tbuckley/cabot-search huggingface dataset:
Association of Cardiovascular Outcomes With Low‐Dose Glucocorticoid Prescription in Patients With Rheumatoid Arthritis
Authors: Brian W. Coburn, Joshua F. Baker, Jesse Y. Hsu, Qufei Wu, Fenglong Xie, Jeffrey R. Curtis, Michael D. George
Journal: Arthritis & Rheumatology (2024)

Objective Many guidelines recommend limiting glucocorticoids in patients with rheumatoid arthritis (RA), but 40% of patients remain on glucocorticoids long term. We evaluated the cardiovascular risk of long‐term glucocorticoid prescription by studying patients on stable disease‐modifying antirheumatic drugs (DMARDs). Methods Using two claims databases, we identified patients with RA on stable DMARD therapy for &gt;180 days. Proportional hazards models with inverse‐probability weights and clustering to account for multiple observations were used to estimate the effect of glucocorticoid dose on composite cardiovascular outcomes (stroke or myocardial infarction [MI]). Results There were 135,583 patients in Medicare and 39,272 in Optum's de‐identified Clinformatics Data Mart (CDM) database. Medicare and CDM patients had an incidence of 1.3 and 0.8 composite cardiovascular outcomes per 100 person‐years, respectively. In the older, comorbid Medicare cohort, glucocorticoids were associated with a dose‐dependent increase in composite cardiovascular outcomes in adjusted models with predicted one‐year incidence of 1.4% (95% confidence interval [CI] 1.2%–1.6%) for ≤5 mg, 1.6% (95% CI 1.4%–1.9%) for &gt;5 to 10 mg, and 1.8% (95% CI 1.2%–2.5%) for &gt;10 mg versus 1.1% (95% CI 1.1%–1.2%) among patients not receiving glucocorticoids. There was no significant association among the CDM cohort. However, in the subgroup of younger patients with RA and higher cardiovascular risk, glucocorticoids were associated with a dose‐dependent increase in composite cardiovascular outcomes. Conclusion Among older patients with more comorbidities and younger patients with higher cardiovascular risk with RA on stable DMARD therapy, glucocorticoids were associated with a dose‐dependent increased risk of MI and stroke, even at doses ≤5 mg/day. By contrast, no association was noted among younger, healthier patients with RA. image
Autologous CD19‐ targeting CAR T cells in refractory juvenile dermatomyositis
Authors: Rebecca Nicolai, Pietro Merli, Patricia Moran Alvarez, Claudia Bracaglia, Francesca Del Bufalo, Emiliano Marasco, Ivan Caiello, Giusi Prencipe, Mattia Algeri, Maria G. Cefalo, Marco Becilli, Concetta Quintarelli, Matilde Sinibaldi, Linda Hanssens, Fabrizio De Benedetti, Franco Locatelli
Journal: Arthritis & Rheumatology (2024)

Objective The aim of this study is to report the safety and efficacy of CD19‐targeting chimeric antigen receptor (CAR) T cells in a child with refractory juvenile dermatomyositis (JDM). Methods We describe a 12‐year‐old White boy with severe, chronically active JDM refractory to multiple immunosuppressive treatment lines, including B cell depletion with rituximab. The patient received a single infusion of fresh, autologous, second‐generation anti‐CD19 CAR T cell product (lentiviral vector) manufactured on the Prodigy device (1 × 10 6 CAR T cells/kg), after lymphodepletion with cyclophosphamide (1,000 mg/m 2 over two days) and fludarabine (90 mg/m 2 over three days). Immunosuppressive and glucocorticoid treatment were withdrawn before leukapheresis and CAR T cell infusion. Results Before anti‐CD19 CAR T cell therapy, the patient had persistent severe skin and muscular disease activity. CAR T cells expanded significantly (peak at day 7, 32.69 cells/μL). Complete B cell depletion was documented on day 5 in the blood and at week 2 in the bone marrow. The patient presented with fever as part of mild cytokine release syndrome (grade 1), transient anemia (grade 2), and neutropenia (grade 4). Neither infection nor neurotoxicity were observed. Laboratory tests, magnetic resonance imaging, Physician Global Assessment of disease activity, Childhood Myositis Assessment Scale, and Cutaneous Assessment Tool for myositis were performed at baseline and follow‐up to assess treatment response, showing remarkable progressive improvement that persists over time, even after B cell recovery. Conclusion This patient with JDM with severe chronic disease, refractory to multiple treatments, achieved sustained B cell depletion and ongoing immunosuppressive drug‐free clinical and radiologic improvement eight months after a single infusion of anti‐CD19 CAR T cells. image
Highlighting the need for consensus: diverse classification strategies in contemporary research on Idiopathic Inflammatory myopathies
Authors: Keeran Shivakumar, Emily Sun, Ocean Ma, Latika Gupta, Jessica Day
Journal: Arthritis & Rheumatology (2024)

Appendix S1: Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
CP-Net: Instance-aware part segmentation network for biological cell parsing
Authors: Wenyuan Chen, Haocong Song, Changsheng Dai, Zongjie Huang, Andrew Wu, Guanqiao Shan, Hang Liu, Aojun Jiang, Xingjian Liu, Changhai Ru, Khaled Abdalla, Shivani N Dhanani, Katy Fatemeh Moosavi, Shruti Pathak, Clifford Librach, Zhuoran Zhang, Yu Sun
Journal: Medical Image Analysis (2024)

Instance segmentation of biological cells is important in medical image analysis for identifying and segmenting individual cells, and quantitative measurement of subcellular structures requires further cell-level subcellular part segmentation. Subcellular structure measurements are critical for cell phenotyping and quality analysis. For these purposes, instance-aware part segmentation network is first introduced to distinguish individual cells and segment subcellular structures for each detected cell. This approach is demonstrated on human sperm cells since the World Health Organization has established quantitative standards for sperm quality assessment. Specifically, a novel Cell Parsing Net (CP-Net) is proposed for accurate instance-level cell parsing. An attention-based feature fusion module is designed to alleviate contour misalignments for cells with an irregular shape by using instance masks as spatial cues instead of as strict constraints to differentiate various instances. A coarse-to-fine segmentation module is developed to effectively segment tiny subcellular structures within a cell through hierarchical segmentation from whole to part instead of directly segmenting each cell part. Moreover, a sperm parsing dataset is built including 320 annotated sperm images with five semantic subcellular part labels. Extensive experiments on the collected dataset demonstrate that the proposed CP-Net outperforms state-of-the-art instance-aware part segmentation networks.
Study of the Structure of Hyperbranched Polyglycerol Coatings and their Anti‐Biofouling and Anti‐Thrombotic Applications
Authors: Eli Moore, Alexander J. Robson, Amy R. Crisp, Michaelia P. Cockshell, Anouck L. S. Burzava, Raja Ganesan, Nirmal Robinson, Sameer Al‐Bataineh, Victoria Nankivell, Lauren Sandeman, Markus Tondl, Glen Benveniste, John W. Finnie, Peter J. Psaltis, Laurine Martocq, Alessio Quadrelli, Samuel P. Jarvis, Craig Williams, Gordon Ramage, Ihtesham U. Rehman, Christina A. Bursill, Tony Simula, Nicolas H. Voelcker, Hans J. Griesser, Robert D Short, Claudine S. Bonder
Journal: Advanced Healthcare Materials (2024)

While blood-contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings. Herein, a novel but simple strategy is described for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma-grafting of an ultrathin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O─C─O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface. In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3 log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG-coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice shows no evidence of toxicity nor inflammation.
Diagnostic methods/parameters to monitor peri‐implant conditions
Authors: Alberto Monje, Giovanni E. Salvi
Journal: Periodontology 2000 (2024)

