tbuckley/cabot-search huggingface dataset:
Genomics predicting prognosis in Metastatic Extramammary Paget’s Disease
Authors: Aideen M McInerney-Leo, Erin K McMeniman
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Genomics predicting prognosis in Metastatic Extramammary Paget's Disease Get access Aideen M McInerney-Leo, Aideen M McInerney-Leo Frazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Queensland, Australia Correspondence: Aideen M. McInerney-Leo Email:a.mcinerney@uq.edu.au https://orcid.org/0000-0002-0059-5732 Search for other works by this author on: Oxford Academic Google Scholar Erin K McMeniman Erin K McMeniman Frazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Queensland, AustraliaDepartment of Dermatology, Princess Alexandra Hospital, Brisbane, Australia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae387, https://doi.org/10.1093/bjd/ljae387 Published: 09 October 2024 Article history Received: 25 September 2024 Accepted: 07 October 2024 Published: 09 October 2024
Chromosome 8 Inversion Mutation in Congenital Generalized Hypertrichosis: Precise Breakpoints Localization
Authors: Anqi Zhao, Qiaoyu Cao, Chaolan Pan, Xiaoxiao Wang, Yumeng Wang, Ming Li
Journal: British Journal of Dermatology (2024)

We report a three-generation family with congenital generalized hypertrichosis (CGH), identifying an inversion variant on chromosome 8: inv(8)(q24.13q24.3) through comprehensive genetics analysis. Our report enriches the spectrum of CGH and its mutation profile.
The developing immune system in preterm born infants: From contributor to potential solution for respiratory tract infections and wheezing
Authors: Inger C. van Duuren, Oscar R. J. van Hengel, John Penders, Liesbeth Duijts, Hermelijn H. Smits, Gerdien A. Tramper‐Stranders
Journal: Allergy (2024)

Abstract Moderate‐late preterm‐born infants experience more frequent and severe respiratory tract infections and wheezing compared to term‐born infants. Decreasing the risk on respiratory tract infections and wheezing in this group is vital to improve quality of life and reduce medical consumption during infancy, but also to reduce the risk on asthma and COPD later in life. Until now, moderate‐late preterm infants are underrepresented in research and mechanisms underlying their morbidity are largely unknown, although they represent 80% of all preterm‐born infants. In order to protect these infants effectively, it is essential to understand the role of the immune system in early life respiratory health and to identify strategies to optimize immune development and respiratory health. This review elaborates on risk factors and preventative measures concerning respiratory tract infections and wheezing in preterm‐born infants, exploring their impact on the immune system and microbiome. Factors discussed are early life antibiotic use, birth mode, feeding type and living environment. Further, differences in adaptive and innate immune maturation between term and preterm infants are discussed, as well as differences in local immune reactions in the lungs. Finally, preventative strategies are being explored, including microbiota transplantation, immune modulation (through pre‐, pro‐, syn‐ and postbiotics, bacterial lysates, vaccinations, and monoclonal antibodies) and antibiotic prophylaxis.
Cardiovascular outcomes with exenatide in type 2 diabetes according to ejection fraction: The <scp>EXSCEL</scp> trial
Authors: João Sérgio Neves, Ana Rita Leite, Robert J. Mentz, Rury R. Holman, Faiez Zannad, Javed Butler, Milton Packer, João Pedro Ferreira
Journal: European Journal of Heart Failure (2024)
CREB3L1 deficiency impairs odontoblastic differentiation and molar dentin deposition partially through the TMEM30B
Authors: Yuanyuan Li, Yuxiu Lin, Jinqiang Guo, Delan Huang, Huanyan Zuo, Hanshu Zhang, Guohua Yuan, Huan Liu, Zhi Chen
Journal: International Journal of Oral Science (2024)

Odontoblasts are primarily responsible for synthesizing and secreting extracellular matrix proteins, which are crucial for dentinogenesis. Our previous single-cell profile and RNAscope for odontoblast lineage revealed that cyclic adenosine monophosphate responsive element-binding protein 3 like 1 (Creb3l1) was specifically enriched in the terminal differentiated odontoblasts. In this study, deletion of Creb3l1 in the Wnt1+ lineage led to insufficient root elongation and dentin deposition. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing were performed to revealed that in CREB3L1-deficient mouse dental papilla cells (mDPCs), the genes near the closed chromatin regions were mainly associated with mesenchymal development and the downregulated genes were primarily related to biological processes including cell differentiation, protein biosynthesis and transport, all of which were evidenced by a diminished ability of odontoblastic differentiation, a significant reduction in intracellular proteins, and an even greater decline in extracellular supernatant proteins. Dentin matrix protein 1 (Dmp1), dentin sialophosphoprotein (Dspp), and transmembrane protein 30B (Tmem30b) were identified as direct transcriptional regulatory targets. TMEM30B was intensively expressed in the differentiated odontoblasts, and exhibited a significant decline in both CREB3L1-deficient odontoblasts in vivo and in vitro. Deletion of Tmem30b impaired the ability of odontoblastic differentiation, protein synthesis, and protein secretion in mDPCs. Moreover, overexpressing TMEM30B in CREB3L1-deficient mDPCs partially rescued the extracellular proteins secretion. Collectively, our findings suggest that CREB3L1 participates in dentinogenesis and facilitates odontoblastic differentiation by directly enhancing the transcription of Dmp1, Dspp, and other differentiation-related genes and indirectly promoting protein secretion partially via TMEM30B.
Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer’s disease
Authors: Xuemei Zeng, Tara K. Lafferty, Anuradha Sehrawat, Yijun Chen, Pamela C. L. Ferreira, Bruna Bellaver, Guilherme Povala, M. Ilyas Kamboh, William E. Klunk, Ann D. Cohen, Oscar L. Lopez, Milos D. Ikonomovic, Tharick A. Pascoal, Mary Ganguli, Victor L. Villemagne, Beth E. Snitz, Thomas K. Karikari
Journal: Molecular Neurodegeneration (2024)

Blood-based biomarkers are gaining grounds for the detection of Alzheimer's disease (AD) and related disorders (ADRDs). However, two key obstacles remain: the lack of methods for multi-analyte assessments and the need for biomarkers for related pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction. A novel proteomic method for pre-selected analytes, based on proximity extension technology, was recently introduced. Referred to as the NULISAseq CNS disease panel, the assay simultaneously measures ~ 120 analytes related to neurodegenerative diseases, including those linked to both core (i.e., tau and amyloid-beta (Aβ)) and non-core AD processes. This study aimed to evaluate the technical and clinical performance of this novel targeted proteomic panel.
Rainfall events and daily mortality across 645 global locations: two stage time series analysis
Authors: Cheng He, Susanne Breitner-Busch, Veronika Huber, Kai Chen, Siqi Zhang, Antonio Gasparrini, Michelle Bell, Haidong Kan, Dominic Royé, Ben Armstrong, Joel Schwartz, Francesco Sera, Ana Maria Vicedo-Cabrera, Yasushi Honda, Jouni J K Jaakkola, Niilo Ryti, Jan Kyselý, Yuming Guo, Shilu Tong, Francesca de’Donato, Paola Michelozzi, Micheline de Sousa Zanotti Staglior Coelho, Paulo Hilario Nascimento Saldiva, Eric Lavigne, Hans Orru, Ene Indermitte, Mathilde Pascal, Patrick Goodman, Ariana Zeka, Yoonhee Kim, Magali Hurtado Diaz, Eunice Elizabeth Félix Arellano, Ala Overcenco, Jochem Klompmaker, Shilpa Rao, Alfonso Diz-Lois Palomares, Gabriel Carrasco, Xerxes Seposo, Susana das Neves Pereira da Silva, Joana Madureira, Iulian-Horia Holobaca, Noah Scovronick, Fiorella Acquaotta, Ho Kim, Whanhee Lee, Masahiro Hashizume, Aurelio Tobias, Carmen Íñiguez, Bertil Forsberg, Martina S Ragettli, Yue Leon Guo, Shih-Chun Pan, Samuel Osorio, Shanshan Li, Antonella Zanobetti, Tran Ngoc Dang, Do Van Dung, Alexandra Schneider
Journal: BMJ (2024)

