tbuckley/cabot-search huggingface dataset:
High‐Strength Hydrogel Attachment through Nanofibrous Reinforcement
Authors: Jiacheng Zhao, Alina Kirillova, Cambre N. Kelly, Heng Xu, William J. Koshut, Feichen Yang, Ken Gall, Benjamin J. Wiley
Journal: Advanced Healthcare Materials (2020)

Abstract The repair of a cartilage lesion with a hydrogel requires a method for long‐term fixation of the hydrogel in the defect site. Attachment of a hydrogel to a base that allows for integration with bone can enable long‐term fixation of the hydrogel, but current methods of forming bonds to hydrogels have less than a tenth of the shear strength of the osteochondral junction. This communication describes a new method, nanofiber‐enhanced sticking (NEST), for bonding a hydrogel to a base with an adhesive shear strength three times larger than the state‐of‐the‐art. An example of NEST is described in which a nanofibrous bacterial cellulose sheet is bonded to a porous base with a hydroxyapatite‐forming cement followed by infiltration of the nanofibrous sheet with hydrogel‐forming polymeric materials. This approach creates a mineralized nanofiber bond that mimics the structure of the osteochondral junction, in which collagen nanofibers extend from cartilage into a mineralized region that anchors cartilage to bone.
Let’s stop talking about covid-safe and covid-secure—it’s covid-mitigated
Authors: Catherine E Urch, Andrew J T George
Journal: BMJ (2020)

We have been in countless meetings that have included discussions about making the workplace covid-secure or covid-safe (or even covid-friendly).1 This language is problematic as “safe” implies that we can make places 100% safe for staff, which will never be possible, and “secure” indicates a very high degree of certainty requiring excessive measures.

This language can drive irrational behaviour. Covid-secure transport to hospital, for example, requires patients not to use taxis …
The CXCL12/CXCR4/ACKR3 Axis in the Tumor Microenvironment: Signaling, Crosstalk, and Therapeutic Targeting
Authors: Martine J. Smit, Géraldine Schlecht-Louf, Maria Neves, Jelle van den Bor, Petronila Penela, Marco Siderius, Françoise Bachelerie, Federico Mayor
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Elevated expression of the chemokine receptors CXCR4 and ACKR3 and of their cognate ligand CXCL12 is detected in a wide range of tumors and the tumor microenvironment (TME). Yet, the molecular mechanisms by which the CXCL12/CXCR4/ACKR3 axis contributes to the pathogenesis are complex and not fully understood. To dissect the role of this axis in cancer, we discuss its ability to impinge on canonical and less conventional signaling networks in different cancer cell types; its bidirectional crosstalk, notably with receptor tyrosine kinase (RTK) and other factors present in the TME; and the infiltration of immune cells that supporttumor progression. We discuss current and emerging avenues that target the CXCL12/CXCR4/ACKR3 axis. Coordinately targeting both RTKs and CXCR4/ACKR3 and/or CXCL12 is an attractive approach to consider in multitargeted cancer therapies. In addition, inhibiting infiltrating immune cells or reactivating the immune system along with modulating the CXCL12/CXCR4/ACKR3 axis in the TME has therapeutic promise.
Mental health problems among female sex workers in low- and middle-income countries: A systematic review and meta-analysis
Authors: Tara S. Beattie, Boryana Smilenova, Shari Krishnaratne, April Mazzuca
Journal: PLoS Medicine (2020)

