tbuckley/cabot-search huggingface dataset:
Non-invasive monitoring of morphologic changes after mTHPC mediated photodynamic therapy (PDT) in a mouse tumor model using optical coherence tomography (OCT)
Authors: Martijn Triesscheijn, Paul Baas, Marjan Ruevekamp, Fiona A. Stewart, Maurice Aalders
Journal: Cancer Research (2005)

4736  Evidence suggests that effective mTHPC mediated PDT is dependent on early vascular damage. Various methods can be used to evaluate vascular changes but most have the drawback of being invasive. OCT is a novel, non-invasive imaging technique that can detect structural and functional changes (including perfusion) in superficial tissues. We used OCT to measure PDT induced changes in perfusion and compared these results with histological assessments of vascular damage and response to PDT. Materials and Methods: Nude mice bearing subcutaneous HNXOE tumors were injected with mTHPC (0.3 mg/kg) at 3 or 48 h before illumination (652 nm, 30 J/cm2, 100 mW/cm2). Sequential OCT measurements were made before and up to 24 h after PDT. Histological assessments of perfusion (Hoechst 33342 and collagen IV staining) and tissue hypoxia (EF3 staining) were made for tumors at 1 h after PDT. Separate groups of mice were used to evaluate tumor response to PDT (regrowth delay and cure). Results: OCT could visualize different structural layers of tumor and overlying skin with a maximal penetration of 2 mm. PDT with a 3 h drug-light interval (D-L) reduced perfusion of superficial tumor tissue by 60-80% within 30 minutes and for at least 3 h after illumination. PDT with a D-L of 48 h did not produce significant OCT changes. These results corresponded with histological assessments of PDT induced changes, which also showed ablation of perfused blood vessels and increased tumor hypoxia for the 3 h D-L interval only. Long term follow-up of tumor response showed that protocols that induced an early vascular response (3 h D-L) resulted in 100% cure, whereas protocols that did not produce an early vascular response (48 h D-L) resulted in rapid regrowth of most tumors. Conclusion: OCT may offer the possibility to predict response to PDT treatment, or even to adjust the light dose delivered to ensure that an adequate vascular response is achieved.
Abstract P4-14-13: Tamoxifen induced ovarian hyperstimulation during hormonal therapy for breast cancer
Authors: MK Kim, H-c Shin
Journal: Cancer Research (2019)

Abstract Introduction Adjuvant endocrine therapy is an integral compo-nent of care for endocrine-dependent breast cancer. To date, international consensus statements recommend tamoxifen (20 mg/day) for five years as the standard adjuvant endocrine therapy for premenopausal women. Tamoxifen is a potent inducer of ovarian function and consequent hyper-estrogenism in premenopausal women. However, the incidence rate and risk factors associated this phenomenone were not clarified. Methods Among consecutive patients who were operated under diagnosis of breast cancer from March 2012 to December 2016 in Chung-Ang university hospital, patients who received post-operative tamoxifen therapy for endocrine-dependent breast cancer (stage 0-III) at age under 60 were selected and retrospectively analysed. Serial data on serum estradiol and follicular stimulating hormone(FSH) were collected. When the serum concentration of estradiol was higher than 400 pg/mL, which exceeds the normal estradiol production by a single preovulatory follicle, we classified them as tamoxifen induced ovarian hyperstimulation group. Clinicopathologic factors were analyzed between ovarian hyperstimulation group and non-hyperstimulation group by x2 and student t-test. Results Among 205 patients, 19 patients(9.3%) showed high values of serum estradiol during tamoxifen therapy. They showed 44 times of high estradiol level during follow up period. The serum concentrations of estradiol and FSH were 1047.97638.8pg/mL and 11.57.3 mIu/mL, respectively. The mean duration from the start of the single administration of tamoxifen to the initial detection of a high concentration of estradiol was 666.4+433.1 days. Univariate and multivariate analysis between ovarian hyperstimulation and non-hyperstimulation groups showed younger age(&amp;lt;40years) and only endocrine therapy without chemotherapy were related to higher prevalence of ovarian hyperstimulation significantly. (p &amp;lt;0.001, =0.031 each) Pathologic stages and progesterone receptor expressions on breast tumor were not related to manifestation of ovarian hyperstimulation. Conclusions The Incidence rate and occurrence time of ovarian hyperstimulation associated with adjuvant tamoxifen treatment in breast cancer patients under age 60 were 9.3% and around 2-year after treatment with tamoxifen. Young age under 40 years old and endocrine treatment without chemotherapy were risk factors predicting occurrence of ovarian hyperstimulation during tamoxifen treatment. It should be noted that tamoxifen is a potent inducer of ovarian function and close monitoring of the endocrine parameters during treatment with tamoxifen would be essential. Citation Format: Kim MK, Shin H-c. Tamoxifen induced ovarian hyperstimulation during hormonal therapy for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-13.
Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL)
Authors: Georg Maschmeyer, Julien De Greef, Sibylle C. Mellinghoff, Annamaria Nosari, Anne Thiebaut-Bertrand, Anne Bergeron, Tomas Franquet, Nicole M. A. Blijlevens, Johan A. Maertens
Journal: Leukemia (2019)