To examine the associations between characteristics of daily rainfall (intensity, duration, and frequency) and all cause, cardiovascular, and respiratory mortality.
The Lancet Commission on self-harm
Authors: Paul Moran, Amy Chandler, Pat Dudgeon, Olivia J Kirtley, Duleeka Knipe, Jane Pirkis, Mark Sinyor, Rosie Allister, Jeffrey Ansloos, Melanie A Ball, Lai Fong Chan, Leilani Darwin, Kate L Derry, Keith Hawton, Veronica Heney, Sarah Hetrick, Ang Li, Daiane B Machado, Emma McAllister, David McDaid, Ishita Mehra, Thomas Niederkrotenthaler, Matthew K Nock, Victoria M O'Keefe, Maria A Oquendo, Joseph Osafo, Vikram Patel, Soumitra Pathare, Shanna Peltier, Tessa Roberts, Jo Robinson, Fiona Shand, Fiona Stirling, Jon P A Stoor, Natasha Swingler, Gustavo Turecki, Svetha Venkatesh, Waikaremoana Waitoki, Michael Wright, Paul S F Yip, Michael J Spoelma, Navneet Kapur, Rory C O'Connor, Helen Christensen
Journal: The Lancet (2024)
Dynamic choice HIV prevention with cabotegravir long-acting injectable in rural Uganda and Kenya: a randomised trial extension
Authors: Moses R Kamya, Laura B Balzer, James Ayieko, Jane Kabami, Elijah Kakande, Gabriel Chamie, Nicole Sutter, Helen Sunday, Janice Litunya, Joshua Schwab, John Schrom, Melanie Bacon, Catherine A Koss, Alex R Rinehart, Maya Petersen, Diane V Havlir
Journal: The Lancet HIV (2024)
Mucosal nirsevimab levels in respiratory syncytial virus breakthrough bronchiolitis
Authors: Sylvie Pillet, Aymeric Cantais, Blandine Noailly, Fabienne Jospin, Franck Zekre, Oulfa Boussetta-Charfi, Sara Chenafi-Adham, Thomas Bourlet, Slim Fourati, Stéphane Paul
Journal: The Lancet Infectious Diseases (2024)
Weighing the Risks of Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy
Authors: Cynthia E Dunbar
Journal: New England Journal of Medicine (2024)

More than 30 years ago, the first transplantation with autologous hematopoietic stem cells modified with integrated murine retroviral vectors carrying potentially therapeutic genes was performed in patients with serious human disorders. The past decade has been marked by an acceleration in the publication of data from clinical trials and in regulatory approvals for therapies that use viral gene addition to treat hemoglobinopathies, immunodeficiencies, and metabolic neurologic disorders such as cerebral adrenoleukodystrophy.1 After the induction of numerous hematologic cancers linked to activation or dysregulation of nearby oncogenes by viral promoter–enhancers contained within the retroviral vector among patients enrolled in early clinical . . .
Intertriginous Rash in Secondary Syphilis
Authors: Jetanat Chantrapitak, Mati Chuamanochan
Journal: New England Journal of Medicine (2024)

