tbuckley/cabot-search huggingface dataset:
<i>Notes from the Field</i>: Potential Outbreak of Extrapulmonary <i>Mycobacterium abscessus</i> subspecies <i>massiliense</i> Infections from Stem Cell Treatment Clinics in Mexico — Arizona and Colorado, 2022
Authors: Minh-Vu H. Nguyen, Nabeeh A. Hasan, Vinicius Calado Nogueira De Moura, L. Elaine Epperson, Christopher A. Czaja, Helen Johnston, Nicholas Laramee, Kelsey Orten, JulieAnna Rivas, Siru Prasai, Marissa K. Grossman, Kiran M. Perkins, David E. Griffith, Reeti Khare, Michael Strong, Charles L. Daley
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Mycobacterium abscessus is an intrinsically drug-resistant, rapidly growing, nontuberculous mycobacterium; extrapulmonary infections have been reported in association with medical tourism (1).During November-December 2022, two Colorado hospitals (hospitals A and B) treated patient A, a Colorado woman aged 30-39 years, for M. abscessus meningitis.In October 2022, she had received intrathecal donor embryonic stem cell injections in Baja California, Mexico to treat multiple sclerosis and subsequently experienced headaches and fevers, consistent with meningitis.Her cerebrospinal fluid revealed neutrophilic pleocytosis and grew M. abscessus in culture at hospital A. Hospital A's physicians consulted hospital B's infectious diseases (ID) physicians to co-manage this patient (2).In spring 2023, hospital B's ID physicians identified two additional patients with M. abscessus infections acquired after receiving stem cell injections performed at different clinics in Mexico.The first of these, patient B, an Arizona man aged 60-69 years, developed a right elbow osteoarticular infection after receiving donor embryonic stem cell injections for psoriatic arthritis at a Baja California, Mexico clinic different from the one that treated patient A, in April 2022.The second, patient C, a Colorado man aged 60-69 years, developed bilateral knee infections after receiving donor embryonic stem cell injections in both knees for osteoarthritis at a clinic in Guadalajara, Mexico, in October 2022.
Shiga Toxin–Producing <i>Escherichia coli</i> O157:H7 Illness Outbreak Associated with Untreated, Pressurized, Municipal Irrigation Water — Utah, 2023
Authors: BreAnne Osborn, Jennifer Hatfield, William Lanier, Jennifer Wagner, Kelly Oakeson, Ravyn Casey, Jacob Bullough, Pallavi Kache, Shanna Miko, Jasen Kunz, Grace Pederson, Molly Leeper, Nancy Strockbine, Haley McKeel, Jessica Hofstetter, Alexis Roundtree, Amy Kahler, Mia Mattioli
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

During July-September 2023, an outbreak of Shiga toxinproducing Escherichia coli O157:H7 illness among children in city A, Utah, caused 13 confirmed illnesses; seven patients were hospitalized, including two with hemolytic uremic syndrome.Local, state, and federal public health partners investigating the outbreak linked the illnesses to untreated, pressurized, municipal irrigation water (UPMIW) exposure in city A; 12 of 13 ill children reported playing in or drinking UPMIW.Clinical isolates were genetically highly related to one another and to environmental isolates from multiple locations within city A's UPMIW system.Microbial source tracking, a method to indicate possible contamination sources, identified birds and ruminants as potential sources of fecal contamination of UPMIW.Public health and city A officials issued multiple press releases regarding the outbreak reminding residents that UPMIW is not intended for drinking or recreation.Public education and UPMIW management and operations interventions, including assessing and mitigating potential contamination sources, covering UPMIW sources and reservoirs, indicating UPMIW lines and spigots with a designated color, and providing conspicuous signage to communicate risk and intended use might help prevent future UPMIW-associated illnesses.
A Multifunctional Nanoreactor‐Induced Dual Inhibition of HSP70 Strategy for Enhancing Mild Photothermal/Chemodynamic Synergistic Tumor Therapy
Authors: Shutong Wu, Mengting Gao, Lin Chen, Yuhang Wang, Xiaochun Zheng, Binyue Zhang, Juan Li, Xiao‐Dong Zhang, Rong Dai, Ziliang Zheng, Ruiping Zhang
Journal: Advanced Healthcare Materials (2024)

Mild photothermal therapy (PTT) is a spatiotemporally controllable method that utilizes the photothermal effect at relatively low temperatures (40-45 °C) to especially eliminate tumor tissues with negligible side effects on the surrounding normal tissues. However, the overexpression of heat shock protein 70 (HSP70) and limited effect of single treatment drastically impede the therapeutic efficacy. Herein, the constructed multifunctional core-shell structured Ag-Cu@SiO
Abstract PO1-06-01: Clinical Efficacy of Tumor Organoid-Guided Cancer Therapy for Locally Advanced Unresectable or Metastatic Breast Cancer
Authors: Ying-Yi Lin, Hong-Fei Gao, Hong Li, Bo-Lei Du, Min-Yi Cheng, Jia-Chen Zou, Xing-xing Zheng, Teng Zhu, Ting-Ting Li, Sheng Li, Kun Wang
Journal: Cancer Research (2024)

Abstract Purpose: Patient-derived organoids (PDOs) may facilitate treatment selection, but the feasibility of using breast cancer PDOs to guide personalized treatment in clinical practice has not been fully investigated. This study aimed to assess the clinical efficacy of treatment guided by PDO drug sensitivity tests (OGT) versus treatment of physician’s choice (TPC) in patients with locally advanced unresectable or metastatic breast cancer (MBC) and to explore the potential of PDOs to reveal mechanisms underlying treatment resistance. Methods: Patients diagnosed with MBC were recruited between January 2020 and August 2022. PDOs were established from biopsies specimens or malignant effusion samples. The efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving OGT were matched 1:2 by nearest neighbor propensity scores with patients receiving TPC. The primary clinical outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Results: 46 PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 81.1% (95% CI 67.6%-91.9%) in predicting patients' clinical responses. 36 OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs 5.0 months; unadjusted hazard ratio 0.53 [95% CI 0.33-0.85]; P=0.01) and improved disease control (88.9% vs 63.8%; unadjusted odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis uncovered differentially modulated pathways implicated in DNA repair and transcriptional regulation in patients less sensitive to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in patients less sensitive to palbociclib. Conclusions: MBC patients treated with OGT were associated with superior progression-free survival and disease control compared with TPC. PDO-based functional precision medicine is a feasible strategy for treatment optimization and customization in MBC and may enhance our understanding of therapeutic resistance. Citation Format: Ying-Yi Lin, Hong-Fei Gao, Hong Li, Bo-Lei Du, Min-Yi Cheng, Jia-Chen Zou, Xing-xing Zheng, Teng Zhu, Ting-Ting Li, Sheng Li, Kun Wang. Clinical Efficacy of Tumor Organoid-Guided Cancer Therapy for Locally Advanced Unresectable or Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-06-01.
Developing biomarker assays to accelerate tuberculosis drug development: defining target product profiles
Authors: Stephen H Gillespie, Andrew R DiNardo, Sophia B Georghiou, Wilber Sabiiti, Mikashmi Kohli, Ursula Panzner, Irina Kontsevaya, Norbert Hittel, Lieven J Stuyver, Jia Bin Tan, Reinout van Crevel, Christoph Lange, Thuong Nguyen Thuy Thuong, Jan Heyckendorf, Morten Ruhwald, Norbert Heinrich
Journal: The Lancet Microbe (2024)
Increased PSMA-Targeted 18F-DCFPyL Uptake in Peripheral T-Cell Lymphoma
Authors: Charles J. Milrod, Cory Brown, Anthony E. Mega
Journal: Clinical Nuclear Medicine (2024)

Abstract Peripheral T-cell lymphomas are a heterogenous group of lymphomas with a high rate of extranodal disease. We present a case of increased 18 F-DCFPyL uptake in peripheral T-cell lymphoma of subcutaneous tissue and bone. Familiarity with the increased 18 F-DCFPyL uptake and extranodal presentation of peripheral T-cell lymphomas can avoid misinterpretation for metastatic disease.
BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug
Authors: Takuya Fujimoto, Fuminori Teraishi, Noriyuki Kanehira, Tomoyuki Tajima, Yoshinori Sakurai, Natsuko Kondo, Masahiro Yamagami, Atsushi Kuwada, Akira Morihara, Mizuki Kitamatsu, Atsushi Fujimura, Minoru Suzuki, Yutaka Takaguchi, Kunitoshi Shigeyasu, Toshiyoshi Fujiwara, Hiroyuki Michiue
Journal: Biomaterials (2024)
Comparison of fidaxomicin, thuricin CD, vancomycin and nisin highlights the narrow spectrum nature of thuricin CD
Authors: L. Walsh, A. Lavelle, PM O’Connor, C. Hill, R. P. Ross
Journal: Gut Microbes (2024)

Vancomycin and metronidazole are commonly used treatments for Clostridioides difficile infection (CDI). However, these antibiotics have been associated with high levels of relapse in patients. Fidaxomicin is a new treatment for CDI that is described as a narrow spectrum antibiotic that is minimally active on the commensal bacteria of the gut microbiome. The aim of this study was to compare the effect of fidaxomicin on the human gut microbiome with a number of narrow (thuricin CD) and broad spectrum (vancomycin and nisin) antimicrobials. The spectrum of activity of each antimicrobial was tested against 47 bacterial strains by well-diffusion assay. Minimum inhibitory concentrations (MICs) were calculated against a select number of these strains. Further, a pooled fecal slurry of 6 donors was prepared and incubated for 24 h with 100 µM of each antimicrobial in a mini-fermentation system together with a no-treatment control. Fidaxomicin, vancomycin, and nisin were active against most gram positive bacteria tested in vitro, although fidaxomicin and vancomycin produced larger zones of inhibition compared to nisin. In contrast, the antimicrobial activity of thuricin CD was specific to C. difficile and some Bacillus spp. The MICs showed similar results. Thuricin CD exhibited low MICs (<3.1 µg/mL) for C. difficile and Bacillus firmus, whereas fidaxomicin, vancomycin, and nisin demonstrated lower MICs for all other strains tested when compared to thuricin CD. The narrow spectrum of thuricin CD was also observed in the gut model system. We conclude that the spectrum of activity of fidaxomicin is comparable to that of the broad-spectrum antibiotic vancomycin in vitro and the broad spectrum bacteriocin nisin in a complex community.
A Soft‐Tissue Driven Bone Remodeling Algorithm for Mandibular Residual Ridge Resorption Based on Patient CT Image Data
Authors: Jingxiao Zhong, Wenwei Huang, Rohana Ahmad, Junning Chen, Chi Wu, Jingrui Hu, Keke Zheng, Michael V. Swain, Qing Li
Journal: Advanced Healthcare Materials (2024)

The role of the biomechanical stimulation generated from soft tissue has not been well quantified or separated from the self-regulated hard tissue remodeling governed by Wolff's Law. Prosthodontic overdentures, commonly used to restore masticatory functions, can cause localized ischemia and inflammation as they often compress patients' oral mucosa and impede local circulation. This biomechanical stimulus in mucosa is found to accelerate the self-regulated residual ridge resorption (RRR), posing ongoing clinical challenges. Based on the dedicated long-term clinical datasets, this work develops an in-silico framework with a combination of techniques, including advanced image post-processing, patient-specific finite element models and unsupervised machine learning Self-Organizing map algorithm, to identify the soft tissue induced RRR and quantitatively elucidate the governing relationship between the RRR and hydrostatic pressure in mucosa. The proposed governing equation has not only enabled a predictive simulation for RRR as showcased in this study, providing a biomechanical basis for optimizing prosthodontic treatments, but also extended the understanding of the mechanobiological responses in the soft-hard tissue interfaces and the role in bone remodeling.
A genetically engineered neuronal membrane-based nanotoxoid elicits protective immunity against neurotoxins
Authors: Zhongyuan Guo, Audrey T. Zhu, Xiaoli Wei, Yao Jiang, Yiyan Yu, Ilkoo Noh, Weiwei Gao, Ronnie H. Fang, Liangfang Zhang
Journal: Bioactive Materials (2024)

Given their dangerous effects on the nervous system, neurotoxins represent a significant threat to public health. Various therapeutic approaches, including chelating agents, receptor decoys, and toxin-neutralizing antibodies, have been explored. While prophylactic vaccines are desirable, it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins. To address this, we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles. A genetically modified cell line with constitutive overexpression of the α7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind to α-bungarotoxin, a model neurotoxin. This abrogates the biological activity of the toxin, enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system. When co-administered with an immunological adjuvant, a strong humoral response against α-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin. Overall, this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.
Ultrasound-triggered three dimensional hyaluronic acid hydrogel promotes in vitro and in vivo reprogramming into induced pluripotent stem cells
Authors: Deogil Kim, Min-Ju Lee, Yoshie Arai, Jinsung Ahn, Gun Woo Lee, Soo-Hong Lee
Journal: Bioactive Materials (2024)

Cellular reprogramming technologies have been developed with different physicochemical factors to improve the reprogramming efficiencies of induced pluripotent stem cells (iPSCs). Ultrasound is a clinically applied noncontact biophysical factor known for regulating various cellular behaviors but remains uninvestigated for cellular reprogramming. Here, we present a new reprogramming strategy using low-intensity ultrasound (LIUS) to improve cellular reprogramming of iPSCs in vitro and in vivo. Under 3D microenvironment conditions, increased LIUS stimulation shows enhanced cellular reprogramming of the iPSCs. The cellular reprogramming process facilitated by LIUS is accompanied by increased mesenchymal to epithelial transition and histone modification. LIUS stimulation transiently modulates the cytoskeletal rearrangement, along with increased membrane fluidity and mobility to increase HA/CD44 interactions. Furthermore, LIUS stimulation with HA hydrogel can be utilized in application of both human cells and in vivo environment, for enhanced reprogrammed cells into iPSCs. Thus, LIUS stimulation with a combinatorial 3D microenvironment system can improve cellular reprogramming in vitro and in vivo environments, which can be applied in various biomedical fields.
SMYD2 induced PGC1α methylation promotes stemness maintenance of glioblastoma stem cells
Authors: Mengdie Li, Zhixiang Zhang, Liuguijie He, Xiefeng Wang, Jianxing Yin, Xiuxing Wang, Yongping You, Xu Qian, Xin Ge, Zhumei Shi
Journal: Neuro-Oncology (2024)

The high fatality rate of glioblastoma (GBM) is attributed to glioblastoma stem cells (GSCs), which exhibit heterogeneity and therapeutic resistance. Metabolic plasticity of mitochondria is the hallmark of GSCs. Targeting mitochondrial biogenesis of GSCs is crucial for improving clinical prognosis in GBM patients.
Reduced congestion and improved response to a fluid/sodium challenge in chronic heart failure patients after initiation of sacubitril/valsartan: The <scp>NATRIUM‐HF</scp> study
Authors: Alexandre Mebazaa, Beth A. Davison, Jan Biegus, Christopher Edwards, Gillian Murtagh, Christos Varounis, Hamlet Hayrapetyan, Hamayak Sisakian, Victor R. Ter‐Grigoryan, Koji Takagi, Maria Novosadova, Piotr Ponikowski, Gad Cotter
Journal: European Journal of Heart Failure (2024)
Quantifying the stochastic component of epigenetic aging
Authors: Huige Tong, Varun B. Dwaraka, Qingwen Chen, Qi Luo, Jessica A. Lasky-Su, Ryan Smith, Andrew E. Teschendorff
Journal: Nature Aging (2024)

Abstract DNA methylation clocks can accurately estimate chronological age and, to some extent, also biological age, yet the process by which age-associated DNA methylation (DNAm) changes are acquired appears to be quasi-stochastic, raising a fundamental question: how much of an epigenetic clock’s predictive accuracy could be explained by a stochastic process of DNAm change? Here, using DNAm data from sorted immune cells, we build realistic simulation models, subsequently demonstrating in over 22,770 sorted and whole-blood samples from 25 independent cohorts that approximately 66–75% of the accuracy underpinning Horvath’s clock could be driven by a stochastic process. This fraction increases to 90% for the more accurate Zhang’s clock, but is lower (63%) for the PhenoAge clock, suggesting that biological aging is reflected by nonstochastic processes. Confirming this, we demonstrate that Horvath’s age acceleration in males and PhenoAge’s age acceleration in severe coronavirus disease 2019 cases and smokers are not driven by an increased rate of stochastic change but by nonstochastic processes. These results significantly deepen our understanding and interpretation of epigenetic clocks.
Influence of grandchildren on COVID-19 vaccination uptake among older adults in China: a parallel-group, cluster-randomized controlled trial
Authors: Junye Bian, Weijie Zhang, Zhihui Guo, Xinyi Li, Leiwen Fu, Zhen Lu, Thomas Fitzpatrick, Yinghui Sun, Yanxiao Gao, Yuanyi Chen, Qi Liu, Longtao He, Caijun Sun, Huachun Zou
Journal: Nature Aging (2024)
Single-cell transcriptomic analyses reveal distinct immune cell contributions to epithelial barrier dysfunction in checkpoint inhibitor colitis
Authors: Molly Fisher Thomas, Kamil Slowikowski, Kasidet Manakongtreecheep, Pritha Sen, Nandini Samanta, Jessica Tantivit, Mazen Nasrallah, Leyre Zubiri, Neal P. Smith, Alice Tirard, Swetha Ramesh, Benjamin Y. Arnold, Linda T. Nieman, Jonathan H. Chen, Thomas Eisenhaure, Karin Pelka, Yuhui Song, Katherine H. Xu, Vjola Jorgji, Christopher J. Pinto, Tatyana Sharova, Rachel Glasser, PuiYee Chan, Ryan J. Sullivan, Hamed Khalili, Dejan Juric, Genevieve M. Boland, Michael Dougan, Nir Hacohen, Bo Li, Kerry L. Reynolds, Alexandra-Chloé Villani
Journal: Nature Medicine (2024)
Systematic epigenome editing captures the context-dependent instructive function of chromatin modifications
Authors: Cristina Policarpi, Marzia Munafò, Stylianos Tsagkris, Valentina Carlini, Jamie A. Hackett
Journal: Nature Genetics (2024)

