tbuckley/cabot-search huggingface dataset:
A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern
Authors: Marit J. van Gils, Hugo D.G. van Willigen, Elke Wynberg, Alvin X. Han, Karlijn van der Straten, Judith A. Burger, Meliawati Poniman, Melissa Oomen, Khadija Tejjani, Joey H. Bouhuijs, Anouk Verveen, Romy Lebbink, Maartje Dijkstra, Brent Appelman, A.H. Ayesha Lavell, Tom G. Caniels, Ilja Bontjer, Lonneke A. van Vught, Alexander P.J. Vlaar, Jonne J. Sikkens, Marije K. Bomers, Colin A. Russell, Neeltje A. Kootstra, Rogier W. Sanders, Maria Prins, Godelieve J. de Bree, Menno D. de Jong, Ivette Agard, Jane Ayal, Anders Boyd, Floor Cavdar, Marianne Craanen, Udi Davidovich, Annemarieke Deuring, Annelies van Dijk, Ertan Ersan, Laura del Grande, Joost Hartman, Nelleke Koedoot, Tjalling Leenstra, Dominique Loomans, Agata Makowska, Tom du Maine, Ilja de Man, Amy Matser, Lizenka van der Meij, Marleen van Polanen, Maria Oud, Clark Reid, Leeann Storey, Marije de Wit, Marc van Wijk, Joyce van Assem, Joost van den Aardweg, Marijne van Beek, Thyra Blankert, Brigitte Boeser-Nunnink, Eric Moll van Charante, Karel van Dort, Orlane Figaroa, Leah Frenkel, Arginell Girigorie, Jelle van Haga, Agnes Harskamp-Holwerda, Mette Hazenberg, Soemeja Hidad, Nina de Jong, Marcel Jonges, Suzanne Jurriaans, Hans Knoop, Lara Kuijt, Anja Lok, Marga Mangas Ruiz, Irma Maurer, Pythia Nieuwkerk, Ad van Nuenen, Annelou van der Veen, Bas Verkaik, Gerben-Rienk Visser
Journal: Cell Reports Medicine (2021)

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.
Supraphysiologic Testosterone Induces Ferroptosis and Activates Immune Pathways through Nucleophagy in Prostate Cancer
Authors: Rajendra Kumar, Janet Mendonca, Olutosin Owoyemi, Kavya Boyapati, Naiju Thomas, Suthicha Kanacharoen, Max Coffey, Deven Topiwala, Carolina Gomes, Busra Ozbek, Tracy Jones, Marc Rosen, Liang Dong, Sadie Wiens, W. Nathaniel Brennen, John T. Isaacs, Angelo M. De Marzo, Mark C. Markowski, Emmanuel S. Antonarakis, David Z. Qian, Kenneth J. Pienta, Drew M. Pardoll, Michael A. Carducci, Samuel R. Denmeade, Sushant K. Kachhap
Journal: Cancer Research (2021)

Abstract The discovery that androgens play an important role in the progression of prostate cancer led to the development of androgen deprivation therapy (ADT) as a first line of treatment. However, paradoxical growth inhibition has been observed in a subset of prostate cancer upon administration of supraphysiologic levels of testosterone (SupraT), both experimentally and clinically. Here we report that SupraT activates cytoplasmic nucleic acid sensors and induces growth inhibition of SupraT-sensitive prostate cancer cells. This was initiated by the induction of two parallel autophagy-mediated processes, namely, ferritinophagy and nucleophagy. Consequently, autophagosomal DNA activated nucleic acid sensors converge on NFκB to drive immune signaling pathways. Chemokines and cytokines secreted by the tumor cells in response to SupraT resulted in increased migration of cytotoxic immune cells to tumor beds in xenograft models and patient tumors. Collectively, these findings indicate that SupraT may inhibit a subset of prostate cancer by activating nucleic acid sensors and downstream immune signaling. Significance: This study demonstrates that supraphysiologic testosterone induces two parallel autophagy-mediated processes, ferritinophagy and nucleophagy, which then activate nucleic acid sensors to drive immune signaling pathways in prostate cancer.
Adjunctive Therapies in Parkinson Disease—Have We Made Meaningful Progress?
Authors: Tanya Simuni, Michael S. Okun
Journal: JAMA Neurology (2021)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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 2023 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 Neurology journal
TAMI-31. GLIOBLASTOMA GENETIC DRIVERS DICTATE THE FUNCTION OF TUMOR-ASSOCIATED MACROPHAGES/MICROGLIA AND RESPONSES TO CSF1R INHIBITION
Authors: Rohit Rao, Rong Han, Sean Ogurek, Lai Man Wu, Liguo Zhang, Jian Hu, Matthew Garrett, Tim Phoenix, Stephen N Waggoner, Qing Richard Lu
Journal: Neuro-Oncology (2021)

