tbuckley/cabot-search huggingface dataset:
Persistent ST-Segment Elevation in a Young Man
Authors: Hao-Yu Wu, Yi-Wei Cao, Lei Liang
Journal: JAMA Internal Medicine (2021)

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House dust mite sensitization and frequent antibiotic courses may suppress remission of rhinosinusitis and asthma symptoms in young children
Authors: Katarzyna Molińska, Marta Latek, Błażej Rychlik, Jakub Lach, Dominik Strapagiel, Joanna Majak, Łukasz Błażowski, Joanna Jerzyńska, Piotr Kuna, Pawel Majak
Journal: Allergy (2021)

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Rare genetic coding variants associated with human longevity and protection against age-related diseases
Authors: Jhih-Rong Lin, Patrick Sin-Chan, Valerio Napolioni, Guillermo G. Torres, Joydeep Mitra, Quanwei Zhang, M. Reza Jabalameli, Zhen Wang, Nha Nguyen, Tina Gao, Matthias Laudes, Siegfried Görg, Andre Franke, Almut Nebel, Michael D. Greicius, Gil Atzmon, Kenny Ye, Vera Gorbunova, Warren C. Ladiges, Alan R. Shuldiner, Laura J. Niedernhofer, Paul D. Robbins, Sofiya Milman, Yousin Suh, Jan Vijg, Nir Barzilai, Zhengdong D. Zhang
Journal: Nature Aging (2021)
Release of basic fibroblast growth factor from acoustically-responsive scaffolds promotes therapeutic angiogenesis in the hind limb ischemia model
Authors: Hai Jin, Carole Quesada, Mitra Aliabouzar, Oliver D. Kripfgans, Renny T. Franceschi, Jianhua Liu, Andrew J. Putnam, Mario L. Fabiilli
Journal: Journal of Controlled Release (2021)
Real-world utilization and costs with biosimilar and reference filgrastim in patients with breast cancer receiving myelosuppressive chemotherapy in a community oncology setting from 2015 to 2017.
Authors: Robert M. Rifkin, Lisa Herms, Chuck Wentworth, Anupama Vasudevan, Kimberley Campbell, Edward C. Li
Journal: Journal of Clinical Oncology (2021)

57 Background: Biosimilars have potential to reduce healthcare costs and increase access in the United States, but lack of uptake has contributed to lost savings. Filgrastim-sndz was the first FDA-approved biosimilar, and much can be learned by evaluating its uptake. In February 2016, the US Oncology Network converted to filgrastim-sndz as its short-acting granulocyte colony-stimulating factor (GCSF) of choice for prevention of febrile neutropenia (FN) following myelosuppressive chemotherapy (MCT). To understand utilization and cost patterns, this study analyzes real-world data of GCSFs within a community oncology network during the initial period of conversion to the first biosimilar available in the US. Methods: This descriptive retrospective observational study used electronic health record data for female breast cancer (BC) patients receiving GCSF and MCT at high risk of FN. Patient cohorts were defined by first receipt of either filgrastim or filgrastim-sndz during the 410 days before and after biosimilar conversion. Healthcare resource utilization (HCRU) and costs for GCSF and complete blood counts (CBC) were collected at GCSF initiation through the earliest of 30 days following end of MCT, loss to follow up, death, or data cutoff. Results: 146 patients were identified: 81 (55.5%) filgrastim and 65 (44.5%) filgrastim-sndz. No directional differences existed in baseline characteristics between the cohorts. Higher proportions of filgrastim-sndz patients received dose-dense MCT (33.8% vs 22.2%). Time trends show an initial spike in HCRU and cost for filgrastim-sndz patients after formulary conversion, which subsequently decreased and converged to that of the filgrastim cohort after 12 months. When aggregated, the overall median total administration counts, per patient per month (PPPM) and dosage, were marginally higher for filgrastim-sndz (5 vs 3; 2.9 vs 1.4; 1920 vs 1440 mcg, respectively). Median PPPM costs were higher for filgrastim-sndz ($803 vs $545). Median CBC utilization and costs were higher for filgrastim-sndz (2.8 vs 2.5; $28 vs $23, respectively). Conclusions: This study provides insight into real-world HCRU and cost patterns after formulary conversion to a biosimilar for BC patients receiving MCT and GCSF. As a descriptive study, causal inferences cannot be made and an underlying effect from index chemotherapy cannot be excluded. Convergence of HCRU and costs after 12 months suggests that overall results may be driven by behavior at initial formulary switch. Since filgrastim-sndz was the first US biosimilar approved, the uptake may be indicative of an experience with biosimilar acceptance in general. Future real-world studies of biosimilars must consider inconsistent utilization and practice trends during the time frame directly following formulary conversion.
