tbuckley/cabot-search huggingface dataset:
Evans blue-modified radiolabeled fibroblast activation protein inhibitor as long-acting cancer therapeutics
Authors: Xuejun Wen, Pengfei Xu, Mengqi Shi, Jia Liu, Xinying Zeng, Yiren Zhang, Changrong Shi, Jingchao Li, Zhide Guo, Xianzhong Zhang, Pek-Lan Khong, Xiaoyuan Chen
Journal: Theranostics (2021)

Rationale: Fibroblast activation protein (FAP) targeted molecular imaging radiotracers have shown promising preclinical and clinical results in tumor diagnosis. However, rapid clearance and inadequate tumor retention of these molecules have hindered them for further clinical translation in cancer therapy. In this study, we aimed to develop a series of albumin binder-truncated Evans blue (EB) modified FAP targeted radiotracers, and optimize the pharmacokinetic (PK) characteristics to overcome the existing limitations in order to apply in the radionuclide therapy of cancer. Methods: A series of compounds with the general structure of EB-FAPI-Bn were synthesized based on a FAP inhibitor (FAPI) variant (FAPI-02) and radiolabeled with 177LuCl3. To verify the binding affinity and FAP targeting specificity of these tracers in vitro, U87MG cell uptake and competition assays were performed. Preclinical PK was evaluated in U87MG tumor-bearing mice using SPECT imaging and biodistribution studies. The lead compound EB-FAPI-B1 was selected and cancer therapeutic efficacy of 177Lu-EB-FAPI-B1 was assessed in U87MG tumor-bearing mice. Results:177Lu-EB-FAPI-B1, B2, B3, B4 were stable in PBS (pH 7.4) and saline for at least 24 h. EB-FAPI-B1 showed high binding affinity (IC50 = 16.5 nM) to FAP in vitro, which was comparable with that of FAPI-02 (IC50 = 10.9 nM). SPECT imaging and biodistribution studies of 177Lu-EB-FAPI-B1, B2, B3, B4 have proved their prominently improved tumor accumulation and retention at 96 h post-injection, especially for 177Lu-EB-FAPI-B1, high tumor uptake and low background signal make it the optimal compound. Compared to the saline group, noteworthy tumor growth inhibitions of 177Lu-EB-FAPI-B1 have been observed after administration of different dosages. Conclusion: In this study, several EB modified FAPI-02 related radiopharmaceuticals have been synthesized successfully and evaluated. High binding affinity and FAP targeting specificity were identified in vitro and in vivo. Remarkably enhanced tumor uptake and retention of EB-FAPI-B1 were found over the unmodified FAPI-02. 177Lu-EB-FAPI-B1 showed remarkable tumor growth suppression in U87MG tumor model with negligible side effects, indicating that 177Lu-EB-FAPI-B1 is promising for clinical application and transformation.
154P Results of an open-label, phase Ia/Ib study of olaratumab plus pembrolizumab in patients with unresectable, locally advanced or metastatic soft tissue sarcoma
Authors: P. Schöffski, R. Bahleda, A.J. Wagner, M. Burgess, N. Junker, M. Chisamore, P. Peterson, M. Ceccarelli, T. William
Journal: Annals of Oncology (2021)
Third BNT162b2 Vaccination Neutralization of SARS-CoV-2 Omicron Infection
Authors: Ital Nemet, Limor Kliker, Yaniv Lustig, Neta Zuckerman, Oran Erster, Carmit Cohen, Yitshak Kreiss, Sharon Alroy-Preis, Gili Regev-Yochay, Ella Mendelson, Michal Mandelboim
Journal: New England Journal of Medicine (2021)
Positing numerosities may be metaphysically extravagant; positing representation of numerosities is not
Authors: Simon A. B. Brown
Journal: Behavioral and Brain Sciences (2021)

Clarke and Beck (C&B) assume that approximate number system (ANS) representations should be assigned referents from our scientific ontology. However, many representations, both in perception and cognition, do not straightforwardly refer to such entities. If we reject C&B's assumption, many possible contents for ANS representations besides number are compatible with the evidence C&B cite.
Prevalence and Treatment of Diabetes in China, 2013-2018
Authors: Limin Wang, Wen Peng, Zhenping Zhao, Mei Zhang, Zumin Shi, Ziwei Song, Xiao Zhang, Chun Li, Zhengjing Huang, Xiaomin Sun, Linhong Wang, Maigeng Zhou, Jing Wu, Youfa Wang
Journal: JAMA (2021)

