tbuckley/cabot-search huggingface dataset:
Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis
Authors: Wenqi Yu, Ruyi Lin, Xueqin He, Xiaotong Yang, Huilin Zhang, Chuan Hu, Rui Liu, Yuan Huang, Yi Qin, Huile Gao
Journal: Acta Pharmaceutica Sinica B (2021)
Prognostic Implication of RV Coupling to Pulmonary Circulation for Successful Weaning From Extracorporeal Membrane Oxygenation
Authors: Darae Kim, Yoonjee Park, Ki Hong Choi, Taek Kyu Park, Joo Myung Lee, Yang Hyun Cho, Jin-Oh Choi, Eun-Seok Jeon, Jeong Hoon Yang
Journal: JACC. Cardiovascular imaging (2021)
Abstract 3510: PAR1(1–26): The Putative Signal Peptide of Protease-Activated Receptor 1 Confers Potent Protection From Myocardial Ischemia and Reperfusion Injury Through a Gi-Protein Signaling Pathway
Authors: Jennifer L Strande, Kasi V Routhu
Journal: Circulation (2009)

Background The Protease-Activated Receptor 1 (PAR1) is activated by the proteolytic release of the N-terminal 41 amino acids. Exogenously administered PAR1(1– 41) peptides protect against myocardia...
Abstract 379: Nursing Perspectives on Neuro-Prognostication for Post-Cardiac Arrest Patients and Their Integral Role in Supporting Surrogate Decision Makers
Authors: Sarah M Perman, Bonnie J Siry, Stacie L Daugherty, Edward Havranek
Journal: Circulation (2019)

Introduction: Post cardiac arrest patients frequently rely on surrogate decision makers (SDM) for critical decisions during their hospitalization. Our prior research has shown that bedside nurses are key resources for SDMs. Nurses’ understanding of post-arrest guidelines is therefore crucial if post-arrest care is to be concordant with guidelines. Objective: To explore critical care nurses familiarity with neuroprognostic guidelines and learn how they support families with decision making in the ICU. Methods: This inductive qualitative study consists of interviews with critical care nurses at an urban academic hospital. Subjects were identified by reviewing the care team of recent cardiac arrest patients. Nurses were invited by email to participate. Using a standardized interview guide, one on one interviews were conducted, audio recorded, and transcribed. Transcripts were read in entirety and thematically coded by two investigators. Results: Seven critical care nurses participated in this study. The participants were predominately female (6/7), mean age 32.4 years and had worked in critical care nursing from 1 year to 16 years. The nurses interviewed were based in the medical (3), cardiac (2) and neuro (2) ICUs. Major themes identified were: 1) discussion regarding prognosis is a team approach; 2) interpretation of neuroprognostic guidelines by nurses is variable; 3) communicating uncertainty to families and setting expectations is challenging. Excerpts to support these themes are identified in the table. Conclusion: Nurses are critical stakeholders in supporting surrogate decision makers in their decision-making. Ensuring that they are supported in relaying similar messages as the physician team, provided with more information regarding neurologic prognostication and supported in how to communicate uncertainty/set expectations will assist nurses in the integral and unique roll they play at the bedside of the post-cardiac arrest patient.
IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells
Authors: Philipp Starkl, Nicolas Gaudenzio, Thomas Marichal, Laurent L. Reber, Riccardo Sibilano, Martin L. Watzenboeck, Frédéric Fontaine, André C. Mueller, Mindy Tsai, Sylvia Knapp, Stephen J. Galli
Journal: Allergy (2021)

In contrast to their clearly defined roles in allergic diseases, the physiologic functions of Immunoglobulin E antibodies (IgEs) and mast cells (MCs) remain enigmatic. Recent research supports the toxin hypothesis, showing that MCs and IgE-related type 2 immune responses can enhance host defense against certain noxious substances, including honeybee venom (BV). However, the mechanisms by which MCs can interfere with BV toxicity are unknown. In this study, we assessed the role of IgE and certain MC products in MC-mediated BV detoxification.
To Recognize Child Physical Abuse Early, Frontline Clinicians Need Subspecialty Expertise
Authors: Daniel M. Lindberg
Journal: JAMA Network Open (2021)