日本循環器学会及び日本心電図学会により作成された抗不整脈薬療法に関するCD-ROMガイドラインの妥当性に関する多施設調査-個々の治療による不整脈管理に関する日本のガイドライン(J-GAMBIT)の調査に関する予備的報告-
Authors: Katoh Takao, Ohara Toshihiko, Ogawa Satoshi, Kodama Itsuo
Journal: Circulation (2005)
Impact of the methylation classifier and ancillary methods on CNS tumor diagnostics
Authors: Zhichao Wu, Zied Abdullaev, Drew Pratt, Hye-Jung Chung, Shannon Skarshaug, Valerie Zgonc, Candice Perry, Svetlana Pack, Lola Saidkhodjaeva, Sushma Nagaraj, Manoj Tyagi, Vineela Gangalapudi, Kristin Valdez, Rust Turakulov, Liqiang Xi, Mark Raffeld, Antonios Papanicolau-Sengos, Kayla O’Donnell, Michael Newford, Mark R Gilbert, Felix Sahm, Abigail K Suwala, Andreas von Deimling, Yasin Mamatjan, Shirin Karimi, Farshad Nassiri, Gelareh Zadeh, Eytan Ruppin, Martha Quezado, Kenneth Aldape
Journal: Neuro-Oncology (2021)

Abstract Background Accurate CNS tumor diagnosis can be challenging, and methylation profiling can serve as an adjunct to classify diagnostically difficult cases. Methods An integrated diagnostic approach was employed for a consecutive series of 1258 surgical neuropathology samples obtained primarily in a consultation practice over 2-year period. DNA methylation profiling and classification using the DKFZ/Heidelberg CNS tumor classifier was performed, as well as unsupervised analyses of methylation data. Ancillary testing, where relevant, was performed. Results Among the received cases in consultation, a high-confidence methylation classifier score (&amp;gt;0.84) was reached in 66.4% of cases. The classifier impacted the diagnosis in 46.7% of these high-confidence classifier score cases, including a substantially new diagnosis in 26.9% cases. Among the 289 cases received with only a descriptive diagnosis, methylation was able to resolve approximately half (144, 49.8%) with high-confidence scores. Additional methods were able to resolve diagnostic uncertainty in 41.6% of the low-score cases. Tumor purity was significantly associated with classifier score (P = 1.15e−11). Deconvolution demonstrated that suspected glioblastomas (GBMs) matching as control/inflammatory brain tissue could be resolved into GBM methylation profiles, which provided a proof-of-concept approach to resolve tumor classification in the setting of low tumor purity. Conclusions This work assesses the impact of a methylation classifier and additional methods in a consultative practice by defining the proportions with concordant vs change in diagnosis in a set of diagnostically challenging CNS tumors. We address approaches to low-confidence scores and confounding issues of low tumor purity.
P14.79 Differentiation of treatment-related changes from tumor progression following brachytherapy in patients with WHO II and III gliomas using FET PET
Authors: E K Bauer, J Werner, A Brunn, M Deckert, D Ruess, M Ruge, E Celik, G R Fink, K Langen, N Galldiks
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Following brachytherapy, the differentiation of radiation-induced changes (e.g., radiation necrosis) from actual tumor progression using MRI is challenging. To overcome this diagnostic uncertainty, we evaluated the diagnostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in glioma patients treated with brachytherapy. MATERIAL AND METHODS From 2006–2019, we retrospectively identified WHO grade II or III glioma patients (i) treated with brachytherapy using Iodine-125 seeds, (ii) equivocal or progressive MRI findings inside the radiation field, and (iii) additional FET PET imaging for diagnostic evaluation. Static FET PET parameters such as maximum and mean tumor-to-brain ratios (TBR) and dynamic FET PET parameters (i.e., time-to-peak, slope) were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses and Fisher’s exact test. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS Following brachytherapy, suspect MRI findings occurred after a median time of 33 months (range, 5–111 months). In 10 of 21 patients (WHO grade II, n=5; WHO grade III, n=16), treatment-related changes were diagnosed. The best diagnostic performance for identification of treatment-related changes was obtained using maximum TBRs (threshold &amp;lt;3.20; accuracy, 86%; sensitivity, 100%; specificity, 73%; P=0.007). Mean TBRs reached an accuracy of 76% (threshold &amp;lt;2.05; sensitivity, 89%; specificity, 64%; P=0.010). Dynamic PET parameters did not reach statistically significant results. CONCLUSION Our data suggest that static FET PET parameters add valuable diagnostic information to diagnose radiation-induced changes in glioma patients treated with brachytherapy.
