tbuckley/cabot-search huggingface dataset:
Effect of human H3N2 influenza virus reassortment on influenza incidence and severity during the 2017–18 influenza season in the USA: a retrospective observational genomic analysis
Authors: Hsuan Liu, Kathryn Shaw-Saliba, Jason Westerbeck, David Jacobs, Katherine Fenstermacher, Chia-Yu Chao, Yu-Nong Gong, Harrison Powell, Zexu Ma, Thomas Mehoke, Amanda W Ernlund, Amanda Dziedzic, Siddhant Vyas, Jared Evans, Lauren M Sauer, Chin-Chieh Wu, Shu-Hui Chen, Richard E Rothman, Peter Thielen, Kuan-Fu Chen, Andrew Pekosz
Journal: The Lancet Microbe (2024)

BackgroundDuring the 2017–18 influenza season in the USA, there was a high incidence of influenza illness and mortality. However, no apparent antigenic change was identified in the dominant H3N2 viruses, and the severity of the season could not be solely attributed to a vaccine mismatch. We aimed to investigate whether the altered virus properties resulting from gene reassortment were underlying causes of the increased case number and disease severity associated with the 2017–18 influenza season.MethodsSamples included were collected from patients with influenza who were prospectively recruited during the 2016–17 and 2017–18 influenza seasons at the Johns Hopkins Hospital Emergency Departments in Baltimore, MD, USA, as well as from archived samples from Johns Hopkins Health System sites. Among 647 recruited patients with influenza A virus infection, 411 patients with whole-genome sequences were available in the Johns Hopkins Center of Excellence for Influenza Research and Surveillance network during the 2016–17 and 2017–18 seasons. Phylogenetic trees were constructed based on viral whole-genome sequences. Representative viral isolates of the two seasons were characterised in immortalised cell lines and human nasal epithelial cell cultures, and patients' demographic data and clinical outcomes were analysed.FindingsUnique H3N2 reassortment events were observed, resulting in two predominant strains in the 2017–18 season: HA clade 3C.2a2 and clade 3C.3a, which had novel gene segment constellations containing gene segments from HA clade 3C.2a1 viruses. The reassortant re3C.2a2 viruses replicated with faster kinetics and to a higher peak titre compared with the parental 3C.2a2 and 3C.2a1 viruses (48 h vs 72 h). Furthermore, patients infected with reassortant 3C.2a2 viruses had higher Influenza Severity Scores than patients infected with the parental 3C.2a2 viruses (median 3·00 [IQR 1·00–4·00] vs 1·50 [1·00–2·00]; p=0·018).InterpretationOur findings suggest that the increased severity of the 2017–18 influenza season was due in part to two intrasubtypes, cocirculating H3N2 reassortant viruses with fitness advantages over the parental viruses. This information could help inform future vaccine development and public health policies.FundingThe Center of Excellence for Influenza Research and Response in the US, National Science and Technology Council, and Chang Gung Memorial Hospital in Taiwan.
Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial
Authors: Jean-Michel Molina, Giuliano Rizzardini, Catherine Orrell, Alejandro Afani, Alexandra Calmy, Shinichi Oka, Federico Hinestrosa, Princy Kumar, Pablo Tebas, Sharon Walmsley, Anjana Grandhi, Stephanie Klopfer, Isaias Gendrano, Karen Eves, Todd A Correll, Michelle C Fox, Jason Kim
Journal: The Lancet HIV (2024)
Charting a new course in healthcare: early-stage AI algorithm registration to enhance trust and transparency
Authors: Michel E. van Genderen, Davy van de Sande, Lotty Hooft, Andreas Alois Reis, Alexander D. Cornet, Jacobien H. F. Oosterhoff, Björn J. P. van der Ster, Joost Huiskens, Reggie Townsend, Jasper van Bommel, Diederik Gommers, Jeroen van den Hoven
Journal: npj Digital Medicine (2024)

