tbuckley/cabot-search huggingface dataset:
Carbon Dots with Intrinsic Bioactivities for Photothermal Optical Coherence Tomography, Tumor‐Specific Therapy and Postoperative Wound Management
Authors: Hao Liu, Luoqi Mo, Haolin Chen, Chao Chen, Jiayi Wu, Zhilie Tang, Zhouyi Guo, Chaofan Hu, Zhiming Liu
Journal: Advanced Healthcare Materials (2021)

Abstract Carbon dots (CDs) are considered as promising candidates with superior biocompatibilities for multimodel cancer theranostics. However, incorporation of exogenous components, such as targeting molecules and chemo/photo therapeutic drugs, is often required to improve the therapeutic efficacy. Herein, an “all‐in‐one” CDs that exhibit intrinsic bioactivities for bioimaging, potent tumor therapy, and postoperative management is proposed. The multifunctional CDs derived from gallic acid and tyrosine (GT‐CDs) consist of a graphitized carbon core and N, O‐rich functional groups, which endow them with a high near‐infrared (NIR) photothermal conversion efficiency of 33.9% and tumor‐specific cytotoxicity, respectively. A new imaging modality, photothermal optical coherence tomography, is introduced using GT‐CDs as the contrast agent, offering the micrometer‐scale resolution 3D tissue morphology of tumor. For cancer therapy, GT‐CDs initiate the intracellular generation of reactive oxygen species in tumor cells but not normal cells, further induce the mitochondrial collapse and subsequent tumor cellular apoptosis. Combined with NIR photothermal treatment, synergistic antitumor therapy is achieved in vitro and in vivo. GT‐CDs also promote the healing process of bacteria‐contaminated skin wound, demonstrating their potential to prevent postoperative infection. The integrated theranostic strategy based on versatile GT‐CDs supplies an alternative easy‐to‐handle pattern for disease management.
CSIG-13. A DYNAMIC CAUSAL MODEL OF GLIOBLASTOMA STEM CELL SIGNALING PREDICTS EFFECTS OF KINASE INHIBITORS
Authors: Emilee Holzapple, Natasa Miskov-Zivanov, Brent Cochran
Journal: Neuro-Oncology (2021)

Abstract Glioblastomas and glioblastoma stem cells are heterogeneous with respect to mutations, gene expression, and response to drugs. To make predictive responses of individual GBM stem cell lines to kinase inhibitors, we have constructed a causal model of glioblastoma stem cell signaling. The core model was built starting from pathways identified from TCGA mutation data with the addition of the Jak/STAT, Hedgehog, and Notch pathways. Elements and relations between them were validated and extended using the PCNet interaction database and the INDRA database which includes machine read extractions from the biomedical literature. The result is a high confidence executable model consisting of 209 elements (proteins, genes, RNAs) and 370 regulatory logic rules between the elements. Stochastic simulations of the model provide dynamic (quantile) changes in time and responses to perturbations. The output simulates activity of individual nodes as well as cell cycle progression, apoptosis, and differentiation. To simulate the responses of individual cell lines to kinase inhibitors, the model was initialized using DNA sequencing data, RNA-seq, and reverse phase protein array (RPPA) data from each cell line. Comparing the results of the simulations to the drug responses of 11 different kinase targets in 3 cell lines, the model was 88% accurate in predicting effects on growth and survival. The model was further tested by comparing the effects of Mek inhibition of each of the cell lines in the model to the results observed in the RPPA data which overlap by 127 elements. In this case, there was less than 65% concordance between the model and the data for individual nodes. Discrepancies between the model predictions and the data are being investigated to determine whether the model logic or extent needs to be revised to improve the model. This modeling approach is a step toward developing algorithms for personalized therapeutics for GBM.
Kamran Abbasi appointed as editor in chief of<i>The BMJ</i>
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Kamran's editorial experience, clear sense of purpose, and strong commitment to The BMJ's values of credibility and integrity are what distinguished his candidacy."As BMJ heads into a new and exciting phase of investment and growth, I look forward to working with Kamran to build on this success and continue to develop The BMJ and the wider business for a digital future.BMJ is committed to diversity and inclusion, and we are proud to appoint a British Asian to this important role.This is a first in our history, but Kamran is also the first person of Asian origin to be editor in chief of any of the top four
Health and Health Care Among Transgender Adults in the United States
Authors: Ayden I. Scheim, Kellan E. Baker, Arjee J. Restar, Randall L. Sell
Journal: Annual Review of Public Health (2021)

Transgender (trans) communities in the USA and globally have long organized for health and social equity but have only recently gained increased visibility within public health. In this review, we synthesize evidence demonstrating that trans adults in the USA are affected by disparities in physical and mental health and in access to health care, relative to cisgender (nontrans) persons. We draw on theory and data to situate these disparities in their social contexts, explicating the roles of gender affirmation, multilevel and intersectional stigmas, and public policies in reproducing or ameliorating trans health disparities. Until recently, trans health disparities were largely made invisible by exclusionary data collection practices. We highlight the importance of, and methodological considerations for, collecting inclusive sex and gender data. Moving forward, we recommend routine collection of gender identity data, an emphasis on intervention research to achieve trans health equity, public policy advocacy, and investment in supporting gender-diverse public health leadership.
Injectable cartilage matrix hydrogel loaded with cartilage endplate stem cells engineered to release exosomes for non-invasive treatment of intervertebral disc degeneration
Authors: Liwen Luo, Junfeng Gong, Zhouguang Wang, Yao Liu, Jiaming Cao, Jinghao Qin, Rui Zuo, Hongyu Zhang, Shuai Wang, Ping Zhao, Di Yang, Mengjie Zhang, Yanqiu Wang, Junfeng Zhang, Yue Zhou, Changqing Li, Bing Ni, Zhiqiang Tian, MingHan Liu
Journal: Bioactive Materials (2021)

Low back pain, mainly caused by intervertebral disc degeneration (IVDD), is a common health problem; however, current surgical treatments are less than satisfactory. Thus, it is essential to develop novel non-invasive surgical methods for IVDD treatment. Here, we describe a therapeutic strategy to inhibit IVDD by injecting hydrogels modified with the extracellular matrix of costal cartilage (ECM-Gels) that are loaded with cartilage endplate stem cells (CESCs). After loaded with CESCs overexpressing Sphk2 (Lenti-Sphk2-CESCs) and injected near the cartilage endplate (CEP) of rats in vivo, ECM-Gels produced Sphk2-engineered exosomes (Lenti-Sphk2-Exos). These exosomes penetrated the annulus fibrosus (AF) and transported Sphk2 into the nucleus pulposus cells (NPCs). Sphk2 activated the phosphatidylinositol 3-kinase (PI3K)/p-AKT pathway as well as the intracellular autophagy of NPCs, ultimately ameliorating IVDD. This study provides a novel and efficient non-invasive combinational strategy for IVDD treatment using injectable ECM-Gels loaded with CESCs that express Sphk2 with sustained release of functional exosomes.
TBK1 recruitment to STING mediates autoinflammatory arthritis caused by defective DNA clearance
Authors: Tong Li, Seoyun Yum, Minghao Li, Xiang Chen, Xiaoxia Zuo, Zhijian J. Chen
Journal: The Journal of Experimental Medicine (2021)

Defective DNA clearance in DNase II−/− mice leads to lethal inflammatory diseases that can be rescued by deleting cGAS or STING, but the role of distinct signaling pathways downstream of STING in the disease manifestation is not known. We found that the STING S365A mutation, which abrogates IRF3 binding and type I interferon induction, rescued the embryonic lethality of DNase II−/− mice. However, the STING S365A mutant retains the ability to recruit TBK1 and activate NF-κB, and DNase II−/−STING-S365A mice exhibited severe polyarthritis, which was alleviated by neutralizing antibodies against TNF-α or IL-6 receptor. In contrast, the STING L373A mutation or C-terminal tail truncation, which disrupts TBK1 binding and therefore prevents activation of both IRF3 and NF-κB, completely rescued the phenotypes of DNase II−/− mice. These results demonstrate that TBK1 recruitment to STING mediates autoinflammatory arthritis independently of type I interferons. Inhibiting TBK1 binding to STING may be a therapeutic strategy for certain autoinflammatory diseases instigated by self-DNA.
A Naked Eye‐Invisible Ratiometric Fluorescent Microneedle Tattoo for Real‐Time Monitoring of Inflammatory Skin Conditions
Authors: Samuel Babity, Frédéric Couture, Estefânia V. R. Campos, Sarah Hedtrich, Raphael Hagen, Daniel Fehr, Mathias Bonmarin, Davide Brambilla
Journal: Advanced Healthcare Materials (2021)

Abstract The field of portable healthcare monitoring devices has an urgent need for the development of real‐time, noninvasive sensing and detection methods for various physiological analytes. Currently, transdermal sensing techniques are severely limited in scope (i.e., measurement of heart rate or sweat composition), or else tend to be invasive, often needing to be performed in a clinical setting. This study proposes a minimally invasive alternative strategy, consisting of using dissolving polymeric microneedles to deliver naked eye‐invisible functional fluorescent ratiometric microneedle tattoos directly to the skin for real‐time monitoring and quantification of physiological and pathological parameters. Reactive oxygen species are overexpressed in the skin in association with various pathological conditions. Here, one demonstrates for the first time the microneedle‐based delivery to the skin of active fluorescent sensors in the form of an invisible, ratiometric microneedle tattoo capable of sensing reactive oxygen species in a reconstructed human‐based skin disease model, as well as an in vivo model of UV‐induced dermal inflammation. One also elaborates a universal ratiometric quantification concept coupled with a custom‐built, multiwavelength portable fluorescence detection system. Fully realized, this approach presents an opportunity for the minimally invasive monitoring of a broad range of physiological parameters through the skin.
Reply to Abhay Singh and Prasant Nayak’s Letter to the Editor re: Luke Harper, T. Blanc, M. Peycelon, et al. Circumcision and Risk of Febrile Urinary Tract Infection in Boys with Posterior Urethral Valves: Result of the CIRCUP Randomized Trial. Eur Urol. 2022;81:64–72
Authors: Luke Harper
Journal: European Urology (2021)
Findings from 4C-T Study demonstrate an increased cardiovascular burden in girls with end stage kidney disease and kidney transplantation
Authors: Rizky I. Sugianto, Nima Memaran, Bernhard M.W. Schmidt, Anke Doyon, Daniela Thurn-Valsassina, Harika Alpay, Ali Anarat, Klaus Arbeiter, Karolis Azukaitis, Aysun K. Bayazit, Ipek K. Bulut, Salim Caliskan, Nur Canpolat, Ali Duzova, Jutta Gellerman, Jerome Harambat, Denise Homeyer, Mieczyslaw Litwin, Francesca Mencarelli, Lukasz Obrycki, Dusan Paripovic, Bruno Ranchin, Rukshana Shroff, Uwe Tegtbur, Jeannine von der Born, Ebru Yilmaz, Uwe Querfeld, Elke Wühl, Franz Schaefer, Anette Melk
Journal: Kidney International (2021)

Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre- and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum follow-up time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz +0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4 ml/min/1.73 m2 per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m2 per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure.
Correction: Manipulation of Nephron-Patterning Signals Enables Selective Induction of Podocytes from Human Pluripotent Stem Cells
Journal: Journal of the American Society of Nephrology (2021)

Yoshimura Y, Taguchi A, Tanigawa S, Yatsuda J, Kamba T, Takahasi S, Kurihara H, Mukoyama M, Nishinakamura R: Manipulation of Nephron-Patterning Signals Enables Selective Induction of Podocytes from Human Pluripotent Stem Cells. J Am Soc Nephrol 30: 304–321, 2019; DOI: <https://doi.org/10.1681/ASN.
Meet the authors: Joakim Lundeberg and Eva Gracia Villacampa
Journal: Cell Genomics (2021)

Joakim Lundeberg and Eva Gracia Villacampa are senior and first authors, respectively, of “Genome-wide spatial expression profiling in formalin-fixed tissues,” a Technology article in this issue of Cell Genomics. In an interview with Cell Genomics, the authors discuss a procedure they developed to perform genome-wide spatial analysis of mRNA in FFPE fixed tissue sections.
Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)
Authors: Michael Gnant, Amylou C. Dueck, Sophie Frantal, Miguel Martin, Hal J. Burstein, Richard Greil, Peter Fox, Antonio C. Wolff, Arlene Chan, Eric P. Winer, Georg Pfeiler, Kathy D. Miller, Marco Colleoni, Jennifer M. Suga, Gabor Rubovsky, Judith M. Bliss, Ingrid A. Mayer, Christian F. Singer, Zbigniew Nowecki, Olwen Hahn, Jacqui Thomson, Norman Wolmark, Kepa Amillano, Hope S. Rugo, Guenther G. Steger, Blanca Hernando Fernández de Aránguiz, Tufia C. Haddad, Antonia Perelló, Meritxell Bellet, Hannes Fohler, Otto Metzger Filho, Anita Jallitsch-Halper, Kadine Solomon, Céline Schurmans, Kathy P. Theall, Dongrui R. Lu, Kathleen Tenner, Christian Fesl, Angela DeMichele, Erica L. Mayer
Journal: Journal of Clinical Oncology (2021)

Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor-positive breast cancer has not been confirmed.
Assembled Cell‐Decorated Collagen (AC‐DC) Fiber Bioprinted Implants with Musculoskeletal Tissue Properties Promote Functional Recovery in Volumetric Muscle Loss
Authors: Kyle W. Christensen, Jonathan Turner, Kelly Coughenour, Yas Maghdouri‐White, Anna A. Bulysheva, Olivia Sergeant, Michael Rariden, Alessia Randazzo, Andrew J. Sheean, George J. Christ, Michael P. Francis
Journal: Advanced Healthcare Materials (2021)

Musculoskeletal tissue injuries, including volumetric muscle loss (VML), are commonplace and often lead to permanent disability and deformation. Addressing this healthcare need, an advanced biomanufacturing platform, assembled cell-decorated collagen (AC-DC) bioprinting, is invented to rapidly and reproducibly create living biomaterial implants, using clinically relevant cells and strong, microfluidic wet-extruded collagen microfibers. Quantitative analysis shows that the directionality and distribution of cells throughout AC-DC implants mimic native musculoskeletal tissue. AC-DC bioprinted implants further approximate or exceed the strength and stiffness of human musculoskeletal tissue and exceed collagen hydrogel tensile properties by orders of magnitude. In vivo, AC-DC implants are assessed in a critically sized muscle injury in the hindlimb, with limb torque generation potential measured over 12 weeks. Both acellular and cellular implants promote functional recovery compared to the unrepaired group, with AC-DC implants containing therapeutic muscle progenitor cells promoting the highest degree of recovery. Histological analysis and automated image processing of explanted muscle cross-sections reveal increased total muscle fiber count, median muscle fiber size, and increased cellularization for injuries repaired with cellularized implants. These studies introduce an advanced bioprinting method for generating musculoskeletal tissue analogs with near-native biological and biomechanical properties with the potential to repair myriad challenging musculoskeletal injuries.
Head and neck tumor segmentation in PET/CT: The HECKTOR challenge
Authors: Valentin Oreiller, Vincent Andrearczyk, Mario Jreige, Sarah Boughdad, Hesham Elhalawani, Joel Castelli, Martin Vallieres, Simeng Zhu, Juanying Xie, Ying Peng, Andrei Iantsen, Mathieu Hatt, Yading Yuan, Jun Ma, Xiaoping Yang, Chinmay Rao, Suraj Pai, Kanchan Ghimire, Xue Feng, Mohamed A. Naser, Clifton D. Fuller, Fereshteh Yousefirizi, Arman Rahmim, Huai Chen, Lisheng Wang, John O. Prior, Adrien Depeursinge
Journal: Medical Image Analysis (2021)

This paper relates the post-analysis of the first edition of the HEad and neCK TumOR (HECKTOR) challenge. This challenge was held as a satellite event of the 23rd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020, and was the first of its kind focusing on lesion segmentation in combined FDG-PET and CT image modalities. The challenge's task is the automatic segmentation of the Gross Tumor Volume (GTV) of Head and Neck (H&N) oropharyngeal primary tumors in FDG-PET/CT images. To this end, the participants were given a training set of 201 cases from four different centers and their methods were tested on a held-out set of 53 cases from a fifth center. The methods were ranked according to the Dice Score Coefficient (DSC) averaged across all test cases. An additional inter-observer agreement study was organized to assess the difficulty of the task from a human perspective. 64 teams registered to the challenge, among which 10 provided a paper detailing their approach. The best method obtained an average DSC of 0.7591, showing a large improvement over our proposed baseline method and the inter-observer agreement, associated with DSCs of 0.6610 and 0.61, respectively. The automatic methods proved to successfully leverage the wealth of metabolic and structural properties of combined PET and CT modalities, significantly outperforming human inter-observer agreement level, semi-automatic thresholding based on PET images as well as other single modality-based methods. This promising performance is one step forward towards large-scale radiomics studies in H&N cancer, obviating the need for error-prone and time-consuming manual delineation of GTVs.
Multifactorial falls prevention programme compared with usual care in UK care homes for older people: multicentre cluster randomised controlled trial with economic evaluation
Authors: Pip A Logan, Jane C Horne, John R F Gladman, Adam L Gordon, Tracey Sach, Allan Clark, Katie Robinson, Sarah Armstrong, Sue Stirling, Paul Leighton, Janet Darby, Fran Allen, Lisa Irvine, Ed C F Wilson, Chris Fox, Simon Conroy, Gail Mountain, Karen McCartney, Maureen Godfrey, Erika Sims
Journal: BMJ (2021)

Abstract Objectives To determine the clinical and cost effectiveness of a multifactorial fall prevention programme compared with usual care in long term care homes. Design Multicentre, parallel, cluster randomised controlled trial. Setting Long term care homes in the UK, registered to care for older people or those with dementia. Participants 1657 consenting residents and 84 care homes. 39 were randomised to the intervention group and 45 were randomised to usual care. Interventions Guide to Action for Care Homes (GtACH): a multifactorial fall prevention programme or usual care. Main outcome measures Primary outcome measure was fall rate at 91-180 days after randomisation. The economic evaluation measured health related quality of life using quality adjusted life years (QALYs) derived from the five domain five level version of the EuroQoL index (EQ-5D-5L) or proxy version (EQ-5D-5L-P) and the Dementia Quality of Life utility measure (DEMQOL-U), which were self-completed by competent residents and by a care home staff member proxy (DEMQOL-P-U) for all residents (in case the ability to complete changed during the study) until 12 months after randomisation. Secondary outcome measures were falls at 1-90, 181-270, and 271-360 days after randomisation, Barthel index score, and the Physical Activity Measure-Residential Care Homes (PAM-RC) score at 91, 180, 270, and 360 days after randomisation. Results Mean age of residents was 85 years. 32% were men. GtACH training was delivered to 1051/1480 staff (71%). Primary outcome data were available for 630 participants in the GtACH group and 712 in the usual care group. The unadjusted incidence rate ratio for falls between 91 and 180 days was 0.57 (95% confidence interval 0.45 to 0.71, P&lt;0.001) in favour of the GtACH programme (GtACH: six falls/1000 residents v usual care: 10 falls/1000). Barthel activities of daily living indices and PAM-RC scores were similar between groups at all time points. The incremental cost was £108 (95% confidence interval −£271.06 to 487.58), incremental QALYs gained for EQ-5D-5L-P was 0.024 (95% confidence interval 0.004 to 0.044) and for DEMQOL-P-U was 0.005 (−0.019 to 0.03). The incremental costs per EQ-5D-5L-P and DEMQOL-P-U based QALY were £4544 and £20 889, respectively. Conclusions The GtACH programme was associated with a reduction in fall rate and cost effectiveness, without a decrease in activity or increase in dependency. Trial registration ISRCTN34353836 .