tbuckley/cabot-search huggingface dataset:
PF258 REAL‐WORLD DATA ON DOSE‐RELATED EFFECT OF ARSENIC TRIOXIDE IN THE RELAPSE OF ACUTE PROMYELOCYTIC LEUKEMIA
Authors: H. Wang, S. Gong, H. Zhang, X. Zhang
Journal: HemaSphere (2019)

Background: Acute promyelocytic leukemia (APL) has evolved from a highly fatal to a highly curable disease because of all‐trans retinoic acid (ATRA) based regimens. Although the cure rate has been improved with the addition of arsenic trioxide (ATO), the relapse rate is still 1–10%. It is not known whether ATO dosage is related to the relapse rate in real‐world. Aims: This study was designed to elucidate the relationship between the dosage of ATO in post‐remission therapy and relapse rate in APL, and to explore the optimum dosage of ATO. Methods: According to 2019 NCCN guideline, the recommended ATO dosage in post‐remission therapy is 12 mg/kg in low‐risk and 7.95–12 mg/kg in high‐risk APL. 112 patients with newly diagnosed APL, receiving the combination of ATRA and anthracycline‐based chemotherapy and different dose of ATO for variable cycles, were divided into the high‐dose group (ATO dosage ≥12 mg/kg) and low‐dose group (ATO dosage &lt;12 mg/kg). The 4‐year cumulative relapse‐free survival(RFS) was compared. Receiver operating characteristic (ROC) curve was used to determine the cutoff value. Results: Based on the total ATO dosage in post‐remission therapy, 72 (64.3%) patients were in the low‐dose group, whereas 40 (35.7%) patients were in the high‐dose group. There was no significant difference in the baseline characteristics between the two groups. After a median follow‐up time of 53 months, the 4‐year cumulative relapse‐free survival was 83% in the low‐dose group and 100% in the high‐dose group respectively (p = 0.008). ROC analysis indicated if the dose of ATO in post‐remission reached 5.49 mg/kg, the relapse rate had no significant difference with the dose of ATO more than 12 mg/kg ( p &lt; 0.001). In the binary logistic regression analysis, an increased ATO dosage has an independent protective factor in terms of probability of relapse (odds ratio = 0.67, 95%CI, 0.51–0.88, p = 0.004). Age, WBC count, and the occurrence of differentiation syndrome had no relationship with relapse rate (p &gt; 0.05). Summary/Conclusion: The results indicate that the relapse rate of APL is significantly associated with the dosage of ATO in post‐remission therapy. Regardless of low or high‐risk APL, the ATO dosage should be 12 mg/kg or at least more than 5.49 mg/kg. image
Proteomic Architecture of Human Coronary and Aortic Atherosclerosis
Authors: David M. Herrington, Chunhong Mao, Sarah J. Parker, Zongming Fu, Guoqiang Yu, Lulu Chen, Vidya Venkatraman, Yi Fu, Yizhi Wang, Timothy D. Howard, Goo Jun, Caroline F. Zhao, Yongmei Liu, Georgia Saylor, Weston R. Spivia, Grace B. Athas, Dana Troxclair, James E. Hixson, Richard S. Vander Heide, Yue Wang, Jennifer E. Van Eyk
Journal: Circulation (2018)

The inability to detect premature atherosclerosis significantly hinders implementation of personalized therapy to prevent coronary heart disease. A comprehensive understanding of arterial protein networks and how they change in early atherosclerosis could identify new biomarkers for disease detection and improved therapeutic targets.