A 25-year-old woman receiving daily prednisolone treatment for systemic lupus erythematosus presented with a 3-month history of erosive, violaceous plaques in the antecubital fossae, popliteal fossae, and inguinal regions.
CXCL12+ Tumor-associated Endothelial Cells Promote Immune Resistance in Hepatocellular Carcinoma.
Authors: Yajie Lu, Yunpeng Liu, Xiaoshuang Zuo, Guodong Li, Jianlin Wang, Jianshan Liu, Xiangxu Wang, Shuning Wang, Wangqian Zhang, Kuo Zhang, Xiaoying Lei, Qiang Hao, Weina Li, Lei Liu, Meng Li, Cun Zhang, Hongmei Zhang, Yingqi Zhang, Yuan Gao
Journal: Journal of Hepatology (2024)
DNA demethylation triggers cell free DNA release in colorectal cancer cells
Authors: Valeria Pessei, Marco Macagno, Elisa Mariella, Noemi Congiusta, Vittorio Battaglieri, Paolo Battuello, Marco Viviani, Giulia Gionfriddo, Simona Lamba, Annalisa Lorenzato, Daniele Oddo, Fariha Idrees, Alessandro Cavaliere, Alice Bartolini, Simonetta Guarrera, Michael Linnebacher, Laura Monteonofrio, Luca Cardone, Michele Milella, Andrea Bertotti, Silvia Soddu, Elena Grassi, Giovanni Crisafulli, Alberto Bardelli, Ludovic Barault, Federica Di Nicolantonio
Journal: Genome Medicine (2024)

Liquid biopsy based on cell-free DNA (cfDNA) analysis holds significant promise as a minimally invasive approach for the diagnosis, genotyping, and monitoring of solid malignancies. Human tumors release cfDNA in the bloodstream through a combination of events, including cell death, active and passive release. However, the precise mechanisms leading to cfDNA shedding remain to be characterized. Addressing this question in patients is confounded by several factors, such as tumor burden extent, anatomical and vasculature barriers, and release of nucleic acids from normal cells. In this work, we exploited cancer models to dissect basic mechanisms of DNA release.
Collagenase Injection versus Limited Fasciectomy for Dupuytren’s Contracture
Authors: Joseph Dias, Puvanendran Tharmanathan, Catherine Arundel, Charlie Welch, Qi Wu, Paul Leighton, Maria Armaou, Nick Johnson, Sophie James, John Cooke, Lionel Bainbridge, Michael Craigen, David Warwick, Samantha Brady, Lydia G. Flett, Judy Jones, Catherine N. Knowlson, Michelle Watson, Ada Keding, Catherine E. Hewitt, David Torgerson
Journal: New England Journal of Medicine (2024)

Treatments for Dupuytren's contracture include limited fasciectomy and collagenase injection. Comparisons of the effectiveness of these treatments have been limited.
Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer
Authors: Lars Holmberg, Hans Garmo, Swen-Olof Andersson, Ove Andrén, Eva Johansson, Kimmo Taari, Michael Häggman, Stig Nordling, Christer Busch, Hans-Olov Adami, Jan-Erik Johansson, Anna Bill-Axelson
Journal: New England Journal of Medicine (2024)

In this randomized trial, conducted between 1989 and 2022 to compare radical prostatectomy with watchful waiting, radical prostatectomy led to a 48% lower risk of death from prostate cancer and to 2.2 life-years gained.
Case 31-2024: A 37-Year-Old Man with Fever, Myalgia, Jaundice, and Respiratory Failure
Authors: William C Hillmann, Ryan Chung, Amir M Mohareb, Miranda E Machacek, Robyn A Stoddard
Journal: New England Journal of Medicine (2024)

A 37-year-old man was transferred to the hospital because of fever, myalgia, and hypoxemia. Evaluation revealed leukocytosis, acute kidney failure, and conjugated hyperbilirubinemia. A diagnosis was made.
A platform to map the mind–mitochondria connection and the hallmarks of psychobiology: the MiSBIE study
Authors: Catherine Kelly, Caroline Trumpff, Carlos Acosta, Stephanie Assuras, Jack Baker, Sophia Basarrate, Alexander Behnke, Ke Bo, Natalia Bobba-Alves, Frances A Champagne, Quinn Conklin, Marissa Cross, Philip De Jager, Kris Engelstad, Elissa Epel, Soah G Franklin, Michio Hirano, Qiuhan Huang, Alex Junker, Robert-Paul Juster, Darshana Kapri, Clemens Kirschbaum, Mangesh Kurade, Vincenzo Lauriola, Shufang Li, Cynthia C Liu, Grace Liu, Bruce McEwen, Marlon A McGill, Kathleen McIntyre, Anna S Monzel, Jeremy Michelson, Aric A Prather, Eli Puterman, Xiomara Q Rosales, Peter A Shapiro, David Shire, George M Slavich, Richard P Sloan, Janell L M Smith, Marisa Spann, Julie Spicer, Gabriel Sturm, Sophia Tepler, Michel Thiebaut de Schotten, Tor D Wager, Martin Picard
Journal: Trends in Endocrinology and Metabolism (2024)
Hairy-Cell Leukemia
Authors: Brunangelo Falini, Enrico Tiacci
Journal: New England Journal of Medicine (2024)

