tbuckley/cabot-search huggingface dataset:
Curating genomic disease-gene relationships with Gene2Phenotype (G2P)
Authors: T. Michael Yates, Morad Ansari, Louise Thompson, Sarah E. Hunt, Elena Cibrian Uhalte, Rachel J. Hobson, Joseph A. Marsh, Caroline F. Wright, Helen V. Firth
Journal: Genome Medicine (2024)

Abstract Genetically determined disorders are highly heterogenous in clinical presentation and underlying molecular mechanism. The evidence underpinning these conditions in the peer-reviewed literature requires robust critical evaluation for diagnostic use. Here, we present a structured curation process for Gene2Phenotype (G2P). This draws on multiple lines of clinical, bioinformatic and functional evidence. The process utilises and extends existing terminologies, allows for precise definition of the molecular basis of disease, and confidence levels to be attributed to a given gene-disease assertion. In-depth disease curation using this process will prove useful in applications including in diagnostics, research and development of targeted therapeutics. G2P: www.ebi.ac.uk/gene2phenotype .
Unlocking the potential of Extracellular Vesicles in Nephrology – what does MISEV2023 add?
Authors: Monica Suet Ying Ng, Dylan Burger, Per Svenningsen, Elena Martens, Uta Erdbrügger, Fabian Braun
Journal: Kidney International (2024)

Extracellular vesicles, small membrane-bound packages secreted by virtually all cells of the body, have become a focus of interest in Nephrology over the recent years. After the first characterization of their proteomic and transcriptomic content, the scientific attention shifted towards their potential as biomarkers for kidney diseases both as diagnostic and monitoring tools. More recently, researchers have begun exploring whether extracellular vesicles mediate intercellular signaling inside the nephron and between the kidney and other organs throughout the body. Nevertheless, the field of extracellular vesicle research has struggled to translate major findings to the clinical context due to numerous methods to separate extracellular vesicles yielding fractions of different sizes and varying purity, unclear terminology, and, hence, limitations concerning reproducibility. The International Society of Extracellular Vesicles, therefore, has striven to reduce these barriers by an ongoing initiative to increase rigor and standardization of extracellular vesicle research. The "Minimal information for studies of extracellular vesicles" MISEV-guideline is the result of this initiative and, in its now 3rd iteration, provides the most concise suggestions for investigating extracellular vesicles to date. This mini review illustrates the advances made in extracellular vesicle research in nephrology so far using informative examples, outlines the advances made by the former MISEV guidelines and what potential utilizing the latest iteration holds.
Evaluating the risk of cardiovascular events associated with different immunosuppression treatments for glomerular diseases.
Authors: Mark Canney, Mohammad Atiquzzaman, Yuyan Zheng, Dilshani Induruwage, Yinshan Zhao, Lee Er, Christopher B. Fordyce, Sean J. Barbour
Journal: Kidney International (2024)

Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials.Graphical abstract
The glomerular circadian clock temporally regulates basement membrane dynamics and the podocyte glucocorticoid response.
Authors: Rebecca Preston, Ruby Chrisp, Michal Dudek, Mychel R.P.T. Morais, Pinyuan Tian, Emily Williams, Richard W. Naylor, Bernard Davenport, Dharshika R.J. Pathiranage, Emma Benson, David G. Spiller, James Bagnall, Leo Zeef, Craig Lawless, Syed Murtuza Baker, Qing-Jun Meng, Rachel Lennon
Journal: Kidney International (2024)

