tbuckley/cabot-search huggingface dataset:
Disclose and Manage Conflicts of Interest at Cancer Centers
Authors: Roy A. Jensen, Karen E. Knudsen, Leonidas C. Platanias
Journal: JAMA Internal Medicine (2020)

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Abstract 14509: Three-Dimensional Beating Human Myocardial Tissues Fabricated From Induced Pluripotent Stem Cells and Cell Sheet Technology
Authors: Hyoe Komae, Hidekazu Sekine, Katsuhisa Matsuura, Izumi Dobashi, Tatsuya Shimizu, Minoru Ono, Teruo Okano
Journal: Circulation (2013)

The only radical surgical treatment for severe heart failure is heart transplantation. However, the number of donor hearts available for transplant is limited; so many waiting patients die as their...
Epigenetic therapy of myelodysplastic syndromes connects to cellular differentiation independently of endogenous retroelement derepression
Authors: Anastasiya Kazachenka, George R. Young, Jan Attig, Chrysoula Kordella, Eleftheria Lamprianidou, Emmanuela Zoulia, George Vrachiolias, Menelaos Papoutselis, Elsa Bernard, Elli Papaemmanuil, Ioannis Kotsianidis, George Kassiotis
Journal: Genome Medicine (2019)

Abstract Background Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) are characterised by abnormal epigenetic repression and differentiation of bone marrow haematopoietic stem cells (HSCs). Drugs that reverse epigenetic repression, such as 5-azacytidine (5-AZA), induce haematological improvement in half of treated patients. Although the mechanisms underlying therapy success are not yet clear, induction of endogenous retroelements (EREs) has been hypothesised. Methods Using RNA sequencing (RNA-seq), we compared the transcription of EREs in bone marrow HSCs from a new cohort of MDS and chronic myelomonocytic leukaemia (CMML) patients before and after 5-AZA treatment with HSCs from healthy donors and AML patients. We further examined ERE transcription using the most comprehensive annotation of ERE-overlapping transcripts expressed in HSCs, generated here by de novo transcript assembly and supported by full-length RNA-seq. Results Consistent with prior reports, we found that treatment with 5-AZA increased the representation of ERE-derived RNA-seq reads in the transcriptome. However, such increases were comparable between treatment responses and failures. The extended view of HSC transcriptional diversity offered by de novo transcript assembly argued against 5-AZA-responsive EREs as determinants of the outcome of therapy. Instead, it uncovered pre-treatment expression and alternative splicing of developmentally regulated gene transcripts as predictors of the response of MDS and CMML patients to 5-AZA treatment. Conclusions Our study identifies the developmentally regulated transcriptional signatures of protein-coding and non-coding genes, rather than EREs, as correlates of a favourable response of MDS and CMML patients to 5-AZA treatment and offers novel candidates for further evaluation.
Germ-Cell Testicular Cancer in Adults
Authors: Elwin E. Fraley, Paul H. Lange, B. J. Kennedy
Journal: New England Journal of Medicine (1979)

(Second of Two Parts)TreatmentManagement of the Primary TumorAlthough it is well known that a tumorous testis should be removed through an inguinal incision with complete excision of the spermatic cord, many patients have a transscrotal biopsy or orchiectomy or incomplete excision of the cord. Any of these maneuvers may spill tumor into the scrotum, where it can gain access to the inguinal lymphatics or the subcutaneous lymphatics of the lower abdomen. These patients, as well as those whose tumors have penetrated the tunica albuginea or spread to the spermatic cord, should probably have a hemiscrotectomy. They may . . .
Per cent low attenuation volume and fractal dimension of low attenuation clusters on CT predict different long-term outcomes in COPD
Authors: Kaoruko Shimizu, Naoya Tanabe, Nguyen Van Tho, Masaru Suzuki, Hironi Makita, Susumu Sato, Shigeo Muro, Michiaki Mishima, Toyohiro Hirai, Emiko Ogawa, Yasutaka Nakano, Satoshi Konno, Masaharu Nishimura
Journal: Thorax (2020)