Hairy-cell leukemia, a rare B-cell cancer driven by a BRAF mutation and manifesting with cytopenias and splenomegaly, is responsive to purine analogue chemotherapy and to BRAF inhibitors combined with anti-CD20 antibodies.
Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy
Authors: Christine N. Duncan, Jacob R. Bledsoe, Bartosz Grzywacz, Amy Beckman, Melissa Bonner, Florian S. Eichler, Jörn-Sven Kühl, Marian H. Harris, Sarah Slauson, Richard A. Colvin, Vinod K. Prasad, Gerald F. Downey, Francis J. Pierciey, Melissa A. Kinney, Marianna Foos, Ankit Lodaya, Nicole Floro, Geoffrey Parsons, Andrew C. Dietz, Ashish O. Gupta, Paul J. Orchard, Himal L. Thakar, David A. Williams
Journal: New England Journal of Medicine (2024)

Gene therapy with elivaldogene autotemcel (eli-cel) consisting of autologous CD34+ cells transduced with lentiviral vector containing
Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy
Authors: Florian Eichler, Christine N Duncan, Patricia L Musolino, Troy C Lund, Ashish O Gupta, Satiro De Oliveira, Adrian J Thrasher, Patrick Aubourg, Jörn-Sven Kühl, Daniel J Loes, Hernan Amartino, Nicholas Smith, Juliana Folloni Fernandes, Caroline Sevin, Raman Sankar, Shaun A Hussain, Paul Gissen, Jean-Hugues Dalle, Uwe Platzbecker, Gerald F Downey, Elizabeth McNeil, Laura Demopoulos, Andrew C Dietz, Himal L Thakar, Paul J Orchard, David A Williams
Journal: New England Journal of Medicine (2024)

Cerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing
Genetic Heterogeneity Across Dimensions of Alcohol Use Behaviors
Authors: Jeanne E. Savage, Peter B. Barr, Tanya Phung, Younga H. Lee, Yingzhe Zhang, Vivia V. McCutcheon, Tian Ge, Jordan W. Smoller, Lea K. Davis, Jacquelyn Meyers, Bernice Porjesz, Danielle Posthuma, Travis T. Mallard, Sandra Sanchez-Roige
Journal: American Journal of Psychiatry (2024)

Objective: Increasingly large samples in genome-wide association studies (GWASs) for alcohol use behaviors (AUBs) have led to an influx of implicated genes, yet the clinical and functional understanding of these associations remains low, in part because most GWASs do not account for the complex and varied manifestations of AUBs. This study applied a multidimensional framework to investigate the latent genetic structure underlying heterogeneous dimensions of AUBs. Methods: Multimodal assessments (self-report, interview, electronic health records) were obtained from approximately 400,000 UK Biobank participants. GWAS was conducted for 18 distinct AUBs, including consumption, drinking patterns, alcohol problems, and clinical sequelae. Latent genetic factors were identified and carried forward to GWAS using genomic structural equation modeling, followed by functional annotation, genetic correlation, and enrichment analyses to interpret the genetic associations. Results: Four latent factors were identified: Problems, Consumption, BeerPref (declining alcohol consumption with a preference for drinking beer), and AtypicalPref (drinking fortified wine and spirits). The latent factors were moderately correlated (rg values, 0.12–0.57) and had distinct patterns of associations, with BeerPref in particular implicating many novel genomic regions. Patterns of regional and cell type–specific gene expression in the brain also differed between the latent factors. Conclusions: Deep phenotyping is an important next step to improve understanding of the genetic etiology of AUBs, in addition to increasing sample size. Further effort is required to uncover the genetic heterogeneity underlying AUBs using methods that account for their complex, multidimensional nature.
The Neurocircuitry of Substance Use Disorder, Treatment, and Change: A Resource for Clinical Psychiatrists
Authors: Caesar G. Imperio, Frances R. Levin, Diana Martinez
Journal: American Journal of Psychiatry (2024)