Kidney physiology shows diurnal variation, and a disrupted circadian rhythm is associated with kidney disease. However, it remains largely unknown whether glomeruli, the filtering units in the kidney, are under circadian control. Here, we investigated core circadian clock components in glomeruli, together with their rhythmic targets and modes of regulation. With clock gene reporter mice, cell-autonomous glomerular clocks which likely govern rhythmic fluctuations in glomerular physiology were identified. Using circadian time-series transcriptomic profiling, the first circadian glomerular transcriptome with 375 rhythmic transcripts, enriched for extracellular matrix and glucocorticoid receptor signaling ontologies, were identified. Subsets of rhythmic matrix-related genes required for basement membrane assembly and turnover, and circadian variation in matrix ultrastructure, coinciding with peak abundance of rhythmic basement membrane proteins, were uncovered. This provided multiomic evidence for interactions between glomerular matrix and intracellular time-keeping mechanisms. Furthermore, glucocorticoids, which are frequently used to treat glomerular disease, reset the podocyte clock and induce rhythmic expression of potential glomerular disease genes associated with nephrotic syndrome that included NPHS1 (nephrin) and NPHS2 (podocin). Disruption of the clock with pharmacological inhibition altered the expression of these disease genes, indicating an interplay between clock gene expression and key genes required for podocyte health. Thus, our results provide a strong basis for future investigations of the functional implications and therapeutic potential of chronotherapy in glomerular health and disease.Graphical abstract
First and Second-line Treatments in Metastatic Renal Cell Carcinoma
Authors: Regina Barragan-Carrillo, Eddy Saad, Renee-Maria Saliby, Maxine Sun, Laurence Albiges, Axel Bex, Daniel Heng, Arnaud Mejean, Robert J Motzer, Elizabeth R Plimack, Thomas Powles, Brian I Rini, Tian Zhang, Toni K Choueiri
Journal: European Urology (2024)
Feasibility of Early 68Ga-FAP-2286 PET Imaging: A Case Study
Authors: Seyedeh Somayyeh Banihashemian, Ghasemali Divband, Abdolghafar Abolhosseini Shahrnoy, Reza Nami, Meysam Nasiri, Mohammad Esmaeil Akbari
Journal: Clinical Nuclear Medicine (2024)

Abstract Fibroblast activation protein (FAP) has emerged as a promising molecular target for diagnostic and therapeutic strategies. Previous research, including our own study and other published reports, has highlighted the potential of FAP inhibitors labeled with 68 Ga as effective diagnostic radiopharmaceuticals. In this study, we present a comparative analysis of early and late PET/CT scans, using 68 Ga-FAP-2286, for the detection of tumor lesions in a patient with metastatic breast adenocarcinoma.
Utilizing 99mTc-FAPI-46 SPECT/CT in Detection of Peritoneal Carcinomatosis in Gastric Poorly Differentiated Adenocarcinoma
Authors: Nasrin Raeisi, Amin Saber Tanha, Kamran Aryana, Ehsan Soltani, Somaye Barashki
Journal: Clinical Nuclear Medicine (2024)

We introduce a 61-year-old man with poorly differentiated gastric adenocarcinoma, who previously underwent surgical treatment. In this presentation, he complained of a newly appeared midabdominal mass after the latest chemotherapy session. He was a candidate for diagnostic laparotomy, but in the setting of trial, 99mTc-FAPI-46 SPECT/CT was performed revealing 2 peritoneal masses, which were the only findings of diagnostic surgery subsequent to the scan. This report presents the first case of 99mTc-FAPI-46 SPECT/CT in metastasis workup of gastric adenocarcinoma.
The Importance of 18F-FDG PET/CT in a Rare Case of Multiple Myeloma Presenting With Nasal Plasmacytoma
Authors: Özge Erol Fenercioğlu, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2024)

Nasopharyngeal plasmacytoma is a rare presentation of multiple myeloma. We emphasize the importance of imaging by presenting the 18F-FDG PET/CT findings of a patient with nasopharyngeal plasmacytoma and lytic hypermetabolic bone lesions.
Exploring the FAP-Targeted Therapeutics for Adrenocortical Carcinoma
Authors: Sejal Chopra, Rama Walia, Komalpreet Kaur, Frank Roesch, Euy Sung Moon, Bhagwant Rai Mittal, Jaya Shukla
Journal: Clinical Nuclear Medicine (2024)

