tbuckley/cabot-search huggingface dataset:
The association of mutant allele frequency of TP53 with response of chemotherapy in advanced gastric cancer patients.
Authors: Shu Zhang
Journal: Journal of Clinical Oncology (2019)

42 Background: The tumor suppressor gene TP53 is one of the most commonly altered genes in advanced gastric cancer (AGC). However, the predictive role of mutant allele frequency (AF) of TP53 on response of chemotherapy in AGC patients remains unclear. This study aims to explore the predictive value of mutant allele frequency of TP53 on efficacy of chemotherapy in AGC. Methods: We obtained a new biopsy using gastroscope and collected blood samples at baseline and at time of 3 cycles of chemotherapy (2 weeks each cycle) in 8 patients with AGC, and the circulating tumor DNA (ctDNA) and tumor tissue DNA were analyzed using next generation sequencing (NGS). The efficacy was evaluated at time of 3 cycles of chemotherapy by CT imaging according to the RECIST’s standard. Results: We selected 8 patients with advanced gastric adenocarcinoma confirmed pathologically, including 5 female, 3 male. Their Median age is 53 (32-78) years old. The sequencing depths of tissue samples and blood samples were greater than 1000x and 10000x, respectively. Of 8 patients, except for one patient with no mutation of TP53, 7 AGC patients had the mutations in the different sites of TP53 gene. The results showed that 5 patients had partial response (PR), and 2 patients revealed stable disease (SD) after chemotherapy. Five patients with PR showed more than 10% of mutant AF of TP53, but two patients with SD had less than 3% of the mutant AF. Of 5 AGC patients with PR, two patients showed that the mutant AF of TP53 had become from 77.0%, 20.20% to negative in the blood samples, three patients exhibited the decrease of mutant AF of TP53 from 36.99%, 21.61% and 10.04% to 15.77%, 0.40% and 0.69%, respectively. In two patients with SD, one patient revealed that the mutant AF of TP53 had decreased from 2.20% to negative, another one from 1.91% to 1.11%, respectively. Conclusions: Our results suggested that the decrease of mutant allele frequency of TP53 in blood sample can predict response to chemotherapy in patients with advanced gastric cancer. The AGC patients with more than 10% of mutant AF of TP53 maybe have a good outcome for chemotherapy but needs to be further explored.
CCL27/CCL28–CCR10 Chemokine Signaling Mediates Migration of Lymphatic Endothelial Cells
Authors: Tara Karnezis, Rae H. Farnsworth, Nicole C. Harris, Steven P. Williams, Carol Caesar, David J. Byrne, Prad Herle, Maria L. Macheda, Ramin Shayan, You-Fang Zhang, Sezer Yazar, Simon J. Takouridis, Craig Gerard, Stephen B. Fox, Marc G. Achen, Steven A. Stacker
Journal: Cancer Research (2019)

Metastasis via the lymphatic vasculature is an important step in cancer progression. The formation of new lymphatic vessels (lymphangiogenesis), or remodeling of existing lymphatics, is thought to facilitate the entry and transport of tumor cells into lymphatic vessels and on to distant organs. The migration of lymphatic endothelial cells (LEC) toward guidance cues is critical for lymphangiogenesis. While chemokines are known to provide directional navigation for migrating immune cells, their role in mediating LEC migration during tumor-associated lymphangiogenesis is not well defined. Here, we undertook gene profiling studies to identify chemokine-chemokine receptor pairs that are involved in tumor lymphangiogenesis associated with lymph node metastasis. CCL27 and CCL28 were expressed in tumor cells with metastatic potential, while their cognate receptor, CCR10, was expressed by LECs and upregulated by the lymphangiogenic growth factor VEGFD and the proinflammatory cytokine TNFα. Migration assays demonstrated that LECs are attracted to both CCL27 and CCL28 in a CCR10-dependent manner, while abnormal lymphatic vessel patterning in CCR10-deficient mice confirmed the significant role of CCR10 in lymphatic patterning. In vivo analyses showed that LECs are recruited to a CCL27 or CCL28 source, while VEGFD was required in combination with these chemokines to enable formation of coherent lymphatic vessels. Moreover, tumor xenograft experiments demonstrated that even though CCL27 expression by tumors enhanced LEC recruitment, the ability to metastasize was dependent on the expression of VEGFD. These studies demonstrate that CCL27 and CCL28 signaling through CCR10 may cooperate with inflammatory mediators and VEGFD during tumor lymphangiogenesis. SIGNIFICANCE: The study shows that the remodeling of lymphatic vessels in cancer is influenced by CCL27 and CCL28 chemokines, which may provide a future target to modulate metastatic spread.
Abstract 20211: Perceived Control in Patients With Implantable Cardioverter Defibrillator: A Cross-Sectional Survey From US and Australia
Authors: Muna H Hammash, Jennifer Miller, Misook Chung, Timothy Crawford, Christine Haedtke, Samy Claude Elayi, Kyoung Suk Lee, Mary Czarapata, Samantha McEvedy, Jan Cameron, Jessica Harman, Martha Bidle, Debra Moser
Journal: Circulation (2017)

