tbuckley/cabot-search huggingface dataset:
Organoids‐On‐a‐Chip for Personalized Precision Medicine
Authors: Yunqi Man, Yanfei Liu, Qiwen Chen, Zhirou Zhang, Mingfeng Li, Lishang Xu, Yifu Tan, Zhenbao Liu
Journal: Advanced Healthcare Materials (2024)

Abstract The development of personalized precision medicine has become a pivotal focus in modern healthcare. Organoids‐on‐a‐Chip (OoCs), a groundbreaking fusion of organoid culture and microfluidic chip technology, has emerged as a promising approach to advancing patient‐specific treatment strategies. In this review, the diverse applications of OoCs are explored, particularly their pivotal role in personalized precision medicine, and their potential as a cutting‐edge technology is highlighted. By utilizing patient‐derived organoids, OoCs offer a pathway to optimize treatments, create precise disease models, investigate disease mechanisms, conduct drug screenings, and individualize therapeutic strategies. The emphasis is on the significance of this technological fusion in revolutionizing healthcare and improving patient outcomes. Furthermore, the transformative potential of personalized precision medicine, future prospects, and ongoing advancements in the field, with a focus on genomic medicine, multi‐omics integration, and ethical frameworks are discussed. The convergence of these innovations can empower patients, redefine treatment approaches, and shape the future of healthcare.
Glutathione‐Depleted Photodynamic Nanoadjuvant for Triggering Nonferrous Ferroptosis to Amplify Radiotherapy of Breast Cancer
Authors: Jiangnan Shi, Guoqing Cui, Yaqi Jin, Boyu Mi, Kenan Liu, Linqian Zhao, Kewang Bao, Ziyao Lu, Jie Liu, Yuwei Wang, Hui He, Zhengqing Guo
Journal: Advanced Healthcare Materials (2024)

Abstract Radiotherapy plays a crucial role in the treatment of advanced breast cancer, but the increased antioxidant system, especially the rise in glutathione (GSH), presents a significant obstacle to its effectiveness. To address this challenge, a versatile GSH‐depleted photodynamic nanoadjuvant is developed to augment the efficacy of radiotherapy for breast cancer treatment. This nanoadjuvant operates within the tumor microenvironment to effectively deplete intracellular GSH through a sequence of cascaded processes, including GSH exhaustion, biosynthetic inhibition, and photodynamic oxidation. This leads to a notable accumulation of lipid peroxides (LPO) and subsequent suppression of glutathione peroxidase 4 (GPX4) activity. Consequently, the combined GSH depletion induced by the nanoadjuvant markedly promotes nonferrous ferroptosis, thereby contributing to the augmentation of antitumor efficiency during radiotherapy in breast cancer. This work presents an innovative approach to designing and synthesizing biocompatible nanoadjuvants with the goal of improving the efficacy of radiotherapy for breast cancer in prospective clinical scenarios.
Glove Phenomenon Detected by Total-Body PET/CT With 68GA-DOTATATE
Authors: Hande Nalbant, Clemens Mingels, Fatma Sen, Benjamin A. Spencer, Jonathan W. Riess, Lorenzo Nardo
Journal: Clinical Nuclear Medicine (2024)

Accidental intra-arterial injections of radiotracers are rare events resulting in a specific imaging pattern, described as "hot-forearm," "hot-hand," "glove-phenomenon," or "glove-like pattern." We present a case 68 Ga-DOTATATE total-body PET/CT for restaging of a neuroendocrine tumor, where intra-arterial misinjection resulted in a glove phenomenon. Since patients may present with minimal symptoms, like in this case, and PET findings may only be seen at the distal upper extremity (placed above the head), these accidental injections may be more frequently detected with total-body PET/CT due to the longer field-of-view. Radiologists and technologists should be aware of this possibility to avoid accidental misinjections.
Negative 18F-FDG and Positive 68Ga-FAPI-04 Findings in a Patient With Acute Exacerbation of Chronic Cholecystitis
Authors: Na Qi, Jie Ding, Haiyan Wang, Jun Zhao
Journal: Clinical Nuclear Medicine (2024)

Abstract Acute cholecystitis typically exhibits intense FDG uptake of the gallbladder wall. Radiolabeled fibroblast activation protein inhibitor (FAPI) is considered as a potential alternative agent for tumor-specific imaging. We report 18 F-FDG and 68 Ga-FAPI-04 PET/MR findings in a 44-year-old woman with acute exacerbation of chronic cholecystitis. The lesions show negative 18 F-FDG uptake but intense 68 Ga-FAPI-04 uptake in PET/MR. This case highlights the imperative for nuclear medicine clinicians to exercise vigilance when evaluating gallbladder lesions exhibiting intense 68 Ga-FAPI-04 but negative 18 F-FDG uptake.
Multifocal Hemorrhagic Choriocarcinoma With Diffuse Pancreatic FDG Uptake on 18F-FDG PET/CT
Authors: Sheng Dai, Youwen Dong
Journal: Clinical Nuclear Medicine (2024)

Abstract Choriocarcinoma is a rare and highly malignant trophoblastic tumor. We present a case involving a 30-year-old woman with abdominal pain, hemoptysis, and elevated serum amylase levels. Initial clinical suspicion included acute pancreatitis. Noncontrast and contrast-enhanced CT revealed hemorrhagic and hypervascular lesions in the lungs, pancreas, liver, and kidneys. 18 F-FDG PET/CT showed diffuse pancreatic enlargement with increased FDG uptake (SUV max , 5.3), consistent with malignancy. Histopathology confirmed choriocarcinoma with elevated HCG levels. Following chemotherapy, HCG levels declined, indicating a positive therapeutic response. 18 F-FDG PET/CT effectively detected choriocarcinoma and assessed its systemic involvement.
Lymphoscintigraphy With SPECT-CT in Detecting the Site of Chyle Leak in Postoperative Patient
Authors: Shefali M. Gokhale, Manish Bhatia
Journal: Clinical Nuclear Medicine (2024)

Abstract Here is a case of chyle leak post McKeown esophagectomy. Lymphoscintigraphy with 99m Tc-filtered sulfur colloid revealed tracer accumulation along the thoracic duct and in the left hemithorax. Precise localization of leak was done by SPECT-CT imaging. This enabled timely surgical intervention and reduced further morbidity. This procedure is not only precise but also cost-effective as compared with the other available investigations.
Reversal of Basal Ganglia Hypermetabolism Following Surgical Removal of Adrenocorticotropic Hormone–Producing Lung Carcinoid in a Patient of Cushing Syndrome With Unusual Presentation of Acute Psychosis
Authors: Gaurav Malhotra, Rajeev Kasaliwal, Karishma Rupani, Anurag R. Lila, Trupti Upadhye, Tushar Bandgar, Nalini S. Shah
Journal: Clinical Nuclear Medicine (2024)

Abstract A 34-year-old woman who presented with severe psychosis and clinical features of Cushing syndrome underwent 18 F-FDG PET/CT that revealed hypermetabolic lung lesion along with predominantly increased metabolism of bilateral basal ganglia, a scintigraphic correlate of acute psychosis. The lesion was surgically excised and histopathologically proven to be adrenocorticotropic hormone–producing lung carcinoid. Posttreatment 18 F-FDG PET scan showed restoration of normal brain metabolism with complete reversal of psychosis. Even though rare, one should be aware of psychosis as an initial presentation of Cushing syndrome and use of 18 F-FDG PET/CT for mapping brain metabolism as shown in this case.
68Ga-DOTATATE and 18F-FDG PET/CT in a Rapidly Progressing Lymphoma
Authors: Ashwin Singh Parihar, Richard L. Wahl, Amin H. Jahromi
Journal: Clinical Nuclear Medicine (2024)

Abstract 68 Ga-DOTATATE PET/CT targeting somatostatin receptors is commonly utilized in the imaging of neuroendocrine tumors. However, other malignancies such as lymphomas (both Hodgkin and non-Hodgkin) also have expression of somatostatin receptors, albeit to a lesser degree compared with the neuroendocrine tumors, and thus can be positive on a 68 Ga-DOTATATE PET/CT. We describe an atypical presentation of an aggressive large B-cell lymphoma mimicking a metastatic neuroendocrine tumor at initial presentation with high somatostatin receptor expression demonstrated on the 68 Ga-DOTATATE PET/CT and a rapidly progressing course on the subsequent 18 F-FDG PET/CT.
Diagnostic Accuracy of PSMA PET-Guided Prostate Biopsy in Prostate Cancer—A Systematic Review and Meta-analysis
Authors: Piyush Aggarwal, Vinisha Gunasekaran, Harmandeep Singh, Rajender Kumar, Swayamjeet Satapathy, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2024)