PB2308 THE EFFECT OF SICKLE CELL DISEASE ON PREGNANCY IN AL‐AHSA, KSA 2012‐2017
Authors: S. Abdulrahman, E. Alsaleh, S. Algadeeb, J. Algadeeb, M. Algadeeb, R. algadeeb
Journal: HemaSphere (2019)

Background: Pregnant women with SCD are at an increased risk for maternal and fetal morbidity and mortality (1,2). The numerous potential maternal complications include anaemia, acute crisis, preeclampsia, eclampsia, urinary tract infection, pneumonia, and acute chest syndrome (3,4,5,6). In addition, Pregnant women with SCD had lower maternal weight and gestational weight gain (7,8). Aims: The aim of this study was to compare the pregnancy outcomes between pregnant women with Sickle Cell Disease and pregnant women without Sickle Cell Disease and to measure the difference in weight gain between two groups. Methods: A quantitative retrospective cohort study carried out between January 2012 and December 2017 in Maternal and Children Hospital and Primary Health Care centres in Al‐Ahsa, an eastern region of the Kingdom of Saudi Arabia (KSA). The study population included all SCD patients who were registered for antenatal care follow up in the MCH and, on the other side, pregnant women without SCD from the primary health care centres depending on inclusion and exclusion criteria. The total sample size was 429. One hundred forty‐three pregnant women with Sickle Cell at the Maternity and Children Hospital and 286 pregnant non‐Sickle Cell from PHCCs were recruited by matching in residency. The data collection sheet used to gather patient information was prepared based on the card of antenatal care in the Ministry of Health and literature review. Results: Weight, BMI, and haemoglobin level at the first antenatal visit showed a significant difference between the two groups (P &lt; 0.001). Forty‐three present of women with SCD had cesarean sections, compared to 13.9% of women without SCD, and there was a statistically significant association between them (P &lt; 0.001). Maternal weight gain was lower in women with Sickle Cell Disease and showed statistically significant (P &lt; 0.001). Women with Sickle Cell Disease had an increased risk of Caesarean section (AOR = 3.807, 95%CI = 2.074‐6.987, P &lt; 0.001). Summary/Conclusion: Women with Sickle Cell Disease are more likely to have adverse pregnancy outcomes compared to women without Sickle Cell Disease. Women with Sickle Cell Disease had lower weight gain during pregnancy.
Blocking CD30 on T Cells by a Dual Specific CAR for CD30 and Colon Cancer Antigens Improves the CAR T Cell Response against CD30− Tumors
Authors: Andreas A. Hombach, Gunter Rappl, Hinrich Abken
Journal: Molecular Therapy (2019)

Chimeric antigen receptor (CAR)-engineered T cells are efficacious in controlling advanced leukemia and lymphoma, however, they fail in the treatment of solid cancer, which is thought to be due to insufficient T cell activation. We revealed that the immune response of CAR T cells with specificity for carcinoembryonic antigen (CEA) was more efficacious against CEA+ cancer cells when simultaneously incubated with an anti-CD30 immunotoxin or anti-CD30 CAR T cells, although the targeted cancer cells lack CD30. The same effect was achieved when the anti-CD30 single-chain variable fragment (scFv) was integrated into the extracellular domain of the anti-CEA CAR. Improvement in T cell activation was due to interfering with the T cell CD30-CD30L interaction by the antagonistic anti-CD30 scFv HRS3; an agonistic anti-CD30 scFv or targeting the high-affinity interleukin-2 (IL-2) receptor was not effective. T cells with the anti-CD30/CEA CAR showed superior immunity against established CEA+ CD30- tumors in a mouse model. The concept is broadly applicable since anti-CD30/TAG72 CAR T cells also showed improved elimination of TAG72+ CD30- cancer cells. Taken together, targeting CD30 on CAR T cells by the HRS3 scFv within the anti-tumor CAR improves the redirected immune response against solid tumors.
Abstract P267: Brain Health and Ideal Cardiovascular Health. The Polish Norwegian Study (PONS)
Authors: Georgeta Vaidean, Marta Manczuk
Journal: Circulation (2018)

Introduction: The relation between brain- and cardiovascular health has been mainly described through cognitive function. Less is known about the relation of ideal cardiovascular health (CVH) and other brain health characteristics. Hypothesis: We assessed the hypothesis that cardiovascular health is associated with brain health constructs: depressive symptoms, sleep quality and duration, self-rated health. As an additional exposure we investigated excessive TV watching, considered an addictive behavior. Methods: We used cross-sectional, baseline data of 10687 participants, age 45 to 64 years free of cardiovascular diseases in an ongoing cohort study (PONS). Data were collected through structured questionnaires and fasting blood samples. Ideal CV health was defined according to the American Heart Association criteria (7 metrics assessed at 3 levels: ideal, intermediate, and poor). Brain health was assessed as: 1) depressive mood (PHQ questionnaire, scale 0-7); 2) sleep hours; 3) self-rated overall health (SRH) (1 item, on a scale from 1 to 10); 4) hours watching TV. We used multivariable logistic models and adjusted for age, sex, education, place of residence, antidepressant medication use and past depressive episodes. Results: The prevalence of poor CVH (0-2 ideal metrics) was 63% and of ideal CVH (6, 7 ideal metrics) was 0.07%. Reporting 4 or more current depressive symptoms was associated with poor CVH (OR, 95%CI 1.13, 1.02-1.27) after multivariable adjustment. The relation was mainly driven by somatic affective rather than cognitive affective depressive symptoms. Difficulties falling asleep or sleep duration were not associated with CVH after controlling for depression. Watching TV more than 20h/week was associated with poor CVH (OR 1.40, 95% 1.27-1.55) after multivariable adjustment. A SRH score of 6 or lower was associated with poor CVH (OR 1.33, 95% CI 1.22-1.46) after multivariable adjustment. We observed similar relations in a sensitivity analysis after excluding those taking current antidepressant medication. Conclusion: In this community-based study we found that there is a moderate association between poor cardiovascular health and current depressive symptoms, independent of past depression episodes or antidepressant treatment. In addition to Life’s Simple 7, monitoring depressive symptoms, sleep, self-rated-health and/or addictive TV-watching may benefit both brain- and heart wellness.
