tbuckley/cabot-search huggingface dataset:
Risedronate-functionalized manganese-hydroxyapatite amorphous particles: A potent adjuvant for subunit vaccines and cancer immunotherapy
Authors: Xiuli Zhang, Mingjing Wei, Zhigang Zhang, Yarong Zeng, Feihong Zou, Sibo Zhang, Zhiping Wang, Fentian Chen, Hualong Xiong, Yufang Li, Lizhi Zhou, Tingting Li, Qingbing Zheng, Hai Yu, Jun Zhang, Ying Gu, Qinjian Zhao, Shaowei Li, Ningshao Xia
Journal: Journal of Controlled Release (2024)

The cGAS-STING pathway and the Mevalonate Pathway are druggable targets for vaccine adjuvant discovery. Manganese (Mn) and bisphosphonates are known to exert adjuvant effects by targeting these two pathways, respectively. This study found the synergistic potential of the two pathways in enhancing immune response. Risedronate (Ris) significantly amplified the Mn adjuvant early antibody response by 166-fold and fortified its cellular immunity. However, direct combination of Mn2+ and Ris resulted in increased adjuvant toxicity (40% mouse mortality). By the combination of doping property of hydroxyapatite (HA) and its high affinity for Ris, we designed Ris-functionalized Mn-HA micro-nanoparticles as an organic-inorganic hybrid adjuvant, named MnHARis. MnHARis alleviated adjuvant toxicity (100% vs. 60% survival rate) and exhibited good long-term stability. When formulated with the varicella-zoster virus glycoprotein E (gE) antigen, MnHARis triggered a 274.3-fold increase in IgG titers and a 61.3-fold surge in neutralization titers while maintaining a better long-term humoral immunity compared to the aluminum adjuvant. Its efficacy spanned other antigens, including ovalbumin, HPV18 VLP, and SARS-CoV-2 spike protein. Notably, the cellular immunity elicited by the group of gE + MnHARis was comparable to the renowned Shingrix®. Moreover, intratumoral co-administration with an anti-trophoblast cell surface antigen 2 nanobody revealed synergistic antitumor capabilities. These findings underscore the potential of MnHARis as a potent adjuvant for augmenting vaccine immune responses and improving cancer immunotherapy outcomes.
Combined biolistic and cell penetrating peptide delivery for the development of scalable intradermal DNA vaccines
Authors: Roizza Beth So, Gang Li, Victoria Brentville, Janet M. Daly, James E. Dixon
Journal: Journal of Controlled Release (2024)

Physical-based gene delivery via biolistic methods (such as the Helios gene gun) involve precipitation of nucleic acids onto microparticles and direct transfection through cell membranes of exposed tissue (e.g. skin) by high velocity acceleration. The glycosaminoglycan (GAG)-binding enhanced transduction (GET) system exploits novel fusion peptides consisting of cell-binding, nucleic acid condensing, and cell-penetrating domains, which enable enhanced transfection across multiple cell types. In this study, we combined chemical (GET) and physical (gene gun) DNA delivery systems, and hypothesized the combination would generate enhanced distribution and effective uptake in cells not initially transfected by biolistic penetration. Physicochemical characterization, optimization of bullet contents and transfection experiments in vitro in cell monolayers and engineered tissue demonstrated these formulations transfected efficiently, including DC2.4 dendritic cells. We incorporated these formulations into a biolistic format for gene gun by forming fireable dry bullets obtained via lyophilization (freeze drying). This system is simple and with enhanced scalability compared to conventional methods to generate bullets. Flushed GET bullet contents retained their ability to mediate transfection (17-fold greater and 13-fold greater reporter gene expression than standard spermidine bullets in the absence and presence of serum, respectively). Fired GET bullets in vitro (in cells and collagen gels) and in vivo (mice) showed increased reporter gene transfection compared to untreated controls, whilst maintaining cell viability in vitro and having no obvious toxicity in vivo. Lastly, a SARS-CoV-2 plasmid DNA vaccine with spike (S) protein-receptor binding domain (S-RBD) was delivered by gene gun using GET bullets. Specific T cell and antibody responses comparable to the conventional system were generated. The non-physical and physical combination of GET‑gold-DNA carriers using gene gun shows potential as an alternative DNA delivery method that is scalable for mass deployable vaccination and intradermal gene delivery.
ATP-adenosine axis regulation combined with microneedle assisted photoimmunotherapy to boost the immunotherapy efficiency
Authors: Chaonan Shi, Minglong Chen, Xiaodie Li, Yanping Fu, Dan Yang, Ting Wen, Wanchen Zhao, Ying Sun, Wenhao Wang, Chao Lu, Qiaoli Wu, Chuanbin Wu, Xin Pan, Guilan Quan
Journal: Journal of Controlled Release (2024)
Monitoring of urinary iodine concentration in naval pilots: should iodine be supplemented or limited at coastal stations?
Authors: Jia Zeng, Qi Li, Xiang Lu, Dan-Dan Liu, Rong-Guan Jiao, Yan-Qing Jiang, Yan-Bing Liu, Wan-Qing Xu, Jun Ma, Guo-Li Gu
Journal: Military Medical Research (2024)
Mass Spectrometry Imaging of Organoids to Improve Preclinical Research
Authors: Cristina Zivko, Tae‐Hun Hahm, Cay Tressler, Dalton Brown, Kristine Glunde, Vasiliki Mahairaki
Journal: Advanced Healthcare Materials (2024)

Preclinical models are essential research tools before novel therapeutic or diagnostic methods can be applied to humans. These range from in vitro cell monocultures to vastly more complex animal models, but clinical translation to humans often fails to deliver significant results. Three-dimensional (3D) organoid systems are being increasingly studied to establish physiologically relevant in vitro platforms in a trade-off between the complexity of the research question and the complexity of practical experimental setups. The sensitivity and precision of analytical tools are yet another limiting factors in what can be investigated, and mass spectrometry (MS) is one of the most powerful analytical techniques available to the scientific community. Its innovative use to spatially resolve biological samples has opened many research avenues in the field of MS imaging (MSI). Here, this work aims to explore the current scientific landscape in the application of MSI on organoids, with an emphasis on their combined potential to facilitate and improve preclinical studies.
Neuromodulation interventions in the management of heart failure
Authors: Amr Abdin, Lucas Lauder, Marat Fudim, William T. Abraham, Stefan D. Anker, Michael Böhm, Felix Mahfoud
Journal: European Journal of Heart Failure (2024)

Abstract Despite remarkable improvements in the management of heart failure (HF), HF remains one of the most rapidly growing cardiovascular condition resulting in a substantial burden on healthcare systems worldwide. In clinical practice, however, a relevant proportion of patients are treated with suboptimal combinations and doses lower than those recommended in the current guidelines. Against this background, it remains important to identify new targets and investigate additional therapeutic options to alleviate symptoms and potentially improve prognosis in HF. Therefore, non‐pharmacological interventions targeting autonomic imbalance in HF have been evaluated. This paper aims to review the physiology, available clinical data, and potential therapeutic role of device‐based neuromodulation in HF.
The American Heart Association Emergency Cardiovascular Care 2030 Impact Goals and Call to Action to Improve Cardiac Arrest Outcomes: A Scientific Statement From the American Heart Association
Authors: Raina M. Merchant, Lance B. Becker, Steven C. Brooks, Paul S. Chan, Marina Del Rios, Mary E. McBride, Robert W. Neumar, Jeanette K. Previdi, Anezi Uzendu, Comilla Sasson
Journal: Circulation (2024)

