tbuckley/cabot-search huggingface dataset:
Enhanced Anti-Tumor Efficacy through a Combination of Integrin αvβ6-Targeted Photodynamic Therapy and Immune Checkpoint Inhibition
Authors: Liquan Gao, Chenran Zhang, Duo Gao, Hao Liu, Xinhe Yu, Jianhao Lai, Fan Wang, Jian Lin, Zhaofei Liu
Journal: Theranostics (2016)

Training" the host immune system to recognize and systemically eliminate residual tumor lesions and micrometastases is a promising strategy for cancer therapy.In this study, we investigated whether integrin αvβ6-targeted photodynamic therapy (PDT) of tumors using a phthalocyanine dye-labeled probe (termed DSAB-HK) could trigger the host immune response, and whether PDT in combination with anti-PD-1 immune checkpoint inhibition could be used for the effective therapy of primary tumors and metastases.By near-infrared fluorescence imaging, DSAB-HK was demonstrated to specifically target either subcutaneous tumors in a 4T1 mouse breast cancer model or firefly luciferase stably transfected 4T1 (4T1-fLuc) lung metastatic tumors.Upon light irradiation, PDT by DSAB-HK significantly inhibited the growth of subcutaneous 4T1 tumors, and in addition promoted the maturation of dendritic cells and their production of cytokines, which subsequently stimulated the tumor recruitment of CD8 + cytotoxic T lymphocytes.Furthermore, DSAB-HK PDT of the first tumor followed by PD-1 blockade markedly suppressed the growth of a second subcutaneous tumor, and also slowed the growth of 4T1-fLuc lung metastasis as demonstrated by serial bioluminescence imaging.Together, our results demonstrated the synergistic effect of tumor-targeted PDT and immune checkpoint inhibition for improving anti-tumor immunity and suppressing tumor growth/metastasis.
Coping with germs and people: Investigating the link between pathogen threat and human social cognition
Authors: Carlos David Navarrete
Journal: Behavioral and Brain Sciences (2012)

Group assortative biases are stronger in regions where pathogen stress has been historically prevalent. Pushing the logic of this approach, extensions should include investigations of how cultural norms related to prosociality and relational striving may also covary with regional pathogen stress. Likewise, the pan-specific observation that diseased animals show decreased motor activity to facilitate recovery suggests that norms relevant to sickness behaviors may also vary as a function of regional parasite stress.
Summary and Future Research Needs
Authors: P. A. Bromberg, D. B. Menzel
Journal: Environmental Health Perspectives (1980)

Dr. Bromberg: This is a remarkable meeting in that, with very few exceptions, almost no mention was made of pulmonary mechanics and of gas exchange. That doesn't happen very often in meetings devoted primarily to lung research, but perhaps has been happening more frequently in the recent past and it may indicate a trend for the future. Another interesting note was that almost everyone is working or collaborating with an ultrastructuralist, or would like to have access to ultrastructural techniques. Dr. Reid, among others, gave us a very nice demonstration of how ultrastructural techniques can be combined with biochemical techniques in experimental studies of the reaction of the lung to insults. Dr. Satir presented most elegant ultrastructural biochemical data on the mechanism of ciliary motion. The organization of the meeting, as I perceive it, looks at the lung as having three segments. There was a large area of attention to the epithelium, and at the end, there was a large area of attention to the endothelium. In the middle, I suppose appropriately, there were a number of speakers who talked about cells that more or less fit between the epithelium and the endothelium. Notably missing, or in large measure missing, were discussions of smooth muscle and of neural function at more than a passing level. The keynote of the epithelial sections was set by Dr. Boucher and Dr. Gatzy, who pointed to the barrier function of the epithelium and the attempts to quantitate the nature and the site of this barrier. They paid special attention to the intercellularjunctions and the so-called tight junctions of the epithelium and defined their properties by electrical measurements and by using a variety of non-charged probe molecules.
Abstract 244: Lung adenocarcinomas show genetic-morphologic correlations in three dimensional culture
Authors: Daisuke Matsubara, Shumpei Ishikawa, Masashi Fukayama, Toshiro Niki
Journal: Cancer Research (2011)

