tbuckley/cabot-search huggingface dataset:
Does Histological Type Matter in Malignant Appendiceal Neoplasms?
Authors: ME O'Donnell, J Carson, WIH Garstin
Journal: Endoscopy (2006)

Aims: Malignant appendiceal neoplasms (MAN) are rare. Pre-operative diagnosis is invariably difficult, and once identified, precise treatment protocols remain unclear. We reviewed our experience for this condition and searched published evidence to produce management guidelines.
Successful Repeated Hepatic Gene Delivery in Mice and Non-human Primates Achieved by Sequential Administration of AAV5 ch and AAV1
Authors: Anna Majowicz, David Salas, Nerea Zabaleta, Estefania Rodríguez-Garcia, Gloria González-Aseguinolaza, Harald Petry, Valerie Ferreira
Journal: Molecular Therapy (2017)

In the gene therapy field, re-administration of adeno-associated virus (AAV) is an important topic because a decrease in therapeutic protein expression might occur over time. However, an efficient re-administration with the same AAV serotype is impossible due to serotype-specific, anti-AAV neutralizing antibodies (NABs) that are produced after initial AAV treatment. To address this issue, we explored the feasibility of using chimeric AAV serotype 5 (AAV5ch) and AAV1 for repeated liver-targeted gene delivery. To develop a relevant model, we immunized animals with a high dose of AAV5ch-human secreted embryonic alkaline phosphatase (hSEAP) that generates high levels of anti-AAV5ch NAB. Secondary liver transduction with the same dose of AAV1-human factor IX (hFIX) in the presence of high levels of anti-AAV5ch NAB proved to be successful because expression/activity of both reporter transgenes was observed. This is the first time that two different transgenes are shown to be produced by non-human primate (NHP) liver after sequential administration of clinically relevant doses of both AAV5ch and AAV1. The levels of transgene proteins achieved after delivery with AAV5ch and AAV1 illustrate the possibility of both serotypes for liver targeting. Furthermore, transgene DNA and RNA biodistribution patterns provided insight into the potential cause of decrease or loss of transgene protein expression over time in NHPs.
The relationship between performance status and sleep quality in cancer patients.
Authors: Silviya Velinova, Rasa Kazlauskaite, Roxana Aguirre, Khosrow Zarei, Lily Parhad Hussein, Wendy Rogowski, Susan H. McDunn, Thomas E. Lad
Journal: Journal of Clinical Oncology (2013)

e20544 Background: Poor sleep is common, and is linked to impaired cognitive, psychological, and physical functioning and a lower quality of life. The purpose of this study is to measure quality of sleep in cancer patients and determine the relationship between quality of sleep and performance status. Methods: Patients with cancer (n=139) were recruited at the public hospital between November 2011 and January 2012 and asked to complete the Pittsburgh Sleep Quality Index (PSQI) and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) questionnaires. Twenty patients repeated the questionnaires after 3 months. For the purpose of this study PSQI global score &gt;5 was considered insomnia. PS score 0-1 was considered good, and PS 2-4 was considered poor. Results: The mean age of participants was 55±11 years, 56% were women, 78% were ethnic minority, 77% had advanced cancer, and 71% were undergoing cancer treatment. Among all patients, 73% reported good PS. Median PSQI score was 7 (IQR 4; 11) and 62% had insomnia. Sleep medication was used by 25%. Patients with poor PS had worse PSQI score (Mann-Whitney test, p&lt; 0.0001), and 7.34 (95%CI 2.11-25.49) higher odds of insomnia (p=0.0002) compared to patients with good PS.(Table1) No significant correlation was found between insomnia and gender, ethnicity, primary tumor type, tumor stage, or treatment status. Conclusions: The incidence of insomnia among cancer patients is high. There is a higher incidence of sleep disturbance and worse sleep quality among patients with poorer performance status. [Table: see text]
Successful retrieval of an immovable pancreatic stent using a novel thin-tipped balloon catheter
Authors: Tadahisa Inoue, Norimitsu Ishii, Yuji Kobayashi, Kiyoaki Ito, Masashi Yoneda
Journal: Endoscopy (2017)

Endoscopic pancreatic stenting for symptomatic strictures is beneficial to patients with chronic pancreatitis [1]. However, stent-related problems occur, including migration and immobility, which are more serious for pancreatic stents than for biliary stents because the pancreatic duct bends and is narrow [2]. We encountered a rare case with a pancreatic stent that could not be removed using forceps and was successfully retrieved using a novel thin-tipped balloon catheter.
Real-world safety data for tbo-filgrastim.
Authors: Nicole Lang, Andreas Lammerich, Udo W. Mueller, Peter Bias
Journal: Journal of Clinical Oncology (2014)

e17540 Background: Medical products registered in the European Union (EU) are subject to Periodic Safety Update Reports (PSURs), which provide comprehensive worldwide safety data assessments and benefit-risk analyses. Methods: The present PSUR for tbo-filgrastim-containing products within the TEVA group (Tevagrastim, Biograstim, Ratiograstim [marketed in the US as Granix]) analyzed safety data accumulated between April 1, 2012 and March 31, 2013 in 38 countries. Cumulative data were collected from clinical trials and post-marketing sources from September 15, 2008 (initial approval) to the end of the current PSUR period, March 31, 2013. Data were collected from spontaneous reports from healthcare professionals, consumers, scientific literature, competent authorities, and solicited case reports. Adverse reactions were categorized by system organ class (SOC), source, and seriousness. Teva pharmacovigilance requires screening of all adverse reaction reports and antibody assessment for cases of suspected immunogenicity. Results: From September 15, 2008 (initial approval) to the end of the current PSUR period, March 31, 2013, the estimated cumulative exposure to products containing tbo-filgrastim was ~4,474,929 patient-days. Estimated cumulative exposure to tbo-filgrastim in clinical trials in healthy subjects and patients with cancer was 190 and 22,099 patient-days, respectively. The global safety database processed 254 tbo-filgrastim case reports from initial product approval through March 31, 2013 (~4.5 years), including 61 (24%) from the PSUR period. Post-marketing data sources cumulatively reported 461 adverse reactions, 131 (28%) from the PSUR period. The most commonly occurring preferred terms in association with important identified and potential risks over the cumulative period were allergic type reactions (11), interstitial pneumonia (4), and splenomegaly (2). Eleven new cases were identified that required immunogenicity testing during the PSUR period. The most common reasons for requiring testing were lack of efficacy (n=7) and type II hypersensitivity (n=2). Conclusions: No new safety risks were identified for tbo-filgrastim based on PSUR data from the most recent reporting period ending March 31, 2013.
Bispecific antibody targets multiple Pseudomonas aeruginosa evasion mechanisms in the lung vasculature
Authors: Ajitha Thanabalasuriar, Bas G.J. Surewaard, Michelle E. Willson, Arpan S. Neupane, Charles K. Stover, Paul Warrener, George Wilson, Ashley E. Keller, Bret R. Sellman, Antonio DiGiandomenico, Paul Kubes
Journal: Journal of Clinical Investigation (2017)

Pseudomonas aeruginosa is a major cause of severe infections that lead to bacteremia and high patient mortality. P. aeruginosa has evolved numerous evasion and subversion mechanisms that work in concert to overcome immune recognition and effector functions in hospitalized and immunosuppressed individuals. Here, we have used multilaser spinning-disk intravital microscopy to monitor the blood-borne stage in a murine bacteremic model of P. aeruginosa infection. P. aeruginosa adhered avidly to lung vasculature, where patrolling neutrophils and other immune cells were virtually blind to the pathogen's presence. This cloaking phenomenon was attributed to expression of Psl exopolysaccharide. Although an anti-Psl mAb activated complement and enhanced neutrophil recognition of P. aeruginosa, neutrophil-mediated clearance of the pathogen was suboptimal owing to a second subversion mechanism, namely the type 3 secretion (T3S) injectisome. Indeed, T3S prevented phagosome acidification and resisted killing inside these compartments. Antibody-mediated inhibition of the T3S protein PcrV did not enhance bacterial phagocytosis but did enhance killing of the few bacteria ingested by neutrophils. A bispecific mAb targeting both Psl and PcrV enhanced neutrophil uptake of P. aeruginosa and also greatly increased inhibition of T3S function, allowing for phagosome acidification and bacterial killing. These data highlight the need to block multiple evasion and subversion mechanisms in tandem to kill P. aeruginosa.
Abstract P070: NEU3 Sialidase Overexpression Activates Cell Survival in Murine Skeletal Myoblasts C2C12 and Protects Them from Hypoxia
Authors: Luigi Anastasia, Raffaella Scaringi, Nadia Papini, Andrea Garatti, Lorenzo Menicanti, Pietro Allevi, Bruno Venerando, Guido Tettamanti, Cecilia Gelfi, Annarosa Leri
Journal: Circulation Research (2011)

