tbuckley/cabot-search huggingface dataset:
Blurred streamlines: A novel representation to reduce redundancy in tractography
Authors: Ilaria Gabusi, Matteo Battocchio, Sara Bosticardo, Simona Schiavi, Alessandro Daducci
Journal: Medical Image Analysis (2024)

Tractography is a powerful tool to study brain connectivity in vivo, but it is well known to suffer from an intrinsic trade-off between sensitivity and specificity. A critical - but usually underrated - parameter to choose that can heavily impact the quality of the estimates is the number of streamlines to be reconstructed for a given data set. In fact, sensitivity can be improved by generating more and more streamlines, as all real anatomical connections are likely reconstructed, but lots of false positives are inevitably introduced, too. Consequently, so-called tractography filtering techniques have become increasingly popular to get rid of these false positives and improve specificity. However, increasing number of streamlines introduces redundancy in tractography reconstructions, which may negatively impact the performance of filtering algorithms, especially those based on linear formulations. To address this problem, we introduce a novel streamlines representation, called "blurred streamlines", which drastically reduces the redundancy among streamlines by (i) clustering similar trajectories and (ii) spatially blurring the corresponding signal contributions. We tested the effectiveness of the blurred streamlines both on synthetic and in vivo data. Our results clearly show that this new representation is as accurate as state-of-the-art methods despite using only 5% of the input streamlines, thus significantly decreasing the computational complexity of filtering algorithms as well as storage requirements of the resulting reconstructions.
Long-term outcome measures of atopic dermatitis gain importance: a validation study filling a research gap
Authors: Laura B von Kobyletzki, Åke Svensson
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Long-term outcome measures of atopic dermatitis gain importance: a validation study filling a research gap Get access Laura B von Kobyletzki, Laura B von Kobyletzki Conceptualization, Writing - original draft Orebro UniversityDepartment of Occupational and Environmental Dermatology, Lund University Faculty of Medicine Correspondence: Laura B. von Kobyletzki. Email: laura.von_kobyletzki@med.lu.se Search for other works by this author on: Oxford Academic Google Scholar Åke Svensson Åke Svensson Conceptualization, Writing - original draft Department of Dermatology, Malmö University Hospital, Malmö, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae049, https://doi.org/10.1093/bjd/ljae049 Published: 05 February 2024 Article history Received: 29 January 2024 Accepted: 31 January 2024 Published: 05 February 2024 Corrected and typeset: 04 March 2024
Adaptive Evolution of Nearctic Deepwater Fish Vision: Implications for Assessing Functional Variation for Conservation
Authors: Alexander Van Nynatten, Alexander T Duncan, Ryan Lauzon, Tom A Sheldon, Steven K Chen, Nathan R Lovejoy, Nicholas E Mandrak, Belinda S W Chang
Journal: Molecular Biology and Evolution (2024)

Abstract Intraspecific functional variation is critical for adaptation to rapidly changing environments. For visual opsins, functional variation can be characterized in vitro and often reflects a species’ ecological niche but is rarely considered in the context of intraspecific variation or the impact of recent environmental changes on species of cultural or commercial significance. Investigation of adaptation in postglacial lakes can provide key insight into how rapid environmental changes impact functional evolution. Here, we report evidence for molecular adaptation in vision in 2 lineages of Nearctic fishes that are deep lake specialists: ciscoes and deepwater sculpin. We found depth-related variation in the dim-light visual pigment rhodopsin that evolved convergently in these 2 lineages. In vitro characterization of spectral sensitivity of the convergent deepwater rhodopsin alleles revealed blue-shifts compared with other more widely distributed alleles. These blue-shifted rhodopsin alleles were only observed in deep clear postglacial lakes with underwater visual environments enriched in blue light. This provides evidence of remarkably rapid and convergent visual adaptation and intraspecific functional variation in rhodopsin. Intraspecific functional variation has important implications for conservation, and these fishes are of conservation concern and great cultural, commercial, and nutritional importance to Indigenous communities. We collaborated with the Saugeen Ojibway Nation to develop and test a metabarcoding approach that we show is efficient and accurate in recovering the ecological distribution of functionally relevant variation in rhodopsin. Our approach bridges experimental analyses of protein function and genetics-based tools used in large-scale surveys to better understand the ecological extent of adaptive functional variation.
Four-dimensional analysis of aortic root motion in normal population using retrospective multiphase computed tomography
Authors: Xun Yuan, Xiaoxin Kan, Jianpeng Li, Yang Yan, Saeed Mirsadraee, Tarun Mittal, Andrew Shah, Debbie Saunders, Xiao Yun Xu, Christoph A Nienaber
Journal:  (2024)