Contact Lens Technology: From Fundamentals to Applications
Authors: Rosalia Moreddu, Daniele Vigolo, Ali K. Yetisen
Journal: Advanced Healthcare Materials (2019)

Abstract Contact lenses are ocular prosthetic devices used by over 150 million people worldwide. Primary applications of contact lenses include vision correction, therapeutics, and cosmetics. Contact lens materials have significantly evolved over time to minimize adverse effects associated with contact lens wearing, to maintain a regular corneal metabolism, and to preserve tear film stability. This article encompasses contact lens technology, including materials, chemical and physical properties, manufacturing processes, microbial contamination, and ocular complications. The function and the composition of the tear fluid are discussed to assess its potential as a diagnostic media. The regulatory standards of contact lens devices with regard to biocompatibility and contact lens market are presented. Future prospects in contact lens technology are evaluated, with particular interest given to theranostic applications for in situ continuous monitoring the ocular physiology.
AB0807 FOLLOW-UP OF PATIENTSWITH HIP OSTEOARTHRITIS WHO RECEIVED VISCOSUPPLEMENTATION: HOW NEW TECHNOLOGIES CAN HELP
Authors: Mariaeva Romano, Laura Belloli, Elisa Verduci, Cinzia Casu, Valeria Campanella, Marina Muscarà, Davide Antonio Filippini, Emanuela Schito, Maria DI Cicco, Oscar Massimiliano Epis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Digital health innovations have opened up several opportunities to help patients with rheumatologic conditions and their treating clinicians in improving routine healthcare. <h3>Objectives</h3> To evaluate the applicability of a wearable smartwatch for monitoring patients with hip osteoarthritis who received viscosupplementation. Samsung Electronics Italia and MDApp srl supported the present study. <h3>Methods</h3> Consecutive patients with hip osteoarthritis who received viscosupplementation with jaluronic acid between November 2017 and May 2018 were enrolled in this observational study. All patients gave their informed consent. A Samsung Gear smartwatch was given to each patient and was worn during the day for measuring daily steps, walking distance, and mean velocity. Patients were asked to wear the smartwatch starting from one week before infiltration (T0), until two weeks before (T1). Patients were assessed with Lequesne index and WOMAC score at T0 and T1. <h3>Results</h3> Overall, 24 patients (7 male and 17 female, mean age 44 years-old) were enrolled. Of these, 70% has worn the smartwatch for most of the time (range 90-100%). An improvement of velocity (45%), an increase of daily steps (29%), and walking distance (25%) were seen. Similarly, Lequesne index and WOMAC score were consistent with subjective improvement. Most of the patients (95%) declared to be satisfied with this digital health study. <h3>Conclusion</h3> Samsung smartwatches proved to be an effective tool for tracking and recording medical parameters linked with perceived general health. Health technologies are more than an accessories and could be useful in chronic musculo-skeletal diseases because they allow to ease remote diagnosis and to monitor patients’ symptoms and clinical response. Telemedicine could fill the gap between patients and healthcare, with a reproducible and objective tool, enhancing patients’ engagement with the treatment plan. The high patients’ satisfaction further support the use of digital health technology. <h3>Reference</h3> [1] Kataria S, Digital Health: a new dimension in rheumatology patient care. Rheumatol Int. 2018 <h3>Disclosure of Interests</h3> Mariaeva Romano Speakers bureau: janssen, Laura Belloli: None declared, Elisa Verduci: None declared, Cinzia Casu: None declared, Valeria Campanella: None declared, Marina Muscarà: None declared, Davide Antonio Filippini: None declared, Emanuela Schito: None declared, Maria Di Cicco: None declared, Oscar Massimiliano Epis Speakers bureau: BMS
Postnatal Alveologenesis Depends on FOXF1 Signaling in c-KIT<sup>+</sup> Endothelial Progenitor Cells
Authors: Xiaomeng Ren, Vladimir Ustiyan, Minzhe Guo, Guolun Wang, Craig Bolte, Yufang Zhang, Yan Xu, Jeffrey A. Whitsett, Tanya V. Kalin, Vladimir V. Kalinichenko
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Disruption of alveologenesis is associated with severe pediatric lung disorders, including bronchopulmonary dysplasia (BPD). Although c-KIT
AB0279 RENAL INVOLVEMANT AND CAUSES OF DEATH IN RHEUMATOID ARTHRITIS PATIENTS ACCORDING TO THE AUTOPSY DATA
Authors: Anastasia Tushina, Natalia Dostanko, Viktor Yagur, Nikolaj Soroka, Viktoria Dostanko
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Renal involvement is a clinically significant manifestation in rheumatoid arthritis (RA) patients with potential influence on the treatment, prognosis and outcome of this disease while rare publications are available on kidney damage in RA [1,2]. <h3>Objectives</h3> To estimate the frequency and characteristics of renal involvement and causes of death in RA patients on the basis of autopsy data reports and postmortem microscopic examinations. <h3>Methods</h3> We have analyzed 21 814 autopsy data reports performed during 10-year period (2001-2010) and 6720 cases of autopsy performed 5 years later (2016-2018) in the Minsk City Clinical Pathologoanatomic Bureau (The Republic of Belarus). <h3>Results</h3> For the period 2001-2010 autopsies were performed in 110 RA patients: 91 women and 19 men of 67.0 (13.1) years old, M (SD). Renal involvement was revealed in 75 patients (68.2%). The most common type of renal involvement was secondary AA amyloidosis - 44 patients (40%). Other types of revealed renal lesions (n=31, 28.2%) were mesangial proliferative glomerulonephritis (n=3; 2.7%), nephroangiosclerosis (n=14, 12.8%), tubulointerstitial nephritis (n=2, 1.8%), chronic pyelonephritis (n=10, 9.1%) and renal vessel vasculitis (n=2, 1.8%). The main cause of death in RA patients with amyloidosis was end-stage renal disease (ESRD, 43.2%), whereas in other patients the common causes of death were cardiovascular events (43.2%) and secondary infections (33.3%). In case of secondary amyloidosis the deposits of amyloid were found in kidney of all RA patients (100%), in adrenal glands – in 36.4% and in spleen – in 34.1% of RA patients. Amyloid deposits in other internal organs were not nearly as common. In 2016-2018 50 patients with RA have been autopsied with mean age of death 72.0 (15.2) years old. Renal involvement was revealed in 34 (68.0%) of autopsies: as secondary amyloidosis in 29 patients (58.0%) and as focal segmental glomerulosclerosis or mesangial proliferative glomerulonephritis in 5 patients (10.0%). The most common cause of death in this group of RA patients were cardiovascular events (58.0%), fatal infectious complications developed in 16.0% of patients, ESRD was revealed only in 4.0% of patients. <h3>Conclusion</h3> 1. We have revealed an increase in secondary amyloidosis frequency in RA patients over the studied period of time from 40% to 58% (p=0.041, Fisher's exact test) while ESRD as a cause of death in RA patients decreased from 17.3% to 4% (p=0.023, Fisher's exact test). 2. Secondary amyloidosis is the most common type of renal involvement in RA according to the autopsy data. <h3>References</h3> [1] Makino H. et al. //Mod. Rheumatol. 2002;12(2):148-54. [2] Icardi A. et al. //Reumatismo. 2003;55(2):76-85. <h3>Disclosure of Interests</h3> None declared
Unique cardiac phenotype in ALPK3-related disease: Progression from dilated cardiomyopathy to hypertrophic cardiomyopathy
Authors: Johanna C. Herkert, Judith M. Verhagen, Dean G. Phelan, Paul A. James, Natasha J. Brown, Chloe Stutterd, Ivan Macciocca, Anu Aggarwal, Bert Timmer, Marion L. Bulthuis, Yolande Van Bever, Amy E. Roberts, Christine E. Seidman, Neal K. Lakdawala, Michael A. Burke, Mary Ella Pierpont, Irene M. Van Langen, Jan D. Jongbloed, Paul J. Lockhart, David J. Amor, Ingrid M. Van De Laar
Journal: Circulation (2018)

