tbuckley/cabot-search huggingface dataset:
Intelligent polymeric hydrogen sulfide delivery systems for therapeutic applications
Authors: Fan Rong, Tengjiao Wang, Qian Zhou, Haowei Peng, Jingtian Yang, Quli Fan, Peng Li
Journal: Bioactive Materials (2022)

Hydrogen sulfide (H2S) plays an important role in regulating various pathological processes such as protecting mammalian cell from harmful injuries, promoting tissue regeneration, and regulating the process of various diseases caused by physiological disorders. Studies have revealed that the physiological effects of H2S are highly associated with its concentrations. At relatively low concentration, H2S shows beneficial functions. However, long-time and high-dose donation of H2S would inhibit regular biological process, resulting in cell dysfunction and apoptosis. To regulate the dosage of H2S delivery for precision medicine, H2S delivery systems with intelligent characteristics were developed and a variety of biocompatibility polymers have been utilized to establish intelligent polymeric H2S delivery systems, with the abilities to specifically target the lesions, smartly respond to pathological microenvironments, as well as real-timely monitor H2S delivery and lesion conditions by incorporating imaging-capable moieties. In this review, we focus on the design, preparation, and therapeutic applications of intelligent polymeric H2S delivery systems in cardiovascular therapy, inflammatory therapy, tissue regenerative therapy, cancer therapy and bacteria-associated therapy. Strategies for precise H2S therapies especially imaging-guided H2S theranostics are highlighted. Since H2S donors with stimuli-responsive characters are vital components for establishing intelligent H2S delivery systems, the development of H2S donors is also briefly introduced.
Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1
Authors: Xiangliang Yuan, Yimin Duan, Yi Xiao, Kai Sun, Yutao Qi, Yuan Zhang, Zamal Ahmed, Davide Moiani, Jun Yao, Hongzhong Li, Lin Zhang, Arseniy E. Yuzhalin, Ping Li, Chenyu Zhang, Akosua Badu-Nkansah, Yohei Saito, Xianghua Liu, Wen-Ling Kuo, Haoqiang Ying, Shao-Cong Sun, Jenny C. Chang, John A. Tainer, Dihua Yu
Journal: Cancer Discovery (2022)

Despite the popular use of dietary supplements during conventional cancer treatments, their impacts on the efficacies of prevalent immunotherapies, including immune-checkpoint therapy (ICT), are unknown. Surprisingly, our analyses of electronic health records revealed that ICT-treated patients with cancer who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DC). VitE entered DCs via the SCARB1 receptor and restored tumor-associated DC functionality by directly binding to and inhibiting protein tyrosine phosphatase SHP1, a DC-intrinsic checkpoint. SHP1 inhibition, genetically or by VitE treatment, enhanced tumor antigen cross-presentation by DCs and DC-derived extracellular vesicles (DC-EV), triggering systemic antigen-specific T-cell antitumor immunity. Combining VitE with DC-recruiting cancer vaccines or immunogenic chemotherapies greatly boosted ICT efficacy in animals. Therefore, combining VitE supplement or SHP1-inhibited DCs/DC-EVs with DC-enrichment therapies could substantially augment T-cell antitumor immunity and enhance the efficacy of cancer immunotherapies. The impacts of nutritional supplements on responses to immunotherapies remain unexplored. Our study revealed that dietary vitamin E binds to and inhibits DC checkpoint SHP1 to increase antigen presentation, prime antitumor T-cell immunity, and enhance immunotherapy efficacy. VitE-treated or SHP1-silenced DCs/DC-EVs could be developed as potent immunotherapies. This article is highlighted in the In This Issue feature, p. 1599.
Evaluation of clinically relevant changes in the lung clearance index in children with cystic fibrosis and healthy controls
Authors: Lucy Perrem, Sanja Stanojevic, Melinda Solomon, Hartmut Grasemann, Neil Sweezey, Valerie Waters, Don B Sanders, Stephanie D Davis, Felix Ratjen
Journal: Thorax (2022)