Purpose Early diagnosis and treatment of prostate cancer (PC) are crucial for effective management and improved patient outcomes. Newer imaging modalities like prostate-specific membrane antigen PET have shown superior diagnostic performance in detecting PC and clinically significant PC (csPC). This systematic review and meta-analysis aims to synthesize evidence on the diagnostic performance of PSMA PET-guided prostate biopsy in detecting PC and csPC. Patients and Methods The study followed the PRISMA-DTA guidelines. Using a predefined search strategy, 3 databases (PubMed, Embase, and Web of Science) were systematically searched using appropriate keywords. A meta-analysis was conducted using diagnostic accuracy parameters of the included studies. Risk of bias assessment was done using the QUADAS-2 tool. Results Out of 378 articles, 20 were assessed for full-text screening and 10 articles with 874 patients were finally included. Eight studies reported a pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of 0.90 (95%confidence interval [CI], 0.82–0.95), 0.93 (95% CI, 0.57–0.99), 12.3 (95% CI, 1.5–98.9), 0.10 (95% CI, 0.05–0.20), and 117 (95% CI, 12–1178), respectively, for detecting PC using PSMA PET-guided prostate biopsy with an area under the summary receiver operating characteristics curve of 0.94 (95% CI, 0.92–0.96). Similarly, 6 studies reported a pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of 0.89 (95% CI, 0.82–0.94), 0.65 (95% CI, 0.49–0.79), 2.6 (95% CI, 1.6–4.1), 0.17 (95% CI, 0.09–0.31), and 15 (95% CI, 6–41), respectively, for detecting csPC using PSMA PET-guided prostate biopsy with area under summary receiver operating characteristics curve of 0.86 (95% CI, 0.82–0.88). Conclusions PSMA PET-guided prostate biopsy has a high diagnostic accuracy in detecting PC and csPC in patients with clinical suspicion of PC, and provides a 1-stop solution for early diagnosis and staging of PC.
zMAP toolset: model-based analysis of large-scale proteomic data via a variance stabilizing z-transformation
Authors: Xiuqi Gui, Jing Huang, Linjie Ruan, Yanjun Wu, Xuan Guo, Ruifang Cao, Shuhan Zhou, Fengxiang Tan, Hongwen Zhu, Mushan Li, Guoqing Zhang, Hu Zhou, Lixing Zhan, Xin Liu, Shiqi Tu, Zhen Shao
Journal: Genome biology (2024)

Isobaric labeling-based mass spectrometry (ILMS) has been widely used to quantify, on a proteome-wide scale, the relative protein abundance in different biological conditions. However, large-scale ILMS data sets typically involve multiple runs of mass spectrometry, bringing great computational difficulty to the integration of ILMS samples. We present zMAP, a toolset that makes ILMS intensities comparable across mass spectrometry runs by modeling the associated mean-variance dependence and accordingly applying a variance stabilizing z-transformation. The practical utility of zMAP is demonstrated in several case studies involving the dynamics of cell differentiation and the heterogeneity across cancer patients.
Functional variant rs9344 at 11q13.3 regulates CCND1 expression in multiple myeloma with t(11;14)
Authors: Hongwei Tang, Huihuang Yan, Suganti Shivaram, Stacey Lehman, Neeraj Sharma, James Smadbeck, Cinthya Zepeda-Mendoza, Shulan Tian, Yan Asmann, Celine Vachon, Alexandre Gaspar Maia, Jonathan Keats, P. Leif Bergsagel, Rafael Fonseca, A. Keith Stewart, Joel-Sean Hsu, Richard K. Kandasamy, Akhilesh Pandey, Marcella A. Kaddoura, Francesco Maura, Amit Mitra, S. Vincent Rajkumar, Shaji K. Kumar, Eran Elhaik, Esteban Braggio, Linda B. Baughn
Journal: Leukemia (2024)

Multiple myeloma (MM) is a plasma cell (PC) malignancy characterized by cytogenetic abnormalities, such as t(11;14)(q13;q32), resulting in CCND1 overexpression. The rs9344 G allele within CCND1 is the most significant susceptibility allele for t(11;14). Sequencing data from 2 independent cohorts, CoMMpass (n = 698) and Mayo Clinic (n = 661), confirm the positive association between the G allele and t(11;14). Among 80% of individuals heterozygous for rs9344 with t(11;14), the t(11;14) event occurs on the G allele, demonstrating a biological preference for the G allele in t(11;14). Within t(11;14), the G allele is associated with higher CCND1 expression and elevated H3K27ac and H3K4me3. CRISPR/Cas9 mediated A to G conversion resulted in increased H3K27ac over CCND1 and elevated CCND1 expression. ENCODE ChIP-seq data supported a PAX5 binding site within the enhancer region covering rs9344, showing preferential binding to the G allele. Overexpression of PAX5 resulted in increased CCND1 expression. These results support the importance of rs9344 G enhancer in increasing CCND1 expression in MM.
When less is more: sketching with minimizers in genomics
Authors: Malick Ndiaye, Silvia Prieto-Baños, Lucy M. Fitzgerald, Ali Yazdizadeh Kharrazi, Sergey Oreshkov, Christophe Dessimoz, Fritz J. Sedlazeck, Natasha Glover, Sina Majidian
Journal: Genome biology (2024)

The exponential increase in sequencing data calls for conceptual and computational advances to extract useful biological insights. One such advance, minimizers, allows for reducing the quantity of data handled while maintaining some of its key properties. We provide a basic introduction to minimizers, cover recent methodological developments, and review the diverse applications of minimizers to analyze genomic data, including de novo genome assembly, metagenomics, read alignment, read correction, and pangenomes. We also touch on alternative data sketching techniques including universal hitting sets, syncmers, or strobemers. Minimizers and their alternatives have rapidly become indispensable tools for handling vast amounts of data.
The ribosome profiling landscape of yeast reveals a high diversity in pervasive translation
Authors: Chris Papadopoulos, Hugo Arbes, David Cornu, Nicolas Chevrollier, Sandra Blanchet, Paul Roginski, Camille Rabier, Safiya Atia, Olivier Lespinet, Olivier Namy, Anne Lopes
Journal: Genome biology (2024)

Pervasive translation is a widespread phenomenon that plays a critical role in the emergence of novel microproteins, but the diversity of translation patterns contributing to their generation remains unclear. Based on 54 ribosome profiling (Ribo-Seq) datasets, we investigated the yeast Ribo-Seq landscape using a representation framework that allows the comprehensive inventory and classification of the entire diversity of Ribo-Seq signals, including non-canonical ones.
Correction: Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy
Authors: Hui Wang, Timothy S. Chang, Beth A. Dombroski, Po-Liang Cheng, Vishakha Patil, Leopoldo Valiente-Banuet, Kurt Farrell, Catriona Mclean, Laura Molina-Porcel, Alex Rajput, Peter Paul De Deyn, Nathalie Le Bastard, Marla Gearing, Laura Donker Kaat, John C. Van Swieten, Elise Dopper, Bernardino F. Ghetti, Kathy L. Newell, Claire Troakes, Justo G. de Yébenes, Alberto Rábano-Gutierrez, Tina Meller, Wolfgang H. Oertel, Gesine Respondek, Maria Stamelou, Thomas Arzberger, Sigrun Roeber, Ulrich Müller, Franziska Hopfner, Pau Pastor, Alexis Brice, Alexandra Durr, Isabelle Le Ber, Thomas G. Beach, Geidy E. Serrano, Lili-Naz Hazrati, Irene Litvan, Rosa Rademakers, Owen A. Ross, Douglas Galasko, Adam L. Boxer, Bruce L. Miller, Willian W. Seeley, Vivanna M. Van Deerlin, Edward B. Lee, Charles L. White, Huw Morris, Rohan de Silva, John F. Crary, Alison M. Goate, Jeffrey S. Friedman, Yuk Yee Leung, Giovanni Coppola, Adam C. Naj, Li-San Wang, Clifton Dalgard, Dennis W. Dickson, Günter U. Höglinger, Gerard D. Schellenberg, Daniel H. Geschwind, Wan-Ping Lee
Journal: Molecular Neurodegeneration (2024)
Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency
Authors: Andreas Obers, Tobias Poch, Grace Rodrigues, Susan N Christo, Luke C Gandolfo, Raissa Fonseca, Ali Zaid, Joey En Yu Kuai, Hongjin Lai, Pirooz Zareie, Marina H Yakou, Lachlan Dryburgh, Thomas N Burn, James Dosser, Frank A Buquicchio, Caleb A Lareau, Calum Walsh, Louise Judd, Maria Rafailia Theodorou, Katharina Gutbrod, Peter Dörmann, Jenny Kingham, Tim Stinear, Axel Kallies, Jan Schroeder, Scott N Mueller, Simone L Park, Terence P Speed, Ansuman T Satpathy, Tri Giang Phan, Christoph Wilhelm, Colby Zaph, Maximilien Evrard, Laura K Mackay
Journal: Immunity (2024)
Long-read sequencing of an advanced cancer cohort resolves rearrangements, unravels haplotypes, and reveals methylation landscapes
Authors: Kieran O'Neill, Erin Pleasance, Jeremy Fan, Vahid Akbari, Glenn Chang, Katherine Dixon, Veronika Csizmok, Signe MacLennan, Vanessa Porter, Andrew Galbraith, Cameron J Grisdale, Luka Culibrk, John H Dupuis, Richard Corbett, James Hopkins, Reanne Bowlby, Pawan Pandoh, Duane E Smailus, Dean Cheng, Tina Wong, Connor Frey, Yaoqing Shen, Eleanor Lewis, Luis F Paulin, Fritz J Sedlazeck, Jessica M T Nelson, Eric Chuah, Karen L Mungall, Richard A Moore, Robin Coope, Andrew J Mungall, Melissa K McConechy, Laura M Williamson, Kasmintan A Schrader, Stephen Yip, Marco A Marra, Janessa Laskin, Steven J M Jones
Journal: Cell Genomics (2024)

The Long-Read Personalized OncoGenomics (POG) dataset comprises a cohort of 189 patient tumors and 41 matched normal samples sequenced using the Oxford Nanopore Technologies PromethION platform. This dataset from the POG program and the Marathon of Hope Cancer Centres Network includes DNA and RNA short-read sequence data, analytics, and clinical information. We show the potential of long-read sequencing for resolving complex cancer-related structural variants, viral integrations, and extrachromosomal circular DNA. Long-range phasing facilitates the discovery of allelically differentially methylated regions (aDMRs) and allele-specific expression, including recurrent aDMRs in the cancer genes RET and CDKN2A. Germline promoter methylation in MLH1 can be directly observed in Lynch syndrome. Promoter methylation in BRCA1 and RAD51C is a likely driver behind homologous recombination deficiency where no coding driver mutation was found. This dataset demonstrates applications for long-read sequencing in precision medicine and is available as a resource for developing analytical approaches using this technology.
Complex structural variation is prevalent and highly pathogenic in pediatric solid tumors
Authors: Ianthe A E M van Belzen, Marc van Tuil, Shashi Badloe, Alex Janse, Eugène T P Verwiel, Marcel Santoso, Sam de Vos, John Baker-Hernandez, Hindrik H D Kerstens, Nienke Solleveld-Westerink, Michael T Meister, Jarno Drost, Marry M van den Heuvel-Eibrink, Johannes H M Merks, Jan J Molenaar, Weng Chuan Peng, Bastiaan B J Tops, Frank C P Holstege, Patrick Kemmeren, Jayne Y Hehir-Kwa
Journal: Cell Genomics (2024)

In pediatric cancer, structural variants (SVs) and copy-number alterations contribute to cancer initiation as well as progression, thereby aiding diagnosis and treatment stratification. Although suggested to be of importance, the prevalence and biological relevance of complex genomic rearrangements (CGRs) across pediatric solid tumors is largely unexplored. In a cohort of 120 primary tumors, we systematically characterized patterns of extrachromosomal DNA, chromoplexy, and chromothripsis across five pediatric solid cancer types. CGRs were identified in 56 tumors (47%), and in 42 of these tumors, CGRs affect cancer driver genes or result in unfavorable chromosomal alterations. This demonstrates that CGRs are prevalent and pathogenic in pediatric solid tumors and suggests that selection likely contributes to the structural variation landscape. Moreover, carrying CGRs is associated with more adverse clinical events. Our study highlights the potential for CGRs to be incorporated in risk stratification or exploited for targeted treatments.
Analysis of single-cell CRISPR perturbations indicates that enhancers predominantly act multiplicatively
Authors: Jessica L Zhou, Karthik Guruvayurappan, Shushan Toneyan, Hsiuyi V Chen, Aaron R Chen, Peter Koo, Graham McVicker
Journal: Cell Genomics (2024)

A single gene may have multiple enhancers, but how they work in concert to regulate transcription is poorly understood. To analyze enhancer interactions throughout the genome, we developed a generalized linear modeling framework, GLiMMIRS, for interrogating enhancer effects from single-cell CRISPR experiments. We applied GLiMMIRS to a published dataset and tested for interactions between 46,166 enhancer pairs and corresponding genes, including 264 "high-confidence" enhancer pairs. We found that enhancer effects combine multiplicatively but with limited evidence for further interactions. Only 31 enhancer pairs exhibited significant interactions (false discovery rate <0.1), none of which came from the high-confidence set, and 20 were driven by outlier expression values. Additional analyses of a second CRISPR dataset and in silico enhancer perturbations with Enformer both support a multiplicative model of enhancer effects without interactions. Altogether, our results indicate that enhancer interactions are uncommon or have small effects that are difficult to detect.
Persistent activity during working memory maintenance predicts long-term memory formation in the human hippocampus
Authors: Jonathan Daume, Jan Kamiński, Yousef Salimpour, Andrea Gómez Palacio Schjetnan, William S Anderson, Taufik A Valiante, Adam N Mamelak, Ueli Rutishauser
Journal: Neuron (2024)

Working memory (WM) and long-term memory (LTM) are often viewed as separate cognitive systems. Little is known about how these systems interact when forming memories. We recorded single neurons in the human medial temporal lobe while patients maintained novel items in WM and completed a subsequent recognition memory test for the same items. In the hippocampus, but not in the amygdala, the level of WM content-selective persistent activity during WM maintenance was predictive of whether the item was later recognized with high confidence or forgotten. By contrast, visually evoked activity in the same cells was not predictive of LTM formation. During LTM retrieval, memory-selective neurons responded more strongly to familiar stimuli for which persistent activity was high while they were maintained in WM. Our study suggests that hippocampal persistent activity of the same cells supports both WM maintenance and LTM encoding, thereby revealing a common single-neuron component of these two memory systems.
Autophagy, aging, and age-related neurodegeneration
Authors: Jennifer E Palmer, Niall Wilson, Sung Min Son, Pawel Obrocki, Lidia Wrobel, Matea Rob, Michael Takla, Viktor I Korolchuk, David C Rubinsztein
Journal: Neuron (2024)

Autophagy is a conserved mechanism that degrades damaged or superfluous cellular contents and enables nutrient recycling under starvation conditions. Many neurodegeneration-associated proteins are autophagy substrates, and autophagy upregulation ameliorates disease in many animal models of neurodegeneration by enhancing the clearance of toxic proteins, proinflammatory molecules, and dysfunctional organelles. Autophagy inhibition also induces neuronal and glial senescence, a phenomenon that occurs with increasing age in non-diseased brains as well as in response to neurodegeneration-associated stresses. However, aging and many neurodegeneration-associated proteins and mutations impair autophagy. This creates a potentially detrimental feedback loop whereby the accumulation of these disease-associated proteins impairs their autophagic clearance, facilitating their further accumulation and aggregation. Thus, understanding how autophagy interacts with aging, senescence, and neurodegenerative diseases in a temporal, cellular, and genetic context is important for the future clinical application of autophagy-modulating therapies in aging and neurodegeneration.