Abstract Tumor-associated macrophages/microglia (TAMs) are prominent microenvironment components in human glioblastoma (GBM) that are potential targets for anti-tumor therapy. However, TAM depletion by CSF1R inhibition showed mixed results in clinical trials. We hypothesized that GBM subtype-specific tumor microenvironment convey distinct sensitivities to TAM targeting. We generated syngeneic PDGFB-driven and RAS-driven GBM models that resemble proneural-like and mesenchymal-like gliomas, and determined the effect of TAM targeting by CSF1R inhibitor PLX3397 on glioma growth and progression. We also investigated the co-targeting of TAMs and angiogenesis on PLX3397-resistant RAS-driven GBM. Using single-cell transcriptomic profiling, we further explored differences in tumor microenvironment compositions and functions between the proneural-like and mesenchymal-like glioma models. We found that the growth of PDGFB-driven tumors was markedly inhibited by PLX3397. In contrast, depletion of TAMs at the early phase accelerated RAS-driven tumor growth and had no effects on other proneural and mesenchymal human GBM models. In addition, PLX3397-resistant RAS-driven tumors did not respond to PI3K signaling inhibition. Single-cell transcriptomic profiling revealed that PDGFB-driven gliomas induced expansion and activation of pro-tumor microglia, whereas mesenchymal RAS-driven gliomas elicited TAMs enriched in pro-inflammatory and angiogenic signaling. Co-targeting of TAMs and angiogenesis decreased cell proliferation and tumor mass in RAS-driven gliomas. Our work identifies functionally distinct TAM subpopulations in the growth of different glioma subtypes. Notably, we uncover a potential responsiveness of resistant mesenchymal-like gliomas to combined anti-angiogenic therapy and CSF1R inhibition. These data highlight the importance of microenvironment landscape characterization to optimally stratify glioma patients for TAM-targeted therapy.
With covid-19, single measures aren’t enough
Authors: John Middleton, Henrique Lopes
Journal: BMJ (2021)

Recently, the director general of the World Health Organization, Tedros Adhanom Ghebreyesus, said "vaccines alone will not get any country out of this crisis.Countries can-and must-prevent the spread of omicron with measures that work today.It's not vaccines instead of masks.It's not vaccines instead of distancing.It's not vaccines instead of ventilation or hand hygiene.Do it all.Do it consistently.Do it well."As the pandemic progresses, we are understanding the weaknesses of each of the interventions we have in the armoury to combat covid-19.Some countries, including England, have put all their eggs in the vaccination basket and neglected other measures that need to be implemented at the same time.
Second installment of Special Issue on expanding the scale and scope of gene editing
Authors: Robert M. Frederickson, Roland W. Herzog
Journal: Molecular Therapy (2021)