<h3>Importance</h3> Recent data on prevalence, awareness, treatment, and risk factors of diabetes in China is necessary for interventional efforts. <h3>Objective</h3> To estimate trends in prevalence, awareness, treatment, and risk factors of diabetes in China based on national data. <h3>Design, Setting, and Participants</h3> Cross-sectional nationally representative survey data collected in adults aged 18 years or older in mainland China from 170 287 participants in the 2013-2014 years and 173 642 participants in the 2018-2019 years. <h3>Exposures</h3> Fasting plasma glucose and hemoglobin A<sub>1c</sub>levels were measured for all participants. A 2-hour oral glucose tolerance test was conducted for all participants without diagnosed diabetes. <h3>Main Outcomes and Measures</h3> Primary outcomes were diabetes and prediabetes defined according to American Diabetes Association criteria. Secondary outcomes were awareness, treatment, and control of diabetes and prevalence of risk factors. A hemoglobin A<sub>1c</sub>level of less than 7.0% (53 mmol/mol) among treated patients with diabetes was considered adequate glycemic control. <h3>Results</h3> In 2013, the median age was 55.8 years (IQR, 46.4-65.2 years) and the weighted proportion of women was 50.0%; in 2018, the median age was 51.3 years (IQR, 42.1-61.6 years), and the weighted proportion of women was 49.5%. The estimated prevalence of diabetes increased from 10.9% (95% CI, 10.4%-11.5%) in 2013 to 12.4% (95% CI, 11.8%-13.0%) in 2018 (<i>P</i> &lt; .001). The estimated prevalence of prediabetes was 35.7% (95% CI, 34.2%-37.3%) in 2013 and 38.1% (95% CI, 36.4%-39.7%) in 2018 (<i>P</i> = .07). In 2018, among adults with diabetes, 36.7% (95% CI, 34.7%-38.6%) reported being aware of their condition, and 32.9% (95% CI, 30.9%-34.8%) reported being treated; 50.1% (95% CI, 47.5%-52.6%) of patients receiving treatment were controlled adequately. These rates did not change significantly from 2013. From 2013 to 2018, low physical activity, high intake of red meat, overweight, and obesity significantly increased in prevalence. <h3>Conclusions and Relevance</h3> In this survey study, the estimated diabetes prevalence was high and increased from 2013 to 2018. There was no significant improvement in the estimated prevalence of adequate treatment.
Doubt at the core: Unspoken vaccine hesitancy among healthcare workers
Authors: Leonardo W. Heyerdahl, Stef Dielen, ToTran Nguyen, Carla Van Riet, Tarun Kattumana, Clarissa Simas, Nico Vandaele, Anne-Mieke Vandamme, Corinne Vandermeulen, Tamara Giles-Vernick, Heidi Larson, Koen Peeters Grietens, Charlotte Gryseels
Journal: The Lancet Regional Health - Europe (2021)
Management of Gout
Authors: Irsk J. Anderson, Andrew M. Davis, Reem H. Jan
Journal: JAMA (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 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
Mutations Highly Specific for Secondary AML Are Associated with Poor Outcomes in Patients with <i>NPM1</i>-Mutated ELN Favorable Risk AML
Authors: Onyee Chan, Najla Al Ali, Hammad Tashkandi, Austin Ellis, Somedeb Ball, Ling Zhang, Mohammad Hussaini, Jinming Song, Seongseok Yun, Chetasi Talati, Andrew T. Kuykendall, Eric Padron, David A. Sallman, Kendra Sweet, Rami S. Komrokji, Jeffrey E. Lancet
Journal: Blood (2021)
An engineered oncolytic vaccinia virus encoding a single-chain variable fragment against TIGIT induces effective antitumor immunity and synergizes with PD-1 or LAG-3 blockade
Authors: Shuguang Zuo, Min Wei, Tiancheng Xu, Lingkai Kong, Bohao He, Shiqun Wang, Shibing Wang, Junhua Wu, Jie Dong, Jiwu Wei
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background In addition to directly lysing tumors, oncolytic viruses also induce antitumor immunity by recruiting and activating immune cells in the local tumor microenvironment. However, the activation of the immune cells induced by oncolytic viruses is always accompanied by high-level expression of immune checkpoints in these cells, which may reduce the efficacy of the oncolytic viruses. The aim of this study is to arm the oncolytic vaccinia virus (VV) with immune checkpoint blockade to enhance its antitumor efficacy. Methods Through homologous recombination with the parental VV, an engineered VV-scFv-TIGIT was produced, which encodes a single-chain variable fragment (scFv) targeting T-cell immunoglobulin and ITIM domain (TIGIT). The antitumor efficacy of the VV-scFv-TIGIT was explored in several subcutaneous and ascites tumor models. The antitumor efficacy of VV-scFv-TIGIT combined with programmed cell death 1 (PD-1) or lymphocyte-activation gene 3 (LAG-3) blockade was also investigated. Results The VV-scFv-TIGIT effectively replicated in tumor cells and lysed them, and prompt the infected tumor cells to secret the functional scFv-TIGIT. Compared with control VV, intratumoral injection of VV-scFv-TIGIT in several mouse subcutaneous tumor models showed superior antitumor efficacy, accompanied by more T cell infiltration and a higher degree of CD8 + T cells activation. Intraperitoneal injection of VV-scFv-TIGIT in a mouse model of malignant ascites also significantly improved T cell infiltration and CD8 + T cell activation, resulting in more than 90% of the tumor-bearing mice being cured. Furthermore, the antitumor immune response induced by VV-scFv-TIGIT was dependent on CD8 + T cells which mediated a long-term immunological memory and a systemic antitumor immunity against the same tumor. Finally, the additional combination of PD-1 or LAG-3 blockade further enhanced the antitumor efficacy of VV-scFv-TIGIT, increasing the complete response rate of tumor-bearing mice. Conclusions Oncolytic virotherapy using engineered VV-scFv-TIGIT was an effective strategy for cancer immunotherapy. Administration of VV-scFv-TIGIT caused a profound reshaping of the suppressive tumor microenvironment from ‘cold’ to ‘hot’ status. VV-scFv-TIGIT also synergized with PD-1 or LAG-3 blockade to achieve a complete response to tumors with poor response to VV or immune checkpoint blockade monotherapy.
Development and Evaluation of a Holistic and Mechanistic Modeling Framework for Chemical Emissions, Fate, Exposure, and Risk
Authors: Li Li, Alessandro Sangion, Frank Wania, James M. Armitage, Liisa Toose, Lauren Hughes, Jon A. Arnot
Journal: Environmental Health Perspectives (2021)

