tbuckley/cabot-search huggingface dataset:
Typical Bone Scintigraphy Presentation of Erdheim-Chester Disease in a Patient Diagnosed With IgG4-Related Disease
Authors: Chloé François, Clémentine Rousselin, Thomas Quemeneur, Franck Demailly, Guillaume Collet, Alexandre Fagart
Journal: Clinical Nuclear Medicine (2024)

Abstract A 50-year-old woman presented a dry syndrome, joint pain, inflammatory syndrome, polyclonal hypergammaglobulinemia, and tubulointerstitial nephritis. Imaging studies (including FDG PET/CT) revealed infrarenal retroperitoneal fibrosis with periaortitis and hypermetabolic osteosclerotic lesions. Bone scintigraphy demonstrated intense uptake in the femoral, tibial, and radial regions, suggestive of non-Langerhans histiocytosis, specifically Erdheim-Chester disease. A bone biopsy confirmed the presence of IgG4-positive plasma cells but no histiocytes. The patient received corticosteroid therapy followed by rituximab, resulting in a complete response. This case suggests an atypical manifestation of bone lesions in IgG4-related disease, emphasizing the diagnostic challenge between IgG4-related disease and Erdheim-Chester disease.
Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial
Authors: Michiel Coppens, Steven W Pipe, Wolfgang Miesbach, Jan Astermark, Michael Recht, Paul van der Valk, Bruce Ewenstein, Karen Pinachyan, Nicholas Galante, Sandra Le Quellec, Paul E Monahan, Frank W G Leebeek
Journal: The Lancet Haematology (2024)
MACE in COPD: addressing cardiopulmonary risk
Authors: John R Hurst, Chris P Gale, John R. Hurst, Mohit Bhutani, Jean Bourbeau, MeiLan Han, Nathaniel M. Hawkins, Carolyn S.P. Lam, Darcy D. Marciniuk, David Price, Daiana Stolz, Shelley Zieroth, Chris P. Gale
Journal: The Lancet Respiratory Medicine (2024)
Increased Prostate-Specific Membrane Antigen Uptake in a Gallbladder Stone
Authors: Hui Li, Le Song, Meixin Zhao, Weifang Zhang
Journal: Clinical Nuclear Medicine (2024)

Abstract An Al 18 F–prostate-specific membrane antigen (PSMA) Q PET/CT scan was performed in a 67-year-old man to identify any potential recurrent prostate cancer lesions, which revealed no recurrent or metastatic lesions. However, a large gallbladder stone with increased PSMA uptake was incidentally detected, which could be a potential pitfall in the interpretation of PSMA PET imaging.
Kidney Disease Modeling with Organoids and Organs-on-Chips
Authors: Samira Musah, Rohan Bhattacharya, Jonathan Himmelfarb
Journal: Annual Review of Biomedical Engineering (2024)

Kidney disease is a global health crisis affecting more than 850 million people worldwide. In the United States, annual Medicare expenditures for kidney disease and organ failure exceed $81 billion. Efforts to develop targeted therapeutics are limited by a poor understanding of the molecular mechanisms underlying human kidney disease onset and progression. Additionally, 90% of drug candidates fail in human clinical trials, often due to toxicity and efficacy not accurately predicted in animal models. The advent of ex vivo kidney models, such as those engineered from induced pluripotent stem (iPS) cells and organ-on-a-chip (organ-chip) systems, has garnered considerable interest owing to their ability to more accurately model tissue development and patient-specific responses and drug toxicity. This review describes recent advances in developing kidney organoids and organ-chips by harnessing iPS cell biology to model human-specific kidney functions and disease states. We also discuss challenges that must be overcome to realize the potential of organoids and organ-chips as dynamic and functional conduits of the human kidney. Achieving these technological advances could revolutionize personalized medicine applications and therapeutic discovery for kidney disease.
Histatin 5‐Inspired Short‐Chain Peptides Selectively Combating Pathogenic Fungi with Multifaceted Mechanisms
Authors: Guojun Lu, Xiaoyan Ju, Meng Zhu, Jinzhao Ou, Dandan Xu, Kejia Li, Wei Jiang, Chenxiao Wan, Ye Tian, Zhongwei Niu
Journal: Advanced Healthcare Materials (2024)