Covid-19 associated thrombotic thrombocytopenic purpura (ttp);A case series and mini-review
Authors: S. Haghighi, H. A. Tehrani, M. Darnahal
Journal: HemaSphere (2021)

Background: Thrombotic microangiopathies are a group of disorders that are mainly related to endothelial dysfunction. This category of endothelial dysfunction results of several imbalances between platelets, endothelium and immune system, also cytokine production Aims: To report cases with thrombotic thrombocytopenic purpura (TTP) and COVID-19 and review COVID-19 endothelial dysfunction literature. Methods: Primary laboratory data, peripheral blood smear, ADAMTS13 antigen activity level, and antibody ordered for each of these four patients. Treatments for COVID-19 administered for all patients. Traditional treatments for TTP also were administered. Results: There were numerous schistocytes (more than 5%) in peripheral blood smears for each patient. ADAMTS13 antigen activity level was below 10%, and ADAMTS13 antibody was elevated for each patient. COVID-19 PCR was positive for all patients, and CT-Scans were indicative of the involvement of COVID-19. Summary/Conclusion: Conclusion: In this case series, we reported four COVID-19 patients who presented with signs and symptoms of anemia and thrombocytopenia, resulting in thrombotic thrombocytopenic purpura.
Endosomal disentanglement of a transducible artificial transcription factor targeting endothelin receptor A
Authors: Claudia C. Bippes, Corina Kohler, Esther Garcia-Tirado, Reto Burri, Tina Frauenknecht, Marie-Apolline Gerard, Marie Salat, Roy Allenspach, Cavit Agca, Zongsong Wu, Andrea Trost, Barbara Bogner, Peter Meyer, Hendrik P.N. Scholl, Herbert Reitsamer, Josef Flammer, Albert Neutzner
Journal: Molecular Therapy (2021)

Cell-penetrating peptides (CPPs) hold great promise for intracellular delivery of therapeutic proteins. However, endosomal entrapment of transduced cargo is a major bottleneck hampering their successful application. While developing a transducible zinc finger protein-based artificial transcription factor targeting the expression of endothelin receptor A, we identified interaction between the CPP and the endosomal membrane or endosomal entanglement as a main culprit for endosomal entrapment. To achieve endosomal disentanglement, we utilized endosome-resident proteases to sever the artificial transcription factor from its CPP upon arrival inside the endosome. Using this approach, we greatly enhanced the correct subcellular localization of the disentangled artificial transcription factor, significantly increasing its biological activity and distribution in vivo. With rational engineering of proteolytic sensitivity, we propose a new design principle for transducible therapeutic proteins, helping CPPs attain their full potential as delivery vectors for therapeutic proteins. Cell-penetrating peptides (CPPs) hold great promise for intracellular delivery of therapeutic proteins. However, endosomal entrapment of transduced cargo is a major bottleneck hampering their successful application. While developing a transducible zinc finger protein-based artificial transcription factor targeting the expression of endothelin receptor A, we identified interaction between the CPP and the endosomal membrane or endosomal entanglement as a main culprit for endosomal entrapment. To achieve endosomal disentanglement, we utilized endosome-resident proteases to sever the artificial transcription factor from its CPP upon arrival inside the endosome. Using this approach, we greatly enhanced the correct subcellular localization of the disentangled artificial transcription factor, significantly increasing its biological activity and distribution in vivo. With rational engineering of proteolytic sensitivity, we propose a new design principle for transducible therapeutic proteins, helping CPPs attain their full potential as delivery vectors for therapeutic proteins.
