tbuckley/cabot-search huggingface dataset:
Expert Panel Recommendations: Practical Clinical Applications for Initiating and Monitoring Resmetirom in Patients with MASH/NASH and Moderate to Noncirrhotic Advanced Fibrosis
Authors: Mazen Noureddin, Michael R Charlton, Stephen A Harrison, Meena B Bansal, Naim Alkhouri, Rohit Loomba, Arun J Sanyal, Mary E Rinella
Journal: Clinical Gastroenterology and Hepatology (2024)

Metabolic dysfunction-associated steatotic liver disease affects 1 in 4 people in the United States and western Europe, with an important proportion developing metabolic dysfunction-associated steatohepatitis (MASH), the progressive subtype of metabolic dysfunction-associated steatotic liver disease. Cirrhosis caused by MASH is a leading indication for liver transplantation and the most common cause of hepatocellular carcinoma. Hitherto, there have been no specific pharmacotherapies for MASH. The recent conditional approval by the Food and Drug Administration of resmetirom for the treatment of moderate or advanced MASH presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH. Specifically, the intended population for resmetirom are patients with MASH and fibrosis stages 2 or 3. The approval of resmetirom also presents important challenges, including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population. Herein we consider the available literature with regard to identifying the intended population for treatment with resmetirom and in proposing criteria for stopping treatment.
Cardiomyocyte LGR6 alleviates ferroptosis in diabetic cardiomyopathy via regulating mitochondrial biogenesis
Authors: Mengmeng Zhao, Zican Shen, Zihui Zheng, Yao Xu, Jishou Zhang, Jianfang Liu, Shanshan Peng, Jun Wan, Juan-Juan Qin, Menglong Wang
Journal: Metabolism (2024)
Dupilumab treatment decreases MBC2s, correlating with reduced IgE levels in pediatric atopic dermatitis
Authors: Margot E Starrenburg, Manal Bel Imam, Juan F Lopez, Laura Buergi, N Tan Nguyen, Anouk E M Nouwen, Nicolette J T Arends, Peter J Caspers, Mübeccel Akdis, Suzanne G M A Pasmans, Willem van de Veen
Journal: Journal of Allergy and Clinical Immunology (2024)

BackgroundA preference for type 2 immunity plays a central role in the pathogenesis of atopic dermatitis (AD). Dupilumab, an mAb targeting the IL-4 receptor α (IL-4Rα) subunit, inhibits IL-4 and IL-13 signaling. These cytokines contribute significantly to IgE class switch recombination in B cells, critical in atopic diseases. Recent studies indicate IgG+CD23hiIL-4Rα+ type 2 memory B cells (MBC2s) as IgE-producing B-cell precursors, linked to total IgE serum levels in atopic patients. Total IgE serum levels decreased during dupilumab treatment in previous studies.ObjectiveWe sought to assess the effects of dupilumab treatment in comparison with alternative therapies on the frequency of MBC2s and the correlation to total IgE levels in pediatric patients with AD.MethodsPediatric patients with AD, participating in an ongoing trial, underwent randomization into 3 treatment groups: dupilumab (n = 12), cyclosporine (n = 12), and topical treatment (n = 12). Plasma samples and PBMCs were collected at baseline (T0) and at 6 months after starting therapy (T6). Flow cytometry was used for PBMC phenotyping, and ELISA was used to assess total IgE levels in plasma.ResultsOur findings revealed a significant reduction in MBC2 frequency and total IgE levels among patients treated with dupilumab. In addition, a significant correlation was observed between MBC2s and total IgE levels.ConclusionsSystemic blocking of the IL-4Rα subunit leads to a decrease in circulating MBC2 cells and total IgE levels in pediatric patients with AD. Our findings unveiled a novel mechanism through which dupilumab exerts its influence on the atopic signature.
Estimating the household secondary attack rate and serial interval of COVID-19 using social media
Authors: Aarzoo Dhiman, Elad Yom-Tov, Lorenzo Pellis, Michael Edelstein, Richard Pebody, Andrew Hayward, Thomas House, Thomas Finnie, David Guzman, Vasileios Lampos, Rob Aldridge, Sarah Beale, Thomas Byrne, Jana Kovar, Isobel Braithwaite, Ellen Fragaszy, Wing Lam Erica Fong, Cyril Geismar, Susan Hoskins, Annalan Navaratnam, Vincent Nguyen, Parth Patel, Maddie Shrotri, Alexei Yavlinsky, Pia Hardelid, Linda Wijlaars, Eleni Nastouli, Moira Spyer, Anna Aryee, Rachel McKendry, Tao Cheng, Anne Johnson, Susan Michie, Jo Gibbs, Richard Gilson, Alison Rodger, Ingemar J. Cox
Journal: npj Digital Medicine (2024)