The editors of Molecular Therapy are thrilled to present in this issue a second installment of our Special Issue on Gene Editing. The first installment appeared in November of this past year but owing to the tremendous response to our call for papers, we were forced to split the issue in two. The first installment largely comprised our commissioned reviews, whereas the majority of the regular research articles appear in this second installment. We thank the authors, reviewers, and editors for their work making this Special Issue a reality. In fact, as the journal heads into its 23rd year of publication, it is useful to remember who does the “heavy lifting” in making the Molecular Therapy family of journals such a tremendous success: the reviewers and the associate editors in particular, who donate a significant amount of their time on the journals' behalf despite their other many research, administrative, teaching, clinical, and other professional duties. As many are aware, the journal family has experienced unprecedented and unpredicted growth over the past few years, which has strained our resources and staff. We are happy to report that ASGCT are now growing the editorial staff and should continue to do so as the numbers of submissions and publications continues to climb. The latest addition to the team is Courtney Bricker-Anthony, who joins as another professional scientific editor to support the journals' Associate Editorial boards. In addition to the great increase in submissions, we have, as previously discussed, also been faced with the growing issue of scientific fraud, which has plagued all journals and complicated the work of our reviewers and editors alike. All papers are now carefully vetted to identify and verify all authors and their institutions, their publication records, and they are subjected to both plagiarism detection software and image manipulation software. Of course, as we get better at detecting fraud so too are the perpetrators improving their skills at producing it, and we continue to monitor these processes, including identification of institutions associated with such practices, such as the use of the so-called “paper mill” companies. And, as noted previously, offenders will be treated accordingly, and individuals and even entire groups found to be engaging in scientific fraud or simultaneous submission to more than one journal will lose the ability to have future submissions considered for publication. More importantly, however, and much to our delight, the vast majority of manuscripts submitted to Molecular Therapy and its sibling journals is of exceptional quality, reflecting the strong support by the gene and cell therapy communities world-wide and allowing us to further excel as one of the leading families of journals in biomedical research.
The Role of Healthy Lifestyle in Cancer Incidence and Temporal Transitions to Cardiometabolic Disease
Authors: Zhi Cao, Chenjie Xu, Hongxi Yang, Shu Li, Yaogang Wang
Journal: JACC CardioOncology (2021)

Cardiometabolic disease, including cardiovascular disease (CVD) and type 2 diabetes (T2D), can result in serious late effects in patients with cancer. Preventing long-term complications in this population is an increasingly important priority in public health and clinical practice.The aim of this study was to investigate the role of a healthy lifestyle in the transition from a healthy status to the development of cancer and subsequent CVD and T2D.The analysis was based on data from the UK Biobank and included 2 subsamples: a cancer-free cohort of 397,136 individuals in the general population and a cancer-prevalent cohort of 35,564 patients with cancer. All participants were 40 to 70 years of age and were free of CVD and T2D at recruitment. A healthy lifestyle that included no current smoking, regular physical activity, a healthy diet, and moderate alcohol consumption and sleep duration were included in a healthy lifestyle index (HLI).In the cancer-free cohort, during a maximum follow-up period of 15 years, 6.38% and 4.18% of patients with cancer developed CVD and T2D, respectively. A healthy lifestyle significantly mitigated the risk for transition from cancer to subsequent CVD and T2D, with HRs per 1-point increment in HLI of 0.90 (95% CI: 0.86-0.94) and 0.84 (95% CI: 0.79-0.89), respectively. In the cancer-prevalent cohort, each 1-point increment in HLI was similarly associated with lower risk for CVD (HR: 0.90; 95% CI: 0.87-0.93) and T2D (HR: 0.87; 95% CI: 0.83-0.91) in cancer survivors.A healthy lifestyle is associated with a slower transition from cancer development to the subsequent development of CVD and T2D. Moreover, among patients with cancer, a healthy lifestyle is associated with lower risk for CVD and T2D. This study highlights the practical benefits of adherence to a healthy lifestyle.
Subtotal esophageal endoscopic submucosal dissection for long-segment Barrett’s esophagus and adenocarcinoma
Authors: Dai Kubota, Yoshiki Sakaguchi, Sayaka Nagao, Yosuke Tsuji, Mitsuhiro Fujishiro
Journal: Endoscopy (2021)