AI holds the potential to transform healthcare, promising improvements in patient care. Yet, realizing this potential is hampered by over-reliance on limited datasets and a lack of transparency in validation processes. To overcome these obstacles, we advocate the creation of a detailed registry for AI algorithms. This registry would document the development, training, and validation of AI models, ensuring scientific integrity and transparency. Additionally, it would serve as a platform for peer review and ethical oversight. By bridging the gap between scientific validation and regulatory approval, such as by the FDA, we aim to enhance the integrity and trustworthiness of AI applications in healthcare.
An updated framework for SARS-CoV-2 variants reflects the unpredictability of viral evolution
Authors: Lorenzo Subissi, James Richard Otieno, Nathalie Worp, Homa Attar Cohen, Bas B. Oude Munnink, Laith J. Abu-Raddad, Erik Alm, Amal Barakat, Wendy S. Barclay, Jinal N. Bhiman, Leon Caly, Meera Chand, Mark Chen, Ann Cullinane, Tulio de Oliveira, Christian Drosten, Julian Druce, Paul Effler, Ihab El Masry, Adama Faye, Elodie Ghedin, Rebecca Grant, Bart L. Haagmans, Christian Happi, Belinda L. Herring, Emma B. Hodcroft, Juniorcaius Ikejezie, Victoria Katawera, Zyleen Alnashir Kassamali, Yee-Sin Leo, Gabriel M. Leung, Rebecca J. Kondor, Marco Marklewitz, Jairo Mendez-Rico, Nada M. Melhem, Vincent Munster, Karen Nahapetyan, Dhamari Naindoo, Djin-Ye Oh, Thomas P. Peacock, Malik Peiris, Zhibin Peng, Leo L. M. Poon, Andrew Rambaut, Senjuti Saha, Yinzhong Shen, Marilda M. Siqueira, Erik Volz, Sofonias K. Tessema, Volker Thiel, Henda Triki, Sylvie van der Werf, Karin von Eije, Jane Cunningham, Marion P. G. Koopmans, Anne von Gottberg, Anurag Agrawal, Maria D. Van Kerkhove
Journal: Nature Medicine (2024)
Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images
Authors: Yu Liu, Rui Xie, Lifeng Wang, Hongpeng Liu, Chen Liu, Yimin Zhao, Shizhu Bai, Wenyong Liu
Journal: International Journal of Oral Science (2024)

Abstract Accurate segmentation of oral surgery-related tissues from cone beam computed tomography (CBCT) images can significantly accelerate treatment planning and improve surgical accuracy. In this paper, we propose a fully automated tissue segmentation system for dental implant surgery. Specifically, we propose an image preprocessing method based on data distribution histograms, which can adaptively process CBCT images with different parameters. Based on this, we use the bone segmentation network to obtain the segmentation results of alveolar bone, teeth, and maxillary sinus. We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks. The tooth segmentation results can obtain the order information of the dentition. The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods. Its average Dice scores on the tooth, alveolar bone, maxillary sinus, and mandibular canal segmentation tasks were 96.5%, 95.4%, 93.6%, and 94.8%, respectively. These results demonstrate that it can accelerate the development of digital dentistry.
Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK
Authors: Dexuan Zhuang, Shuangshuang Wang, Huiting Deng, Yuxin Shi, Chang Liu, Xue Leng, Qun Zhang, Fuxiang Bai, Bin Zheng, Jing Guo, Xunwei Wu
Journal: International Journal of Oral Science (2024)

Abstract The efficient clinical treatment of oral squamous cell carcinoma (OSCC) is still a challenge that demands the development of effective new drugs. Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors, however, not much is known about the influence of phenformin on OSCC cells. We found that phenformin suppresses OSCC cell proliferation, and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro. RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4 (DNA damage inducible transcript 4) and NIBAN1 (niban apoptosis regulator 1). We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy. Further, the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4 (activation transcription factor 4), which was induced by phenformin treatment in OSCC cells. Mechanistically, these results revealed that phenformin triggers endoplasmic reticulum (ER) stress to activate PERK (protein kinase R-like ER kinase), which phosphorylates the transitional initial factor eIF2, and the increased phosphorylation of eIF2 leads to the increased translation of ATF4. In summary, we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth. Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.
Mitochondria targeted drug delivery system overcoming drug resistance in intrahepatic cholangiocarcinoma by reprogramming lipid metabolism
Authors: Yi Duan, Mengqiong Deng, Bin Liu, Xianwei Meng, Jinghan Liao, Yijie Qiu, Zhihua Wu, Jiangtao Lin, Yi Dong, Yourong Duan, Ying Sun
Journal: Biomaterials (2024)
A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity
Authors: Chang Liu, Daming Zhou, Aiste Dijokaite-Guraliuc, Piyada Supasa, Helen M.E. Duyvesteyn, Helen M. Ginn, Muneeswaran Selvaraj, Alexander J. Mentzer, Raksha Das, Thushan I. de Silva, Thomas G. Ritter, Megan Plowright, Thomas A.H. Newman, Lizzie Stafford, Barbara Kronsteiner, Nigel Temperton, Yuan Lui, Martin Fellermeyer, Philip Goulder, Paul Klenerman, Susanna J. Dunachie, Michael I. Barton, Mikhail A. Kutuzov, Omer Dushek, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R. Screaton
Journal: Cell Reports Medicine (2024)

BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants responsible for many infections in 2023. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading to a new wave of infection. Here, we examine the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. We locate BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. We demonstrate, and provide a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility.
Early Liver Transplant for Alcohol-associated Liver Disease Has Excellent Survival but Higher Rates of Harmful Alcohol Use
Authors: Jessica A. Musto, Geralyn Palmer, Mary Nemer, Trevor Schell, Gabrielle Waclawik, Quarshie Glover, Michael R. Lucey, Fay Osman, John P. Rice
Journal: Clinical Gastroenterology and Hepatology (2024)
2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines
Authors: Steve R. Ommen, Carolyn Y. Ho, Irfan M. Asif, Seshadri Balaji, Michael A. Burke, Sharlene M. Day, Joseph A. Dearani, Kelly C. Epps, Lauren Evanovich, Victor A. Ferrari, José A. Joglar, Sadiya S. Khan, Jeffrey J. Kim, Michelle M. Kittleson, Chayakrit Krittanawong, Matthew W. Martinez, Seema Mital, Srihari S. Naidu, Sara Saberi, Christopher Semsarian, Sabrina Times, Cynthia Burstein Waldman
Journal: Circulation (2024)

The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy.
Cre recombinase promotes leukemogenesis in the presence of both homozygous and heterozygous FLT3-ITD
Authors: Min Yang, Zhiyuan Ma, Chonggang Wang, Muammer Cihan Agca, Hongyun Liu, Kezhi Huang, Silke Glage, Regina Rumpel, Alexander Gerbaulet, Axel Roers, Xuemei Liu, Fatih Noyan, Nils von Neuhoff, Arnold Ganser, Ligen Liu, Haiyang Yun, Zhixiong Li
Journal: Leukemia (2024)
Prostate-specific membrane antigen-targeted surgery in prostate cancer: Accurate identification, real-time diagnosis, and precise resection
Authors: Jianhua Jiao, Jingjing Zhang, Weihong Wen, Weijun Qin, Xiaoyuan Chen
Journal: Theranostics (2024)

Radical prostatectomy (RP) combined with pelvic lymph node dissection (PLND) is the first step in multimodal treatment of prostate cancer (PCa) without distant metastases.For a long time, the surgical resection range has been highly dependent on the surgeon's visualization and experience with preoperative imaging.With the rapid development of prostate-specific membrane antigen positron emission tomography and single-photon emission computed tomography (PSMA-PET and PSMA-SPECT), PSMA-targeted surgery has been introduced for a more accurate pathological diagnosis and complete resection of positive surgical margins (PSMs) and micro-lymph node metastases (LNMs).We reviewed PSMA-targeted surgeries, including PSMA-PET-guided prostatic biopsy (PSMA-TB), PSMA-targeted radio-guided surgery (PSMA-RGS), PSMA-targeted fluorescence-guided surgery (PSMA-FGS), and multi-modality/multi-targeted PSMA-targeted surgery.We also discuss the strengths and challenges of PSMA-targeted surgery, and propose that PSMA-targeted surgery could be a great addition to existing surgery protocols, thereby improving the accuracy and convenience of surgery for primary and recurrent PCa in the near future.
<i>Bifidobacterium breve</i>-derived indole-3-lactic acid ameliorates colitis-associated tumorigenesis by directing the differentiation of immature colonic macrophages
Authors: Yuke Li, Qingxiang Li, Ruoshui Yuan, Yifei Wang, Chuanbin Guo, Lin Wang
Journal: Theranostics (2024)