A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTOR inhibitors, ruxolitinib, and venetoclax, a detailed review of data available until August 2018 has been conducted, and specific recommendations for prophylaxis, diagnostic and differential diagnostic procedures as well as for clinical management have been developed.
Abstract 15054: Predictive Factors of the Magnitude of Response to Alirocumab Dose Increase in Patients With Dyslipidemia
Authors: Antonio J Vallejo-Vaz, Eli M Roth, G. Kees Hovingh, Michael J Louie, Velichka Valcheva, Desmond E Thompson, Kausik K Ray
Journal: Circulation (2017)

Introduction: Eight ODYSSEY Phase 3 trials allowed for alirocumab dose increase at Week 12 for patients who did not achieve pre-specified LDL cholesterol (LDL-C) levels at Week 8. Objective: To ana...
Abstract 19554: Immediate and Late Outcomes of Pedal-plantar Loop Technique for Revascularization of Below-the-knee Arteries in Patients With Critical Limb Ischemia
Authors: Haewon Jung, Chul-Min Ahn, Young-Guk Ko, Donghoon Choi
Journal: Circulation (2017)

Introduction: Endovascular treatment of below-the knee and below-the-ankle artery disease is challenging, but important for limb salvage in critical limb ischemia. The pedal-plantar loop technique ...
Abstract 17297: 9p21 CAD Risk Allele is Protective Against Calcific Aortic Stenosis
Authors: Muntaser D Musameh, Peter S Braund, Christopher P Nelson, Jay Gracey, Matthew Denniff, John Thompson, Gerry P McCann, Matthew J Bown, David Sprigings, Nilesh J Samani
Journal: Circulation (2014)

The 9p21 locus has emerged as one of the strongest risk variants associated with coronary artery disease (CAD). The risk allele for CAD is also associated with other vascular pathologies, including abdominal aortic aneurysms and intracranial aneurysms. Calcific aortic stenosis (AS) and CAD share some risk factors and histopathologic features. However, a considerable proportion of severe AS patients have no significant CAD, indicating the presence of unique mechanisms underlying each condition. To date only one common genetic variant, rs10455872 in the LPA gene, has been robustly associated with risk of AS. Here we investigated the association of the lead CAD-associated variant (rs1333049) at the 9p21 locus with the risk of AS in 1044 cases and 4527 controls. We also typed the LPA SNP (rs10455872) as a validated variant. All cases had either echo confirmed AS of abnormal valve morphology and peak velocity across the aortic valve of more than 2.5 meters/second, or they had previously undergone surgery for severe AS. We used logistic regression analysis to investigate the additive effect of both variants on risk of AS, adjusting for CAD status. For the LPA locus, we observed the previously reported association of the G allele at rs10455872 with risk of AS (OR 1.23; 95% CI, 1.06 to 1.44, P= 0.008). Interestingly for the 9p21 locus, the CAD associated allele (C) for rs1333049 was associated with a lower risk of AS (OR 0.88; 95% CI, 0.80 to 0.98, P= 0.014). In an additional analysis, we examined the association of rs1333049 with AS in our 1044 cases against an independent set of 828 controls with no history of AS, and the results were consistent with the initial findings (OR 0.76; 95% CI, 0.66 to 0.87, P= 0.0001). This unexpected finding requires further validation, but suggests that the 9p21 locus CAD-associated variant is not uniformly deleterious for other vascular pathologies - and for AS may be protective. If the 9p21 finding is confirmed, then understanding the differential effect of this locus on AS and CAD may help to better understand the specific pathogenesis of each condition.
Active Medical Management for Patients With Advanced Kidney Disease
Authors: Keren Ladin, Alexander K. Smith
Journal: JAMA Internal Medicine (2019)

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Biological Characterization of the U2af1 S34F Mutation in the Pathogenesis of Myelodysplasia
Authors: Ayana Kon, Yasuhito Nannya, Masahiro Nakagawa, Keisuke Kataoka, Masashi Sanada, Manabu Nakayama, Haruhiko Koseki, Seishi Ogawa
Journal: Blood (2018)
Multi-Parametric Single Cell Profiling Defines Distinct Drug Responses in Healthy Hematological Cell Lineages That Are Retained in Corresponding Malignant Cell Types
Authors: Muntasir M Majumder, Maija Leppä, Monica Hellesoy, Paul Dowling, Alina Malyutina, Despina Bazou, Emma Irene Andersson, Alun Parsons, Jing Tang, Olli Kallioniemi, Satu Mustjoki, Peter O'Gorman, Krister Wennerberg, Kimmo Porkka, Bjorn Gjertsen, Caroline A Heckman
Journal: Blood (2018)
<i>Pseudomonas aeruginosa</i> stimulates nuclear sphingosine-1-phosphate generation and epigenetic regulation of lung inflammatory injury
Authors: David L Ebenezer, Evgeny V Berdyshev, Irina A Bronova, Yuru Liu, Chinnaswamy Tiruppathi, Yulia Komarova, Elizaveta V Benevolenskaya, Vidyani Suryadevara, Alison W Ha, Anantha Harijith, Rubin M Tuder, Viswanathan Natarajan, Panfeng Fu
Journal: Thorax (2019)

Introduction Dysregulated sphingolipid metabolism has been implicated in the pathogenesis of various pulmonary disorders. Nuclear sphingosine-1-phosphate (S1P) has been shown to regulate histone acetylation, and therefore could mediate pro-inflammatory genes expression. Methods Profile of sphingolipid species in bronchoalveolar lavage fluids and lung tissue of mice challenged with Pseudomonas aeruginosa ( PA ) was investigated. The role of nuclear sphingosine kinase (SPHK)2 and S1P in lung inflammatory injury by PA using genetically engineered mice was determined. Results Genetic deletion of Sphk2 , but not Sphk1 , in mice conferred protection from PA -mediated lung inflammation. PA infection stimulated phosphorylation of SPHK2 and its localisation in epithelial cell nucleus, which was mediated by protein kinase C (PKC) δ. Inhibition of PKC δ or SPHK2 activity reduced PA -mediated acetylation of histone H3 and H4, which was necessary for the secretion of pro-inflammatory cytokines, interleukin-6 and tumour necrosis factor-α. The clinical significance of the findings is supported by enhanced nuclear localisation of p-SPHK2 in the epithelium of lung specimens from patients with cystic fibrosis (CF). Conclusions Our studies define a critical role for nuclear SPHK2/S1P signalling in epigenetic regulation of bacterial-mediated inflammatory lung injury. Targeting SPHK2 may represent a potential strategy to reduce lung inflammatory pulmonary disorders such as pneumonia and CF.
Abstract 19237: Single Right Ventricle Hearts Had Similar Total and Apical Intraventricular Pressure Gradient/Ventricular Suction/to Single Left Ventricle Hearts From Birth to Post Fontan
Authors: Nassiba Alami Laroussi, Kana Ohno, Nee Khoo, Mrioko Yamada, Edythe Tham, Sachie Shigemitsu, Silvia Goncalvez Villa Alvarez, Keiichi Itatani, Kandice Mah, Ken Takahashi
Journal: Circulation (2016)