A 73-year-old man was referred to our department with a diagnosis of esophageal adenocarcinoma (EAC) in long-segment Barrett’s esophagus (BE), Prague classification C12M14. The long-segment BE extended to the upper thoracic esophagus and non-detectable adenocarcinoma was confirmed in multiple areas of the long-segment BE by random biopsies ([Fig. 1]). Esophageal endoscopic submucosal dissection (ESD) of the entire area of long-segment BE was therefore performed, with the patient under general anesthesia ([Video 1]). The lesion was resected en bloc ([Fig. 2]), in 220 minutes, with no adverse events. The total circumferential wound was 16 cm in length, and steroid injection and polyglycolic acid shielding were performed to prevent stenosis [1]. Histological assessment showed a curative resection, with adenocarcinoma invasion limited to the superficial muscularis mucosa, no lymphovascular invasion, and tumor-free margins ([Fig. 3]). After the patient’s discharge, local steroid injections were performed periodically. Squamous epithelium regeneration was found in the post-ESD area 6 months after ESD, with no recurrence of BE, and no evidence of stenosis ([Fig. 4]).
Generation of Alveolar Epithelium Using Reconstituted Basement Membrane and hiPSC‐Derived Organoids
Authors: Yong He, Elrade Rofaani, Xiaochen Huang, Boxin Huang, Feng Liang, Li Wang, Jian Shi, Juan Peng, Yong Chen
Journal: Advanced Healthcare Materials (2021)

In vitro modeling of alveolar epithelium needs to recapitulate features of both cellular and noncellular components of the lung tissues. Herein, a method is presented to generate alveolar epithelium by using human induced pluripotent stem cells (hiPSCs) and reconstituted or artificial basement membrane (ABM). The ABM is obtained by self-assembling type IV collagen and laminin with a monolayer of crosslinked gelatin nanofibers as backbone and a patterned honeycomb microframe for handling. Alveolar organoids are obtained from hiPSCs and then dissociated into single cells. After replating the alveolar cells on the ABM and a short-period incubation under submerged and air-liquid interface culture conditions, an alveolar epithelium is achieved, showing high-level expressions of both alveolar cell-specific proteins and characteristic tight junctions. Besides, endothelial cells derived from the same hiPSCs are cocultured on the backside of the epithelium, forming an air-blood barrier. The method is generic and can potentially be applied to other types of artificial epithelium and endothelium.
Correction to: Palliative care interventions in intensive care unit patients
Authors: Victoria Metaxa, Despina Anagnostou, Savvas Vlachos, Nishkantha Arulkumaran, Sherihane Bensemmane, Ingeborg van Dusseldorp, Rebecca A. Aslakson, Judy E. Davidson, Rik T. Gerritsen, Christiane Hartog, J. Randall Curtis
Journal: Intensive Care Medicine (2021)
Rethinking the chemokine cascade in brain metastasis: Preventive and therapeutic implications
Authors: Shailendra Kumar Maurya, Parvez Khan, Asad Ur Rehman, Ranjana K Kanchan, Naveenkumar Perumal, Sidharth Mahapatra, Hitendra S Chand, Juan A Santamaria-Barria, Surinder K Batra, Mohd Wasim Nasser
Journal: Seminars in Cancer Biology (2021)
An adhesive and resilient hydrogel for the sealing and treatment of gastric perforation
Authors: Jing Chen, Julia S. Caserto, Ida Ang, Kaavian Shariati, James Webb, Bo Wang, Xi Wang, Nikolaos Bouklas, Minglin Ma
Journal: Bioactive Materials (2021)

Adhesive hydrogels have been recently proposed as a potential option to seal and treat gastric perforation (GP) which causes high mortality despite advancements in surgical treatments. However, to be effective, the hydrogels must have sufficient tissue adhesiveness, tough mechanical property, tunable biodegradability and ideally are easy to apply and form. Herein, we report an adhesive and resilient hydrogel for the sealing and treatment of gastric perforation. The hydrogel consists of a bioactive, transglutaminase (TG)-crosslinked gelatin network and a dynamic, borate-crosslinked poly-N-[Tris(hydroxymethyl)methyl]acrylamide (PTH) network. The hydrogel can be formed in situ, facilitating easy delivery to the GP and allowing for precise sealing of the defects. In vivo experiments, using a perforated stomach mouse model, shows that the adhesive hydrogel plug effectively seals GP defects and promotes gastric mucosa regeneration. Overall, this hydrogel represents a promising biomaterial for GP treatment.
Cardiac Computed Tomography in Cardio-Oncology
Authors: Juan C. Lopez-Mattei, Eric H. Yang, Maros Ferencik, Lauren A. Baldassarre, Susan Dent, Matthew J. Budoff
Journal: JACC CardioOncology (2021)

