tbuckley/cabot-search huggingface dataset:
Plasminogen activation system and growth factors in tumors of the female reproductive system in perimenopausal patients.
Authors: Larisa Kozlova, Elena Mikhaylovna Frantsiyants, Marina Ilyinichna Vereskunova, Tatiana Moiseenko, Natalia Viktorovna Chernikova, Viktor Viktorovich Gurnak, Ludmila Petrovna Kuchkina, Mariya Yezhova
Journal: Journal of Clinical Oncology (2015)

e22247 Background: Plasminogen (Pg) activators and growth factors play an important role in growth and metastasis of malignant tumors. The purpose of the study was to reveal changes in fibrinolytic system components and growth factors in hyperplastic tissues of breast and uterus during the decline in menstrual function. Methods: Plasminogen activation system and growth factors in tumor tissues of 116 patients aged 49.3±3.5 years were studied. Tissues of solitary breast cancer (BC, T2N0M0) and endometrial cancer (EC, T2N0M0), nodular form of fibrocystic breast disease (NFBD), hysteromyoma (HM), and combined BC+HM were studied. Intact breast tissue (IBT) obtained during breast reduction surgery and unaffected endometrial and myometrial tissue (conditionally healthy tissue, CHT) obtained during surgery for HM served as the control. Plasmin (P), Pg, content and activity of uPA and tPA (uPA-AG, uPA-act, tPA-AG, tPA-act), growth factors (VEGF-А and EGF, IFR1 and IFR2) in cytosolic fraction were determined by the ELISA method. Results: uPA-AG, uPA-act, tPA-AG, tPA-act and P increased in solitary BC, EC and in BC in BC+HM (p < 0.01); tPA (р < 0,01), Pg and P (p < 0.05 and p < 0.01) – in HM tissue in BC+HM. Both uPA and Pg increased in NFBD (p < 0.01), Pg only – in solitary HM (p < 0.05). In CHT significant differences were not observed, but P in endometrium was higher than in myometrium (р < 0.01). VEGF and EGF in solitary BC and EC increased in comparison with IBT and CHT respectively, with VEGF predominance (p < 0.01 in all cases). VEGF and EGF in BC in BC+HM increased up to practically equal values (p < 0.01). EGF increased in HM in BC+HM (p < 0.01), VEGF did not change; IGF1 increased in solitary HM; IGF2 increased in solitary BC, NFBD, EC and in HM in BC+HM. In CHT of endometrium in solitary HM VEGF and IGF2 content was higher than in CHT of myometrium, while EGF was lower (p < 0.01 in all cases). Conclusions: The results show the direct relationship between indices of local neoangiogenesis of benign tumor and malignant process in combined cancer of the reproductive organs.
Interaction of redox-regulatory systems in cancer and not malignant tissues in various histological types of tumours.
Authors: Ekaterina Igorevna Surikova, Irina Aleksandrovna Goroshinskaya, Galina Andreevna Nerodo, Elena Mikhaylovna Frantsiyants, Elena Vladimirovna Shalashnaya, Polina Sergeevna Kachesova, Ludmila Anatolievna Nemashkalova, Anastasia Victorovna Leonova
Journal: Journal of Clinical Oncology (2015)

e22243 Background: The development of new anti-cancer strategies based on the effects on the redox state of the tumor and surrounding tissue requires an understanding of the biology of redox processes in a particular tumor. The aim was a comparative evaluation of the correlation between the enzymes of first line antioxidant defense and glutathione system in the tumor tissues of different histology, peritumoral area and not malignant tissues. Methods: The activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase and the content of reduced glutathione and malondialdehyde were studied by conventional methods in samples of tumor, peritumoral area and in healthy tissue samples (taken along the line of resection) obtained in the surgical treatment of 23 patients with adenocarcinoma of the stomach stage II-III and 8 patients with squamous cell carcinoma of the vulva stage II-III. The neoadjuvant chemotherapy at these patients was missed. The Spearman correlation coefficients were calculated for all indicators. Results: carcinoma of the vulva and adenocarcinoma of the stomach have similar reduced glutathione content. At the same time, vulva cancer has a lot of strong correlations inside tumor tissue and with surrounding tissues which exists through glutathione-dependent enzymes. Negative correlations were detected between peritumoral area and healthy tissue. Adenocarcinoma of the stomach has a few number of correlations, they are weak or moderate and exist through superoxide dismutase. Negative correlations were found between tumor tissue and peritumoral area. Conclusions: Thus the picture of the interactions of studied enzymes in tumor tissue and its environment differs in tumors of different histological type. Carcinoma of the vulva in comparison with adenocarcinoma of the stomach squamous cell in tumor tissue is characterized by greater activity of glutathione system, the greater need for reduced glutathione. By installing a larger number of correlations, squamous cell carcinoma provides better control over the oxidative processes and provides a more intense effect on the peritumoral area and not malignant tissue.