Background: Large numbers of chemicals require evaluation to determine if their production and use pose potential risks to ecological and human health. For most chemicals, the inadequacy and uncertainty of chemical-specific data severely limit the application of exposure- and risk-based methods for screening-level assessments, priority setting, and effective management. Objective: We developed and evaluated a holistic, mechanistic modeling framework for ecological and human health assessments to support the safe and sustainable production, use, and disposal of organic chemicals. Methods: We consolidated various models for simulating the PROduction-To-EXposure (PROTEX) continuum with empirical data sets and models for predicting chemical property and use function information to enable high-throughput (HT) exposure and risk estimation. The new PROTEX-HT framework calculates exposure and risk by integrating mechanistic computational modules describing chemical behavior and fate in the socioeconomic system (i.e., life cycle emissions), natural and indoor environments, various ecological receptors, and humans. PROTEX-HT requires only molecular structure and chemical tonnage (i.e., annual production or consumption volume) as input information. We evaluated the PROTEX-HT framework using 95 organic chemicals commercialized in the United States and demonstrated its application in various exposure and risk assessment contexts. Results: Seventy-nine percent and 97% of the PROTEX-HT human exposure predictions were within one and two orders of magnitude, respectively, of independent human exposure estimates inferred from biomonitoring data. PROTEX-HT supported screening and ranking chemicals based on various exposure and risk metrics, setting chemical-specific maximum allowable tonnage based on user-defined toxicological thresholds, and identifying the most relevant emission sources, environmental media, and exposure routes of concern in the PROTEX continuum. The case study shows that high chemical tonnage did not necessarily result in high exposure or health risks. Conclusion: Requiring only two chemical-specific pieces of information, PROTEX-HT enables efficient screening-level evaluations of existing and premanufacture chemicals in various exposure- and risk-based contexts. https://doi.org/10.1289/EHP9372
Repurposing ferumoxytol: Diagnostic and therapeutic applications of an FDA-approved nanoparticle
Authors: Yue Huang, Jessica C. Hsu, Hyun Koo, David P. Cormode
Journal: Theranostics (2021)