Abstract We propose a method to estimate the household secondary attack rate (hSAR) of COVID-19 in the United Kingdom based on activity on the social media platform X, formerly known as Twitter. Conventional methods of hSAR estimation are resource intensive, requiring regular contact tracing of COVID-19 cases. Our proposed framework provides a complementary method that does not rely on conventional contact tracing or laboratory involvement, including the collection, processing, and analysis of biological samples. We use a text classifier to identify reports of people tweeting about themselves and/or members of their household having COVID-19 infections. A probabilistic analysis is then performed to estimate the hSAR based on the number of self or household, and self and household tweets of COVID-19 infection. The analysis includes adjustments for a reluctance of Twitter users to tweet about household members, and the possibility that the secondary infection was not acquired within the household. Experimental results for the UK, both monthly and weekly, are reported for the period from January 2020 to February 2022. Our results agree with previously reported hSAR estimates, varying with the primary variants of concern, e.g. delta and omicron. The serial interval (SI) is based on the time between the two tweets that indicate a primary and secondary infection. Experimental results, though larger than the consensus, are qualitatively similar. The estimation of hSAR and SI using social media data constitutes a new tool that may help in characterizing, forecasting and managing outbreaks and pandemics in a faster, affordable, and more efficient manner.
Evaluation of anticancer therapy-related dermatologic adverse events: Insights from Food and Drug Administration's Adverse Event Reporting System dataset
Authors: Samir Salah, Delphine Kerob, Cecile Pages Laurent, Mario Lacouture, Vincent Sibaud
Journal: Journal of the American Academy of Dermatology (2024)

New anticancer therapies have improved patient outcomes but associated dermatologic adverse events (AEs) may cause morbidity and treatment discontinuation. A comprehensive estimation of associations between cancer drugs and skin AEs is lacking.
Targeted reprogramming of tumor-associated macrophages for overcoming glioblastoma resistance to chemotherapy and immunotherapy
Authors: Jianan Li, Jun Yang, Shaoping Jiang, Yunxin Tian, Yuquan Zhang, Lin Xu, Bo Hu, Huiping Shi, Zhaohan Li, Guangyao Ran, Yuanyu Huang, Shaobo Ruan
Journal: Biomaterials (2024)
Protective non-neutralizing SARS-CoV-2 monoclonal antibodies
Authors: Arman Izadi, Pontus Nordenfelt
Journal: Trends in Immunology (2024)

Recent studies show an important role for non-neutralizing anti-spike antibodies, including monoclonal antibodies (mAbs), in robustly protecting against SARS-CoV-2 infection. These mAbs use Fc-mediated functions such as complement activation, phagocytosis, and cellular cytotoxicity. There is an untapped potential for using non-neutralizing mAbs in durable antibody treatments; because of their available conserved epitopes, they may not be as sensitive to virus mutations as neutralizing mAbs. Here, we discuss evidence of non-neutralizing mAb-mediated protection against SARS-CoV-2 infection. We explore how non-neutralizing mAb Fc-mediated functions can be enhanced via novel antibody-engineering techniques. Important questions remain to be answered regarding the characteristics of protective non-neutralizing mAbs, including the models and assays used for study, the risks of ensuing detrimental inflammation, as well as the durability and mechanisms of protection.
Injectable immunoregulatory hydrogels sequentially drive phenotypic polarization of macrophages for infected wound healing
Authors: Yuxiang Wang, Chen Zhou, Zhulian Li, Gong Li, Yaping Zou, Xing Li, Peiyang Gu, Jingyi Liu, Lang Bai, Hong Yan, Jie Liang, Xingdong Zhang, Yujiang Fan, Yong Sun
Journal: Bioactive Materials (2024)

Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents.
The impact of microaggressions on the mental health of trans and gender-diverse people: A scoping review
Authors: Bethany Kimber, Melissa Oxlad, Louise Twyford
Journal: International Journal of Transgender Health (2024)

Background Trans and gender-diverse individuals experience disproportionate rates of discrimination and poor mental health. Discrimination often occurs as microaggressions (i.e. intentional or unintentional behaviors and statements that communicate hostile or derogatory messages toward members of marginalized groups). Microaggressions adversely impact the mental health of marginalized groups. However, little is known about their impact on the mental health of trans and gender-diverse people. We aimed to summarize existing research on the impact of microaggressions on the mental health of trans and gender-diverse people and provide insight into limitations, directions for future research, and clinical implications.
Carrier-free cryptotanshinone-peptide conjugates self-assembled nanoparticles: An efficient and low-risk strategy for acne vulgaris
Authors: Quanfu Zeng, Hongkai Chen, Zhuxian Wang, Yinglin Guo, Yufan Wu, Yi Hu, Peiyi Liang, Zeying Zheng, Tao Liang, Dan Zhai, Yaling Guo, Li Liu, Chunyan Shen, Cuiping Jiang, Qun Shen, Yankui Yi, Qiang Liu
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Acne vulgaris ranks as the second most prevalent dermatological condition worldwide, and there are still insufficient safe and reliable drugs to treat it. Cryptotanshinone (CTS), a bioactive compound derived from traditional Chinese medicine
From sunbeds to sunscreen: A curriculum empowering oregon adolescents to take charge of their skin health
Authors: Victoria E Orfaly, Gina N Bash, Erin Risotto-Urbanowicz, Claire B Higgins, Nicole M Santucci, Ashley M Hoff, Mary M Ryan, Adam D Roscher, Nina Kostur, Eleanor McCreary, Stephen Aldous, Candace H Chan, Bailey Reynolds, Abigale Shettig, Jonathan Sisley, Jacob Smith, Jade N Young, Allison M Zhou, Erika Koh, Carter K Haag, Emile Latour, Samuel J Callis, Elizabeth Stoos, Sancy A Leachman
Journal: Journal of the American Academy of Dermatology (2024)
Autophagy in aging-related diseases and cancer: Principles, regulatory mechanisms and therapeutic potential
Authors: Na Wu, Wenhui Zheng, Yundong Zhou, Yu Tian, Min Tang, Xiaoqiang Feng, Milad Ashrafizadeh, Yuzhuo Wang, Xiaojia Niu, Murtaza Tambuwala, Lingzhi Wang, Vinay Tergaonkar, Gautam Sethi, Daniel Klionsky, Li Huang, Ming Gu
Journal: Ageing Research Reviews (2024)
Extracellular Vesicle Surface Display Enhances the Therapeutic Efficacy and Safety Profile of Cancer Immunotherapy
Authors: Migara Kavishka Jayasinghe, Yock Sin Lay, Dawn Xiao Tian Liu, Chang Yu Lee, Chang Gao, Brendon Zhijie Yeo, Faith Yuan Xin How, Rebecca Carissa Prajogo, Dong Van Hoang, Hong Anh Le, Thach Tuan Pham, Boya Peng, Cao Dai Phung, Daniel G. Tenen, Minh T.N. Le
Journal: Molecular Therapy (2024)

Immunotherapy has emerged as a mainstay in cancer therapy, yet its efficacy is constrained by the risk of immune-related adverse events. In this study, we present a nanoparticle-based delivery system that enhances the therapeutic efficacy of immunomodulatory ligands while concurrently limiting systemic toxicity. We demonstrate that extracellular vesicles (EVs), lipid bilayer enclosed particles released by cells, can be efficiently engineered via inverse electron demand Diels-Alder (iEDDA)-mediated conjugation to display multiple immunomodulatory ligands on their surface. Display of immunomodulatory ligands on the EV surface conferred substantial enhancements in signaling efficacy, particularly for tumor necrosis factor receptor superfamily (TNFRSF) agonists, where the EV surface display served as an alternative FcγR-independent approach to induce ligand multimerization and efficient receptor crosslinking. EVs displaying a complementary combination of immunotherapeutic ligands were able to shift the tumor immune milieu toward an anti-tumorigenic phenotype and significantly suppress tumor burden and increase survival in multiple models of metastatic cancer to a greater extent than an equivalent dose of free ligands. In summary, we present an EV-based delivery platform for cancer immunotherapeutic ligands that facilitates superior anti-tumor responses at significantly lower doses with fewer side effects than is possible with conventional delivery approaches.
Preclinical studies of gene replacement therapy for CDKL5 deficiency disorder
Authors: Gregory Voronin, Jana Narasimhan, Jamila Gittens, Josephine Sheedy, Philip Lipari, Melinda Peters, Steven DeMarco, Liangxian Cao, Yakov Varganov, Min Jung Kim, Lisset Pear, Eman Fotouh, Supriya Sinha, Balmiki Ray, Michael C Wu, Padmaja Yalamanchili, Christopher Southgate, Joseph Pick, Khalil Saadipour, Stephen Jung, Jeanee Lee, Anna Mollin, Ellen M Welch, Zhijian Wu, Marla Weetall
Journal: Molecular Therapy (2024)
Synergic activity of FGFR2 and MEK inhibitors in the treatment of FGFR2-amplified cancers of unknown primary
Authors: Andrea Cavazzoni, Irene Salamon, Claudia Fumarola, Giulia Gallerani, Noemi Laprovitera, Francesco Gelsomino, Mattia Riefolo, Karim Rihawi, Elisa Porcellini, Tania Rossi, Martina Mazzeschi, Maria Naddeo, Salvatore Serravalle, Elisabetta Broseghini, Federico Agostinis, Olivier Deas, Roberta Roncarati, Giorgio Durante, Ilaria Pace, Mattia Lauriola, Ingrid Garajova, George A. Calin, Massimiliano Bonafè, Antonia D’Errico, Pier Giorgio Petronini, Stefano Cairo, Andrea Ardizzoni, Gabriele Sales, Manuela Ferracin
Journal: Molecular Therapy (2024)