Aim: To elucidate dynamics and functions in colonic macrophage subsets, and their regulation by Bifidobacterium breve (B.breve) and its associated metabolites in the initiation of colitis-associated colorectal cancer (CAC).Methods: Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to create a CAC model.The tumor-suppressive effect of B. breve and variations of macrophage subsets were evaluated.Intestinal macrophages were ablated to determine their role in the protective effects of B. breve.Efficacious molecules produced by B. breve were identified by non-targeted and targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.The molecular mechanism was further verified in murine bone marrow-derived macrophages (BMDMs), macrophages derived from human peripheral blood mononuclear cells (hPBMCs), and demonstrated in CAC mice.Results: B. breve alleviated colitis symptoms, delayed colonic tumorigenesis, and promoted phenotypic differentiation of immature inflammatory macrophages into mature homeostatic macrophages.On the contrary, the ablation of intestinal macrophages largely annulled the protective effects of B. breve.Microbial analysis of colonic contents revealed the enrichment of probiotics and the depletion of potential pathogens following B. breve supplementation.Moreover, indole-3-lactic acid (ILA) was positively correlated with B. breve in CAC mice and highly enriched in the culture supernatant of B. breve.Also, the addition of ILA directly promoted AKT phosphorylation and restricted the pro-inflammatory response of murine BMDMs and macrophages derived from hPBMCs in vitro.The effects of ILA in murine BMDMs and macrophages derived from hPBMCs were abolished by the aryl hydrocarbon receptor (AhR) antagonist CH-223191 or the AKT inhibitor MK-2206.Furthermore, ILA could protect against tumorigenesis by regulating macrophage differentiation in CAC mice; the AhR antagonist largely abrogated the effects of B. breve and ILA in relieving colitis and tumorigenesis.Conclusion: B. breve-mediated tryptophan metabolism ameliorates the precancerous inflammatory intestinal milieu to inhibit tumorigenesis by directing the differentiation of immature colonic macrophages.
Hyperglycemia facilitates EV71 replication: Insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity
Authors: Rai-Hua Lai, Yen-Hung Chow, Yi-Wen Lin, Nai-Hsiang Chung, Shu-Wei Nien, Jyh-Lyh Juang
Journal: Theranostics (2024)

Background: Neurotropic virus infections actively manipulate host cell metabolism to enhance virus neurovirulence.Although hyperglycemia is common during severe infections, its specific role remains unclear.This study investigates the impact of hyperglycemia on the neurovirulence of enterovirus 71 (EV71), a neurovirulent virus relying on internal ribosome entry site (IRES)-mediated translation for replication.Methods: Utilizing hSCARB2-transgenic mice, we explore the effects of hyperglycemia in EV71 infection and elucidate the underlying mechanisms.Results: Remarkably, administering insulin alone to reduce hyperglycemia in hSCARB2-transgenic mice results in a decrease in brainstem encephalitis and viral load.Conversely, induced hyperglycemia exacerbates neuropathogenesis, highlighting the pivotal role of hyperglycemia in neurovirulence.Notably, miR-206 emerges as a crucial mediator induced by viral infection, with its expression further heightened by hyperglycemia and concurrently repressed by insulin.The use of antagomiR-206 effectively mitigates EV71-induced brainstem encephalitis and reduces viral load.Mechanistically, miR-206 facilitates IRES-driven virus replication by repressing the stress granule protein G3BP2.Conclusions: Novel therapeutic approaches against severe EV71 infections involve managing hyperglycemia and targeting the miR-206-stress granule pathway to modulate virus IRES activity.
Small extracellular vesicles (sEVs)-based gene delivery platform for cell-specific CRISPR/Cas9 genome editing
Authors: Sunil Dubey, Zhe Chen, Yuxiao Jarvan Jiang, Austin Talis, Andrei Molotkov, Alessandra Ali, Akiva Mintz, Fatemeh Momen-Heravi
Journal: Theranostics (2024)