Abstract Metastatic or recurrent adrenocortical carcinoma is a potentially lethal malignancy, presenting significant challenges in disease management owing to absence of effective systemic treatments. Significantly diminished survival rates necessitate rapid identification of specific molecules for the development of targeted therapeutics. Fibroblast activation protein (FAP)–expressing cancer-associated fibroblasts have been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. The effectiveness of various FAP inhibitors (FAPis) and FAP targeting peptide has been extensively documented in diverse clinical investigations. We have evaluated 3 molecules, that is, DOTA.SA.FAPi (SA.FAPi), FAPi46, and FAP2286, as potential theranostic probes for adrenocortical carcinoma.
Paraganglioma With Intracranial Invasion Demonstrated on 68Ga-DOTATATE PET/CT
Authors: Selin Kesim, Nuh Filizoglu
Journal: Clinical Nuclear Medicine (2024)

Abstract 68 Ga-DOTATATE PET/CT demonstrates superior sensitivity compared with other cross-sectional and functional imaging techniques in detecting head and neck paragangliomas. It is the primary recommended imaging modality for the evaluation of head and neck paragangliomas, especially in patients suspected of having locally aggressive, multifocal, or metastatic disease, as well as those being considered for targeted peptide-receptor therapy. Herein, we demonstrate the 68 Ga-DOTATATE PET/CT findings of a skull base paraganglioma with extensive local invasion and intracranial extension.
A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer
Authors: Shaoqiu Chen, Fangfang Liu, Yuanyuan Fu, Chris K Deng, Jeffrey A Borgia, Abdul-Ghani Ayman, Masaki Nasu, Mayumi Jijiwa, Hua Yang, Ting Gong, Junlong Wang, Zhougui Ling, Xiaoyan Wang, Hongwei Wang, Qian Chu, Youping Deng
Journal: Molecular Cancer (2024)

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC.
Giardia antagonizes beneficial functions of indigenous and therapeutic intestinal bacteria during protein deficiency
Authors: Aadra P. Bhatt, Jason W. Arnold, Muyiwa Awoniyi, Shan Sun, Verônica Feijoli Santiago, Deniz Coskuner, Pedro Henrique Quintela, Kenneth Walsh, Jamie Xiao, Renay Ngobeni-Nyambi, Brenna Hansen, Ajay S. Gulati, Ian M. Carroll, M. Andrea Azcarate-Peril, Anthony A. Fodor, Jonathan Swann, Luther A. Bartelt
Journal: Gut Microbes (2024)

Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp. and an increase in Bifidobacterium spp. This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp. mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia, despite not inhibiting Lactobacillus colonization. These results highlight Giardia's potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.
Body weight control via protein kinase CK2: diet-induced obesity counteracted by pharmacological targeting
Authors: Laura M Buchwald, Ditte Neess, Daniel Hansen, Thomas K Doktor, Vignesh Ramesh, Lasse B Steffensen, Blagoy Blagoev, David W Litchfield, Brage S Andresen, Kim Ravnskjaer, Nils J Færgeman, Barbara Guerra
Journal: Metabolism (2024)
Next-generation 3D printed multipurpose prevention intravaginal ring for prevention of HIV, HSV-2, and unintended pregnancy
Authors: Denali K Dahl, Priya Srinivasan, Rima Janusziewicz, Jasmine L King, Roopali Shrivastava, Jining Zhang, Dawn Little, Shanon Bachman, Kristen Kelley, Mackenzie L Cottrell, Amanda P Schauer, Craig Sykes, Angela D M Kashuba, James Smith, S Rahima Benhabbour
Journal: Journal of Controlled Release (2024)
Multifocal Soft Contact Lenses for the Treatment of Myopia Progression in Children
Authors: Kara M. Cavuoto, Rupal H. Trivedi, S. Grace Prakalapakorn, Julius T. Oatts, Sudha Nallasamy, David G. Morrison, Stacy L. Pineles, Melinda Y. Chang
Journal: Ophthalmology (2024)
Ultrasound-activated microbubbles mediate F-actin disruptions and endothelial gap formation during sonoporation
Authors: Bram Meijlink, H Rhodé van der Kooij, Yuchen Wang, Hongchen Li, Stephan Huveneers, Klazina Kooiman
Journal: Journal of Controlled Release (2024)