Background The limits of reproducibility of the lung clearance index (LCI) are higher in children with cystic fibrosis (CF) compared with healthy children, and it is currently unclear what defines a clinically meaningful change. Methods In a prospective multisite observational study of children with CF and healthy controls (HCs), we measured LCI, FEV 1 % predicted and symptom scores at quarterly visits over 2 years. Two reviewers performed a detailed review of visits to evaluate the frequency that between visit LCI changes outside ±10%, ±15%, ±20% represented a clinically relevant signal. In the setting of acute respiratory symptoms, we used a generalised estimating equation model, with a logit link function to determine the ability of LCI worsening at different thresholds to predict failure of lung function recovery at follow-up. Results Clinically relevant LCI changes outside ±10%, ±15% and ±20% were observed at 25.7%, 15.0% and 8.3% of CF visits (n=744), respectively. The proportions of LCI changes categorised as noise, reflecting biological variability, were comparable between CF and HC at the 10% (CF 9.9% vs HC 13.0%), 15% (CF 4.3% vs HC 3.1%) and 20% (CF 2.4% vs HC 1.0%) thresholds. Compared with symptomatic CF visits without a worsening in LCI, events with ≥10% LCI increase were more likely to fail to recover baseline LCI at follow-up. Conclusion The limits of reproducibility of the LCI in healthy children can be used to detect clinically relevant changes and thus inform clinical care in children with CF.
Pediatric Acute Myeloid Leukemia Enters the Molecularly Targeted Era Via FLT3 Inhibition
Authors: Alexander E. Perl
Journal: Journal of Clinical Oncology (2022)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Sorafenib in Combination With Standard Chemotherapy for Children With High Allelic Ratio FLT3/ITD+ Acute Myeloid Leukemia: A Report From the Children's Oncology Group Protocol AAML1031. March 29, 2022 ARTICLE CITATION DOI: 10.1200/JCO.22.00499 Journal of Clinical Oncology - published online before print April 18, 2022 PMID: 35436158 Pediatric Acute Myeloid Leukemia Enters the Molecularly Targeted Era Via FLT3 Inhibition Alexander E. Perl , MD1xAlexander E. PerlSearch for articles by this author Show More 1Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA https://doi.org/10.1200/JCO.22.00499 First Page Full Text PDF Figures and Tables © 2022 by American Society of Clinical OncologyAUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTPediatric Acute Myeloid Leukemia Enters the Molecularly Targeted Era Via FLT3 InhibitionThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Alexander E. PerlHonoraria: Astellas Pharma, Daiichi SankyoConsulting or Advisory Role: Astellas Pharma, Actinium Pharmaceuticals, Daiichi Sankyo, AbbVie, FORMA Therapeutics, Sumitomo Dainippon, Celgene/Bristol Myers Squibb, Syndax, Genentech, BerGenBio, ImmunogenResearch Funding: Astellas Pharma (Inst), Bayer (Inst), Daiichi Sankyo (Inst), Fujifilm (Inst), AbbVie (Inst), Syndax (Inst)No other potential conflicts of interest were reported. Companion Sorafenib in Combination With Standard Chemotherapy for Children With High Allelic Ratio FLT3/ITD+ Acute Myeloid Leukemia: A Report From the Children's Oncology Group Protocol AAML1031
Covid-19: UK approves Valneva vaccine for adults under 50
Authors: Elisabeth Mahase
Journal: BMJ (2022)

The UK's Medicines and Healthcare Products Regulatory Agency (MHRA) has granted Valneva's covid-19 vaccine (VLA2001) conditional marketing authorisation for use in people aged 18 to 50 years, with the first and second doses to be taken at least 28 days apart.Competing interests: EM is a participant in the Valneva covid-19 vaccine trial. 1 Valneva.Valneva announces major covid-19 vaccine partnership with UK government.https://valneva.
Perspectives of Triage Team Members Participating in Statewide Triage Simulations for Scarce Resource Allocation During the COVID-19 Pandemic in Washington State
Authors: Catherine R. Butler, Laura B. Webster, Douglas S. Diekema, Megan M. Gray, Vicki L. Sakata, Mark R. Tonelli, Kelly C. Vranas
Journal: JAMA Network Open (2022)