Patients with cancer of unknown primary (CUP) carry the double burden of an aggressive disease and reduced access to therapies. Experimental models are pivotal for CUP biology investigation and drug testing. We derived two CUP cell lines (CUP#55 and #96) and corresponding patient-derived xenografts (PDXs), from ascites tumor cells. CUP cell lines and PDXs underwent histological, immune-phenotypical, molecular, and genomic characterization confirming the features of the original tumor. The tissue-of-origin prediction was obtained from the tumor microRNA expression profile and confirmed by single-cell transcriptomics. Genomic testing and fluorescence in situ hybridization analysis identified FGFR2 gene amplification in both models, in the form of homogeneously staining region (HSR) in CUP#55 and double minutes in CUP#96. FGFR2 was recognized as the main oncogenic driver and therapeutic target. FGFR2-targeting drug BGJ398 (infigratinib) in combination with the MEK inhibitor trametinib proved to be synergic and exceptionally active, both in vitro and in vivo. The effects of the combined treatment by single-cell gene expression analysis revealed a remarkable plasticity of tumor cells and the greater sensitivity of cells with epithelial phenotype. This study brings personalized therapy closer to CUP patients and provides the rationale for FGFR2 and MEK targeting in metastatic tumors with FGFR2 pathway activation.
An in vitro study of the impact of IL-17A and IL-22 on ciliogenesis in nasal polyps epithelium via the Hippo-YAP pathway
Authors: Huijun Qiu, Jing Liu, Qingwu Wu, Hsiaohui Ong, Yana Zhang, Xuekun Huang, Tian Yuan, Rui Zheng, Huiyi Deng, Weihao Wang, Weifeng Kong, Xinyue Wang, Deyun Wang, Qintai Yang
Journal: Journal of Allergy and Clinical Immunology (2024)
The Effect of Racial, Ethnic, and Socioeconomic Differences on Visual Impairment before Cataract Surgery
Authors: Abdelhalim A Awidi, Fasika A Woreta, Ahmed Sabit, Haihong Hu, Niteesh Potu, Eva Devience, Jiangxia Wang, Suma Vupputuri
Journal: Ophthalmology (2024)
Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial
Authors: Matteo Giovanni Della Porta, Guillermo Garcia-Manero, Valeria Santini, Amer M Zeidan, Rami S Komrokji, Jake Shortt, David Valcárcel, Anna Jonasova, Sophie Dimicoli-Salazar, Ing Soo Tiong, Chien-Chin Lin, Jiahui Li, Jennie Zhang, Richard Pilot, Sandra Kreitz, Veronika Pozharskaya, Karen L Keeperman, Shelonitda Rose, Thomas Prebet, Yinzhi Lai, Andrius Degulys, Stefania Paolini, Thomas Cluzeau, Pierre Fenaux, Uwe Platzbecker
Journal: The Lancet Haematology (2024)
Computer-aided detection of tuberculosis from chest radiographs in a tuberculosis prevalence survey in South Africa: external validation and modelled impacts of commercially available artificial intelligence software
Authors: Zhi Zhen Qin, Martie Van der Walt, Sizulu Moyo, Farzana Ismail, Phaleng Maribe, Claudia M Denkinger, Sarah Zaidi, Rachael Barrett, Lindiwe Mvusi, Nkateko Mkhondo, Khangelani Zuma, Samuel Manda, Lisa Koeppel, Thuli Mthiyane, Jacob Creswell
Journal: The Lancet Digital Health (2024)
Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial
Authors: Glenda E Gray, Kathryn Mngadi, Ludo Lavreys, Steven Nijs, Peter B Gilbert, John Hural, Ollivier Hyrien, Michal Juraska, Alex Luedtke, Philipp Mann, M Juliana McElrath, Jackline A Odhiambo, Daniel J Stieh, Janine van Duijn, Azwidihwi N Takalani, Wouter Willems, Asa Tapley, Georgia D Tomaras, Johan Van Hoof, Hanneke Schuitemaker, Edith Swann, Dan H Barouch, James G Kublin, Lawrence Corey, Maria G Pau, Susan Buchbinder, Frank Tomaka, Jon Allagappen, Jessica Andriesen, Alison Ayres, Linda-Gail Bekker, Caroline Borremans, William Brumskine, Roma Chilengi, Thozama Dubula, Nigel Garrett, Huub Gelderblom, Katherine Gill, Zaheer Hoosain, Mina Hosseinipour, Julia Hutter, Mubiana Inambao, Craig Innes, William Kilembe, Philippus Kotze, Sheena Kotze, Fatima Laher, Imre Laszlo, Erica Lazarus, Mookho Malahleha, Matsontso Mathebula, Mitch Matoga, Rachael McClennen, Pamela Mda, Peter Meerts, Vimla Naicker, Logashvari Naidoo, Tricia Philip, Annah Pitsi, Lorenz Scheppler, Carrie Sopher, Simbarashe G. Takuva, Edna Viegas, Mo Weijtens, Olive Yuan
Journal: The Lancet Infectious Diseases (2024)

HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain. Thus, a population-based approach, such as an HIV-1 vaccine, is needed. The current study aimed to evaluate the efficacy and safety of a heterologous HIV-1 vaccine regimen, consisting of a tetravalent mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) and aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140, in young women at risk of acquiring HIV-1 in southern Africa.
A subepithelial lesion algorithm for endoscopic (SAFE) resection in the upper gastrointestinal tract
Authors: Sunil Gupta, Julia Gauci, Timothy O'Sullivan, Oliver Cronin, Anthony Whitfield, Ana Craciun, Halim Awadie, Jing Yang, Vu Kwan, Eric Y. T. Lee, Nicholas G. Burgess, Michael J. Bourke
Journal: Endoscopy (2024)

Abstract Background Complete excision of upper gastrointestinal subepithelial lesions (U-SELs) eliminates diagnostic uncertainty, obviates the need for surveillance, and may be necessary for definitive diagnosis and management. Current guidelines lack precision and cohesion, and surgery is associated with significant morbidity. We describe and report on the outcomes of our SEL algorithm for endoscopic (SAFE) resection. Methods U-SELs were enrolled prospectively over 115 months until March 2023. All subjects underwent axial (computed tomography) imaging and endoscopic ultrasonography (EUS) to exclude a large exophytic component or invasion into local structures, and assess for muscularis propria (MP) involvement. Results 106 U-SELs (41 esophageal, 65 gastric) were resected (mean patient age 60.6 [SD 13.4]; 51.9% male). Esophageal U-SELs underwent endoscopic submucosal dissection (ESD; n = 22) or submucosal tunneling endoscopic resection (STER) if MP involvement was suspected (n = 19). Gastric U-SELs underwent STER (n = 6 at cardia), ESD (n = 47), or exposing endoscopic full-thickness resection (e-EFTR; n = 12). Technical success rates were 97.6% and 92.3%, respectively. Among the noncardiac gastric U-SELs, five resections (9.6%) were completed laparoscopically owing to deep and broad full-thickness involvement; five (9.6%) required laparoscopic gastrotomy and surgical retrieval after successful resection and closure owing to a large lesion size (mean 47 mm). There was no delayed bleeding, perforation, or recurrence at 13 months. Conclusion U-SELs may be effectively and safely treated by endoscopic resection. The SAFE approach provides a framework that facilitates structured decision-making. Esophageal U-SELs suspected of involving the MP should undergo STER. Gastric SELs are best managed by ESD, with a view to proceeding to e-EFTR. A laparoscopic upper gastrointestinal surgeon should be available in case surgical retrieval of the specimen or laparoscopic completion is required.
Comparative outcomes of endoscopic mucosal resection for laterally spreading lesions in inflammatory bowel disease
Authors: Varun Teja Angajala, James Buxbaum, Jennifer Phan, Jennifer L Dodge, Collin Mayemura, Melissa Ho, Aaron Lit, Christine Tien, Patrick W. Chang, Maziar Amini, Sarah Sheibani, Ara B Sahakian
Journal: Endoscopy (2024)

The role of endoscopic mucosal resection (EMR) for laterally spreading lesions (LSLs) in inflammatory bowel disease (IBD) remains controversial despite its effectiveness in the general population. We aimed to characterize outcomes of EMR for IBD-associated LSLs compared with controls without IBD.