Abstract EGFR mutation is associated with papillary morphology suggesting a genetic-histologic link. In this study we analyzed the relationship between gene expression, mutation, and morphology on Matrigel. Based on EGFR and MET abnormality combined with gene expression pattern, lung adenocarcinoma could be classified into two groups: Group I (Bronchial epithelial phenotype) with high expressions of CK7, MUC1, TTF-1, and E-cadherin, and Group II (non-Bronchial epithelial phenotype) with high vimentin expression (Matsubara et al, Am J Pathol, 2010). On Matrigel, cell lines formed either round (n=30), grape-like (n=4) or stellate-shaped (n=6) colonies. Most of the Group I cell lines formed round colonies. Most of the cell lines that formed grape-like or stellate-shaped colonies belonged to Group II. Virtually all cell lines with EGFR, HER2, and MET gene abnormality belonged to Group I and formed round colonies. In contrast, KRAS mutants were heterogeneous and formed either round, grape-like or stellate-shaped colonies. All KRAS-mutated Group I cell lines formed round colonies, while KRAS-mutated Group II cell lines frequently formed non-round colonies. Strikingly, non-round colony formation was correlated with loss of LKB1 expression in KRAS mutants. Thus, lung adenocarcinomas show genetic-morphologic correlations in three dimensional culture. The results reinforce the genetic-histologic correlations previously documented in primary tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 244. doi:10.1158/1538-7445.AM2011-244
OP0212 The Risk of Myocardial Infarction and Cerebrovascular Accident in Patients with SjÖGren's Syndrome: A General Population-Based Cohort Study: Table 1.
Authors: M. Yurkovich, E.C. Sayre, K. Shojania, A. Avina-Zubieta
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> There is limited data on the risk of myocardial infarction (MI) and cerebrovascular accident (CVA) in patients with Sjögren9s Syndrome (SjS). <h3>Objectives</h3> To fill this knowledge gap we estimated the future risk of newly recorded MI and CVA events among incident cases, with SjS compared to controls from the general population using physician billing and hospitalization databases that cover the entire population of the province of British Columbia, Canada. <h3>Methods</h3> Our data include all visits to health professionals and all hospital admissions from 1990 to 2010 and all dispensed medications from1995 to 2010 for all individuals. We conducted a retrospective matched cohort study among patients satisfying at least one of the following criteria: a) diagnosis of SjS (ICD-9-CM code 710.2, ICD-10-CM code M35.0) in adults on at least two visits within a two-year period between 1996 and 2010 by a non-rheumatologist physician; b) diagnosis of SjS on at least one visit by a rheumatologist or from hospitalization. Ten non-SLE controls matched by birth year, sex and calendar year of follow-up, were selected from the general population for each case. <i>Outcomes:</i> Incident MI and CVA events based on hospitalization or death certificate were recorded as an outcome. We estimated relative risks (RRs) comparing SjS with age-, sex- and entry time-matched comparison cohorts, adjusting for potential cardiovascular risk factors. <h3>Results</h3> Among 1,176 (MI cohort) and 1,195 (CVA cohort) incident SjS cases, 28 developed a first time MI and 19 CVA events with an incident rate (IR) of 7.7 and 5.1 per 1000 person-years, respectively. Compared with the age, sex, and entry matched controls the RRs were 2.2 (95% CI 1.41-3.32) and 1.5 (0.9-2.4), respectively (see table) After adjusting for covariates the results remained similar for both MI and CVA. The risk of developing MI was highest within the first year following diagnosis of SjS, and persisted up to five years following the initial diagnosis. <h3>Conclusions</h3> This is the first general population-based study investigating the risk of MI and CVA in SjS. We found a significantly increased risk of MI in patients with SjS, particularly in the first year following diagnosis, indicating that the acute inflammatory state in SjS, particularly at disease onset, is likely the main driver for this increased risk. We also found a trend towards an increased risk for CVA. Our results support increased monitoring for coronary artery disease in addition to management and modification of risk factors to reduce the risk of MI in patients with SjS. <h3>Acknowledgements</h3> Research funded by an operating grant by the Canadian Arthritis Network/The Arthritis Society and the BC Lupus Society (Grant 10-SRP-IJD-01) <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3108
Cat Scratch Disease
Authors: M Giladi, B Avidor
Journal: New England Journal of Medicine (1999)