Substance use disorder (SUD) is common in psychiatric patients and has a negative impact on health and well-being. However, SUD often goes untreated, and there is a need for psychiatrists, of all specialties, to address this pervasive clinical problem. In this review, the authors' goal is to provide a resource that describes treatments for SUD, using neuroscience as a framework. They discuss the effect of pharmacotherapy on craving, intoxication, and withdrawal and its ability to interrupt the cycle of substance use in SUD. The neuroscience of stress is reviewed, including medications targeting neurotransmitter systems activated by alarm and fear. Neuroplasticity and promising treatments that use this mechanism, including ketamine, psilocybin, and transcranial magnetic stimulation (TMS), are discussed. The authors conclude by listing resources and practice guidelines for physicians interested in learning more about treatments for SUD.
Distinct immune profiles and clinical outcomes in sepsis subphenotypes based on temperature trajectories
Authors: Sivasubramanium V Bhavani, Alexandra Spicer, Pratik Sinha, Albahi Malik, Carlos Lopez-Espina, Lee Schmalz, Gregory L Watson, Akhil Bhargava, Shah Khan, Dennys Urdiales, Lincoln Updike, Alon Dagan, Hugo Davila, Carmen Demarco, Neil Evans, Falgun Gosai, Karthik Iyer, Niko Kurtzman, Ashok V Palagiri, Matthew Sims, Scott Smith, Anwaruddin Syed, Deesha Sarma, Bobby Reddy, Philip A Verhoef, Matthew M Churpek
Journal: Intensive Care Medicine (2024)
Prodrug Nanomedicine for Synovium Targeted Therapy of Inflammatory Arthritis: Insights from Animal Model and Human Synovial Joint Fluid
Authors: Zeynab Nosrati, Yun An Chen, Marta Bergamo, Cristina Rodríguez‐Rodríguez, Jonathan Chan, Kam Shojania, Raheem B. Kherani, Carson Chin, John T. Kelsall, Natasha Dehghan, Ann Marie Colwill, David Collins, Katayoun Saatchi, Urs O. Häfeli
Journal: Advanced Healthcare Materials (2024)

Abstract Many patients cannot tolerate low‐dose weekly methotrexate (MTX) therapy for inflammatory arthritis treatment due to life‐threatening toxicity. Although biologics offer a target‐specific therapy, it raises the risk of serious infections and even cancer due to immune system suppression. We introduce an anti‐inflammatory arthritis MTX ester prodrug using a long‐circulating biocompatible polymeric macromolecule: folic acid (FA) functionalized hyperbranched polyglycerol (HPG). In vitro the drug MTX is incrementally released through pH and enzymatic degradation over 2 weeks. The role of matrix metalloproteinases (MMPs) in site‐specific prodrug activation was verified using synovial fluid (SF) of 26 rheumatology patients and 4 healthy controls. Elevated levels of specific MMPs‐markers of joint inflammation‐positively correlated with enhanced prodrug release explained by acid‐catalyzed hydrolysis of esters by proteases. Intravenously administered 111 In‐radiolabeled prodrug confirmed by SPECT/CT imaging that it accumulated preferentially in inflamed joints while reducing off‐target side‐effects in a mouse model of rheumatoid arthritis (RA). Added FA as a targeting vector prolonged prodrug action; prodrug with 4x less MTX applied every 2 weeks was as effective as weekly MTX therapy. The preclinical results suggest a prodrug‐based strategy for the treatment of inflammatory joint diseases, with potential for other chronic inflammatory diseases and cancer.