at this DL, 88% achieved ORR and 75% CR. With the median follow‐up of 24 months, the 1-year event-free survival was 61% (95% CI, 45 to 82) and 14 patients remain in continuous CR beyond 12 months. In all cohorts, grade ≥3 cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome rates were low at 4% and 7%, respectively. 1XX CAR T-cell products contain a higher proportion of CD8 T cells with memory features, and CAR T-cell persistence has been detected beyond 1-2 years in patients with ongoing remission. CONCLUSION The calibrated potency of the 1XX CAR affords excellent efficacy at low cell doses with favorable toxicity profiles and may benefit the treatment of other hematologic malignancies, solid tumors, and autoimmunity.
Surrogate End Points for Overall Survival in Neoadjuvant Randomized Clinical Trials for Early Breast Cancer
Authors: Fabio Conforti, Valentina Nekljudova, Isabella Sala, Roberto Ascari, Christine Solbach, Michael Untch, Carsten Denkert, Vincenzo Bagnardi, Laura Pala, Peter A. Fasching, Andreas Schneeweiss, Hans-Joachim Lück, Eleonora Pagan, Tommaso De Pas, Marion van Mackelenbergh, Jens Huober, Volkmar Müller, Theresa Link, Thomas Karn, Mattea Reinisch, Frederik Marmé, Vesna Bjelic-Radisic, Christian Schem, Andreas Hartkopf, Elmar Stickeler, Claus Hanusch, Jens-Uwe Blohmer, Tanja Fehm, Kerstin Rhiem, Johannes Holtschmidt, Richard D. Gelber, Sibylle Loibl
Journal: Journal of Clinical Oncology (2025)

PURPOSE To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC). METHODS Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination R 2 from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points. RESULTS Eleven RCTs, for a total of 15 treatment comparisons and 12,247 patients, were included in the analysis. There was a weak association between hazard ratios (HRs) for OS and odds ratio of pCR overall ( R 2 , 0.07; 95% CI, 0.00 to 0.48), as well as in all the subgroups explored. Overall, the R 2 for the association between HR OS and HR iDFS was 0.46 (95% CI, 0.08 to 0.71), which is just below the cutoff of 0.5 for moderate surrogacy. In the majority of subgroups explored, the R 2 ranged from 0.5 to &lt;0.7, while in hormone receptor–/human epidermal growth factor receptor 2– subtype, histologic grade 1-2 tumors, and lobular tumors, surrogacy was strong (ie, R 2 ≥0.7). The surrogacy value of iDFS for OS was affected by follow-up (FUP) length: R 2 substantially increased up to 36 months of FUP, with little further improvement after 48 months of FUP. CONCLUSION iDFS with sufficient FUP is an acceptable surrogate end point to confidently anticipate final OS results of neoadjuvant RCTs for early BC. This recommendation holds true across many subgroups, with the notable exception of HR+ disease. There is definite need to reassess whether OS is the optimal end point for treatment efficacy measurement in HR+ early BC.
Identification of indirect CD4+ T cell epitopes associated with transplant rejection provides a target for donor-specific tolerance induction
Authors: Zhuldyz Zhanzak, Aileen C Johnson, Petra Foster, Maria A Cardenas, Anna B Morris, Joan Zhang, Geeta Karadkhele, I Raul Badell, Alanna A Morris, Byron B Au-Yeung, Fernanda M Roversi, Juliete A F Silva, Cynthia Breeden, Annette Hadley, Weiwen Zhang, Christian P Larsen, Haydn T Kissick
Journal: Immunity (2025)
Breaking Barriers with Data Equity: The Essential Role of Data Disaggregation in Achieving Health Equity
Authors: Ninez A. Ponce, Tara Becker, Riti Shimkhada
Journal: Annual Review of Public Health (2025)

Achieving health equity necessitates high-quality data to address disparities that have remained stagnant or even worsened over time despite public health interventions. Data disaggregation, the breakdown of data into detailed subcategories, is crucial in health disparities research. It reveals and contextualizes hidden trends and patterns about marginalized populations and guides resource allocation and program development for specific needs in these populations. Data disaggregation underpins data equity, which uses community engagement to democratize data and develop better solutions for communities. Years of research on disaggregation show that researchers must collaborate closely with communities for adequate representation. However, despite generally positive support for this approach in health disparities research, data disaggregation faces methodological and political challenges. This review offers a framework for understanding data disaggregation in the context of data equity and highlights critical aspects of implementation, including challenges, opportunities, and recent policy and community-based efforts to address hurdles.
Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer
Authors: Xinyi Guo, Hu Nie, Wenwen Zhang, Jiesheng Li, Jing Ge, Bowen Xie, Wenbo Hu, Yicheng Zhu, Na Zhong, Xinmei Zhang, Xiaohong Zhao, Xiaoshuang Wang, Qinli Sun, Kun Wei, Xiaoyuan Chen, Ling Ni, Ting Zhang, Shichun Lu, Lei Zhang, Chen Dong
Journal: Cancer Cell (2025)
Lactate homeostasis is maintained through regulation of glycolysis and lipolysis
Authors: Won Dong Lee, Daniel R Weilandt, Lingfan Liang, Michael R MacArthur, Natasha Jaiswal, Olivia Ong, Charlotte G Mann, Qingwei Chu, Craig J Hunter, Rolf-Peter Ryseck, Wenyun Lu, Anna M Oschmann, Alexis J Cowan, Tara A TeSlaa, Caroline R Bartman, Cholsoon Jang, Joseph A Baur, Paul M Titchenell, Joshua D Rabinowitz
Journal: Cell Metabolism (2025)
Endoscopic Ultrasound Guided Portosystemic Pressure Gradient Correlates with Clinical Parameters and Liver Histology
Authors: Jennifer M Kolb, Marc Monachese, Raymond A Rubin, Thomas J Wang, Alyssa Choi, Ahmad N Bazarbashi, Bhaumik Brahmbhatt, Ali Zakaria, Pedro Cortes, Varun Kesar, William F Abel, Wen-Pin Chen, Christine McLaren, Amirali Tavangar, Amit G Singal, Pushpak Taunk, Michael B Wallace, Prashant Kedia, David Lee, Ali Abbas, Paul Yeaton, Natalie Cosgrove, Vivek Kesar, Kenneth J Chang, Marvin Ryou, Jason Samarasena
Journal: Clinical Gastroenterology and Hepatology (2025)
Sickle Cell Trait Does Not Cause "Sickle Cell Crisis" Leading to Exertion-Related Death: A Systematic Review
Authors: Lachelle D. Weeks, Allecia M. Wilson, Rakhi P. Naik, Yvonne A. Efebera, Mohammad Hassan Murad, Anjlee Mahajan, Patrick T. McGann, Madeleine Verhovsek, Angela C. Weyand, Ahmar Urooj Zaidi, Michael R DeBaun, Chancellor Donald, Roger A. Mitchell
Journal: Blood (2025)
Diagnosis of Retrograde Cricopharyngeus dysfunction using high resolution impedance manometry and comparison with control subjects
Authors: Karlien Raymenants, Friedel Vulsteke, Tim Vanuytsel, Nathalie Rommel, Filip Baert, Kathelijne Delsupehe, Alexandre Bohyn, Jan Tack, Joris Arts
Journal: Clinical Gastroenterology and Hepatology (2025)
Barriers to Lung Cancer Screening in a Multi-Disciplinary Thoracic Oncology Program Cohort: Effects of an Incidental Pulmonary Nodule Program.
Authors: Wei Liao, Meredith A Ray, Anita Patel, Jessica Roma, Hope Marshall, Carrie Fehnel, Jordan Goss, Osarenren Ogbeide, Anurag Mehrotra, Philip Lammers, Keith Tonkin, Ann Bishop, Matthew P Smeltzer, Raymond U Osarogiagbon
Journal: Journal of Thoracic Oncology (2025)
CAR T cells, CAR NK cells, and CAR macrophages exhibit distinct traits in glioma models but are similarly enhanced when combined with cytokines
Authors: Thomas Look, Roman Sankowski, Manon Bouzereau, Serena Fazio, Miaomiao Sun, Alicia Buck, Niklas Binder, Maximilian Mastall, Francesco Prisco, Frauke Seehusen, Julia Frei, Conrad Wyss, Berend Snijder, Cesar Nombela Arrieta, Michael Weller, Steve Pascolo, Tobias Weiss
Journal: Cell Reports Medicine (2025)

Chimeric antigen receptor (CAR) T cell therapy is a promising immunotherapy against cancer. Although there is a growing interest in other cell types, a comparison of CAR immune effector cells in challenging solid tumor contexts is lacking. Here, we compare mouse and human NKG2D-CAR-expressing T cells, natural killer (NK) cells, and macrophages against glioblastoma, the most aggressive primary brain tumor. Invitro we show that T cell cancer killing is CAR dependent, whereas intrinsic cytotoxicity overrules CAR dependence for NK cells, and CAR macrophages reduce glioma cells in co-culture assays. In orthotopic immunocompetent glioma mouse models, systemically administered CAR T cells demonstrate superior accumulation in the tumor, and each immune cell type induces distinct changes in the tumor microenvironment. An otherwise low therapeutic efficacy is significantly enhanced by co-expression of pro-inflammatory cytokines in all CAR immune effector cells, underscoring the necessity for multifaceted cell engineering strategies to overcome the immunosuppressive solid tumor microenvironment.
Neoadjuvant immunotherapy with or without chemotherapy in locally advanced oral squamous cell carcinoma: Randomized, two-arm, phase 2 trial
Authors: Hai-Ming Liu, Xue-Peng Xiong, Zi-Li Yu, Zhe Shao, Gai-Li Chen, Yu-Tong Liu, Xin-Xin Wang, Qiu-Yun Fu, Xiao-Xia Cheng, Jing Li, Jia-Li Zhang, Bo Li, Hong-Yun Gong, Ya-Hua Zhong, Wei Zhang, Jun Jia, Bing Liu, Gang Chen
Journal: Cell Reports Medicine (2025)

Patients with locally advanced oral squamous cell carcinoma (OSCC) have poor outcomes with standard care. Neoadjuvant therapy is shown to be effective for these patients. In the randomized, two-arm, phase 2, non-comparative trial, we investigate the efficacy and safety of the neoadjuvant programmed cell death 1 (PD-1) inhibitor camrelizumab with or without docetaxel-cisplatin-5-fluorouracil (TPF) chemotherapy in patients with resectable locally advanced OSCC. Patients with stage III-IVA OSCC receive neoadjuvant therapy with three cycles of camrelizumab (arm Cam) with or without two cycles of TPF chemotherapy (arm Cam+TPF), followed by surgery and adjuvant therapy. Major pathological response (MPR) is achieved in both arm Cam (5/34, 14.7%) and arm Cam+TPF (26/34, 76.4%). With a median follow-up of 32 months, the 2-year event-free survival (EFS) rate of arm Cam and Cam+TPF is 52.9% and 91.2%, respectively. This work demonstrates feasibility and safety for immunochemotherapy in the neoadjuvant setting for OSCC. This study was registered at ClinicalTrials.gov (NCT04649476).
Moving beyond the prevalent exposure design for causal inference in dementia research
Authors: Lachlan Cribb, Margarita Moreno-Betancur, Zimu Wu, Rory Wolfe, Matthew Pasé, Joanne Ryan
Journal: The Lancet Healthy Longevity (2025)

As randomised trials are not always feasible or practical, observational studies remain crucial for addressing many causal questions in the dementia prevention field. Through a systematic search, we found that 84 (72%) of the 116 latest observational cohort studies that investigated factors hypothesised to reduce the risk of dementia (hearing aids, physical activity, antihypertensives, antidiabetics, and antidepressants) used a prevalent exposure design. The approach of using a prevalent exposure design, which compares dementia risk between individuals with and without prevalent exposure at the start of follow-up, has several limitations, including ill-defined interventions, selection biases, and challenges in adjusting for confounders. This Personal View discusses these limitations using physical activity as a case study and describes an alternative approach based on the target trial framework that can help to overcome such limitations. This approach aligns observational analyses with the design and analysis principles of randomised trials and can, thereby, improve the robustness and relevance of evidence for dementia prevention, which is the ultimate goal.