Figure 1. A 17-year-old boy presented with a two-week history of a painful mass on the right side of the neck, fever, malaise, headache, and night sweats. The fever and other systemic symptoms gradually abated during the first 10 days of his illness, but the cervical mass increased in size. The patient owned a kitten, which often scratched him. On examination, a hard, immobile mass measuring 3.5 by 3 cm that was tender to the touch was palpable (Panel A). Serum enzyme immunoassay was positive for IgG antibodies to Bartonella henselae, and the patient was given a 14-day course of . . .
NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets
Authors: Morten Nielsen, Massimo Andreatta
Journal: Genome Medicine (2016)

Binding of peptides to MHC class I molecules (MHC-I) is essential for antigen presentation to cytotoxic T-cells.Here, we demonstrate how a simple alignment step allowing insertions and deletions in a pan-specific MHC-I binding machine-learning model enables combining information across both multiple MHC molecules and peptide lengths. This pan-allele/pan-length algorithm significantly outperforms state-of-the-art methods, and captures differences in the length profile of binders to different MHC molecules leading to increased accuracy for ligand identification. Using this model, we demonstrate that percentile ranks in contrast to affinity-based thresholds are optimal for ligand identification due to uniform sampling of the MHC space.We have developed a neural network-based machine-learning algorithm leveraging information across multiple receptor specificities and ligand length scales, and demonstrated how this approach significantly improves the accuracy for prediction of peptide binding and identification of MHC ligands. The method is available at www.cbs.dtu.dk/services/NetMHCpan-3.0 .
Usefulness of Endoscopic Ultrasound-Guided Fine Needle Aspiration in the Management of Mediastinal Lymph Nodes in Patients with Suspicion of Lung Cancer: Can Surgical Procedures be Avoided?
Authors: J Lariño-Noia, J Iglesias-García, S Seijo-Rios, M Vilariño-Insua, JE Dominguez-Muñoz
Journal: Endoscopy (2006)

Background: Endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) has been recently introduced in the routine evaluation of patients with mediastinal lymph nodes (LN) in the context of lung cancer. Data about the usefulness of this procedure in the management of these patients are limited. Aim: To evaluate the usefulness of EUS-guided FNA in the management of patients with mediastinal LN and suspicion of lung cancer, in terms of ability to avoid diagnostic or therapeutic surgical procedures. Methods: Patients referred to our EUS Unit for the study of mediastinal LN and with the suspicion of lung cancer, previously detected by CT scanning, were included. EUS and EUS-guided FNA were performed by two echoendoscopists using the lineal scanning Pentax FG-38UX. For puncture, 19G and 22G needles were used. All procedures were performed under conscious sedation with midazolam and meperidine. Vital signs were continuously monitored. Samples were processed for cytological and histological analysis. Further diagnostic or therapeutic surgical procedures were avoided in case of conclusive lung cancer LN metastasis, or conclusive benign nature of LN. Results: A total of 22 consecutive patients (20 male, mean age 55 years, range 41–80 years) were included. Cytological and histological analysis of the material obtained by EUS guided-FNA provided with a definite diagnosis, either benign or malignant, in 19 patients (86.4%) (13 patients with NSCLC lung cancer, 3 cases with SCL lung cancer, and one case of lymphoma; and three patients had benign LN); however, in 3 patients (13.6%) diagnosis was inconclusive. Sensitivity, specificity and overall accuracy were 84.2%, 100% and 86.4% respectively. EUS-guided FNA avoided a further surgical procedure in 22 cases (77.3%). There were no complications related to the technique. Conclusion: EUS-guided FNA is a safe and useful procedure for the evaluation of mediastinal LN in patients with suspicion of lung cancer. Inclusion of this procedure in the diagnostic workout of these patients avoids surgical procedures in up to three out of each four patients.
A case of gastric aberrant pancreas diagnosed with EUS-FNA
Authors: Fujii Masakuni
Journal: Endoscopy (2011)

