tbuckley/cabot-search huggingface dataset:
Evolution in the Management of Left-Sided Obstructive Colon Cancer in the Netherlands During a 9-Year Period
Authors: Julie M.L. Sijmons, Jan Willem T. Dekker, Jurriaan B. Tuynman, Femke J. Amelung, Esther C.J. Consten, Henderik L. van Westreenen, Johannes H.W. de Wilt, Rob A.E.M. Tollenaar, Pieter J. Tanis
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: There is growing evidence that bridge to surgery with stent or decompressing stoma for left-sided obstructive colon cancer (LSOCC) is better than emergency resection (ER), especially in elderly patients (age ≥70 years). This was already incorporated in Dutch guideline recommendations in 2014. The aim of this study was to evaluate time trends and interhospital variability in treatment approaches for LSOCC, and to compare short-term outcomes between approaches. Patients and Methods: Data of patients undergoing resection for LSOCC between 2012 and 2020 were extracted from the Dutch ColoRectal Audit. Results: A total of 4,535 patients were included (3,155 ER, 573 semielective resection [SER], 807 resection after stent or stoma [RSS]). A decrease in ER over time was observed (79.7% in 2012–2014, 68.8% in 2015–2017, and 54.7% in 2018–2020) in favor of RSS (9.2%, 17.9%, and 31.2%, respectively). Compared with SER and RSS, ER was associated with higher 30-day mortality (6.2% ER, 2.8% SER, and 1.0% RSS; P &lt;.001) and complication rates (45.4%, 31.2%, 31.5%, respectively; P &lt;.001). There were still 19 hospitals with &gt;75% ER in 2018–2020. For hospitals with &gt;75% ER, mortality was significantly higher compared with hospitals mainly performing SER and RSS (5.6% vs 4.2%; P =.038). The proportion of ER in patients (age ≥70 years) decreased from 80.7% in 2012–2014 to 54.3% in 2018–2020 ( P &lt;.001). Mortality in patients aged ≥70 years was significantly lower after RSS than after ER (1.6% vs 9.5%; P &lt;.001). Conclusions: A significant decrease in ER for LSOCC at a national level was observed, although with a variable degree of adherence to revised guidelines among hospitals. The high risk of mortality after ER, especially in elderly patients, strongly supports the guideline recommendations to perform bridge to surgery in these patients.
Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology
Authors: Rachel Hodan, Samir Gupta, Jennifer M. Weiss, Lisen Axell, Carol A. Burke, Lee-May Chen, Daniel C. Chung, Katherine M. Clayback, Seth Felder, Zachariah Foda, Francis M. Giardiello, William Grady, Susan Gustafson, Andrea Hagemann, Michael J. Hall, Heather Hampel, Gregory Idos, Nora Joseph, Nawal Kassem, Bryson Katona, Kaitlyn Kelly, AnnMarie Kieber-Emmons, Sonia Kupfer, Katie Lang, Xavier Llor, Arnold J. Markowitz, Mariana Moreno Prats, Mariana Niell-Swiller, Darryl Outlaw, Sara Pirzadeh-Miller, Niloy Jewel Samadder, David Shibata, Peter P. Stanich, Benjamin J. Swanson, Brittany M. Szymaniak, Jeanna Welborn, Georgia L. Wiesner, Matthew B. Yurgelun, Mary Dwyer, Susan Darlow, Zeenat Diwan
Journal: Journal of the National Comprehensive Cancer Network (2024)

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing. This manuscript also describes recent updates to these guidelines regarding de-implementation of colon cancer screening in individuals with CHEK2 pathogenic/likely pathogenic variants, based on the most up-to-date evidence regarding the association between CHEK2 pathogenic/likely pathogenic variants and colon cancer risk.
The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation
Authors: Janire Castelo, Sarai Araujo-Aris, Diego Barriales, Samuel Tanner Pasco, Iratxe Seoane, Ainize Peña-Cearra, Ainhoa Palacios, Carolina Simó, Virginia Garcia-Cañas, Muthita Khamwong, Itziar Martín-Ruiz, Monika Gonzalez-Lopez, Laura Barcena, José Ezequiel Martín Rodríguez, José Luís Lavín, Naiara Gutiez, Raquel Marcos, Estibaliz Atondo, Arantza Cobela, Laura Plaza-Vinuesa, Adrián Plata, Eneko Santos-Fernandez, Alberto Fernandez-Tejada, Mari Carmen Villarán, José Miguel Mancheño, Juana Maria Flores, Ana María Aransay, Aize Pellón, Blanca de las Rivas, Rosario Muñoz, Abelardo Margolles, Patricia Ruas-Madiedo, Maria Victoria Selma, Mercedes Gomez de Agüero, Leticia Abecia, Juan Anguita, Héctor Rodríguez
Journal: Gut Microbes (2024)