Cancer patients and survivors have elevated cardiovascular risk when compared with noncancer patients. Cardio-oncology has emerged as a new subspecialty to comanage and address cardiovascular complications in cancer patients such as heart failure, atherosclerotic cardiovascular disease (ASCVD), valvular heart disease, pericardial disease, and arrhythmias. Cardiac computed tomography (CT) can be helpful in identifying both clinical and subclinical ASCVD in cancer patients and survivors. Radiation therapy treatment planning CT scans and cancer staging/re-staging imaging studies can quantify calcium scores which can identify pre-existing subclinical ASCVD. Cardiac CT can be helpful in the evaluation of cardiac tumors and pericardial diseases, especially in patients who cannot tolerate or have a contraindication to cardiac magnetic resonance. In this review, we describe the optimal utilization of cardiac CT in cancer patients, including risk assessment for ASCVD and identification of cancer treatment-related cardiovascular toxicity.
Suppression of breast cancer-associated bone loss with osteoblast proteomes via Hsp90ab1/moesin-mediated inhibition of TGFβ/FN1/CD44 signaling
Authors: Xun Sun, Kexin Li, Misato Hase, Rongrong Zha, Yan Feng, Bai-Yan Li, Hiroki Yokota
Journal: Theranostics (2021)

Background: Bone is a frequent site of metastases from breast cancer, but existing therapeutic options are not satisfactory. Although osteoblasts have active roles in cancer progression by assisting the vicious bone-destructive cycle, we employed a counterintuitive approach of activating pro-tumorigenic Wnt signaling and examined the paradoxical possibility of developing osteoblast-derived tumor-suppressive, bone-protective secretomes. Methods: Wnt signaling was activated by the overexpression of Lrp5 and β-catenin in osteoblasts as well as a pharmacological agent (BML284), and the therapeutic effects of their conditioned medium (CM) were evaluated using in vitro cell cultures, ex vivo breast cancer tissues, and a mouse model of osteolysis. To explore the unconventional regulatory mechanism of the action of Wnt-activated osteoblasts, whole-genome proteomics analysis was conducted, followed by immunoprecipitation and gain- and loss-of-function assays. Results: While osteoblasts did not present any innate tumor-suppressing ability, we observed that the overexpression of Lrp5 and β-catenin in Wnt signaling made their CM tumor-suppressive and bone-protective. The growth of breast cancer cells and tissues was inhibited by Lrp5-overexpressing CM (Lrp5 CM), which suppressed mammary tumors and tumor-driven bone destruction in a mouse model. Lrp5 CM also inhibited the differentiation and maturation of bone-resorbing osteoclasts by downregulating NFATc1 and cathepsin K. The overexpression of Lrp5 upregulated osteopontin that enriched Hsp90ab1 (Hsp90 beta) and moesin (MSN) in Lrp5 CM. Hsp90ab1 and MSN are atypical tumor-suppressing proteins since they are multi-tasking, moonlighting proteins that promote tumorigenesis in tumor cells. Importantly, Hsp90ab1 immuno-precipitated latent TGFβ and inactivated TGFβ, whereas MSN interacted with CD44, a cancer stem-cell marker, as well as fibronectin 1, an ECM protein. Furthermore, Hsp90ab1 and MSN downregulated KDM3A that demethylated histones, together with PDL1 that inhibited immune responses. Conclusion: In contrast to inducing tumor-enhancing secretomes and chemoresistance in general by inhibiting varying oncogenic pathways in chemotherapy, this study presented the unexpected outcome of generation tumor-suppressive secretomes by activating the pro-tumorigenic Wnt pathway. The results shed light on the contrasting role of oncogenic signaling in tumor cells and osteoblast-derived secretomes, suggesting a counterintuitive option for the treatment of breast cancer-associated bone metastasis.