Introduction: Perceived control is essential to both the physical and psychological aspects of quality of life (QOL) among individuals with chronic conditions, and it is possible to increase perceived control with appropriate intervention. Little is known about the relationship between perceived control and QOL in implantable cardioverter defibrillator (ICD) recipients Purpose: To determine predictors of perceived control and the relationship between perceived control and QOL in ICD recipients Methods: A total of 274 ICD recipients (27% female, age 61 ± 13 years) from the US (n=201) and Australia (n= 73) completed the Control Attitude Scale-Revised to measure perceived control, and completed self-reported measures on potential correlates of perceived control (i.e., depressive symptoms, anxiety, social support , and ICD concerns. The EuroQol-5D was used to measure QOL in 5 dimensions: pain, mobility, self-care, usual activity, and anxiety/depression. Each dimension has 3 levels: no problems, some problems,...
Cardiac Abnormalities in Alzheimer Disease
Authors: Giuseppe D. Sanna, Giuseppe Nusdeo, Maria Rita Piras, Antonietta Forteleoni, Maria Rita Murru, Pier Sergio Saba, Simone Dore, Giovanni Sotgiu, Guido Parodi, Antonello Ganau
Journal: JACC Heart Failure (2019)

This case control study sought to assess the presence and characteristics of cardiac abnormalities in patients with Alzheimer disease (AD).Protein misfolding is involved in the pathophysiology of neurodegenerative disorders such as AD. Recently, amyloid-beta (Aβ) aggregates were identified within the cardiomyocytes and interstitium of patients with AD, suggesting that Aβ oligomers may reach and damage the heart.The authors studied 32 patients with AD and 34 controls matched by age and sex, all of whom were free from cardiac or systemic diseases. A clinical evaluation, an electrocardiogram, and an echocardiogram were performed in all subjects. Furthermore, patients with AD underwent genetic analyses (of the PSEN1, PSEN2, APP, and APOE genes).Compared to the control group, patients with AD had a higher prevalence of low-voltage electrocardiographic QRS complexes (28% vs. 3%, respectively; p = 0.004), a lower voltage/mass ratio (p = 0.05), a greater echocardiographic interventricular septum (10.1 ± 1.3 mm vs. 9.3 ± 1.1 mm, respectively; p = 0.01), a greater maximum wall thickness (10.8 ± 1.7 mm vs. 9.3 ± 1.1 mm, respectively; p = 0.0001), and a 2-fold higher prevalence of diastolic dysfunction (70% vs. 35%, respectively; p = 0.007). Symptoms and signs of heart failure were absent in all patients with AD.This study shows that electrocardiographic and echocardiographic abnormalities, including diastolic dysfunction, are present in patients with AD and that these studies reproduce the pattern of cardiac amyloidosis. These findings suggest that, in AD, there may be subclinical cardiac involvement likely associated with Aβ amyloid deposition. The clinical relevance of these cardiac abnormalities should be evaluated in larger prospective studies.
Discussion on critical points for a tailored therapy to cure hepatitis C virus infection
Authors: Nadia Marascio, Angela Quirino, Giorgio Settimo Barreca, Luisa Galati, Chiara Costa, Vincenzo Pisani, Maria Mazzitelli, Giovanni Matera, Maria Carla Liberto, Alfredo Focà, Carlo Torti
Journal: Clinical and Molecular Hepatology (2019)

Hepatitis C virus (HCV) infects around 71 million people worldwide and in 2018 it is still a major health problem. Since 2011, anti-HCV therapy with availability of direct-acting antiviral drugs has revolutionized the clinical response and paved the way to eradication strategies. However, despite the high rate of sustained virological response, treatment failure may occur in a limited percentage of patients, possibly due to resistance-associated substitutions (RASs), either emergent or pre-existent even in minority viral populations. Clearly this problem may impair success of eradication strategies. With this background, several questions marks still exist around HCV treatment, including whether pan-genotypic treatments with complete effectiveness in any clinical conditions really exist outside clinical trials, the actual cost-effectiveness of genotyping testing, and utility of RAS detection in viral quasispecies by next generation sequencing approach. In this review, we describe these critical points by discussing recent literature data and our research experience.
Multiview Cluster Analysis Identifies Variable Corticosteroid Response Phenotypes in Severe Asthma
Authors: Wei Wu, Seojin Bang, Eugene R. Bleecker, Mario Castro, Loren Denlinger, Serpil C. Erzurum, John V. Fahy, Anne M. Fitzpatrick, Benjamin M. Gaston, Annette T. Hastie, Elliot Israel, Nizar N. Jarjour, Bruce D. Levy, David T. Mauger, Deborah A. Meyers, Wendy C. Moore, Michael Peters, Brenda R. Phillips, Wanda Phipatanakul, Ronald L. Sorkness, Sally E. Wenzel
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Corticosteroids (CSs) are the most effective asthma therapy, but responses are heterogeneous and systemic CSs lead to long-term side effects. Therefore, an improved understanding of the contributing factors in CS responses could enhance precision management. Although several factors have been associated with CS responsiveness, no integrated/cluster approach has yet been undertaken to identify differential CS responses.Objectives: To identify asthma subphenotypes with differential responses to CS treatment using an unsupervised multiview learning approach.Methods: Multiple-kernel k-means clustering was applied to 100 clinical, physiological, inflammatory, and demographic variables from 346 adult participants with asthma in the Severe Asthma Research Program with paired (before and 2–3 weeks after triamcinolone administration) sputum data. Machine-learning techniques were used to select the top baseline variables that predicted cluster assignment for a new patient.Measurements and Main Results: Multiple-kernel clustering revealed four clusters of individuals with asthma and different CS responses. Clusters 1 and 2 consisted of young, modestly CS-responsive individuals with allergic asthma and relatively normal lung function, separated by contrasting sputum neutrophil and macrophage percentages after CS treatment. The subjects in cluster 3 had late-onset asthma and low lung function, high baseline eosinophilia, and the greatest CS responsiveness. Cluster 4 consisted primarily of young, obese females with severe airflow limitation, little eosinophilic inflammation, and the least CS responsiveness. The top 12 baseline variables were identified, and the clusters were validated using an independent Severe Asthma Research Program test set.Conclusions: Our machine learning–based approaches provide new insights into the mechanisms of CS responsiveness in asthma, with the potential to improve disease treatment.
Patient Reported Outcome (PRO) in Patients Receiving High and Moderate Emetogenic Chemotherapy (Ctx) - Results of a German Prospective Non-Interventional Study with Netupitant/Palonosetron Fixed Dose Combination (NEPA)
Authors: Meinolf Karthaus, P Klare, N Gazawi, MO Zahn, B Reimann, S Busch, Joerg Schilling
Journal: Blood (2018)
Abstract 19419: Does Mid-Gestation Fetal Doppler Predict Growth Parameters in the Babies of Women With Congenital Heart Disease
Authors: Kim Haberer, Shabnam Peyvandi, Juan Gonzalez, Anita J Moon-Grady
Journal: Circulation (2017)

Introduction: Fetal Growth Restriction is a significant source of perinatal morbidity. Mothers with congenital heart disease (CHD) have a higher incidence of neonates who are small for gestational ...
Subacromial decompression surgery for adults with shoulder pain: a clinical practice guideline
Authors: Per Olav Vandvik, Tuomas Lähdeoja, Clare Ardern, Rachelle Buchbinder, Jaydeep Moro, Jens Ivar Brox, Jako Burgers, Qiukui Hao, Teemu Karjalainen, Michel van den Bekerom, Julia Noorduyn, Lyubov Lytvyn, Reed A C Siemieniuk, Alexandra Albin, Sean Chua Shunjie, Florian Fisch, Laurie Proulx, Gordon Guyatt, Thomas Agoritsas, Rudolf W Poolman
Journal: BMJ (2019)