Ferumoxytol is an intravenous iron oxide nanoparticle formulation that has been approved by the U.S. Food and Drug Administration (FDA) for treating anemia in patients with chronic kidney disease. In recent years, ferumoxytol has also been demonstrated to have potential for many additional biomedical applications due to its excellent inherent physical properties, such as superparamagnetism, biocatalytic activity, and immunomodulatory behavior. With good safety and clearance profiles, ferumoxytol has been extensively utilized in both preclinical and clinical studies. Here, we first introduce the medical needs and the value of current iron oxide nanoparticle formulations in the market. We then focus on ferumoxytol nanoparticles and their physicochemical, diagnostic, and therapeutic properties. We include examples describing their use in various biomedical applications, including magnetic resonance imaging (MRI), multimodality imaging, iron deficiency treatment, immunotherapy, microbial biofilm treatment and drug delivery. Finally, we provide a brief conclusion and offer our perspectives on the current limitations and emerging applications of ferumoxytol in biomedicine. Overall, this review provides a comprehensive summary of the developments of ferumoxytol as an agent with diagnostic, therapeutic, and theranostic functionalities.
Vaccines 2020: The era of the digital vaccine is here
Authors: Mariagrazia Pizza, Simone Pecetta, Rino Rappuoli
Journal: Science Translational Medicine (2021)

The SARS-CoV-2 pandemic has generated a renaissance in vaccinology, with COVID-19 mRNA vaccines delivering a “digital code” of the viral antigen with no need to purify proteins or inactivate pathogens.
Method of Morphometry of Cartilaginous Part of Ribs for Planning of Auricle Reconstruction
Authors: N. I. Imshenetskaya, D. A. Lezhnev, O. Z. Topol’nitskiy, T. A. Bakshi, E. Y. Lazarenko, A. P. Gurgenadze
Journal: Radiology - Practice (2021)

Ultrasound examination of the skin was performed on 63 women, using a 10–22 MHz high frequency linear transducer on the scanning surface in B-mode and Color Doppler Imaging (CDI) mode with the scanning depth of 7 mm, as well as a 6–18 MHz transducer in B-mode with the scanning depth of 15 mm. The thickness of the dermis was measured between the epidermis and the subcutaneous adipose tissue in the middle and lower third of the face at standard points. To determine the border between the dermis and hypodermis, we used the subdermal vascular plexus as an additional anatomical landmark, which was well visualized in the CDI mode. Comparison of three or more groups of independent quantitative parameters was carried out using ANOVA (Analysis of Variance) for looking for dependencies in the data obtained by determining the significance of differences in means. The level of significance was presented according to F. Fisher’s criterion. As a result of the analysis of variance, a significance level was 0.15, based on which it was concluded that there is no difference in measuring the thickness of the dermis with 6–18 MHz and 10–22 MHz high frequency transducers. The optimal scanning depth for measuring the skin thickness is 7–15 mm. Evaluation of the skin microcirculation should be carried out in the Doppler mode at a pulse recurrence frequency of less than 1 kHz.
Dietary sugar restriction reduces hepatic de novo lipogenesis in boys with fatty liver disease
Authors: Stephanie T. Chung, Sheela N. Magge
Journal: Journal of Clinical Investigation (2021)

Nonalcoholic fatty liver disease (NAFLD) in children resulting from the obesity epidemic is widespread and increasing. Although the complexities of pediatric NAFLD are recognized, screening and therapies in children remain limited. Moreover, pediatric NAFLD diagnosis fails to consider insulin resistance and metabolic dysfunction as important determinants. In this issue of the JCI, Cohen et al. explored the contribution of dietary factors to the pathogenesis of NAFLD in adolescent boys with biopsy-proven NAFLD and control participants. Notably, dietary sugar restriction over 8 weeks decreased de novo lipogenesis (DNL) and hepatic fat. The change in DNL correlated with changes in insulin and weight, but not with changes in hepatic fat, supporting the relevance of metabolic dysfunction to NAFLD. These results confirm the pathological link between excessive dietary sugar intake and NAFLD in children and support recent recommendations to change the nomenclature of NAFLD to metabolic associated fatty liver disease (MAFLD).
Numerical cognition needs more and better distinctions, not fewer
Authors: Hilary Barth, Anna Shusterman
Journal: Behavioral and Brain Sciences (2021)