Membrane-bound sialidase NEU3 increase during skeletal muscle differentiation has been shown to protect myoblasts from apoptosis and drive the differentiation process [1]. Thus, the objective of this study was to assess whether up-regulation of NEU3 would enhance the ability of murine skeletal muscle cells to resist to hypoxia, ultimately opposing cell death. We found that C2C12 myoblasts overexpressing NEU3 (L-NEU3) became highly resistant to 1% oxygen or 200 mM deferoxamine induced hypoxia. Moreover, L-NEU3 myoblasts survived a seven-day treatment of combined hypoxia and low serum (2% horse serum used to induce myoblast differentiation), without any significant cell loss. On the contrary, wild type C2C12 could not resist to these culturing conditions and all died within 48h. Real Time PCR showed NEU3 expression increase during all hypoxic treatments both in C2C12 and L-NEU3 cells, suggesting an endogenous NEU3 activation under these conditions. Moreover, we found that NEU3 over-expression activated pro-survival signalling pathways through up-regulation and activation of EGF receptor. Overall, our data support the hypothesis that NEU3 may play a critical role in the response of skeletal myoblasts to hypoxia and the preservation of cell viability by activating pro-survival signalling pathways. [1] Anastasia L. et al. J.Biol.Chem. 2008, 283 (52): 36265–36271.
Circulating tumor cell (CTC) as a significant clinical marker in epithelioid-type malignant pleural mesothelioma (MPM).
Authors: Kazue Yoneda, Fumihiro Tanaka, Shunichi Fukuda, Hayato Orui, Masaki Hashimoto, Teruhisa Takuwa, Yoshitomo Okumura, Seiji Matsumoto, Nobuyuki Kondo, Ayuko Sato, Tohru Tsujimura, Noriaki Tsubota, Kazuya Fukuoka, Takashi Nakano, Seiki Hasegawa
Journal: Journal of Clinical Oncology (2012)

7080 Background: Circulating tumor cell (CTC) is a surrogate of distant metastasis, and our preliminary study suggested that CTC detected by an EpCAM-based immuno-magnetic separation system (“CellSearch”) was a useful clinical marker in the diagnosis of malignant pleural mesothelioma (MPM) (Tanaka F. et al ASCO 2008). Methods: Patients who presented at our institute to receive pleural biopsy with suspicion of MPM were prospectively enrolled. CTCs in 7.5mL of peripheral blood were quantitatively evaluated with the CellSearch system. Results: Among 136 eligible patients, 104 were finally diagnosed with MPM, and 32 were with non-malignant diseases (NM). CTC was positive (CTC≥1) in 32.7% (37/104) of MPM pts, and in 9.4% (3/32) of NM pts (p=0.011). CTC-count was significantly higher in MPM (range, 0-9) than in NM (range, 0-1; p=0.007). According to a ROC curve analysis, the CTC-test provided a significant diagnostic performance in discrimination between MPM and NM (AUC= 0.623; P=0.036). Among MPM pts, CTC-positivity and CTC-count were significantly increased with tumor progression (p=0.026 and p=0.008, respectively). For all MPM pts, there was no significant difference in overall survival between CTC-positive and negative pts. However, in a planned subset analysis, CTC was a significant factor to predict poor prognosis (median survival time, 8.0 months for CTC-positive pts, and 20.3 months for negative pts; p=0.012) in pts with epithelioid-type MPM in which CTC was exclusively positive; a multivariate analysis confirmed that CTC, along with PS, was an independent prognostic factor (HR=2.38; P=0.006). Conclusions: CTC was a significant diagnostic marker in discrimination between MPM and NM. CTC-positivity was a significant and independent prognostic factor to predict a poor prognosis of epithelioid MPM. [Table: see text]
Survival Improvement for Acute Myeloid Leukemia Patients Treated in Routine Practice By Intensive Chemotherapy Between 2000 and 2014
Authors: Sarah Bertoli, Emilie Bérard, Suzanne Tavitian, Anne Huynh, Cecile Borel, Sarah Guenounou, Isabelle Luquet, Eric Delabesse, Audrey Sarry, Guy Laurent, Michel Attal, Françoise Huguet, Christian Récher
Journal: Blood (2016)
RBCs pin platelets against the (thrombus) wall
Authors: Kellie R. Machlus, Elisabeth M. Battinelli
Journal: Blood (2017)