Background Fractal dimension ( D ) characterises the size distribution of low attenuation clusters on CT and assesses the spatial heterogeneity of emphysema that per cent low attenuation volume (%LAV) cannot detect. This study tested the hypothesis that %LAV and D have different roles in predicting decline in FEV 1 , exacerbation and mortality in patients with COPD. Methods Chest inspiratory CT scans in the baseline and longitudinal follow-up records for FEV 1 , exacerbation and mortality prospectively collected over 10 years in the Hokkaido COPD Cohort Study were examined (n=96). The associations between CT measures and long-term outcomes were replicated in the Kyoto University cohort (n=130). Results In the Hokkaido COPD cohort, higher %LAV, but not D , was associated with a greater decline in FEV 1 and 10-year mortality, whereas lower D , but not %LAV, was associated with shorter time to first exacerbation. Multivariable analysis for the Kyoto University cohort confirmed that lower D at baseline was independently associated with shorter time to first exacerbation and that higher LAV% was independently associated with increased mortality after adjusting for age, height, weight, FEV 1 and smoking status. Conclusion These well-established cohorts clarify the different prognostic roles of %LAV and D , whereby lower D is associated with a higher risk of exacerbation and higher %LAV is associated with a rapid decline in lung function and long-term mortality. Combination of %LAV and fractal D may identify COPD subgroups at high risk of a poor clinical outcome more sensitively.
Hepatosplenic Tuberculosis on Pretherapy and Posttherapy FDG PET/CT
Authors: Xiaona Jin, Li Huo, Tong Wang, Yu Liu, Fang Li
Journal: Clinical Nuclear Medicine (2019)

A 65-year-old woman underwent FDG PET/CT for presumed hepatosplenic malignancy suggested by an abdominal CT. The images revealed multiple foci of intense FDG activity in both the liver and the spleen. However, a splenic biopsy result revealed no malignant cells, and either tuberculosis or sarcoidosis was proposed. Following an incomplete antituberculosis therapy, a repeat FDG PET/CT showed resolution of the abnormal activity in the liver and the spleen.
Specific molecules are found to be increased in people with alopecia areata, and may be associated with an individual’s level of depression
Authors: K.A. Bain, E. McDonald, F. Moffat, M. Tutino, M. Castelino, A. Barton, J. Cavanagh, U.Z. Ijaz, S. Siebert, I.B. McInnes, A. Astrand, S. Holmes, S.W.F. Milling
Journal: British Journal of Dermatology (2020)

Alopecia areata (AA) is a common disease that causes hair loss. Approximately 2% of the population are affected by AA at least once in their lifetime. The disease usually begins as a patch of hair loss on the scalp, but it can develop to affect the entire scalp or body. The hair loss is caused by cells of the immune system attacking the structures in the skin that grow hair. Unfortunately, 60% of people with AA will also develop depression, anxiety or a related condition. This study, from Scotland, aimed to find out if people with AA have different levels of molecules made by the immune system in their blood. The authors found that patients, compared to people without AA, had increased levels of multiple molecules that are produced by activated immune cells. This study also tried to understand if these molecules in blood could be contributing to the depression that some patients suffer from. This idea was based on studies in other diseases, such as rheumatoid arthritis, that have found links between molecules produced by immune cells and depression. The researchers asked patients to complete a questionnaire about their mental health to generate a depression score. Using complex equations, the authors found that two specific molecules that are increased in people with AA are associated with how depressed a patient is. The authors believe that these findings will help to understand what causes AA, and importantly may help to develop better treatments in the future. This summary relates to the study: Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity
Abstract 12912: Efficacy of Calcium Channel Blockers in Comparison to Renin-Angiotensin System Inhibitors on Urinary Albumin Excretion in Hypertensive Patient With Diabetic Nephropathy. A Meta-Analysis of Randomized Control Trials
Authors: Eder H Cativo Calderon, Persio D Lopez Loyo, Diana Otero, Steven A Atlas, Clive Rosendorff
Journal: Circulation (2019)