Every 10 years, the American Heart Association (AHA) Emergency Cardiovascular Care Committee establishes goals to improve survival from cardiac arrest. These goals align with broader AHA Impact Goals and support the AHA’s advocacy efforts and strategic investments in research, education, clinical care, and quality improvement programs. This scientific statement focuses on 2030 AHA emergency cardiovascular care priorities, with a specific focus on bystander cardiopulmonary resuscitation, early defibrillation, and neurologically intact survival. This scientific statement also includes aspirational goals, such as establishing cardiac arrest as a reportable disease and mandating reporting of standardized outcomes from different sources; advancing recognition of and knowledge about cardiac arrest; improving dispatch system response, availability, and access to resuscitation training in multiple settings and at multiple time points; improving availability, access, and affordability of defibrillators; providing a focus on early defibrillation, in-hospital programs, and establishing champions for debriefing and review of cardiac arrest events; and expanding measures to track outcomes beyond survival. The ability to track and report data from these broader aspirational targets will potentially require expansion of existing data sets, development of new data sets, and enhanced integration of technology to collect process and outcome data, as well as partnerships of the AHA with national, state, and local organizations. The COVID-19 (coronavirus disease 2019) pandemic, disparities in COVID-19 outcomes for historically excluded racial and ethnic groups, and the longstanding disparities in cardiac arrest treatment and outcomes for Black and Hispanic or Latino populations also contributed to an explicit focus and target on equity for the AHA Emergency Cardiovascular Care 2030 Impact Goals.
Nonsugar Sweeteners—Time for Transparency and Caution
Authors: Allison C. Sylvetsky, Natalia Rebolledo, James W. Krieger
Journal: JAMA Pediatrics (2024)

This Viewpoint discusses the growing presence of nonsugar sweeteners (NSSs) in the food supply and mounting concerns about their use, which suggest that disclosure of the amounts of NSS in food and beverages and restrictions on their use in products marketed to children are warranted.
Prenatal Opioid Use Disorder Treatment—the Importance of Shared Decision-Making
Authors: Max Jordan Nguemeni Tiako, Kelly R. Knight, Davida M. Schiff
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Evaluation of a Large Language Model to Identify Confidential Content in Adolescent Encounter Notes
Authors: Naveed Rabbani, Conner Brown, Michael Bedgood, Rachel L. Goldstein, Jennifer L. Carlson, Natalie M. Pageler, Keith E. Morse
Journal: JAMA Pediatrics (2024)

This cross-sectional study assesses the ability of a language learning model to classify whether a progress note contains confidential information and to identify the specific confidential content in the note.
Diffusely Enhancing Lesions on MRI in DPPX Antibody-Associated Encephalitis
Authors: Mao Liu, Chuan Qin, Dai-Shi Tian
Journal: JAMA Neurology (2024)

This case report describes a diagnosis of dipeptidyl-peptidaselike protein-6 antibody-associated encephalitis in a woman aged 51 years who presented with progressive gait instability, memory impairment, and weight loss.
In vivo imaging of synaptic density in neurodegenerative disorders with positron emission tomography: A systematic review
Authors: Malouke Visser, John T. O’Brien, Elijah Mak
Journal: Ageing Research Reviews (2024)

Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2 A (SV2A) enables quantification of synaptic density in the living human brain. Assessing the regional distribution and severity of synaptic density loss will contribute to our understanding of the pathological processes that precede atrophy in neurodegeneration. In this systematic review, we provide a discussion of in vivo SV2A PET imaging research for quantitative assessment of synaptic density in various dementia conditions: amnestic Mild Cognitive Impairment and Alzheimer’s disease, Frontotemporal dementia, Progressive supranuclear palsy and Corticobasal degeneration, Parkinson’s disease and Dementia with Lewy bodies, Huntington’s disease, and Spinocerebellar Ataxia. We discuss the main findings concerning group differences and clinical-cognitive correlations, and explore relations between SV2A PET and other markers of pathology. Additionally, we touch upon synaptic density in healthy ageing and outcomes of radiotracer validation studies. Studies were identified on PubMed and Embase between 2018 and 2023; last searched on the 3rd of July 2023. A total of 36 studies were included, comprising 5 on normal ageing, 21 clinical studies, and 10 validation studies. Extracted study characteristics were participant details, methodological aspects, and critical findings. In summary, the small but growing literature on in vivo SV2A PET has revealed different spatial patterns of synaptic density loss among various neurodegenerative disorders that correlate with cognitive functioning, supporting the potential role of SV2A PET imaging for differential diagnosis. SV2A PET imaging shows tremendous capability to provide novel insights into the aetiology of neurodegenerative disorders and great promise as a biomarker for synaptic density reduction. Novel directions for future synaptic density research are proposed, including (a) longitudinal imaging in larger patient cohorts of preclinical dementias, (b) multi-modal mapping of synaptic density loss onto other pathological processes, and (c) monitoring therapeutic responses and assessing drug efficacy in clinical trials.
Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension
Authors: Yanjiang Xing, Yangfeng Hou, Tianfei Fan, Ran Gao, Xiaohang Feng, Bolun Li, Junling Pang, Wenjun Guo, Ting Shu, Jinqiu Li, Jie Yang, Qilong Mao, Ya Luo, Xianmei Qi, Peiran Yang, Chaoyang Liang, Hongmei Zhao, Wenhui Chen, Jing Wang, Chen Wang
Journal: Acta Pharmaceutica Sinica B (2024)

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH; however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA-CREB-BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.
Enrichment of Bacteroides fragilis and enterotoxigenic Bacteroides fragilis in CpG island methylator phenotype-high colorectal carcinoma
Authors: Yasutoshi Takashima, Hidetaka Kawamura, Kazuo Okadome, Satoko Ugai, Koichiro Haruki, Kota Arima, Kosuke Mima, Naohiko Akimoto, Jonathan A. Nowak, Marios Giannakis, Wendy S. Garrett, Cynthia L. Sears, Mingyang Song, Tomotaka Ugai, Shuji Ogino
Journal: Clinical Microbiology and Infection (2024)
Safety and efficacy of platelet glycoprotein VI inhibition in acute ischaemic stroke (ACTIMIS): a randomised, double-blind, placebo-controlled, phase 1b/2a trial
Authors: Mikaël Mazighi, Martin Köhrmann, Robin Lemmens, Philippe A Lyrer, Carlos A Molina, Sébastien Richard, Danilo Toni, Yannick Plétan, Anouar Sari, Adeline Meilhoc, Martine Jandrot-Perrus, Sophie Binay, Gilles Avenard, Andrea Comenducci, Jean-Marie Grouin, James C Grotta, Jean François Albucher, Angelika Alonso, Jörg Berrouschot, Charlotte Cordonnier, Sylvie de Raedt, Philippe Desfontaines, Emilie Doche, Dimitri Hemelsoet, Francisco Macian-Montoro, Jaime Masjuan, Michael Obadia, André Peeters, Johann Pelz, Peggy Reiner, Tomas Segura, Joaquin Serena, Igor Sibon, Jose I. Tembl, Stéphane Vannier, Mathieu Zuber
Journal: The Lancet Neurology (2024)
A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research
Authors: Tanya Simuni, Lana M Chahine, Kathleen Poston, Michael Brumm, Teresa Buracchio, Michelle Campbell, Sohini Chowdhury, Christopher Coffey, Luis Concha-Marambio, Tien Dam, Peter DiBiaso, Tatiana Foroud, Mark Frasier, Caroline Gochanour, Danna Jennings, Karl Kieburtz, Catherine M Kopil, Kalpana Merchant, Brit Mollenhauer, Thomas Montine, Kelly Nudelman, Gennaro Pagano, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Caroline M Tanner, Eduardo Tolosa, Daniel Weintraub, Yuge Xiao, Andrew Siderowf, Billy Dunn, Kenneth Marek
Journal: The Lancet Neurology (2024)
Venglustat in GBA1-related Parkinson's disease – Authors' reply
Authors: S Pablo Sardi, Nir Giladi, Roy N Alcalay, Gary Cuer, Thomas Gasser, Tanya Gurevich, Günter U Höglinger, Kenneth Marek, Claudio PaccheE, Anthony H V Schapira, Clemens R Scherzer, Tanya Simuni, Pascal Minini, M Judith Peterschmi
Journal: The Lancet Neurology (2024)
Efficacy and safety of mTOR inhibition in cutaneous sarcoidosis: a single-centre trial
Authors: Anna Redl, Konstantin Doberer, Luisa Unterluggauer, Lisa Kleissl, Christoph Krall, Carolina Mayerhofer, Bärbel Reininger, Victoria Stary, Nina Zila, Wolfgang Weninger, Thomas Weichhart, Christoph Bock, Thomas Krausgruber, Georg Stary
Journal: The Lancet Rheumatology (2024)
Long-term immunity following yellow fever vaccination: a systematic review and meta-analysis
Authors: Jenny L Schnyder, Hanna K de Jong, Bache E Bache, Frieder Schaumburg, Martin P Grobusch
Journal: The Lancet Global Health (2024)