Locally opening up the endothelial barrier in a safe and controlled way is beneficial for drug delivery into the extravascular tissue. Although ultrasound-induced microbubble oscillations can affect the endothelial barrier integrity, the mechanism remains unknown. Here we uncover a new role for F-actin in microbubble-mediated endothelial gap formation. Unique simultaneous high-resolution confocal microscopy and ultra-high-speed camera imaging (10 million frames per second) reveal that single oscillating microbubbles (radius 1.3-3.8 μm; n = 48) induce sonoporation in all cells in which F-actin remodeling occurred. F-actin disruption only mainly resulted in tunnel formation (75 %), while F-actin stress fiber severing and recoil mainly resulted in cell-cell contact opening within 15 s upon treatment (54 %) and tunnel formation (15 %). F-actin stress fiber severing occurred when the fibers were within reach of the microbubble's maximum radius during oscillation, requiring normal forces of ≥230 nN. In the absence of F-actin stress fibers, oscillating microbubbles induced F-actin remodeling but no cell-cell contact opening. Together, these findings reveal a novel mechanism of microbubble-mediated transendothelial drug delivery, which associates with the underlying cytoskeletal F-actin organization.
Enhancing Capacity for Primary Care Research in Cancer Survivorship: National Cancer Institute Meeting Report
Authors: Shawna V Hudson, Michelle A Mollica, Crystal Reed, Erin E Hahn, Denalee M O’Malley, Archana Radhakrishnan, Jennifer Klemp, Emily Tonorezos
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Many components of long-term cancer follow-up and survivorship care are managed in the primary care context. Given the important role that primary care has in survivorship care, it is critical to ensure that teams in these settings are prepared to address long-term needs. Evidence-based strategies to deliver survivorship care in primary care settings in the United States remain limited. The National Cancer Institute Office of Cancer Survivorship conducted a day-long virtual event, Enhancing Capacity for Primary Care Research in Cancer Survivorship: A Workshop for Action, on February 28, 2024, to discuss research needs addressing the intersection between primary care and cancer survivorship. Topics discussed to advance this area of research included system-level interventions, methods and measurement, and mentorship and research team building, especially for early career researchers. The purpose of this report is to provide a summary of the key findings. Gaps and opportunities include (1) health systems–level research that investigates primary care practice–level capacity, (2) identification and characterization of the targeted cancer survivor populations for primary care research, (3) leveraging electronic medical records to track relevant patient outcomes throughout survivorship, and (4) development and creation of communities of practice to support and build research capacity. Team science approaches were identified as a core strategy to advance survivorship research. The meeting closed with a reflection and call to action focused on building collaborations that span different research areas, disciplines, and organizations and building a broad network of a primary care practice–focused research.
Yellow fever breakthrough infections after yellow fever vaccination: a systematic review and meta-analysis
Authors: Jenny L Schnyder, Bache E Bache, Matthijs R A Welkers, René Spijker, Frieder Schaumburg, Abraham Goorhuis, Martin P Grobusch, Hanna K de Jong
Journal: The Lancet Microbe (2024)

Yellow fever vaccination is considered to provide effective long-term immunity. However, yellow fever breakthrough infections in vaccinated patients have been reported. In this systematic review and meta-analysis we aimed to identify and summarise all documented symptomatic yellow fever breakthrough infections in the literature occurring less than 10 years and 10 years or more after primary yellow fever vaccination.
Burden of infectious diseases in Sudan
Authors: Priya Venkatesan
Journal: The Lancet Microbe (2024)