The COVID-19 pandemic prompted health care institutions worldwide to develop plans for allocation of scarce resources in crisis capacity settings. These plans frequently rely on rapid deployment of institutional triage teams that would be responsible for prioritizing patients to receive scarce resources; however, little is known about how these teams function or how to support team members participating in this unique task.To identify themes illuminating triage team members' perspectives and experiences pertaining to the triage process.This qualitative study was conducted using inductive thematic analysis of observations of Washington state triage team simulations and semistructured interviews with participants during the COVID-19 pandemic from December 2020 to February 2021. Participants included clinician and ethicist triage team members. Data were analyzed from December 2020 through November 2021.Emergent themes describing the triage process and experience of triage team members.Among 41 triage team members (mean [SD] age, 50.3 [11.4] years; 21 [51.2%] women) who participated in 12 simulations and 21 follow-up interviews, there were 5 Asian individuals (12.2%) and 35 White individuals (85.4%); most participants worked in urban hospital settings (32 individuals [78.0%]). Three interrelated themes emerged from qualitative analysis: (1) understanding the broader approach to resource allocation: participants strove to understand operational and ethical foundations of the triage process, which was necessary to appreciate their team's specific role; (2) contending with uncertainty: team members could find it difficult or feel irresponsible making consequential decisions based on limited clinical and contextual patient information, and they grappled with ethically ambiguous features of individual cases and of the triage process as a whole; and (3) transforming mindset: participants struggled to disentangle narrow determinations about patients' likelihood of survival to discharge from implicit biases and other ethically relevant factors, such as quality of life. They cited the team's open deliberative process, as well as practice and personal experience with triage as important in helping to reshape their usual cognitive approach to align with this unique task.This study found that there were challenges in adapting clinical intuition and training to a distinctive role in the process of scarce resource allocation. These findings suggest that clinical experience, education in ethical and operational foundations of triage, and experiential training, such as triage simulations, may help prepare clinicians for this difficult role.
Circadian rhythm affects the magnitude of contact hypersensitivity response in mice
Authors: Toshiya Miyake, Gyohei Egawa, Zachary Chow, Ryota Asahina, Masayuki Otsuka, Saeko Nakajima, Takashi Nomura, Rintaro Shibuya, Yoshihiro Ishida, Satoshi Nakamizo, Teruasa Murata, Akihiko Kitoh, Kenji Kabashima
Journal: Allergy (2022)

Abstract Background The circadian rhythm controls multiple biological processes, including immune responses; however, its impact on cutaneous adaptive immune response remains unclear. Methods We used a well‐established cutaneous type IV allergy model, contact hypersensitivity (CHS). We induced CHS using dinitrofluorobenzene (DNFB). Mice were sensitized and elicited with DNFB in the daytime or at night. Results In mice, a nocturnally active animal, we found that ear swelling increased when mice were sensitized at night compared with in the daytime. In addition, cell proliferation and cytokine production in the draining lymph nodes (LNs) were promoted when sensitized at night. We hypothesized that these differences were due to the oscillation of leukocyte distribution in the body through the circadian production of adrenergic hormones. Administration of a β2‐adrenergic receptor (β2AR) agonist salbutamol in the daytime decreased the number of immune cells in blood and increased the number of immune cells in LNs. In contrast, a β2AR antagonist ICI18551 administration at night increased the number of immune cells in blood and decreased the number of immune cells in LNs. Accordingly, the severity of CHS response was exacerbated by salbutamol administration in the daytime and attenuated by ICI18551 administration at night. Conclusion Our study demonstrated that the magnitude of adaptive CHS response depends on the circadian rhythm and this knowledge may improve the management of allergic contact dermatitis (ACD) in humans.
A Love Letter to Grief
Authors: Neha Pal
Journal: JAMA (2022)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Correction: BATF2 Deficiency Promotes Progression in Human Colorectal Cancer via Activation of HGF/MET Signaling: A Potential Rationale for Combining MET Inhibitors with IFNs
Authors: Zebing Liu, Ping Wei, Yu Yang, Wenli Cui, Bing Cao, Cong Tan, Baohua Yu, Rui Bi, Kaiqin Xia, Weixiang Chen, Yiqin Wang, Youyuan Zhang, Xiang Du, Xiaoyan Zhou
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), four images were duplicated: in Fig. 2F, the Mock and NC dot plots for SW620 were the same (Mock is correct); in Fig. 3A, the Mock and NC images for 0 and 12 hours were the same (Mock is correct); in Fig. 3E, the Mock and NC images were overlapped (NC is correct); and in Fig. 6, Fig. 6C Ki-67 Lenti.BATF2 ×400 and Fig. 6G Combination ×400 were the same (Fig. 6G is correct). These errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret the errors.
A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis
Authors: Zhejie Chen, Wei Hao, Caifang Gao, Yangyang Zhou, Chen Zhang, Jinming Zhang, Ruibing Wang, Yitao Wang, Shengpeng Wang
Journal: Acta Pharmaceutica Sinica B (2022)

