tbuckley/cabot-search huggingface dataset:
Abstract 17605: Cost-Effectiveness of Contemporary Endovascular Treatment Compared to Open Surgical Revascularization for Cardioembolic Acute Limb Ischemia
Authors: Elizabeth A Genovese, Kenneth J Smith, Neal R Barshes, Michel S Makaroun, Donald T Baril
Journal: Circulation (2015)

Introduction: Treatment of acute limb ischemia (ALI) has a high morbidity and mortality given patients’ multiple comorbidities, poor physiologic reserve, and the need for emergent intervention. Traditionally ALI of embolic origin has been treated with open revascularization (OR), however with increasing experience with thrombolytic therapy and adjuvant techniques, endovascular revascularization (ER) for ALI has become a more common treatment due to the lower associated morbidity and mortality. Hypothesis: Although associated with higher initial costs and lower technical success rates, ER will be cost effective given the decreased adverse event rate and mortality in a frail patient population. Methods: A Markov state-transition model was created to simulate patient oriented outcomes, including technical success, adverse events, limb salvage, discharge facility and quality adjusted life years (QALY) for patients presenting with Rutherford Classification I/IIa/IIb ALI secondary to cardiac embolism. A societal perspective was assumed with a 10-year time horizon. Parameter estimates were derived from published literature and primary data of cardioembolic ALI patients treated at our institution from 2005-2011 with either ER or OR. Costs were adjusted to 2013 U.S. dollars. Results: In the model, OR was technically successful in 87% patients, with a $23,881 cost for the initial hospitalization and a 11.5% perioperative mortality rate; ER was technically successful in 71% of patients, with a $39,619 initial cost, and a 4% mortality rate. At 10 years, the ER strategy cost $92,659/QALY gained compared to OR. Sensitivity analyses demonstrated that ER was favorable at a willingness to pay (WTP) threshold of $100,000/QALY when ER technical success was &gt;70%, initial ER hospitalization cost was &lt;$41,052 or if OR mortality was &gt;10%. At a WTP of $50,000/QALY, ER was cost effective if technical success reached 79%, if ER cost was &lt;$31,287 or if OR mortality was &gt;23%. Conclusions: Contemporary endovascular treatment of cardioembolic ALI carries a greater cost compared to open revascularization, however it is associated with a decreased mortality rate. ER is potentially cost-effective in patients who are at high risk of post-operative mortality following OR.
Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
Authors: Vinod A. Pullarkat, Norman J. Lacayo, Elias Jabbour, Jeffrey E. Rubnitz, Ashish Bajel, Theodore W. Laetsch, Jessica Leonard, Susan I. Colace, Seong Lin Khaw, Shaun A. Fleming, Ryan J. Mattison, Robin Norris, Joseph T. Opferman, Kathryn G. Roberts, Yaqi Zhao, Chunxu Qu, Mohamed Badawi, Michelle Schmidt, Bo Tong, John C. Pesko, Yan Sun, Jeremy A. Ross, Deeksha Vishwamitra, Lindsey Rosenwinkel, Su Young Kim, Amanda Jacobson, Charles G. Mullighan, Thomas B. Alexander, Wendy Stock
Journal: Cancer Discovery (2021)

Combining venetoclax, a selective BCL2 inhibitor, with low-dose navitoclax, a BCL-XL/BCL2 inhibitor, may allow targeting of both BCL2 and BCL-XL without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase I dose-escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment. A recommended phase II dose of 50 mg navitoclax for adults and 25 mg for patients <45 kg with 400 mg adult-equivalent venetoclax was identified. Delayed hematopoietic recovery was the primary safety finding. The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen patients (28%) proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population. SIGNIFICANCE: In this phase I study, venetoclax with low-dose navitoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Responses were observed in patients across histologic and genomic subtypes and in those who failed available therapies including stem cell transplant.See related commentary by Larkin and Byrd, p. 1324.This article is highlighted in the In This Issue feature, p. 1307.
Bio‐Compliant Composites: Biocompliant Composite Au/pHEMA Plasmonic Scaffolds for 3D Cell Culture and Noninvasive Sensing of Cellular Metabolites (Adv. Healthcare Mater. 4/2021)
Authors: Sean E. Lehman, Joselle M. McCracken, Lou Ann Miller, Sanjaya Jayalath, Ralph G. Nuzzo
Journal: Advanced Healthcare Materials (2021)

A 3D-printable composite material consisting of gold nanoparticles embedded within a poly-2-hydroxyethylmethacrylate matrix, that serves dual functions as both host framework scaffold for pre-osteoblasts, as well as a non-invasive plasmonic biosensor for cellular metabolites, is presented in article number 2001040 by Ralph G. Nuzzo and co-workers. The 3D printing ink is particle-free and the gold nanoparticles are generated in the 3D-printed scaffolds via a postprint chemical reduction method. Pre-osteoblast cells are successfully grown and differentiated into mature osteoblasts over the 3D printed scaffolds. Cellular metabolites are detected using surface-enhanced Raman spectroscopy during different stages of cell growth and differentiation. Common cellular, as well as some free amino acids, are detected using SERS demonstrating the ability of the composite material to function as a biologically compliant plasmonic biosensor in cell culture applications.
Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?
Authors: Andrea Giaccari, Anna Solini, Simona Frontoni, Stefano Del Prato
Journal: Diabetes Care (2021)

Since the UK Prospective Diabetes Study (UKPDS), metformin has been considered the first-line medication for patients with newly diagnosed type 2 diabetes. Though direct evidence from specific trials is still lacking, several studies have suggested that metformin may protect from diabetes- and nondiabetes-related comorbidities, including cardiovascular, renal, neurological, and neoplastic diseases. In the past few decades, several mechanisms of action have been proposed to explain metformin's protective effects, none being final. It is certain, however, that metformin increases lactate production, concentration, and, possibly, oxidation. Once considered a mere waste product of exercising skeletal muscle or anaerobiosis, lactate is now known to act as a major energy shuttle, redistributed from production sites to where it is needed. Through the direct uptake and oxidation of lactate produced elsewhere, all end organs can be rapidly supplied with fundamental energy, skipping glycolysis and its possible byproducts. Increased lactate production (and consequent oxidation) could therefore be considered a positive mechanism of action of metformin, except when, under specific circumstances, metformin and lactate become excessive, increasing the risk of lactic acidosis. We are proposing that, rather than considering metformin-induced lactate production as dangerous, it could be considered a mechanism through which metformin exerts its possible protective effect on the heart, kidneys, and brain and, to some extent, its antineoplastic action.
Temporal Arteritis Revealing Antineutrophil Cytoplasmic Antibody–Associated Vasculitides: Are the Visual Outcomes Different From Giant Cell Arteritis? Comment on the Article by Delaval et al
Authors: Joydeep Samanta, GSRSNK Naidu, Sakshi Mittal, Ritambhra Nada, Amanjit Bal, Ramandeep Singh, Vishali Gupta, Amod Gupta, Aman Sharma, Benzeeta Pinto
Journal: Arthritis & Rheumatology (2021)
Cytoplasmic DROSHA and non-canonical mechanisms of MiR-155 biogenesis in FLT3-ITD acute myeloid leukemia
Authors: Le Xuan Truong Nguyen, Bin Zhang, Dinh Hoa Hoang, Dandan Zhao, Huafeng Wang, Herman Wu, Yu-Lin Su, Haojie Dong, Sonia Rodriguez-Rodriguez, Brian Armstrong, Lucy Y. Ghoda, Danilo Perrotti, Flavia Pichiorri, Jianjun Chen, Ling Li, Marcin Kortylewski, Russell C. Rockne, Ya-Huei Kuo, Samer Khaled, Nadia Carlesso, Guido Marcucci
Journal: Leukemia (2021)
Optimal symptom combinations to aid COVID-19 case identification: Analysis from a community-based, prospective, observational cohort
Authors: M. Antonelli, J. Capdevila, A. Chaudhari, J. Granerod, L.S. Canas, M.S. Graham, K. Klaser, M. Modat, E. Molteni, B. Murray, C.H. Sudre, R. Davies, A. May, L.H. Nguyen, D.A. Drew, A. Joshi, A.T. Chan, J.P. Cramer, T. Spector, J. Wolf, S. Ourselin, C.J. Steves, A.E. Loeliger
Journal: Journal of Infection (2021)
Interleukin-20 exacerbates acute hepatitis and bacterial infection by downregulating IκBζ target genes in hepatocytes
Authors: Yong He, Dechun Feng, Seonghwan Hwang, Bryan Mackowiak, Xiaolin Wang, Xiaogang Xiang, Robim M. Rodrigues, Yaojie Fu, Jing Ma, Tianyi Ren, Yeni Ait-Ahmed, Mingjiang Xu, Suthat Liangpunsakul, Bin Gao
Journal: Journal of Hepatology (2021)
Making human milk matter: the need for EU regulation
Authors: Johanna Kostenzer, Enrico Bertino, Tanya Cassidy, Mandy Daly, Magnus Domellöf, Antoni Gaya, Johannes B. van Goudoever, Johanna Kostenzer, Silke Mader, Guido E. Moro, Jean-Charles Picaud, Miguel Saenz de Pipaon, Małgorzata Gawrońska, James S. Taylor, Eleni Vavouraki, Aleksandra Wesolowska, Luc J.I. Zimmermann
Journal: The Lancet Child & Adolescent Health (2021)
Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence
Authors: Xiu Han, Xiang Xu, Ziheng Wu, Zhenghong Wu, Xiaole Qi
Journal: Acta Pharmaceutica Sinica B (2021)

