tbuckley/cabot-search huggingface dataset:
Ionized jet deposition of antimicrobial and stem cell friendly silver-substituted tricalcium phosphate nanocoatings on titanium alloy
Authors: Gabriela Graziani, Katia Barbaro, Inna V. Fadeeva, Daniele Ghezzi, Marco Fosca, Enrico Sassoni, Gianluca Vadalà, Martina Cappelletti, Francesco Valle, Nicola Baldini, Julietta V. Rau
Journal: Bioactive Materials (2021)

Orthopedic infections pose severe societal and economic burden and interfere with the capability of the implanted devices to integrate in the host bone, thus significantly increasing implants failure rate. To address infection and promote integration, here nanostructured antibacterial and bioactive thin films are proposed, obtained, for the first time, by Ionized Jet Deposition (IJD) of silver-substituted tricalcium phosphate (Ag-TCP) targets on titanium. Coatings morphology, composition and mechanical properties are characterized and proof-of-concept of biocompatibility is shown. Antimicrobial efficacy is investigated against four Gram positive and Gram negative bacterial strains and against C. albicans fungus, by investigating the modifications in planktonic bacterial growth in the absence and presence of silver. Then, for all bacterial strains, the capability of the film to inhibit bacterial adhesion is also tested. Results indicate that IJD permits a fine control over films composition and morphology and deposition of films with suitable mechanical properties. Biological studies show a good efficacy against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis and against fungus Candida albicans, with evidences of efficacy against planktonic growth and significant reduction of bacterial cell adhesion. No cytotoxic effects are evidenced for equine adipose tissue derived mesenchymal stem cells (ADMSCs), as no reductions are caused to cells viability and no interference is assessed in cells differentiation towards osteogenic lineage, in the presence of silver. Instead, thanks to nanostructuration and biomimetic composition, tricalcium phosphate (TCP) coatings favor cells viability, also when silver-substituted. These findings show that silver-substituted nanostructured coatings are promising for orthopedic implant applications.
Vaccination as Immunotherapy in Hematologic Malignancies
Authors: Jessica Liegel, Matthew Weinstock, Jacalyn Rosenblatt, David Avigan
Journal: Journal of Clinical Oncology (2021)

Article Tools REVIEW ARTICLES Immunotherapy for Hematologic Malignancies Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.20.01706 Journal of Clinical Oncology - published online before print January 12, 2021 PMID: 33434056 Vaccination as Immunotherapy in Hematologic Malignancies Jessica Liegel, MD1xJessica LiegelSearch for articles by this author; Matthew Weinstock, MD1xMatthew WeinstockSearch for articles by this author; Jacalyn Rosenblatt, MD1xJacalyn RosenblattSearch for articles by this author; and David Avigan, MD1xDavid AviganSearch for articles by this author Show More 1Beth Israel Deaconess Medical Center, Department of Medicine, Division of Hematology and Hematologic Malignancies, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.20.01706 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyContextKey ObjectiveTo understand vaccination approaches in hematologic malignancies and review clinical outcomes to date.Knowledge GeneratedVaccination strategies in hematologic malignancies have demonstrated capacity to evoke immune responses. Clinical responses are also being realized, particularly in the setting of low-volume disease.RelevanceVaccination in hematologic malignancies is poised to provide durable protection from disease progression and is being evaluated in combination with immunotherapies.AUTHOR CONTRIBUTIONSConception and design: All authorsCollection and assembly of data: All authorsData analysis and interpretation: All authorsManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTVaccination as Immunotherapy in Hematologic MalignanciesThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Jacalyn RosenblattEmployment: ParexelHonoraria: Bristol Myers Squibb, MerckConsulting or Advisory Role: Amgen, Imaging Endpoints, Partners TXResearch Funding: Celgene (Inst), Bristol Myers Squibb (Inst)Other Relationship: DAVAOncologyDavid AviganEmployment: ParexelConsulting or Advisory Role: Celgene, Kite/Gilead, Chugai Pharma, Karyopharm Therapeutics, Juno Therapeutics, Legend Biotech, TakedaResearch Funding: PharmacyclicsNo other potential conflicts of interest were reported.
Abstract 20438: The Myocardial Infarct-Exacerbating Effect of Cell-Free DNA is Mediated by the HMGB1-RAGE Pathway
Authors: Yikui Tian, Eric J Charles, Zhen Yan, Di Wu, Brent A French, Irving L Kron, Zequan Yang
Journal: Circulation (2017)

Introduction: Damage associated molecular patterns (DAMPs), such as HMGB1 and cell-free DNA (cfDNA), play critical roles in mediating ischemia/reperfusion injury (IRI). HMGB1 activates RAGE to exac...
IL-2 regulates tumor-reactive CD8+ T cell exhaustion by activating the aryl hydrocarbon receptor
Authors: Yuying Liu, Nannan Zhou, Li Zhou, Jing Wang, Yabo Zhou, Tianzhen Zhang, Yi Fang, Jinwei Deng, Yunfeng Gao, Xiaoyu Liang, Jiadi Lv, Zhenfeng Wang, Jing Xie, Yuanbo Xue, Huafeng Zhang, Jingwei Ma, Ke Tang, Yiliang Fang, Feiran Cheng, Chengjuan Zhang, Bing Dong, Yuzhou Zhao, Peng Yuan, Quanli Gao, Haizeng Zhang, F. Xiao-Feng Qin, Bo Huang
Journal: Nature Immunology (2021)
The advantages, pitfalls and limitations of guideline‐directed medical therapy in patients with valvular heart disease
Authors: Harminder Gill, Omar Chehab, Christopher Allen, Tiffany Patterson, Simon Redwood, Ronak Rajani, Bernard Prendergast
Journal: European Journal of Heart Failure (2021)

Abstract Heart failure is an inevitable end‐stage consequence of significant valvular heart disease (VHD) that is left untreated and increasingly encountered in an ageing society. Recent advances in transcatheter procedures and improved outcomes after valve surgery mean that intervention can (and should) be considered in all patients – even the elderly and those with multiple comorbidities ‐ at earlier stages of the natural history of primary VHD, before the onset of irreversible left ventricular dysfunction (and frequently before the onset of symptoms). All patients with known VHD should be monitored carefully in the setting of a heart valve clinic and those who meet guideline criteria for surgical or transcatheter intervention referred for intervention without delay. High quality evidence for the use of medical therapy in VHD is limited and achieving target doses in an elderly and comorbid population frequently challenging. Furthermore, determining whether the valve or ventricle is the principal disease driver is crucial (although the distinction is not always binary, and often unclear). Guideline‐directed medical therapy remains the mainstay of treatment for secondary mitral regurgitation ‐ although up to 50% of patients may fail to respond and should be considered for cardiac resynchronization, transcatheter or surgical valve intervention. Early and definitive management strategies are essential and should be overseen by a specialist Heart Team that includes a Heart Failure specialist. In this article, we provide an evidence‐based summary of approaches to the medical treatment of VHD and clinical guidance for the best management of patients in situations where high quality evidence is lacking.
Observations on the use of Bruton’s tyrosine kinase inhibitors in SAR-CoV-2 and cancer
Authors: Brooke Benner, William E. Carson
Journal: Journal of Hematology & Oncology (2021)

Bruton's tyrosine kinase (BTK) inhibitors, drugs utilized in cancer, are being repurposed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (COVID-19). Recently, BTK inhibitors acalabrutinib and ibrutinib have been found to protect against pulmonary injury in a small group of patients infected with SARS-CoV-2. The high levels of pro-inflammatory cytokines found in the circulation of COVID-19 patients with severe lung disease suggest the involvement of the innate immune system in this process. Understanding the potential mechanism of action of BTK inhibition in SARS-CoV-2 is clearly of importance to determine how acalabrutinib, ibrutinib and possibly other BTK inhibitors may provide protection against lung injury.
Changes in Diffuse Optical Tomography Images During Early Stages of Neoadjuvant Chemotherapy Correlate with Tumor Response in Different Breast Cancer Subtypes
Authors: Mirella L. Altoe, Kevin Kalinsky, Alessandro Marone, Hyun K. Kim, Hua Guo, Hanina Hibshoosh, Mariella Tejada, Katherine D. Crew, Melissa K. Accordino, Meghna S. Trivedi, Dawn L. Hershman, Andreas H. Hielscher
Journal: Clinical Cancer Research (2021)

Abstract Purpose: This study's primary objective was to evaluate the changes in optically derived parameters acquired with a diffuse optical tomography breast imaging system (DOTBIS) in the tumor volume of patients with breast carcinoma receiving neoadjuvant chemotherapy (NAC). Experimental Design: In this analysis of 105 patients with stage II–III breast cancer, normalized mean values of total hemoglobin (ctTH{b_N}$), oxyhemoglobin (ct{O_2}H{b_N}$), deoxy-hemoglobin concentration (ctHH{b_N}$), water, and oxygen saturation (St{O_2}_N$) percentages were collected at different timepoints during NAC and compared with baseline measurements. This report compared changes in these optical biomarkers measured in patients who did not achieve a pathologic complete response (non-pCR) and those with a pCR. Differences regarding molecular subtypes were included for hormone receptor–positive and HER2-negative, HER2-positive, and triple-negative breast cancer. Results: At baseline, ctHH{b_N}$ was higher for pCR tumors (3.97 ± 2.29) compared with non-pCR tumors (3.00 ± 1.72; P = 0.031). At the earliest imaging point after starting therapy, the mean change of ctHH{b_N}$ compared with baseline ({\Delta _{TP1}}ctHH{b_N}$) was statistically significantly higher in non-pCR (1.23 ± 0.67) than in those with a pCR (0.87 ± 0.61; P &amp;lt; 0.0005), and significantly correlated to residual cancer burden classification (r = 0.448; P &amp;lt; 0.0005). {\Delta _{TP1}}ctHH{b_N}$ combined with HER2 status was proposed as a two-predictor logistic model, with AUC = 0.891; P &amp;lt; 0.0005; and 95% confidence interval, 0.812–0.969. Conclusions: This study demonstrates that DOTBIS measured features change over time according to tumor pCR status and may predict early in the NAC treatment course whether a patient is responding to NAC.
Customary physical activity and odds of depression: a systematic review and meta-analysis of 111 prospective cohort studies
Authors: Rodney K Dishman, Cillian P McDowell, Matthew Payton Herring
Journal: British Journal of Sports Medicine (2021)

Objective To explore whether physical activity is inversely associated with the onset of depression, we quantified the cumulative association of customary physical activity with incident depression and with an increase in subclinical depressive symptoms over time as reported from prospective observational studies. Design Systematic review and meta-analysis. Data sources MEDLINE, PsycINFO, PsycARTICLES and CINAHL Complete databases, supplemented by Google Scholar. Eligibility criteria Prospective cohort studies in adults, published prior to January 2020, reporting associations between physical activity and depression. Study appraisal and synthesis Multilevel random-effects meta-analysis was performed adjusting for study and cohort or region. Mixed-model meta-regression of putative modifiers. Results Searches yielded 111 reports including over 3 million adults sampled from 11 nations in five continents. Odds of incident cases of depression or an increase in subclinical depressive symptoms were reduced after exposure to physical activity (OR, 95% CI) in crude (0.69, 0.63 to 0.75; I 2 =93.7) and adjusted (0.79, 0.75 to 0.82; I 2 =87.6) analyses. Results were materially the same for incident depression and subclinical symptoms. Odds were lower after moderate or vigorous physical activity that met public health guidelines than after light physical activity. These odds were also lower when exposure to physical activity increased over time during a study period compared with the odds when physical activity was captured as a single baseline measure of exposure. Conclusion Customary and increasing levels of moderate-to-vigorous physical activity in observational studies are inversely associated with incident depression and the onset of subclinical depressive symptoms among adults regardless of global region, gender, age or follow-up period.
A phase I/ <scp>II</scp> study of the combination of panobinostat and carfilzomib in patients with relapsed or relapsed/refractory multiple myeloma: Final analysis of second dose‐expansion cohort
Authors: Jesus G. Berdeja, Tara K. Gregory, Edward A. Faber, Lowell L. Hart, Joseph R. Mace, Edward R. Arrowsmith, Ian W. Flinn, Jeffrey V. Matous
Journal: American Journal of Hematology (2021)

Abstract The maximum tolerated dose of the panobinostat and carfilzomib combination in patients with relapsed/refractory multiple myeloma (RRMM) was not reached in our previous dose‐escalation study. We report additional dose levels in the phase I/II, single‐arm, multicenter, standard 3 + 3 dose‐escalation expansion‐cohort study (NCT01496118). Patients with RRMM were treated with panobinostat 30 mg, carfilzomib 20/56 mg/m 2 (N = 3), or panobinostat 20 mg, carfilzomib 20/56 mg/m 2 (N = 33). Treatment cycles lasted 28 days; panobinostat: days 1, 3, 5, 15, 17, 19; carfilzomib: days 1, 2, 8, 9, 15, 16. For dose level 6 (DL 6), median age was 63 years (range, 49–91 years), 60.6% were male, 42.4% were high risk. Patients received a median of two prior therapies (range 1–7); proteasome inhibitors (PI; 100%), immunomodulatory imide drugs (IMiD; 78.8%), and stem cell transplant (36.4%); 48.5%, 51.1%, and 24.2% were refractory to prior PI or prior IMiD treatment or both, respectively. Patients completed a median of seven (range 1–40) treatment cycles. Overall response rate (primary endpoint) of evaluable patients in the expansion cohort (N = 32): 84.4%; clinical benefit rate: 90.6%. With a median follow‐up of 26.1 months (range, 0–72.5 months), median (95% CI) progression‐free survival, time‐to‐progression and overall survival of patients was 10.3 (6.1, 13.9), 11.7 (5.6, 14.5), and 44.6 (20.8, N/A) months, respectively. Common adverse events (AEs) included thrombocytopenia (78.8%), nausea (63.6%), fatigue (63.6%), diarrhea (51.5%), and vomiting (51.5%). Seven patients had serious treatment‐related AEs. There was one treatment‐related death. In conclusion, panobinostat plus carfilzomib is an effective steroid‐sparing regimen for RRMM.
Reduced Intensity Conditioning for Allogeneic Transplantation: Modified Fludarabine Dose Plus Cyclophosphamide/Total Body Irradiation Yields Promising Outcomes
Authors: Erica D. Warlick, Todd E. DeFor, Celalettin Ustun, Nelli Bejanyan, Claudio G Brunstein, Margaret L. MacMillan, Daniel J. Weisdorf
Journal: Blood (2017)
OA05.08 Trends of Incidence and Burden of Metastatic Disease at Diagnosis of Lung Cancer after Implementation of Low Dose CT Screening in the United States
Authors: M.P. Rai, P. Bedi, B. Ansari, S.S. Malleshappa, P. Neupane, C. Huang, J. Zhang, K. Mehta
Journal: Journal of Thoracic Oncology (2021)
Pregnancy in Hidradenitis Suppurativa—Patient Perspectives and Practice Gaps
Authors: Ademide A. Adelekun, Natalie M. Villa, Jennifer L. Hsiao, Robert G. Micheletti
Journal: JAMA Dermatology (2021)

This survey study reports on patients' concerns about the implications of hidradenitis suppurativa for sexual and reproductive health, heritability of the condition, and pregnancy and childbirth as well as the inadequate information and support from clinicians.
Assessment of rAAVrh.74.MHCK7.micro-dystrophin Gene Therapy Using Magnetic Resonance Imaging in Children With Duchenne Muscular Dystrophy
Authors: Rebecca J. Willcocks, Sean C. Forbes, Glenn A. Walter, Lee Sweeney, Louise R. Rodino-Klapac, Jerry R. Mendell, Krista Vandenborne
Journal: JAMA Network Open (2021)

This case-control study uses magnetic resonance imaging and spectroscopy to evaluate the association between treatment with recombinant adeno-associated virus serotype rh74 (rAAVrh74) and muscle quality in children with Duchenne muscular dystrophy.
Abstract 16511: Hybrid Magnetic Resonance Imaging and Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Guided Cardiac Sarcoidosis Treatment
Authors: Maria Giovanna Trivieri, Phil Robson, Gina LaRocca, Vittoria Vergani, Angelica Romero, Nicolas Karakatsanis, Ronan Abragal, Aditya Parikh, Christia Panagiota, Anna Palmisano, Louis DePalo, Rima Fayad, Marc Miller, Valentin Fuster, Jagat Narula, Maria Padilla, Marc Dweck, Jason Kovacic, Zahi Fayad
Journal: Circulation (2018)

Hypothesis: Serial PET/MR imaging is useful in guiding treatment of patients with suspected cardiac sarcoidosis. Introduction: Sarcoidosis manifests clinically with cardiac involvement in 5% to 10%...
Targeting the p300/CBP Axis in Lethal Prostate Cancer
Authors: Jonathan Welti, Adam Sharp, Nigel Brooks, Wei Yuan, Christopher McNair, Saswati N. Chand, Abhijit Pal, Ines Figueiredo, Ruth Riisnaes, Bora Gurel, Jan Rekowski, Denisa Bogdan, William West, Barbara Young, Meera Raja, Amy Prosser, Jordan Lane, Stuart Thomson, Jenny Worthington, Stuart Onions, Jonathan Shannon, Silvia Paoletta, Richard Brown, Don Smyth, Gareth W. Harbottle, Veronica S. Gil, Susana Miranda, Mateus Crespo, Ana Ferreira, Rita Pereira, Nina Tunariu, Suzanne Carreira, Antje J. Neeb, Jian Ning, Amanda Swain, David Taddei, Matthew J. Schiewer, Karen E. Knudsen, Neil Pegg, Johann S. de Bono
Journal: Cancer Discovery (2021)

Resistance to androgen receptor (AR) blockade in castration-resistant prostate cancer (CRPC) is associated with sustained AR signaling, including through alternative splicing of AR (AR-SV). Inhibitors of transcriptional coactivators that regulate AR activity, including the paralog histone acetyltransferase proteins p300 and CBP, are attractive therapeutic targets for lethal prostate cancer. Herein, we validate targeting p300/CBP as a therapeutic strategy for lethal prostate cancer and describe CCS1477, a novel small-molecule inhibitor of the p300/CBP conserved bromodomain. We show that CCS1477 inhibits cell proliferation in prostate cancer cell lines and decreases AR- and C-MYC-regulated gene expression. In AR-SV-driven models, CCS1477 has antitumor activity, regulating AR and C-MYC signaling. Early clinical studies suggest that CCS1477 modulates KLK3 blood levels and regulates CRPC biopsy biomarker expression. Overall, CCS1477 shows promise for the treatment of patients with advanced prostate cancer. SIGNIFICANCE: Treating CRPC remains challenging due to persistent AR signaling. Inhibiting transcriptional AR coactivators is an attractive therapeutic strategy. CCS1477, an inhibitor of p300/CBP, inhibits growth and AR activity in CRPC models, and can affect metastatic CRPC target expression in serial clinical biopsies.
Letter by Jian et al Regarding Article, “Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes Mellitus”
Authors: Wen Jian, Lang Li, Chun Gui
Journal: Circulation (2021)

We have read with great interest the article published in Circulation by Hoyer et al, 1 which showed that bone marrow endothelial cells participate in the dysregulation of bone marrow hematopoiesis, and enhanced endothelial epithelial growth factor receptor (Egfr) signaling dampens excessive myelopoiesis in diabetes.We believe that the following points should be considered.First, emerging evidence suggests that the pathogenesis of various cardiovascular disorders is associated with the cognate ligand-independent Egfr activation referred to as transactivation.Endothelial Egfr can be transactivated by factors related to diabetes and obesity, such as endothelin-1, angiotensin II, and leptin. 2 Amphiregulin might not be the main source that mediates Egfr activation despite the authors having found its high expression in the serum of diabetic mice.In addition, as for vascular smooth muscle cell, increased Egfr signaling is detrimental rather than protective, 2 which increases difficulties for endothelial cell-specific drug development in the future.Second, the authors showed that Ang1 (angiopoietin-1) endothelial expression was significantly decreased in diabetic Cdh5 Cre Egfr fl/fl mice in comparison with controls, but they did not measure Ang2 (angiopoietin-2) expression.Ang1 maintains endothelial quiescence and integrity through binding to Tie2 receptor, whereas Ang2 acts as a context-dependent Tie2 antagonist interfering with Ang1-induced Tie2 phosphorylation. 3Vascular permeability will be significantly augmented when Ang1/Ang2 balance is in favor of Ang2, which allows more direct interaction of blood molecules, S100A8/A9, for example, with hematopoietic stem and progenitor cells.Circulating S100A8/A9 produced by neutrophils is a well-established factor that promotes myelopoiesis through the receptor for advanced glycation end products on myeloid progenitor cells. 4Thus, this endothelial effect of Ang/Tie2 signaling disrupted by Egfr deletion on regulating myelopoiesis should not be neglected.Likewise, Ang/Tie2 signaling can also influence inflammation and play a role in atherosclerosis, 5 which may contribute to plaque formation independently of enhanced myelopoiesis in diabetic Cdh5 Cre Egfr fl/fl mice.We think that readers would have benefited if the authors had discussed these issues.
Environmental Health Threats to Latino Migrant Farmworkers
Authors: Federico Castillo, Ana M. Mora, Georgia L. Kayser, Jennifer Vanos, Carly Hyland, Audrey R. Yang, Brenda Eskenazi
Journal: Annual Review of Public Health (2021)

Approximately 75% of farmworkers in the United States are Latino migrants, and about 50% of hired farmworkers do not have authorization to work in the United States. Farmworkers face numerous chemical, physical, and biological threats to their health. The adverse effects of these hazards may be amplified among Latino migrant farmworkers, who are concurrently exposed to various psychosocial stressors. Factors such as documentation status, potential lack of authorization to work in the United States, and language and cultural barriers may also prevent Latino migrants from accessing federal aid, legal assistance, and health programs. These environmental, occupational, and social hazards may further exacerbate existing health disparities among US Latinos. This population is also likely to be disproportionately impacted by emerging threats, including climate change and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Latino migrant farmworkers are essential to agriculture in the United States, and actions are needed to protect this vulnerable population.