Phloroglucinol is a key byproduct of gut microbial metabolism that has been widely used as a treatment for irritable bowel syndrome. Here, we demonstrate that phloroglucinol tempers macrophage responses to pro-inflammatory pathogens and stimuli.
Publisher Correction: Growth hormone-releasing hormone and its analogues in health and disease
Authors: Riccarda Granata, Sheila Leone, Xianyang Zhang, Iacopo Gesmundo, Charlotte Steenblock, Renzhi Cai, Wei Sha, Ezio Ghigo, Joshua M. Hare, Stefan R. Bornstein, Andrew V. Schally
Journal: Nature Reviews Endocrinology (2024)
Reply to: Short‐term risk of cardiovascular events in people newly diagnosed with gout: comment on the article by Cipolletta et al.
Authors: Edoardo Cipolletta, Laila J. Tata, Abhishek Abhishek
Journal: Arthritis & Rheumatology (2024)

Disclosure Form 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.
The oral microbiota in persons at risk for rheumatoid arthritis: follow‐up data
Authors: Johanna M. Kroese, Bernd W. Brandt, Mark J. Buijs, Wim Crielaard, Frank Lobbezoo, Bruno G. Loos, Laurette van Boheemen, Dirkjan van Schaardenburg, Egija Zaura, Catherine M.C. Volgenant
Journal: Arthritis & Rheumatology (2024)
Association of Therapies for Axial Spondyloarthritis on the Risk of Hip and Spine Fractures
Authors: Devin Driscoll, Navya George, Christine Peloquin, S. Reza Jafarzadeh, Jean W. Liew, Maureen Dubreuil
Journal: Arthritis & Rheumatology (2024)

Objective People with axial spondyloarthritis (axSpA) have increased fracture risk relative to the general population, possibly related to chronic inflammation. We assessed the impact of treatment with tumor necrosis factor inhibitors (TNFi) and non‐biologic conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) on hip and spine fractures in axSpA, relative to nonsteroidal anti‐inflammatory drugs (NSAIDs). Methods We conducted a nested case‐control study using 2006‐2021 data from the Merative TM MarketScan® Database. We included adults 18‐65 years old with ≥1 inpatient or ≥2 outpatient axSpA ICD‐9 or 10 diagnosis codes separated by ≥7 days. The primary outcome was hip and/or spine fracture, defined by ICD‐9 or 10 diagnosis or procedure codes. For each fracture case, we selected up to 10 controls without fracture. We evaluated medication exposure (TNFi, csDMARDs, NSAIDs [referent], or none) hierarchically using pharmacy claims and procedure codes. We assessed the relation of medication exposure with hip and spine fracture risk using unconditional logistic regression with confounder adjustment. Results Our main analysis included 13,519 individuals with axSpA, comprising 1,229 cases and 12,290 controls. Individuals on TNFi had 29% lower odds of fracture compared to those on NSAIDs (OR 0.71, 95% CI 0.59‐0.85), accounting for age, sex, and diagnosis year. Results were similar in the fully adjusted model (OR 0.75, 95% CI 0.62‐0.91) and when stratified by sex. Conclusion Using a large US insurance claims database, we found evidence for a protective effect of TNFi on fracture risk in axSpA underscoring a potential impact of TNFi in diminishing comorbidities linked with axSpA.
Changes in descending pain modulation during anti‐<scp>TNF</scp> therapy. A prospective study in rheumatoid arthritis and spondyloarthritis
Authors: Anne‐Priscille Trouvin, Arielle Simunek, Joël Coste, Terkia Medkour, Alice Combier, Lucile Poiroux, François Vidal, Sandrine Carvès, Didier Bouhassira, Serge Perrot
Journal: Arthritis & Rheumatology (2024)

In rheumatoid arthritis (RA) and spondyloarthritis (SpA), managing persistent pain remains challenging. Little is known regarding impaired pain pathways in these patients and the impact of bDMARDs. The objective of the RAPID (Rheumatism Pain Inhibitory Descending pathways) study was to assess pain thresholds and descending pain modulation in patients with active RA or SpA following introduction of a TNF inhibitor. (TNFi) METHODS: Patients with active disease (50RA and 50SpA), naïve to bDMARD/tsDMARD and starting a TNFi were included. Patients were followed for 6 months after TNFi initiation with clinical, psychological, and pain assessment. At all visits, participants underwent quantitative sensory testing with heat and cold pain thresholds (HPT-CPT) and descending inhibition by conditioned pain modulation (CPM). Descending pain control (CPM effect) was assessed as the change in HPT (°C) following a conditioning stimulus. Of the 100 patients (59 women, mean age 45.8 ±14.6years), 74 completed the 6-month follow-up. Thermal pain thresholds did not significantly change during follow-up. CPM effect improved significantly during follow-up: 0.25 ±2.57°C (baseline) and 2.96 ±2.50°C at 6months (p<0.001). At the end of follow-up, mean CPM effect was significantly higher in patients without significant pain compared with patients with persistent pain >3/10 (3.25°C ±2.68 vs 2.47°C ±2.11; p=0.04) and in patients achieving remission/low disease activity compared with patients with active rheumatism (3.31°C ±2.68 vs 2.18°C ±1.87; p=0.01). In active inflammatory rheumatisms, impaired descending pain modulation, but not thermal pain thresholds, is improved after TNFi treatment, suggesting a possible effect of TNFi on central pain modulation.
Enhancing Knee Osteoarthritis Prediction: Comment on the Article by Li et al
Authors: Qin Guo, Hui Li, Chengshan Guo
Journal: Arthritis & Rheumatology (2024)

Disclosure Form 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.
Exploring Occupational Asthmagen‐Related Asthma Phenotypes: A Cluster Analysis and Machine Learning Study
Authors: Tzu‐Ching Liao, Pei‐Chien Tsai, Meng‐Chih Lin, Chao‐Chien Wu, Hung‐Chen Chen, Pei‐Shih Chen, Yuan‐Chung Lin, Kang‐Shin Chen, Tsu‐Nai Wang
Journal: Allergy (2024)

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Figure S1. Figure S2. Data S1. 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.
The Bronchodilator and Anti‐Inflammatory Effect of Long‐Acting Muscarinic Antagonists in Asthma: An <scp>EAACI</scp> Position Paper
Authors: I. Agache, I. M. Adcock, C. A. Akdis, M. Akdis, G. Bentabol‐Ramos, M. van den Berge, C. Boccabella, W. G. Canonica, C. Caruso, M. Couto, I. Davila, D. Drummond, J. Fonseca, A. Gherasim, S. del Giacco, D. J. Jackson, M. Jutel, A. Licari, S. Loukides, A. Moreira, M. Mukherjee, I. Ojanguren, O. Palomares, A. Papi, L. Perez de Llano, O. J. Price, M. Rukhazde, M. H. Shamji, D. Shaw, S. Sanchez‐Garcia, A. Testera‐Montes, M. J. Torres, I. Eguiluz‐Gracia
Journal: Allergy (2024)

As cholinergic innervation is a major contributor to increased vagal tone and mucus secretion, inhaled long-acting muscarinic antagonists (LAMA) are a pillar for the treatment of chronic obstructive pulmonary disease and asthma. By blocking the muscarinic receptors expressed in the lung, LAMA improve lung function and reduce exacerbations in asthma patients who remained poorly controlled despite treatment with inhaled corticosteroids and long-acting β2 agonists. Asthma guidelines recommend LAMA as a third controller to be added on before the initiation of biologicals. In addition to bronchodilation, LAMA also exert anti-inflammatory and anti-fibrotic effects by inhibiting muscarinic receptors present in neutrophils, macrophages, fibroblasts and airway smooth muscle cells. Thus, besides bronchodilation, LAMA might provide additional therapeutic effects, thereby supporting an endotype-driven approach to asthma management. The Position Paper, developed by the Asthma Section of the European Academy of Allergy and Clinical Immunology, discusses the main cholinergic pathways in the lung, reviews the findings of significant clinical trials and real-life studies on LAMA use in asthma, examines the placement of these drugs in asthma clinical guidelines, and considers the potential for personalised medicine with LAMA in both adult and paediatric asthma patients.
ET-3/ETBR Mediates Na <sup>+</sup> -Activated Immune Signaling and Kidney Lymphatic Dynamics
Authors: Ashley L. Mutchler, Jianyong Zhong, Hai-Chun Yang, Shilin Zhao, Rachelle Crescenzi, Shannon Taylor, Roy L. Rao, Elaine L. Shelton, Annet Kirabo, Valentina Kon
Journal: Circulation Research (2024)

BACKGROUND: Lymphatic collecting vessels in the kidney are critical in clearing interstitial fluid, macromolecules, and infiltrating immune cells. Dysfunction of the lymphatic vessels can disrupt this process and exacerbate injury-associated inflammation in many disease conditions. We previously found that sodium accumulates within the kidney interstitium during proteinuric kidney injury and elevated sodium environments stimulate isolevuglandin production in antigen-presenting cells, stimulating T cells, and modulating inflammatory responses. In the present study, we investigated whether proteinuric injury increases production of isolevuglandin-adduct formation in antigen-presenting cells, their effects on lymphatic endothelial cells (LECs), and the role of the ET-3 (endothelin-3)/ETBR (endothelin type B receptor) on lymphatic vessel function. METHODS: We used a mouse model of nephrotoxin-induced proteinuric injury to show that proteinuric injury expanded the kidney lymphatic network and to immunophenotype the infiltrating immune cells. To determine mechanisms, we analyzed the interaction of migratory immune cells and LECs using an in vitro transwell migration assay, bulk RNA sequencing, and flow cytometric analysis. To determine the effect of ET-3/ETBR axis on lymphatic vessel contractility, we analyzed microdissected lymphangions utilizing a vessel perfusion chamber. RESULTS: We found that animals with proteinuric injury have increased kidney lymphangiogenesis, isolevuglandin-producing dendritic cells, and IFN (interferon)-γ–producing CD4+T cells. The sodium avid environment present in kidney injury enhances the interaction between LECs and migratory antigen-presenting cells and LEC production of isolevuglandin-adducts. Elevated sodium environment-induced isolevuglandin-adduct formation facilitates the ET-3/ETBR communication between LECs and dendritic cells. In addition, the ET-3/ETBR axis modulates lymphatic collecting vessel pumping dynamics. CONCLUSIONS: These findings reveal a novel mechanism linking the isolevuglandin-mediated ET-3/ETBR axis with LECs and infiltrating dendritic cells. ET-3/ETBR signaling in lymphatic vessel dynamics is a novel pathogenic component and a possible therapeutic target in kidney disease.
Phenotype/Immunologic Profiling in ircAEs—Letter
Authors: Sindhuja Sominidi Damodaran, Julia S. Lehman
Journal: Clinical Cancer Research (2024)

We congratulate Lacouture and colleagues on their important work, "Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways" (1). In this study, the authors classified clinical lesions of immune-related cutaneous adverse events (ircAE) into various morphologic categories and characterized their biomarker profiles. Given recent expert consensus that dermatologic precision be used when diagnosing cutaneous ircAEs (2), this work is particularly timely. By studying actionable cytokine profiles for each of the various classification categories, the authors provide additional mechanistic justification for the use of rationally selected biological agents in lieu of nonspecific and potentially toxic immunosuppressive agents, such as systemic glucocorticoids.When reviewing the data presented in the work by Lacouture and colleagues (1), we observed that a proportion of cases classified as pruritus, maculopapular, eczematous, or lichenoid subsets were found to have basement membrane zone (i.e., linear) deposition of IgG and/or complement 3 with direct immunofluorescence (DIF) testing. These findings are highly suggestive of pemphigoid diseases (of which bullous pemphigoid is the prototype) and implicate humoral immunity. We were not particularly surprised that these DIF changes were observed in patients with varied clinical morphologies, given that pemphigoid may also present with pruritus, dermatitic, or urticarial lesions or lichenoid lesions [particularly in lichen planus pemphigoides (LPP), a rare but well-described subset of pemphigoid known to develop as an ircAE (3)]. However, given that pemphigoid has a different etiopathology than purer T-cell processes such as those usually classified as being dermatitic, urticarial, or lichenoid, we would advocate that these DIF changes be weighted heavily when classifying ircAEs into various categories.In future studies and in clinical practice, it may be useful to screen for linear IgG and/or complement 3 deposition and classify positive cases separately, so as not to muddy findings observed in other categories sharing similar clinical morphologies. In addition, it may also be helpful to assess other biomarkers of pemphigoid diseases, such as indirect immunofluorescence with salt-split skin and esophageal substrates or ELISA for NC16A-BP180 and BP230 antibodies, to more definitively and accurately subclassify these cases. Finally, it is worth considering that in LPP, the lag time from lichenoid lesions to blister development can range from weeks to several months. In the study cohort, the mean time of presentation for lichenoid lesions was 98 days (60, 190), whereas for bullous dermatoses, it was 352 days (300, 421). Extended longitudinal follow-up of the lichenoid cohort may help determine whether there would be evolution to LPP, which may prompt reclassification into other more precise clinicopathologic categories.No disclosures were reported.
C-Reactive Protein Facilitates Premetastatic Niche Formation in the Lungs
Authors: Jonas Saal, Niklas Klümper, Michael Hölzel
Journal: Cancer Research (2024)

C-reactive protein (CRP) has long been recognized as a marker of inflammation, but its evolving role in immunomodulation and cancer has increasingly been recognized. In recent years, multiple studies have explored CRP as a biomarker for prognosis and therapy response, particularly in the context of cancer immunotherapy. In this issue of Cancer Research, Feng and colleagues investigate the role of CRP in the development of lung metastasis. They provide evidence for a direct role of CRP acting together with commensal bacteria to instruct an immune-tolerant state of pulmonary macrophages through Fc gamma receptor IIb signaling. By suppressing immune surveillance in the lungs, CRP facilitates the formation of a premetastatic niche, allowing circulating tumor cells to establish metastases. See related article by Feng et al., p. 4184
Correction: The Retinoblastoma Tumor Suppressor Modulates DNA Repair and Radioresponsiveness
Authors: Chellappagounder Thangavel, Ettickan Boopathi, Steve Ciment, Yi Liu, Raymond O’Neill, Ankur Sharma, Steve B. McMahon, Hestia Mellert, Sankar Addya, Adam Ertel, Ruth Birbe, Paolo Fortina, Adam P. Dicker, Karen E. Knudsen, Robert B. Den
Journal: Clinical Cancer Research (2024)
Correction: Single-Cell Transcriptomic Heterogeneity in Invasive Ductal and Lobular Breast Cancer Cells
Authors: Fangyuan Chen, Kai Ding, Nolan Priedigkeit, Ashuvinee Elangovan, Kevin M. Levine, Neil Carleton, Laura Savariau, Jennifer M. Atkinson, Steffi Oesterreich, Adrian V. Lee
Journal: Cancer Research (2024)
Streamlining the Highly Reproducible Fabrication of Fibrous Biomedical Specimens toward Standardization and High Throughput
Authors: Zan Lamberger, Camilla Mussoni, Nicoletta Murenu, Mateo Andrade Mier, Philipp Stahlhut, Taufiq Ahmad, Natascha Schaefer, Carmen Villmann, Sarah Zwingelberg, Jürgen Groll, Gregor Lang
Journal: Advanced Healthcare Materials (2024)

Soft nano- and microfiber-based polymer scaffolds bear enormous potential for their use in cell culture and tissue engineering since they mimic natural collagen structures and may thus serve as biomimetic adhesive substrates. They have, however, so far been restricted to small-scale production in research labs with high batch-to-batch variation. They are commonly produced via electrospinning or melt electrowriting and their delicate nature poses obstacles in detachment, storage, and transportation. This study focuses on overcoming challenges in the high throughput production and practical handling, introducing new methods to reproducibly prepare such scaffolds suitable for quantitative cell culture applications. Attention is given to the seamless handling and transfer of samples without compromising structural integrity. Challenges in detaching fibers without damage as well as storage, and transport are addressed. Cell culture studies demonstrate the methodological advantages, emphasizing the potential for standardized testing and biological readouts of these delicate fiber materials. The developed methods are applicable across various electrospinning and melt electrowriting approaches and can essentially contribute to their utilization in laboratory research and commercial applications.
A Nattokinase‐Loaded Nanozyme for Alleviating Acute Myocardial Infarction via Thrombolysis and Antioxidation
Authors: Yingchao Shi, Chuanfen Liu, Yuesheng Gui, Yike Guo, Yuanhao Zhang, Jiangpeng Pan, Hao Tang, Chuanyu Gao, Junyue Xing, Yu Han, Wei Jiang
Journal: Advanced Healthcare Materials (2024)

Acute myocardial infarction (MI) induced by thrombus formation is a prevalent cardiovascular disorder, and thrombolytic therapy continues to be a principal treatment modality. Prior research indicates a substantial association among MI, thrombosis, and the activation of oxidative stress pathways. The effectiveness of current thrombolytic drugs is relatively constrained, and the need for innovative and versatile thrombolytic medications remains critical. Nattokinase (NK) is a naturally-occurring enzyme known for its thrombolytic characteristics. Nonetheless, nattokinase's limited stability and susceptibility to inactivation in biological systems have impeded its clinical utility. This study designs a manganese oxide nanozyme (MnOx) loaded with NK (MnOx@NK), which exhibits both antioxidant and thrombolytic function. The administration of MnOx@NK through tail vein injection significantly restores vascular function and further reduces myocardial injury in a mouse model of myocardial infarction, demonstrating a pronounced protective effect against oxidative stress. These findings indicate that nattokinase-loaded nanozymes can be a promising approach for treating acute myocardial infarction, providing a new strategy for clinical application.