The functionality of DNA biomacromolecules has been widely excavated, as therapeutic drugs, carriers, and functionalized modification derivatives. In this study, we developed a series of DNA tetrahedron nanocages (Td), via synchronous conjugating different numbers of i-(X) and therapeutic siRNA on four vertexes of tetrahedral DNA nanocage (aX-Td@bsiRNA, a+b = 4). This i-motif-conjugated Td exhibited good endosomal escape behaviours in A549 tumor cells, and the escape efficiency was affected by the number of i-motif. Furthermore, the downregulating mRNA and protein expression level of epidermal growth factor receptor (EGFR) caused by this siRNA embedded Td were verified in A549 cells. The tumor growth inhibition efficiency of the 2X-Td@2siRNA treated group in tumor-bearing mice was significantly higher than that of non-i-motif-conjugated Td@2siRNA (3.14-fold) and free siRNA (3.63-fold). These results demonstrate a general strategy for endowing DNA nanostructures with endosomal escape behaviours to achieve effective in vivo gene delivery and therapy.
Primary Ewing Sarcoma of Seminal Vesicle on PET/CT
Authors: Guohua Shen, Cheng Yi, Lili Pan, Anren Kuang
Journal: Clinical Nuclear Medicine (2021)

Ewing sarcoma is an aggressive malignancy that most often presents as an undifferentiated primary bone tumor; less commonly, it arises in extraosseous soft tissues of mesenchymal cell origin. Primary extraosseous involvement of seminal vesicle is rarely reported. Herein, we describe FDG PET/CT and MRI findings of a 55-year-old man who presented with a pelvic mass, which was confirmed to be primary Ewing sarcoma/primitive neuroectodermal tumor arising from seminal vesicle by histopathologic findings.
Radiological dynamics and SITC-defined resistance types of advanced melanoma during anti-PD-1 monotherapy: an independent single-blind observational study on an international cohort
Authors: Xue Bai, Michelle Kim, Gyulnara Kasumova, Lu Si, Bixia Tang, Chuanliang Cui, Xiaoling Yang, Xiaoting Wei, Justine Cohen, Donald Lawrence, Christine Freedman, Riley Fadden, Krista Rubin, Tatyana Sharova, Dennie Frederick, Keith Flaherty, Ryan Sullivan, Jun Guo, Genevieve Boland
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Although the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Taskforce recently defined primary and secondary resistance to anti-programmed cell death protein 1 (anti-PD-1) therapy, there is lack of real-world data regarding differences in these resistance subtypes with respect to radiological dynamics and clinical manifestations. Methods We performed single-blind re-evaluations of radiological images by independent radiologists on a retrospectively assembled cohort of patients with advanced melanoma (n=254, median follow-up 31 months) receiving anti-PD-1 monotherapy at Massachusetts General Hospital and Peking University Cancer Hospital. Radiological characteristics and timing at multiple crucial time points were analyzed and correlated with each other and with survival. Primary and secondary resistance was defined as per the SITC Immunotherapy Resistance Taskforce definitions. Results The most significant target lesion measurement change took place within the first 3 months after anti-PD-1 initiation. Patients with stable disease with versus without tumor shrinkage at the initial evaluation exhibited distinct disease trajectory, as the rate of further upgrade to a partial or complete remission (CR/PR) was 44% and 0%, respectively. Eleven per cent of PR patients ultimately achieved a CR. In multivariate analyses, deeper response depth was independently associated with a more limited progression pattern, fewer involved organs, lower tumor burden, slower growth rate at disease progression (PD) (all p≤0.001), and longer post-progression survival (PPS) (bivariate analysis, p=0.005). Compared with primary resistance, secondary resistance was associated with less widespread PD pattern, lower tumor burden and slower tumor growth (all p≤0.001). Patients with secondary resistance were less likely to receive further systemic therapy (28% vs 57%, p&lt;0.001) yet had significantly better PPS (HR 0.503, 95% CI 0.288 to 0.879, p=0.02). Conclusions Radiological dynamics were variable, yet significantly correlated with survival outcomes. SITC-defined primary and secondary resistance are distinct clinical manifestations in patients with melanoma, suggesting the possibility of resistance-type-based therapeutic decision-making and clinical trial design, once further validated by future prospective studies.
Prognostic Utility of High-Sensitivity Troponin I Among Hospitalized COVID-19 Positive Patients in Michigan - A Retrospective Analysis
Authors: A. M. Altibi, R. Sheth, A. Leduc, L. Al Jebbawi, A. Masri, A. Slota, H. Liaqat, M. George, S. Jain, E. Abdallah, L. Russell, N. Shirvanian, B. D. Patel, P. Bhargava, V. Kak
Journal: Circulation (2020)
Updates from the British Association of Dermatologists 84th Annual Meeting, 6-9 July 2004, Belfast, U.K.
Authors: D.J. Eedy, J.S.C. English
Journal: British Journal of Dermatology (2005)

Herein is a synopsis of the main research and clinical findings presented at the British Association of Dermatologists meeting held during 6–9 July 2004, in Belfast, U.K. The conference highlighted the progress that has been made in understanding the increasing biological, epidemiological and therapeutic advances that have been made recently in the field of dermatology. The authors highlight the more important advances or summaries, but this is not meant as a substitute for reading the conference proceedings and related references quoted in this article.
Intratumoral Plasmid IL12 Expands CD8+ T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti–PD-1 Therapy
Authors: Melinda L. Telli, Hiroshi Nagata, Irene Wapnir, Chaitanya R. Acharya, Kaitlin Zablotsky, Bernard A. Fox, Carlo B. Bifulco, Shawn M. Jensen, Carmen Ballesteros-Merino, Mai Hope Le, Robert H. Pierce, Erica Browning, Reneta Hermiz, Lauren Svenson, Donna Bannavong, Kim Jaffe, Jendy Sell, Kellie Malloy Foerter, David A. Canton, Christopher G. Twitty, Takuya Osada, H. Kim Lyerly, Erika J. Crosby
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed. Patients and Methods: Using mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (tavokinogene telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets. Results: Single-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8+ T-cell infiltration following treatment. One patient, previously unresponsive to anti–PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti–PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response. Conclusions: These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.
Graphene Oxide‐Doped Gellan Gum–PEGDA Bilayered Hydrogel Mimicking the Mechanical and Lubrication Properties of Articular Cartilage
Authors: Diego Trucco, Lorenzo Vannozzi, Eti Teblum, Madina Telkhozhayeva, Gilbert Daniel Nessim, Saverio Affatato, Hind Al‐Haddad, Gina Lisignoli, Leonardo Ricotti
Journal: Advanced Healthcare Materials (2021)

Abstract Articular cartilage (AC) is a specialized connective tissue able to provide a low‐friction gliding surface supporting shock‐absorption, reducing stresses, and guaranteeing wear‐resistance thanks to its structure and mechanical and lubrication properties. Being an avascular tissue, AC has a limited ability to heal defects. Nowadays, conventional strategies show several limitations, which results in ineffective restoration of chondral defects. Several tissue engineering approaches have been proposed to restore the AC's native properties without reproducing its mechanical and lubrication properties yet. This work reports the fabrication of a bilayered structure made of gellan gum (GG) and poly (ethylene glycol) diacrylate (PEGDA), able to mimic the mechanical and lubrication features of both AC superficial and deep zones. Through appropriate combinations of GG and PEGDA, cartilage Young's modulus is effectively mimicked for both zones. Graphene oxide is used as a dopant agent for the superficial hydrogel layer, demonstrating a lower friction than the nondoped counterpart. The bilayered hydrogel's antiwear properties are confirmed by using a knee simulator, following ISO 14243. Finally, in vitro tests with human chondrocytes confirm the absence of cytotoxicity effects. The results shown in this paper open the way to a multilayered synthetic injectable or surgically implantable filler for restoring AC defects.
Abstract 15828: Cyanobacteria-alginate Microgels For Sustained Photosynthetic Oxygen Delivery To Rescue Cardiomyocytes In An Ischemic Milieu
Authors: Lyndsay M Stapleton, Justin M Farry, Haley J Lucian, Hanjay Wang, Kailey P Totherow, Michael J Paulsen, Gillie Agmon, Mariana Cabatu, Akshara D Thakore, Anahita N Eskandari, Shreya D Anilkumar, Frank J Buncom, Eric A Appel, Y Joseph Y Woo
Journal: Circulation (2019)

Objective: Current therapies for acute myocardial infarction often fail to address microvascular perfusion deficits. Our team recently harnessed the photosynthetic metabolism of cyanobacteria to de...
Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality
Authors: David J.A. Jenkins, Mahshid Dehghan, Andrew Mente, Shrikant I. Bangdiwala, Sumathy Rangarajan, Kristie Srichaikul, Viswanathan Mohan, Alvaro Avezum, Rafael Díaz, Annika Rosengren, Fernando Lanas, Patricio Lopez-Jaramillo, Wei Li, Aytekin Oguz, Rasha Khatib, Paul Poirier, Noushin Mohammadifard, Andrea Pepe, Khalid F. Alhabib, Jephat Chifamba, Afzal Hussein Yusufali, Romaina Iqbal, Karen Yeates, Khalid Yusoff, Noorhassim Ismail, Koon Teo, Sumathi Swaminathan, Xiaoyun Liu, Katarzyna Zatońska, Rita Yusuf, Salim Yusuf
Journal: New England Journal of Medicine (2021)

Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population.
Risk Factors and Mortality of COVID-19 in Patients With Lymphoma: A Multicenter Study
Authors: Isabel Regalado-Artamendi, Ana Jiménez-Ubieto, José Ángel Hernández-Rivas, Belén Navarro, Lucía Núñez, Concha Alaez, Raúl Córdoba, Francisco Javier Peñalver, Jimena Cannata, Pablo Estival, Keina Quiroz-Cervantes, Rosalía Riaza Grau, Alberto Velasco, Rafael Martos, Amalia Domingo-González, Laurentino Benito-Parra, Elvira Gómez-Sanz, Javier López-Jiménez, Arturo Matilla, María Regina Herraez, María José Penalva, Julio García-Suárez, José Luis Díez-Martín, Mariana Bastos-Oreiro
Journal: HemaSphere (2021)

Patients with cancer are poorly represented in coronavirus disease 2019 (COVID-19) series, and heterogeneous series concerning hematology patients have been published. This study aimed to analyze the impact of COVID-19 in patients with lymphoma. We present a multicenter retrospective study from 19 centers in Madrid, Spain, evaluating risk factors for mortality in adult patients with COVID-19 and lymphoma. About 177 patients (55.9% male) were included with a median follow-up of 27 days and a median age of 70 years. At the time of COVID-19 diagnosis, 49.7% of patients were on active treatment. The overall mortality rate was 34.5%. Age &gt;70 years, confusion, urea concentration, respiratory rate, blood pressure, and age &gt;65 score ≥2, heart disease, and chronic kidney disease were associated with higher mortality risk ( P &lt; 0.05). Active disease significantly increased the risk of death (hazard ratio, 2.43; 95% confidence interval, 1.23-4.77; P = 0.01). However, active treatment did not modify mortality risk and no differences were found between the different therapeutic regimens. The persistence of severe acute respiratory syndrome coronavirus 2-positive polymerase chain reaction after week 6 was significantly associated with mortality (54.5% versus 1.4%; P &lt; 0.001). We confirm an increased mortality compared with the general population. In view of our results, any interruption or delay in the start of treatment should be questioned given that active treatment has not been demonstrated to increase mortality risk and that achieving disease remission could lead to better outcomes.