Abstract Aims Aortic root motion is suspected to contribute to proximal aortic dissection. While motion of the aorta in four dimensions can be traced with real-time imaging, displacement and rotation in quantitative terms remain unknown. The hypothesis was to show feasibility of quantification of three-dimensional aortic root motion from dynamic CT imaging. Methods and results Dynamic CT images of 40 patients for coronary assessment were acquired using a dynamic protocol. Scans were ECG-triggered and segmented in 10 time-stepped phases (0–90%) per cardiac cycle. With identification of the sinotubular junction (STJ), a patient-specific co-ordinate system was created with the z-axis (out-of-plane) parallel to longitudinal direction. The left and right coronary ostia were traced at each time-step to quantify downward motion in reference to the STJ plane, motion within the STJ plane (in-plane), and the degree of rotation. Enrolled individuals had an age of 65 ± 12, and 14 were male (35%). The out-of-plane motion was recorded with the largest displacement of 10.26 ± 2.20 and 8.67 ± 1.69 mm referenced by left and right coronary ostia, respectively. The mean downward movement of aortic root was 9.13 ± 1.86 mm. The largest in-plane motion was recorded at 9.17 ± 2.33 mm and 6.51 ± 1.75 mm referenced by left and right coronary ostia, respectively. The largest STJ in-plane motion was 7.37 ± 1.96 mm, and rotation of the aortic root was 11.8 ± 4.60°. Conclusion In vivo spatial and temporal displacement of the aortic root can be identified and quantified from multiphase ECG-gated contrast-enhanced CT images. Knowledge of normal 4D motion of the aortic root may help understand its biomechanical impact in patients with aortopathy and pre- and post-surgical or transcatheter aortic valve replacement.
Retraction Notice to: Exosome-Mediated miR-155 Transfer from Smooth Muscle Cells to Endothelial Cells Induces Endothelial Injury and Promotes Atherosclerosis
Authors: Bin Zheng, Wei-na Yin, Toru Suzuki, Xin-hua Zhang, Yu Zhang, Li-li Song, Li-shuang Jin, Hong Zhan, Hong Zhang, Jin-shui Li, Jin-kun Wen
Journal: Molecular Therapy (2024)

(Molecular Therapy 25, 1279–1294; June 2017) This article has been retracted at the request of the editors. The editorial office received emails from the corresponding authors of this article requesting that this article be corrected due to image duplication in Figure 3D initially identified in a PubPeer post (https://pubpeer.com/publications/27DB27049037B0035A83F35E244A8B). Image analysis conducted by the editorial office indicated inappropriate post processing of images in Figure 3D, image duplication within Figures 3D and 5D, and image recycling between Figure 5D of the Molecular Therapy article and Figure 3B of an article in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (Zheng et al., 2018, Biochim. Biophys. Acta Mol. Basis Dis. 1864, 374–386. https://doi.org/10.1016/j.bbadis.2017.10.021). While some original data was provided in response to the editors' request, discrepancies exist between the data provided and the published data. Given these issues, the editors have lost faith in the findings presented in the article. This reuse (and in part misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. Exosome-Mediated miR-155 Transfer from Smooth Muscle Cells to Endothelial Cells Induces Endothelial Injury and Promotes AtherosclerosisZheng et al.Molecular TherapyMarch 28, 2017In BriefZheng et al. show that KLF5 exerts a pro-atherosclerotic effect by regulating the secretion miR-155. miR-155-rich exosomes from KLF5-overexpressing VSMCs are taken up by ECs. miR-155-rich exosomes inhibit the proliferation and migration of ECs and impair endothelial cell barrier function by suppressing the expression of tight junction proteins. Targeting miR-155 might represent a therapeutic strategy in atherosclerosis. Full-Text PDF Open Archive
The multitarget faecal immunochemical test for improving stool-based colorectal cancer screening programmes: a Dutch population-based, paired-design, intervention study
Authors: Pieter H A Wisse, Willemijn de Klaver, Francine van Wifferen, Frejanne G van Maaren-Meijer, Huub E van Ingen, Lana Meiqari, Iris Huitink, Mariska Bierkens, Margriet Lemmens, Marjolein J E Greuter, Monique E van Leerdam, Manon C W Spaander, Evelien Dekker, Veerle M H Coupé, Beatriz Carvalho, Meike de Wit, Gerrit A Meijer
Journal: The Lancet Oncology (2024)
Long-Term Follow-Up of the Anthracyclines in Early Breast Cancer Trials (USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 [NRG Oncology])
Authors: Charles E. Geyer, Joanne L. Blum, Greg Yothers, Lina Asmar, Patrick J. Flynn, Nicholas J. Robert, Judith O. Hopkins, Joyce A. O'Shaughnessy, Priya Rastogi, Shannon L. Puhalla, Christie J. Hilton, Chau T. Dang, Henry Leonidas Gómez, Svetislava J. Vukelja, Alan P. Lyss, Devchand Paul, Adam M. Brufsky, Linda H. Colangelo, Sandra M. Swain, Eleftherios P. Mamounas, Norman Wolmark
Journal: Journal of Clinical Oncology (2024)

