tbuckley/cabot-search huggingface dataset:
Abstract 19248: Endothelial Overexpression of LOX-1 Protects From in vivo Arterial Thrombosis and Modulates Oct-1 and SIRT1 Expression
Authors: Alexander Akhmedov, Giovani G Camici, Simona Stivala, Erik W Holy, Alexander Breitenstein, Christine Lohmann, Francesco Paneni, Juerg-Hans Beer, Felix C Tanner, Christian M Matter, Thomas F Luescher
Journal: Circulation (2013)

Background: The hallmark of the initiation of atherosclerotic lesion is foam cell formation, and oxidized LDL (oxLDL) is believed to play a key role in the initiation of the atherosclerotic process. OxLDL is internalized by several receptors, such as SR-AI/II, SR-BI, CD36, and CD68. OxLDL is also internalized by EC, but this uptake depends on receptors other than the classic scavenger receptors. In 1997, a lectin-like oxidized LDL receptor-1 (LOX-1, OLR1) was identified in bovine aortic endothelial cells. LOX-1 is a type II membrane glycoprotein with an apparent molecular weight of 50 kDa. It has a C-terminal extracellular C-type lectin-like domain. This lectin-like domain is essential for binding to oxLDL. Binding of oxLDL to LOX-1 induces several cellular events in endothelial cells, such as activation of transcription factor NF-kB, upregulation of MCP-1, and reduction in intracellular NO, which may trigger the onset of cardiovascular events. Methods and Results: We generated endothelial-specific LOX-1 transgenic mice using the Tie2 promoter ( LOX-1TG ). 12-wk-old male LOX-1TG and wild-type (WT) mice were applied for carotid artery thrombosis model. LOX-1TG mice developed carotid artery thrombosis within a mean occlusion time of 36.96±4.83 min, while WT mice occluded within a mean time period of 22.75±3.87 min (n=10, P &lt; 0.05). Initial blood flow in carotid artery did not differ between both groups. Decreased occlusion time in LOX-1TG mice was further associated with decreased tissue factor expression and surface activity as shown by qPCR and ELISA. Furthermore, LOX-1TG mice showed increased mRNA and protein expression of transcription factor Oct-1 and histone deacetylase SIRT1 in carotid artery, pointing out that Oct-1 and SIRT1 both may be involved in the observed downregulation of tissue factor through its known target NF-kB. Indeed, in vivo knockdown of either Oct-1 or SIRT1 by siRNA further confirmed their role in arterial thrombosis. Conclusions: Thus, our data suggest that LOX-1 plays a protective role in the arterial thrombosis and that both Oct-1 and SIRT1 are involved representing new LOX-1-mediating signaling pathway. Hence, modulation of LOX-1 may represent novel therapeutic options for targeting arterial thrombosis.
A novel humanized anti-CTLA-4 antibody compared to ipilimumab in preclinical studies.
Authors: Qian Shi, YanLi Liu, Lan Yang, Hongli Ma, Wencui Ma, Ziyong Sun
Journal: Journal of Clinical Oncology (2019)

32 Background: The efficacy of ipilimumab as a single agent and in combination for the treatment of melanoma and other malignancies has validated the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) blockade in immunotherapy. Clinical trials that include anti-CTLA-4 in a combination design have gained traction. However, ipilimumab is the only anti-CTLA-4 antibody therapeutic approved worldwide. Therefore, novel anti-CTLA-4 therapeutics that may overcome the shortcomings of ipilimumab to fulfill the unmet medical needs is desperately desired. Methods: Mouse hybridoma cells were screened, cloned, and lead antibodies were humanized to obtain candidates with high activity in blocking CTLA-4/CD80 interaction. The resulting lead antibody was further characterized with in vitro binding and blocking assays, as well as mixed lymphocyte reaction assay. A humanized CTLA-4-B6 mouse model was used to evaluate the in vivo tumor growth inhibition activity of the antibody. Results: CBT-509, a novel IgG1 humanized monoclonal antibody against CTLA-4 was obtained. EC50 of CBT-509 binding with CTLA-4 and IC50 of CBT-509 blocking CTLA4/CD80 interaction were comparable to ipilimumab. CBT-509 binds to a distinct epitope, and has a high affinity with CTLA-4 (KD = 2.73E-10 M), more than 4-fold stronger than ipilimumab (KD = 1.21E-9 M). Compared with ipilimumab, CBT-509 was more active in mixed lymphocyte reaction, suggesting that it is more potent in human T-cell activation. Importantly, the efficacy of CBT-509 in killing tumor cells in vivo is much stronger than that of ipilimumab. In a MC38 murine colorectal cancer model under huCTLA-4 B6 mice background, CBT-509 eradicated tumors in 7 of 8 mice at a dose of 3 mg/kg, while ipilimumab eradicated tumors in 4 of 8 mice at the same dosage. Conclusions: Taken together, CBT-509 demonstrated an improvement over ipilimumab. Future efforts will focus on developing molecules that can further improve the efficacy and safety of anti-CTLA-4 based therapeutics.
A Wearable Paper‐Based Sweat Sensor for Human Perspiration Monitoring
Authors: Marc Parrilla, Tomàs Guinovart, Jordi Ferré, Pascal Blondeau, Francisco J. Andrade
Journal: Advanced Healthcare Materials (2019)

The fabrication and performance of a wearable paper-based chemiresistor for monitoring perspiration dynamics (sweat rate and sweat loss) are detailed. A novel approach is introduced to measure the amount of aqueous solution in the order of microliters delivered to the sensor by monitoring a linear change in resistance along a conducting paper. The wearable sensor is based on a single-walled carbon nanotubes and surfactant (sodium dodecylbenzenesulfonate) nanocomposite integrated within cellulose fibers of a conventional filter paper. The analytical performance and the sensing mechanism are presented. Monitoring sweat loss in the human body while exercising is demonstrated using the integration of a wireless reader and a user-friendly interface. By addressing the barriers of cost, simplicity, and the truly in situ demanding measurements, this unique wearable sensor is expected to serve in the future in many different applications involving the on-body detection of biofluids, such as a monitoring tool of dehydration levels for athletes as well as a tool for enhancing the sport performance by providing an accurate recovery of the hydration status in daily exercises.
Роль ротавірусної інфекції, що потребує лікування в стаціонарних умовах, при діарейному синдромі у дітей
Authors: Yu.Yu. Stepanova, O.L. Kryvusha, L.L. Petrenko
Journal: GASTROENTEROLOGY (2013)

Метою даної роботи було вивчення прогностичного та діагностичного значення деяких клініко-біологічних факторів у процесі розвитку ротавірусної інфекції у дітей. Під спостереженням перебувала 161 дитина віком від 1 місяця до 6 років. У 81 дитини було діагностовано ротавірусну інфекцію, а у 80 — секреторну діарею невстановленої етіології. Лікування дітей проводилося в умовах стаціонару. Аналіз клінічних та анамнестичних даних дозволив обрати найбільш прогностично і діагностично вагомі предиктори з 117 вивчених факторів ризику. Авторами вивчена кореляція клініко-біологічних факторів та тяжкості ротавірусної інфекції, що дозволить виділити групи ризику дітей із підвищеною вірогідністю розвитку ротавірусної інфекції, яка потребує лікування в стаціонарних умовах. Практичним застосуванням результатів проведеної роботи має стати оптимізація ранньої діагностики ротавірусних інфекцій і своєчасне проведення профілактичних заходів.
Association analysis of polymorphisms in genes related to sunitinib pharmacokinetics.
Authors: Meta Diekstra, Heinz Josef Klümpen, Martijn P. J. K. Lolkema, Huixin Yu, Jacqueline S.L. Kloth, Hans Gelderblom, Ron H.N. van Schaik, Howard Gurney, Jesse J Swen, Alwin D.R. Huitema, Neeltje Steeghs, Ron H.J. