tbuckley/cabot-search huggingface dataset:
Investigation of Presumptive HIV Transmission Associated with Receipt of Platelet-Rich Plasma Microneedling Facials at a Spa Among Former Spa Clients — New Mexico, 2018–2023
Authors: Anna M. Stadelman-Behar, Mika N. Gehre, Liana Atallah, Tegan Clarke, Ana-Alicia Leonso, Francella Jojola, HaoQiang Zheng, Hongwei Jia, Sheryl B. Lyss, William M. Switzer, Scott P. Grytdal, Miranda Durham, N. Mariam Salas, Marla Sievers, Chad Smelser
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

HIV transmitted through cosmetic injection services via contaminated blood has not been previously documented. During summer 2018, the New Mexico Department of Health (NMDOH) was notified of a diagnosis of HIV infection in a woman with no known HIV risk factors who reported exposure to needles from cosmetic platelet-rich plasma microneedling facials (vampire facials) received at a spa in spring 2018. An investigation of the spa's services began in summer 2018, and NMDOH and CDC identified four former spa clients, and one sexual partner of a spa client, all of whom received HIV infection diagnoses during 2018-2023, despite low reported behavioral risks associated with HIV acquisition. Nucleotide sequence analysis revealed highly similar HIV strains among all cases. Although transmission of HIV via unsterile injection practices is a known risk, determining novel routes of HIV transmission among persons with no known HIV risk factors is important. This investigation identified an HIV cluster associated with receipt of cosmetic injection services at an unlicensed facility that did not follow recommended infection control procedures or maintain client records. Requiring adequate infection control practices and maintenance of client records at spa facilities offering cosmetic injection services can help prevent the transmission of HIV and other bloodborne pathogens and ensure adequate traceback and notification in the event of adverse clinical outcomes, respectively.
Development of composite functional tissue sheets using hiPSC-CMs and hADSCs to improve the cardiac function after myocardial infarction
Authors: Jingbo Zhang, Junjun Li, Xiang Qu, Yuting Liu, Lifu Sun, Akima Harada, Ying Hua, Nagako Sougawa, Akiko Tabata, Li Liu, Shigeru Miyagawa
Journal: Bioactive Materials (2024)

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in therapy of ischemic heart disease. However, there are still remaining issues that limit the therapeutic efficacy, such as immune rejection and low retention of hiPSC-CMs. Human adipose mesenchymal stromal cells (hADSCs) have been reported to be able to regulate the immune response, promote angiogenesis and promote the maturation of hiPSC-CMs. In this study, we co-cultured these two types of cells on fiber scaffold made of biodegradable poly (D,L-lactic-
Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction
Authors: Kevin Wiehe, Kevin O. Saunders, Victoria Stalls, Derek W. Cain, Sravani Venkatayogi, Joshua S. Martin Beem, Madison Berry, Tyler Evangelous, Rory Henderson, Bhavna Hora, Shi-Mao Xia, Chuancang Jiang, Amanda Newman, Cindy Bowman, Xiaozhi Lu, Mary E. Bryan, Joena Bal, Aja Sanzone, Haiyan Chen, Amanda Eaton, Mark A. Tomai, Christopher B. Fox, Ying K. Tam, Christopher Barbosa, Mattia Bonsignori, Hiromi Muramatsu, S. Munir Alam, David C. Montefiori, Wilton B. Williams, Norbert Pardi, Ming Tian, Drew Weissman, Frederick W. Alt, Priyamvada Acharya, Barton F. Haynes
Journal: Cell Host & Microbe (2024)
Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms
Authors: Xilong Cui, Fanhui Liu, Shuang Cai, Tingting Wang, Sidi Zheng, Xinshu Zou, Linlin Wang, Siqi He, Yanhua Li, Zhiyun Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2024)

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.
Proteomics couples electrical remodelling to inflammation in a murine model of heart failure with sinus node dysfunction
Authors: Konstantin Kahnert, Luca Soattin, Robert W Mills, Claire Wilson, Svetlana Maurya, Andrea Sorrentino, Sami Al-Othman, Roman Tikhomirov, Yordi J van de Vegte, Finn B Hansen, Jonathan Achter, Wei Hu, Min Zi, Matthew Smith, Pim van der Harst, Morten S Olesen, Kristine Boisen Olsen, Jytte Banner, Thomas H L Jensen, Henggui Zhang, Mark R Boyett, Alicia D’Souza, Alicia Lundby
Journal: Cardiovascular Research (2024)

Abstract Aims In patients with heart failure (HF), concomitant sinus node dysfunction (SND) is an important predictor of mortality, yet its molecular underpinnings are poorly understood. Using proteomics, this study aimed to dissect the protein and phosphorylation remodelling within the sinus node in an animal model of HF with concurrent SND. Methods and results We acquired deep sinus node proteomes and phosphoproteomes in mice with heart failure and SND and report extensive remodelling. Intersecting the measured (phospho)proteome changes with human genomics pharmacovigilance data, highlighted downregulated proteins involved in electrical activity such as the pacemaker ion channel, Hcn4. We confirmed the importance of ion channel downregulation for sinus node physiology using computer modelling. Guided by the proteomics data, we hypothesized that an inflammatory response may drive the electrophysiological remodeling underlying SND in heart failure. In support of this, experimentally induced inflammation downregulated Hcn4 and slowed pacemaking in the isolated sinus node. From the proteomics data we identified proinflammatory cytokine-like protein galectin-3 as a potential target to mitigate the effect. Indeed, in vivo suppression of galectin-3 in the animal model of heart failure prevented SND. Conclusion Collectively, we outline the protein and phosphorylation remodeling of SND in heart failure, we highlight a role for inflammation in electrophysiological remodelling of the sinus node, and we present galectin-3 signalling as a target to ameliorate SND in heart failure.
Large language models for preventing medication direction errors in online pharmacies
Authors: Cristobal Pais, Jianfeng Liu, Robert Voigt, Vin Gupta, Elizabeth Wade, Mohsen Bayati
Journal: Nature Medicine (2024)

Abstract Errors in pharmacy medication directions, such as incorrect instructions for dosage or frequency, can increase patient safety risk substantially by raising the chances of adverse drug events. This study explores how integrating domain knowledge with large language models (LLMs)—capable of sophisticated text interpretation and generation—can reduce these errors. We introduce MEDIC (medication direction copilot), a system that emulates the reasoning of pharmacists by prioritizing precise communication of core clinical components of a prescription, such as dosage and frequency. It fine-tunes a first-generation LLM using 1,000 expert-annotated and augmented directions from Amazon Pharmacy to extract the core components and assembles them into complete directions using pharmacy logic and safety guardrails. We compared MEDIC against two LLM-based benchmarks: one leveraging 1.5 million medication directions and the other using state-of-the-art LLMs. On 1,200 expert-reviewed prescriptions, the two benchmarks respectively recorded 1.51 (confidence interval (CI) 1.03, 2.31) and 4.38 (CI 3.13, 6.64) times more near-miss events—errors caught and corrected before reaching the patient—than MEDIC. Additionally, we tested MEDIC by deploying within the production system of an online pharmacy, and during this experimental period, it reduced near-miss events by 33% (CI 26%, 40%). This study shows that LLMs, with domain expertise and safeguards, improve the accuracy and efficiency of pharmacy operations.
A dietary commensal microbe enhances antitumor immunity by activating tumor macrophages to sequester iron
Authors: Garima Sharma, Amit Sharma, Inhae Kim, Dong Gon Cha, Somi Kim, Eun Seo Park, Jae Gyun Noh, Juhee Lee, Ja Hyeon Ku, Yoon Ha Choi, JungHo Kong, Haena Lee, Haeun Ko, Juhun Lee, Anna Notaro, Seol Hee Hong, Joon Haeng Rhee, Sang Geon Kim, Cristina De Castro, Antonio Molinaro, Kunyoo Shin, Sanguk Kim, Jong Kyoung Kim, Dipayan Rudra, Sin-Hyeog Im
Journal: Nature Immunology (2024)
SPTLC3 Is Essential for Complex I Activity and Contributes to Ischemic Cardiomyopathy
Authors: Anna Kovilakath, Adolfo G. Mauro, Yolander A. Valentine, Frank J. Raucci, Maryam Jamil, Christiane Carter, Jeremy Thompson, Qun Chen, Gisela Beutner, Yang Yue, Jeremy Allegood, Xiaoxin X. Wang, Jordan Dail, Teja Devarakonda, Komuraiah Myakala, Jolene J. Windle, Mark A. Subler, David Montefusco, Belinda Willard, Ali Javaheri, Tytus Bernas, Sushil K. Mahata, Moshe Levi, Jinze Liu, George A. Porter, Edward J. Lesnefsky, Fadi N. Salloum, L. Ashley Cowart
Journal: Circulation (2024)

Dysregulated metabolism of bioactive sphingolipids, including ceramides and sphingosine-1-phosphate, has been implicated in cardiovascular disease, although the specific species, disease contexts, and cellular roles are not completely understood. Sphingolipids are produced by the serine palmitoyltransferase enzyme, canonically composed of 2 subunits, SPTLC1 (serine palmitoyltransferase long chain base subunit 1) and SPTLC2 (serine palmitoyltransferase long chain base subunit 2). Noncanonical sphingolipids are produced by a more recently described subunit, SPTLC3 (serine palmitoyltransferase long chain base subunit 3).
Identifying latent genetic interactions in genome-wide association studies using multiple traits
Authors: Andrew J Bass, Shijia Bian, Aliza P Wingo, Thomas S Wingo, David J Cutler, Michael P Epstein
Journal: Genome Medicine (2024)

Abstract The "missing" heritability of complex traits may be partly explained by genetic variants interacting with other genes or environments that are difficult to specify, observe, and detect. We propose a new kernel-based method called Latent Interaction Testing (LIT) to screen for genetic interactions that leverages pleiotropy from multiple related traits without requiring the interacting variable to be specified or observed. Using simulated data, we demonstrate that LIT increases power to detect latent genetic interactions compared to univariate methods. We then apply LIT to obesity-related traits in the UK Biobank and detect variants with interactive effects near known obesity-related genes (URL: https://CRAN.R-project.org/package=lit ).
Improving Patient Information and Enhanced Consent in Urology: The Impact of Simulation and Multimedia Tools. A Systematic Literature Review from the European Association of Urology Patient Office
Authors: Carlotta Nedbal, Patrick Juliebø-Jones, Eamonn Rogers, James N'Dow, Maria Ribal, Jens Rassweiler, Evangelos Liatsikos, Hein Van Poppel, Bhaskar Kumar Somani
Journal: European Urology (2024)
Combination of a <scp>TGF</scp>‐β ligand trap (<scp>RAP‐GRL</scp>) and <scp><i>TMPRSS6</i>‐ASO</scp> is superior for correcting β‐thalassemia
Authors: Amaliris Guerra, Nolan Hamilton, Ariel Rivera, Perry Demsko, Shuling Guo, Stefano Rivella
Journal: American Journal of Hematology (2024)

Abstract A recently approved drug that induces erythroid cell maturation (luspatercept) has been shown to improve anemia and reduce the need for blood transfusion in non‐transfusion‐dependent as well as transfusion‐dependent β‐thalassemia (BT) patients. Although these results were predominantly positive, not all the patients showed the expected increase in hemoglobin (Hb) levels or transfusion burden reduction. Additional studies indicated that administration of luspatercept in transfusion‐dependent BT was associated with increased erythropoietic markers, decreased hepcidin levels, and increased liver iron content. Altogether, these studies suggest that luspatercept may necessitate additional drugs for improved erythroid and iron management. As luspatercept does not appear to directly affect iron metabolism, we hypothesized that TMPRSS6 ‐ASO could improve iron parameters and iron overload when co‐administered with luspatercept. We used an agent analogous to murine luspatercept (RAP‐GRL) and another novel therapeutic, IONIS TMPRSS6‐LRx ( TMPRSS6‐ ASO), a hepcidin inducer, to treat non‐transfusion‐dependent BT‐intermedia mice. Our study shows that RAP‐GRL alone improved red blood cell (RBC) production, with no or limited effect on splenomegaly and iron parameters. In contrast, TMPRSS6‐ ASO improved RBC measurements, ameliorated splenomegaly, and improved iron overload most effectively. Our results provide pre‐clinical support for combining TMPRSS6‐ ASO and luspatercept in treating BT, as these drugs together show potential for simultaneously improving both erythroid and iron parameters in BT patients.
Ambient pollen exposure and pollen allergy symptom severity in the EPOCHAL study
Authors: Axel Luyten, Alexandra Bürgler, Sarah Glick, Marek Kwiatkowski, Regula Gehrig, Minaya Beigi, Karin Hartmann, Marloes Eeftens
Journal: Allergy (2024)

Abstract Background Ambient pollen exposure causes nasal, ocular, and pulmonary symptoms in allergic individuals, but the shape of the exposure–response association is not well characterized. We evaluated this association and determined (1) whether symptom severity differs between subpopulations; (2) how the association changes over the course of the pollen season; and (3) which pollen exposure time lags affect symptoms. Methods Adult study participants ( n = 396) repeatedly scored severity of nasal, ocular, and pulmonary allergic symptoms, resulting in three composite symptom scores. We calculated hourly individually relevant pollen exposure to seven allergenic plants (alder, ash, birch, hazel, grasses, mugwort, and ragweed) considering personal sensitization and exposure time lags of up to 96 h. We fitted generalized additive mixed models, with a random personal intercept, adjusting for weather and air pollution as potential time‐varying confounders. Results We identified a clear nonlinear positive association between pollen exposure and ocular and nasal symptom severity in the pollen allergy group: Symptom severity increased steeply with increasing exposure initially, but attenuated beyond approximately 80 pollen/m 3 . We found no evidence of an exposure threshold, below which no symptoms occur. While recent pollen exposure in the last approximately 5 h affected symptoms most, associations lingered for up to 60 h. Grass pollen exposure (compared to tree pollen) and younger age (18–30 years, as opposed to 30–65 years) were both associated with higher nasal and ocular symptom severity. Conclusions The lack of a threshold and attenuated dose–response curve may have implications for pollen warning systems, which may be revised to include multiday pollen concentrations in the future.
Continuous improvement of FEV<sub>1</sub> in severe eosinophilic asthmatics on anti‐interleukin‐5 therapy
Authors: Alain Michils, Jean‐Pierre Makhoul, Nathan Blekic, Amaryllis Haccuria, Silvia Perez‐Bogerd, Andreï Malinovschi, Alain Van Muylem
Journal: Allergy (2024)
Genetic and microbial determinants of azoxymethane-induced colorectal tumor susceptibility in Collaborative Cross mice and their implication in human cancer
Authors: Dan Li, Chenhan Zhong, Mengyuan Yang, Li He, Hang Chang, Ning Zhu, Susan E Celniker, David W Threadgill, Antoine M Snijders, Jian-Hua Mao, Ying Yuan
Journal: Gut Microbes (2024)

The insights into interactions between host genetics and gut microbiome (GM) in colorectal tumor susceptibility (CTS) remains lacking. We used Collaborative Cross mouse population model to identify genetic and microbial determinants of Azoxymethane-induced CTS. We identified 4417 CTS-associated single nucleotide polymorphisms (SNPs) containing 334 genes that were transcriptionally altered in human colorectal cancers (CRCs) and consistently clustered independent human CRC cohorts into two subgroups with different prognosis. We discovered a set of genera in early-life associated with CTS and defined a 16-genus signature that accurately predicted CTS, the majority of which were correlated with human CRCs. We identified 547 SNPs associated with abundances of these genera. Mediation analysis revealed GM as mediators partially exerting the effect of SNP UNC3869242 within Duox2 on CTS. Intestine cell-specific depletion of Duox2 altered GM composition and contribution of Duox2 depletion to CTS was significantly influenced by GM. Our findings provide potential novel targets for personalized CRC prevention and treatment.
Reducing the risks of prenatal opioid exposure in children
Authors: Xuerong Wen, Todd Brothers, Kristina E Ward, Stephen Kogut
Journal: BMJ (2024)

