tbuckley/cabot-search huggingface dataset:
Intestinal carbapenem-resistant <i>Klebsiella pneumoniae</i> undergoes complex transcriptional reprogramming following immune activation
Authors: Clement David, Aleksander Czauderna, Liqing Cheng, Marion Lagune, Hea-Jin Jung, Sohn G. Kim, Eric G. Pamer, Julien Prados, Liang Chen, Simone Becattini
Journal: Gut Microbes (2024)

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is a significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract. There, the bacterium is usually present at low density but can bloom following antibiotic treatment, mostly in hospital settings. The impact of disturbances in the intestinal environment on the fitness, survival, expansion, and drug susceptibility of this pathogen is not well-understood, yet it may be relevant to devise strategies to tackle CR-Kp colonization and infection. Here, we adopted an in vivo model to examine the transcriptional adaptation of a CR-Kp clinical isolate to immune activation in the intestine. We report that as early as 6 hours following host treatment with anti-CD3 antibody, CR-Kp underwent rapid transcriptional changes including downregulation of genes involved in sugar utilization and amino acid biosynthesis and upregulation of genes involved in amino acid uptake and catabolism, antibiotic resistance, and stress response. In agreement with these findings, treatment increased the concentration of oxidative species and amino acids in the mouse intestine. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were strongly upregulated, however their deletion did not impair CR-Kp fitness in vivo upon immune activation. Transcription factor enrichment analysis identified the global regulator cAMP-Receptor Protein, CRP, as a potential orchestrator of the observed transcriptional signature. In keeping with the recognized role of CRP in regulating utilization of alternative carbon sources, crp deletion in CR-Kp resulted in strongly impaired gut colonization, although this effect was not amplified by immune activation. Thus, following intestinal colonization, which occurs in a CRP-dependent manner, CR-Kp can rapidly respond to immune cues by implementing a well-defined and complex transcriptional program whose direct relevance toward bacterial fitness warrants further investigation. Additional analyses utilizing this model may identify key factors to tackle CR-Kp colonization of the intestine.
Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the <i>Lactobacillus</i>–bile acid–intestinal farnesoid X receptor axis based on multiomics integration analysis
Authors: Xiaohang Zhou, Hui Sun, Junling Ren, Guangli Yan, Le Yang, Honglian Zhang, Haitao Lu, Xinghua Li, Toshiaki Makino, Fengting Yin, Jing Li, Xijun Wang
Journal: MedComm (2024)

Abstract Mineral crude drug has revolutionized the treatment landscape in precision oncology niche that leads to the improvement in therapeutic efficiency on various tumor subtypes. Mangxiao (MX), a mineral crude drug in traditional Chinese medicine, has been used for treating gastrointestinal diseases for thousands of years. However, the action mechanisms are still ambiguous. Here, we attempt to explore inhibitory roles and associated pharmacological mechanisms of MX upon colorectal cancer (CRC) in APC Min/+ male mice by integrating metabolomics, 16S rDNA sequencing analyses, and metagenomic‐based microbiota analysis. We found that MX can significantly inhibit the occurrence of CRC through the regulation of the dysregulated gut microbe metabolism. Furthermore, the correlation analysis of metabolomes and 16S rDNA revealed that MX could restore the disorders of gut microbes by specifically enriching the abundance of Lactobacilli to improve bile acid metabolism, which further activated the farnesoid X receptor (FXR) in CRC mice, then the improvement of gut dysbiosis could inhibit the development of CRC. Collectively, our effort confirmed MX has the capacity to intervene the development of CRC and further discovered that it targets Lactobacillus –bile acid–intestinal FXR axis, which can be regarded as a candidate medicine for future drug discovery and development against CRC.
Clinical applicability of AI‐based prognosis prediction for a rare ocular surface disease
Authors: Mayumi Ueta, Yasuhito Watanabe, Charles Melby‐Thompson, Chie Sotozono, Shigeru Kinoshita
Journal: Allergy (2024)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. Figure S1. Table S1. Appendix S1. Appendix S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association
Authors: Laura J. Davidson, Gilbert H.L. Tang, Edwin C. Ho, Marat Fudim, Tiberio Frisoli, Anton Camaj, Margaret T. Bowers, Sofia Carolina Masri, Pavan Atluri, Joanna Chikwe, Peter J. Mason, Jason C. Kovacic, George D. Dangas
Journal: Circulation (2024)

Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options. The tricuspid valve is complex anatomically, lying adjacent to important anatomic structures such as the right coronary artery and the atrioventricular node, and is the passageway for permanent pacemaker leads into the right ventricle. In addition, the mechanism of tricuspid pathology varies widely between patients, which can be due to primary, secondary, or a combination of causes, meaning that it is not possible for 1 type of device to be suitable for treatment of all cases of tricuspid valve disease. To best visualize the pathology, several modalities of advanced cardiac imaging are often required, including transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, to best visualize the pathology. This detailed imaging provides important information for choosing the ideal transcatheter treatment options for patients with tricuspid valve disease, taking into account the need for the lifetime management of the patient. This review highlights the important background, anatomic considerations, therapeutic options, and future directions with regard to treatment of tricuspid valve disease.
Comparison of Incidence and Prognostic Impact of Ischemic, Major Bleeding and Heart Failure Events in Patients With Chronic Coronary Syndrome: Insights From the CORONOR Registry
Authors: Gilles Lemesle, Nicolas Lamblin, Guillaume Schurtz, Julien Labreuche, Alain Duhamel, Basile Verdier, Philippe Gabriel Steg, Christophe Bauters
Journal: Circulation (2024)

Evaluation of the residual risk in patient with chronic coronary syndrome is challenging in daily practice. Several types of events (myocardial infarction, ischemic stroke, bleeding, and heart failure [HF]) may occur, and their impact on subsequent mortality is unclear in the era of modern evidence-based pharmacotherapy.
The incorporation of acetylated LAP-TGF-β1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis
Authors: Pei Yu, Yubao Han, Lulu Meng, Zengying Tang, Zhiwei Jin, Zhenzhen Zhang, Yunjiang Zhou, Jun Luo, Jianguang Luo, Chao Han, Chao Zhang, Lingyi Kong
Journal: Molecular Cancer (2024)

Abstract Triple-negative breast cancer (TNBC) stands as the breast cancer subtype with the highest recurrence and mortality rates, with the lungs being the common site of metastasis. The pulmonary microenvironment plays a pivotal role in the colonization of disseminated tumor cells. Herein, this study highlights the crucial role of exosomal LAP-TGF-β1, the principal form of exosomal TGF-β1, in reshaping the pulmonary vascular niche, thereby facilitating TNBC lung metastasis. Although various strategies have been developed to block TGF-β signaling and have advanced clinically, their significant side effects have limited their therapeutic application. This study demonstrates that in lung metastatic sites, LAP-TGF-β1 within exosomes can remarkably reconfigure the pulmonary vascular niche at lower doses, bolstering the extravasation and colonization of TNBC cells in the lungs. Mechanistically, under the aegis of the acetyltransferase TIP60, a non-canonical KFERQ-like sequence in LAP-TGF-β1 undergoes acetylation at the K304 site, promoting its interaction with HSP90A and subsequent transport into exosomes. Concurrent inhibition of both HSP90A and TIP60 significantly diminishes the exosomal burden of LAP-TGF-β1, presenting a promising therapeutic avenue for TNBC lung metastasis. This study not only offers fresh insights into the molecular underpinnings of TNBC lung metastasis but also lays a foundation for innovative therapeutic strategies.
Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition
Authors: Elisenda Bueichekú, Ibai Diez, Chan-Mi Kim, John Alex Becker, Elouise A. Koops, Kenneth Kwong, Kathryn V. Papp, David H. Salat, David A. Bennett, Dorene M. Rentz, Reisa A. Sperling, Keith A. Johnson, Jorge Sepulcre, Heidi I. L. Jacobs
Journal: Nature Aging (2024)

Abstract Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer’s disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined whether LC changes precede allocortical tau deposition and whether specific genetic features underlie LC’s selective vulnerability to tau. We found that LC integrity changes preceded medial temporal lobe tau accumulation, and together these processes were associated with lower cognitive performance. Common gene expression profiles between LC–medial temporal lobe–limbic regions map to biological functions in protein transport regulation. These findings advance our understanding of the spatiotemporal patterns of initial tau spreading from the LC and LC’s selective vulnerability to Alzheimer’s disease pathology. LC integrity measures can be a promising indicator for identifying the time window when individuals are at risk of disease progression and underscore the importance of interventions mitigating initial tau spread.
Author Correction: Cell-type-specific and disease-associated expression quantitative trait loci in the human lung
Authors: Heini M. Natri, Christina B. Del Azodi, Lance Peter, Chase J. Taylor, Sagrika Chugh, Robert Kendle, Mei-i Chung, David K. Flaherty, Brittany K. Matlock, Carla L. Calvi, Timothy S. Blackwell, Lorraine B. Ware, Matthew Bacchetta, Rajat Walia, Ciara M. Shaver, Jonathan A. Kropski, Davis J. McCarthy, Nicholas E. Banovich
Journal: Nature Genetics (2024)

eQTLs that were nominally significant (P < 1 × 10 -6 ) in the IPF GWAS meta-analysis" and has now been corrected in the HTML and PDF versions of the article.
Use of an Additional Updated 2023–2024 COVID-19 Vaccine Dose for Adults Aged ≥65 Years: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024
Authors: Lakshmi Panagiotakopoulos, Monica Godfrey, Danielle L. Moulia, Ruth Link-Gelles, Christopher A. Taylor, Kevin Chatham-Stephens, Oliver Brooks, Matthew F. Daley, Katherine E. Fleming-Dutra, Megan Wallace
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

COVID-19 remains an important public health threat, despite overall decreases in COVID-19-related severe disease since the start of the COVID-19 pandemic. COVID-19-associated hospitalization rates remain higher among adults aged ≥65 years relative to rates in younger adults, adolescents, and children; during October 2023-January 2024, 67% of all COVID-19-associated hospitalizations were among persons aged ≥65 years. On September 12, 2023, CDC's Advisory Committee on Immunization Practices (ACIP) recommended updated (2023-2024 Formula) COVID-19 vaccination with a monovalent XBB.1.5-derived vaccine for all persons aged ≥6 months to protect against severe COVID-19-associated illness and death. Because SARS-CoV-2 continues to circulate throughout the year, and because of the increased risk for COVID-19-related severe illness in persons aged ≥65 years, the protection afforded by updated vaccines against JN.1 and other currently circulating variants, and the expected waning of vaccine-conferred protection against disease, on February 28, 2024, ACIP recommended all persons aged ≥65 years receive 1 additional dose of the updated (2023-2024 Formula) COVID-19 vaccine. Implementation of these recommendations is expected to enhance immunity that might have waned and decrease the risk for severe COVID-19-associated outcomes, including death, among persons aged ≥65 years.
Centrifuger: lossless compression of microbial genomes for efficient and accurate metagenomic sequence classification
Authors: Li Song, Ben Langmead
Journal: Genome biology (2024)

Abstract Centrifuger is an efficient taxonomic classification method that compares sequencing reads against a microbial genome database. In Centrifuger, the Burrows-Wheeler transformed genome sequences are losslessly compressed using a novel scheme called run-block compression. Run-block compression achieves sublinear space complexity and is effective at compressing diverse microbial databases like RefSeq while supporting fast rank queries. Combining this compression method with other strategies for compacting the Ferragina-Manzini (FM) index, Centrifuger reduces the memory footprint by half compared to other FM-index-based approaches. Furthermore, the lossless compression and the unconstrained match length help Centrifuger achieve greater accuracy than competing methods at lower taxonomic levels.
A commentary on “Health-related quality of life trajectories up to 15 years after curative treatment for esophageal cancer: a prospective cohort study”
Authors: Hua Ji, Lin Yang, Wenjuan Li
Journal: International Journal of Surgery (2024)

aIntensive Care Unit, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Shanxi, China, 030013 bDepartment of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Shanxi, China, 030013 cIntensive Care Unit, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Shanxi, China, 030013 A commentary on "Health-related quality of life trajectories up to 15 years after curative treatment for esophageal cancer: a prospective cohort study"( Int J Surg. 2024 Mar 1;110(3):1537-1545.) Hua Ji and Lin Yang equally contributed to the study Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Intensive Care Unit, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Shanxi, China, 030013. E-mail address: [email protected] (W. Li). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Regulation of pulmonary plasma cell responses during secondary infection with influenza virus
Authors: Andrew J. MacLean, Joao P.P.L. Bonifacio, Sophia L. Oram, Mona O. Mohsen, Martin F. Bachmann, Tal I. Arnon
Journal: The Journal of Experimental Medicine (2024)

During secondary infection with influenza virus, plasma cells (PCs) develop within the lung, providing a local source of antibodies. However, the site and mechanisms that regulate this process are poorly defined. Here, we show that while circulating memory B cells entered the lung during rechallenge and were activated within inducible bronchus-associated lymphoid tissues (iBALTs), resident memory B (BRM) cells responded earlier, and their activation occurred in a different niche: directly near infected alveoli. This process required NK cells but was largely independent of CD4 and CD8 T cells. Innate stimuli induced by virus-like particles containing ssRNA triggered BRM cell differentiation in the absence of cognate antigen, suggesting a low threshold of activation. In contrast, expansion of PCs in iBALTs took longer to develop and was critically dependent on CD4 T cells. Our work demonstrates that spatially distinct mechanisms evolved to support pulmonary secondary PC responses, and it reveals a specialized function for BRM cells as guardians of the alveoli.
State Department of Motor Vehicles Reporting Mandates of Dementia Diagnoses and Dementia Underdiagnosis
Authors: Hankyung Jun, Ying Liu, Emily Chen, Andrew Becker, Soeren Mattke
Journal: JAMA Network Open (2024)

With older drivers representing the fastest growing segment of the driver population and dementia prevalence increasing with age, policymakers face the challenge of balancing road safety and mobility of older adults. In states that require reporting a dementia diagnosis to the Department of Motor Vehicles (DMV), individuals with dementia may be reluctant to disclose symptoms of cognitive decline, and clinicians may be reluctant to probe for those symptoms, which may be associated with missed or delayed diagnoses.
J‐Aggregate Promoting NIR‐II Emission for Fluorescence/ Photoacoustic Imaging‐Guided Phototherapy
Authors: Changjin Ou, Ziqi Zhao, Lei An, Liangyu Zheng, Fan Gao, Qin Zhu, Wenjun Wang, Jinjun Shao, Linghai Xie, Xiaochen Dong
Journal: Advanced Healthcare Materials (2024)

Abstract J‐aggregate is a promising strategy to enhance second near‐infrared window (NIR‐II) emission, while the controlled synthesis of J‐aggregated NIR‐II dyes is a huge challenge because of the lack of molecular design principle. Herein, bulk spiro[fluorene‐9,9′‐xanthene] functionalized benzobisthiadiazole‐based NIR‐II dyes (named BSFX‐BBT and OSFX‐BBT) are synthesized with different alkyl chains. The weak repulsion interaction between the donor and acceptor units and the S…N secondary interactions make the dyes to adopt a co‐planar molecular conformation and display a peak absorption &gt;880 nm in solution. Importantly, BSFX‐BBT can form a desiring J‐aggregate in the condensed state, and femtosecond transient absorption spectra reveal that the excited states of J‐aggregate are the radiative states, and J‐aggregate can facilitate stimulated emission. Consequently, the J‐aggregated nanoparticles (NPs) display a peak emission at 1124 nm with a high relative quantum yield of 0.81%. The efficient NIR‐II emission, good photothermal effect, and biocompatibility make the J‐aggregated NPs demonstrate efficient antitumor efficacy via fluorescence/photoacoustic imaging‐guided phototherapy. The paradigm illustrates that tuning the aggregate states of NIR‐II dye via spiro‐functionalized strategy is an effective approach to enhance photo‐theranostic performance.
Cranio-Orbital Fibrous Dysplasia Manifesting as Contralateral Optic Neuropathy
Authors: Daniel B. Azzam, M. Reza Vagefi, Laurel N. Vuong
Journal: Ophthalmology (2024)

A 38-year-old woman with longstanding right facial malformation presented for blurred vision in her left eye (OS). Examination revealed right zygomaticotemporal prominence (A), left afferent pupillary defect, dyschromatopsia, and optic disc pallor with 20/20 vision. Automated perimetry demonstrated nonspecific losses OS, and OCT exhibited retinal nerve fiber and ganglion cell thinning (B). Magnetic resonance imaging showed right extracranial bone mass (arrowheads), sparing the ipsilateral orbit, with left optic canal involvement (C, arrow). The optic canal was decompressed, and tumor resected via craniotomy. Histopathology showed curvilinear bony trabeculae without osteoblastic rimming, confirming fibrous dysplasia (D; hematoxylin and eosin, ×2-×4). Five months postoperatively, vision measured 20/30 with inferior field losses. (Magnified version of Figure A-D is available online at www.aaojournal.org).
Clarification Regarding Breast Cancer Stage in France
Authors: Florence Molinié, Lionel Lafay, Agnès Rogel
Journal: JAMA Oncology (2024)

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Keeping Up With ChatGPT
Authors: Julian M.M. Rogasch, Hans V. Jochens, Giulia Metzger, Christoph Wetz, Jonas Kaufmann, Christian Furth, Holger Amthauer, Imke Schatka
Journal: Clinical Nuclear Medicine (2024)

Purpose The latest iteration of GPT4 (generative pretrained transformer) is a large multimodal model that can integrate both text and image input, but its performance with medical images has not been systematically evaluated. We studied whether ChatGPT with GPT-4V(ision) can recognize images from common nuclear medicine examinations and interpret them. Patients and Methods Fifteen representative images (scintigraphy, 11; PET, 4) were submitted to ChatGPT with GPT-4V(ision), both in its Default and “Advanced Data Analysis (beta)” version. ChatGPT was asked to name the type of examination and tracer, explain the findings and whether there are abnormalities. ChatGPT should also mark anatomical structures or pathological findings. The appropriateness of the responses was rated by 3 nuclear medicine physicians. Results The Default version identified the examination and the tracer correctly in the majority of the 15 cases (60% or 53%) and gave an “appropriate” description of the findings or abnormalities in 47% or 33% of cases, respectively. The Default version cannot manipulate images. “Advanced Data Analysis (beta)” failed in all tasks in &gt;90% of cases. A “major” or “incompatible” inconsistency between 3 trials of the same prompt was observed in 73% (Default version) or 87% of cases (“Advanced Data Analysis (beta)” version). Conclusions Although GPT-4V(ision) demonstrates preliminary capabilities in analyzing nuclear medicine images, it exhibits significant limitations, particularly in its reliability (ie, correctness, predictability, and consistency).