tbuckley/cabot-search huggingface dataset:
Development of novel patient-reported outcome instruments to assess atopic dermatitis-associated dyspigmentation and xerosis in patients with skin of colour
Authors: Christopher Hartford, Andrew Alexis, Zhixiao Wang, Noah A Levit, Benjamin Banderas, Andrew Yaworsky, Emily Love, Brad Shumel, Gaëlle Bégo-Le-Bagousse, Diana Rofail
Journal: British Journal of Dermatology (2025)

The prevalence and burden of atopic dermatitis (AD) are disproportionately high in individuals with skin of colour (SOC). Previous research shows that risk for xerosis and/or dyspigmentation is heightened in this population and may be more bothersome. However, there are no patient-reported instruments developed specifically for these disease sequelae in patients with SOC. To develop and perform content validation of patient-reported outcome (PRO) questionnaires to assess AD-related xerosis and dyspigmentation in patients with SOC. A targeted literature review was conducted to understand and identify AD-related disease sequelae and quality-of-life impacts relevant to patients with SOC and any instruments used to assess AD in the target population. Two draft PRO questionnaires assessing xerosis (X-AD) and dyspigmentation (D-AD) were developed and refined following advice meetings with clinical experts (N = 3). Questionnaire content validity was explored during hybrid concept elicitation (CE) and cognitive-debriefing (CD) interviews with adult and adolescent patients with SOC who have moderate-to-severe AD (N = 15). Ten concept-focused articles, three websites, 17 labels, one United States Food and Drug Administration compendium and one clinical trial confirmed xerosis and dyspigmentation were important AD-related disease sequelae. Patients with SOC (46.7% female; age range 12.2-76.1 years) reported that each questionnaire was relevant to their AD experience in an appropriate recall timeframe, were readily understood and meaningful responses were easy to select. The final X-AD consisted of one 11-point numeric rating scale (NRS) assessing xerosis severity and two items assessing the level of bother associated with xerosis appearance and feeling over the past week (0-4 verbal rating scale). The final D-AD consisted of two 11-point NRS items assessing dyspigmentation severity and two items assessing the level of bother associated with how dyspigmentation looked over the past week. The X-AD/D-AD questionnaires were well understood and effective in capturing the experiences of xerosis and dyspigmentation in the target population in an appropriate and comprehensive way. The study supports the initial development of the questionnaires in accordance with regulatory guidelines and best practices, however psychometric validation is required to evaluate the properties of each questionnaire and develop score interpretation guidelines.
Making the Case for an International Childhood Cancer Data Partnership
Authors: Gonçalo Forjaz, Betsy Kohler, Michel P Coleman, Eva Steliarova-Foucher, Serban Negoita, Jaime M Guidry Auvil, Fernanda Silva Michels, Johanna Goderre, Charles Wiggins, Eric B Durbin, Gijs Geleijnse, Marie-Charlotte Henrion, Candice Altmayer, Thomas Dubois, Lynne Penberthy
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Childhood cancers are a heterogeneous group of rare diseases, accounting for less than 2% of all cancers diagnosed worldwide. Most countries, therefore, do not have enough cases to provide robust information on epidemiology, treatment, and late effects, especially for rarer types of cancer. Thus, only through a concerted effort to share data internationally will we be able to answer research questions that could not otherwise be answered. With this goal in mind, the U.S. National Cancer Institute and the French National Cancer Institute co-sponsored the Paris Conference for an International Childhood Cancer Data Partnership in November 2023. This meeting convened more than 200 participants from 17 countries to address complex challenges in pediatric cancer research and data sharing. This Commentary delves into some key topics discussed during the Paris Conference and describes pilots that will help move this international effort forward. Main topics presented include: 1) the wide variation in interpreting the European Union's General Data Protection Regulation among Member States; 2) obstacles with transferring personal health data outside of the European Union; 3) standardization and harmonization, including common data models; and 4) novel approaches to data sharing such as federated querying and federated learning. We finally provide a brief description of three ongoing pilot projects. The International Childhood Cancer Data Partnership is the first step in developing a process to better support pediatric cancer research internationally through combining data from multiple countries.
Randomized comparison of precut papillotomy and endosonography guided rendezvous procedure for difficult biliary access in Malignant distal biliary obstruction
Authors: Vinay Dhir, Vivek Kumar Singh, Ankit Dalal, Gaurav Patil, Amit Maydeo
Journal: Endoscopy (2025)

Difficult biliary cannulation (DBC) is a marker for prolonged procedure time and a higher rate of adverse events (AEs) during endoscopic retrograde cholangiopancreatography (ERCP). We previously showed that endoscopic ultrasound-assisted rendezvous (EUS-RV) procedures had a higher single-session success rate than precut papillotomy (PCP) in cases of DBC. The present randomized study aimed to compare the technical success and AE rates of the two approachesThis was an open-label randomized controlled trial in a tertiary care setting. Patients with malignant distal biliary obstruction (MDBO) and DBC were enrolled. The patients were randomized to PCP with a needle-knife or EUS-RV. The primary outcome was technical success; secondary outcomes were the AE rate, procedure duration, and length of hospital stay (LOS).208 patients were enrolled, 104 in each group. There were no statistically significant differences in technical success (93.3% PCP vs. 97.1% EUS-RV; P = 0.33; odds ratio [OR] 0.4, 95%CI 0.1-1.6) and overall AE rate (11.5% PCP vs. 5.8% EUS-RV; P=0.14; OR 0.5, 95%CI 0.8-5.9). Pancreatitis was higher in the PCP group (8.7% vs. 1.9%; P=0.06; OR 4.8, 95%CI 1.0-22.9). The mean duration of the procedure was significantly higher for EUS-RV (47 vs. 27 minutes; P<0.001). LOS was similar in the two groups (1.2 PCP vs. 1.1 days EUS-RV; P=0.25).Both PCP and EUS-RV have comparable rates of success, AEs, mortality, and LOS. EUS-RV could be used as an alternative to PCP in patients with MDBO and DBC.
Serum cAMP levels are increased in patients with asthma
Authors: Steven S An, Gaoyuan Cao, Kwangmi Ahn, Jordan Lee, Dae Young Jung, Loren Denlinger, John Fahy, Elliot Israel, Wendy Moore, Brenda Phillips, David Mauger, Sally Wenzel, Reynold A Panettieri
Journal: Journal of Clinical Investigation (2025)
Erythema variation in dermatomyositis across subtypes and racial groups: importance of outcome measure for dermatomyositis clinical trials
Authors: Catherine Shen, Ari Zeidi, Lillian Xie, Lais Lopes Almeida Gomes, Rui Feng, Victoria P Werth
Journal: British Journal of Dermatology (2025)

Two measurement tools are currently used to assess skin disease activity in dermatomyositis (DM) clinical trials: the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and the Cutaneous Dermatomyositis Investigator Global Assessment (CDM-IGA). This cross-sectional study assessed variability in erythema presentation across DM subtypes and among racial groups by comparing these two measurement tools: the CDASI and the CDM-IGA. With the increasing need to standardize DM trial outcome measures for cutaneous disease, our findings support the use of the CDASI as the primary scoring tool to determine cutaneous trial outcomes.
Co-activating STING-TLR9 pathways promotes radiotherapy-induced cancer vaccination
Authors: Yu Sun, Liang Liu, Huilan He, Guanhong Cui, Yun Zheng, Chunlian Ye, Liping Qu, Yinping Sun, Jinlong Ji, Twan Lammers, Ying Zhang, Zhiyuan Zhong
Journal: Journal of Controlled Release (2025)
Disparities in cervical cancer elimination timeframes in the United States: a comparative modeling study
Authors: Emily A Burger, Erik E L Jansen, Daniël de Bondt, James Killen, Jennifer C Spencer, Mary Caroline Regan, Megan A Smith, Stephen Sy, Karen Canfell, Inge M C M de Kok, Jane J Kim, Jan A C Hontelez
Journal: JNCI Journal of the National Cancer Institute (2025)

Population-level estimates in timeframes for reaching cervical cancer (CC) elimination (ie, <4 cases per 100,000 women) in the United States may mask potential disparities in achieving elimination among sub-populations. We used three independent Cancer Intervention and Surveillance Modeling Network (CISNET) models to estimate differences in the time to CC elimination across seven strata of correlated screening and human papillomavirus vaccination uptake, based on national survey data. Compared to the average population, elimination was achieved ≥22 years earlier for the high-uptake strata and ≥27 years later for the most extreme low-uptake strata. Accounting for correlated uptake impacted the population average timeframe by ≤ 1 year. Consequently, national average elimination timeframes mask substantial disparities in reaching elimination among sub-populations. Addressing inequalities in CC control could shorten elimination timeframes and would ensure more equitable elimination across populations. Furthermore, country-level elimination monitoring could be supplemented by monitoring progress in sub-populations.
TIPPo: A User-Friendly Tool for De Novo Assembly of Organellar Genomes with High-Fidelity Data
Authors: Wenfei Xian, Ilja Bezrukov, Zhigui Bao, Sebastian Vorbrugg, Anupam Gautam, Detlef Weigel
Journal: Molecular Biology and Evolution (2025)

Abstract Plant cells have two major organelles with their own genomes: chloroplasts and mitochondria. While chloroplast genomes tend to be structurally conserved, the mitochondrial genomes of plants, which are much larger than those of animals, are characterized by complex structural variation. We introduce TIPPo, a user-friendly, reference-free assembly tool that uses PacBio high-fidelity long-read data and that does not rely on genomes from related species or nuclear genome information for the assembly of organellar genomes. TIPPo employs a deep learning model for initial read classification and leverages k-mer counting for further refinement, significantly reducing the impact of nuclear insertions of organellar DNA on the assembly process. We used TIPPo to completely assemble a set of 54 complete chloroplast genomes. No other tool was able to completely assemble this set. TIPPo is comparable with PMAT in assembling mitochondrial genomes from most species but does achieve even higher completeness for several species. We also used the assembled organelle genomes to identify instances of nuclear plastid DNA (NUPTs) and nuclear mitochondrial DNA (NUMTs) insertions. The cumulative length of NUPTs/NUMTs positively correlates with the size of the nuclear genome, suggesting that insertions occur stochastically. NUPTs/NUMTs show predominantly C:G to T:A changes, with the mutated cytosines typically found in CG and CHG contexts, suggesting that degradation of NUPT and NUMT sequences is driven by the known elevated mutation rate of methylated cytosines. Small interfering RNA loci are enriched in NUPTs and NUMTs, consistent with the RdDM pathway mediating DNA methylation in these sequences.
<scp>UV</scp> Light Exposure Induces a Type I Interferon Dependent Activation and Migration of Inflammatory Dendritic Cells to Local Lymph Nodes
Authors: Xizhang Sun, Jaime L. Chao, Michael Gerner, Keith B. Elkon
Journal: Arthritis & Rheumatology (2025)

Objective Photosensitivity occurs in ~75% of patients with lupus. Although UV light radiation (UVR) stimulates type I interferon (IFN‐I) in the skin, how UVR‐induced skin inflammation leads to downstream effects is poorly understood. Tissue inflammation causes dendritic cells (DCs) to migrate from organs to draining lymph nodes (dLN), including a recently identified inflammatory conventional DC subset (inf cDC2) that are potent antigen‐presenting cells. To explore links between UVR and the early immune response, we examined DC and lymphocyte subset migration to dLN in normal and lupus‐prone mouse strains as well as the role of IFN‐I. Methods Mice received a single dose of UV (500 mJ/cm 2 ) on the dorsal skin. Brachial and inguinal dLN were harvested at one or two days post‐UVR. Flow cytometry using the Symphony A3 cytometer and 15‐color staining identified myeloid and lymphoid subsets. Statistical significance was determined by Student's t ‐test. Results Higher numbers of CD64+ myeloid cells as well as inf cDC2 were detected in the dLN after UVR in B6 mice, but not in IFN receptor knockout (IFNAR KO) mice. In contrast, Trex1 mutant mice had an exaggerated IFN‐I response in the skin and a higher proportion of inf cDC2 in the dLN. Conclusion These findings reveal a previously unknown relationship between skin UVR and the migration of the inf cDC2 population to dLN. They highlight the role of IFN‐I in this process, and the differences between Trex1 mutant and normal mice suggest that this may be of relevance to lupus. image
Critical role for Transglutaminase 2 in scleroderma skin fibrosis and in the development of dermal sclerosis in a mouse model of scleroderma
Authors: Angela Y.Y. Tam, Korsa Khan, Shiwen Xu, Marianne Bergin, Linghong Huang, Erik Arroyo Colon, Danyi Cheng, Elisabetta AM Verderio, Voon Ong, Christopher P Denton, John Atkinson, Tim S Johnson, David J. Abraham
Journal: Arthritis & Rheumatology (2025)

Objective Scleroderma is a life‐threatening autoimmune disease characterized by inflammation, tissue remodelling, and fibrosis. This study aimed to investigate the expression and function of transglutaminase 2 (TGM2) in scleroderma skin and experimentally‐induced dermal fibrosis to determine its potential role and therapeutic implications. Methods We performed immunohistochemistry on skin sections to assess TGM2 expression and localisation, and protein biochemistry of both SSc‐derived and healthy control dermal fibroblasts to assess TGM2 expression, function and ECM deposition in the presence of a TGM2 and TGFβ neutralizing antibodies and a small molecule inhibitor of the TGFβRI kinase. Mice with a complete deficiency of TGM2 ( Tgm2‐/‐) were investigated in the bleomycin‐induced model of skin fibrosis. Results TGM2 was found to be widely expressed in both control and scleroderma skin samples, as well as in cultured fibroblasts. Scleroderma fibroblasts exhibited elevated TGM2 expression, which correlated with increased expression of fibrosis markers (collagen type 1, αSMA and CCN2). Inhibition of TGM2 using a neutralizing antibody reduced the expression of key markers of fibrosis. The effects of TGM2 inhibition were similar to those observed with TGFβ neutralization, suggesting a potential cross‐talk between TGM2 and TGFβ signalling. Moreover, TGM2 knock‐out mice showed significantly reduced dermal fibrosis compared to wild‐type mice. In vitro experiments with TGM2‐deleted fibroblasts demonstrated impaired cell migration and collagen matrix contraction, which could be partially restored by exogenous TGFβ. Conclusion TGM2 can regulate several key pro‐fibrotic activities of TGFβ suggesting that attenuating TGM2 function may be of benefit in severe forms of connective tissue disease with skin fibrosis. image
Emerging role of exosomes in cancer therapy: progress and challenges
Authors: Jiale Li, Jiachong Wang, Zigui Chen
Journal: Molecular Cancer (2025)

This review highlights recent progress in exosome-based drug delivery for cancer therapy, covering exosome biogenesis, cargo selection mechanisms, and their application across multiple cancer types. As small extracellular vesicles, exosomes exhibit high biocompatibility and low immunogenicity, making them ideal drug delivery vehicles capable of efficiently targeting cancer cells, minimizing off-target damage and side effects. This review aims to explore the potential of exosomes in cancer therapy, with a focus on applications in chemotherapy, gene therapy, and immunomodulation. Additionally, challenges related to exosome production and standardization are analyzed, highlighting the importance of addressing these issues for their clinical application. In conclusion, exosome-based drug delivery systems offer promising potential for future cancer therapies. Further research should aim to enhance production efficiency and facilitate clinical translation, paving the way for innovative cancer treatment strategies.
Visualizing Cancer Heterogeneity at the Molecular and Cellular Levels: Lessons from Rosetta
Authors: Richard J.A. Goodwin, John F. Marshall, George Poulogiannis, Mariia Yuneva, Kevin M. Brindle, Zoltán Takáts, Owen J. Sansom, Josephine Bunch, Simon T. Barry, Ala Al-Afeef, Ala Amgheib, Sara Azarian, Frederic Brochu-Williams, Amy Burton, Andrew Campbell, Vanina Cristaudo, Ali Demircali, Alex Dexter, Efstathios Elia, Maria Fala, Magali Garrett, Avinash Ghanate, Ian Gilmore, Ariadna Gonzalez, Paul Grant, Amit Gupta, Dipa Gurung, Harry Hall, Gregory Hamm, Paolo Inglese, Najah Islam, Stewart Jones, Evi Karali, Emine Kazanc, Hanifa Koguna, Manas Kohli, Hanifa Koquna, Nikolaos Koundouros, Peter Kreuzaler, Melina Kyriazi, Sharanpreet Kall Lall, David Y. Lewis, Stephanie Ling, Xavier Loizeau, Dominika Luptakova, Stefania Maneta-Stravrakaki, Daniel McGill, Daniel McGill, James McKenzie, Greg McMahon, Martin Metodiev, Jaynish Mistry, Alvaro Perdones Monteiro, Erica Montezuma, Jennifer Morton, Catherine Munteanu, Teresa Murta, Arafath Najumudeen, Chandan Seth Nanda, Ammar Nasif, Chelsea J. Nikula, Madelon Paauwe, Petra Paiz, Yulia Panina, Robin Philip, Liam Poynter, Pamela Pruski, Alan M. Race, Jyotsna Rao, Jack Richings, Adele Savage, Chandan Seth Nanda, Shreya Sharma, Renata Filipe Soares, Dmitry Soloviev, Amy Spicer-Hadlington, Caroline Sproat, Rory T. Steven, David Sumpton, Adam J. Taylor, Spencer Thomas, Daria Thompson, Aurelien Tripp, Thanasis Tsalikis, Anastasia Tsyben, Seyma Turseven, Johan Vande-Voorde, Jean-Luc Vorng, Emma White, Alan Wright, Vincen Wu, Yuchen Xiang, Bin Yan, Jinshi Zao, Lucas Zeiger, Junting Zhang, Weiwei Zhou
Journal: Cancer Discovery (2025)

Understanding tumor heterogeneity is a major challenge that was recognized as one of the first Cancer Grand Challenges, with a call to provide solutions to visualize tumor heterogeneity. The Rosetta team took on this challenge, exploiting advances in spatial-omics approaches centered around mass spectrometry imaging to map tumor heterogeneity at the cellular and molecular scales with different levels of resolution. See related article by Bressan et al., p. 16 See related article by Stratton et al., p. 22 See related article by Bhattacharjee et al., p. 28.
Acknowledgment to Reviewers
Journal: Cancer Discovery (2025)

Acknowledgment to Reviewers| January 13 2025 Acknowledgment to Reviewers Author & Article Information Online ISSN: 2159-8290 Print ISSN: 2159-8274 ©2024 American Association for Cancer Research2024American Association for Cancer Research Cancer Discov (2025) 15 (1): 246–249. https://doi.org/10.1158/2159-8290.CD-15-1-AR Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record January 13 2025 Citation Acknowledgment to Reviewers. Cancer Discov 1 January 2025; 15 (1): 246–249. https://doi.org/10.1158/2159-8290.CD-15-1-AR Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search The Cancer Discovery editors wish to acknowledge with sincere appreciation the assistance of the following reviewers who have generously contributed their time and effort during the past year1 in the appraisal of manuscripts. These reviewers have been enormously helpful in assessing the merit of original articles: their careful analysis and critique and their constructive recommendations have greatly enhanced the value of manuscripts they have handled. The quality of the journal can be attributed in large measure to the quality of their effort. We are sincerely grateful. Abate-Shen, C. Abdel-Wahab, O. Adams, D. Adrover, J. Agami, R. Agarwal, N. Aggen, D. Agnihotri, S. Aguirre, A. Ahmed, N. Aifantis, I. Ali, H. Alimonti, A. Allen, C. Alon, U. Alonso, M. Altman, B. Ambrogio, C. Amit, I. Amit, M. Amunts, A. Anagnostou, V. Anders, R. Andre, F. Aplenc, R. Aplin, A. Arteaga, C. Ashworth, A. Astsaturov, I. Auslander, N. Azad, N. Baca,... You do not currently have access to this content.
Cancer Neuroscience of Brain Tumors: From Multicellular Networks to Neuroscience-Instructed Cancer Therapies
Authors: Varun Venkataramani, Yvonne Yang, Sebastian Ille, Bogdana Suchorska, Sonja Loges, Heike Tost, Felix Sahm, Stefan M. Pfister, Andreas Trumpp, Sandro M. Krieg, Thomas Kuner, Wolfgang Wick, Frank Winkler
Journal: Cancer Discovery (2025)

Abstract Deepening our understanding of neuro-cancer interactions can innovate brain tumor treatment. This mini review unfolds the most relevant and recent insights into the neural mechanisms contributing to brain tumor initiation, progression, and resistance, including synaptic connections between neurons and cancer cells, paracrine neuro-cancer signaling, and cancer cells’ intrinsic neural properties. We explain the basic and clinical–translational relevance of these findings, identify unresolved questions and particularly interesting future research avenues, such as central nervous system neuro-immunooncology, and discuss the potential transferability to extracranial cancers. Lastly, we conceptualize ways toward clinical trials and develop a roadmap toward neuroscience-instructed brain tumor therapies. Significance: Neural influences on brain tumors drive their growth and invasion. Herein, we develop a roadmap to use these fundamentally new insights into brain tumor biology for improved outcomes.
Peto’s Paradox Is Dead. Long Live Peto’s Paradox
Authors: Michael J. Metzger
Journal: Cancer Discovery (2025)

Summary: In this issue, Compton and colleagues report the prevalence of neoplasia and malignant cancer in 292 species, based on 16,049 necropsy records, shedding light on susceptibility to cancer and the evolution of mechanisms that protect against cancer across a broad array of vertebrates. See related article by Compton et al., p. 227
Taking a Swing at TIMP1-Armed Immunosuppressive Astrocytes Unleashes T cell Immunity against Brain Metastases
Authors: Mihaela Lorger, Fiona James
Journal: Cancer Discovery (2025)

Summary: Priego and colleagues identify a secreted glycoprotein TIMP1, expressed downstream of the transcription factor STAT3, in a subpopulation of STAT3+ reactive astrocytes as a mediator of immunosuppression in late-stage brain metastases. The STAT3 inhibitor silibinin enhances the preclinical efficacy of the combined PD-1/CTLA4 immune checkpoint blockade, providing a rationale to translate the combination therapy into clinical use for this underserved patient group with poor prognosis. See related article by Priego et al., p. 179