Do adults with atraumatic shoulder pain for more than 3 months diagnosed as subacromial pain syndrome (SAPS), also labelled as rotator cuff disease, benefit from subacromial decompression surgery? This guideline builds on to two recent high quality trials of shoulder surgery.SAPS is the common diagnosis for shoulder pain with several first line treatment options, including analgesia, exercises, and injections. Surgeons frequently perform arthroscopic subacromial decompression for prolonged symptoms, with guidelines providing conflicting recommendations.The guideline panel makes a strong recommendation against surgery.A guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines and the GRADE system. The recommendation is based on two linked systematic reviews on (a) the benefits and harms of subacromial decompression surgery and (b) the minimally important differences for patient reported outcome measures. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of surgery in multilayered evidence summaries and decision aids available in MAGIC (www.magicapp.org) to support shared decisions and adaptation.Surgery did not provide important improvements in pain, function, or quality of life compared with placebo surgery or other options. Frozen shoulder may be more common with surgery.The panel concluded that almost all informed patients would choose to avoid surgery because there is no benefit but there are harms and it is burdensome. Subacromial decompression surgery should not be offered to patients with SAPS. However, there is substantial uncertainty in what alternative treatment is best.
Localization of treatment‐resistant areas in patients with psoriasis on biologics
Authors: K.F. Hjuler, L. Iversen, M.K. Rasmussen, K. Kofoed, L. Skov, C. Zachariae
Journal: British Journal of Dermatology (2019)

BackgroundTraditionally, psoriasis in certain body sites such as the scalp, nails, palms, soles and intertriginous areas has been acknowledged as difficult to treat.
Treatment of hepatocellular carcinoma (HCC) after sorafenib (S) over the last 10 years.
Authors: Andrea S. Fung, Richard M. Lee-Ying, Daniel E. Meyers, Hao-Wen Sim, Jennifer J. Knox, Valeriya O. Zaborska, Janine Marie Davies, Yoo-Joung Ko, Eugene Batuyong, Winson Y. Cheung, Haider Samawi, Vincent C. Tam
Journal: Journal of Clinical Oncology (2019)

438 Background: Until recently there were no standard treatments for HCC patients after S. This study characterizes subsequent treatments (STx) received by HCC patients over the past 10 years and assesses their impact on survival. Methods: HCC patients treated with S between 01/2008 – 06/2017 in British Columbia, Alberta, and two cancer centers in Toronto, Ontario, Canada (Princess Margaret and Sunnybrook Cancer Centre) were included. Clinical, pathologic, laboratory, treatment, and outcome data were collected. The Kaplan-Meier method was used to assess overall survival (OS) based on STx, and stratified according to a better prognostic group (BPG), defined as ECOG 0-1 and CP-A, and worse prognostic group (WPG), defined as ECOG≥2 or CP-B/C. Results: A total of 730 patients were identified. 177 (24.2%) received STx (table). Patients who received STx had longer median OS (mOS) than those who had no further treatment (12.1 vs. 3.3 months; p &lt; 0.001). For patients treated with localized, systemic, or palliative radiation treatment, mOS was 16.8, 10.5 and 8.6 months, respectively (p &lt; 0.001). After S, there were 206 (30.7%) patients in the BPG and 464 (69.3%) in the WPG. BPG patients were more likely to receive STx compared to WPG patients (60.5% vs. 39.5%, p &lt; 0.001). BPG patients who received STx had better mOS than those who did not (15.9 vs. 7.0 months; p &lt; 0.001). WPG patients also had better mOS if they received STx compared to those who did not (6.0 vs. 2.6 months; p &lt; 0.001). Conclusions: Only a small proportion of HCC patients received subsequent treatment after sorafenib. This is likely due to poor performance status, liver dysfunction, or lack of treatment options. Patients who received subsequent treatment had improved mOS, regardless of whether they were in the better or worse prognostic group. [Table: see text]
Primary cervical screening with high risk human papillomavirus testing: observational study
Authors: Matejka Rebolj, Janet Rimmer, Karin Denton, John Tidy, Christopher Mathews, Kay Ellis, John Smith, Chris Evans, Thomas Giles, Viki Frew, Xenia Tyler, Alexandra Sargent, Janet Parker, Miles Holbrook, Katherine Hunt, Penny Tidbury, Tanya Levine, David Smith, Julietta Patnick, Ruth Stubbs, Sue Moss, Henry Kitchener
Journal: BMJ (2019)

