tbuckley/cabot-search huggingface dataset:
Reactive oxygen species (ROS)-responsive size-reducible nanoassemblies for deeper atherosclerotic plaque penetration and enhanced macrophage-targeted drug delivery
Authors: Jianhua He, Wenli Zhang, Xiaoju Zhou, Fengfei Xu, Jiahui Zou, Qiqi Zhang, Yi Zhao, Hongliang He, Hu Yang, Jianping Liu
Journal: Bioactive Materials (2022)

Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis; however, the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells. Here, we report reactive oxygen species (ROS)-responsive and size-reducible nanoassemblies, formed by multivalent host-guest interactions between β-cyclodextrins (β-CD)-anchored discoidal recombinant high-density lipoprotein (NP3ST) and hyaluronic acid-ferrocene (HA-Fc) conjugates. The HA-Fc/NP3ST nanoassemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP3ST, allowing for further plaque penetration, macrophage-targeted cholesterol efflux and drug delivery. In vivo pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP3ST reduces plaque size by 53%, plaque lipid deposition by 63%, plaque macrophage content by 62% and local inflammatory factor level by 64% compared to the saline group. Meanwhile, HA-Fc/NP3ST alleviates systemic inflammation characterized by reduced serum inflammatory factor levels. Collectively, HA-Fc/NP3ST nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability, thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.
Frequent HLA-DR loss on hematopoietic stem progenitor cells in patients with cyclosporine-dependent aplastic anemia carrying HLA-DR15
Authors: Noriaki Tsuji, Kohei Hosokawa, Ryota Urushihara, Mikoto Tanabe, Yoshitaka Zaimoku, Takamasa Katagiri, Tatsuhiko Ozawa, Hiroyuki Takamatsu, Ken Ishiyama, Hirohito Yamazaki, Hiroyuki Kishi, Seishi Ogawa, Shinji Nakao
Journal: Leukemia (2022)
Response to ‘Isotretinoin and adverse neuropsychiatric outcomes: retrospective cohort study using routine data’
Authors: Renin Chang, Chih-Cheng Lai, Yao-Min Hung, Shiow-Ing Wang, James Cheng-Chung Wei
Journal: British Journal of Dermatology (2022)

Abstract Linked Article: Paljarvi et al. Br J Dermatol 2022; 187:64–72.
Utility of a Model for Predicting the Risk of Sentinel Lymph Node Metastasis in Patients With Cutaneous Melanoma
Authors: Michael A. Marchetti, Stephen W. Dusza, Edmund K. Bartlett
Journal: JAMA Dermatology (2022)

A neural network-based model (i31-GEP-SLNB) that uses clinicopathologic factors (thickness, mitoses, ulceration, patient age) plus molecular analysis (31-gene expression profiling) has become commercially available to guide selection for sentinel lymph node (SLN) biopsy in cutaneous melanoma, but its clinical utility is not well characterized.To determine if use of the i31-GEP-SLNB model is associated with clinical benefit when used to select patients for SLN biopsy.This decision-analytic study used data derived from a published external validation study of the i31-GEP-SLNB prediction model. Participants included patients with primary cutaneous melanoma.The primary outcome was the net benefit associated with using the i31-GEP-SLNB model for SLN biopsy selection compared with other selection strategies (SLN biopsy for all patients and SLN biopsy for no patients) at a 5% risk threshold. Analyses were stratified by American Joint Committee on Cancer (AJCC) T category. The reduction in the number of avoidable SLN biopsies and relative utility were also calculated.Compared with other SLN biopsy selection strategies, use of the i31-GEP-SLNB model had greater net benefit for patients with T1b (+0.012), T2a (+0.002), and T2b melanoma (+0.002) but not for those with high-risk T1a (-0.003) disease. The improvement in relative utility was +22% in patients with T1b, +1% in T2a, and +2% in T2b melanoma. Compared with SLN biopsy for all patients, use of the model would equate to a 23% decrease in SLN biopsies among patients with T1b disease without an SLN metastasis with no increase in the number of patients with an SLN metastasis left untreated; among patients with T2a and T2b melanoma, the net decrease in avoidable biopsies compared with SLN biopsy for all was 3% and 4%, respectively.The findings of this decision-analytic study suggest that i31-GEP SLNB has significant potential for risk-stratifying patients with T1b melanoma if using a 5% risk threshold; its role among patients with T1a and T2 melanoma or using other risk thresholds requires further study. A prospective validation study confirming the added clinical benefit and cost-effectiveness of i31-GEP-SLNB compared with free clinicopathologic-based prediction models is needed in patients with T1b melanoma.
Epigenetic regulator UHRF1 orchestrates proinflammatory gene expression in rheumatoid arthritis in a suppressive manner
Authors: Noritaka Saeki, Kazuki Inoue, Maky Ideta-Otsuka, Kunihiko Watamori, Shinichi Mizuki, Katsuto Takenaka, Katsuhide Igarashi, Hiromasa Miura, Shu Takeda, Yuuki Imai
Journal: Journal of Clinical Investigation (2022)

Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation with aberrant epigenetic alterations, eventually leading to joint destruction. However, the epigenetic regulatory mechanisms underlying RA pathogenesis remain largely unknown. Here, we showed that ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is a central epigenetic regulator that orchestrates multiple pathogeneses in RA in a suppressive manner. UHRF1 expression was remarkably upregulated in synovial fibroblasts (SFs) from arthritis model mice and patients with RA. Mice with SF-specific Uhrf1 conditional knockout showed more severe arthritic phenotypes than littermate controls. Uhrf1-deficient SFs also exhibited enhanced apoptosis resistance and upregulated expression of several cytokines, including Ccl20. In patients with RA, DAS28, CRP, and Th17 accumulation and apoptosis resistance were negatively correlated with UHRF1 expression in synovium. Finally, Ryuvidine administration stabilized UHRF1 ameliorated arthritis pathogeneses in a mouse model of RA. This study demonstrated that UHRF1 expressed in RA SFs can contribute to negative feedback mechanisms that suppress multiple pathogenic events in arthritis, suggesting that targeting UHRF1 could be one of the therapeutic strategies for RA.
Assessment of Antibody and T-Cell Responses to the SARS-CoV-2 Virus and Omicron Variant in Unvaccinated Individuals Recovered From COVID-19 Infection in Wuhan, China
Authors: Li Guo, Qiao Zhang, Chongyang Zhang, Tingxuan Huang, Lili Ren, Bin Cao, Jianwei Wang
Journal: JAMA Network Open (2022)

This cohort study examines immune system responses to the Omicron strain of the SARS-CoV-2 virus among unvaccinated individuals in Wuhan, China, who recovered from infection with the initial strain of the virus.
Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis
Authors: Wenbin Kuang, Haolin Zhang, Xiao Wang, Peng Yang
Journal: Acta Pharmaceutica Sinica B (2022)

Mycobacterium tuberculosis (MTB) utilizes multiple mechanisms to obtain antibiotic resistance during the treatment of infections. In addition, the biofilms, secreted by MTB, can further protect the latter from the contact with drug molecules and immune cells. These self-defending mechanisms lay a formidable challenge to develop effective therapeutic agents against chronic and recurring antibiotic-tolerant MTB infections. Although several inexpensive and effective drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) have been discovered for the treatment regimen, MTB continues to cause considerable morbidity and mortality worldwide. Antibiotic resistance and tolerance remain major global issues, and innovative therapeutic strategies are urgently needed to address the challenges associated with pathogenic bacteria. Gratifyingly, the cell wall synthesis of tubercle bacilli requires the participation of many enzymes which exclusively exist in prokaryotic organisms. These enzymes, absent in human hepatocytes, are recognized as promising targets to develop anti-tuberculosis drug. In this paper, we discussed the critical roles of potential drug targets in regulating cell wall synthesis of MTB. And also, we systematically reviewed the advanced development of novel bioactive compounds or drug leads for inhibition of cell wall synthesis, including their discovery, chemical modification, in vitro and in vivo evaluation.
Histological R0 classification after colorectal endoscopic submucosal dissection: a gold standard with feet of clay
Authors: Pierre Lafeuille, Clara Yzet, Nicolas Benech, Florian Rostain, Thierry Ponchon, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2022)

The residual tumor (R) classification is the gold standard for the evaluation of residual tumors after treatment [1]. As an important predictor of prognosis, it is of considerable clinical significance. It takes into account the clinical and pathological examination of the tumor. In the field of colorectal lesion resection, a resection is considered R0 when the tumor is removed in a single piece (en bloc) with tumor-free lateral and vertical margins. For resection of a superficial lesion to be considered curative, an R0 en bloc resection with histology no more advanced than a well-differentiated adenocarcinoma and submucosal invasion of less than 1 mm without lymphovascular invasion is currently required [2].
Letter to the editor: Hepatitis B virus genotype: A significant risk factor in determining which patients with chronic hepatitis B virus infection should undergo surveillance for hepatocellular carcinoma: The hepatitis B Alaska study
Authors: Aashish Kumar, Deepak Rajani, Satesh Kumar
Journal: Hepatology (2022)

To the editor, We read with great interest the article entitled “HBV Genotype: A Significant Risk Factor in Determining Which Patients with Chronic HBV Infection Should Undergo Surveillance for HCC: The Hepatitis B Alaska Study” by McMahon et al.[1] We acknowledge all the efforts made by the authors in elucidating the strong association between hepatitis B virus (HBV) and hepatocellular carcinoma (HCC), but there are a few concerns that need to be addressed. First, the author emphasized genotype predisposition of HBV type for HCC.[1] At the same time, other potential risk factors contribute to HBV‐concomitant HCC progression, one of which includes alcohol, as per a study in 2013.[2] Patients who are alcohol consumers and HBV positive are more susceptible to develop HCC than those with HBV alone. Secondly, apart from HBV genotypes, additional known risk elements include diabetes and hypercholesteremia. Even in areas where hepatitis infection is endemic, diabetes plays a significant role in mounting HCC in patients with HBV or who are hepatitis C virus negative. The high total level of cholesterol is also found to be associated with HCC.[3] Third, a phenotypically silent disorder, hereditary hemochromatosis (HH), is well known for causing liver cirrhosis; however, it is noteworthy to mention the prevalence of HCC in patients with HH.[4] HCC can present with or without cirrhosis in patients with HH. The risk of having HCC is increased 20‐fold in the presence of HH. Lastly, the authors should have mentioned if any genetic mutation was present. For instance, small nucleolar RNA (snoRNA) and small noncoding RNA overexpression is proved to be oncogenic, primarily HCC. An orphan C/D box snoRNA, SNORD126, is highly expressed in patients with HCC and acts via the PI3K−AKT pathway by upregulating FGFR2.[5] We suggest that screening for the mutation will enable us to diagnose HCC ahead of time, which will have a positive impact on disease prognosis. CONFLICT OF INTEREST Nothing to report.
Disentangling the relative importance of T cell responses in COVID-19: leading actors or supporting cast?
Authors: Stephen J. Kent, David S. Khoury, Arnold Reynaldi, Jennifer A. Juno, Adam K. Wheatley, Eva Stadler, E. John Wherry, James Triccas, Sarah C. Sasson, Deborah Cromer, Miles P. Davenport
Journal: Nature reviews. Immunology (2022)
Endoscopic scissors for removal of plastic tubes trapped with silk lines
Authors: Zhihui Duan, Shengyun Zhou
Journal: Endoscopy (2022)

Endoscopic scissors have the advantage of preventing potential complications associated with thermal and mechanical damage to surrounding structures [1]. They can be used on insulated cores, metallic coils, fish bones, and nasogastric tubes [1] [2] [3]. However, there have been no reports of endoscopic scissors being used to cut through silk line.
Association Between Pharmacological Treatment of Attention-Deficit/Hyperactivity Disorder and Long-term Unemployment Among Working-Age Individuals in Sweden
Authors: Lin Li, Zheng Chang, Jiangwei Sun, Andreas Jangmo, Le Zhang, Lars Magnus Andersson, Tamara Werner-Kiechle, Ewa Ahnemark, Brian M. D’Onofrio, Henrik Larsson
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Adults with attention-deficit/hyperactivity disorder (ADHD) are at greater risk for unemployment. Pharmacological treatment is effective in reducing the core symptoms of ADHD, but whether it helps to reduce the unemployment rate among adult patients remains unclear. <h3>Objective</h3> To investigate the association between use of ADHD medication and long-term unemployment in working-age adults with ADHD. <h3>Design, Setting, and Participants</h3> Data for this population-based cohort study were extracted from Swedish national registers. Among 25 358 individuals with ADHD born from 1958 to 1978, 12 875 middle-aged adults among the workforce were included. The longitudinal cohort was followed up from January 1, 2008, to December 31, 2013. Data were analyzed from March 1, 2020, through May 31, 2021. <h3>Exposures</h3> Use of medication for ADHD during the previous 2 years was the main exposure, as both categorical and continuous variables. <h3>Main Outcomes and Measures</h3> Yearly accumulated unemployed days were derived from the Public Employment Service, and long-term unemployment was defined as 90 or more days of unemployment per year. Overall and sex-specific relative risks (RRs) with 95% CIs were estimated using generalized estimating equations. <h3>Results</h3> Among 12 875 individuals with ADHD (5343 women [41.50%] and 7532 men [58.50%]; mean [SD] age, 37.9 [5.6] years), the use of ADHD medications during the previous 2 years was associated with a 10% lower risk of long-term unemployment in the following year (adjusted RR, 0.90 [95% CI, 0.87-0.95]). An association between use of ADHD medications and long-term unemployment was found among women (RR, 0.82 [95% CI, 0.76-0.89]) but not men (RR, 0.96 [95% CI, 0.91-1.01]). Longer treatment duration was associated with a lower risk of subsequent long-term unemployment among women (RR for use of 1-6 months, 0.86 [95% CI, 0.78-0.95]; RR for use of 18-24 months, 0.72 [95% CI, 0.58-0.90];<i>P</i>&lt; .001 for trend). Within-individual comparisons showed that the long-term unemployment rate was lower during periods of ADHD medication treatment compared with nontreatment periods (RR, 0.89; 95% CI, 0.85-0.94). <h3>Conclusions and Relevance</h3> The findings of this cohort study suggest that the use of ADHD medication is associated with a lower risk of subsequent long-term unemployment for middle-aged women. These findings should be considered together with the existing knowledge of risks and benefits of ADHD medication when developing treatment plans for working-age adults.
Current Landscape and Future Directions of Coronary Revascularization in Patients With Heart Failure
Authors: Yousif Ahmad, Alexandra J. Lansky, Eric J. Velazquez
Journal: JAMA Cardiology (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 Cardiology 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 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 Cardiology journal
EGFR suppresses p53 function by promoting p53 binding to DNA-PKcs: a noncanonical regulatory axis between EGFR and wild-type p53 in glioblastoma
Authors: Jie Ding, Xiaolong Li, Sabbir Khan, Chen Zhang, Feng Gao, Shayak Sen, Amanda R Wasylishen, Yang Zhao, Guillermina Lozano, Dimpy Koul, W K Alfred Yung
Journal: Neuro-Oncology (2022)

Epidermal growth factor receptor (EGFR) amplification and TP53 mutation are the two most common genetic alterations in glioblastoma multiforme (GBM). A comprehensive analysis of the TCGA GBM database revealed a subgroup with near mutual exclusivity of EGFR amplification and TP53 mutations indicative of a role of EGFR in regulating wild-type-p53 (wt-p53) function. The relationship between EGFR amplification and wt-p53 function remains undefined and this study describes the biological significance of this interaction in GBM.
Passing the Stethoscope
Authors: Tim Sanborn
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Aerosol delivery of star polymer-siRNA nanoparticles as a therapeutic strategy to inhibit lung tumor growth
Authors: Z. Ma, S.W. Wong, H. Forgham, L. Esser, M. Lai, M.N. Leiske, K. Kempe, G. Sharbeen, J. Youkhana, F. Mansfeld, J.F. Quinn, P.A. Phillips, T.P. Davis, M. Kavallaris, J.A. McCarroll
Journal: Biomaterials (2022)
Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia
Authors: Andrea Trombetti, Nasser Al-Daghri, Maria Luisa Brandi, Jorge B. Cannata-Andía, Etienne Cavalier, Manju Chandran, Catherine Chaussain, Lucia Cipullo, Cyrus Cooper, Dieter Haffner, Pol Harvengt, Nicholas C. Harvey, Muhammad Kassim Javaid, Famida Jiwa, John A. Kanis, Andrea Laslop, Michaël R. Laurent, Agnès Linglart, Andréa Marques, Gabriel T. Mindler, Salvatore Minisola, María Concepción Prieto Yerro, Mario Miguel Rosa, Lothar Seefried, Mila Vlaskovska, María Belén Zanchetta, René Rizzoli
Journal: Nature Reviews Endocrinology (2022)

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease. This Consensus Statement provides robust clinical evidence on the multidisciplinary management of children and adults with X-linked hypophosphataemia, with an emphasis on patients' experiences and needs. It is the outcome of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases.
Systematic evaluation of colorectal cancer organoid system by single-cell RNA-Seq analysis
Authors: Rui Wang, Yunuo Mao, Wendong Wang, Xin Zhou, Wei Wang, Shuai Gao, Jingyun Li, Lu Wen, Wei Fu, Fuchou Tang
Journal: Genome biology (2022)

Abstract Background Patient-derived organoid culture is a powerful system for studying the molecular mechanisms of cancers, especially colorectal cancer (CRC), one of the most prevalent cancers worldwide. There are two main types of 3D culture methods for colonic cells, but the similarities and differences between gene expression patterns in different culture media remain largely unexplored. Results Here, we establish patient-derived organoids from colorectal cancer patients and perform single-cell RNA-Seq for pairwise samples from seven patients for both organoids and their corresponding tumor and normal tissues in vivo. We find that organoids derived from tumor tissues faithfully recapitulate the main gene expression signatures of cancer cells in vivo. On the other hand, organoids derived from normal tissues exhibited some tumor-like features at the whole transcriptome level but retained normal genomic features, such as CNVs, point mutations, and normal global DNA methylation levels, for both cultural media. More importantly, we show that conditioned medium outperforms chemical-defined medium in long-term culture of tumor epithelial cells. Finally, we mutually exchange the culture medium for the organoids and find that after interchanging the medium, the organoid cells basically maintain the transcriptome characteristics of the original medium. Conclusions Our work gives a thorough evaluation of both the cultural conditions and the biological features of organoids of CRC patients.