Mary Clyde Pierce, MD; Kim Kaczor, MS; Douglas J. Lorenz, PhD; Gina Bertocci, PhD; Amanda K. Fingarson, DO; Kathi Makoroff, MD, MEd; Rachel P. Berger, MD, MPH; Berkeley Bennett, MD, MS; Julia Magana, MD; Shannon Staley, MD; Veena Ramaiah, MD; Kristine Fortin, MD; Melissa Currie, MD; Bruce E. Herman, MD; Sandra Herr, MD; Kent P. Hymel, MD; Carole Jenny, MD, MBA; Karen Sheehan, MD, MPH; Noel Zuckerbraun, MD, MPH; Sheila Hickey, MSW, MJ; Gabriel Meyers, MSW; John M. Leventhal, MD
Re: Svetlana Avulova, John C. Cheville, Christine M. Lohse, et al. Grading of Chromophobe Renal Cell Carcinoma: Evidence for a Four-tiered Classification Incorporating Coagulative Tumor Necrosis. Eur Urol 2021;79:225–31
Authors: Brett Delahunt, Hemamali Samaratunga, Lars Egevad
Journal: European Urology (2021)
Chondroitin sulfate-mediated albumin corona nanoparticles for the treatment of breast cancer
Authors: Tiantian Tan, Qin Yang, Dan Chen, Juan Zhao, Ling Xiang, Jiaxing Feng, Xu Song, Yao Fu, Tao Gong
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Chondroitin sulfate-mediated albumin corona nanoparticles were readily prepared without any chemical reaction, and their active tumor targeting and therapeutic effects were examined. Negatively charged chondroitin sulfate (CS) and positively charged doxorubicin (DOX) self-assembled into nanoparticles (CS-DOX-NPs) via electrostatic interactions. Bovine serum albumin (BSA) was then adsorbed on the surface of CS-DOX-NPs to form albumin corona nanoparticles (BC-DOX-NPs) protected from endogenous proteins. Due to the dual effect of BSA and CS, BC-DOX-NPs interacted with the gp60, SPARC and CD44 receptors on tumor cells, facilitating their rapid and efficient transcytosis and improving their accumulation and uptake within tumor tissues. The simultaneous presence of BSA and CS also allowed BC-DOX-NPs to target CD44 efficiently, leading to greater cellular uptake and cytotoxicity against 4T1 cells than CS-DOX-NPs or free DOX. Intravenous injection of BC-DOX-NPs into orthotopic 4T1 tumor-bearing mice led to greater drug accumulation at the tumor site than with CS-DOX-NPs or free DOX, resulting in significant inhibition of tumor growth and lower exposure of major organs to the drug.
Assessing risk for healthcare workers during the pandemic: don’t forget workplace safety committees or airborne transmission
Authors: Raymond M Agius, Lewis T Hughes, Denise Kendrick, John F R Robertson, Marcia Stewart
Journal: BMJ (2021)

Khunti and colleagues advocate integrating "the workplace, the workforce, and the individual" in "assessing risk for healthcare workers during the covid-19 pandemic." 1 The same approach is relevant to other workers, notably in social care.It also warrants highlighting that health and safety law requires a "suitable and sufficient" risk assessment and the involvement of workers and their representatives.
The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder
Authors: Gabriel D. Bosse, Roberto Cadeddu, Gabriele Floris, Ryan D. Farero, Eva Vigato, Suhjung J. Lee, Tejia Zhang, Nilesh W. Gaikwad, Kristen A. Keefe, Paul E.M. Phillips, Marco Bortolato, Randall T. Peterson
Journal: Journal of Clinical Investigation (2021)

Opioid use disorder (OUD) has become a leading cause of death in the United States, yet current therapeutic strategies remain highly inadequate. To identify potential treatments for OUD, we screened a targeted selection of over 100 drugs using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride reduced the physical signs associated with opioid withdrawal. In rat models of neuropathic pain, finasteride did not alter the antinociceptive effect of opioids and reduced withdrawal-induced hyperalgesia. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish in a fashion akin to the effects of finasteride. These results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new treatment option for this disorder.
A commentary on “Are we curing by cutting? A call for long-term follow up and outcomes research in global surgery interventions – Perspective” (Int J Surg 2021; 87:105885)
Authors: María Manuela Rodríguez-Gutiérrez, Ivan David Lozada-Martínez, Pedro Jose Cabarcas-Sabbag, María Carolina Díaz-Rivera
Journal: International Journal of Surgery (2021)
Beyond Programmed Death-Ligand 1: B7-H6 Emerges as a Potential Immunotherapy Target in SCLC
Authors: Portia L. Thomas, Sarah M. Groves, Yun-Kai Zhang, Jia Li, Paula Gonzalez-Ericsson, Shamilene Sivagnanam, Courtney B. Betts, Hua-Chang Chen, Qi Liu, Cindy Lowe, Heidi Chen, Kelli L. Boyd, Prasad R. Kopparapu, Yingjun Yan, Lisa M. Coussens, Vito Quaranta, Darren R. Tyson, Wade Iams, Christine M. Lovly
Journal: Journal of Thoracic Oncology (2021)

IntroductionThe programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors, atezolizumab and durvalumab, have received regulatory approval for the first-line treatment of patients with extensive-stage SCLC. Nevertheless, when used in combination with platinum-based chemotherapy, these PD-L1 inhibitors only improve overall survival by 2 to 3 months. This may be due to the observation that less than 20% of SCLC tumors express PD-L1 at greater than 1%. Evaluating the composition and abundance of checkpoint molecules in SCLC may identify molecules beyond PD-L1 that are amenable to therapeutic targeting.MethodsWe analyzed RNA-sequencing data from SCLC cell lines (n = 108) and primary tumor specimens (n = 81) for expression of 39 functionally validated inhibitory checkpoint ligands. Furthermore, we generated tissue microarrays containing SCLC cell lines and patient with SCLC specimens to confirm expression of these molecules by immunohistochemistry. We annotated patient outcomes data, including treatment response and overall survival.ResultsThe checkpoint protein B7-H6 (NCR3LG1) exhibited increased protein expression relative to PD-L1 in cell lines and tumors (p < 0.05). Higher B7-H6 protein expression correlated with longer progression-free survival (p = 0.0368) and increased total immune infiltrates (CD45+) in patients. Furthermore, increased B7-H6 gene expression in SCLC tumors correlated with a decreased activated natural killer cell gene signature, suggesting a complex interplay between B7-H6 expression and immune signature in SCLC.ConclusionsWe investigated 39 inhibitory checkpoint molecules in SCLC and found that B7-H6 is highly expressed and associated with progression-free survival. In addition, 26 of 39 immune checkpoint proteins in SCLC tumors were more abundantly expressed than PD-L1, indicating an urgent need to investigate additional checkpoint targets for therapy in addition to PD-L1.
Transcriptomic Evaluation of Juvenile Localized Scleroderma Skin With Histologic and Clinical Correlation
Authors: Christina Schutt, Emily Mirizio, Claudia Salgado, Miguel Reyes‐Mugica, Xinjun Wang, Wei Chen, Lorelei Grunwaldt, Kaila L. Schollaert, Kathryn S. Torok
Journal: Arthritis & Rheumatology (2021)

Juvenile localized scleroderma (LS) is an autoimmune disease of the skin whose pathogenesis is not well understood due to the rarity of the disease. This study was undertaken to determine the skin transcriptome in skin biopsy tissue from children with juvenile LS compared to pediatric healthy controls, with identification of significant molecular targets using RNA sequencing (RNA-Seq). In this study, differentially expressed genes (DEGs) were assessed for correlations with histopathologic and clinical features in children with juvenile LS, and were used to group the children into distinct genetic clusters based on immunophenotype.RNA-Seq was performed on sections of paraffin-embedded skin tissue obtained from 28 children with juvenile LS and 10 pediatric healthy controls. RNA-Seq was carried out using an Illumina HTS TruSeq RNA Access library prep kit, with data aligned using STAR and data analysis using a DESeq2 platform. A standardized histologic scoring system was used to score skin sections for the severity of inflammation and levels of collagen deposition. Histologic scoring was completed by 2 pathologists who were blinded with regard to the status of each sample. Spearman's rank correlation coefficients were used to assess significant correlations between DEG expression profiles and skin histologic findings in patients with juvenile LS.We identified 589 significant DEGs in children with juvenile LS as compared to healthy controls. Hierarchical clustering was used to demonstrate 3 distinct juvenile LS immunophenotype clusters. The histologic scores of skin inflammation (based on numbers and categories of inflammatory cell infiltrates) were significantly correlated with the expression levels of HLA-DPB1, HLA-DQA2, HLA-DRA, and STAT1 genes (rs > 0.5, P < 0.01). Collagen thickness correlated with the expression levels of collagen organization genes as well as with genes found to be correlated with the severity of inflammation, including genes for major histocompatibility complex (MHC) class I, MHC class II, and interferon-γ signaling.Among children with juvenile LS, 3 distinct genetic signatures, or clusters, were identified. In one cluster, inflammation-related pathways were up-regulated, corresponding to the histologic skin inflammation score. In the second cluster, fibrosis-related pathways were up-regulated. In the third cluster, gene expression in the skin corresponded to the patterns seen in healthy controls. Up-regulation of HLA class II genes was observed within the first cluster (characterized by predominant inflammation), a feature that has also been observed in the peripheral blood of patients with morphea and in the skin of patients with systemic sclerosis.
Development of gut microbiota and bifidobacterial communities of neonates in the first 6 weeks and their inheritance from mother
Authors: Bo Yang, Mengfan Ding, Yingqi Chen, Fengzhen Han, Chunyan Yang, Jianxin Zhao, Patrice Malard, Catherine Stanton, R. Paul Ross, Hao Zhang, Wei Chen
Journal: Gut Microbes (2021)