A 42-year-old man had abdominal pain. Endoscopic examination disclosed a submucosal tumor (SMT) in the greater curvature of the gastric body. Under CT examination, this SMT had a cystic lesion and inflammatory reaction was found outside of the gastric wall. Endoscopic ultrasonography (EUS) was performed and a hypoechoic mass with anechoic capillary areas occupied the third layer of the gastric wall. We suspected gastric aberrant pancreas. To confirm a diagnosis, we performed an EUS-guided fine-needle aspiration biopsy (EUS-FNA) with Echotip Ultra 22G. In addition, we punctured the cyst and measured pancreatic enzymes. The histology of the SMT was a normal pancreatic acinus. The cystic fluid AMY and Lipase level were 41360 IU/and 204000IU/l, respectively. Consequently, the confirmative diagnosis was an aberrant pancreas of the stomach. Although the symptoms were improved with conservative treatment, the patient had abdominal pain again. The CT imaging showed inflammatory exudates on the liver surface which was contiguous from aberrant pancreas. Subtotal gastrectomy was performed and resected specimen contained excretory duct, islets of Langerhans, and acinar cells, which meant an aberrant pancreas of Heinrich. Two months after the treatment, the patient had no symptoms. EUS-FNA is a powerful tool for the preoperative diagnosis of the aberrant pancreas of the stomach.
Abstract P1-01-04: Axillary Intervention in Patients Undergoing Neoadjuvant Therapy (NST) — First Results from the SENTINA Study
Authors: K Thorsten, I Bauerfeind, T Fehm, B Fleige, H Gisela, A Lebeau, C Liedtke, M Mai, G Von Minckwitz, P Schrenk, A Staebler, M. Untch
Journal: Cancer Research (2010)

Abstract Background: The optimal scheduling for sentinel lymph node biopsy (SLNB) among patients with breast cancer undergoing neoadjuvant systemic therapy (NST) is unclear. SENTINA-study is the first prospective multicenter trial that systematically examines the feasibilty and reliability of SLNB prior to and after (NST). Here we present results of a first exploratory analysis by examining distribution of N-stages in the different treatment arms and correlating the axillary status with the type of breast surgery (breast conserving therapy [BCT] vs mastectomy [ME]). Methods: The SENTINA study is a four-arm multicenter (n= XXX) observation study. Patients will be stratified based on their clinical lymph node status prior to treatment. If the lymph node status is clinically negative SLNB is performed before NST. Patients with a negative SLN will undergo no further axillary surgery (Arm A), whereas patients with a positive SLN will be treated with sentinel-node-guided axillary dissection (SLNB-AD) after NST (Arm B). If the lymph node is clinically positive upon initial presentation, patients will undergo NST prior to any axillary intervention. If patients convert to a clinically negative lymph node status through NST they will undergo SLNB-AD (ARM C). Patients with persistent positive nodes or whose tumors progress under NST undergo primary axillary dissection (Arm D). Clinically node positive patients will be endcouraged to undergo FNA to confirm their lymph node status. A total of 1508 patients in the entire study will be needed to calculate the false-negative rate in this group with a one-sided 95% confidence interval not exceeding 10%. Results: 873 patients have been accrued into SENTINA until may 31th 2010, 523 (59,9%) have completed their treatment. 180 (34,4%) women have been treated in Arm A and 117 (22,4%) in Arm B. In 170 (32,5%) patients the clinical axillary status converted from a clinical positive to a clinical negative status (Arm C). In 65 pts (12,4%) the axillary status remained positive or the tumor progressed under NCHT (Arm D). BCT rates in Arm A-D were 88.3%, 75.2%, 61.8% and 22.2% respectively. Conclusion: First results of the SENTINA study show a strong correlation between the axillary status and the type of breast surgery in patients, who are treated with NST. Importantly, we demonstrate that the clinical assessment of the axillary status is unprecise. There is an urgent need to optimize the tailoring of axillary intervention in the setting of NST Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-04.
Abstract 3132: C6orf69 is down-modulated by protein kinase C epsilon and exhibits increased expression in breast cancers
Authors: Dorota Garczarczyk, Doris Hinger, Peter Gruber, Johann Hofmann
Journal: Cancer Research (2011)