Abstract We agree that the approximate number system (ANS) truly represents number. We endorse the authors' conclusions on the arguments from confounds, congruency, and imprecision, although we disagree with many claims along the way. Here, we discuss some complications with the meanings that undergird theories in numerical cognition, and with the language we use to communicate those theories.
Genomic Landscape of PHD Finger Protein 6 (<i>PHF6</i>) Mutant Myeloid Neoplasia
Authors: Laila Terkawi, Carmelo Gurnari, Sunisa Kongkiatkamon, Simona Pagliuca, Minako Mori, Hassan Awada, Ishani Pandit, Christopher Haddad, Tariq Kewan, Waled Bahaj, Misam Zawit, Babal K. Jha, Hetty E. Carraway, Anjali Advani, Jaroslaw P. Maciejewski, Valeria Visconte
Journal: Blood (2021)
Surgeries and Diagnostic Procedures in Hemophilia Patients on Concizumab Prophylaxis: Results from the Phase 2 Explorer4 and Explorer5 Trials
Authors: Allison P. Wheeler, Gary Benson, Hermann Eichler, Sidsel Marie Tønder, Katarina Cepo, Victor Jimenez Yuste, Kaan Kavakli, Lily LL Wong, Tadashi Matsushita
Journal: Blood (2021)
Clinical translation of advanced colonic drug delivery technologies
Authors: Atheer Awad, Christine M. Madla, Laura E. McCoubrey, Fabiana Ferraro, Francesca K.H. Gavins, Asma Buanz, Simon Gaisford, Mine Orlu, Florence Siepmann, Juergen Siepmann, Abdul W. Basit
Journal: Advanced Drug Delivery Reviews (2021)
High-wearable EEG-based transducer for engagement detection in pediatric rehabilitation
Authors: Andrea Apicella, Pasquale Arpaia, Salvatore Giugliano, Giovanna Mastrati, Nicola Moccaldi
Journal: Brain-Computer Interfaces (2021)

A method for high-wearable EEG-based assessment of pediatric emotional and cognitive engagement in neuro-motor rehabilitation is proposed. A specific easy calibration is provided in the perspective of a personalized medicine. Due to the lack of studies evaluating pediatric multidimensional engagement, an observational non-interventional protocol was adopted for collecting the EEG data related to the high/low levels of engagement. The experimental validation of the proposed method involved four children performing a rehabilitation exercise in five 8-min sessions. Due to the age and frailty of the subjects, no negative emotions were expressly induced and an unbalanced dataset was obtained. Different Synthetic Minority Oversampling Technique (SMOTE)-based strategies for unbalanced dataset management and classification methods were compared. The highest performances were achieved by combining Artificial Neural Network (ANN) models with the KMeansSMOTE oversampling method. Balanced accuracies of 71.2 % and 74.5 % for the emotional engagement and the cognitive engagement are obtained, respectively.
PCR amplicons identify widespread copy number variation in human centromeric arrays and instability in cancer
Authors: Leonardo Gomes de Lima, Edmund Howe, Vijay Pratap Singh, Tamara Potapova, Hua Li, Baoshan Xu, Jemma Castle, Steve Crozier, Christine J. Harrison, Steve C. Clifford, Karen H. Miga, Sarra L. Ryan, Jennifer L. Gerton
Journal: Cell Genomics (2021)

Centromeric α-satellite repeats represent ∼6% of the human genome, but their length and repetitive nature make sequencing and analysis of those regions challenging. However, centromeres are essential for the stable propagation of chromosomes, so tools are urgently needed to monitor centromere copy number and how it influences chromosome transmission and genome stability. We developed and benchmarked droplet digital PCR (ddPCR) assays that measure copy number for five human centromeric arrays. We applied them to characterize natural variation in centromeric array size, analyzing normal tissue from 37 individuals from China and 39 individuals from the US and UK. Each chromosome-specific array varies in size up to 10-fold across individuals and up to 50-fold across chromosomes, indicating a unique complement of arrays in each individual. We also used the ddPCR assays to analyze centromere copy number in 76 matched tumor-normal samples across four cancer types, representing the most-comprehensive quantitative analysis of centromeric array stability in cancer to date. In contrast to stable transmission in cultured cells, centromeric arrays show gain and loss events in each of the cancer types, suggesting centromeric α-satellite DNA represents a new category of genome instability in cancer. Our methodology for measuring human centromeric-array copy number will advance research on centromeres and genome integrity in normal and disease states.
Contributions of obesity to kidney health and disease: insights from Mendelian randomization and the human kidney transcriptomics
Authors: Xiaoguang Xu, James M Eales, Xiao Jiang, Eleanor Sanderson, Maciej Drzal, Sushant Saluja, David Scannali, Bryan Williams, Andrew P Morris, Tomasz J Guzik, Fadi J Charchar, Michael V Holmes, Maciej Tomaszewski
Journal: Cardiovascular Research (2021)

Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney.