tbuckley/cabot-search huggingface dataset:
Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSERT): a phase 3, double-blind, randomised, placebo-controlled trial
Authors: Nadia Ovchinsky, Madeleine Aumar, Alastair Baker, Ulrich Baumann, Philip Bufler, Mara Cananzi, Piotr Czubkowski, Özlem Durmaz, Ryan Fischer, Giuseppe Indolfi, Wikrom W Karnsakul, Florence Lacaille, Way S Lee, Giuseppe Maggiore, Philip Rosenthal, Mathias Ruiz, Etienne Sokal, Ekkehard Sturm, Wendy van der Woerd, Henkjan J Verkade, Andrew Wehrman, Christine Clemson, Qifeng Yu, Quanhong Ni, Jessica Ruvido, Susan Manganaro, Jan P Mattsson
Journal: The Lancet. Gastroenterology & hepatology (2024)

In patients with Alagille syndrome, cholestasis-associated clinical features can include high serum bile acids and severe pruritus that can necessitate liver transplantation. We aimed to evaluate the efficacy and safety of the ileal bile acid transporter inhibitor odevixibat versus placebo in patients with Alagille syndrome.
Commentary
Authors: Giacomo E. M. Rizzo, Ilaria Tarantino
Journal: Endoscopy (2024)

Comment on: Endoscopic ultrasound-directed transgastric ERCP for disconnected pancreatic duct syndrome: finding the edge to bridge the gapEndoscopy 2024; 56(S 01): E41-E42DOI: 10.1055/a-2213-1220
The Human Insulin Thermal Solution project—a private sector initiative to address the thermostability of insulin
Authors: Mats Rasmussen, Morten Hach, Jørgen Iwersen, Gayathri Anil, Henrik Rosborg, Jens Larsen, Lise Camilla Hoffmann, Peter Kurtzhals
Journal: The Lancet Diabetes & Endocrinology (2024)
A transdiagnostic group exercise intervention for mental health outpatients in Germany (ImPuls): results of a pragmatic, multisite, block-randomised, phase 3 controlled trial
Authors: Sebastian Wolf, Britta Seiffer, Johanna-Marie Zeibig, Anna Katharina Frei, Thomas Studnitz, Jana Welkerling, Edith Meinzinger, Leonie Louisa Bauer, Julia Baur, Stephanie Rosenstiel, David Victor Fiedler, Florian Helmhold, Andreas Ray, Eva Herzog, Keisuke Takano, Tristan Nakagawa, Mia Maria Günak, Saskia Kropp, Stefan Peters, Anna Lena Flagmeier, Lena Zwanzleitner, Leonie Sundmacher, Ander Ramos-Murguialday, Martin Hautzinger, Gorden Sudeck, Thomas Ehring
Journal: The Lancet Psychiatry (2024)

Globally, mental health conditions pose a substantial burden of disease. Despite the availability of evidence-based pharmacological and psychological treatments, the symptoms of a substantial subgroup of patients do not respond to these interventions, and only a minority of patients have access to them. This study aimed to assess the efficacy of ImPuls, a 6-month transdiagnostic group exercise intervention, plus treatment-as-usual, compared with treatment-as-usual alone in outpatients with various mental disorders.
Urgent action needed to achieve viral hepatitis elimination
Authors: None The Lancet Gastroenterology & Hepatology
Journal: The Lancet. Gastroenterology & hepatology (2024)

The headline figures from WHO's 2024 Global Hepatitis Report, released at the World Hepatitis Summit in Lisbon, Portugal, on April 9, make for stark reading. 1·3 million people died from viral hepatitis in 2022: the same number as killed by tuberculosis, second only to COVID-19 as the leading communicable cause of death, and an increase on the 2019 estimate of 1·1 million. There were 1·2 million new hepatitis B infections and almost 1 million new hepatitis C infections in 2022—marginally lower than 2019 estimates, but not substantially so.
Respiratory syncytial virus seasonality, transmission zones, and implications for seasonal prevention strategy in China: a systematic analysis
Authors: Ling Guo, Shuyu Deng, Shiqi Sun, Xin Wang, You Li
Journal: The Lancet Global Health (2024)

Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income countries. RSV exhibits seasonality in most areas globally, and a comprehensive understanding of within-country variations in RSV seasonality could help to define the timing of RSV immunisation programmes. This study focused on China, and aimed to describe the geographical distribution of RSV seasonality, identify distinct RSV transmission zones, and evaluate the potential suitability of a seasonal RSV prevention strategy.
Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Santé prospective cohort study
Authors: Clara Salame, Guillaume Javaux, Laury Sellem, Emilie Viennois, Fabien Szabo de Edelenyi, Cédric Agaësse, Alexandre De Sa, Inge Huybrechts, Fabrice Pierre, Xavier Coumoul, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Léopold K Fezeu, Serge Hercberg, Mélanie Deschasaux-Tanguy, Emmanuel Cosson, Sopio Tatulashvili, Benoit Chassaing, Bernard Srour, Mathilde Touvier
Journal: The Lancet Diabetes & Endocrinology (2024)

Experimental studies have suggested potential detrimental effects of emulsifiers on gut microbiota, inflammation, and metabolic perturbations. We aimed to investigate the associations between exposures to food additive emulsifiers and the risk of type 2 diabetes in a large prospective cohort of French adults.
Ethical and regulatory challenges of large language models in medicine
Authors: Jasmine Chiat Ling Ong, Shelley Yin-Hsi Chang, Wasswa William, Atul J Butte, Nigam H Shah, Lita Sui Tjien Chew, Nan Liu, Finale Doshi-Velez, Wei Lu, Julian Savulescu, Daniel Shu Wei Ting
Journal: The Lancet Digital Health (2024)

With the rapid growth of interest in and use of large language models (LLMs) across various industries, we are facing some crucial and profound ethical concerns, especially in the medical field. The unique technical architecture and purported emergent abilities of LLMs differentiate them substantially from other artificial intelligence (AI) models and natural language processing techniques used, necessitating a nuanced understanding of LLM ethics. In this Viewpoint, we highlight ethical concerns stemming from the perspectives of users, developers, and regulators, notably focusing on data privacy and rights of use, data provenance, intellectual property contamination, and broad applications and plasticity of LLMs. A comprehensive framework and mitigating strategies will be imperative for the responsible integration of LLMs into medical practice, ensuring alignment with ethical principles and safeguarding against potential societal risks.
Gastric endoscopic submucosal dissection in Western countries: current and future perspective
Authors: Yasutoshi Shiratori, Anthony Kalloo
Journal: Endoscopy (2024)

Letter to: Predictors of long-term outcomes of endoscopic submucosal dissection of early gastric neoplasia in the West: a multicenter studyEndoscopy 2023; 55(10): 898-906DOI: 10.1055/a-2100-2258
Outcomes of endoscopic submucosal dissection of early gastric cancer neoplasia in the West and change in the absolute indications
Authors: Glòria Fernández-Esparrach, José C. Marín-Gabriel
Journal: Endoscopy (2024)

Letter to: Predictors of long-term outcomes of endoscopic submucosal dissection of early gastric neoplasia in the West: a multicenter studyEndoscopy 2023; 55(10): 898-906DOI: 10.1055/a-2100-2258
Reply to Fernández-Esparrach et al.
Authors: Mohamed Abdelrahim, Pradeep Bhandari
Journal: Endoscopy (2024)

Letter to: Outcomes of endoscopic submucosal dissection of early gastric cancer neoplasia in the West and change in the absolute indicationsEndoscopy 2024; 56(05): 390-390DOI: 10.1055/a-2215-5644
Human Airway and Alveolar Organoids from BAL Fluid
Authors: Monica Yun Liu, Belinda Chen, Mehdi Borji, Carolina Garcia de Alba Rivas, Antonella F. M. Dost, Aaron L. Moye, Nusrath Movval Abdulla, Margherita Paschini, Stuart D. Rollins, Ruobing Wang, Lynn M. Schnapp, Hassan A. Khalil, Catherine J. Wu, Nirmal S. Sharma, Carla F. Kim
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Human Airway and Alveolar Organoids from Bronchoalveolar Lavage Fluid." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Salvage Reirradiation for Locally Recurrent Prostate Cancer: Results From a Prospective Study With 7.2 Years of Follow-Up
Authors: Christian Ekanger, Svein Inge Helle, Lars Reisæter, Liv Bolstad Hysing, Rune Kvåle, Alfred Honoré, Karsten Gravdal, Sara Pilskog, Olav Dahl
Journal: Journal of Clinical Oncology (2024)