Microbiota especially Bifidobacterium play an important role in adjusting and maintaining homeostatic balance within the infant intestine. The aim of this study was to elucidate the relationship between maternal and infant gut microbiota and identify the Bifidobacterium species that may transfer from mother to infant over the first 42 days of the infant's life. Nineteen mother-infant-pair fecal samples were collected and the diversity and composition of the total bacterial and Bifidobacterium communities were analyzed via 16S rDNA and bifidobacterial groEL gene high throughput sequencing. The results revealed that the relative abundance of Bifidobacterium was significantly higher in the infant gut while Parabacteroides, Blautia, Coprococcus, Lachnospira and Faecalibacterium were at lower relative abundance in 7-day and 42-day infant fecal samples compared to the maternal samples. The maternal gut has more B. pseudocatenulatum. In the infant group, B. breve and B. dentium relative abundance increased while B. animalis subsp. lactis decreased from days 7 to 42. Additionally, B. longum subsp. longum isolated from FGZ16 and FGZ35 may have transferred from mother to infant and colonized the infant gut. The results of the current study provide insight toward the infant gut microbiota composition and structure during the first 42 days and may help guide Bifidobacterium supplementation strategies in mothers and infants.
Recent Advances in Aptamer-Based Biosensors for Global Health Applications
Authors: Lia A. Stanciu, Qingshan Wei, Amit K. Barui, Noor Mohammad
Journal: Annual Review of Biomedical Engineering (2021)

Since aptamers were first reported in the early 2000s, research on their use for the detection of health-relevant analytical targets has exploded. This review article provides a brief overview of the most recent developments in the field of aptamer-based biosensors for global health applications. The review provides a description of general aptasensing principles and follows up with examples of recent reports of diagnostics-related applications. These applications include detection of proteins and small molecules, circulating cancer cells, whole-cell pathogens, extracellular vesicles, and tissue diagnostics. The review also discusses the main challenges that this growing technology faces in the quest of bringing these new devices from the laboratory to the market.
Abstract 266: The Effect of Different Kinds of Chest Compression Waveforms on the Heart Ischemia-Reperfusion Injury After Cardiac Arrest
Authors: Tang Songling, Yarong He, Peng Yao, Yu Cao
Journal: Circulation (2019)

Purpose: This study was aimed to compare the effect of different kinds of chest compression waveforms on the heart ischemia-reperfusion injury after cardiac arrest (CA) in a rat model. Materials and methods: After the CA model was successfully established with continuous electrical stimulation of ventricular fibrillation, rats were divided into four different chest compression groups randomly, including manual group, triangular wave group, sine wave group and trapezoidal wave group. The success rates of return of spontaneous circulation (ROSC) of those four groups were calculated, and all ROSC rats were executed 30 minutes after ROSC. Further comparisons were made among those four groups, including pathological changes, superoxide dismutase (SOD) activities, malondialdehyde (MDA) and superoxide (O 2 - ) content. Results: The success ROSC rates for those four groups (manual group, triangular wave group, sine wave group and trapezoidal wave group) were 30%, 40%, 40% and 90% respectively. There were inflammatory cell infiltration and edema in the heart tissue of those four groups. The activities of SOD in trapezoidal wave group were 85.91±1.91 U/mg, much higher than those of the other three groups (P &lt;0.05). On the other hand, the MDA and O 2 - levels of trapezoidal wave group were much lower than those of the other three groups (p&lt;0.05). Conclusion: Our study demonstrated that trapezoidal wave chest compression may be beneficial in improving the success rate of ROSC and alleviate heart injury. Its possible mechanism might lie in its anti-oxidative stress capability during the chest compression.
Oxidation of PKA-RI alpha Protects Against Ischemia-reperfusion Injury by Inhibiting Lysosomal-triggered Calcium Release
Authors: J N Simon, B Vrellaku, S Monterisi, S Chu, N Rawlings, O Lomas, G A Marchal, D Waithe, P R Gajendragadkar, R Jayaram, R Sayeed, K M Channon, P Swietach, M Zaccolo, P Eaton, B Casadei
Journal: Circulation (2020)
Multiple Myeloma and the Kidney
Authors: Giovanni Cancarini, Vincenzo Terlizzi, Letizia Zeni
Journal: HemaSphere (2021)