Introduction: Inhibitors of the renin-angiotensin system (RAS) are a cornerstone of the management of hypertension in patients with diabetic nephropathy (DN). Calcium channel blockers (CCB ) have b...
Targeting of tumor cells and tumor stem cells by antibodies specific for the cell-bound alpha/beta junction of MUC1.
Authors: Edward Pichinuk, Itai Benhar, Oded Jacobi, Ravit Ziv, Nechama Smorodinsky, Daniel B. Rubinstein, Daniel H. Wreschner
Journal: Journal of Clinical Oncology (2012)

e13018 Background: MUC1 is a glycoprotein over-expressed on the cell surface of a variety of malignancies and has long been a subject of interest in targeted therapy.Cleavage of MUC1 yields two unequal chains, a large extracellular a subunit non-covalently bound to a smaller b subunit in an on-and-off mechanism. Because it is released into the peripheral circulation, the MUC1 a subunit readily sequesters antibodies directed against it. In order to avoid such peripheral sequestration, Abs directed against MUC1 must be engineered as to target cell bound moieties of MUC1. Methods: Seven anti-MUC1 monoclonal antibodies were generated, five Ig-gamma1 and two IgA, all directed against the MUC1 a/b junction, a structure which remains cell bound at all times. Results: In addition to their binding differentiated breast cancer cells at pico Molar concentrations, the anti-MUC1 mAbs strongly bind breast cancer stem cells. With a view for clinical application, the DMB5F3 anti-MUC1 mAb was partially humanized with resultant production of chimeric IgG1. In order to demonstrate that chimeric anti-MUC1 antibodies can be used in tumor cell killing, mAb DMB5F3 was linked to the pseudomonas bacterial exotoxin ZZ-PE38. The resultant anti-MUC1 immunotoxin not only efficiently internalized the toxin, it resulted in strong cytotoxicity of MUC1+ breast cancer. In fact, DMB5F3:PE38 immunotoxin bound MUC1+ cancer cells with an affinity (Ab concentrations as low as 20pM) exceeding that seen with cetuximab (anti-EGFR1)-PE38 and tratuzumab (anti-erbB2)-PE38 immunotoxins. Conclusions: Taken together, these findings indicate [1] the therapeutic use of targeting cell-bound MUC1 [2] high affinity activity against both tumor and tumor stem cells suggests that the anti-MUC1 mAbs target not only 'mature' differentiated malignancy but self-reproducing cells giving rise to new malignant growth as well [3]tumor can be targeted directly by anti-MUC1 antibodies or by linking anti-MUC1 to toxin, resulting in efficient immunotoxin cytotoxicity [4] as it was shown to be a targetable entity, the SEA domain represents a promising immunogen for MUC1 tumor vaccines.
Pathogenic Bhlhe40+ GM-CSF+ CD4+ T cells promote indirect alloantigen presentation in the GI tract during GVHD
Authors: Clint Piper, Vivian Zhou, Richard Komorowski, Aniko Szabo, Benjamin Vincent, Jonathan Serody, Maria-Luisa Alegre, Brian T. Edelson, Reshma Taneja, William R. Drobyski
Journal: Blood (2019)
Abstract 15649: Fracture Resistance of Fibrin Clots
Authors: Valerie Tutwiler, Jaspreet Singh, Rustem I Litvinov, John Bassani, Prashant Purohit, John W Weisel
Journal: Circulation (2019)

Fibrin, a polymeric proteinaceous network resulting from blood clotting, naturally acts as the mechanical scaffold of hemostatic blood clots and obstructive thrombi. In addition, fibrin-based bioma...
Estimation of expected survival time using gene expression profiling for tumor site origin.
Authors: William David Henner, J. Scott Nystrom, John D. Hainsworth, Gauri R. Varadhachary, Frank A. Greco, Mahul Amin, Michael Walker, Shawn Becker, Raji Pillai, Sandy Stein, John C. Hornberger
Journal: Journal of Clinical Oncology (2012)

10584 Background: Expected survival is an important factor in treatment selection and patient decision making. Gene expression profiling for tissue of origin (GEP TOO) can be used to classify metastatic and poorly-differentiated tumors according to the most likely primary site for difficult-to-diagnose tumors. The Pathwork Tissue of Origin Test, (Redwood City, CA) generates Similarity Scores (SS), one for each of the 15 tissues on the Tissue of Origin Test Panel and sum to 100. The highest SS has been validated as the most likely tissue of origin in a large validation study (Pillai et al. 2010). This abstract reports the relationship between the highest SS for a sample and patient survival. Methods: Two cohorts were analyzed in IRB-approved studies. Cohort 1 consisted of 45 patients with carcinoma of unknown primary treated empirically with therapy for carcinoma of unknown primary with known outcome data including survival. Cohort 2 consisted of 107 patients receiving the TOO test in routine clinical practice and included in a decision impact registry study. The relationship between the highest SS generated by the TOO test was examined using parametric (Gamma) and non-parametric (Cox Proportional Hazards) regression models with covariates of age, gender and median survival of the cancer type indicated. Logrank tests were performed to compare survival in patients with SS above or below 50 in each cohort. Results: The highest SS generated by the TOO Test was strongly and positively correlated with patient survival in both Cohort 1 (p = 0.0093, Cox PH) and in Cohort 2 (p=0.0045, Gamma). In Cohort 1, survival for patients with a SS &lt; 50 was 5.9 mos and for patients with a SS ≥ 50 was 9.7 mos (p=0.03, logrank). In Cohort 2, survival for patients with a SS &lt; 50 was 10.6 mos and 22.6 mos for patients with a SS ≥ 50 (p=0.0073, logrank). Conclusions: The Similarity Scores generated by GEP TOO Test have been validated as an aid to diagnosis for difficult-to-diagnose malignancies. Two independent studies of this GEP TOO Test demonstrated a strong positive relationship between the highest SS and survival. This has the potential to expand the clinical utility of this test beyond diagnosis to include prognosis. Further studies to examine this question are underway.
18F-FDG PET/CT in a Patient With Thymoma-Associated Paraneoplastic Polymyositis
Authors: Zhanli Fu, Guoqian Chen, Xueqi Chen, Qian Li
Journal: Clinical Nuclear Medicine (2019)

Abstract A 43-year-old woman presented with progressive muscle weakness and myalgia for 1 month. Laboratory tests revealed the elevation of myogenic enzymes. MRI of the thighs demonstrated a pattern of edema for inflammatory myopathy. Electromyography showed diffuse myopathic disorder, and muscle biopsy indicated polymyositis. 18 F-FDG PET/CT was performed to investigate the potential paraneoplastic syndrome and revealed a soft tissue lesion with 18 F-FDG avidity in the right anterior mediastinum, as well as diffusely increased activity throughout the body muscles. The patient's symptoms and biochemical abnormalities were gradually relieved after the tumor resection, and the histopathology indicated a type AB thymoma.
Progress in treating inherited retinal diseases: Early subretinal gene therapy clinical trials and candidates for future initiatives
Authors: Alexandra V. Garafalo, Artur V. Cideciyan, Elise Héon, Rebecca Sheplock, Alexander Pearson, Caberry WeiYang Yu, Alexander Sumaroka, Gustavo D. Aguirre, Samuel G. Jacobson
Journal: Progress in Retinal and Eye Research (2019)

Due to improved phenotyping and genetic characterization, the field of 'incurable' and 'blinding' inherited retinal diseases (IRDs) has moved substantially forward. Decades of ascertainment of IRD patient data from Philadelphia and Toronto centers illustrate the progress from Mendelian genetic types to molecular diagnoses. Molecular genetics have been used not only to clarify diagnoses and to direct counseling but also to enable the first clinical trials of gene-based treatment in these diseases. An overview of the recent reports of gene augmentation clinical trials by subretinal injections is used to reflect on the reasons why there has been limited success in this early venture into therapy. These first-in human experiences have taught that there is a need for advancing the techniques of delivery of the gene products - not only for refining further subretinal trials, but also for evaluating intravitreal delivery. Candidate IRDs for intravitreal gene delivery are then suggested to illustrate some of the disorders that may be amenable to improvement of remaining central vision with the least photoreceptor trauma. A more detailed understanding of the human IRDs to be considered for therapy and the calculated potential for efficacy should be among the routine prerequisites for initiating a clinical trial.
HPMA-based star polymer biomaterials with tuneable structure and biodegradability tailored for advanced drug delivery to solid tumours
Authors: Libor Kostka, Lenka Kotrchová, Vladimír Šubr, Alena Libánská, Carolina A. Ferreira, Iva Malátová, Hye Jin Lee, Todd E. Barnhart, Jonathan W. Engle, Weibo Cai, Milada Šírová, Tomáš Etrych
Journal: Biomaterials (2019)
Decision confidence: EEG correlates of confidence in different phases of an old/new recognition task
Authors: Tanja Krumpe, Peter Gerjets, Wolfgang Rosenstiel, Martin Spüler
Journal: Brain-Computer Interfaces (2019)

We use an old-new recognition memory task to investigate the correlates of high and low decision confidence throughout all stages of the memory process. Group-level ERP analysis and single-trial and single-subject classification are performed on four stages of the task (information encoding, retrieval, old/new decision formation, and evaluative feedback processing). The study shows that decision confidence is significantly reflected on a group, as well as on a single-trial basis, in all investigated stages at the neural level, except during encoding. The most pronounced differences between high and low confidence can be found in the ERPs during feedback presentation after a correct answer, whereas almost no differences can be found following a wrong answers. In the feedback stage, the two levels of confidence can be separated with classification accuracies of up to 70 % on average, therefore showing potential to be used as a control state in a BCI application.
Network meta-analysis of randomized controlled trials comparing the procedure for prolapse and hemorrhoids, Milligan-Morgan hemorrhoidectomy and tissue-selecting therapy stapler in the treatment of grade III and IV internal hemorrhoids(Meta-analysis)
Authors: Guoxing Zhang, Ruiwen Liang, Jing Wang, Minhui Ke, Zuqing Chen, Juan Huang, Rong Shi
Journal: International Journal of Surgery (2019)
Improving the integrative memory model by integrating the temporal dynamics of memory
Authors: Jonathan Curot, Emmanuel J. Barbeau
Journal: Behavioral and Brain Sciences (2019)

Abstract Despite highlighting the role of the attribution system and proposing a coherent large-scale architecture of declarative memory, the integrative memory model would be more “integrative” if the temporal dynamics of the interactions between its components was clarified. This is necessary to make predictions in patients with brain injury and hypothesize dissociations.
Ovarian stimulation for freeze-all IVF cycles: a systematic review
Authors: Yossi Mizrachi, Eran Horowitz, Jacob Farhi, Arieh Raziel, Ariel Weissman
Journal: Human Reproduction Update (2019)

Freeze-all IVF cycles are becoming increasingly prevalent for a variety of clinical indications. However, the actual treatment objectives and preferred treatment regimens for freeze-all cycles have not been clearly established.We aimed to conduct a systematic review of all aspects of ovarian stimulation for freeze-all cycles.A comprehensive search in Medline, Embase and The Cochrane Library was performed. The search strategy included keywords related to freeze-all, cycle segmentation, cumulative live birth rate, preimplantation genetic diagnosis, preimplantation genetic testing for aneuploidy, fertility preservation, oocyte donation and frozen-thawed embryo transfer. We included relevant studies published in English from 2000 to 2018.Our search generated 3292 records. Overall, 69 articles were included in the final review. Good-quality evidence indicates that in freeze-all cycles the cumulative live birth rate increases as the number of oocytes retrieved increases. Although the risk of severe ovarian hyperstimulation syndrome (OHSS) is virtually eliminated in freeze-all cycles, there are certain risks associated with retrieval of large oocyte cohorts. Therefore, ovarian stimulation should be planned to yield between 15 and 20 oocytes. The early follicular phase is currently the preferred starting point for ovarian stimulation, although luteal phase stimulation can be used if necessary. The improved safety associated with the GnRH antagonist regimen makes it the regimen of choice for ovarian stimulation in freeze-all cycles. Ovulation triggering with a GnRH agonist almost completely eliminates the risk of OHSS without affecting oocyte and embryo quality and is therefore the trigger of choice. The addition of low-dose hCG in a dual trigger has been suggested to improve oocyte and embryo quality, but further research in freeze-all cycles is required. Moderate-quality evidence indicates that in freeze-all cycles, a moderate delay of 2-3 days in ovulation triggering may result in the retrieval of an increased number of mature oocytes without impairing the pregnancy rate. There are no high-quality studies evaluating the effects of sustained supraphysiological estradiol (E2) levels on the safety and efficacy of freeze-all cycles. However, no significant adverse effects have been described. There is conflicting evidence regarding the effect of late follicular progesterone elevation in freeze-all cycles.Ovarian stimulation for freeze-all cycles is different in many aspects from conventional stimulation for fresh IVF cycles. Optimisation of ovarian stimulation for freeze-all cycles should result in enhanced treatment safety along with improved cumulative live birth rates and should become the focus of future studies.