tbuckley/cabot-search huggingface dataset:
Long genetic and social isolation in Neanderthals before their extinction
Authors: Ludovic Slimak, Tharsika Vimala, Andaine Seguin-Orlando, Laure Metz, Clément Zanolli, Renaud Joannes-Boyau, Marine Frouin, Lee J Arnold, Martina Demuro, Thibaut Devièse, Daniel Comeskey, Michael Buckley, Hubert Camus, Xavier Muth, Jason E Lewis, Hervé Bocherens, Pascale Yvorra, Christophe Tenailleau, Benjamin Duployer, Hélène Coqueugniot, Olivier Dutour, Thomas Higham, Martin Sikora
Journal: Cell Genomics (2024)
Introduction and overview on autogenous Platelet concentrates
Authors: Marc Quirynen, Anton Sculean, J. Blanco, Hom‐Lay Wang, Nikos Donos
Journal: Periodontology 2000 (2024)

Abstract This special issue on autologous platelet concentrates (APCs) provides clinicians with an overview on the current understanding of the use of these biomaterials for soft and hard tissue regeneration. The included papers summarize scientific evidence and the clinical findings, presented in simple tables that outline potential benefits including Patient Reported Outcome Measures (PROMs). This approach enables clinicians to assess clinical relevance and researchers to identify significant gaps in the literature. The first part provides a comprehensive summary of the basic science surrounding APC, with particular focus on their preparation methods. Clear recommendations are outlined, which are crucial for obtaining high‐quality APCs, alongside an exploration of how APCs may influence both soft and hard tissue healing processes. Part 2 delves into the clinical evidence for the potential benefits of APCs across a range of applications: alveolar ridge preservation, sinus floor elevation, periodontal plastic surgery, guided tissue regeneration, guided bone regeneration, the healing of Medication‐Related Osteonecrosis of the Jaw (MRONJ), and endodontic surgery. In the part 3, the discussion turns to the effects of APCs on the healing of extra‐oral wounds, including diabetic foot ulcers, venous leg ulcers, pressure injuries, burns, and more. The fourth section offers a detailed, step‐by‐step flowchart for each treatment modality, providing a clear guide for clinical application.
Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy
Authors: Valérie Long, Gracia El Gebeily, Élisabeth Leblanc, Marwa Senhadji, Céline Fiset
Journal: Cardiovascular Research (2024)

Pregnant (P) women have a significantly elevated resting heart rate (HR), which makes cardiac arrhythmias more likely to occur. Although electrical remodelling of the sinoatrial node (SAN) has been documented, the underlying mechanism is not fully understood. The acetylcholine-activated potassium current (IKACh), one of the major repolarizing currents in the SAN, plays a critical role in HR control by hyperpolarizing the maximal diastolic potential (MDP) of the SAN action potential (AP), thereby reducing SAN automaticity and HR. Thus, considering its essential role in cardiac automaticity, this study aims to determine whether changes in IKACh are potentially involved in the increased HR associated with pregnancy. Experiments were conducted on non-pregnant (NP) and pregnant (P; 17-18 days gestation) female CD-1 mice aged 2 to 4 months. IKACh was recorded on spontaneously beating SAN cells using the muscarinic agonist carbachol (CCh). Voltage-clamp data showed a reduction in IKACh density during pregnancy, which returned to control values shortly after delivery. The reduction in IKACh was explained by a decrease in protein expression of Kir3.1 channel subunit and the muscarinic type 2 receptor. In agreement with these findings, current-clamp data showed that the MDP of SAN cells from P mice were less hyperpolarized following CCh administration. Surface electrocardiograms (ECGs) recorded on anaesthetized mice revealed that the cholinergic antagonist atropine and the selective KACh channel blocker tertiapin-Q increased HR in NP mice and had only a minimal effect on P mice. AP and ECG data also showed that pregnancy is associated with a decrease in beating and HR variability, respectively. IKACh function and expression are decreased in the mouse SAN during pregnancy, strongly suggesting that, in addition to other electrical remodelling of the SAN, reduced IKACh also plays an important role in the pregnancy-induced increased HR.
The non-canonical BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia
Authors: Daniel Hägerstrand, Blaž Oder, Diego Cortese, Ying Qu, Amrei Binzer-Panchal, Cecilia Österholm, Teresa Del Peso Santos, Leily Rabbani, Hassan Foroughi Asl, Aron Skaftason, Viktor Ljungström, August Lundholm, Maria Koutroumani, Zahra Haider, Cecilia Jylhä, John Mollstedt, Larry Mansouri, Karla Plevova, Andreas Agathangelidis, Lydia Scarfò, Marine Armand, Alice F Muggen, Neil E Kay, Tait Shanafelt, Davide Rossi, Lukas M Orre, Sarka Pospisilova, Konstantin Barylyuk, Frederic Davi, Mattias Vesterlund, Anton W Langerak, Janne Lehtiö, Paolo Ghia, Kostas Stamatopoulos, Lesley-Ann Sutton, Richard Rosenquist
Journal: Leukemia (2024)
Wnt/β-Catenin Signaling in Liver Pathobiology
Authors: Matthew D. Carson, Kari Nejak-Bowen
Journal: Annual Review of Pathology Mechanisms of Disease (2024)

The liver has a critical role in regulating host metabolism, immunity, detoxification, and homeostasis. Proper liver function is essential for host health, and dysregulation of hepatic signaling pathways can lead to the onset of disease. The Wnt/β-catenin signaling pathway is an important regulator of liver homeostasis and function. Throughout life, hepatic Wnt/β-catenin signaling contributes to liver development and growth, metabolic zonation, and regeneration. Extensive research has demonstrated that aberrant Wnt/β-catenin signaling drives liver pathologies, including cancers, steatohepatitis, and cholestasis. In this review, we discuss the Wnt/β-catenin pathway as it pertains to liver function and how disruptions in this pathway contribute to the onset and progression of liver diseases. Further, we discuss ongoing research that targets the Wnt/β-catenin pathway for the treatment of liver pathologies.
The use of Reflectance Confocal Microscopy to diagnose Basal Cell Carcinoma in the United Kingdom: A Prospective Observational Trial at a Single Centre
Authors: Howard P Stevens, Riccardo Pampena, Francesca Farnetani, Giovanni Pellicani, Colin Angus, Joseph N El-Jabbour
Journal: British Journal of Dermatology (2024)

Abstract Background Previous work with Reflectance Confocal Microscopy (RCM) imaging has shown high sensitivity and specificity for Basal Cell Carcinoma (BCC), but to date there have been few studies on a UK cohort. Objectives The study hypothesised that RCM could be used prospectively to accurately diagnose BCC in a private UK secondary care, single clinician setting. The study assessed the potential for RCM to be used as a routine diagnostic procedure. Methods 522 lesions were recruited prospectively where BCC featured in the differential diagnosis after clinical examination. 78 were subsequently excluded. Imaging used the arm-mounted confocal microscope unless access was restricted and required the handheld probe. The likelihood of BCC was scored for each modality, each diagnosis building on the last. Histology was assessed by a single blinded histopathologist [JJ]. Results 444 lesions from 326 patients were included in the analysis, including 327 BCCs. Median maximum diameter was 6 mm. The sensitivity and specificity for BCC was 69.42% (64.11% to 74.37%) and 52.99% (43.55% to 62.28%) for clinical examination alone; 91.77% (88.25% to 94.51%) and 41.03% (32.02% to 50.50%) plus dermoscopy; 98.78% (96.91% to 99.67%) and 85.47% (77.76% to 91.30%) plus RCM. For RCM PPV was 95.01% (92.14% to 97.07%) and NPV was 96.15% (90.44% to 98.94%). Area under the curve increased from 0.61 to 0.66 to 0.92 as modalities were added. Conclusion This study demonstrates that RCM can, reliably and quickly, diagnose BCC, and that the addition of RCM to dermoscopy permits higher diagnostic accuracy for BCC in the UK. The specificity and sensitivity of the RCM diagnosis did not alter significantly with experience, reflecting the ease and speed of acquiring the skill. Clinical Trial Registration NCT03509415
Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study
Authors: Susan R Rheingold, Deepa Bhojwani, Lingyun Ji, Xinxin Xu, Meenakshi Devidas, John A Kairalla, Mary Shago, Nyla A Heerema, Andrew J Carroll, Heather Breidenbach, Michael Borowitz, Brent L Wood, Anne L Angiolillo, Barbara L Asselin, W Paul Bowman, Patrick Brown, ZoAnn E Dreyer, Kimberly P Dunsmore, Joanne M Hilden, Eric Larsen, Kelly Maloney, Yousif Matloub, Leonard A Mattano, Stuart S Winter, Lia Gore, Naomi J Winick, William L Carroll, Stephen P Hunger, Elizabeth A Raetz, Mignon L Loh
Journal: Leukemia (2024)
A robust image segmentation and synthesis pipeline for histopathology
Authors: Muhammad Jehanzaib, Yasin Almalioglu, Kutsev Bengisu Ozyoruk, Drew F K Williamson, Talha Abdullah, Kayhan Basak, Derya Demir, G Evren Keles, Kashif Zafar, Mehmet Turan
Journal: Medical Image Analysis (2024)
Disease prediction with multi-omics and biomarkers empowers case–control genetic discoveries in the UK Biobank
Authors: Manik Garg, Marcin Karpinski, Dorota Matelska, Lawrence Middleton, Oliver S Burren, Fengyuan Hu, Eleanor Wheeler, Katherine R Smith, Margarete A Fabre, Jonathan Mitchell, Amanda O'Neill, Euan A Ashley, Andrew R Harper, Quanli Wang, Ryan S Dhindsa, Slavé Petrovski, Dimitrios Vitsios
Journal: Nature Genetics (2024)
Association of ADAM family members with proliferation signaling and disease progression in multiple myeloma
Authors: Marietheres Evers, Thorsten Stühmer, Martin Schreder, Torsten Steinbrunn, Martina Rudelius, Franziska Jundt, Regina Ebert, Tanja Nicole Hartmann, Ralf Christian Bargou, Andreas Rosenwald, Ellen Leich
Journal: Blood Cancer Journal (2024)
ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells
Authors: Laura Carretero-Iglesia, Olivia J. Hall, Jérémy Berret, Daniela Pais, Carole Estoppey, Myriam Chimen, Thierry Monney, Jeremy Loyau, Cyrille Dreyfus, Julie Macoin, Cynthia Perez, Vinu Menon, Isabelle Gruber, Amélie Laurendon, Lydia N. Caro, Girish S. Gudi, Tomomi Matsuura, Piet H. van der Graaf, Stanislas Blein, M. Lamine Mbow, Rebecca Croasdale-Wood, Ankita Srivastava, Michael R. Dyson, Thomas Matthes, Zeynep Kaya, Claire M. Edwards, James R. Edwards, Sophie Maiga, Catherine Pellat-Deceunynck, Cyrille Touzeau, Philippe Moreau, Cyril Konto, Adam Drake, Eugene A. Zhukovsky, Mario Perro, Maria Pihlgren
Journal: Nature Cancer (2024)
Biodegradable WE43 Mg alloy/hydroxyapatite interpenetrating phase composites with reduced hydrogen evolution
Authors: Lenka Drotárová, Karel Slámečka, Tomáš Balint, Michaela Remešová, Radovan Hudák, Jozef Živčák, Marek Schnitzer, Ladislav Čelko, Edgar B Montufar
Journal: Bioactive Materials (2024)
Hierarchically Structured Biodegradable Microspheres Promote Therapeutic Angiogenesis
Authors: Eseelle K. Hendow, Francesco Iacoviello, Mar Casajuana Ester, Caroline Pellet‐Many, Richard M. Day
Journal: Advanced Healthcare Materials (2024)

Abstract Promoting neovascularization is a prerequisite for many tissue engineering applications and the treatment of cardiovascular disease. Delivery of a pro‐angiogenic stimulus via acellular materials offers several benefits over biological therapies but has been hampered by interaction of the implanted material with the innate immune response. However, macrophages, a key component of the innate immune response, release a plurality of soluble factors that can be harnessed to stimulate neovascularization and restore blood flow to damaged tissue. This study investigates the ability of biodegradable poly(D,L‐lactic‐co‐glycolic acid) (PLGA) microspheres to restore tissue perfusion in a hind limb model of ischaemia. Microspheres exhibiting a hierarchical porous structure are associated with an increase in blood flow at day 21 post‐implantation compared with solid microspheres composed of the same polymer. This corresponds with an increase in blood vessel density in the surrounding tissue. In vitro simulation of the foreign body response observed demonstrates M2‐like macrophages incubated with the porous microspheres secreted increased amounts of vascular endothelial growth factor (VEGF) compared with M1‐like macrophages providing a potential mechanism for the increased neovascularization. The results from this study demonstrate implantable biodegradable porous microspheres provide a novel approach for increasing neovascularization that could be exploited for therapeutic applications.
Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update
Authors: Sibylle Loibl, Jacek Jassem, Amir Sonnenblick, Damien Parlier, Eric Winer, Jonas Bergh, Richard D. Gelber, Eleonora Restuccia, Young-Hyuck Im, Chiun-Sheng Huang, Florence Dalenc, Isabel Calvo, Marion Procter, Carmela Caballero, Emma Clark, Alice Raimbault, Robin McConnell, Estefania Monturus, Evandro de Azambuja, Henry L. Gomez, Judith Bliss, Giuseppe Viale, Jose Bines, Martine Piccart, Stefan Aebi, Michael Andersson, Jonas Bergh, José Bines, Judith Bliss, Hervé Bonnefoi, Carmela Caballero, David Cameron, Fatima Cardoso, Emma Clark, Evandro de Azambuja, Sanne de Haas, Susan Dent, Luis Fein, Elizabeth Frank, Richard Gelber, Michael Gnant, Henry Gomez Moreno, Seock-Ah Im, Christian Jackisch, Wolfgang Janni, Jacek Jassem, Ian Krop, Sherko Kümmel, Tsang-Wu Liu, Sherene Loi, Sibylle Loibl, Norikazu Masuda, Einav Nili Gam-Yal, Beatrice Nyawira, Tomas Pascual, Martine Piccart, Tadeusz Pienkowski, Marion Procter, Eleonora Restuccia, Álvaro Rodríguez-Lescure, Thomas Suter, Christoph Thomssen, Vivianne Tjan-Heijnen, Gianluca Tomasello, Manuel Roberto Torres Ulloa, Chris Twelves, Giuseppe Viale, Janice Walshe, Nicholas Wilcken, Eric Winer
Journal: Journal of Clinical Oncology (2024)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The APHINITY trial (ClinicalTrials.gov identifier: NCT01358877 ) previously demonstrated that pertuzumab added to adjuvant trastuzumab and chemotherapy improved invasive disease-free survival (iDFS) for patients with early human epidermal growth factor receptor 2–positive (HER2+) breast cancer (BC). Here, we report the preplanned third interim analysis of overall survival (OS) and a descriptive updated iDFS analysis with 8.4 years of median follow-up of 4,804 patients in the intent-to-treat population. The 8-year OS was 92.7% in the pertuzumab versus 92.0% in the placebo group (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .078, above the 0.006 significance threshold). The HR was 0.80 [95% CI 0.63 to 1.00] in the node-positive cohort and 0.99 [95% CI, 0.64 to 1.55] in the node-negative cohort. Updated results of 8-year iDFS in the node-positive cohort showed an absolute improvement of 4.9% favoring pertuzumab (86.1% v 81.2%; HR, 0.72 [95% CI, 0.60 to 0.87]). The node-negative cohort did well without adding pertuzumab (8-year iDFS and OS in the placebo group were 93.3% and 96.4%, respectively). The iDFS benefit was seen in the hormone receptor–negative (HR, 0.82 [95% CI, 0.64 to 1.06]) and HR+ cohorts (HR of 0.75 [95% CI, 0.61 to 0.92]). Despite improvement in overall iDFS, the addition of pertuzumab did not improve OS at this third interim analysis.
PEI‐Engineered Lipid@PLGA Hybrid Nanoparticles for Multimodal Delivery of Antigens and Immune Adjuvants to the Respiratory Mucosa
Authors: Susy Brusco, Gemma Conte, Annunziata Corteggio, Teresa Silvestri, Andrea Spitaleri, Paola Brocca, Agnese Miro, Fabiana Quaglia, Ivana d'Angelo, Luciana D'Apice, Paola Italiani, Gabriella Costabile, Francesca Ungaro
Journal: Advanced Healthcare Materials (2024)

Abstract Antigen delivery via respiratory mucosal surfaces is an interesting needle‐free option for vaccination. Nonetheless, it demands for the design of especially tailored formulations. Here, lipid/poly(lactic‐co‐glycolic) acid (PLGA) hybrid nanoparticles (hNPs) for the combined delivery of an antigen, ovalbumin (Ova), and an adjuvant, synthetic unmethylated cytosine‐phosphate‐guanine oligodeoxynucleotide (CpG) motifs, is developed. A panel of Ova/CpG‐loaded lipid@PLGA hNPs with tunable size and surface is attained by exploiting two lipid moieties, 1,2 distearoil‐sn‐glycero‐3‐phosphoethanolamine‐poly(ethylene glycol) (DSPE‐PEG) and monophosphoryl lipid A (MPLA), with or without polyethyleneimine (PEI). It is gained insights on the lipid@PLGA hNPs through a combination of techniques to analytically determine the specific moiety on the surface, the spatial distribution of the components and the internal structure of the nanoplatforms. The collected results suggest that PEI plays a role of paramount importance not only in promoting in vitro antigen escape from lysosomes and enhancing antigen cross‐presentation, but also in determining the arrangement of the moieties in the final architecture of the hNPs. Though multicomponent PEI‐engineered lipid@PLGA hNPs turn out as a viable strategy for delivery of antigens and adjuvant to the respiratory mucosa, tunable nanoparticle features are achievable only through the optimal selection of the components and their relative amounts.
Heart failure in Europe: Guideline‐directed medical therapy use and decision making in chronic and acute, pre‐existing and de novo, heart failure with reduced, mildly reduced, and preserved ejection fraction – the ESC EORP Heart Failure III Registry
Authors: Lars H. Lund, Maria Generosa Crespo‐Leiro, Cécile Laroche, Diana Zaliaduonyte, Aly M. Saad, Candida Fonseca, Jelena Čelutkienė, Marija Zdravkovic, Agata M. Bielecka‐Dabrowa, Piergiuseppe Agostoni, Robert G. Xuereb, Kseniya V. Neronova, Malgorzata Lelonek, Yuksel Cavusoglu, Barnabas Gellen, Magdy Abdelhamid, Naima Hammoudi, Stefan D. Anker, Ovidiu Chioncel, Gerasimos Filippatos, Mitja Lainscak, Theresa A. McDonagh, Alexandre Mebazaa, Massimo Piepoli, Frank Ruschitzka, Petar M. Seferović, Gianluigi Savarese, Marco Metra, Giuseppe M.C. Rosano, Aldo P. Maggioni
Journal: European Journal of Heart Failure (2024)
Machine‐learning based subgroups of <scp>AL</scp> amyloidosis and cumulative incidence of mortality and end stage kidney disease
Authors: Shankara K. Anand, Andrew Staron, Lisa M. Mendelson, Tracy Joshi, Natasha Burke, Vaishali Sanchorawala, Ashish Verma
Journal: American Journal of Hematology (2024)

Abstract Immunoglobulin light chain ( AL ) amyloidosis is a multisystem disease with varied treatment options and disease‐related outcomes. Current staging systems rely on a limited number of cardiac, renal, and plasma cell dyscrasia biomarkers. To improve prognostication for all‐cause mortality and end‐stage kidney disease ( ESKD ), we applied unsupervised machine learning using a comprehensive set of clinical and laboratory parameters. Our study cohort comprised 2067 patients with newly diagnosed, biopsy‐proven AL amyloidosis from the Boston University Amyloidosis Center. Variables included 31 clinical symptoms and 28 baseline laboratory values. Our clustering algorithm identified three subgroups of AL amyloidosis (low‐risk, intermediate‐risk, and high‐risk) with distinct clinical phenotypes and median overall survival ( OS ) estimates of 6.1, 3.7, and 1.2 years, respectively. The 10‐year adjusted cumulative incidences of all‐cause mortality were 66.8% (95% CI 63.4–70.1), 75.4% (95% CI 72.1–78.6), and 90.6% (95% CI 87.4–93.3) for low, intermediate, and high‐risk subgroups. The 10‐year adjusted cumulative incidences of end‐stage kidney disease ( ESKD ) were 20.4% (95% CI 6.1–24.5), 37.6% (95% CI 31.8–43.8), and 6.7% (95% CI 2.8–11.3) for low‐risk, intermediate‐risk, and high‐risk subgroups. Finally, we trained a classifier for external validation with high cross‐validation accuracy (85% [95% CI 83–86]) using a subset of easily obtainable clinical parameters. This marks an initial stride toward integrating precision medicine into risk stratification of AL amyloidosis for both all‐cause mortality and ESKD .
Vascular Remodeling in Coronary Microvascular Dysfunction
Authors: Carlos Collet, Koshiro Sakai, Takuya Mizukami, Hirofumi Ohashi, Frederic Bouisset, Serena Caglioni, Lieven van Hoe, Emanuele Gallinoro, Dario Tino Bertolone, Sofie Pardaens, Sofie Brouwers, Tatyana Storozhenko, Ruiko Seki, Daniel Munhoz, Atomu Tajima, Dimitri Buytaert, Marc Vanderheyden, Eric Wyffels, Jozef Bartunek, Jeroen Sonck, Bernard De Bruyne
Journal: JACC. Cardiovascular imaging (2024)
Inpatient Use of Guideline-Directed Medical Therapy During Heart Failure Hospitalizations Among Community-Based Health Systems
Authors: Jimmy Zheng, Alexander T Sandhu, Ankeet S Bhatt, Sean P Collins, Kelsey M Flint, Gregg C Fonarow, Marat Fudim, Stephen J Greene, Paul A Heidenreich, Anuradha Lala, Jeffrey M Testani, Anubodh S Varshney, Ryan S K Wi, Andrew P Ambrosy
Journal: JACC Heart Failure (2024)
Head-to-Head Comparison of Near-Infrared Spectroscopy–Intravascular Ultrasound and Coronary Computed Tomography Angiography in Assessing Atheroma Characteristics
Authors: Anantharaman Ramasamy, Francesca Pugliese, Ibrahim Halil Tanboga, Pieter Kitslaar, Jouke Dijkstra, Anthony Mathur, Ryo Torii, James C. Moon, Andreas Baumbach, Christos V. Bourantas
Journal: JACC. Cardiovascular imaging (2024)
Engineering extracellular vesicles derived from endothelial cells sheared by laminar flow for anti-atherosclerotic therapy through reprogramming macrophage
Authors: Chunli Li, Fei Fang, Erxiang Wang, Hanqiao Yang, Xinrui Yang, Qiwei Wang, Longlong Si, Zhen Zhang, Xiaoheng Liu
Journal: Biomaterials (2024)
Determinants of Persistence and Recovery of Chronic COVID19 Chemosensory Dysfunction
Authors: Dante G Minichetti, Amelia Boyd, Evan Lemire, Jonathan Hacker, Adam L Haber, Rachel E Roditi, Mark W Albers, Stella Lee, Kathleen M Buchheit, Tanya M Laidlaw, Lora G Bankova
Journal: Journal of Allergy and Clinical Immunology (2024)