Abstract Protein kinase C (PKC) comprises a serine/threonine kinase family of at least ten related isozymes. Protein kinase C epsilon (PKCε) has been shown previously to act as an oncogene, contributing to malignancy by tumor cell invasion, metastasis and inhibiting cell death. However, the precise function is not known at present. We investigated whether PKCε expression leads to alterations in the expression of other genes. We found by gene array after overexpression of constitutively active PKCε that EST AA167550, of which 348 bases were known, was down-modulated. We obtained the full-length sequence of AA167550. It was identified as chromosome 6 open reading frame 69 gene (C6orf69). At least two distinct mRNAs were found to be transcribed from this gene. We generated an antibody and as shown by Western blotting, two proteins (47 and 40 kDa) were detected. The full length sequence of C6orf69 contains a BTB-BACK-Kelch domain usually involved in protein-protein interactions and implicated in the stability of actin filaments. C6orf69 co-immunoprecipitated with PKCε and bound to actin. PKCε/C6orf69 interaction was additionally confirmed by a yeast two-hybrid screen using C6orf69 full length as bait. C6orf69 is expressed in many tissues except in heart, ovary, small intestine and leukocytes. In nine out of nine breast cancers, the expression levels were higher than in matched normal mammary tissue. C6orf69 contains four putative PKC phosphorylation sites. The C6orf69 protein is phosphorylated but is not a direct substrate of PKC isozymes, as demonstrated by in vitro PKC assays. Recently, BTB-domain containing proteins have been reported to regulate protein stability by recruiting proteins to the Cullin3 (Cul3) ubiquitin ligase leading to their degradation via ubiquitin/proteasome. By a yeast two-hybrid screen and co-immunoprecipitation we could demonstrate that C6orf69 is interacting specifically with Cul3. In addition, an in vivo ubiquitylation assay showed that overexpressed C6orf69 protein is efficiently polyubiquitylated, indicating to be a substrate of E3 ligase itself. In summary, C6orf6 is down-modulated by PKCε, shows elevated expression in breast cancers compared to corresponding normal breast tissue, contains a BTB domain, interacts with PKCε, actin and Cul3. C6orf69 is phosporylated but not substrate of PKC isozymes and it is ubiquitylated. This work was supported by grants P15039 and P19878 from the Austrian Science Fund (FWF). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3132. doi:10.1158/1538-7445.AM2011-3132
PREVALENCE AND SIGNIFICANCE OF INCIDENTAL FINDINGS IN CARDIAC COMPUTED TOMOGRAPHY PRIOR TO ATRIAL FIBRILLATION ABLATION
Authors: Sandia Iskandar, Mamatha Vodapally, Ravali Neerumalla, Maruthsakhi Molugu, RajaRajeswari Swarna, Quratulain Javed, Karthik Gangu, Anirudh Gone, Muhammad Afzal, Donita Atkins, Sudharani Bommana, Madhu Reddy, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2016)
SAT0495 Evaluation of Pain-Related Behavior in the Hindlimb-Unloaded Mouse Model of Bone Loss
Authors: T. Nakagawa, H. Wakabayashi, Y. Naito, A. Sudo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteoporotic patients with no evidence of fractures sometimes experience vague low back pain. However, there have been few reports regarding the correlation between osteoporosis and pain-related behavior. <h3>Objectives</h3> The objective of the current study was to investigate pain-related behavior in osteoporotic mice. <h3>Methods</h3> Male ddY mice (8 weeks old) were either hindlimb-unloaded (HU) by tail suspension for 2 Week or hindlimb-loaded (control). The femoral distal metaphyses and the proximal tibial metaphyses (HU group; 12 hindlimbs, control group; 8 hindlimbs) were analyzed three-dimensionally by micro-computed tomography (μCT) 2 weeks after tail suspension. Mechanical sensitivity was tested using von Frey filaments 2 weeks after tail suspension (HU group; 12 hindlimbs, control group; 8 hindlimbs). The frequency of the withdrawal response and the withdrawal threshold to the application of von Frey filaments to the planter surface of the hindpaws was examined. To evaluate the frequency of the withdrawal response, three von Frey filaments with forces of 0.4, 0.6 and 1.4 were applied 5 times each in ascending order of force, and the number and intensity of withdrawal responses were noted. Results were expressed as the percent response frequency of paw withdrawals. To evaluate the withdrawal threshold, each von Frey filament was applied once, starting with 0.008g and increasing until a withdrawal response was reached, which was considered a positive response. The lowest force producing a response was considered the withdrawal threshold. <h3>Results</h3> μCT analysis of the distal femoral metaphysis and the proximal tibial metaphysis (Figs. 1, 2) showed that bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) were significantly less in the HU group than in the control group, whereas trabecular separation (Tb.Sp) was significantly greater in the HU group than in the control group. The paw-withdrawal-frequency stimulated by von Frey filaments with strength of 0.4, 0.6 and 1.4 g was significantly higher in the HU group than in the control group (Fig. 3). The withdrawal threshold was significantly lower in the HU group than in the control group (Fig. 4). <h3>Conclusions</h3> In this study, hindlimb-unloading induced bone loss and mechanical hyperalgesia in hindlimb. The results suggest that hindlimb-unloaded mouse provides a useful model for osteoporotic pain. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1669