Background The psychological health of female sex workers (FSWs) has emerged as a major public health concern in many low- and middle-income countries (LMICs). Key risk factors include poverty, low education, violence, alcohol and drug use, human immunodeficiency virus (HIV), and stigma and discrimination. This systematic review and meta-analysis aimed to quantify the prevalence of mental health problems among FSWs in LMICs, and to examine associations with common risk factors. Method and findings The review protocol was registered with PROSPERO, number CRD42016049179. We searched 6 electronic databases for peer-reviewed, quantitative studies from inception to 26 April 2020. Study quality was assessed with the Centre for Evidence-Based Management (CEBM) Critical Appraisal Tool. Pooled prevalence estimates were calculated for depression, anxiety, post-traumatic stress disorder (PTSD), and suicidal behaviour. Meta-analyses examined associations between these disorders and violence, alcohol/drug use, condom use, and HIV/sexually transmitted infection (STI). A total of 1,046 studies were identified, and 68 papers reporting on 56 unique studies were eligible for inclusion. These were geographically diverse (26 countries), representing all LMIC regions, and included 24,940 participants. All studies were cross-sectional and used a range of measurement tools; none reported a mental health intervention. Of the 56 studies, 14 scored as strong quality, 34 scored as moderate, and 8 scored as weak. The average age of participants was 28.9 years (age range: 11–64 years), with just under half (46%) having up to primary education or less. The pooled prevalence rates for mental disorders among FSWs in LMICs were as follows: depression 41.8% (95% CI 35.8%–48.0%), anxiety 21.0% (95% CI: 4.8%–58.4%), PTSD 19.7% (95% CI 3.2%–64.6%), psychological distress 40.8% (95% CI 20.7%–64.4%), recent suicide ideation 22.8% (95% CI 13.2%–36.5%), and recent suicide attempt 6.3% (95% CI 3.4%–11.4%). Meta-analyses found significant associations between violence experience and depression, violence experience and recent suicidal behaviour, alcohol use and recent suicidal behaviour, illicit drug use and depression, depression and inconsistent condom use with clients, and depression and HIV infection. Key study limitations include a paucity of longitudinal studies (necessary to assess causality), non-random sampling of participants by many studies, and the use of different measurement tools and cut-off scores to measure mental health problems and other common risk factors. Conclusions In this study, we found that mental health problems are highly prevalent among FSWs in LMICs and are strongly associated with common risk factors. Study findings support the concept of overlapping vulnerabilities and highlight the urgent need for interventions designed to improve the mental health and well-being of FSWs.
Acute-on-chronic liver failure as a major predictive factor for mortality in patients with variceal bleeding
Authors: Jongbeom Shin, Jung Hwan Yu, Young-Joo Jin, Hyung Joon Yim, Young Kul Jung, Jin Mo Yang, Do Seon Song, Young Seok Kim, Sang Gyune Kim, Dong Joon Kim, Ki Tae Suk, Eileen L. Yoon, Sang Soo Lee, Chang Wook Kim, Hee Yeon Kim, Jae Young Jang, Soung Won Jeong
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: This study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients.Methods: This study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium.Results: Among a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (&lt;i&gt;P&lt;/i&gt;&lt;0.001), and patients with higher ACLF grades had a lower OS rate (&lt;i&gt;P&lt;/i&gt;&lt;0.001). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score was identified as a significant prognostic factor in patients hospitalized with variceal bleeding (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.30–1.50; &lt;i&gt;P&lt;/i&gt;&lt;0.001), even in ACLF patients with variceal bleeding (HR, 1.32; 95% CI, 1.19–1.46, &lt;i&gt;P&lt;/i&gt;&lt;0.001). Concerning the prediction of the mortality risk at 28- and 90-day using CLIF-SOFA scores, c-statistics were 0.895 (95% CI, 0.829–0.962) and 0.897 (95% CI, 0.842–0.951), respectively, and the optimal cut-off values were 6.5 and 6.5, respectively.Conclusions: In cirrhotic patients hospitalized with variceal bleeding, the prognosis was poor when accompanied by ACLF, especially depending upon CLIF-SOFA score. CLIF-SOFA model well predicted the 28-day or 90-day mortality for cirrhotic patients who experienced variceal bleeding.
Safety and efficacy of the Russian COVID-19 vaccine: more information needed
Authors: Enrico Bucci, Konstantin Andreev, Anders Björkman, Raffaele Adolfo Calogero, Ernesto Carafoli, Piero Carninci, Paola Castagnoli, Andrea Cossarizza, Cristina Mussini, Philippe Guerin, Brian Lipworth, Gianluca Sbardella, Teresa Stocki, Loretta Tuosto, Christoffer van Tulleken, Antonella Viola
Journal: The Lancet (2020)
Atrial Metastasis From Sarcomatoid Renal Cell Carcinoma
Authors: Luca Filippi, Angelo Iannarelli, Cesare Ambrogi, Oreste Bagni
Journal: Clinical Nuclear Medicine (2020)

Abstract We describe the case of a 54-year-old woman, previously submitted to nephrectomy for sarcomatoid renal cell carcinoma and treated with antibiotics because of central venous catheter infection. An 18 F-FDG PET/CT scan was obtained that demonstrated bone and lymph node metastases and also disclosed an irregular area of highly increased uptake (SUVmax 19.4) in the right atrium. Clinical data did not suggest a relapsed infection. A contrast-enhanced CT examination of the heart enabled the diagnosis of intra-atrial metastasis. Furthermore, integration between PET and cardiac 3-dimensional volume rendering proved useful for defining the anatomical relationships between atrial metastasis and large vessels.
Insights into how innocuous foods or proteins deserving of immune ignorance can become allergens
Authors: Larry Borish
Journal: Journal of Clinical Investigation (2020)

Allergic disorders include food allergy, allergic rhinitis, and certain forms of asthma resulting from the inappropriate development of immune responses to otherwise innocuous aeroallergens and foods. In this issue of the JCI, Thouvenot and Roitel et al. explore transcription infidelity as a mechanism that underlies the ability of these benign proteins to become allergens. Some foods and bioaerosols that produce allergies have RNA polymerase with a propensity to generate RNA gaps, thereby causing translational frameshifts. These frameshifts often create cationic carboxy-terminus residues that replace hydrophobic amino acids and have enhanced MHC binding, resulting in the tendency to provoke immune responses. IgE antibody responses initiated by these variant transcripts can later lead to IgE against the native molecule and also explain how anaphylaxis may occur in individuals who lacked specific IgE when tested using native protein reagents. This study has the potential to transform the diagnosis and treatment of allergic disorders.
Physicians and Social Determinants of Health
Authors: Annelise Brochier, Emily Messmer, Arvin Garg
Journal: JAMA (2020)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML
Authors: Sheng Li, Xiaowen Chen, Jiahui Wang, Cem Meydan, Jacob L. Glass, Alan H. Shih, Ruud Delwel, Ross L. Levine, Christopher E. Mason, Ari M. Melnick
Journal: Cancer Discovery (2020)

Epigenetic allele diversity is linked to inferior prognosis in acute myeloid leukemia (AML). However, the source of epiallele heterogeneity in AML is unknown. Herein we analyzed epiallele diversity in a genetically and clinically annotated AML cohort. Notably, AML driver mutations linked to transcription factors and favorable outcome are associated with epigenetic destabilization in a defined set of susceptible loci. In contrast, AML subtypes linked to inferior prognosis manifest greater abundance and highly stochastic epiallele patterning. We report an epiallele outcome classifier supporting the link between epigenetic diversity and treatment failure. Mouse models with TET2 or IDH2 mutations show that epiallele diversity is especially strongly induced by IDH mutations, precedes transformation to AML, and is enhanced by cooperation between somatic mutations. Furthermore, epiallele complexity was partially reversed by epigenetic therapies in AML driven by TET2/IDH2, suggesting that epigenetic therapy might function in part by reducing population complexity and fitness of AMLs. SIGNIFICANCE: We show for the first time that epigenetic clonality is directly linked to specific mutations and that epigenetic allele diversity precedes and potentially contributes to malignant transformation. Furthermore, epigenetic clonality is reversible with epigenetic therapy agents.This article is highlighted in the In This Issue feature, p. 1775.
Review of Integrin‐Targeting Biomaterials in Tissue Engineering
Authors: Prachi Dhavalikar, Andrew Robinson, Ziyang Lan, Dana Jenkins, Malgorzata Chwatko, Karim Salhadar, Anupriya Jose, Ronit Kar, Erik Shoga, Aparajith Kannapiran, Elizabeth Cosgriff‐Hernandez
Journal: Advanced Healthcare Materials (2020)

Abstract The ability to direct cell behavior has been central to the success of numerous therapeutics to regenerate tissue or facilitate device integration. Biomaterial scientists are challenged to understand and modulate the interactions of biomaterials with biological systems in order to achieve effective tissue repair. One key area of research investigates the use of extracellular matrix‐derived ligands to target specific integrin interactions and induce cellular responses, such as increased cell migration, proliferation, and differentiation of mesenchymal stem cells. These integrin‐targeting proteins and peptides have been implemented in a variety of different polymeric scaffolds and devices to enhance tissue regeneration and integration. This review first presents an overview of integrin‐mediated cellular processes that have been identified in angiogenesis, wound healing, and bone regeneration. Then, research utilizing biomaterials are highlighted with integrin‐targeting motifs as a means to direct these cellular processes to enhance tissue regeneration. In addition to providing improved materials for tissue repair and device integration, these innovative biomaterials provide new tools to probe the complex processes of tissue remodeling in order to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.
High Glucose Metabolism in the Right Ventricular Myocardium Due to Extrinsic Pulmonary Stenosis by Mediastinal Lymphoma
Authors: Girish Kumar Parida, Sujata Mitra, Akchata Suman, Gopal Sonai Muthu
Journal: Clinical Nuclear Medicine (2020)

Acquired pulmonary stenosis in adults is rare and is usually caused by extrinsic compression from a mediastinal tumor. We present a case of anterior mediastinal Hodgkin lymphoma, who presented with cough and hemoptysis. Compression of the bilateral pulmonary arteries by the mediastinal mass was demonstrated by transthoracic echocardiography and CT pulmonary angiography. FDG PET/CT showed diffusely increased FDG uptake in right ventricular myocardium in addition to lymphomatous involvement of the lymph nodes and spleen.
Osimertinib in Resected<i>EGFR</i>-Mutated Non–Small-Cell Lung Cancer
Authors: Yi-Long Wu, Masahiro Tsuboi, Jie He, Thomas John, Christian Grohe, Margarita Majem, Jonathan W. Goldman, Konstantin Laktionov, Sang-We Kim, Terufumi Kato, Huu-Vinh Vu, Shun Lu, Kye-Young Lee, Charuwan Akewanlop, Chong-Jen Yu, Filippo de Marinis, Laura Bonanno, Manuel Domine, Frances A. Shepherd, Lingmin Zeng, Rachel Hodge, Ajlan Atasoy, Yuri Rukazenkov, Roy S. Herbst
Journal: New England Journal of Medicine (2020)

Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation–positive advanced non–small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown.
Cancers from Novel <i>Pole</i>-Mutant Mouse Models Provide Insights into Polymerase-Mediated Hypermutagenesis and Immune Checkpoint Blockade
Authors: Melissa A. Galati, Karl P. Hodel, Miki S. Gams, Sumedha Sudhaman, Taylor Bridge, Walter J. Zahurancik, Nathan A. Ungerleider, Vivian S. Park, Ayse B. Ercan, Lazar Joksimovic, Iram Siddiqui, Robert Siddaway, Melissa Edwards, Richard de Borja, Dana Elshaer, Jiil Chung, Victoria J. Forster, Nuno M. Nunes, Melyssa Aronson, Xia Wang, Jagadeesh Ramdas, Andrea Seeley, Tomasz Sarosiek, Gavin P. Dunn, Jonathan N. Byrd, Oz Mordechai, Carol Durno, Alberto Martin, Adam Shlien, Eric Bouffet, Zucai Suo, James G. Jackson, Cynthia E. Hawkins, Cynthia J. Guidos, Zachary F. Pursell, Uri Tabori
Journal: Cancer Research (2020)

Abstract POLE mutations are a major cause of hypermutant cancers, yet questions remain regarding mechanisms of tumorigenesis, genotype–phenotype correlation, and therapeutic considerations. In this study, we establish mouse models harboring cancer-associated POLE mutations P286R and S459F, which cause rapid albeit distinct time to cancer initiation in vivo, independent of their exonuclease activity. Mouse and human correlates enabled novel stratification of POLE mutations into three groups based on clinical phenotype and mutagenicity. Cancers driven by these mutations displayed striking resemblance to the human ultrahypermutation and specific signatures. Furthermore, Pole-driven cancers exhibited a continuous and stochastic mutagenesis mechanism, resulting in intertumoral and intratumoral heterogeneity. Checkpoint blockade did not prevent Pole lymphomas, but rather likely promoted lymphomagenesis as observed in humans. These observations provide insights into the carcinogenesis of POLE-driven tumors and valuable information for genetic counseling, surveillance, and immunotherapy for patients. Significance: Two mouse models of polymerase exonuclease deficiency shed light on mechanisms of mutation accumulation and considerations for immunotherapy. See related commentary by Wisdom and Kirsch p. 5459
Dual Blockade of c-MET and the Androgen Receptor in Metastatic Castration-resistant Prostate Cancer: A Phase I Study of Concurrent Enzalutamide and Crizotinib
Authors: Abhishek Tripathi, Jeffrey G. Supko, Kathryn P. Gray, Zachary J. Melnick, Meredith M. Regan, Mary-Ellen Taplin, Atish D. Choudhury, Mark M. Pomerantz, Joaquim Bellmunt, Channing Yu, Zijie Sun, Sandy Srinivas, Philip W. Kantoff, Christopher J. Sweeney, Lauren C. Harshman
Journal: Clinical Cancer Research (2020)

