tbuckley/cabot-search huggingface dataset:
Gadolinium-Chelated Conjugated Polymer-Based Nanotheranostics for Photoacoustic/Magnetic Resonance/NIR-II Fluorescence Imaging-Guided Cancer Photothermal Therapy
Authors: Xiaoming Hu, Yufu Tang, Yuxuan Hu, Feng Lu, Xiaomei Lu, Yuqi Wang, Jie Li, Yuanyuan Li, Yu Ji, Wenjun Wang, Deju Ye, Quli Fan, Wei Huang
Journal: Theranostics (2019)

Our exploiting versatile multimodal theranostic agent aims to integrate the complementary superiorities of photoacoustic imaging (PAI), second near-infrared (NIR-II, 1000-1700) fluorescence and T1-weighted magnetic resonance imaging (MRI) with an ultimate objective of perfecting cancer diagnosis, thus improving cancer therapy efficacy.Herein, we engineered and prepared a water-soluble gadolinium-chelated conjugated polymer-based theranostic nanomedicine (PFTQ-PEG-Gd NPs) for in vivo tri-mode PA/MR/NIR-II imaging-guided tumor photothermal therapy (PTT).Methods: We firstly constructed a semiconducting polymer composed of low-bandgap donor-acceptor (D-A) which afforded the strong NIR absorption for PAI/PTT and long fluorescence emission to NIR-II region for in vivo imaging.Then, the remaining carboxyl groups of the polymeric NPs could effectively chelate with Gd 3+ ions for MRI.The in vitro characteristics of the PFTQ-PEG-Gd NPs were studied and the in vivo multimode imaging as well as anti-tumor efficacy of the NPs was evaluated using 4T1 tumor-bearing mice.Results: The obtained theranostic agent showed excellent chemical and optical stability as well as low biotoxicity.After 24 h of systemic administration using PQTF-PEG-Gd NPs, the tumor sites of living mice exhibited obvious enhancement in PA, NIR-II fluorescence and positive MR signal intensities.Better still, a conspicuous tumor growth restraint was detected under NIR light irradiation after administration of PQTF-PEG-Gd NPs, indicating the efficient photothermal potency of the nano-agent.Conclusion: we triumphantly designed and synthesized a novel and omnipotent semiconducting polymer nanoparticles-based theranostic platform for PAI, NIR-II fluorescence imaging as well as positive MRI-guided tumor PTT in living mice.We expect that such a novel organic nano-platform manifests a great promise for high spatial resolution and deep penetration cancer theranostics.
AB0498 GYNECOLOGICAL SYMPTOMS AND SEXUALITY IN SJOGREN’S SYNDROME
Authors: Özlem Özdemir Işık, Ayten Yazici, Ayse Cefle
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients with Sjogren's syndrome (SS) have symptoms such as vaginal dryness and dyspareunia. <h3>Objectives</h3> In this study we aimed to present of primary SS (pSS) and secondary SS (sSS) patient's gynecological symptoms and effects of the disease on sexuality. <h3>Methods</h3> 60 pSS, 42 sSS, 52 healthy controls (HC) were interviewed. It was asked questions about sexuality, SF-36, HAD scale, pSS and sSS patients were also administered HAQ and Modified Hiil questionnaire¹. <h3>Results</h3> The mean age of the patients was 52 ± 11 years in the pSS, 54 ± 11years in the sSS and 46 ± 9 years in the HC. Although there was no significant difference in term of age in pSS and sSS groups, mean age was lower in HC group. There were no significant differences in SF-36 mental index score, SF-36 physical index score, HAD-Anxiety score and HAD-Depression score among 3 groups. 62% of patients in the pSS, 79% in the sSS and 33% in HC were in menopause. Vaginal and vulvar dryness were significantly higher in SS, especially in the pSS than HC. The proportion of sexually active women was lower in sSS group. Spontaneous genital pain and dyspareunia were found to be high in pSS and it was statistically significant. Decreased sexual desire was significantly higher in SS groups (Table1). HAQ score was significantly lower in pSS group than sSS group. Dyspareunia, dysuria, vaginal dryness and fatigue were significantly higher in pSS (Table2). There was no significant difference between two groups in terms of the effect of vulvar, vaginal dryness, dyspareunia, decreased sexual desire, myalgia, arthralgia and fatigue on sexuality In the pSS group, it was seen that disease had a negative effect on sexuality. There were no significant differences between the two groups when asked whether they enjoyed sexuality and the sexual problems create problems between their partners. In both groups, 97% of patients stated that they had not been questioned about their sexuality before. 