Introduction: Single right ventricle (SRV) myocardial fiber architecture may not be efficient in generating ventricular twist, hence ventricular suction. Intraventricular pressure difference (IVPD)...
Abstract 11712: A First Look at Potential Linguistic or Cultural Factors Regarding Bystander CPR Education and Performance in Arab-Americans in Southeastern Michigan
Authors: Ali Shams, Robert Swor
Journal: Circulation (2015)

Introduction: Cultural and community specific barriers were identified as reasons for low bystander CPR/AED rates in minorities. No literature exists that explores this issue in the Arab American population, a large ethnic community in the state. Methods: We performed a cross sectional survey of clients receiving services from ACCESS (Arab Community Center for Economic &amp; Social Services), the largest Arabic nonprofit organization in Michigan, during a 3 month period. The survey was presented verbally or in writing in English/Arabic. The questions were regarding demographics, CPR/AED knowledge, barriers to CPR training, and how best to inform and train respondents. A 5 point Likert scale was used and descriptive statistics are presented. Results: Of 434 potential respondents, 192(44.3%) completed the survey. Respondents were majority female (58%), adult (mean age 37) and first generation immigrant (73.9%). They were low income (66% &lt; $30K/year) and well educated (65% &gt; H.S. education). They were predominantly Muslims (81%), 23.8% lacked English proficiency, and 42% completed the survey in Arabic. About a third (30.4%) had prior CPR training. The vast majority (83.8%) support public CPR education and performance, with 63.1% believing they are currently capable of understanding and implementing CPR instructions given over the phone. Perceived barriers to CPR performance are listed in Table 1. The most common barrier to learning CPR was availability of nearby CPR courses (17.4%). Respondents identified the Internet as their preferred source of information and community centers as their preferred site for CPR training. Conclusions: Members of the Arabic community are aware of the importance of bystander CPR/AED and are willing to learn and perform CPR. Language and female chest exposure are two specific issues to address when designing community specific CPR/AED program. Internet and community center based initiative were preferred sites for educational programs.
Abstract 11695: An Anti-Interleukin-1β Antibody Suppresses Both Angiotensin II-induced Renal Inflammation and Hypertension
Authors: Kenichi Kitamura, Kikuo Isoda, Koji Akita, Yayoi Okabayashi, Tomoyasu Kadoguchi, Kazunori Shimada, Hiroyuki Daida
Journal: Circulation (2017)

Aims: Angiotensin II (AngII) increases arterial pressure and activates components of inflammatory cascade, which promotes development of renal injury. Clinical hypertension is associated with renal inflammation and elevated circulating levels of proinflammatory cytokines. IL-1 receptor antagonist (IL-1Ra) is one of the most important anti-inflammatory cytokines and plays a crucial role in inflammation. Inhibition of IL-1 may contribute to modulation of the AngII-induced hypertension response. This study aimed to elucidate the effects of IL-1Ra and anti-IL-1beta antibody (01BSUR) on AngII-induced hypertension and renal inflammation. Methods and Results: To determine the contrition of IL-1Ra to AngII-induced renal inflammation, male wild-type (WT) (n=8) and IL-1Ra-deficient (IL-1Ra-/-) (n=8) mice were infused with AngII (1000ng/kg/min) using subcutaneous osmotic pumps for 14 days. 14 days after infusion, systolic blood pressure (149±2 vs 126±3 mmHg, p<0.001) in IL-1Ra-/- mice significantly increased compare...
Prominin‐1 Promotes Biliary Fibrosis Associated With Biliary Atresia
Authors: Jessica A. Zagory, Michael Fenlon, William Dietz, Menghan Zhao, Marie V. Nguyen, Pavin Trinh, Maeva Adoumie, Alex Park, Jiabo Xu, Elaa Mahdi, Alison Glazier, Nicolas Malkoff, Nirmala Mavila, Kasper S. Wang
Journal: Hepatology (2019)

In patients with biliary atresia (BA), the extent of intrahepatic biliary fibrosis negatively correlates with successful surgical bypass of the congenital cholangiopathy as well as subsequent transplant‐free survival. We recently linked the expansion of a population of prominin‐1 ( Prom1 )‐expressing hepatic progenitor cells to biliary fibrogenesis. Herein, we hypothesized that Prom1 ‐expressing progenitor cells play a role in BA‐associated fibrosis. Rhesus rotavirus (RRV)‐mediated experimental BA was induced in newborn mice homozygous for the transgene Prom1cre‐ert2‐nlacz , which was knocked in to the Prom1 gene locus, thus creating functional Prom1 knockout (KO) mice, and their wildtype (WT) littermates. Clinical data and tissue samples from BA infants from the Childhood Liver Disease Research Consortium were analyzed. Extrahepatic biliary obliteration was present in both WT and KO mice; there was no difference in serum total bilirubin (TBili) levels. The intrahepatic periportal expansion of the PROM1 pos cell population, typically observed in RRV‐induced BA, was absent in KO mice. RRV‐treated KO mice demonstrated significantly fewer cytokeratin‐19 (CK19)‐positive ductular reactions ( P = 0.0004) and significantly less periportal collagen deposition ( P = 0.0001) compared with WT. RRV‐treated KO mice expressed significantly less integrin‐β6 , which encodes a key biliary‐specific subunit of a transforming growth factor (TGF) β activator ( P = 0.0004). Infants with successful biliary drainage (Tbili ≤1.5 mg/dL within 3 months postoperatively), which is highly predictive of increased transplant‐free survival, expressed significantly less hepatic PROM1 , CK19 , and COLLAGEN‐1α compared with those with TBili &gt;1.5 ( P &lt; 0.05). Conclusion: Prom1 plays an important role in biliary fibrogenesis, in part through integrin‐mediated TGF pathway activation.
Prioritization of <i> <scp>PLEC</scp> </i> and <i> <scp>GRINA</scp> </i> as Osteoarthritis Risk Genes Through the Identification and Characterization of Novel Methylation Quantitative Trait Loci
Authors: Sarah J. Rice, Maria Tselepi, Antony K. Sorial, Guillaume Aubourg, Colin Shepherd, David Almarza, Andrew J. Skelton, Ioanna Pangou, David Deehan, Louise N. Reynard, John Loughlin
Journal: Arthritis & Rheumatology (2019)

Objective To identify methylation quantitative trait loci ( mQTL s) correlating with osteoarthritis ( OA ) risk alleles and to undertake mechanistic characterization as a means of target gene prioritization. Methods We used genome‐wide genotyping and cartilage DNA methylation array data in a discovery screen of novel OA risk loci. This was followed by methylation, gene expression analysis, and genotyping studies in additional cartilage samples, accompanied by in silico analyses. Results We identified 4 novel OA mQTL s. The most significant mQTL contained 9 CpG sites where methylation correlated with OA risk genotype, with 5 of the CpG sites having P values &lt;1 × 10 −10 . The 9 CpG sites reside in an interval of only 7.7 kb within the PLEC gene and form 2 distinct clusters. We were able to prioritize PLEC and the adjacent gene GRINA as independent targets of the OA risk. We identified PLEC and GRINA expression QTL s operating in cartilage, as well as methylation‐expression QTL s operating on the 2 genes. GRINA and PLEC also demonstrated differential expression between OA hip and non‐ OA hip cartilage. Conclusion PLEC encodes plectin, a cytoskeletal protein that maintains tissue integrity by regulating intracellular signaling in response to mechanical stimuli. GRINA encodes the ionotropic glutamate receptor TMBIM 3 (transmembrane BAX inhibitor 1 motif–containing protein family member 3), which regulates cell survival. Based on our results, we hypothesize that in a joint predisposed to OA , expression of these genes alters in order to combat aberrant biomechanics, and that this is epigenetically regulated. However, carriage of the OA risk–conferring allele at this locus hinders this response and contributes to disease development.