The recent guidelines by the European Hematology Association (EHA) and European Society for Medical Oncology (ESMO)1 address the complexity of the treatment in multiple myeloma (MM). The section on supportive care for renal impairment in the supplementary materials suggests the preferred drugs or the change in their doses according to renal function. MM can affect the kidney function in several ways, either as monoclonal gammopathy of renal significance (MGRS) or as acute kidney injury (AKI) as in light chain cast nephropathy (LCCN). Surprisingly, renal complications in MM are not mentioned throughout the paper. A recent work by the International Kidney and Monoclonal Gammopathy Research Group2 was focused on treatment of AKI in symptomatic MM and suggested some therapeutic strategies to improve AKI-associated outcomes. In patients with very low glomerular filtration rate (GFR), besides chemotherapy and use of high-permeability dialysis filters (HCO), the abovementioned guidelines suggest hydration and urine alkalinization with the aim to increase both tubular flow and urine pH to reduce intraluminal precipitation of light chains (LCs). Since loop diuretics increase sodium concentration in urine so favoring the precipitation of LCs, the authors suggest that their use should be limited to cases of severe fluid overload only. Another way to increase tubular flow with low effect on intratubular sodium concentration could be intravenously mannitol, which causes an osmotic diuresis thus reducing the risk of cast formation; the use of mannitol in LCCN has recently been supported by a pilot study.3 Moreover, it may be the only possibility to remove LCs in countries where HCO dialysis filters are not available due to their high cost Additionally, if prevention of cast nephropathy is widely considered crucial in the management of MM, the guidelines should emphasize the need of accurate information for all patients with MM on the importance of maintaining high-urine output with neutral pH, avoiding nephrotoxic drugs (FANS, ACE-inhibitors, etc), and having prompt referral to physicians when possible causes of dehydration (vomiting or diarrhea) occur. Disclosures The authors have no conflicts of interest to disclose.
Abstract 14282: Association Between Hospitalization Costs and Left Ventricular Ejection Fraction in Patients With Heart Failure in the Advanced Aging Society
Authors: Kaichi Ryota, kyohhei marume, michikazu nakai, Soshiro Ogata, Masanobu Ishii, Takayuki Mori, Soichi Komaki, Reiko Toida, Kazumasa Kurogi, Yoshihiro Miyamoto, Nobuyasu Yamamoto
Journal: Circulation (2020)

Introduction: The economic burden associated with heart failure (HF) is expected to increase in the world due to aging. Left ventricular ejection fraction (LVEF) is a basic clinical index that indicates the severity of HF, and guideline-directed medical therapies are recommended stratified by LVEF. However, there is paucity of information between LVEF and hospitalization costs. Hypothesis: Therefore, we evaluated the association between the hospitalization costs and LVEF in elder HF patients in Japan, which is at forefront of aging. Methods: We studied 346 consecutive patients who admitted to Miyazaki prefectural Nobeoka Hospital due to HF between January 2015 and March 2018. Results: Median hospitalization costs were comparable between the HF reduced EF (HFrEF; LVEF&lt;40%: n=129) and HF preserved EF (HFpEF; LVEF≥40%: n=217) ($7128 vs $6580, P =0.373), LVEF was not correlated with hospitalization costs ( P =0.051) (Figure A). Meanwhile, in the subgroup aged over 75 years, median hospitalization costs were significantly higher in HFrEF than in HFpEF ($7249 vs $6471, P =0.031). The HFrEF group also had higher level of brain natriuretic peptide (1011 vs 479 pg/ml, P &lt;0.001), higher prevalence of ischemic heart disease (40% vs 27%, P =0.004), and higher rate of percutaneous coronary intervention (10% vs 2%, P =0.008) than HFpEF group. In addition, LVEF was significantly correlated with hospitalization costs ( P =0.005) (Figure B), and remained as a significant independent predictor of hospitalization costs in multivariate liner regression analysis (β=—0.173, P =0.014). Conclusions: LVEF was not significantly correlated with hospitalization costs in the entire cohort, but was an independent negative factor for hospitalization costs in the subgroup of aged over 75. This might provide helpful evidence for future novel healthcare strategies that target HF inpatient cost reductions.