Abstract Chromatin modifications are linked with regulating patterns of gene expression, but their causal role and context-dependent impact on transcription remains unresolved. Here we develop a modular epigenome editing platform that programs nine key chromatin modifications, or combinations thereof, to precise loci in living cells. We couple this with single-cell readouts to systematically quantitate the magnitude and heterogeneity of transcriptional responses elicited by each specific chromatin modification. Among these, we show that installing histone H3 lysine 4 trimethylation (H3K4me3) at promoters can causally instruct transcription by hierarchically remodeling the chromatin landscape. We further dissect how DNA sequence motifs influence the transcriptional impact of chromatin marks, identifying switch-like and attenuative effects within distinct cis contexts. Finally, we examine the interplay of combinatorial modifications, revealing that co-targeted H3K27 trimethylation (H3K27me3) and H2AK119 monoubiquitination (H2AK119ub) maximizes silencing penetrance across single cells. Our precision-perturbation strategy unveils the causal principles of how chromatin modification(s) influence transcription and dissects how quantitative responses are calibrated by contextual interactions.
Streptococcus pyogenes carriage and infection within households in The Gambia: a longitudinal cohort study
Authors: Edwin P Armitage, Gabrielle de Crombrugghe, Alexander J Keeley, Elina Senghore, Fatoumata E Camara, Musukoi Jammeh, Amat Bittaye, Haddy Ceesay, Isatou Ceesay, Bunja Samateh, Muhammed Manneh, Beate Kampmann, Claire E Turner, Adam Kucharski, Anne Botteaux, Pierre R Smeesters, Thushan I de Silva, Michael Marks, Abdul Karim Sesay, Saikou Bah, Annette Erhart, Anna Roca, Peggy-Estelle Tiencheu, Sona Jabang, Saffiatou Darboe, Martin Antonio, Lamin Jaiteh, Karen Forrest
Journal: The Lancet Microbe (2024)

Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S pyogenes skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both S pyogenes asymptomatic carriage and infection in a high-burden setting.
Sleep interventions for adults admitted to psychiatric inpatient settings: A systematic scoping review
Authors: Anne M. Aboaja, Lindsay H. Dewa, Amanda E. Perry, Jon F. Carey, Rachel Steele, Ahmed Abdelsamie, Gies T.A. Alhasan, Ishwari S. Sharma, Florence Watson, Scott A. Cairney
Journal: Sleep Medicine Reviews (2024)

Sleep disturbances are common, affecting over half of adults with a mental disorder. For those admitted to a psychiatric ward, difficulties with sleep, particularly insomnia, are compounded by factors relating to the inpatient setting. We conducted a scoping review of sleep intervention studies involving adults admitted to psychiatric settings. We categorised the different types of sleep interventions and identified the effects on sleep and other mental and physical health outcomes. Instruments used to measure sleep were also examined. The search strategy yielded 4780 studies, of which 28 met the inclusion criteria. There was evidence of more non-pharmacological than pharmacological interventions having been tested in inpatient settings. Results indicated that non-pharmacological interventions based on cognitive behaviour therapy for insomnia improve sleep and may improve mental and physical health. Several distinct sleep measures were used in the studies. Gaps in the literature were identified, highlighting the importance of research into a wider range of sleep interventions tested against robust controls, using validated measures of sleep with evaluation of additional mental and physical health outcomes among a large sample size of adults in the psychiatric inpatient settings.
cGAS suppresses β-cell proliferation by a STING-independent but CEBPβ-dependent mechanism
Authors: Zixin Cai, Yan Yang, Jiaxin Zhong, Yujiao Ji, Ting Li, Jing Luo, Shanbiao Hu, Hairong Luo, Yan Wu, Feng Liu, Jingjing Zhang
Journal: Metabolism (2024)
Adjustment of p values for multiple hypotheses: why, when and how
Authors: Stian Lydersen
Journal: Annals of the Rheumatic Diseases (2024)

It is quite common to investigate multiple hypotheses in a single study. For example, a researcher may want to investigate the effect on several outcome variables or at different time points, compare more than two groups or undertake separate analyses for subgroups. This increases the probability of type I errors. Different procedures for multiplicity adjustment are available to control the probability of type I errors. In the present article, we describe some methods for multiplicity adjustment, along with recommendations.