Androgen receptor (AR) inhibition can upregulate c-MET expression, which may be a resistance mechanism driving progression of castration-resistant prostate cancer (CRPC). We conducted a phase I trial investigating the safety and pharmacokinetics of a potent c-MET inhibitor, crizotinib, with the AR antagonist, enzalutamide, in CRPC.Employing a 3+3 dose-escalation design, we tested three dose levels of crizotinib (250 mg daily, 200 mg twice a day, and 250 mg twice a day) with standard-dose enzalutamide (160 mg daily). The primary endpoint was rate of dose-limiting toxicities (DLTs). Tolerability and pharmacokinetics profile were secondary endpoints.Twenty-four patients were enrolled in the dose-escalation (n = 16) and dose-expansion (n = 8) phases. Two DLTs occurred in dose escalation (grade 3 alanine aminotransferase elevation). The MTD of crizotinib was 250 mg twice a day. Most frequent treatment-related adverse events were fatigue (50%), transaminitis (38%), nausea (33%), and vomiting, constipation, and diarrhea (21% each). Grade ≥3 events (25%) included transaminitis (n = 2), fatigue (n = 1), hypertension (n = 1), pulmonary embolism (n = 1), and a cardiac event encompassing QTc prolongation/ventricular arrhythmia/cardiac arrest. Median progression-free survival was 5.5 months (95% confidence interval, 2.8-21.2). Pharmacokinetics analysis at the MTD (n = 12) revealed a mean Cmaxss of 104 ± 45 ng/mL and AUCτss of 1,000 ± 476 ng•h/mL, representing a 74% decrease in crizotinib systemic exposure relative to historical data (Cmaxss, 315 ng/mL and AUCτss, 3,817 ng•h/mL).Concurrent administration of enzalutamide and crizotinib resulted in a clinically significant 74% decrease in systemic crizotinib exposure. Further investigation of this combination in CRPC is not planned. Our results highlight the importance of evaluating pharmacokinetics interactions when evaluating novel combination strategies in CRPC.
The Genomic Basis of Rapid Adaptation to Antibiotic Combination Therapy in <i>Pseudomonas aeruginosa</i>
Authors: Camilo Barbosa, Niels Mahrt, Julia Bunk, Matthias Graßer, Philip Rosenstiel, Gunther Jansen, Hinrich Schulenburg
Journal: Molecular Biology and Evolution (2020)

Combination therapy is a common antibiotic treatment strategy that aims at minimizing the risk of resistance evolution in several infectious diseases. Nonetheless, evidence supporting its efficacy against the nosocomial opportunistic pathogen Pseudomonas aeruginosa remains elusive. Identification of the possible evolutionary paths to resistance in multidrug environments can help to explain treatment outcome. For this purpose, we here performed whole-genome sequencing of 127 previously evolved populations of P. aeruginosa adapted to sublethal doses of distinct antibiotic combinations and corresponding single-drug treatments, and experimentally characterized several of the identified variants. We found that alterations in the regulation of efflux pumps are the most favored mechanism of resistance, regardless of the environment. Unexpectedly, we repeatedly identified intergenic variants in the adapted populations, often with no additional mutations and usually associated with genes involved in efflux pump expression, possibly indicating a regulatory function of the intergenic regions. The experimental analysis of these variants demonstrated that the intergenic changes caused similar increases in resistance against single and multidrug treatments as those seen for efflux regulatory gene mutants. Surprisingly, we could find no substantial fitness costs for a majority of these variants, most likely enhancing their competitiveness toward sensitive cells, even in antibiotic-free environments. We conclude that the regulation of efflux is a central target of antibiotic-mediated selection in P. aeruginosa and that, importantly, changes in intergenic regions may represent a usually neglected alternative process underlying bacterial resistance evolution, which clearly deserves further attention in the future.