Abstract Objective To provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening. Design Observational study. Setting The English Cervical Screening Programme. Participants 578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing. Interventions Routine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations. Main outcome measures Frequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds. Results Baseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23). Conclusions In England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.
Aberrant Regional DNA Hypermethylation As a Preventive and Therapeutic Target for Adult T-Cell Leukemia-Lymphoma
Authors: Tatsuro Watanabe, Hiroshi Ureshino, Yuki Kurahashi, Yuki Fukuda-Kurahashi, Satoshi Yamashita, Toshikazu Ushijima, Seiji Okada, Eisaburo Sueoka, Shinya Kimura
Journal: Blood (2018)
IPH4102; An Anti-KIR3DL2 Monoclonal Antibody in Refractory Sezary Syndrome: Results from a Multicenter Phase 1 Trial
Authors: Martine Bagot, Pierluigi Porcu, Basem M. William, Maxime Battistella, Maarten Vermeer, Sean Whittaker, Caroline Ram-Wolff, Michael S Khodadoust, Helene Sicard, Hatem A Azim, Youn H. Kim
Journal: Blood (2018)
Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An 8-year multicenter study
Authors: Hsien-Yi Chiu, Rosaline Chung-yee Hui, Tsen-Fang Tsai, Yang-Ching Chen, Nien-Feng Chang Liao, Po-Hua Chen, Po-Ju Lai, Ting-Shun Wang, Yu-Huei Huang
Journal: Journal of the American Academy of Dermatology (2019)
Multicentric MFI30 Study: Standardization of CD30 Expression By Flow Cytometry in Non-Hodgkin Lymphoma
Authors: Agathe Pruvot Debliquis, Lucile Baseggio, Marie-Christine Jacob, Sabrina Bouyer, Franck Genevieve, Julien Guy, Caroline Mayeur-Rousse, Nicolas Chapuis, Hind Bennani, Thomas Matthes, Bernard Drenou
Journal: Blood (2018)
Factors predicting persistence of biologic drugs in psoriasis: a systematic review and meta‐analysis
Authors: A. Mourad, S. Straube, S. Armijo‐Olivo, R. Gniadecki
Journal: British Journal of Dermatology (2019)

BackgroundLong‐term therapy for psoriasis is impaired by gradual loss of effectiveness and treatment discontinuation. Identifying factors that affect biologic drug survival may help in treatment optimization.
Lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio independently predict survival in resected small bowel adenocarcinoma.
Authors: Brandon M. Huffman, Shruti Patel, Siddhartha Yadav, Zhaohui Jin, Amit Mahipal
Journal: Journal of Clinical Oncology (2019)

426 Background: Small bowel adenocarcinoma is a rare malignancy affecting approximately 2,000 patients per year. There is a paucity of evidence prognosticating patients with small bowel adenocarcinoma. We aimed to evaluate multiple factors in patients with resected small bowel adenocarcinoma to determine any association with survival outcomes. Methods: Ninety three patients who underwent resection for stage I-III small bowel adenocarcinoma were retrospectively identified utilizing the pathology database at a single tertiary referral institution. All patients had complete follow up data and were included in the survival analysis. JMP software was used for statistical analysis. Overall survival was performed utilizing Kaplan-Meier method, and log-rank tests were used for statistical comparisons. Cox proportional hazards were performed to control for age, gender, location of tumor, tumor size, tumor stage, and adjuvant therapy. Sensitivity analysis was performed to establish best cutoff points for continuous variables. All tests were two sided and a P value of &lt; 0.05 was considered significant. Results: The median age at diagnosis was 65 years (range 32-90). 61% were male. Median tumor size was 4.5 cm. There were 20, 36, and 37 patients with stage I, stage II, and stage III disease, respectively. Median overall survival (OS) was 151 months, 104 months, and 44 months for stages I, II, and III disease. In a multivariate analysis, independent predictor factors included presurgical lymphocyte to monocyte ratio (LMR) &gt; 4.0, with a Hazard Ratio (HR) 0.13 (95% CI 0.007-0.69, p = 0.01), presurgical neutrophil to lymphocyte ratio (NLR) &lt; 8.0, HR 0.39 (95% CI 0.17-0.96, p = 0.04), and tumor size &lt; 7.5 cm, HR 0.22 (95% CI 0.07-0.85, p = 0.03). Stage, age, T stage, and N stage influenced overall survival in univariate analysis, but were not statistically significant on multivariate analysis. Conclusions: LMR and NLR independently predict survival in patients with resected small bowel adenocarcinoma.