Introduction: Biallelic truncating variants in ALPK3 have recently been described to cause pediatric cardiomyopathy (CMP). Functional studies have found disorganized intercalated discs and sarcomeres and calcium mishandling in both patients and mutant stemcellderived cardiomyocytes. Objectives: To delineate the clinical and genetic spectrum of ALPK3related disease and study genotypephenotype correlations. Methods: We collected clinical and genetic data on ALPK3related CMP patients, and performed ALPK3 staining in heart and skeletal muscle of 3 individuals carrying biallelic truncating variants. Results: We report biallelic ALPK3 mutations for a total of 18 patients: 9 previously reported cases and 9 novel patients from 6 families. Nine patients had biallelic truncating variants, 7 had a truncating and a missense variant, and 1 had a homozygous missense variant in ALPK3. Nine of 16 liveborn patients showed (biventricular) DCM during neonatal life that transitioned to predominantly HCM with surveillance. Several patients showed extracardiac features, including short stature (8/13), contractures (6/15), severe scoliosis (5/12), cleft palate (CP) or velopharyngeal insufficiency (5/15), and dysmorphic (Noonanlike) facies (8/14). Biopsy of 4 patients showed focal cardiomyocyte hypertrophy, subendocardial fibroelastosis <4 years of age, and myofibrillar disarray at adult age. ALPK3 staining confirmed its nuclear expression in heart and skeletal muscle, but no differences were observed between patients and controls. Mutations predominantly cluster in exon 6 and the alphakinase domain. No association between mutation type or location and disease severity was observed. Conclusion: Although it has been previously shown that HCM may progress to DCM, we describe a unique cardiac phenotype of DCM transitioning to predominantly HCM. We extend the ALPK3 phenotype to include CP and contractures, however no genotypephenotype correlation could be established. Alpk3 mice displayed a similar cardiac phenotype, but did not show fibrosis or extracardiac features. Expression of a truncated ALPK3 protein in humans may explain the differences in clinical manifestation between the patients and Alpk3 mice that do not produce ALPK3 protein.
Restoration of TFPI-2 in a human glioblastoma cell line triggers caspase mediated pathway and apoptosis
Authors: Joseph George, Christopher Gondi, Dzung Dinh, Meena Gujrati, Jasti Rao
Journal: Cancer Research (2007)

3661  The induction of apoptotic pathways in cancer cells offers a novel and potentially useful approach to improve patient responses to conventional chemotherapy. Tissue factor pathway inhibitor-2 (TFPI-2) is a protease inhibitor that is abundant in the extracellular matrix (ECM) and highly expressed in non-invasive cells, but absent or undetectable in highly invasive human glioblastoma cells. Using a recombinant adeno-associated viral vector carrying human TFPI-2 cDNA (rAAV-TFPI-2), we stably expressed TFPI-2 in U-251 cells, a highly invasive human glioblastoma cell line. Our previous studies demonstrated that restoration of TFPI-2 in glioblastomas effectively prevents cell proliferation, angiogenesis and tumor invasion. In the present study, we determined whether TFPI-2 restoration could induce apoptosis through the caspase mediated signaling pathway. The results of caspase 9 and caspase 3 activity assays showed increased activity, which indicates enhanced apoptosis. Immunofluorescence for cleaved caspase 9 and 3 depicted increased expression and co-localization of both molecules. Western blot analysis demonstrated increased transcriptional activities of FasL, TNF-α, BAX, FADD and TRADD, as well as elevated levels of cleaved caspases and PARP. Semiquantitative RT-PCR depicted increased expression of TNF-α and FasL and the related death domains, TRADD and FADD. Taken together, these results demonstrate that restoration of TFPI-2 activates both intrinsic and extrinsic caspase-mediated, pro-apoptotic signaling pathways and induces apoptosis in U-251 cells. Furthermore, our study suggests that rAAV-mediated gene expression offers a novel and potential tool for cancer gene therapy.