tbuckley/cabot-search huggingface dataset:
Stepwise targeted strategies for improving neurological function by inhibiting oxidative stress levels and inflammation following ischemic stroke
Authors: Yi Li, Jun Liao, Liyan Xiong, Zhicheng Xiao, Fei Ye, Yun Wang, Ting Chen, Linzhang Huang, Min Chen, Zhe-Sheng Chen, Tingfang Wang, Chuan Zhang, Ying Lu
Journal: Journal of Controlled Release (2024)
Genome assemblies of 11 bamboo species highlight diversification induced by dynamic subgenome dominance
Authors: Peng-Fei Ma, Yun-Long Liu, Cen Guo, Guihua Jin, Zhen-Hua Guo, Ling Mao, Yi-Zhou Yang, Liang-Zhong Niu, Yu-Jiao Wang, Lynn G. Clark, Elizabeth A. Kellogg, Zu-Chang Xu, Xia-Ying Ye, Jing-Xia Liu, Meng-Yuan Zhou, Yan Luo, Yang Yang, Douglas E. Soltis, Jeffrey L. Bennetzen, Pamela S. Soltis, De-Zhu Li
Journal: Nature Genetics (2024)

Abstract Polyploidy (genome duplication) is a pivotal force in evolution. However, the interactions between parental genomes in a polyploid nucleus, frequently involving subgenome dominance, are poorly understood. Here we showcase analyses of a bamboo system (Poaceae: Bambusoideae) comprising a series of lineages from diploid (herbaceous) to tetraploid and hexaploid (woody), with 11 chromosome-level de novo genome assemblies and 476 transcriptome samples. We find that woody bamboo subgenomes exhibit stunning karyotype stability, with parallel subgenome dominance in the two tetraploid clades and a gradual shift of dominance in the hexaploid clade. Allopolyploidization and subgenome dominance have shaped the evolution of tree-like lignified culms, rapid growth and synchronous flowering characteristic of woody bamboos as large grasses. Our work provides insights into genome dominance in a remarkable polyploid system, including its dependence on genomic context and its ability to switch which subgenomes are dominant over evolutionary time.
Retraction: Effects of Oligonucleotide N3′→P5′ Thio-phosphoramidate (GRN163) Targeting Telomerase RNA in Human Multiple Myeloma Cells
Authors: Masaharu Akiyama, Teru Hideshima, Masood A. Shammas, Toshiaki Hayashi, Makoto Hamasaki, Yu-Tzu Tai, Paul Richardson, Sergei Gryaznov, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Cancer Research (2024)
FASN Inhibition Decreases MHC-I Degradation and Synergizes with PD-L1 Checkpoint Blockade in Hepatocellular Carcinoma
Authors: Jiao Huang, Wai Ying Tsang, Xiao-Na Fang, Yu Zhang, Jie Luo, Lan-Qi Gong, Bai-Feng Zhang, Ching Ngar Wong, Zhi-Hong Li, Bei-Lei Liu, Jin-Lin Huang, Yu-Ma Yang, Shan Liu, Liu-Xian Ban, Yiu Hong Chan, Xin-Yuan Guan
Journal: Cancer Research (2024)

Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain refractory to ICIs, and druggable targets for upregulating MHC-I are limited. Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Mechanistically, FASN inhibition reduced palmitoylation of MHC-I that led to its lysosomal degradation. The palmitoyltransferase DHHC3 directly bound MHC-I and negatively regulated MHC-I protein levels. In an orthotopic HCC mouse model, Fasn deficiency enhanced MHC-I levels and promoted cancer cell killing by tumor-infiltrating CD8+ T cells. Moreover, the combination of two different FASN inhibitors, orlistat and TVB-2640, with anti-PD-L1 antibody robustly suppressed tumor growth in vivo. Multiplex IHC of human HCC samples and bioinformatic analysis of The Cancer Genome Atlas data further illustrated that lower expression of FASN was correlated with a higher percentage of cytotoxic CD8+ T cells. The identification of FASN as a negative regulator of MHC-I provides the rationale for combining FASN inhibitors and immunotherapy for treating HCC.
A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma
Authors: Grace H. Hwang, Maria F. Pazyra-Murphy, Hyuk-Soo Seo, Sirano Dhe-Paganon, Sylwia A. Stopka, Marina DiPiazza, Nizhoni Sutter, Thomas W. Gero, Alison Volkert, Lincoln Ombelets, Georgia Dittemore, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Nathalie Y.R. Agar, David A. Scott, Rosalind A. Segal
Journal: Cancer Research (2024)

Abstract Medulloblastoma is one of the most common malignant brain tumors of children, and 30% of medulloblastomas are driven by gain-of-function genetic lesions in the Sonic Hedgehog (SHH) signaling pathway. EYA1, a haloacid dehalogenase phosphatase and transcription factor, is critical for tumorigenesis and proliferation of SHH medulloblastoma (SHH-MB). Benzarone and benzbromarone have been identified as allosteric inhibitors of EYA proteins. Using benzarone as a point of departure, we developed a panel of 35 derivatives and tested them in SHH-MB. Among these compounds, DS-1–38 functioned as an EYA antagonist and opposed SHH signaling. DS-1–38 inhibited SHH-MB growth in vitro and in vivo, showed excellent brain penetrance, and increased the lifespan of genetically engineered mice predisposed to fatal SHH-MB. These data suggest that EYA inhibitors represent promising therapies for pediatric SHH-MB. Significance: Development of a benzarone derivative that inhibits EYA1 and impedes the growth of SHH medulloblastoma provides an avenue for improving treatment of this malignant pediatric brain cancer.
Supramolecular nanodrug targeting CDK4/6 overcomes BAG1 mediated cisplatin resistance in oral squamous cell carcinoma
Authors: Borui Zhao, Xuan Qin, Rui Fu, Maosen Yang, Xin Hu, Shaorong Zhao, Yange Cui, Qingxiang Guo, Wei Zhou
Journal: Journal of Controlled Release (2024)
Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology
Authors: Sania Bashir, Ayesha Aiman, Mohammad Shahid, Anis Ahmad Chaudhary, Neha Sami, Seemi Farhat Basir, Imtaiyaz Hassan, Asimul Islam
Journal: Ageing Research Reviews (2024)
Response to “Low-dose oral minoxidil for androgenetic alopecia is not associated with clinically significant blood-pressure changes: A retrospective study”
Authors: Deesha Desai, Ambika Nohria, Michelle Sikora, Soutrik Mandal, Jerry Shapiro, Avrom S Caplan, Michael Garshick, Kristen Lo Sicco
Journal: Journal of the American Academy of Dermatology (2024)
Low-dose oral minoxidil for treatment of androgenetic alopecia: gender differences in blood pressure and hypotension-related adverse effects; Response to Desai et al., “Response to ‘Low-dose oral minoxidil for androgenetic alopecia is not associated with clinically significant blood-pressure changes: a retrospective study’”
Authors: Michael Ong, Shari R Lipner
Journal: Journal of the American Academy of Dermatology (2024)
Rhino-orbital-cerebral Mucormycosis
Authors: Cristian-Mihail Niculae, Laura Craciun
Journal: New England Journal of Medicine (2024)

An 82-year-old man with type 2 diabetes and recent glucocorticoid use presented with a 2-week history of headache and spontaneous bruising around his eye. Black eschars were observed in the nasal cavity (shown in a video).
Into the era of mycobiome-driven cancer research
Authors: Weici Liu, Zheshun Pi, Ning-Ning Liu, Wenjun Mao
Journal: Trends in cancer (2024)

The cancer mycobiome has recently become a research hotspot. While the intratumor mycobiota is implicated in cancer initiation and progression, the gut mycobiota functions as biomarkers for cancer diagnosis and treatment. In this forum article we highlight the involvement of the mycobiome in correlation-, causation-, and prediction-oriented cancer research and discuss the potential of this burgeoning field.
The Combination of Membrane Disruption and FtsZ Targeting by a Chemotherapeutic Hydrogel Synergistically Combats Pathogens Infections
Authors: Xianyuan Wei, Jintong Guo, Xiaorui Geng, Bin Xue, Shaohui Huang, Zhen Yuan
Journal: Advanced Healthcare Materials (2024)

The emergence of multidrug-resistant (MDR) bacteria poses a significant challenge to global health. Due to a shortage of antibiotics, alternative therapeutic strategies are urgently needed. Unfortunately, colistin, the last-resort antibiotic, has unavoidable nephrotoxicity and hepatotoxicity, and its single killing mechanism is prone to drug resistance. To address this challenge, a promising combinatorial approach that includes colistin, a membrane-disrupting antimicrobial agent, and chelerythrine (CHE), a FtsZ protein inhibitor is proposed. This approach significantly reduces antibiotic dose and development of resistance, leading to almost complete inactivation of MDR pathogens in vitro. To address solubility issues and ensure transport, the antimicrobial hydrogel system LNP-CHE-CST@hydrogel, which induced reactive oxygen species (ROS) and apoptosis-like cell death by targeting the FtsZ protein, is used. In an in vivo mouse skin infection model, the combination therapy effectively eliminated MDR bacteria within 24 h, as monitored by fluorescence tracking. The findings demonstrate a promising approach for developing multifunctional hydrogels to combat MDR bacterial infections.
Discovery of first-in-class DOT1L inhibitors against the R231Q gain-of-function mutation in the catalytic domain with therapeutic potential of lung cancer
Authors: Zehui Tan, Ning Guo, Zhi Cao, Shuyu Liu, Jiayu Zhang, Deyi Ma, Jiahao Zhang, Wencai Lv, Nan Jiang, Linghe Zang, Lihui Wang, Xin Zhai
Journal: Acta Pharmaceutica Sinica B (2024)

Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer. Herein, a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q cell. The most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation, self-renewal, migration, and invasion of lung cancer cell lines at low micromolar concentrations. The cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS assays. In the H460R231Q OE cell-derived xenograft (CDX) model, 37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks (TGI= 54.38%), without obvious toxicities. A pharmacokinetic study revealed that 37 possessed tolerable properties (t1/2 = 1.93 ± 0.91 h, F = 97.2%) after intraperitoneal administration in rats. Mechanism study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling pathway. Moreover, analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the "Induced-fit" allosteric model in favor to the discovery of potent DOT1L candidates.
An aligned framework of actively collected and passively monitored clinical outcome assessments (COAs) for measure selection
Authors: Christine Manta Campbell, Courtney Webster, Megan Parisi, Roya Sherafat-Kazemzadeh, Jessica Braid, Thomas Switzer, Marcelo Alves Fávaro, Caprice Sassano, Andrea Coravos
Journal: npj Digital Medicine (2024)

Abstract Regulators increasingly require clinical outcome assessment (COA) data for approval. COAs can be collected via questionnaires or digital health technologies (DHTs), yet no single resource provides a side-by-side comparison of tools that collect complementary or related COA measures. We propose how to align ontologies for actively collected and passively monitored COAs into a single framework to allow for rapid, evidence-based, and fit-for-purpose measure selection.
Beyond the marrow: insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors
Authors: T. Jelinek, D. Zihala, T. Sevcikova, A. Anilkumar Sithara, V. Kapustova, H. Sahinbegovic, O. Venglar, L. Muronova, L. Broskevicova, S. Nenarokov, D. Bilek, T. Popkova, H. Plonkova, J. Vrana, V. Zidlik, P. Hurnik, M. Havel, M. Hrdinka, Z. Chyra, G. Stracquadanio, M. Simicek, R. Hajek
Journal: Leukemia (2024)

Abstract Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma (MM). This study represents the most comprehensive next-generation sequencing analysis of EMM tumors ( N = 14) to date, uncovering key molecular features and describing the tumor microenvironment. We observed the co-occurrence of 1q21 gain/amplification and MAPK pathway mutations in 79% of EMM samples, suggesting that these are crucial mutational events in EMM development. We also demonstrated that patients with mutated KRAS and 1q21 gain/amplification at the time of diagnosis have a significantly higher risk of EMM development (HR = 2.4, p = 0.011) using data from a large CoMMpass dataset. We identified downregulation of CXCR4 and enhanced cell proliferation, along with reduced expression of therapeutic targets (CD38, SLAMF7, GPRC5D, FCRH5), potentially explaining diminished efficacy of immunotherapy. Conversely, we identified significantly upregulated EZH2 and CD70 as potential future therapeutic options. For the first time, we report on the tumor microenvironment of EMM, revealing CD8+ T cells and NK cells as predominant immune effector cells using single-cell sequencing. Finally, this is the first longitudinal study in EMM revealing the molecular changes from the time of diagnosis to EMM relapse.
Physical activity and sleep changes among children during the COVID-19 pandemic
Authors: Karnika Singh, Sarah C. Armstrong, Brooke E. Wagner, Julie Counts, Asheley Skinner, Melissa Kay, Jennifer S. Li, Svati Shah, Nancy Zucker, Cody Neshteruk, Mary Story, Lilianna Suarez, William E. Kraus, Alexandra R. Zizzi, Jessilyn Dunn
Journal: npj Digital Medicine (2024)

Abstract Daily routines, including in-person school and extracurricular activities, are important for maintaining healthy physical activity and sleep habits in children. The COVID-19 pandemic significantly disrupted daily routines as in-person school and activities closed to prevent spread of SARS-CoV-2. We aimed to examine and assess differences in objectively measured physical activity levels and sleep patterns from wearable sensors in children with obesity before, during, and after a period of school and extracurricular activity closures associated with the COVID-19 pandemic. We compared average step count and sleep patterns (using the Mann–Whitney U Test) before and during the pandemic-associated school closures by using data from activity tracker wristbands (Garmin VivoFit 3 ). Data were collected from 94 children (aged 5–17) with obesity, who were enrolled in a randomized controlled trial testing a community-based lifestyle intervention for a duration of 12-months. During the period that in-person school and extracurricular activities were closed due to the COVID-19 pandemic, children with obesity experienced objectively-measured decreases in physical activity, and sleep duration. From March 15, 2020 to March 31, 2021, corresponding with local school closures, average daily step count decreased by 1655 steps. Sleep onset and wake time were delayed by about an hour and 45 min, respectively, while sleep duration decreased by over 12 min as compared with the pre-closure period. Step counts increased with the resumption of in-person activities. These findings provide objective evidence for parents, clinicians, and public health professionals on the importance of in-person daily activities and routines on health behaviors, particularly for children with pre-existing obesity. Trial Registration: Clinical trial registration: NCT03339440
Prophylactic abdominal drainage after distal pancreatectomy (PANDORINA): an international, multicentre, open-label, randomised controlled, non-inferiority trial
Authors: Eduard A van Bodegraven, Alberto Balduzzi, Tess M E van Ramshorst, Giuseppe Malleo, Frederique L Vissers, Jony van Hilst, Sebastiaan Festen, Mohammad Abu Hilal, Horacio J Asbun, Nynke Michiels, Bas Groot Koerkamp, Olivier R C Busch, Freek Daams, Misha D P Luyer, Marco Ramera, Giovanni Marchegiani, Joost M Klaase, I Quintus Molenaar, Matteo de Pastena, Gabriella Lionetto, Pier Giuseppe Vacca, Hjalmar C van Santvoort, Martijn W J Stommel, Daan J Lips, Mariëlle M E Coolsen, J Sven D Mieog, Roberto Salvia, Casper H J van Eijck, Marc G Besselink
Journal: The Lancet. Gastroenterology & hepatology (2024)
Diagnostic test accuracy of procalcitonin and C-reactive protein for predicting invasive and serious bacterial infections in young febrile infants: a systematic review and meta-analysis
Authors: Hannah Norman-Bruce, Etimbuk Umana, Clare Mills, Hannah Mitchell, Lisa McFetridge, David McCleary, Thomas Waterfield
Journal: The Lancet Child & Adolescent Health (2024)

Febrile infants presenting in the first 90 days of life are at higher risk of invasive and serious bacterial infections than older children. Modern clinical practice guidelines, mostly using procalcitonin as a diagnostic biomarker, can identify infants who are at low risk and therefore suitable for tailored management. C-reactive protein, by comparison, is widely available, but whether C-reactive protein and procalcitonin have similar diagnostic accuracy is unclear. We aimed to compare the test accuracy of procalcitonin and C-reactive protein in the prediction of invasive or serious bacterial infections in febrile infants.
Versatile Mechanically Tunable Hydrogels for Therapeutic Delivery Applications
Authors: Qiyao Sun, Siyuan Tao, Giovanni Bovone, Garam Han, Dhananjay Deshmukh, Mark W. Tibbitt, Qun Ren, Pascal Bertsch, Gilberto Siqueira, Peter Fischer
Journal: Advanced Healthcare Materials (2024)

Hydrogels provide a versatile platform for biomedical material fabrication that can be structurally and mechanically fine-tuned to various tissues and applications. Applications of hydrogels in biomedicine range from highly dynamic injectable hydrogels that can flow through syringe needles and maintain or recover their structure after extrusion to solid-like wound-healing patches that need to be stretchable while providing a selective physical barrier. In this study, a toolbox is designed using thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) polymeric matrices and nanocelluloses as reinforcing agent to obtain biocompatible hydrogels with altering mechanical properties, from a liquid injectable to a solid-like elastic hydrogel. The liquid hydrogels possess low viscosity and shear-thinning properties at 25 °C, which allows facile injection at room temperature, while they become viscoelastic gels at body temperature. In contrast, the covalently cross-linked solid-like hydrogels exhibit enhanced viscoelasticity. The liquid hydrogels are biocompatible and are able to delay the in vitro release and maintain the bioactivity of model drugs. The antimicrobial agent loaded solid-like hydrogels are effective against typical wound-associated pathogens. This work presents a simple method of tuning hydrogel mechanical strength to easily adapt to applications in different soft tissues and broaden the potential of renewable bio-nanoparticles in hybrid biomaterials with controlled drug release capabilities.
Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions
Authors: Yong Qiu, Chunheng Mo, Lu Chen, Wanlin Ye, Guo Chen, Tao Zhu
Journal: MedComm (2024)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently caused a global pandemic, resulting in more than 702 million people being infected and over 6.9 million deaths. Patients with coronavirus disease (COVID-19) may suffer from diarrhea, sleep disorders, depression, and even cognitive impairment, which is associated with long COVID during recovery. However, there remains no consensus on effective treatment methods. Studies have found that patients with COVID-19 have alterations in microbiota and their metabolites, particularly in the gut, which may be involved in the regulation of immune responses. Consumption of probiotics may alleviate the discomfort caused by inflammation and oxidative stress. However, the pathophysiological process underlying the alleviation of COVID-19-related symptoms and complications by targeting the microbiota remains unclear. In the current study, we summarize the latest research and evidence on the COVID-19 pandemic, together with symptoms of SARS-CoV-2 and vaccine use, with a focus on the relationship between microbiota alterations and COVID-19-related symptoms and vaccine use. This work provides evidence that probiotic-based interventions may improve COVID-19 symptoms by regulating gut microbiota and systemic immunity. Probiotics may also be used as adjuvants to improve vaccine efficacy.
Transcriptomic analysis of rat brain response to alternating current electrical stimulation: unveiling insights via single‐nucleus RNA sequencing
Authors: Yan Wang, Yongchao Ma, Qiuling Zhong, Bing Song, Qian Liu
Journal: MedComm (2024)

Electrical brain stimulation (EBS) has gained popularity for laboratory and clinical applications. However, comprehensive characterization of cellular diversity and gene expression changes induced by EBS remains limited, particularly with respect to specific brain regions and stimulation sites. Here, we presented the initial single-nucleus RNA sequencing profiles of rat cortex, hippocampus, and thalamus subjected to intracranial alternating current stimulation (iACS) at 40 Hz. The results demonstrated an increased number of neurons in all three regions in response to iACS. Interestingly, less than 0.1% of host gene expression in neurons was significantly altered by iACS. In addition, we identified
Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta‐analysis
Authors: Bruno Almeida Costa, Thomaz Alexandre Costa, Sara Diaz Saravia, Nicole Felix, Carlyn Rose Tan, Neha Korde, Joshua Richter
Journal: American Journal of Hematology (2024)

Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.