tbuckley/cabot-search huggingface dataset:
Evaluation of somatic copy number variation detection by NGS technologies and bioinformatics tools on a hyper-diploid cancer genome
Authors: Daniall Masood, Luyao Ren, Cu Nguyen, Francesco G. Brundu, Lily Zheng, Yongmei Zhao, Erich Jaeger, Yong Li, Seong Won Cha, Aaron Halpern, Sean Truong, Michael Virata, Chunhua Yan, Qingrong Chen, Andy Pang, Reyes Alberto, Chunlin Xiao, Zhaowei Yang, Wanqiu Chen, Charles Wang, Frank Cross, Severine Catreux, Leming Shi, Julia A. Beaver, Wenming Xiao, Daoud M. Meerzaman
Journal: Genome biology (2024)

Abstract Background Copy number variation (CNV) is a key genetic characteristic for cancer diagnostics and can be used as a biomarker for the selection of therapeutic treatments. Using data sets established in our previous study, we benchmark the performance of cancer CNV calling by six most recent and commonly used software tools on their detection accuracy, sensitivity, and reproducibility. In comparison to other orthogonal methods, such as microarray and Bionano, we also explore the consistency of CNV calling across different technologies on a challenging genome. Results While consistent results are observed for copy gain, loss, and loss of heterozygosity (LOH) calls across sequencing centers, CNV callers, and different technologies, variation of CNV calls are mostly affected by the determination of genome ploidy. Using consensus results from six CNV callers and confirmation from three orthogonal methods, we establish a high confident CNV call set for the reference cancer cell line (HCC1395). Conclusions NGS technologies and current bioinformatics tools can offer reliable results for detection of copy gain, loss, and LOH. However, when working with a hyper-diploid genome, some software tools can call excessive copy gain or loss due to inaccurate assessment of genome ploidy. With performance matrices on various experimental conditions, this study raises awareness within the cancer research community for the selection of sequencing platforms, sample preparation, sequencing coverage, and the choice of CNV detection tools.
Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons
Authors: Anna Zhuravskaya, Karen Yap, Fursham Hamid, Eugene V. Makeyev
Journal: Genome biology (2024)

Abstract Background The functional coupling between alternative pre-mRNA splicing (AS) and the mRNA quality control mechanism called nonsense-mediated decay (NMD) can modulate transcript abundance. Previous studies have identified several examples of such a regulation in developing neurons. However, the systems-level effects of AS-NMD in this context are poorly understood. Results We developed an R package, factR2, which offers a comprehensive suite of AS-NMD analysis functions. Using this tool, we conducted a longitudinal analysis of gene expression in pluripotent stem cells undergoing induced neuronal differentiation. Our analysis uncovers hundreds of AS-NMD events with significant potential to regulate gene expression. Notably, this regulation is significantly overrepresented in specific functional groups of developmentally downregulated genes. Particularly strong association with gene downregulation is detected for alternative cassette exons stimulating NMD upon their inclusion into mature mRNA. By combining bioinformatic analyses with CRISPR/Cas9 genome editing and other experimental approaches we show that NMD-stimulating cassette exons regulated by the RNA-binding protein PTBP1 dampen the expression of their genes in developing neurons. We also provided evidence that the inclusion of NMD-stimulating cassette exons into mature mRNAs is temporally coordinated with NMD-independent gene repression mechanisms. Conclusions Our study provides an accessible workflow for the discovery and prioritization of AS-NMD targets. It further argues that the AS-NMD pathway plays a widespread role in developing neurons by facilitating the downregulation of functionally related non-neuronal genes.
Vaccination reduces central nervous system IL-1β and memory deficits after COVID-19 in mice
Authors: Abigail Vanderheiden, Jeremy D. Hill, Xiaoping Jiang, Ben Deppen, Gayan Bamunuarachchi, Nadia Soudani, Astha Joshi, Matthew D. Cain, Adrianus C. M. Boon, Robyn S. Klein
Journal: Nature Immunology (2024)
Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: a phase 1 placebo-controlled trial
Authors: Pepijn Eijsvogel, Pinaki Misra, Luis Concha-Marambio, Justin D. Boyd, Shuang Ding, Lauren Fedor, Yueh-Ting Hsieh, Yu Shuang Sun, Madeline M. Vroom, Carly M. Farris, Yihua Ma, Marieke L. de Kam, Igor Radanovic, Maurits F. J. M. Vissers, Dario Mirski, Ghazal Shareghi, Mohammad Shahnawaz, Wolfgang Singer, Philip Kremer, Geert Jan Groeneveld, Hui Jing Yu, Jean-Cosme Dodart
Journal: Nature Medicine (2024)