In this issue of Blood, Walton and colleagues reveal that elevated hematocrit enhances clot formation in vivo via increased platelet accumulation in a growing thrombus.1 Although elevated hematocrit is an independent risk factor for cardiovascular disease, the specific contribution of an increased red blood cell (RBC) count to this etiology has remained elusive. This is largely due to complicating factors in diseases such as polycythemia vera (PV), where patients present with elevated hematocrit, but the specific role of RBCs in thrombotic risk is unclear. To circumvent these additional complications, Walton et al used a model where additional RBCs were infused into healthy mice and arterial clot formation was studied, thus isolating the contribution of the increased RBCs. Notably, the increased number of RBCs changed the hemodynamics of the blood around a growing thrombus, narrowing the near-wall, RBC-free zone (see figure). This narrowed zone created a locale where platelets spend significantly more time in contact with the growing thrombus, increasing the probability of their binding and incorporation into the clot. Thus, elevated hematocrit, perhaps unexpectedly, was shown to enhance thrombotic risk by increasing the number of platelets incorporated into the thrombus.
YouTube and Eosinophilic Esophagitis: An Assessment of the Educational Quality of Information
Authors: Apurva Bansal, Keerthi Reddy, Rufaat Mando, Santiago Alvarez-Arango, Joseph Gabriel, Sumana Reddy, Lyda Cuervo-Pardo, Anjali Malkani, Chakradhar Reddy, Claudia A. Kozinetz, Alexei Gonzalez-Estrada
Journal: Journal of Allergy and Clinical Immunology (2018)
Circulating tumor cell (CTC) as a prognostic marker in primary lung cancer.
Authors: Kazue Yoneda, Fumihiro Tanaka, Nobuyuki Kondo, Masaki Hashimoto, Teruhisa Takuwa, Seiji Matsumoto, Yoshitomo Okumura, Noriaki Tsubota, Ayuko Sato, Tohru Tsujimura, Kozo Kuribayashi, Chiharu Tabata, Takashi Nakano, Seiki Hasegawa
Journal: Journal of Clinical Oncology (2015)

e22041 Background: Circulating tumor cell (CTC) can be a useful marker in early diagnosis and monitoring therapeutic effects for patients with malignant tumors, but clinical significance of CTC in primary lung cancer remains unclear. We previously showed that CTC was a useful surrogate marker of distant metastasis in primary lung cancer (Clin Cancer Res 2009). In this study, we evaluated the prognostic value of CTC in the same cohort of patients. Methods: A total of 125 patients (median age, 67 years; 39 females and 86 males) with primary lung cancer (9 with small cell and 116 with non-small cell) were prospectively evaluated. At the time of enrollment into the study, 7.5 mL of peripheral blood was sampled from each patient, and an EpCAM-based detection system (CellSearch) was used for detection of CTC. CTC was detected in 38 patients (CTC-positive) and not detected in 87 patients (CTC-negative). Results: The median overall survival time (MST) and survival rate at 5 years after enrollment were significantly better in CTC-negative patients (79.4 months and 82.7%, respectively) than in CTC-positive patients (44.2 months and 53.0%, respectively; p < 0.001). Subset analyses according to clinical stage, the prognostic value was significant in stage IV patients (Table). A multivariate analysis showed that CTC-positive was a significant factor to predict a poor prognosis (hazard ratio, 1.64 [95% CI, 1.01-2.66]; P = 0.044). Conclusions: CTC-positivity was a significant prognostic factor to predict a poor prognosis in primary lung cancer. Patients with advanced stage of diseases (stage III-IV) achieved a favorable prognosis (MST, more than 50 months), when CTC was negative. Overall survival (median time): Comparison between CTC-positive and CTC-negative patients. CTC-positive CTC-negative All patients 44.2m 79.4m P < 0.001 Stage I patients 63.8m 70.0m P = 0.490 Stage II patients Not reached Not reached P = 0.637 Stage III patients 15.9m 56.5m P = 0.079 Stage IV patients 28.3m 52.7m P=0.048
Two alternate strategies for innate immunity to Epstein-Barr virus: One using NK cells and the other NK cells and γδ T cells
Authors: Zakia Djaoud, Lisbeth A. Guethlein, Amir Horowitz, Tarik Azzi, Neda Nemat-Gorgani, Daniel Olive, David Nadal, Paul J. Norman, Christian Münz, Peter Parham
Journal: The Journal of Experimental Medicine (2017)