JCO
Corrigendum to “Self-assembling peptide hydrogel enables instant epicardial coating of the heart with mesenchymal stromal cells for the treatment of heart failure” [Biomaterials 154 (2018) 12–23]
Authors: Yuki Ichihara, Masahiro Kaneko, Kenichi Yamahara, Marinos Koulouroudias, Nobuhiko Sato, Rakesh Uppal, Kenji Yamazaki, Satoshi Saito, Ken Suzuki
Journal: Biomaterials (2024)
Mental Disorders Among Adolescents and Young Adults With Cancer: A Canadian Population–Based and Sibling Cohort Study
Authors: Sapna Oberoi, Allan Garland, Adam P. Yan, Pascal Lambert, Lin Xue, Kathleen Decker, Sara J. Israels, Shantanu Banerji, James M. Bolton, Julie M. Deleemans, Bronwen Garand-Sheridan, Deepak Louis, Lisa M. Lix, Alyson L. Mahar
Journal: Journal of Clinical Oncology (2024)

To compare the cumulative incidence of mental disorders among adolescents and young adults (AYAs) diagnosed with cancer with the general population and their unaffected siblings.
Single-Cell Analysis Identifies NOTCH3-Mediated Interactions between Stromal Cells That Promote Microenvironment Remodeling and Invasion in Lung Adenocarcinoma
Authors: Handan Xiang, Yidan Pan, Marc A. Sze, Marta Wlodarska, Ling Li, Karyn Ann van de Mark, Haleema Qamar, Casey J. Moure, Douglas E. Linn, Josephine Hai, Ying Huo, James Clarke, Tze Guan Tan, Samantha Ho, Karen W. Teng, Muhammad N. Ramli, Michael Nebozhyn, Chunsheng Zhang, Julianne Barlow, Corinne E. Gustafson, Savanna Gornisiewicz, Thomas P. Albertson, Stephanie L. Korle, Raphael Bueno, Lily Y. Moy, Elisabeth H. Vollmann, Derek Y. Chiang, Philip E. Brandish, Andrey Loboda
Journal: Cancer Research (2024)

Abstract Cancer immunotherapy has revolutionized the treatment of lung adenocarcinoma (LUAD); however, a significant proportion of patients do not respond. Recent transcriptomic studies to understand determinants of immunotherapy response have pinpointed stromal-mediated resistance mechanisms. To gain a better understanding of stromal biology at the cellular and molecular level in LUAD, we performed single-cell RNA sequencing of 256,379 cells, including 13,857 mesenchymal cells, from 9 treatment-naïve patients. Among the mesenchymal cell subsets, FAP+PDPN+ cancer-associated fibroblasts (CAF) and ACTA2+MCAM+ pericytes were enriched in tumors and differentiated from lung-resident fibroblasts. Imaging mass cytometry revealed that both subsets were topographically adjacent to the perivascular niche and had close spatial interactions with endothelial cells (EC). Modeling of ligand and receptor interactomes between mesenchymal and ECs identified that NOTCH signaling drives these cell-to-cell interactions in tumors, with pericytes and CAFs as the signal receivers and arterial and PLVAPhigh immature neovascular ECs as the signal senders. Either pharmacologically blocking NOTCH signaling or genetically depleting NOTCH3 levels in mesenchymal cells significantly reduced collagen production and suppressed cell invasion. Bulk RNA sequencing data demonstrated that NOTCH3 expression correlated with poor survival in stroma-rich patients and that a T cell–inflamed gene signature only predicted survival in patients with low NOTCH3. Collectively, this study provides valuable insights into the role of NOTCH3 in regulating tumor stroma biology, warranting further studies to elucidate the clinical implications of targeting NOTCH3 signaling. Significance: NOTCH3 signaling activates tumor-associated mesenchymal cells, increases collagen production, and augments cell invasion in lung adenocarcinoma, suggesting its critical role in remodeling tumor stroma.
Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial
Authors: Amrou Sarraj, Michael G Abraham, Ameer E Hassan, Spiros Blackburn, Scott E Kasner, Santiago Ortega-Gutierrez, Muhammad Shazam Hussain, Michael Chen, Hannah Johns, Leonid Churilov, Deep K Pujara, Faris Shaker, Laith Maali, Pere Cardona Portela, Nabeel A Herial, Daniel Gibson, Osman Kozak, Juan F Arenillas, Bernard Yan, Natalia Pérez de la Ossa, Sophia Sundararajan, Yin C Hu, Dennis J Cordato, Nathan W Manning, Ricardo A Hanel, Amin N Aghaebrahim, Ronald F Budzik, William J Hicks, Jordi Blasco, Teddy Y Wu, Jenny P Tsai, Joanna D Schaafsma, Chirag D Gandhi, Fawaz Al-Mufti, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Vignan Yogendrakumar, Felix Ng, Edgar A Samaniego, Mohammad A Abdulrazzak, Mark W Parsons, Mohammad H Rahbar, Thanh N Nguyen, Johanna T Fifi, Vitor Mendes Pereira, Maarten G Lansberg, Greg W Albers, Anthony J Furlan, Pascal Jabbour, Clark W Sitton, Cathy Sila, Nicholas Bambakidis, Stephen M Davis, Lawrence Wechsler, Michael D Hill, James C Grotta, Marc Ribo, Bruce C V Campbell
Journal: The Lancet (2024)
Drug development advances in human genetics‐based targets
Authors: Xiaoxia Zhang, Wenjun Yu, Yan Li, Aiping Wang, Haiqiang Cao, Yuanlei Fu
Journal: MedComm (2024)

Drug development is a long and costly process, with a high degree of uncertainty from the identification of a drug target to its market launch. Targeted drugs supported by human genetic evidence are expected to enter phase II/III clinical trials or be approved for marketing more quickly, speeding up the drug development process. Currently, genetic data and technologies such as genome-wide association studies (GWAS), whole-exome sequencing (WES), and whole-genome sequencing (WGS) have identified and validated many potential molecular targets associated with diseases. This review describes the structure, molecular biology, and drug development of human genetics-based validated beneficial loss-of-function (LOF) mutation targets (target mutations that reduce disease incidence) over the past decade. The feasibility of eight beneficial LOF mutation targets (PCSK9, ANGPTL3, ASGR1, HSD17B13, KHK, CIDEB, GPR75, and INHBE) as targets for drug discovery is mainly emphasized, and their research prospects and challenges are discussed. In conclusion, we expect that this review will inspire more researchers to use human genetics and genomics to support the discovery of novel therapeutic drugs and the direction of clinical development, which will contribute to the development of new drug discovery and drug repurposing.
Single‐Component Photochemical Afterglow Near‐Infrared Luminescent Nano‐Photosensitizers: Bioimaging and Photodynamic Therapy
Authors: Yin Li, Dong He, Qiangfeng Zheng, Ruilin Tang, Qing Wan, Ben Zhong Tang, Zhiming Wang
Journal: Advanced Healthcare Materials (2024)

Long afterglow luminescence-guided photodynamic therapy (PDT) performs advantages of noninvasiveness, spatiotemporal controllability, and higher signal to noise ratio. Photochemical afterglow (PCA) system emitting afterglow in an aqueous environment is highly suitable for biomedical applications, but still faces the challenges of poor tissue penetration depth and responsive sensitivity. In this work, two novel compounds, Iso-TPA and ABEI-TPA, are designed and synthesized to integrate the PCA system as a single component by coupling near-infrared (NIR) photosensitizers with singlet oxygen cache units, respectively. Both compounds emit NIR afterglow based on photochemical reaction. ABEI-TPA exhibits higher photoluminescence quantum efficiency with nonconjugated linkage, while Iso-TPA with conjugated linkage possesses better reactive oxygen species generation efficiency to achieve stronger PCA and effective PDT, which is ascribed to stronger intramolecular charge transfer effect of Iso-TPA. Iso-TPA nanoparticles can achieve effective long-lasting NIR afterglow in vivo bioimaging up to 120 s with higher imaging resolution and outstanding PDT efficacy of tumor, exhibiting promising potential on bioimaging and therapy.
Chromoplexy Is a Frequent Early Clonal Event in <i>EWSR1</i>-Rearranged Round Cell Sarcomas That Can Be Detected Using Clinically Validated Targeted Sequencing Panels
Authors: Josephine K. Dermawan, Emily Slotkin, William D. Tap, Paul Meyers, Leonard Wexler, John Healey, Fabio Vanoli, Chad M. Vanderbilt, Cristina R. Antonescu
Journal: Cancer Research (2024)

Abstract Chromoplexy is a phenomenon defined by large-scale chromosomal chained rearrangements. A previous study observed chromoplectic events in a subset of Ewing sarcomas (ES), which was linked to an increased relapse rate. Chromoplexy analysis could potentially facilitate patient risk stratification, particularly if it could be detected with clinically applied targeted next-generation sequencing (NGS) panels. Using DELLY, a structural variant (SV) calling algorithm that is part of the MSK-IMPACT pipeline, we characterized the spectrum of SVs in EWSR1-fused round cell sarcomas, including 173 ES and 104 desmoplastic small round cell tumors (DSRCT), to detect chromoplexy and evaluate its association with clinical and genomic features. Chromoplectic events were detected in 31% of the ES cases and 19% of the DSRCT cases. EWSR1 involvement accounted for 76% to 93% of these events, being rearranged with diverse noncanonical gene partners across the genome, involving mainly translocations but also intrachromosomal deletions and inversions. A major breakpoint cluster was located on EWSR1 exons 8–13. In a subset of cases, the SVs disrupted adjacent loci, forming deletion bridges. Longitudinal sequencing and breakpoint allele fraction analysis showed that chromoplexy is an early event that remains detectable throughout disease progression and likely develops simultaneously with the driver fusion. The presence of chromoplexy was validated in an external ES patient cohort with whole exome sequencing. Chromoplexy was significantly more likely to be present in cases that were metastatic at presentation. Together, this study identifies chromoplexy as a frequent genomic alteration in diverse EWSR1-rearranged tumors that can be captured by targeted NGS panels. Significance: Chromoplexy is detectable using targeted NGS in a substantial portion of EWSR1-rearranged round cell sarcomas as an early and persistent clonal event, expanding the genomic complexity of fusion-associated sarcomas.
Th17 Cells Secrete TWEAK to Trigger Epithelial–Mesenchymal Transition and Promote Colorectal Cancer Liver Metastasis
Authors: Xin Liu, Xin Wang, Qingxia Yang, Li Luo, Ziqin Liu, Xiaoxue Ren, Kai Lei, Shangru Li, Zonglin Xie, Gaomin Zheng, Yifan Zhang, Yijie Hao, Qianying Zhou, Yingdong Hou, Fei Fang, Wu Song, Ji Cui, Jinping Ma, Wenxuan Xie, Shunli Shen, Ce Tang, Sui Peng, Jun Yu, Ming Kuang, Xinming Song, Fang Wang, Lixia Xu
Journal: Cancer Research (2024)

Liver metastasis is the leading cause of mortality in patients with colorectal cancer. Given the significance of both epithelial-mesenchymal transition (EMT) of tumor cells and the immune microenvironment in colorectal cancer liver metastasis (CRLM), the interplay between them could hold the key for developing improved treatment options. We employed multiomics analysis of 130 samples from 18 patients with synchronous CRLM integrated with external datasets to comprehensively evaluate the interaction between immune cells and EMT of tumor cells in liver metastasis. Single-cell RNA sequencing analysis revealed distinct distributions of nonmalignant cells between primary tumors from patients with metastatic colorectal cancer (mCRC) and non-metastatic colorectal cancer, showing that Th17 cells were predominantly enriched in the primary lesion of mCRC. TWEAK, a cytokine secreted by Th17 cells, promoted EMT by binding to receptor Fn14 on tumor cells, and the TWEAK-Fn14 interaction enhanced tumor migration and invasion. In mouse models, targeting Fn14 using CRISPR-induced knockout or lipid nanoparticle-encapsulated siRNA alleviated metastasis and prolonged survival. Mice lacking Il17a or Tnfsf12 (encoding TWEAK) exhibited fewer metastases compared with wild-type mice, while cotransfer of Th17 with tumor cells promoted liver metastasis. Higher TWEAK expression was associated with a worse prognosis in patients with colorectal cancer. In addition, CD163L1+ macrophages interacted with Th17 cells, recruiting Th17 via the CCL4-CCR5 axis. Collectively, this study unveils the role of immune cells in the EMT process and identifies TWEAK secreted by Th17 as a driver of CRLM.