Small extracellular vesicles (sEVs) are naturally occurring vesicles that have the potential to be manipulated to become promising drug delivery vehicles for on-demand in vitro and in vivo gene editing.Here, we developed the modular safeEXO platform, a prototype sEV delivery vehicle that is mostly devoid of endogenous RNA and can efficaciously deliver RNA and ribonucleoprotein (RNP) complexes to their intended intracellular targets manifested by downstream biologic activity.We also successfully engineered producer cells to produce safeEXO vehicles that contain endogenous Cas9 (safeEXO-CAS) to effectively deliver efficient ribonucleoprotein (RNP)-mediated CRISPR genome editing machinery to organs or diseased cells in vitro and in vivo.We confirmed that safeEXO-CAS sEVs could co-deliver ssDNA, sgRNA and siRNA, and efficaciously mediate gene insertion in a dose-dependent manner.We demonstrated the potential to target safeEXO-CAS sEVs by engineering sEVs to express a tissue-specific moiety, integrin alpha-6 (safeEXO-CAS-ITGA6), which increased their uptake to lung epithelial cells in vitro and in vivo.We tested the ability of safeEXO-CAS-ITGA6 loaded with EMX1 sgRNAs to induce lung-targeted editing in mice, which demonstrated significant gene editing in the lungs with no signs of morbidity or detectable changes in immune cell populations.Our results demonstrate that our modular safeEXO platform represents a targetable, safe, and efficacious vehicle to deliver nucleic acid-based therapeutics that successfully reach their intracellular targets.Furthermore, safeEXO producer cells can be genetically manipulated to produce safeEXO vehicles containing CRISPR machinery for more efficient RNP-mediated genome editing.This platform has the potential to improve current therapies and increase the landscape of treatment for various human diseases using RNAi and CRISPR approaches.
Adaptive plasticity of natural interleukin-35-induced regulatory T cells (Tr35) that are required for T-cell immune regulation
Authors: Xundong Wei, Jianhua Zhang, Jian Cui, Wei Xu, Gang Zhao, Chang Guo, Wei Yuan, Xuyu Zhou, Jie Ma
Journal: Theranostics (2024)

Background: IL-35 potently inhibits immune responses both in vivo and in vitro.However, the specific characteristics of IL-35-producing cells, including their developmental origin, cellular phenotype, and function, are unknown.Methods: By utilized a novel IL-35 reporter mouse (Ebi3-Dre-Thy1.1)and double transgenic fate-mapping reporter mice (35EbiT-Rosa26-rox-tdTomato reporter mice or Foxp3 fate-mapping system), we tracked and analyzed the differentiation and developmental trajectories of Tr35 cells in vivo.And then we investigated the therapeutic effects of OVA-specific Tr35 cells in an OVA-induced allergic airway disease model.Results: We identified a subset of cells, denoted Tr35 cells, that secrete IL-35 but do not express Foxp3.These cells have high expression of molecules associated with T-cell activation and can inhibit T-cell proliferation in vitro.Our analyses showed that Tr35 cells are a distinct subpopulation of cells that are independent of Tr1 cells.Tr35 cells exhibit a unique gene expression profile and tissue distribution.The presence of Thy1.1 (Ebi3) expression in Tr35 cells indicates their active secretion of IL-35.However, the proportion of ex-Tr35 cells (Thy1.1 -) is significantly higher compared to Tr35 cells (Thy1.1 + ).This suggests that Tr35 cells possess the ability to regulate IL-35 expression rapidly in vivo.Tr35 cells downregulated the expression of the inflammatory cytokines IL-4, IFN-γ and IL-17A.However, once Tr35 cells lost IL-35 expression and became exTr35 cells, the expression of inflammatory cytokines was upregulated.Importantly, our findings indicate that Tr35 cells have therapeutic potential.In an OVA-induced allergic airway disease mouse model, Tr35 cell reinfusion significantly reduced airway hyperresponsiveness and histopathological airway and lung inflammation.Conclusions: We have identified a subset of Tregs, Tr35 cells, that are distinct from Tr1 cells.Tr35 cells can dynamically regulate the secretion of inflammatory cytokines by controlling IL-35 expression to regulate inflammatory immune responses.
A non-lipid nucleic acid delivery vector with dendritic cell tropism and stimulation
Authors: Hyung Shik Kim, Elias A. Halabi, Noah Enbergs, Rainer H. Kohler, Fan Fei, Christopher S. Garris, Ralph Weissleder
Journal: Theranostics (2024)

: Nucleic acid constructs are commonly used for vaccination, immune stimulation, and gene therapy, but their use in cancer still remains limited. One of the reasons is that systemic delivery to tumor-associated antigen-presenting cells (dendritic cells and macrophages) is often inefficient, while off-target nucleic acid-sensing immune pathways can stimulate systemic immune responses. Conversely, certain carbohydrate nanoparticles with small molecule payloads have been shown to target these cells efficiently in the tumor microenvironment. Yet, nucleic acid incorporation into such carbohydrate-based nanoparticles has proven challenging.