According to 2019 data from the Centers for Disease Control and Prevention, approximately 7% of women in the United States were prescribed opioids during pregnancy. 1Prescription opioid use among pregnant women with private insurance or Medicaid coverage in the US is prevalent. 2 3In particular, the incidence of neonatal abstinence syndrome, as a result of drug withdrawal, increased by 83% from 2010 to 2017, albeit while declining by 18% between 2016 and 2020. 4 5However, the risk of neurodevelopmental disorders in children with prenatal opioid exposure remains unclear because previous studies had small sample sizes and limited follow-up periods. 6 7The linked study by Kang and colleagues (doi:10.1136/bmj-2023-077664)addressed this research gap using data from the National Health Insurance Service of South Korea. 8Their study cohort included 3 128 571 children and 2 299 664 mothers, further categorized into subgroups according to prescription opioid dose, duration, and exposure periods as well as the frequency of prescriptions.The authors adjusted for many confounding factors, conducted stratification analyses, examined dose responses, and performed interaction analyses between opioid use and corresponding medical indications.
The Definition, Acronyms, Nomenclature, and Classification of Angioedema: AAAAI, ACAAI, ACARE, and APAACI DANCE Consensus
Authors: Avner Reshef, Thomas Buttgereit, Stephen D. Betschel, Teresa Caballero, Henriette Farkas, Anete S. Grumach, Michihiro Hide, Ankur K. Jindal, Hilary Longhurst, Jonathan Peter, Marc A. Riedl, Yuxiang Zhi, Werner Aberer, Mohamed Abuzakouk, Tariq Al Farsi, Nashat Al Sukaiti, Mona Al-Ahmad, Sabine Altrichter, Emel Aygören-Pürsün, Maria Luisa Baeza, Noemi Anna Bara, Andrea Bauer, Jonathan A. Bernstein, Isabelle Boccon-Gibod, Hanna Bonnekoh, Laurence Bouillet, Zenon Brzoza, Anette Bygum, Oscar Calderon, Regis de Albuquerque Campos, Freya Helena Campos Romero, Mauro Cancian, Herberto Jose Chong-Neto, George Christoff, Stefan Cimbollek, Danny M. Cohn, Timothy Craig, Inna Danilycheva, Razvigor Darlenski, Aurélie Du-Thanh, Luis Felipe Ensina, Daria Fomina, Luz Fonacier, Atsushi Fukunaga, Asli Gelincik, Pedro Giavina-Bianchi, Kiran Godse, Mark Gompels, Margarida Goncalo, Maia Gotua, Guillermo Guidos-Fogelbach, Mar Guilarte, Alicja Kasperska-Zajac, Constance H. Katelaris, Tamar Kinaciyan, Pavel Kolkhir, Kanokvalai Kulthanan, Marcin Kurowski, Elena Latysheva, Antti Lauerma, David Launay, Ramon Lleonart, William Lumry, Alejandro Malbran, Ramzy Mohammed Ali, Iman Nasr, Sandra Nieto-Martinez, Claudio Parisi, Ruby Pawankar, Macarena Piñero-Saavedra, Todor A. Popov, Grzegorz Porebski, Alicia Prieto Garcia, Polina Pyatilova, Michael Rudenko, Bulent Enis Sekerel, Faradiba Sarquis Serpa, Farrukh Sheikh, Frank Siebenhaar, Angèle Soria, Maria Staevska, Petra Staubach, Marcin Stobiecki, Simon Francis Thomsen, Massimo Triggiani, Anna Valerieva, Solange Valle, Nguyen Van Dinh, Carolina Elisa Vera Ayala, Anna Zalewska-Janowska, Andrea Zanichelli, Markus Magerl, Marcus Maurer
Journal: Journal of Allergy and Clinical Immunology (2024)
Mutation of neurotrophic tyrosine receptor kinase can promote pan-cancer immunity and the efficacy of immunotherapy
Authors: Congren Wang, Yingying Li, Jinyuan Huang, Huimeng Yan, Bin Zhao
Journal: Molecular Cancer (2024)

The Neurotrophic tyrosine receptor kinase (NTRK) family plays important roles in tumor progression and is involved in tumor immunogenicity. Here, we conducted a comprehensive bioinformatic and clinical analysis to investigate the characteristics of NTRK mutations and their association with the outcomes in pan-cancer immunotherapy. In 3888 patients across 12 cancer types, patients with NTRK-mutant tumors showed more benefit from immunotherapy in terms of objective response rate (ORR; 41.7% vs. 27.5%; P < 0.001), progress-free survival (PFS; HR = 0.80; 95% CI, 0.68-0.96; P = 0.01), and overall survival (OS; HR = 0.71; 95% CI, 0.61-0.82; P < 0.001). We further constructed and validated a nomogram to estimate survival probabilities after the initiation of immunotherapy. Multi-omics analysis on intrinsic and extrinsic immune landscapes indicated that NTRK mutation was associated with enhanced tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses. In summary, NTRK mutation may promote cancer immunity and indicate favorable outcomes in immunotherapy. Our results have implications for treatment decision-making and developing immunotherapy for personalized care.
Big alcohol: Universities and schools urged to throw out industry-funded public health advice
Authors: Madlen Davies, Hristio Boytchev
Journal: BMJ (2024)

Universities and schools are being urged to join a growing movement in Ireland and the UK that seeks to drive out the alcohol industry from any influence on public health advice on drinking.A campaign in Ireland has led to educational programmes funded by the alcohol industry being removed from schools. 1 But industry backed groups still provide alcohol education in UK schools, including a