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF). Exploratory outcomes were changes in clinical scales and biomarker-based target engagement as measured by seed amplification assays. Twenty patients were randomized 7:3 (UB-312:placebo) into 300/100/100 μg or 300/300/300 μg (weeks 1, 5 and 13) intramuscular prime-boost dose groups. Safety was similar across groups; adverse events were mostly mild and transient. Two patients experienced three serious adverse events in total, one possibly treatment related; all resolved without sequalae. Anti-αSyn antibodies in serum from 12/13 and CSF from 5/13 patients who received three UB-312 doses confirmed immunogenicity. Mean serum titers (in log-dilution factor) increased from baseline by 1.398 and 1.354, and peaked at week 29 at 2.520 and 2.133, for 300/100/100 μg and 300/300/300 μg, respectively. CSF titers were 0 at baseline and were 0.182 and 0.032 at week 21, respectively. Exploratory analyses showed no statistical differences in clinical scales but a significant reduction of αSyn seeds in CSF of a subset of UB-312-treated patients. These data support further UB-312 development. ClinicalTrials.gov: NCT04075318 .
Coordinated action of a gut–liver pathway drives alcohol detoxification and consumption
Authors: Yaojie Fu, Bryan Mackowiak, Yu-Hong Lin, Luca Maccioni, Taylor Lehner, Hongna Pan, Yukun Guan, Grzegorz Godlewski, Hongkun Lu, Cheng Chen, Shoupeng Wei, Dechun Feng, Janos Paloczi, Huiping Zhou, Pal Pacher, Li Zhang, George Kunos, Bin Gao
Journal: Nature Metabolism (2024)
Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation
Authors: Mathijs P. Verhagen, Rosalie Joosten, Mark Schmitt, Niko Välimäki, Andrea Sacchetti, Kristiina Rajamäki, Jiahn Choi, Paola Procopio, Sara Silva, Berdine van der Steen, Thierry P. P. van den Bosch, Danielle Seinstra, Annemarie C. de Vries, Michail Doukas, Leonard H. Augenlicht, Lauri A. Aaltonen, Riccardo Fodde
Journal: Nature Genetics (2024)

Abstract According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, has been shown to suppress intestinal stemness. Here, we used Paneth cells as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation in mice. Upon inflammation, Paneth cell-specific Apc mutations led to intestinal tumors reminiscent not only of those arising in patients with inflammatory bowel disease, but also of a larger fraction of human sporadic colon cancers. The latter is possibly because of the inflammatory consequences of western-style dietary habits, a major colon cancer risk factor. Machine learning methods designed to predict the cell-of-origin of cancer from patient-derived tumor samples confirmed that, in a substantial fraction of sporadic cases, the origins of colon cancer reside in secretory lineages and not in stem cells.
Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies
Authors: Robert F J Kullberg, Irina Wikki, Bastiaan W Haak, Anni Kauko, Henrike Galenkamp, Hessel Peters-Sengers, Joe M Butler, Aki S Havulinna, Joonatan Palmu, Daniel McDonald, Chouaib Benchraka, Mahmoud I Abdel-Aziz, Maria Prins, Anke H Maitland van der Zee, Bert-Jan van den Born, Pekka Jousilahti, Willem M de Vos, Veikko Salomaa, Rob Knight, Leo Lahti, Max Nieuwdorp, Teemu Niiranen, W Joost Wiersinga
Journal: The Lancet Microbe (2024)
<i>CYP2C19</i> Genetic Testing for Oral P2Y12 Inhibitor Therapy: A Scientific Statement From the American Heart Association
Authors: Naveen L. Pereira, Sharon Cresci, Dominick J. Angiolillo, Wayne Batchelor, Quinn Capers, Larisa H. Cavallari, Dana Leifer, Jasmine A. Luzum, Dan M. Roden, Konstantinos Stellos, Stephanie L. Turrise, Sony Tuteja
Journal: Circulation (2024)

There is significant variability in the efficacy and safety of oral P2Y12 inhibitors, which are used to prevent ischemic outcomes in common diseases such as coronary and peripheral arterial disease and stroke. Clopidogrel, a prodrug, is the most used oral P2Y12 inhibitor and is activated primarily after being metabolized by a highly polymorphic hepatic cytochrome CYP2C219 enzyme. Loss-of-function genetic variants in
Mis-localization of endogenous TDP-43 leads to ALS-like early-stage metabolic dysfunction and progressive motor deficits
Authors: Yiying Hu, Alexander Hruscha, Chenchen Pan, Martina Schifferer, Michael K. Schmidt, Brigitte Nuscher, Martin Giera, Sarantos Kostidis, Özge Burhan, Frauke van Bebber, Dieter Edbauer, Thomas Arzberger, Christian Haass, Bettina Schmid
Journal: Molecular Neurodegeneration (2024)

The key pathological signature of ALS/ FTLD is the mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm. However, TDP-43 gain of function in the cytoplasm is still poorly understood since TDP-43 animal models recapitulating mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm are missing.
Prevalence and risk factors for milk allergy overdiagnosis in the BEEP trial cohort
Authors: Hilary I. Allen, Olivia Wing, Dara Milkova, Emilia Jackson, Karen Li, Lucy E. Bradshaw, Laura Wyatt, Rachel Haines, Miriam Santer, Andrew W. Murphy, Sara J. Brown, Maeve Kelleher, Michael R. Perkin, Nicola Jay, Timothy D. H. Smith, Frank Moriarty, Alan A. Montgomery, Hywel C. Williams, Robert J. Boyle
Journal: Allergy (2024)

Abstract Background Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual‐level and primary care practice‐level risk factors. Methods We analysed data from 1394 children born in England in 2014–2016 (BEEP trial, ISRCTN21528841). Participants underwent formal CMA diagnosis at ≤2 years. CMA overdiagnosis was defined in three separate ways: parent‐reported milk reaction; primary care record of milk hypersensitivity symptoms; and primary care record of low‐allergy formula prescription. Results CMA was formally diagnosed in 19 (1.4%) participants. CMA overdiagnosis was common: 16.1% had parent‐reported cow's milk hypersensitivity, 11.3% primary care recorded milk hypersensitivity and 8.7% had low‐allergy formula prescription. Symptoms attributed to cow's milk hypersensitivity in participants without CMA were commonly gastrointestinal and reported from a median age of 49 days. Low‐allergy formula prescriptions in participants without CMA lasted a median of 10 months (interquartile range 1, 16); the estimated volume consumed was a median of 272 litres (26, 448). Risk factors for CMA overdiagnosis were high practice‐based low‐allergy formula prescribing in the previous year and maternal report of antibiotic prescription during pregnancy. Exclusive formula feeding from birth was associated with increased low‐allergy formula prescription. There was no evidence that practice prescribing of paediatric adrenaline auto‐injectors or anti‐reflux medications, or maternal features such as anxiety, age, parity and socioeconomic status were associated with CMA overdiagnosis. Conclusion CMA overdiagnosis is common in early infancy. Risk factors include high primary care practice‐based low‐allergy formula prescribing and maternal report of antibiotic prescription during pregnancy.
Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision
Authors: Leisha A Emens, Pedro J Romero, Ana Carrizosa Anderson, Tullia C Bruno, Christian M Capitini, Deborah Collyar, James L Gulley, Patrick Hwu, Avery D Posey, Ann W Silk, Jennifer A Wargo
Journal: Journal for ImmunoTherapy of Cancer (2024)

Cancer immunotherapy has flourished over the last 10–15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor microenvironment. With this rapid clinical and scientific progress, the field of cancer immunotherapy is currently at a critical inflection point, with potential for exponential growth over the next decade. Recognizing this, the Society for Immunotherapy of Cancer convened a diverse group of experts in cancer immunotherapy representing academia, the pharmaceutical and biotechnology industries, patient advocacy, and the regulatory community to identify current opportunities and challenges with the goal of prioritizing areas with the highest potential for clinical impact. The consensus group identified seven high-priority areas of current opportunity for the field: mechanisms of antitumor activity and toxicity; mechanisms of drug resistance; biomarkers and biospecimens; unique aspects of novel therapeutics; host and environmental interactions; premalignant immunity, immune interception, and immunoprevention; and clinical trial design, endpoints, and conduct. Additionally, potential roadblocks to progress were discussed, and several topics were identified as cross-cutting tools for optimization, each with potential to impact multiple scientific priority areas. These cross-cutting tools include preclinical models, data curation and sharing, biopsies and biospecimens, diversification of funding sources, definitions and standards, and patient engagement. Finally, three key guiding principles were identified that will both optimize and maximize progress in the field. These include engaging the patient community; cultivating diversity, equity, inclusion, and accessibility; and leveraging the power of artificial intelligence to accelerate progress. Here, we present the outcomes of these discussions as a strategic vision to galvanize the field for the next decade of exponential progress in cancer immunotherapy.
Perspectives from the leadership of<i>Journal for ImmunoTherapy of Cancer</i>
Authors: Sjoerd H van der Burg, Michael T Lotze
Journal: Journal for ImmunoTherapy of Cancer (2024)

As the new Editor-in-Chief and Deputy Editor-in-Chief for the Journal for ImmunoTherapy of Cancer ( JITC ), we thought it appropriate to pay attention to current issues that confront our patients, scientists, and practitioners as we navigate the next era in the immunotherapy of cancer. We would
Advances in spatial transcriptomics and its applications in cancer research
Authors: Yang Jin, Yuanli Zuo, Gang Li, Wenrong Liu, Yitong Pan, Ting Fan, Xin Fu, Xiaojun Yao, Yong Peng
Journal: Molecular Cancer (2024)

Abstract Malignant tumors have increasing morbidity and high mortality, and their occurrence and development is a complicate process. The development of sequencing technologies enabled us to gain a better understanding of the underlying genetic and molecular mechanisms in tumors. In recent years, the spatial transcriptomics sequencing technologies have been developed rapidly and allow the quantification and illustration of gene expression in the spatial context of tissues. Compared with the traditional transcriptomics technologies, spatial transcriptomics technologies not only detect gene expression levels in cells, but also inform the spatial location of genes within tissues, cell composition of biological tissues, and interaction between cells. Here we summarize the development of spatial transcriptomics technologies, spatial transcriptomics tools and its application in cancer research. We also discuss the limitations and challenges of current spatial transcriptomics approaches, as well as future development and prospects.
Neutrophil‐Mediated Nanozyme Delivery System for Acute Kidney Injury Therapy
Authors: Yu Yang, Jiang Du, Jingjing Gan, Xiang Song, Jiaxin Shu, Chaoli An, Li Lu, Hui Wei, Junyi Che, Xiaozhi Zhao
Journal: Advanced Healthcare Materials (2024)

Reactive oxygen species (ROS) scavenging of nanozymes toward acute kidney injury (AKI) is a current promising strategy, however, the glomerular filtration barrier (GFB) limits their application for treating kidney related diseases. Here, a neutrophil-mediated delivery system able to hijack neutrophil to transport nanozyme-loaded cRGD-liposomes to inflamed kidney for AKI treatment by cRGD targeting integrin αvβ1 is reported. The neutrophil-mediated nanozyme delivery system demonstrated great antioxidant and anti-apoptosis ability in HK-2 and NRK-52E cell lines. Moreover, in ischemia-reperfusion (I/R) induced AKI mice, a single dose of LM@cRGD-LPs 12 h post-ischemia significantly reduces renal function indicators, alleviates renal pathological changes, and inhibits apoptosis of renal tubular cells and the expression of renal tubular injured marker, thus remarkably reducing the damage of AKI. Mechanistically, the treatment of LM@cRGD-LPs markedly inhibits the process of Nrf2 to the nucleus and reduces the expression of the downstream HO-1, achieves a 99.51% increase in renal tissue Nrf2 levels, and an 86.31% decrease in HO-1 levels after LM@cRGD-LPs treatment. In short, the strategy of neutrophil-mediated nanozyme delivery system hold great promise as a potential therapy for AKI or other inflammatory diseases.
Fecal Microbiota Transplantation for Sleep Disturbance in Post-acute COVID-19 Syndrome
Authors: Raphaela I. Lau, Qi Su, Jessica Y.L. Ching, Rashid N. Lui, Ting Ting Chan, Marc T.L. Wong, Louis H.S. Lau, Yun Kwok Wing, Rachel N.Y. Chan, Hanson Y.H. Kwok, Agnes H.Y. Ho, Yee Kit Tse, Chun Pan Cheung, Moses K.T. Li, Wan Ying Siu, Chengyu Liu, Wenqi Lu, Yun Wang, Emily O.L. Chiu, Pui Kuan Cheong, Francis K.L. Chan, Siew C. Ng
Journal: Clinical Gastroenterology and Hepatology (2024)
PneumoLLM: Harnessing the power of large language model for pneumoconiosis diagnosis
Authors: Meiyue Song, Jiarui Wang, Zhihua Yu, Jiaxin Wang, Le Yang, Yuting Lu, Baicun Li, Xue Wang, Xiaoxu Wang, Qinghua Huang, Zhijun Li, Nikolaos I. Kanellakis, Jiangfeng Liu, Jing Wang, Binglu Wang, Juntao Yang
Journal: Medical Image Analysis (2024)
Macrophage P2Y6R activation aggravates psoriatic inflammation through IL-27-mediated Th1 responses
Authors: Li Yin, Enming Zhang, Tianqi Mao, Yifan Zhu, Shurui Ni, Yehong Li, Chunxiao Liu, Yafei Fang, Kexin Ni, Yuhe Lu, Huanqiu Li, Mengze Zhou, Qinghua Hu
Journal: Acta Pharmaceutica Sinica B (2024)

Purinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y
Botulinum Toxin-A for the Treatment of Myogenous Temporomandibular Disorders: An Umbrella Review of Systematic Reviews
Authors: Giancarlo De la Torre Canales, Mariana Barbosa Câmara-Souza, Malin Ernberg, Essam Ahmed Al-Moraissi, Anastasios Grigoriadis, Rodrigo Lorenzi Poluha, Maria Christidis, Hajer Jasim, Anna Lövgren, Nikolaos Christidis
Journal: Drugs (2024)

Temporomandibular disorders (TMDs) encompass several conditions that cause pain and impair function of the masticatory muscles (M-TMDs) and temporomandibular joints. There is a large interest among clinicians and researchers in the use of botulinum toxin-A (BoNT-A) as a treatment for M-TMD. However, due to the lack of consistent evidence regarding the efficacy as well as adverse events of BoNT-A, clinical decision making is challenging. Therefore, this umbrella review aimed to systematically assess systematic reviews (SRs) evaluating BoNT-A treatment effects on pain intensity, mandibular movements, and adverse events in patients with M-TMDs.
Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers
Authors: L. Arecco, M. Bruzzone, R. Bas, H.J. Kim, A. Di Meglio, R. Bernstein-Molho, F.S. Hilbers, K. Pogoda, E. Carrasco, K. Punie, J. Bajpai, E. Agostinetto, N. Lopetegui-Lia, A.H. Partridge, K.A. Phillips, A. Toss, C. Rousset-Jablonski, G. Curigliano, T. Renaud, A. Ferrari, S. Paluch-Shimon, R. Fruscio, W. Cui, S.M. Wong, C. Vernieri, F.J. Couch, M.V. Dieci, A. Matikas, M. Rozenblit, D. Aguilar-y Méndez, L. De Marchis, F. Puglisi, A. Fabi, S.L. Graff, I. Witzel, A. Rodriguez Hernandez, A. Fontana, R. Pesce, R. Duchnowska, H.L. Pais, V. Sini, E. Sokolović, E. de Azambuja, M. Ceppi, E. Blondeaux, M. Lambertini
Journal: Annals of Oncology (2024)

Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes.
Combination of anti-inflammatory therapy and RNA interference by light-inducible hybrid nanomedicine for osteoarthritis treatment
Authors: Li Qiao, Zhiyao Li, Bowen Li, Fu Zhang, Zhuo Yao, Chongzhi Wu, Honglin Tang, Qi Pan, Peihua Shi, Yuan Ping
Journal: Acta Pharmaceutica Sinica B (2024)

Osteoarthritis (OA) is a type of highly prevalent heterogeneous degenerative disease that leads to joint pain, deformity, the destruction of articular cartilage, and eventual disability. The current treatment strategies for OA often suffer from systemic side effects, poor anti-inflammatory efficacy, and persistent pain. To address these issues, we develop light-inducible nanomedicine that enables the co-delivery of anti-inflammatory drug (diacerein, DIA) and small interfering RNA (siRNA) targeting nerve growth factor (NGF) for pain relief to enhance the therapeutic efficacy of OA. The nanomedicine is based on poly(