Cardiovascular Manifestations From Therapeutic Radiation
Authors: Joshua D. Mitchell, Daniel A. Cehic, Marita Morgia, Carmen Bergom, Joanne Toohey, Patricia A. Guerrero, Maros Ferencik, Robin Kikuchi, Joseph R. Carver, Vlad G. Zaha, Jose A. Alvarez-Cardona, Sebastian Szmit, Andrés J. Daniele, Juan Lopez-Mattei, Lili Zhang, Jörg Herrmann, Anju Nohria, Daniel J. Lenihan, Susan F. Dent
Journal: JACC CardioOncology (2021)

Radiation therapy is a cornerstone of cancer therapy, with >50% of patients undergoing therapeutic radiation. As a result of widespread use and improved survival, there is increasing focus on the potential long-term effects of ionizing radiation, especially cardiovascular toxicity. Radiation therapy can lead to atherosclerosis of the vasculature as well as valvular, myocardial, and pericardial dysfunction. We present a consensus statement from the International Cardio-Oncology Society based on general principles of radiotherapy delivery and cardiovascular risk assessment and risk mitigation in this population. Anatomical-based recommendations for cardiovascular management and follow-up are provided, and a priority is given to the early detection of atherosclerotic vascular disease on imaging to help guide preventive therapy. Unique management considerations in radiation-induced cardiovascular disease are also discussed. Recommendations are based on the most current literature and represent a unanimous consensus by the multidisciplinary expert panel.
P04.18 Heterogeneity and plasticity of integrin α5β1 expression in glioblastoma stem cells
Authors: M Messé, C Bernhard, M Mercier, Q Fuchs, S Foppolo, C Herold-Mende, I Namer, C Bund, M Elati, N Entz-Werlé, M Dontenwill
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma (GBM) is the most frequent and deadliest type of central nervous system tumors. Despite the treatment by the Stupp protocol, almost all patients relapse and new therapeutic protocols have been unsuccessful for ameliorating patient survival. Molecular heterogeneity of GBM and existence of glioma stem cells (GSC) may be linked to therapy resistance and recurrence. We demonstrated earlier that α5β1 integrin is a GBM therapeutic target which participate to therapy resistance; a high expression in patient tumors is linked to a worse prognosis. Expression of α5β1 integrin is heterogeneous inter- and intra-tumorally. We particularly addressed the role of glioma stem cell plasticity in the modulation of the integrin expression. Stem cells reside in specific niches (perivascular or hypoxic niches) in the tumor and are at the origin of the more differentiated tumor cell bulk. Metabolism is known to change between the different GSC states and may be affected by or may affect the integrin expression. The aim of our work is therefore to consider the expression of the integrin α5β1 in relationship with GSC differentiation or in hypoxic environment and with cell metabolism. MATERIAL AND METHODS Ten different patient-derived glioma stem cell lines were investigated. Cell culture in stem cell medium (neurospheres) or differentiation medium (adherent cell monolayer) was made in normoxia (21% O2) or hypoxia (1%O2). Alternatively, chemically-induced hypoxia (cobalt chloride/desferoxiamine) was used. Integrin expression was kinetically checked at the mRNA (RT-qPCR) or protein (Western blot) levels. Cell metabolism was investigated with the Seahorse Xfp technology and by HRMAS-NMR. RESULTS No GSC lines (neurospheres) expressed the α5β1 integrin. Interestingly, only half of them did after differentiation suggesting a first level of heterogeneity. A second level of heterogeneity was observed in hypoxic conditions provoking induction of integrin α5β1 expression in only some non-differentiated GSC. Three categories of GSC were thus characterized: one able to express the integrin in hypoxia and after differentiation, one never expressing it and the third one only after differentiation. Cell metabolism differed between GSC before and after differentiation and in presence of integrin α5β1 antagonists. Specific glioma regulator network analysis revealed new targets to be inhibited concomitantly with the integrin. CONCLUSION Data suggest that α5β1 integrin expression may be induced by different signaling pathways. Molecular switches may occur either when stem cells differentiate to tumor cells but also directly in stem cells in hypoxic niches. Characterization of α5β1 integrin expression drivers may help to find new therapeutic targets but also to delineate subpopulation of patients who would benefit from an anti-integrin strategy.
Injectable Natural Polymer Hydrogels for Treatment of Knee Osteoarthritis
Authors: Xiaojie Lin, Ching Ting Tsao, Masayuki Kyomoto, Miqin Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract Osteoarthritis (OA) is a serious chronic and degenerative disease that increasingly occurs in the aged population. Its current clinical treatments are limited to symptom relief and cannot regenerate cartilage. Although a better understanding of OA pathophysiology has been facilitating the development of novel therapeutic regimen, delivery of therapeutics to target sites with minimal invasiveness, high retention, and minimal side effects remains a challenge. Biocompatible hydrogels have been recognized to be highly promising for controlled delivery and release of therapeutics and biologics for tissue repair. In this review, the current approaches and the challenges in OA treatment, and unique properties of injectable natural polymer hydrogels as delivery system to overcome the challenges are presented. The common methods for fabrication of injectable polysaccharide‐based hydrogels and the effects of their composition and properties on the OA treatment are detailed. The strategies of the use of hydrogels for loading and release cargos are also covered. Finally, recent efforts on the development of injectable polysaccharide‐based hydrogels for OA treatment are highlighted, and their current limitations are discussed.
Patient responses to weekly electronic patient-reported outcomes.
Authors: D'Ambra Dent, Stacey A. Ingram, Valerie Lawhon, Omer Jamy, Smith Giri, Julie Scott, Nadia Still, Debra Wujcik, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2021)

182 Background: Home-based symptom monitoring using patient reported outcomes has been shown to reduce symptom burden and hospitalizations, while improving quality of life and overall. The primary goal of this study was to evaluate the early feasibility of home-based symptom monitoring. Methods: This prospective single-arm pilot study evaluated a two-part education and technology intervention (home-based symptom monitoring) for clinicians treating Multiple Myeloma (MM) and Acute Myeloid Leukemia (AML) patients. Inclusion criteria included patients ≥ 60 who were anticipating a treatment decision. Participants completed a baseline survey and then enrolled into the PROmpt® symptom monitoring platform, which used text or email to prompt weekly symptom surveys. Patients receive an auto-generated self-management plan based on electronic patient reported outcomes (ePRO). If severe symptoms were reported (score of &gt; 7/10), alerts were sent to clinical nurses. Outcomes for this study included proportion of patient approach who agreed to participate, patient completion rates (completion of weekly surveys), compliance rate (completion of total surveys), number of alerts generated, and type of alert. Feasibility was defined as a completion rate of &gt; 70%. Results: Between September 1, 2020 –May 19, 2021; 114 patients were screened, 77 were approached, and 35 were enrolled (18) MM, (17) AML patients. Of non-participants, 11 were not seeking care at the institution, 10 patients were uninterested or did not have a smartphone, 9 patients were ineligible, and 9 were unsure and left with information about the study, 3 declined enrollment. The majority (80%) or participants were ages 60-74; 20% of patients were ages 75+. Over the 13-week period, AML patients completed 195/220 (compliance rate of 89%). The average completion rate was 92%. For MM, 192/233 surveys were completed (82% compliance rate). The average completion rate was 94%. For AML, 9 was the average number of completed surveys and the average number for MM was 8. Over 3 months, there were 294 moderate to severe alerts generated for AML and MM patients. For AML patients, there were 40 fatigue, 25 constipation, 21 pain, 17 decreased appetite, 11 insomnia, 11 rash, 6 anxiety, 7 dyspnea/cough, 7 diarrhea, 5 depression/sadness, 4 nausea/ vomiting, 4 mouth/ throat sores, 3 neuropathy, 3 fever, and 2 alerts for other symptoms. Within a 3 month time span for MM patients, there was 35 pain, 21 constipation, 18 fatigue, 11 rash, 10 neuropathy, 9 anxiety, 7 insomnia, 6 depression/sadness, 4 decreased appetite, 4 other symptom, and 1 nausea/vomiting alert. Conclusions: This study demonstrated early feasibility with over 80% of patient completing their surveys with a high compliance rate. Future analysis will include both final implementation outcomes as well as patient outcomes for all patients within the study.
Autoimmune Diseases, Infections, Use of Antibiotics and the Risk of Acute Myeloid Leukemia: A National Population-Based Case-Control Study
Authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Lars Pedersen, René Østgård, Ulrik Malthe Overgaard, Claudia Schöllkopf, Marianne Tang Severinsen, Claus Werenberg Marcher, Morten Krogh Jensen
Journal: Blood (2017)