Short-chain antifungal peptides (AFPs) inspired by histatin 5 have been designed to address the problem of antifungal drug resistance. These AFPs demonstrate remarkable antifungal activity, with a minimal inhibitory concentration as low as 2 µg mL
Single‐Atom Cu Nanozyme‐Loaded Bone Scaffolds for Ferroptosis‐Synergized Mild Photothermal Therapy in Osteosarcoma Treatment
Authors: Zuyun Yan, Xin Wu, Wei Tan, Jinpeng Yan, Jun Zhou, Shijie Chen, Jinglei Miao, Jun Cheng, Cijun Shuai, Youwen Deng
Journal: Advanced Healthcare Materials (2024)

Abstract The rapid multiplication of residual tumor cells and poor reconstruction quality of new bone are considered the major challenges in the postoperative treatment of osteosarcoma. It is a promising candidate for composite bone scaffold which combines photothermal therapy (PTT) and bone regeneration induction for the local treatment of osteosarcoma. However, it is inevitable to damage the normal tissues around the tumor due to the hyperthermia of PTT, while mild heat therapy shows a limited effect on antitumor treatment as the damage can be easily repaired by stress‐induced heat shock proteins (HSP). This study reports a new type of single‐atom Cu nanozyme‐loaded bone scaffolds, which exhibit exceptional photothermal conversion properties as well as peroxidase and glutathione oxidase mimicking activities in vitro experiments. This leads to lipid peroxidation (LPO) and reactive oxygen species (ROS) upregulation, ultimately causing ferroptosis. The accumulation of LPO and ROS also contributes to HSP70 inactivation, maximizing PTT efficiency against tumors at an appropriate therapeutic temperature and minimizing the damage to surrounding normal tissues. Further, the bone scaffold promotes bone regeneration via a continuous release of bioactive ions (Ca 2+ , P 5+ , Si 4+ , and Cu 2+ ). The results of in vivo experiments reveal that scaffolds inhibit tumor growth and promote bone repair.
Challenges and controversies in resectable non-small cell lung cancer: a clinician’s perspective
Authors: Ilias Houda, Chris Dickhoff, Carin A. Uyl-de Groot, Ronald A.M. Damhuis, Noemi Reguart, Mariano Provencio, Antonin Levy, Rafal Dziadziuszko, Cecilia Pompili, Massimo Di Maio, Michael Thomas, Alessandro Brunelli, Sanjay Popat, Suresh Senan, Idris Bahce
Journal: The Lancet Regional Health - Europe (2024)

The treatment landscape of resectable early-stage non-small cell lung cancer (NSCLC) is transforming due to the approval of novel adjuvant and neoadjuvant systemic treatments. The European Medicines Agency (EMA) recently approved adjuvant osimertinib, adjuvant atezolizumab, adjuvant pembrolizumab, and neoadjuvant nivolumab combined with chemotherapy, and the approval of other agents or new indications may follow soon. Despite encouraging results, many unaddressed questions remain. Moreover, the transformed treatment paradigm in resectable NSCLC can pose major challenges to healthcare systems and magnify existing disparities in care as differences in reimbursement may vary across different European countries. This Viewpoint discusses the challenges and controversies in resectable early-stage NSCLC and how existing inequalities in access to these treatments could be addressed.
Abstract B009: Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets
Authors: Kristina Thiel, Andreea Newtson, Eric Devor, Yuping Zhang, Paige K. Malmrose, Haley Losh, Suzy Davies, Lane E. Smith, Jamie Padilla, Stephanie Leiva, Christy Hagan, Miles Pufall, Jay Gertz, Yan Guo, Kimberly K. Leslie
Journal: Clinical Cancer Research (2024)

Abstract Progesterone prevents development of endometrial cancers through its receptor (PR) although the molecular mechanisms have yet to be fully characterized. In this study, we performed a global analysis of gene regulation by progesterone using human endometrial cancer cells that expressed PR endogenously or exogenously. We found progesterone strongly inhibits multiple components of the platelet derived growth factor receptor (PDGFR), Janus kinase (JAK), signal transducer and activator of transcription (STAT) pathway through PR. The PDGFR/JAK/STAT pathway signals to control numerous downstream targets including AP-1 transcription factors Fos and Jun. Treatment with inhibitors of the PDGFR/JAK/STAT pathway significantly blocked proliferation in multiple novel patient-derived organoid models of endometrial cancer, and activation of this pathway was found to be a poor prognostic signal for the survival of patients with endometrial cancer from The Cancer Genome Atlas. Our study identifies this pathway as central to the growth-limiting effects of progesterone in endometrial cancer and suggests that inhibitors of PDGFR/JAK/STAT should be considered for future therapeutic interventions. Citation Format: Kristina Thiel, Andreea Newtson, Eric Devor, Yuping Zhang, Paige K. Malmrose, Haley Losh, Suzy Davies, Lane E. Smith, Jamie Padilla, Stephanie Leiva, Christy Hagan, Miles Pufall, Jay Gertz, Yan Guo, Kimberly K. Leslie. Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B009.
Abstract A012: Genomic landscape of somatic alterations identified in endometrial cancer using liquid biopsy
Authors: Leylah Drusbosky, Ginger Haynes, Brooke Grant, Pamela Sobernis, Stephanie Lheureux
Journal: Clinical Cancer Research (2024)