Aug 27, 2024, marked 500 days of violent conflict and civil war in Sudan between the Sudanese Armed Forces and the Rapid Support Forces, rival factions of the military government. Since then, the situation has only worsened: by Sept 16, more than an estimated 23 015 people had been killed, including a substantial number of civilians, and as of Oct 16 more than 11·3 million people had been displaced, with over 2·3 million fleeing to neighbouring countries, including Chad, South Sudan, Egypt, and Ethiopia.
Identification of complex Plasmodium falciparum genetic backgrounds circulating in Africa: a multicountry genomic epidemiology analysis
Authors: Olivo Miotto, Alfred Amambua-Ngwa, Lucas N Amenga-Etego, Muzamil M Abdel Hamid, Ishag Adam, Enoch Aninagyei, Tobias Apinjoh, Gordon A Awandare, Philip Bejon, Gwladys I Bertin, Marielle Bouyou-Akotet, Antoine Claessens, David J Conway, Umberto D'Alessandro, Mahamadou Diakite, Abdoulaye Djimdé, Arjen M Dondorp, Patrick Duffy, Rick M Fairhurst, Caterina I Fanello, Anita Ghansah, Deus S Ishengoma, Mara Lawniczak, Oumou Maïga-Ascofaré, Sarah Auburn, Anna Rosanas-Urgell, Varanya Wasakul, Nina F D White, Alexandria Harrott, Jacob Almagro-Garcia, Richard D Pearson, Sonia Goncalves, Cristina Ariani, Zbynek Bozdech, William L Hamilton, Victoria Simpson, Dominic P Kwiatkowski
Journal: The Lancet Microbe (2024)
Perspectives on drug development in chronic myelomonocytic leukemia: changing the paradigm
Authors: Anthony M. Hunter, Mrinal M. Patnaik, Raphael Itzykson, Ruben Mesa, Chatchada Karanes, Yanxia Li, R. Angelo de Claro, Kelly J. Norsworthy, Marc Theoret, Elizabeth Pulte, Eric Padron
Journal: Blood (2024)
Performance of Risk Models for Antimicrobial Resistance in Adult Patients With Sepsis
Authors: M. Cristina Vazquez Guillamet, Hanyang Liu, Andrew Atkinson, Victoria J. Fraser, Chenyang Lu, Marin H. Kollef
Journal: JAMA Network Open (2024)

The results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals.
Long-Term Adverse Effects and Complications After Prostate Cancer Treatment
Authors: Joseph M. Unger, Cathee Till, Catherine M. Tangen, Dawn L. Hershman, Phyllis J. Goodman, Michael LeBlanc, William E. Barlow, Riha Vaidya, Lori M. Minasian, Howard L. Parnes, Ian M. Thompson
Journal: JAMA Oncology (2024)

Due to the often indolent nature of prostate cancer (PCA), treatment decisions must weigh the risks and benefits of cancer control with those of treatment-associated morbidities.
Recombinant Human Thyrotropin Plus Radioactive Iodine Among Patients With Thyroid Cancer
Authors: Hui Tan, Yushen Gu, Yan Xiu, Xingmin Han, Qiang Wen, Zhongwei Lv, Wei Fan, Sijin Li, Jian Tan, Feng Wang, Wei Fu, Yifan Zhang, Jun Xin, Wei Ouyang, Xuemei Wang, Bin Liu, Yue Chen, Xuegong Liu, Yi Mo, Quanyong Luo, Jing Wang, Meng Li, Yan Di, Tao Xu, Hongcheng Shi
Journal: JAMA Network Open (2024)

Radioactive iodine (131I or RAI) therapy has long been the standard of care for most patients with differentiated thyroid cancer (DTC) after primary surgery. However, no multicenter prospective studies have identified the optimal administered activity and stimulation method for RAI therapy in patients with intermediate-risk DTC.
Equecabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myeloma
Authors: Chunrui Li, Keshu Zhou, Yongxian Hu, Dehui Zou, Lijuan Chen, Bing Chen, Jing Liu, Xi Zhang, Hanyun Ren, Kai Hu, Peng Liu, Jian-Qing Mi, Zhenyu Li, Kaiyang Ding, Di Wang, Wen Wang, Songbai Cai, Jianyong Li, Yongping Song, He Huang, Lugui Qiu
Journal: JAMA Oncology (2024)

Equecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.