There are no well-established re-treatment options for local recurrence after primary curative radiation therapy for prostate cancer (PCa), as prospective studies with long-term follow-up are lacking. Here, we present results from a prospective study on focal salvage reirradiation with external-beam radiation therapy with a median follow-up of 7.2 years.
Trans-Ancestral Genetic Risk Factors for Treatment-Related Type 2 Diabetes Mellitus in Survivors of Childhood Cancer
Authors: Cindy Im, Achal Neupane, Jessica L. Baedke, Brian Lenny, Angela Delaney, Stephanie B. Dixon, Eric J. Chow, Sogol Mostoufi-Moab, Tianzhong Yang, Melissa A. Richard, M. Monica Gramatges, Philip J. Lupo, Noha Sharafeldin, Smita Bhatia, Gregory T. Armstrong, Melissa M. Hudson, Kirsten K. Ness, Leslie L. Robison, Yutaka Yasui, Carmen L. Wilson, Yadav Sapkota
Journal: Journal of Clinical Oncology (2024)

Type 2 diabetes mellitus (T2D) is a prevalent long-term complication of treatment in survivors of childhood cancer, with marked racial/ethnic differences in burden. In this study, we investigated trans-ancestral genetic risks for treatment-related T2D.
Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study
Authors: Aditya Bardia, Ian E. Krop, Takahiro Kogawa, Dejan Juric, Anthony W. Tolcher, Erika P. Hamilton, Toru Mukohara, Aaron Lisberg, Toshio Shimizu, Alexander I. Spira, Junji Tsurutani, Senthil Damodaran, Kyriakos P. Papadopoulos, Jonathan Greenberg, Fumiaki Kobayashi, Hong Zebger-Gong, Rie Wong, Yui Kawasaki, Tadakatsu Nakamura, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2024)

Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived topoisomerase I inhibitor payload via a plasma-stable, selectively cleavable linker.
Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways
Authors: Mario E. Lacouture, Elena Goleva, Neil Shah, Veronica Rotemberg, Lukas Kraehenbuehl, Kwami F. Ketosugbo, Taha Merghoub, Tara Maier, Alexander Bang, Stephanie Gu, Trina Salvador, Andrea P. Moy, Taras Lyubchenko, Olivia Xiao, Clifton F. Hall, Evgeny Berdyshev, James Crooks, Ryan Weight, Jeffrey A. Kern, Donald Y.M. Leung
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Immune-related cutaneous adverse events (ircAE) occur in ≥50% of patients treated with checkpoint inhibitors, but the underlying mechanisms for ircAEs are poorly understood. Experimental Design: Phenotyping/biomarker analyses were conducted in 200 patients on checkpoint inhibitors [139 with ircAEs and 61 without (control group)] to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip extracts, and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays. Results: Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFNγ mRNA in patients with lichenoid (P &amp;lt; 0.0001) and psoriasiform dermatitis (P &amp;lt; 0.01) as compared with patients without ircAEs, whereas the highest IL13 mRNA levels were detected in patients with eczema (P &amp;lt; 0.0001, compared with control). IL17A mRNA was selectively increased in psoriasiform (P &amp;lt; 0.001), lichenoid (P &amp;lt; 0.0001), bullous dermatitis (P &amp;lt; 0.05), and MPR (P &amp;lt; 0.001) compared with control. Distinct cytokine profiles were confirmed in skin tape strip and plasma. Analysis determined increased skin/plasma IL4 cytokine in pruritus, skin IL13 in eczema, plasma IL5 and IL31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2 cytokine–targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo. Conclusions: Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions.
Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma
Authors: Dickran Kazandjian, Benjamin Diamond, Marios Papadimitriou, Elizabeth Hill, Romanos Sklavenitis-Pistofidis, Bachisio Ziccheddu, Patrick Blaney, Monika Chojnacka, Michael Durante, Kylee Maclachlan, Ryan Young, Saad Usmani, Faith Davies, Gad Getz, Irene Ghobrial, Neha Korde, Gareth Morgan, Francesco Maura, Ola Landgren
Journal: Clinical Cancer Research (2024)

Early intervention for high-risk smoldering multiple myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to the treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered.
Fraction Dose Escalation of Hypofractionated Radiotherapy with Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non–Small Cell Lung Cancer: A Phase I Study
Authors: Rui Zhou, FangJie Liu, HongMei Zhang, DaQuan Wang, PengXin Zhang, ShiYang Zheng, YiMei Liu, Li Chen, JinYu Guo, YingYi Zou, Yu-Ming Rong, Hui Liu, Bo Qiu
Journal: Clinical Cancer Research (2024)

Abstract Purpose: This phase I trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non–small cell lung cancer. Patients and Methods: Split-course hypo-RT and hypoboost combined with concurrent chemotherapy was administered at three dose levels (DL), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved ≥grade 2 (G2+) toxicities after RT received cICI. Each DL aimed to treat six patients. The MTFD was defined as the highest DL at which ≤2 patients of the six who were treated experienced treatment-related G3+ toxicity and ≤1 patient experienced G4+ toxicity within 12 months post-RT. Results: Eighteen patients were enrolled, with six patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rates were 94.4% and 83.3%, respectively. Conclusions: Utilizing the split-course hypo-RT and hypoboost approach, a fraction dose of 5 Gy to a total dose of 60 Gy, combined with concurrent chemotherapy and subsequent cICI, was well tolerated and yielded a promising objective response rate and survival outcomes.
The narrow footprint of ancient balancing selection revealed by heterokaryon incompatibility genes in <i>Aspergillus fumigatus</i>
Authors: Ben Auxier, Jianhua Zhang, Francisca Reyes Marquez, Kira Senden, Joost van den Heuvel, Duur K Aanen, Eveline Snelders, Alfons J M Debets
Journal: Molecular Biology and Evolution (2024)

Abstract In fungi, fusion between individuals leads to localized cell death, a phenomenon termed heterokaryon incompatibility. Generally, the genes responsible for this incompatibility are observed to be under balancing selection resulting from negative frequency-dependent selection. Here, we assess this phenomenon in Aspergillus fumigatus, a human pathogenic fungus with a very low level of linkage disequilibrium as well as an extremely high crossover rate. Using complementation of auxotrophic mutations as an assay for hyphal compatibility, we screened sexual progeny for compatibility to identify genes involved in this process, called het genes. In total, 5/148 (3.4%) offspring were compatible with a parent and 166/2,142 (7.7%) sibling pairs were compatible, consistent with several segregating incompatibility loci. Genetic mapping identified five loci, four of which could be fine mapped to individual genes, of which we tested three through heterologous expression, confirming their causal relationship. Consistent with long-term balancing selection, trans-species polymorphisms were apparent across several sister species, as well as equal allele frequencies within A. fumigatus. Surprisingly, a sliding window genome-wide population-level analysis of an independent dataset did not show increased Tajima's D near these loci, in contrast to what is often found surrounding loci under balancing selection. Using available de novo assemblies, we show that these balanced polymorphisms are restricted to several hundred base pairs flanking the coding sequence. In addition to identifying the first het genes in an Aspergillus species, this work highlights the interaction of long-term balancing selection with rapid linkage disequilibrium decay.
OTULIN and Muller’s morphs
Authors: András N. Spaan
Journal: The Journal of Experimental Medicine (2024)

In this issue of JEM, Davidson et al. (https://doi.org/10.1084/jem.20222171) and Takeda et al. (https://doi.org/10.1084/jem.20231941) independently report on a dominant negative form of OTULIN deficiency in three unrelated patients.
Hydrogel for light delivery in biomedical applications
Authors: Pek Yin Michelle Yew, Pei Lin Chee, Qianyu Lin, Cally Owh, Jiayi Li, Qing Qing Dou, Xian Jun Loh, Dan Kai, Yong Zhang
Journal: Bioactive Materials (2024)