Most humans become infected with Epstein–Barr virus (EBV), which then persists for life. Infrequently, EBV infection causes infectious mononucleosis (IM) or Burkitt lymphoma (BL). Type I EBV infection, particularly type I BL, stimulates strong responses of innate immune cells. Humans respond to EBV in two alternative ways. Of 24 individuals studied, 13 made strong NK and γδ T cell responses, whereas 11 made feeble γδ T cell responses but stronger NK cell responses. The difference does not correlate with sex, HLA type, or previous exposure to EBV or cytomegalovirus. Cohorts of EBV+ children and pediatric IM patients include both group 1 individuals, with high numbers of γδ T cells, and group 2 individuals, with low numbers. The even balance of groups 1 and 2 in the human population points to both forms of innate immune response to EBV having benefit for human survival. Correlating these distinctive responses with the progress of EBV infection might facilitate the management of EBV-mediated disease.
The effect of body mass index on prognosis and survival of ER(-) and PR(+) nonmetastatic breast cancer patients: Single institute experience.
Authors: Mutlu Dogan, Gokmen Umut Erdem, Nebi Serkan Demirci, Nurullah Zengin
Journal: Journal of Clinical Oncology (2015)

e11533 Background: Our aim was to evaluate the effect of body mass index (BMI) on survival of ER(-) and PR(+) nonmetastatic breast cancer (NMBC) patients. Methods: ER(-) and PR(+) NMBC patients were evaluated for BMI, prognosis and survival retrospectively. Results: Five of 104 ER(-) and PR(+) breast cancer patients between 2004 & 2014 at our center were excluded since they had metastasis. ER(-) and PR(+) NMBC patients were analyzed according to BMI ( < 25kg/m2 vs > 25kg/m2). Most of the patients had invasive ductal carcinoma with a median age of 47 (range:41-52) years. The rate of NMBC patients with BMI( > 25kg/m2) was 83.5%. More than half (56.7%) of the patients were premenopausal. Most patients had stage 2 (49.3%) & stage 3 (40.3%) NMBC. Most (82%) of NMBC patients had Her-2/neu negative NMBC. Her-2/neu positivity was determined by immunhistochemistry (15%) and FISH (3%) among those with Her-2/neu positive NMBC patients. Relapse rate was 41.8%. Stage 3 NMBC was significantly higher in those with BMI ( < 25kg/m2) (p:0.04). Median OS & DFS were significantly higher in NMBC with BMI ( > 25kg/m2) [(403 months vs 44 months, p < 0.001), (103 months vs 25 months, p < 0.001), respectively]. BMI had no significant effect on relapse rate during adjuvant hormonotherapy in all patients, but those with BMI ( > 25kg/m2) seemed to have a better trend in DFS (p:0.07). Conclusions: Obesity is a poor risk factor for breast cancer, especially for those with ER(+) postmenopausal patients since aromatization is the major source of estrogen production. Its role in ER(-) and PR(+) ones is not so clear. We found that ER(-) and PR(+) NMBC patients with BMI ( > 25kg/m2) had better OS & DFS with lower rates of stage 3 disease than those with BMI ( < 25kg/m2). However, small number of the patients in this retrospective study seems to be limiting. We consider that further randomized prospective clinical trials with large number of patients are needed in this area.
ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/SCMR 2008 Appropriateness Criteria for Stress Echocardiography⁎⁎Developed in accordance with the principles and methodology outlined by ACCF: Patel MR, Spertus JA, Brindis RG, Hendel RC, Douglas PS, Peterson ED, Wolk MJ, Allen JM, Raskin IE. ACCF proposed method for evaluating the appropriateness of cardiovascular imaging. J Am Coll Cardiol 2005;46:1606–13.
Authors: Pamela S. Douglas, Bijoy Khandheria, Raymond F. Stainback, Neil J. Weissman
Journal: Journal of the American College of Cardiology (2008)
Rltpr Is a Central Scaffold Protein Regulating Human TCR Co-Signaling and Cytoskeletal Dynamics
Authors: Tilmann Schober, Thomas Magg, Melanie Laschinger, Thomas Fröhlich, Meino Rohlfs, Yanshan Liu, Jacek Puchalka, Tanja Weisser, Karin Fehlner, Christoph Walz, Natália Duarte Linhares, Sérgio D. Pena, Bernd H. Belohradsky, Christoph Klein, Fabian Hauck
Journal: Blood (2016)
Use of an on-line at the point of care 13C-Methacetin Breath test as an adjunct tool for decision making in patients with Acute Liver Failure
Authors: Vinod K. Audimlam, Vishal C. Patel, William Bernal, Meir Mizrahi, Julia Wendon, Gadi Lalazar, Yaron Ilan
Journal: Hepatology (2012)