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.
Variation in targetable genomic alterations in non-small cell lung cancer by genetic ancestry, sex, smoking history, and histology
Authors: Elio Adib, Amin H. Nassar, Sarah Abou Alaiwi, Stefan Groha, Elie W. Akl, Lynette M. Sholl, Kesi S. Michael, Mark M. Awad, Pasi A. Jӓnne, Alexander Gusev, David J. Kwiatkowski
Journal: Genome Medicine (2022)

Genomic alterations in 8 genes are now the targets of FDA-approved therapeutics in non-small cell lung cancer (NSCLC), but their distribution according to genetic ancestry, sex, histology, and smoking is not well established.Using multi-institutional genetic testing data from GENIE, we characterize the distribution of targetable genomic alterations in 8 genes among 8675 patients with NSCLC (discovery cohort: DFCI, N = 3115; validation cohort: Duke, Memorial Sloan Kettering Cancer Center, Vanderbilt, N = 5560). For the discovery cohort, we impute genetic ancestry from tumor-only sequencing and identify differences in the frequency of targetable alterations across ancestral groups, smoking pack-years, and histologic subtypes.We identified variation in the prevalence of KRASG12C, sensitizing EGFR mutations, MET alterations, ALK, and ROS1 fusions according to the number of smoking pack-years. A novel method for computing continental (African, Asian, European) and Ashkenazi Jewish ancestries from panel sequencing enables quantitative analysis of the correlation between ancestry and mutation rates. This analysis identifies a correlation between Asian ancestry and EGFR mutations and an anti-correlation between Asian ancestry and KRASG12C mutation. It uncovers 2.7-fold enrichment for MET exon 14 skipping mutations and amplifications in patients of Ashkenazi Jewish ancestry. Among never/light smokers, targetable alterations in LUAD are significantly enriched in those with Asian (80%) versus African (49%) and European (55%) ancestry. Finally, we show that 5% of patients with squamous cell carcinoma (LUSC) and 17% of patients with large cell carcinoma (LCLC) harbor targetable alterations.Among patients with NSCLC, there was significant variability in the prevalence of targetable genomic alterations according to genetic ancestry, histology, and smoking. Patients with LUSC and LCLC have 5% rates of targetable alterations supporting consideration for sequencing in those subtypes.
Deletion of activin A in mesenchymal but not myeloid cells ameliorates disease severity in experimental arthritis
Authors: Vanessa Waltereit-Kracke, Corinna Wehmeyer, Denise Beckmann, Eugenie Werbenko, Julia Reinhardt, Fabienne Geers, Mike Dienstbier, Michelle Fennen, Johanna Intemann, Peter Paruzel, Adelheid Korb-Pap, Thomas Pap, Berno Dankbar
Journal: Annals of the Rheumatic Diseases (2022)