Abstract Background: With advances in understanding the biology of endometrial cancer, molecular sub-groups have been defined to assess prognosis and guide treatment decisions. This classification is based on surrogate markers in archival paraffin-embedded tissues. The landscape of somatic alterations as detected by liquid biopsy has not been well described in advanced endometrial cancer. Methods: A retrospective analysis was performed using de-identified genomic data collected from patients with advanced endometrial cancer who underwent liquid biopsy testing with a 74-83 gene panel as part of clinical care (Guardant360, Guardant Health, Inc.). Results: 1,988 females with a median age of 68 [range 23-95] years were included in the analysis. 45% of patients were tested at diagnosis of advanced disease; 43% were tested at time of disease progression. 91.6% of patients had ≥1 somatic alteration detected and 12% of patients were MSI-High. The most frequently altered genes included TP53 (65%), PIK3CA (31%), PTEN (27%), ARID1A (24%), like prior reports of genomic alterations detected in tissue samples. CCNE1 amplifications were enriched in 11% of samples with TP53 alterations (p&amp;lt;0.0001; q&amp;lt;0.0001) and EGFR amplifications were enriched in samples without TP53 alterations (p&amp;lt;0.0001; q&amp;lt;0.0001). MSI-H samples were enriched for alterations in ARID1A, PTEN, PIK3CA, ATM, MSH6 and others, while samples without MSI were enriched for alterations in TP53 and CCNE1 (p&amp;lt;0.0001; q&amp;lt;0.0001). Oncogenic fusions were rare in this cohort (0.2%) and included FGFR1 and FGFR3 rearrangements. Activating, druggable alterations were identified in PIK3CA, KRAS, ERBB2, and BRCA1/2. Putative pathogenic germline alterations were detected in 61 (3%) patients and included ATM (18%), BRCA1 (33%), BRCA2 (21%), and lower frequencies of CHEK2, FANCA, MLH1, MSH2, MSH6, and PALB2. Conclusions: While descriptive in nature, this analysis is the largest cohort of advanced endometrial cancer analyzed using a clinically available liquid biopsy assay and demonstrates the feasibility of somatic alteration detection. This report paves the way for using liquid biopsy as a potential tool for guiding targeted chemotherapeutic strategies. Citation Format: Leylah Drusbosky, Ginger Haynes, Brooke Grant, Pamela Sobernis, Stephanie Lheureux. Genomic landscape of somatic alterations identified in endometrial cancer using liquid biopsy [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A012.
Abstract B002: ARID1A loss activates MAPK signaling via DUSP4 downregulation: a mechanistic insight in endometrial carcinoma
Authors: Jayaprakash Mandal, Zheng-Cheng Yu, Ie-Ming Shih, Tian-Li Wang
Journal: Clinical Cancer Research (2024)

Abstract The intricate interplay between chromatin remodelers, transcriptional regulation, and downstream cellular processes is gradually unraveling. AT-rich interactive domain-containing protein 1A (ARID1A), a tumor suppressor and chromatin remodeler, is frequently mutated in endometrium-related malignancies including ovarian or uterine clear cell carcinoma (CCC) and endometrioid carcinoma (EMCA). How ARID1A mutation alters downstream signaling is yet to be established. Based on the TCGA proteomics datasets, MAPK and ARID1A are negatively correlated in endometrial cancer. Yet, the underlying molecular mechanism of this association remains unclear. Using ARID1A-proficient and ARID1A-deficient isogenic human endometrial epithelial cells, we explored transcriptomic changes and discovered notable downregulation of a MAPK phosphatase, dual-specificity phosphatase 4 (DUSP4), in ARID1A-deficient cells. This expression pattern was further validated in additional pairs of isogenic cell lines, ES-2, MCF10a, and HCT116. Chromatin immunoprecipitation sequencing (ChIP-seq) was utilized to assess active and repressive transcription histone marks on global and 5’ transcriptional regulatory regions of DUSP4. ChIP-seq demonstrated decreased histone acetylation marks (H3K27Ac, H3K9Ac) on DUSP4 enhancer and promoter regions of ARID1A-deficient cells, suggesting ARID1A's role in modulating chromatin accessibility and gene expression. Furthermore, a positive correlation between ARID1A and DUSP4 expression was established using a Pax8-driven conditional knockout mouse cohort and in human endometroid carcinoma tissues. Moreover, an inverse expression correlation between ARID1A and the phosphatase substrates of DUSP4, including p-p38, p-JNK, and p-ERK in the MAPK signaling pathway, was observed in this genetically engineered murine model and in the TCGA datasets of human uterine carcinomas. Interestingly, ectopic DUSP4 expression decreased cell proliferation, and MAPK pathway targeting, specifically via ERK inhibitor Ulixertinib, significantly mitigated tumor growth in vivo. In conclusion, our findings suggest ARID1A modulates DUSP4 expression by remodeling the chromatin landscape which leads to an inhibitory effect on the MAPK pathway and suppresses tumor progression. ARID1A-DUSP4-MAPK axis offers a promising avenue for developing targeted therapies against ovarian or uterine CCC and EMCA. Citation Format: Jayaprakash Mandal, Zheng-Cheng Yu, Ie-Ming Shih, Tian-Li Wang. ARID1A loss activates MAPK signaling via DUSP4 downregulation: a mechanistic insight in endometrial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B002.
Abstract B018: MYC is sufficient to generate mid-life high-grade serous ovarian and serous endometrial carcinomas in a BRCA wild type p53-R270H mouse model
Authors: Alexandra Blackman, Amy Rees, Rob Bowers, Christian Jones, Silvia Vaena, Shelby Carter, Evan Villamor, Della Evans, George Fullbright, David Long, Laura Spruill, Martin Romeo, Kristi Helke, Anthony Emanuel, Joe Delaney
Journal: Clinical Cancer Research (2024)

Abstract Genetically engineered mouse models (GEMM) have fundamentally changed how cancer etiology, early detection, and treatment can be understood. Mouse models have been developed that support the fallopian tube as the origin of some ovarian cancers. However, serous endometrial cancer is a much rarer gynecologic cancer with fewer models available. The genetics of serous endometrial cancer are very similar that of high-grade serous ovarian cancer. The most common mutation found in both high-grade serous ovarian cancer and serous uterine cancer is p53 and in humans, MYC is amongst the most amplified genes in both tyeps of cancer. We developed a GEMM of high-grade serous ovarian cancer by using a fallopian tube epithelium specific promoter Ovgp1 to express MYC and dominant negative mutant p53-R270H. Female mice developed lethal cancer at an average of 15.1 months. Histopathological examination of mice revealed HGSOC characteristics including nuclear p53 and nuclear MYC in clusters of cells within the fallopian tube epithelium and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the fallopian tube epithelium. Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Histological and transcriptomic findings are consistent with the hypothesis that serous uterine cancer may originate from the fallopian tube epithelium. Citation Format: Alexandra Blackman, Amy Rees, Rob Bowers, Christian Jones, Silvia Vaena, Shelby Carter, Evan Villamor, Della Evans, George Fullbright, David Long, Laura Spruill, Martin Romeo, Kristi Helke, Anthony Emanuel, Joe Delaney. MYC is sufficient to generate mid-life high-grade serous ovarian and serous endometrial carcinomas in a BRCA wild type p53-R270H mouse model [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B018.
Quality control of allergen products with mass spectrometry part I: Positioning within the <scp>EU</scp> regulatory framework
Authors: Jelena Spiric, Thomas Schulenborg, Thomas Holzhauser, Frank Schuler, Andreas Bonertz, Iris Lauer, Detlef Bartel, Stefan Vieths, Vera Mahler, Andreas Reuter
Journal: Allergy (2024)

Abstract Mass spectrometry (MS) has advanced greatly and many of its applications are ready for utilization within regulatory procedures and could significantly contribute to overcome challenges in standardization of allergen products. It seems sensible to discuss MS within the regulatory framework, before addressing technical questions. While the application to purified proteins is well established from product development to manufacturer's release analytics, its application to complex products such as allergen products is still under development. It needs to be determined where it can complement or replace established methods or where MS offers limited improvement. Despite its technical appeal and versatility, currently MS is mentioned in regulatory guidelines only as one possible measurement method. For example, no specific MS method is given in the European Pharmacopoeia. We discuss applications of MS within the EU regulatory framework. This includes their advantages and disadvantages and their positioning between research, characterization, manufacturer's release analytics and official batch testing. We discuss the qualitative detection of single and multiple allergens as proof of identity, qualitative to semi‐quantitative protein profiles for batch to batch consistency testing, and quantification of allergens to state mass units of allergens. MS may also facilitate standardization of allergen products, reference products and reference standards.
Immunoglobulin free light chains in severe asthma patient: Could they be a new biomarker?
Authors: C. Caruso, G. Ciasca, I. Baglivo, R. Di Santo, A. Gasbarrini, D. Firinu, D. Bagnasco, G. Passalacqua, M. Schiappoli, M. Caminati, G. W. Canonica, E. Heffler, C. Crimi, R. Intravaia, V. Basile, M. Marino, S. Colantuono, S. Del Giacco
Journal: Allergy (2024)

Increasing evidence is available about the presence of increased serum concentration of immunoglobulin (Ig) free light chains (FLCs) in both atopic and non-atopic inflammatory diseases, including severe asthma, providing a possible new biomarker of disease.
Efficacy and safety analysis of Dupilumab for atopic dermatitis of all ages in Chinese population: Real‐world data from a single center
Authors: Zijing Yang, Wanting Wen, Ruofei Shi, Lihong Chen, Hailun Wang, Jie Zheng, Haiqin Zhu, Meng Pan, Xiaoqing Zhao
Journal: Allergy (2024)

The data that supports the findings of this study are available in the supplementary material of this article. Tables S1–S4. 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.
Abstract IA017: Spontaneous humoral responses in endometrial cancer provide a rationale for novel tumor-penetrating therapeutic antibodies
Authors: Jose R. Conejo-Garcia
Journal: Clinical Cancer Research (2024)

Abstract The role of humoral responses in endometrial cancer remains insufficiently investigated. Using a cohort of 107 patients with different histological subtypes of endometrial carcinoma, we found that concomitant accumulation of T, B, and plasma cells at tumor beds predicted better survival. However, only B cell markers corresponded with prolonged survival specifically in high-grade endometrioid type and serous tumors. Immune protection was associated with class-switched IgA and, to a lesser extent, IgG. Expression of polymeric immunoglobulin receptor (PIGR) by tumor cells allow dimeric IgA transcytosis. Taking advantage of tumor cell penetration, we demonstrated that mutation-specific dIgA, but not IgG, neutralized KRASG12D inside carcinoma cells and expelled this oncodriver (but not wild-type KRAS) outside tumor cells, abrogating tumor cell proliferation in an antigen-specific manner. Accordingly, KRASG12D-specific dIgA1, but not the same antibody on an IgG backbone, abrogated KRASG12D carcinoma growth in vivo, more effectively than small molecule KRASG12D inhibitors, including in syngeneic tumor-bearing immunocompetent mice. Because &amp;gt;6% of endometrial cancers exhibit KRAS mutations, our results provide a rationale for developing PIGR-targeting tumor cell-penetrating antibodies to effectively target intracellular oncogenes, which could be applicable to many aggressive and frequent human cancers. Citation Format: Jose R. Conejo-Garcia. Spontaneous humoral responses in endometrial cancer provide a rationale for novel tumor-penetrating therapeutic antibodies [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA017.
Bihormonal fully closed-loop system for the treatment of type 1 diabetes: a real-world multicentre, prospective, single-arm trial in the Netherlands
Authors: A C van Bon, H Blauw, T J P Jansen, G D Laverman, T Urgert, J Geessink-Mennink, A H Mulder, M Out, R Groote Veldman, A J Onvlee, B J J W Schouwenberg, M A R Vermeulen, M J M Diekman, M N Gerding, J P H van Wijk, M Klaassen, M Witkop, J H DeVries
Journal: The Lancet Digital Health (2024)

Management of insulin administration for intake of carbohydrates and physical activity can be burdensome for people with type 1 diabetes on hybrid closed-loop systems. Bihormonal fully closed-loop (FCL) systems could help reduce this burden. In this trial, we assessed the long-term performance and safety of a bihormonal FCL system.