BackgroundLong-term immunity following yellow fever vaccination remains controversial. We aimed to summarise the literature regarding the long-term protection (≥10 years) conveyed by a single dose of yellow fever vaccination.MethodsIn this systematic review and meta-analysis, we searched 11 databases from database inception to Aug 24, 2023. We included cohort and cross-sectional studies reporting immunogenicity outcomes for children or adults who received a single dose of yellow fever vaccination 10 or more years ago. Case series and single case reports were excluded. Participants who received more than one dose of yellow fever vaccination before measurement of the outcome were excluded. Identified records were reviewed by two independent reviewers. The primary outcome of the meta-analysis was the pooled seroprotection rate. Risk of bias was assessed with the Risk Of Bias In Non-randomized Studies of Interventions tool, and the Joanna Briggs Institute tool for analytical cross-sectional studies. Studies of moderate or good quality that reported seroprotection were included for random-effects meta-analysis and stratified by endemicity and specific risk groups. The study was registered with PROSPERO, CRD42023384087.FindingsOf the 7363 articles identified by our search, 39 were eligible for inclusion for systematic review. These studies comprised 2895 individuals vaccinated 10–60 years ago. 20 studies were included in the meta-analysis. Pooled seroprotection rates were 94% (95% CI 86–99) among healthy adults in a non-endemic setting (mostly travellers) and 76% (65–85) in an endemic setting (all Brazilian studies). The pooled seroprotection rate was 47% (35–60) in children (aged 9–23 months at time of vaccination) and 61% (38–82) in people living with HIV. Reported criteria for seroprotection were highly heterogeneous.InterpretationThe gathered evidence suggests that a single dose of yellow fever vaccination provides lifelong protection in travellers. However, in people living with HIV and children (younger than 2 years), booster doses might still be required because lower proportions of vaccinees were seroprotected 10 or more years post-vaccination. Lower observed seroprotection rates among residents of endemic areas were partly explained by the use of a higher cutoff for seroprotection that was applied in Brazil. Studies from sub-Saharan Africa were scarce and of low quality; thus no conclusions could be drawn for this region.FundingNone.
What is next for BCG revaccination to prevent tuberculosis?
Authors: Richard G White, Andrew J Fiore-Gartland, Willem A Hanekom, Johan Vekemans, Alberto L Garcia-Basteiro, Gavin Churchyard, Molebogeng X Rangaka, Mike Frick, Marcel A Behr, Philip C Hill, Vidya Mave
Journal: The Lancet Respiratory Medicine (2024)
Open-source code to extend early-onset sepsis calculator accessibility
Authors: Bo M van der Weijden, Sanne W C M Janssen, William E Benitz, Michael W Kuzniewicz, Karen M Puopolo, Frans B Plötz, Niek B Achten
Journal: The Lancet Digital Health (2024)

The Kaiser Permanente Perinatal Research Unit developed an online risk prediction web-based tool that has led to drastic reductions in empiric antibiotic administration: the neonatal early-onset sepsis calculator.1 Use of the tool has been adopted quickly by many neonatal clinics worldwide, both in clinical and research contexts. However, the current international reliance on the Kaiser Permanente web tool might impede accessibility (eg, if the tool became temporarily unavailable) and adherence to local regulations for external users.