Objective The aim of this study was to assess the extent and the mechanism by which activin A contributes to progressive joint destruction in experimental arthritis and which activin A-expressing cell type is important for disease progression. Methods Levels of activin A in synovial tissues were evaluated by immunohistochemistry, cell-specific expression and secretion by PCR and ELISA, respectively. Osteoclast (OC) formation was assessed by tartrat-resistant acid phosphatase (TRAP) staining and activity by resorption assay. Quantitative assessment of joint inflammation and bone destruction was performed by histological and micro-CT analysis. Immunoblotting was applied for evaluation of signalling pathways. Results In this study, we demonstrate that fibroblast-like synoviocytes (FLS) are the main producers of activin A in arthritic joints. Most significantly, we show for the first time that deficiency of activin A in arthritic FLS (ActβA d/d ColVI-Cre) but not in myeloid cells (ActβA d/d LysM-Cre) reduces OC development in vitro, indicating that activin A promotes osteoclastogenesis in a paracrine manner. Mechanistically, activin A enhanced OC formation and activity by promoting the interaction of activated Smad2 with NFATc1, the key transcription factor of osteoclastogenesis. Consistently, ActβA d/d LysM-Cre hTNFtg mice did not show reduced disease severity, whereas deficiency of activin A in ColVI-Cre-expressing cells such as FLS highly diminished joint destruction reflected by less inflammation and less bone destruction. Conclusions The results highly suggest that FLS-derived activin A plays a crucial paracrine role in inflammatory joint destruction and may be a promising target for treating inflammatory disorders associated with OC formation and bone destruction like rheumatoid arthritis.
Photon-Counting Computed Tomography Scan of a Cerebrospinal Fluid Venous Fistula
Authors: Fides R. Schwartz, Michael D. Malinzak, Timothy J. Amrhein
Journal: JAMA Neurology (2022)

This case report describes the use of traditional computed tomography vs photon-counting computed tomography in evaluating the potential cause of spontaneous intracranial hypotension in a 56-year-old female patient.
Low-ratio somatic NLRC4 mutation causes late-onset autoinflammatory disease
Authors: Jun Wang, Qiao Ye, Wenjie Zheng, Xiaomin Yu, Fang Luo, Ran Fang, Yaoyao Shangguan, Zhijun Du, Pui Y Lee, Taijie Jin, Qing Zhou
Journal: Annals of the Rheumatic Diseases (2022)

Objectives We aim to investigate the genetic basis of a case of late-onset autoinflammatory disease characterised by arthritis, recurrent fever and skin rashes. Methods We performed whole-exome/genome sequencing and digital droplet PCR (ddPCR) to identify the pathogenic somatic mutation. We used single-cell RNA sequencing (scRNA-seq), intracellular cytokine staining, quantitative PCR, immunohistochemistry and western blotting to define inflammatory signatures and to explore the pathogenic mechanism. Results We identified a somatic mutation in NLRC4 (p.His443Gln) with the highest mosaicism ratio in the patient’s monocytes (5.69%). The somatic mutation resulted in constitutive NLRC4 activation, spontaneous apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) aggregation, caspase-1 hyperactivation and increased production of interleukin (IL)-1β and IL-18. Moreover, we demonstrated effective suppression of inflammatory cytokine production by targeting gasdermin D, an approach that could be considered as a novel treatment strategy for patients with NLRC4 -associated autoinflammatory syndrome. Conclusions We reported a case of a late-onset autoinflammatory disease caused by a somatic NLRC4 mutation in a small subset of leucocytes. We systemically analysed this condition at a single-cell transcriptomic level and revealed specific enhancement of inflammatory response in myeloid cells.
Flexible patch with printable and antibacterial conductive hydrogel electrodes for accelerated wound healing
Authors: Canran Wang, Xing Jiang, Han-Jun Kim, Shiming Zhang, Xingwu Zhou, Yi Chen, Haonan Ling, Yumeng Xue, Zhaowei Chen, Moyuan Qu, Li Ren, Jixiang Zhu, Alberto Libanori, Yangzhi Zhu, Heemin Kang, Samad Ahadian, Mehmet R. Dokmeci, Peyman Servati, Ximin He, Zhen Gu, Wujin Sun, Ali Khademhosseini
Journal: Biomaterials (2022)