80% of pSS patients and 88% of sSS patients stated that they did not talk about sexuality problems. <h3>Conclusion</h3> Gynecological and sexual problems are seen in SS patients. Menopause also contributes to this situation. Patients should be informed about these problems and directed to gynecologists when necessary, and enough time should be reserved as we do. <h3>References</h3> [1] S. Maddali Bongi at all.Gynaecological Symptoms and Sexual Disability in Women with Primary Sjögren's Syndrome and Sicca Syndrome.Clinical and Experimental Rheumatology 2013; 31: 683-690 <h3>Disclosure of Interests</h3> None declared
PS1223 INTERIM ANALYSIS OF A WT‐1 AND PRAME ‘FAST‐DC’ VACCINE SHOWS SAFETY AS ACTIVE IMMMUNOTHERAPY FOR THE PREVENTION OF AML RELAPSE
Authors: Y. Fløisand, I. Bigalke, D. Josefsen, C. Geiger, K. Pinkernell, G. Kvalheim
Journal: HemaSphere (2019)

Background: Patients with acute myeloid leukemia (AML), not eligible for allogeneic hematopoietic stem cell transplantation (HSCT), have a significant risk of disease relapse due to lack of long‐term disease control. Aims: To investigate the possibility of relapse prevention after initial chemotherapy, a safety and feasibility Phase I/II trial (NCT02405338) is currently being conducted using dendritic cells (DCs), generated with a rapid production protocol of 3 to 4 days. The manufacture uses RNA electroporation encoding the full‐length protein antigens PRAME (Preferentially expressed antigen in Melanoma) and WT‐1 (Wilm's Tumor‐1 Antigen) as well as a cocktail containing a TLR‐7/8 agonist for maturation. Data presented here reflect results of an interim analysis at the 1 year follow up time point, while vaccination continues until all patients reach the end of the trial at a follow up of 2 years. Methods: A total of 20 subjects (median age 59, range 24 to 73) with AML (risk groups good, intermediate, poor: 13, 5, 2), in morphologic complete remission or complete remission with incomplete hematologic recovery after induction or consolidation therapy, not eligible for allogeneic HSCT, were entered in the trial. Subjects had to be positive for WT‐1 with or without positivity for PRAME. DC vaccinations were carried out monthly, with a higher frequency within the first 6 weeks. AML diagnoses were established with a median of 9.8 months before the first vaccination (range 4.5 to 17.5 months), and the last chemotherapy infusion was performed at a median of 6.9 months (range 2 to 14.8 months). Results: The manufacture of the DC vaccine in these chemotherapy‐pretreated subjects was feasible for all 20 patients and aliquots of 5 to 10 x 10 6 cells were used per vaccination. The vaccinations were well tolerated with no serious adverse events (SAEs) related to the treatment. The most common adverse events (AEs) were injection site related, accounting for 35% of all AEs and were mild in nature (Grade 1). A total of 3 grade 3 adverse events, unlikely or not related to the treatment, were recorded: one Herpes zoster infection, one upper respiratory tract infection and 3 decreases in platelet counts. All three platelet count decreases were due to relapses of the leukemia. After a 12‐months treatment period, the overall survival was 89% (18 of 20 patients, 95% confidence interval: 61 to 97%) and the progression free survival was 60% (12 of 20 patients, 95% confidence interval: 36 to 78%). Most relapses, 5 out of 8, occurred within the first 80 days after the start of the vaccination, out of which the 2 deaths were in patients with relapses on days 45 and 64, which could point to a starting relapse upon entering the study. Summary/Conclusion: In summary, at a follow up time of 1 year, DC vaccination against WT‐1 and PRAME appears to be safe and feasible for use in the prevention of AML relapse.
Different Neuronal Activity Patterns Induce Different Gene Expression Programs
Authors: Kelsey M. Tyssowski, Nicholas R. DeStefino, Jin-Hyung Cho, Carissa J. Dunn, Robert G. Poston, Crista E. Carty, Richard D. Jones, Sarah M. Chang, Palmyra Romeo, Mary K. Wurzelmann, James M. Ward, Mark L. Andermann, Ramendra N. Saha, Serena M. Dudek, Jesse M. Gray
Journal: Neuron (2018)
Development of a stem cell tracking platform for ophthalmic applications using ultrasound and photoacoustic imaging
Authors: Kelsey P. Kubelick, Eric J. Snider, C. Ross Ethier, Stanislav Emelianov
Journal: Theranostics (2019)

Glaucoma is the second leading cause of blindness in the world.Disease progression is associated with reduced cellularity in the trabecular meshwork (TM), a fluid drainage tissue in the anterior eye.A promising therapy seeks to deliver stem cells to the TM to regenerate the tissue and restore its function.However, like many stem cell-based regenerative therapies, preclinical development relies heavily on histology to evaluate outcomes.To expedite clinical translation, we are developing an ultrasound/photoacoustic (US/PA) imaging platform for longitudinal tracking of stem cells in the anterior eye.Methods: Mesenchymal stem cells (MSCs) were labeled with gold nanospheres in vitro and injected through the cornea into the anterior chamber of ex vivo porcine eyes.Physiological pressure was imposed to mimic in vivo conditions.AuNS-labeled MSCs were injected through the cornea while single-wavelength US/PA images were acquired.At 5 hours post-injection, three-dimensional multi-wavelength US/PA datasets were acquired and spectroscopic analysis was used to detect AuNS-labeled MSCs.US/PA results were compared to fluorescent microscopy. Results:The US/PA imaging platform was able to provide real-time monitoring of the stem cell injection and distinguish AuNS-labeled MSCs from highly absorbing background tissues in the anterior segment.Conclusion: Our US/PA imaging approach can inform preclinical studies of stem cell therapies for glaucoma treatment, motivating further development of this theranostic imaging tool for ophthalmic applications.
PB1988 CANCER‐ASSOCIATED MECHANISMS OF MESENCHYMAL STEM CELLS REVEALED BY SINGLE‐CELL TRANSCRIPTOME ANALYSIS
Authors: A. Stucky, X. Chen, C. Li, J. cai, X. Zhang, J. Zhong
Journal: HemaSphere (2019)

Background: The detrimental effects of mesenchymal stem cells (MSCs) in some reports eclipse their benefits in clinical application, despite the support and adoption in bone marrow transplantation (BMT). Tumorigenicity has been observed and reported in experimental MSC therapies without clear explanation. Aims: Here we report a subpopulation of MSCs, which are resisted to oste single‐cell transcriptome analysis of individual MSCs at various stages of osteocyte differentiation and gene expression profiles in three discrete stages of osteogenesis. Methods: We identified a subpopulation of osteogenesis‐resistant MSCs which have cancer stem cell chatcteristics. Further pathway analysis indicated that the YAP1, β‐Catenin and Cadherin4/6 pathway involved in osteogenesis‐resistance.. Clinical surveys using 51 clinical databases across 6,965 patients revealed a correlation between YAP1/ β‐Catenin/Cadherin4/6 overexpression and cancer progression. Results: This study suggested that a differentiation‐resistant population of MSC is repsoible for the tumorogenicity of MSC, and intervention of the YAP1, β‐Catenin and Cadherin4/6 pathway could potentially prevent tumorgenicity in MSC therapies. suggests that there is a pre‐exist subpopulation of MSCs with cancer stem cell characteristics. Summary/Conclusion: Those OR‐MSC associated with active YAP1‐Cadherin pathway. Biologically active molecules targeting YAP1/ β‐Catenin/Cadherin could improve MSC therapy for a defined subset of patients by minimize the tumorgenicity of MSCs.
Impact of Travel Time on Health Care Costs and Resource Use by Phase of Care for Older Patients With Cancer
Authors: Gabrielle B. Rocque, Courtney P. Williams, Harold D. Miller, Andres Azuero, Stephanie B. Wheeler, Maria Pisu, Olivia Hull, Rodney P. Rocconi, Kelly M. Kenzik
Journal: Journal of Clinical Oncology (2019)

Many community cancer clinics closed between 2008 and 2016, with additional closings potentially expected. Limited data exist on the impact of travel time on health care costs and resource use.This retrospective cohort study (2012 to 2015) evaluated travel time to cancer care site for Medicare beneficiaries age 65 years or older in the southeastern United States. The primary outcome was Medicare spending by phase of care (ie, initial, survivorship, end of life). Secondary outcomes included patient cost responsibility and resource use measured by hospitalization rates, intensive care unit admissions, and chemotherapy-related hospitalization rates. Hierarchical linear models with patients clustered within cancer care site (CCS) were used to determine the effects of travel time on average monthly phase-specific Medicare spending and patient cost responsibility.Median travel time was 32 (interquartile range, 18-59) minutes for the 23,382 included Medicare beneficiaries, with 24% of patients traveling longer than 1 hour to their CCS. During the initial phase of care, Medicare spending was 14% higher and patient cost responsibility was 10% higher for patients traveling longer than 1 hour than those traveling 30 minutes or less. Hospitalization rates were 4% to 13% higher for patients traveling longer than 1 hour versus 30 minutes or less in the initial (61 v 54), survivorship (27 v 26), and end-of-life (310 v 286) phases of care (all P < .05). Most patients traveling longer than 1 hour were hospitalized at a local hospital rather than at their CCS, whereas the converse was true for patients traveling 30 minutes or less.As health care locations close, patients living farther from treatment sites may experience more limited access to care, and health care spending could increase for patients and Medicare.
S142 FIRST-IN-CLASS ORAL FERROPORTIN INHIBITOR: MODE OF ACTION AND EFFICACY IN A MOUSE MODEL OF BETA-THALASSEMIA INTERMEDIA
Authors: V. Manolova, N. Nyffenegger, A. Flace, P. Altermatt, C. Doucerain, H. Sundström, F. Dürrenberger
Journal: HemaSphere (2019)

Background: β-thalassemia is a rare genetic disease in which ineffective erythropoiesis leads to anemia and iron overload. Currently, no efficacious oral medication with a good tolerability profile is available to patients with β-thalassemia. Correction of unbalanced iron absorption by induction of hepcidin synthesis or supplementation of hepcidin mimetics has been shown to normalize the dysregulated iron metabolism in β-thalassemia1. However, hepcidin modulation or replacement strategies all require parenteral drug administration. Restricting iron availability by VIT-2763, the first-in-class clinical stage oral ferroportin (Fpn) inhibitor, ameliorated anemia and the dysregulated iron homeostasis in the Hbbth3/+ mouse model of β-thalassemia intermedia2. Aims: To address the mode of action and preclinical efficacy of VIT-2763 in a mouse model of β-thalassemia intermedia. Methods: The potency of VIT-2763 and hepcidin in an iron efflux assay was investigated using T47D cells which express endogenous human Fpn. Fpn internalization was studied using MDCK cells constitutively expressing human Fpn with a fluorescent tag. The efficacy of VIT-2763 was studied in a mouse model of β-thalassemia intermedia (Hbbth3/+). Results: The potency and mode of action of VIT-2763 and hepcidin were compared in a set of cell-based assays. Strikingly, VIT-2763 (EC50 = 68 ± 21 nM, mean ± standard deviation, n = 6) blocked iron efflux in cells with similar potency to hepcidin (EC50 = 123 ± 46 nM mean ± standard deviation, n = 6), despite being structurally unrelated and more than five-fold smaller in molecular weight than hepcidin. However, VIT-2763 showed slower kinetics and triggered incomplete Fpn internalization and degradation compared to hepcidin. These data might indicate that VIT-2763 directly and efficiently blocks Fpn-mediated iron export in addition to Fpn internalization. A kinetic study in the Hbbth3/+ mouse model of β-thalassemia intermedia revealed that VIT-2763 dosed for one week significantly reduced hemichromes in red blood cells (RBCs), increased RBC counts and hemoglobin, thereby indicating rapid improvement of erythropoiesis. Over time, VIT-2763 further ameliorated the RBC phenotype, such as decreased formation of reactive oxygen species, improved mitochondria clearance in mature RBCs and extended RBC life-span. Moreover, VIT-2763 corrected the elevated blood leukocyte counts in Hbbth3/+ mice, likely through effects on myeloid precursors in the spleen. A proof-of concept clinical study with VIT-2763 as a novel, first in-class oral drug targeting Fpn for the treatment of β-thalassemia is currently in the planning phase. Summary/Conclusion: Iron restriction by pharmacologically targeting the Fpn-hepcidin axis with the first in-class oral Fpn inhibitor VIT-2763 provides a novel therapeutic opportunity in β-thalassemia.
Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10–producing regulatory B cells
Authors: Yoshiyuki Mishima, Akihiko Oka, Bo Liu, Jeremy W. Herzog, Chang Soo Eun, Ting-Jia Fan, Emily Bulik-Sullivan, Ian M. Carroll, Jonathan J. Hansen, Liang Chen, Justin E. Wilson, Nancy C. Fisher, Jenny P.Y. Ting, Tomonori Nochi, Angela Wahl, J. Victor Garcia, Christopher L. Karp, R. Balfour Sartor
Journal: Journal of Clinical Investigation (2019)

Resident microbiota activate regulatory cells that modulate intestinal inflammation and promote and maintain intestinal homeostasis. IL-10 is a key mediator of immune regulatory function. Our studies described the functional importance and mechanisms by which gut microbiota and specific microbial components influenced the development of intestinal IL-10-producing B cells. We used fecal transplant to germ-free (GF) Il10+/EGFP reporter and Il10-/- mice to demonstrate that microbiota from specific pathogen-free mice primarily stimulated IL-10-producing colon-specific B cells and T regulatory-1 cells in ex-GF mice. IL-10 in turn down-regulated microbiota-activated mucosal inflammatory cytokines. TLR2/9 ligands and enteric bacterial lysates preferentially induced IL-10 production and regulatory capacity of intestinal B cells. Analysis of Il10+/EGFP mice crossed with additional gene-deficient strains and B cell co-transfer studies demonstrated that microbiota-induced IL-10-producing intestinal B cells ameliorated chronic T cell-mediated colitis in a TLR2, MyD88 and PI3K-dependent fashion. In vitro studies implicated PI3Kp110δ and AKT downstream signaling. These studies demonstrated that resident enteric bacteria activated intestinal IL-10-producing B cells through TLR2, MyD88 and PI3K pathways. These B cells reduced colonic T cell activation and maintained mucosal homeostasis in response to intestinal microbiota.
PB2208 MOLECULAR PROFILE AND TELOMERE LENGTH ARE USEFUL MARKERS FOR DIFFERENTIAL DIAGNOSIS OF PRE‐FIBROTIC PRIMARY MYELOFIBROSIS VERSUS ESSENTIAL THROMBOCYTHEMIA
Authors: J. Yun, J.‐A. Kim, N. Yang, S. Ryu, D. Jeong, Y. E. Lee, S.‐M. Kim, K. M. Lim, D. S. Lee
Journal: HemaSphere (2019)

Background: The 2016 revised WHO classification of MPN newly presented pre‐fibrotic PMF. Diagnostic criteria is based on bone marrow morphology, fibrosis, and clinical features (leukoerythroblastosis, anemia, leukocytosis, increased lactate dehydrogenase, and palpable splenomegaly). Since pre‐fibrotic PMF is a new entity characterized by a unique combination of both thrombotic and hemorrhagic risk, a differentiation from essential thrombocythemia (ET) is pivotal for treatment decision. However, the differentiation is difficult in many cases. Aims: In this study, we sought to explore useful markers for the differential diagnosis of ET and pre‐fibrotic PMF. We compared the cytogenetic and molecular profiles, telomere length, survival rate of patients among pre‐fibrotic PMF, overt PMF and ET. Methods: We reviewed BM morphology and clinical data of 59 Korean patients diagnosed with MPN in 2005∼2014. We classified MPN subtypes of them in series of 2001∼2016 WHO criteria. G‐banding/FISH (BCR/ABL1, 20q deletion, 13q deletion) (n = 57), targeted sequencing of 88 genes (n = 59), telomere/centromere ratio using quantitative FISH (n = 44), and survival analysis (n = 59) were performed. Results: Among 15 patients with MPN‐U by WHO 2001∼2014 classification, 7 patients were re‐diagnosed with pre‐fibrotic PMF, 2 with overt PMF, 6 with MPN‐U by WHO 2016 classification. Based on WHO 2016 classification, cytogenetic abnormalities were detected as 0% in ET, 0% in pre‐fibrotic PMF, and 42.3% in overt PMF. The numbers of mutated genes were 1.5 ± 1.3, 2.4 ± 1.3, 2.0 ± 1.2 in ET, pre‐fibrotic PMF, overt PMF, respectively (p = 0.542). The spectrum of mutate genes expanded from ET to overt PMF. Telomere length (telomere/centromere ratio) were 14.5 ± 1.4, 10.1 ± 3.1, 9.2 ± 3.7 in ET, pre‐fibrotic PMF, overt PMF, respectively (p = 0.042). 5‐year survival rates were 100%, 71.4%, 49.5% in ET, pre‐fibrotic PMF, overt PMF, respectively. Summary/Conclusion: Pre‐fibrotic PMF patients were found to harbor more number of mutations than ET. Mutation profile expanded and telomere lengths decreased in order of disease severity. Especially, C SF3R, DNMT3A, SF3B1, SRSF2 mutation can be candidate marker for differential diagnosis between ET and pre‐fibrotic PMF. Telomere length definitely gives information about disease severity, which is a useful indicator in differential diagnosis of MPN. image
A Retinal Circuit Generating a Dynamic Predictive Code for Oriented Features
Authors: Jamie Johnston, Sofie-Helene Seibel, Léa Simone Adele Darnet, Sabine Renninger, Michael Orger, Leon Lagnado
Journal: Neuron (2019)

Sensory systems must reduce the transmission of redundant information to function efficiently. One strategy is to continuously adjust the sensitivity of neurons to suppress responses to common features of the input while enhancing responses to new ones. Here we image the excitatory synaptic inputs and outputs of retinal ganglion cells to understand how such dynamic predictive coding is implemented in the analysis of spatial patterns. Synapses of bipolar cells become tuned to orientation through presynaptic inhibition, generating lateral antagonism in the orientation domain. Individual ganglion cells receive excitatory synapses tuned to different orientations, but feedforward inhibition generates a high-pass filter that only transmits the initial activation of these inputs, removing redundancy. These results demonstrate how a dynamic predictive code can be implemented by circuit motifs common to many parts of the brain.
Response to: ‘Comment on: ‘Anti-Ro52 autoantibodies are associated with interstitial lung disease and more severe disease in patients with juvenile myositis’ by Sabbagh S<i>et al’</i>by Yang<i>et al</i>
Authors: Sara Sabbagh, Iago Pinal Fernandez, Frederick W Miller, Lisa G Rider, Andrew Lee Mammen
Journal: Annals of the Rheumatic Diseases (2019)

We are grateful for the interest in our work1 shown by Drs Yang and Liang. In their correspondence regarding this work,2 they raise concerns about (1) the association between anti-Ro52 autoantibodies and interstitial lung disease (ILD) in juvenile polymyositis (JPM) and juvenile connective tissue disease–myositis (JCTM), (2) the appropriateness of adjusting for duration of follow-up instead of length …