The diagnostic accuracy of clinical parameters, including visual inspection and probing to monitor peri-implant conditions, has been regarded with skepticism. Scientific evidence pointed out that primary diagnostic tools (chairside) seem to be highly specific, while their sensitivity is lower compared with their use in monitoring periodontal stability. Nonetheless, given the association between pocket depth at teeth and implant sites and the aerobic/anaerobic nature of the microbiome, it seems plausible for pocket probing depth to be indicative of disease progression or tissue stability. In addition, understanding the inflammatory nature of peri-implant diseases, it seems reasonable to advocate that bleeding, erythema, ulceration, and suppuration might be reliable indicators of pathology. Nevertheless, single spots of bleeding on probing may not reflect peri-implant disease, since implants are prone to exhibit bleeding related to probing force. On the other side, bleeding in smokers lacks sensitivity owing to the decreased angiogenic activity. Hence, the use of dichotomous scales on bleeding in the general population, in contrast to indices that feature profuseness and time after probing, might lead to false positive diagnoses. The definitive distinction between peri-implant mucositis and peri-implantitis, though, relies upon the radiographic evidence of progressive bone loss that can be assessed by means of two- and three-dimensional methods. Accordingly, the objective of this review is to evaluate the existing clinical and radiographic parameters/methods to monitor peri-implant conditions.
How to explain the beneficial effects of leukocyte‐ and platelet‐rich fibrin
Authors: Juan Blanco, Angel García, Lidia Hermida‐Nogueira, Ana B. Castro
Journal: Periodontology 2000 (2024)

The survival of an organism relies on its ability to repair the damage caused by trauma, toxic agents, and inflammation. This process involving cell proliferation and differentiation is driven by several growth factors and is critically dependent on the organization of the extracellular matrix. Since autologous platelet concentrates (APCs) are fibrin matrices in which cells, growth factors, and cytokines are trapped and delivered over time, they are able to influence that response at different levels. The present review thoroughly describes the molecular components present in one of these APCs, leukocyte- and platelet-rich fibrin (L-PRF), and summarizes the level of evidence regarding the influence of L-PRF on anti-inflammatory reactions, analgesia, hemostasis, antimicrobial capacity, and its biological mechanisms on bone/soft tissue regeneration.
Discovering fragile clades and causal sequences in phylogenomics by evolutionary sparse learning
Authors: Sudip Sharma, Sudhir Kumar
Journal: Molecular Biology and Evolution (2024)

Phylogenomic analyses of long sequences, consisting of many genes and genomic segments, reconstruct organismal relationships with high statistical confidence. But, inferred relationships can be sensitive to excluding just a few sequences. Currently, there is no direct way to identify fragile relationships and the associated individual gene sequences in species. Here, we introduce novel metrics for gene-species sequence concordance and clade probability derived from evolutionary sparse learning models. We validated these metrics using fungi, plant, and animal phylogenomic datasets, highlighting the ability of the new metrics to pinpoint fragile clades and the sequences responsible. The new approach does not necessitate the investigation of alternative phylogenetic hypotheses, substitution models, or repeated data subset analyses. Our methodology offers a streamlined approach to evaluating major inferred clades and identifying sequences that may distort reconstructed phylogenies using large datasets.
Efficacy and Safety of Upadacitinib or Elsubrutinib Alone or in Combination for Patients With Systemic Lupus Erythematosus: A Phase 2 Randomized Controlled Trial
Authors: Joan T. Merrill, Yoshiya Tanaka, David D'Cruz, Karina Vila‐Rivera, Daniel Siri, Xiaofeng Zeng, Amit Saxena, Martin Aringer, Kristin M. D'Silva, Ling Cheng, Mohamed‐Eslam F. Mohamed, Lucia Siovitz, Sumit Bhatnagar, Marie‐Claude Gaudreau, Thao T. Doan, Alan Friedman
Journal: Arthritis & Rheumatology (2024)

The 48-week, phase 2 SLEek study (NCT03978520) evaluated the efficacy and safety of upadacitinib (JAK inhibitor) and elsubrutinib (BTK inhibitor) alone or in combination (ABBV-599) in adults with moderately to severely active systemic lupus erythematosus (SLE).
UV radiation‐induced peptides in frog skin confer protection against cutaneous photodamage through suppressing MAPK signaling
Authors: Tingyi Yang, Fenghao Geng, Xiaoyou Tang, Zuxiang Yu, Yulan Liu, Bin Song, Zhihui Tang, Baoning Wang, Bengui Ye, Daojiang Yu, Shuyu Zhang
Journal: MedComm (2024)

Abstract Overexposure to ultraviolet light (UV) has become a major dermatological problem since the intensity of ultraviolet radiation is increasing. As an adaption to outside environments, amphibians gained an excellent peptide‐based defense system in their naked skin from secular evolution. Here, we first determined the adaptation and resistance of the dark‐spotted frogs (Pelophylax nigromaculatus ) to constant ultraviolet B (UVB) exposure. Subsequently, peptidomics of frog skin identified a series of novel peptides in response to UVB. These UV‐induced frog skin peptides (UIFSPs) conferred significant protection against UVB‐induced death and senescence in skin cells. Moreover, the protective effects of UIFSPs were boosted by coupling with the transcription trans‐activating (TAT) protein transduction domain. In vivo, TAT‐conjugated UIFSPs mitigated skin photodamage and accelerated wound healing. Transcriptomic profiling revealed that multiple pathways were modulated by TAT‐conjugated UIFSPs, including small GTPase/Ras signaling and MAPK signaling. Importantly, pharmacological activation of MAPK kinases counteracted UIFSP‐induced decrease in cell death after UVB exposure. Taken together, our findings provide evidence for the potential preventive and therapeutic significance of UIFSPs in UV‐induced skin damage by antagonizing MAPK signaling pathways. In addition, these results suggest a practicable alternative in which potential therapeutic agents can be mined from organisms with a fascinating ability to adapt.
Targeting the intestinal circadian clock by meal timing ameliorates gastrointestinal inflammation
Authors: Yunhui Niu, Marjolein Heddes, Baraa Altaha, Michael Birkner, Karin Kleigrewe, Chen Meng, Dirk Haller, Silke Kiessling
Journal: Cellular and Molecular Immunology (2024)

Abstract The expression of clock genes has been observed to be impaired in biopsies from patients with inflammatory bowel disease (IBD). Disruption of circadian rhythms, which occurs in shift workers, has been linked to an increased risk of gastrointestinal diseases, including IBD. The peripheral circadian clock in intestinal epithelial cells (IECs) was previously shown to balance gastrointestinal homeostasis by regulating the microbiome. Here, we demonstrated that the intestinal clock is disrupted in an IBD-relevant mouse model ( IL-10 −/− ). A lack of the intestinal clock gene ( Bmal1 ) in intestinal epithelial cells (IECs) in a chemically and a novel genetically induced colitis model (DSS, Bmal1 IEC−/− x IL-10 −/− ) promoted colitis and dramatically reduced survival rates. Germ-free Bmal1 IEC−/− mice colonized with disease-associated microbiota from IL-10 −/− mice exhibited increased inflammatory responses, highlighting the importance of the local intestinal clock for microbiota-induced IBD development. Targeting the intestinal clock directly by timed restricted feeding (RF) in IL-10 −/− mice restored intestinal clock functions, including immune cell recruitment and microbial rhythmicity; improved inflammatory responses; dramatically enhanced survival rates and rescued the histopathological phenotype. In contrast, RF failed to improve IBD symptoms in Bmal1 IEC−/− x IL-10 −/− mice, demonstrating the significance of the intestinal clock in determining the beneficial effect of RF. Overall, we provide evidence that intestinal clock dysfunction triggers host immune imbalance and promotes the development and progression of IBD-like colitis. Enhancing intestinal clock function by RF modulates the pathogenesis of IBD and thus could become a novel strategy to ameliorate symptoms in IBD patients.
Prostate Cancer Among Black Men in Canada
Authors: Patrick Albers, Safaa Bashir, Nikhile Mookerji, Stacey Broomfield, Anaïs Medina Martín, Sunita Ghosh, Adam Kinnaird
Journal: JAMA Network Open (2024)

Prostate cancer is a prevalent disease among men worldwide, exhibiting substantial heterogeneity in presentation and outcomes influenced by various factors, including race and ethnicity. Disparities in incidence, stage at diagnosis, and survival rates have been observed between Black men and those of other races and ethnicities.
Outcomes and relapse patterns in primary central nervous system lymphoma: Longitudinal analysis of 559 patients diagnosed from 1983 to 2020
Authors: Kathryn R Tringale, Michael Scordo, Joachim Yahalom, Charlie White, Zhigang Zhang, Behroze Vachha, Gustav Cederquist, Lauren Schaff, Lisa DeAngelis, Christian Grommes, Brandon S Imber
Journal: Neuro-Oncology (2024)

Abstract Background Contemporary outcomes and relapse patterns in primary CNS lymphoma (PCNSL) are lacking. We analyzed factors associated with relapse in a large cohort with extensive follow-up. Methods T1-post-contrast-enhancing disease was characterized in immunocompetent PCNSL (diffuse large B-cell) patients from 1983 to 2020. Patients were stratified by response to induction and consolidation (complete/unconfirmed [CR/CRu], partial, stable, progression [POD]). Refractory was POD during (or relapse ≤3 months of) induction. Initial relapse site was categorized as local (involving/adjacent to baseline), distant intraparenchymal, leptomeningeal, or other. Progression-free (PFS) and overall survival (OS) were assessed with proportional hazards. Cumulative incidence with competing risks was used to assess local relapse. Results Median follow-up was 7.4 years (N = 559). Most (321, 57%) were recursive partitioning analysis class 2 (age ≥50, Karnosfky Performance Status [KPS] ≥70). Most had supratentorial (420, 81%), multifocal (274, 53%), bilateral (224, 43%), and deep structure involvement (314, 56%). Nearly all received methotrexate-based induction (532, 95%). There was no difference in PFS or OS from consolidation based on initial response to induction (CR/CRu vs PR) in patients who ultimately achieved a CR/CRu to consolidation. PFS at 1-, 5 years for 351 patients with CR/CRu to consolidation was 80% (95% confidence interval [95% CI]: 76%–84%) and 46% (95% CI: 41%–53%), respectively; 1-year cumulative incidence of local versus nonlocal relapse was 1.8% versus 15%, respectively. For 97 refractory patients, 1-year cumulative incidence of local versus nonlocal relapse was 57% versus 42%, respectively. Deep structure involvement (HR 1.89, 95% CI: 1.10%–3.27%) was associated with local relapse in refractory patients. Conclusions We report the first comprehensive relapse patterns in a large PCNSL cohort. While relapses post-CR to consolidation are typically distant and unpredictable, refractory patients had a relatively high incidence of local relapse. These findings can help optimize multimodality therapy for this highest-risk population.
Exploring the accuracy and limits of algorithms for localizing recombination breakpoints
Authors: Shi Cen, David A Rasmussen
Journal: Molecular Biology and Evolution (2024)

Abstract Phylogenetic methods are widely used to reconstruct the evolutionary relationships among species and individuals. However, recombination can obscure ancestral relationships as individuals may inherit different regions of their genome from different ancestors. It is, therefore, often necessary to detect recombination events, locate recombination breakpoints, and select recombination-free alignments prior to reconstructing phylogenetic trees. While many earlier studies have examined the power of different methods to detect recombination, very few have examined the ability of these methods to accurately locate recombination breakpoints. In this study, we simulated genome sequences based on ancestral recombination graphs and explored the accuracy of three popular recombination detection methods: MaxChi, 3SEQ, and Genetic Algorithm Recombination Detection. The accuracy of inferred breakpoint locations was evaluated along with the key factors contributing to variation in accuracy across datasets. While many different genomic features contribute to the variation in performance across methods, the number of informative sites consistent with the pattern of inheritance between parent and recombinant child sequences always has the greatest contribution to accuracy. While partitioning sequence alignments based on identified recombination breakpoints can greatly decrease phylogenetic error, the quality of phylogenetic reconstructions depends very little on how breakpoints are chosen to partition the alignment. Our work sheds light on how different features of recombinant genomes affect the performance of recombination detection methods and suggests best practices for reconstructing phylogenies based on recombination-free alignments.