SAT-163-HBeAg-negative chronic infection: more complex and conserved quasispecies in Hepatitis B X gene
Authors: Carolina González, Maria Francesca Cortese, Josep Gregori, Mar Riveiro Barciela, Rosario Casillas, Marçall Yll, Cristina Godoy, Sara Sopena, Josep Quer, Ariadna Rando, Rosa Lopez-Martinez, Rafael Esteban-Mur, Maria Buti, David Tabernero, Francisco Rodríguez-Frías
Journal: Journal of Hepatology (2019)
GS-16-Safety and tolerability of liver-derived stem cells (HepaStem) infused in patients with acute-on-chronic liver failure or acute decompensation: a European phase I/IIa open-labelled study
Authors: Nevens Frederik, Gustot Thierry, Laterre Pierre-François, Lasser Luc, Haralampiev Lyudmil Enev, Vargas Victor, Barthel Virginie, Nathalie Clerget-Chossat, Etienne Sokal
Journal: Journal of Hepatology (2019)
Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity
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 (2019)

Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+ NKG2D+ T cells dominate hair follicle pathogenesis, but the specific mechanisms driving hair loss are not fully understood.To provide a detailed insight into the systemic cytokine signature associated with AA, and to assess the association between cytokines and depression.We conducted multiplex analysis of plasma cytokines from patients with AA, patients with psoriatic arthritis (PsA) and healthy controls. We used the Hospital Anxiety and Depression Scale (HADS) to assess the occurrence of depression and anxiety in our cohort.Our analysis identified a systemic inflammatory signature associated with AA, characterized by elevated levels of interleukin (IL)-17A, IL-17F, IL-21 and IL-23 indicative of a type 17 immune response. Circulating levels of the type 2 cytokines IL-33, IL-31 and IL-17E (IL-25) were also significantly increased in AA. In comparison with PsA, AA was associated with higher levels of IL-17F, IL-17E and IL-23. We hypothesized that circulating inflammatory cytokines may contribute to wider comorbidities associated with AA. Our assessment of psychiatric comorbidity in AA using HADS scores showed that 18% and 51% of people with AA experienced symptoms of depression and anxiety, respectively. Using linear regression modelling, we identified that levels of IL-22 and IL-17E are positively and significantly associated with depression.Our data highlight changes in both type 17 and type 2 cytokines among people with AA, suggesting that complex systemic cytokine profiles may contribute both to the pathogenesis of AA and to the associated depression. What's already known about this topic? NKG2D+ CD8+ T cells cause hair loss in alopecia areata (AA) but the immunological mechanisms underlying the disease are not fully understood. AA is associated with changes in levels of interleukin (IL)-6, tumour necrosis factor-α, IL-1β and type 17 cytokines. Psychiatric comorbidity is common among people with AA. What does this study add? People with AA have increased plasma levels of the type 2 cytokines IL-33, IL-31 and IL-17E (IL-25), in addition to the type 17 cytokines IL-17A, IL-21, IL-23 and IL-17F. Levels of IL-17E and IL-22 positively predict depression score. What is the translational message? AA is associated with increased levels of multiple inflammatory cytokines, implicating both type 17- and type 2 immune pathways. Our data indicate that therapeutic strategies for treating AA may need to address the underlying type 17- and type 2 immune dysregulation, rather than focusing narrowly on the CD8+ T-cell response. An immunological mechanism might contribute directly to the depression observed in people with AA.
Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models
Authors: Thomas H. Hutson, Claudia Kathe, Ilaria Palmisano, Kay Bartholdi, Arnau Hervera, Francesco De Virgiliis, Eilidh McLachlan, Luming Zhou, Guiping Kong, Quentin Barraud, Matt C. Danzi, Alejandro Medrano-Fernandez, Jose P. Lopez-Atalaya, Anne L. Boutillier, Sarmistha H. Sinha, Akash K. Singh, Piyush Chaturbedy, Lawrence D. F. Moon, Tapas K. Kundu, John L. Bixby, Vance P. Lemmon, Angel Barco, Gregoire Courtine, Simone Di Giovanni
Journal: Science Translational Medicine (2019)

After a spinal cord injury, axons fail to regenerate in the adult mammalian central nervous system, leading to permanent deficits in sensory and motor functions. Increasing neuronal activity after an injury using electrical stimulation or rehabilitation can enhance neuronal plasticity and result in some degree of recovery; however, the underlying mechanisms remain poorly understood. We found that placing mice in an enriched environment before an injury enhanced the activity of proprioceptive dorsal root ganglion neurons, leading to a lasting increase in their regenerative potential. This effect was dependent on Creb-binding protein (Cbp)-mediated histone acetylation, which increased the expression of genes associated with the regenerative program. Intraperitoneal delivery of a small-molecule activator of Cbp at clinically relevant times promoted regeneration and sprouting of sensory and motor axons, as well as recovery of sensory and motor functions in both the mouse and rat model of spinal cord injury. Our findings showed that the increased regenerative capacity induced by enhancing neuronal activity is mediated by epigenetic reprogramming in rodent models of spinal cord injury. Understanding the mechanisms underlying activity-dependent neuronal plasticity led to the identification of potential molecular targets for improving recovery after spinal cord injury.
FRI-492-Long-term outcome according to initial treatment modality in multiple hepatocellular carcinoma within the Milan criteria
Authors: Joo Hyun Oh, Dong Hyun Sinn, wonseok Kang, Geum-Yon Gwak, Yong-Han Paik, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Moon Seok Choi
Journal: Journal of Hepatology (2019)
TCTAP A-108 Predictors of Recurrent Vasospastic Angina: Analysis of Clinical and Angiographic Parameters
Authors: Jin-Hee Park, Gwang-Seok Yoon, Seong-Huan Choi, Yong-Soo Baek, Sung Woo Kwon, Seong-Ill Woo, Dae-Hyeok Kim, Jun Kwan, Sang Don Park
Journal: Journal of the American College of Cardiology (2019)
Pilot results of neoadjuvant chemoimmunotherapy (NCIT) in treatment of patients (pts) with non-small cell lung cancer (NSCLC).
Authors: Yury N. Lazutin, Anna Pavlovna Kharitonova, Sergei A. Zinkovich, Liubov Yu Vladimirova, Sergey P. Pyltsin
Journal: Journal of Clinical Oncology (2015)

e18523 Background: In contrast to adjuvant chemotherapy (CT), neoadjuvant CT (NCT) is not currently a standard treatment for NSCLC, and further clinical trials are required to prove its benefits. However, traditional approaches to improving NCT have been largely exhausted. The development of chemoimmunotherapy with recombinant cytokines and assessment of its clinical efficacy in NSCLC treatment are poorly studied. Methods: 47 pts. With st. 2B-3B NSCLC were divided into main (n = 25) and control groups (n = 22), comparable by clinical and pathological characteristics: men - 22 (88%) vs. 18 (82%), women - 3 (12%) vs. 4 (18%); 40-50 years 7 (28%) vs. 5 (23%), 51-60 years 9 (36%) vs. 9 (41%), over 60 years 9(36%) vs. 8 (36%); 2B st.-2 (8%) vs. 3 (14%), 3A st.-15(66%) vs. 13 (59%), 3B st.-8 (32%) vs. 6 (27%). Squamous-cell carcinoma 14 (56%) vs. 12 (55%), adenocarcinoma in 11 (44%) vs. 10 (45%). Pts. of the control group received a two-cycle NCT: cisplatin 75 mg/m2 i.v. on d. 1 and gemcitabine 1000 mg/m2 i.v. on d. 1 and 8; pts. of the main group received additionally i.v. recombinant protein of tumor necrosis factor fused with thymosin-alpha (TNF-T. Farmaclon. Russia) 50.000 ED/m2 on d. 3, 5 and 7 of the cycle. Direct results of the treatment were assessed according to REGIST 3 weeks after NCIT. Results: By this time, the planned therapy has been completed for 17 (68%) pts. of the main and 14 (64%) of the control groups. A common response was 12 (71%) to NCIT and 7 (50%) to NCT (p = . 06). CR – 3 (18%) vs.1 (7%) (p = .04); PR - 9 (53%) vs. 6 (49%); SD - 4 (23%) vs. 5 (36%); PD - 1 (6%) vs. 2 (14%). 13 (83%) pts. of the main and 8 (89%) of the control groups received radical surgery. Conclusions: Phase I of the clinical trial of NCIT plus immune agent TNF-T showed a tendency to improvement of the overall response to treatment, a significant increase in CR compared to the standard regimen, satisfactory tolerability and feasibility.
Insulin-Driven PI3K-AKT Signaling in the Hepatocyte Is Mediated by Redundant PI3Kα and PI3Kβ Activities and Is Promoted by RAS
Authors: Angela Molinaro, Barbara Becattini, Arianna Mazzoli, Augusto Bleve, Lucia Radici, Ingela Maxvall, Victoria Rotter Sopasakis, Antonio Molinaro, Fredrik Bäckhed, Giovanni Solinas
Journal: Cell Metabolism (2019)
Optimal dilation time for combined small endoscopic sphincterotomy and balloon dilation for common bile duct stones: a multicentre, single-blinded, randomised controlled trial
Authors: Wenbo Meng, Joseph W Leung, Kai Zhang, Wence Zhou, Zhenyu Wang, Leida Zhang, Hao Sun, Ping Xue, Wei Liu, Qi Wang, Jijun Zhang, Xuefeng Wang, Meng Wang, Yingmei Shao, Kailin Cai, Senlin Hou, Qiyong Li, Lei Zhang, Kexiang Zhu, Ping Yue, Haiping Wang, Ming Zhang, Xiangyu Sun, Zhiqing Yang, Jie Tao, Zilong Wen, Qunwei Wang, Bendong Chen, Quan Shao, Mingning Zhao, Ruoyan Zhang, Tiemin Jiang, Ke Liu, Lichao Zhang, Kangjie Chen, Xiaoliang Zhu, Hui Zhang, Long Miao, Zhengfeng Wang, Jiajia Li, Xiaowen Yan, Fangzhao Wang, Lingen Zhang, Azumi Suzuki, Kiyohito Tanaka, Ula Nur, Elisabete Weiderpass, Xun Li
Journal: The Lancet. Gastroenterology & hepatology (2019)
Incidental Detection of a Radiation-Induced Soft-Tissue Sarcoma on 68Ga-PSMA PET/CT in a Patient Previously Treated for Prostate Cancer
Authors: Nicolas Plouznikoff, Erwin Woff, Carlos Artigas, Jean Alexiou, Patrick Flamen
Journal: Clinical Nuclear Medicine (2019)

Radiation-induced sarcoma is a rare complication of radiation therapy. We describe the incidental detection of a radiation-induced undifferentiated soft-tissue sarcoma with increased uptake on Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in a prostate cancer patient previously treated with surgery and external-beam radiotherapy. Results were confirmed by histological analysis. Ga-PSMA is known to bind not only to PSMA-expressing prostate cancer cells but also to the neovasculature of various other solid tumors. A careful Ga-PSMA PET/CT review of previously irradiated areas is warranted so as not to miss radiation-induced sarcoma in prostate cancer patients.
Analysis of error profiles in deep next-generation sequencing data
Authors: Xiaotu Ma, Ying Shao, Liqing Tian, Diane A. Flasch, Heather L. Mulder, Michael N. Edmonson, Yu Liu, Xiang Chen, Scott Newman, Joy Nakitandwe, Yongjin Li, Benshang Li, Shuhong Shen, Zhaoming Wang, Sheila Shurtleff, Leslie L. Robison, Shawn Levy, John Easton, Jinghui Zhang
Journal: Genome biology (2019)

Sequencing errors are key confounding factors for detecting low-frequency genetic variants that are important for cancer molecular diagnosis, treatment, and surveillance using deep next-generation sequencing (NGS). However, there is a lack of comprehensive understanding of errors introduced at various steps of a conventional NGS workflow, such as sample handling, library preparation, PCR enrichment, and sequencing. In this study, we use current NGS technology to systematically investigate these questions. By evaluating read-specific error distributions, we discover that the substitution error rate can be computationally suppressed to 10−5 to 10−4, which is 10- to 100-fold lower than generally considered achievable (10−3) in the current literature. We then quantify substitution errors attributable to sample handling, library preparation, enrichment PCR, and sequencing by using multiple deep sequencing datasets. We find that error rates differ by nucleotide substitution types, ranging from 10−5 for A>C/T>G, C>A/G>T, and C>G/G>C changes to 10−4 for A>G/T>C changes. Furthermore, C>T/G>A errors exhibit strong sequence context dependency, sample-specific effects dominate elevated C>A/G>T errors, and target-enrichment PCR led to ~ 6-fold increase of overall error rate. We also find that more than 70% of hotspot variants can be detected at 0.1 ~ 0.01% frequency with the current NGS technology by applying in silico error suppression. We present the first comprehensive analysis of sequencing error sources in conventional NGS workflows. The error profiles revealed by our study highlight new directions for further improving NGS analysis accuracy both experimentally and computationally, ultimately enhancing the precision of deep sequencing.
Abstract 24031: Machine Learning Detection of Obstructive Hypertrophic Cardiomyopathy Using a Wearable Biosensor
Authors: Eric M Green, Reinier van Mourik, Charles Wolfus, Stephen B Heitner, Onur Dur, Marc J Semigran
Journal: Circulation (2017)

Introduction: Hypertrophic cardiomyopathy (HCM) is a heart muscle disease characterized by left ventricular (LV) hypertrophy without a systemic etiology and is associated with heart failure, stroke and sudden death. Disease prevalence is estimated at 1:500, but ~84% remain undiagnosed. Patients with obstructive HCM (oHCM) have dynamic obstruction of the LV outflow tract and characteristic abnormalities in arterial bloodflow patterns. Hypothesis: Arterial pulsewaves recorded with a wearable biosensor and analyzed with machine learning algorithms could identify a signature of oHCM when compared to unaffected controls. Methods: We compared baseline arterial pulse wave morphology, obtained by photoplethysmography using an investigational wristworn biosensor (Wavelet Health, Mtn. View, CA), from oHCM patients enrolled in a digital health substudy of PIONEER HCM (NCT02842242) to unaffected controls from a Wavelet Health database. Five minute recordings were obtained at rest, and data sets were divided into training and validation cohorts. A beat-by-beat machine learning model was developed using a predefined feature set to calculate an HCM probability score, and an optimal threshold score was determined. The model was evaluated using summary statistics and an ROC area-under-curve metric. Results: Arterial pulsewave recordings were obtained from 14 patients with oHCM at rest and 81 unaffected controls. An oHCM machine learning classifier was developed based on 42 calculated metrics. After training and cross-validation (n=9 oHCM, n=48 control), the model achieved 98% accuracy. Application of this model to a validation cohort (n=5 oHCM, n=33 control) confirmed an increased probability in oHCM patients compared to unaffected controls (0.40 ± 0.13 vs. 0.18 ± 0.10; p=0.006). Analysis of the ROC curve in the pooled cohort shows an area under the curve of 0.88. Conclusion: This first-of-its-kind study suggests that a signature of arterial bloodflow in oHCM can be identified with the combination of a wristworn biosensor and machine learning algorithms. These data raise the possibility of a novel approach to the non-invasive detection of oHCM.
Endoscopic band ligation plus single-incision needle knife biopsy for small subepithelial deep-layer tumor: easy and effective
Authors: Francesc Bas-Cutrina, Claudia F. Consiglieri, Jan Bosch-Schips, Joan B. Gornals
Journal: Endoscopy (2019)

A 61-year-old man was referred for an iron-deficiency anemia diagnostic process. Upper gastrointestinal endoscopy was performed and fortuitously revealed a small gastric subepithelial lesion. Endoscopic ultrasound (EUS) characterization revealed a solid lesion, with fusiform morphology, well-defined by smooth edges and an hypoechoic homogeneous internal pattern, measuring 12.3 × 5.8 mm, and originating in the muscularis propria layer, which confirmed a subepithelial tumor ([Fig. 1]). With the aim of avoiding EUS surveillance of the subepithelial tumor, a minimally invasive removal technique was planned [1] [2] [3].
Effect of surgical treatment on the survival in patients with malignant pleural mesothelioma
Authors: R. Baez-Saldana, M.T. Marmolejo-Torres, M. Iñiguez-García, J.A. Berrios Mejía, U. Rumbo-Nava, O. Arrieta-Rodríguez
Journal: Annals of Oncology (2019)

Background: In patients with malignant pleural mesothelioma (MPM) chemotherapy is the only treatment modality that has been shown to improve survival. Surgery, by either pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP) can be an option of treatment in patients with early stage disease and good functional status, nevertheless, this modality remains questionable. The aim of this study was to evaluate the effect of surgical treatment on the survival in patients with MPM. Methods: Case series of patients with histologically proven MPM between January 2012 and Jun 2015 were reviewed retrospectively. The variables analyzed were: age, sex, asbestos exposure, smoking history, biomass exposure, performance status with ECOG scale, staging and type of treatment. Univariate and multivarite analyses were performed using the Cox regression model. Survival functions were estimated using the Kaplan-Meier statistics. The decision to perform either P/D or EPP was on the basis surgeon's preference. Results: There were 122 cases of MPM; 71% were males and the media age at diagnosis was 63 years. Twenty (16.4%) of the cases received surgery, 8 EPP, 8 P/D, and 4 were unresectable at the moment of the surgery. The 30-day mortality was 5%, one patient after EPP. The median survival in all cases was 8.6 months, while in the surgical vs no surgical group was 15.8 vs 7.2 months respectively (p < 0.05). In comparision to no surgery treatment, surgery alone was associated with significant improvement in survival [adj HR 0.20 (95%CI: 0.07-0.56). At multivariate analysis independent significant predictors of survival were surgery [adj HR 0.21 (95%CI: 0.06-0.71), beign female [adj HR 0.49 (95%CI: 1.06-4.48), chemotherapy [adj HR 0.22 (95%CI: 0.07-0.70), stage early vs advanced [adj HR 0.47 (95%CI: 0.22-1.04) and ECOG < 2 [adj HR 0.21 (95%CI: 0.06-0.76). Conclusions: Our data suggest relative advantage of surgery on survival. Patients who received surgery had better survival than patients who were treated with chemotherapy or palliative care alone. Legal entity responsible for the study: Instituto Nacional de Enfermedades Respiratorias. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.