Traditional optical waveguides or mediums are often silica-based materials, but their applications in biomedicine and healthcare are limited due to the poor biocompatibility and unsuitable mechanical properties. In term of the applications in human body, a biocompatible hydrogel system with excellent optical transparency and mechanical flexibility could be beneficial. In this review, we explore the different designs of hydrogel-based optical waveguides derived from natural and synthetic sources. We highlighted key developments such as light emitting contact lenses, implantable optical fibres, biosensing systems, luminating and fluorescent materials. Finally, we expand further on the challenges and perspectives for hydrogel waveguides to achieve clinical applications.
MMP13-targeted siRNA-loaded micelles for diagnosis and treatment of posttraumatic osteoarthritis
Authors: Dongyang Zhou, Yan Wei, Shihao Sheng, Miaomiao Wang, Jiajing Lv, Bowen Zhao, Xiao Chen, Ke Xu, Long Bai, Yan Wu, Peiran Song, Liehu Cao, Fengjin Zhou, Hao Zhang, Zhongmin Shi, Jiacan Su
Journal: Bioactive Materials (2024)

Posttraumatic osteoarthritis (PTOA) patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective. Early PTOA is characterized by overexpressed matrix metalloprotease 13 (MMP13). Herein, we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable, cyanine 5 (Cy5)-containing PEG, black hole quencher-3 (BHQ3), and cRGD ligands and loaded with siRNA silencing MMP13 (siM13), namely ERMs@siM13. ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell, causing cRGD exposure. Accordingly, the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surface αvβ3 integrin, increasing intracellular siM13 delivery for on-demand MMP13 downregulation. Meanwhile, the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle, precisely reflecting the diseased cartilage state. In particular, the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity, enabling the physicians to adjust the therapeutic regimen. Finally, in the murine PTOA model, ERMs@siM13 could diagnose the early-stage PTOA, perform timely interventions, and monitor the OA progression level during treatment through a real-time detection of MMP13. Therefore, ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics.
Hypoxia‐Responsive Hydrogen‐Bonded Organic Framework‐Mediated Protein Delivery for Cancer Therapy
Authors: Xu He, Jian Wang, Xiao Liu, Qingyu Niu, Zhiqiang Li, Banglin Chen, Qingqing Xiong
Journal: Advanced Healthcare Materials (2024)

The efficient delivery of therapeutic proteins to tumor sites is a promising cancer treatment modality. Hydrogen-bonded organic frameworks (HOFs) are successfully used for the protective encapsulation of proteins; however, easy precipitation and lack of controlled release of existing HOFs limit their further application for protein delivery in vivo. Here, a hypoxia-responsive HOF, self-assembled from azobenzenedicarboxylate/polyethylene glycol-conjugated azobenzenedicarboxylate and tetrakis(4-amidiniumphenyl)methane through charge-assisted hydrogen-bonding, is developed for systemic protein delivery to tumor cells. The newly generated HOF platform efficiently encapsulates representative cytochrome C, demonstrating good dispersibility under physiological conditions. Moreover, it can respond to overexpressed reductases in the cytoplasm under hypoxic conditions, inducing fast intracellular protein release to exert therapeutic effects. The strategy presented herein can be applied to other therapeutic proteins and can be expanded to encompass more intrinsic tumor microenvironment stimuli. This offers a novel avenue for utilizing HOFs in protein-based cancer therapy.
Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis
Authors: Shimeng Zhou, Junlan Liu, Andi Wan, Yi Zhang, Xiaowei Qi
Journal: Journal of Hematology & Oncology (2024)

Abstract Tumor is a local tissue hyperplasia resulted from cancerous transformation of normal cells under the action of various physical, chemical and biological factors. The exploration of tumorigenesis mechanism is crucial for early prevention and treatment of tumors. Epigenetic modification is a common and important modification in cells, including DNA methylation, histone modification, non-coding RNA modification and m6A modification. The normal mode of cell death is programmed by cell death-related genes; however, recent researches have revealed some new modes of cell death, including pyroptosis, ferroptosis, cuproptosis and disulfidptosis. Epigenetic regulation of various cell deaths is mainly involved in the regulation of key cell death proteins and affects cell death by up-regulating or down-regulating the expression levels of key proteins. This study aims to investigate the mechanism of epigenetic modifications regulating pyroptosis, ferroptosis, cuproptosis and disulfidptosis of tumor cells, explore possible triggering factors in tumor development from a microscopic point of view, and provide potential targets for tumor therapy and new perspective for the development of antitumor drugs or combination therapies.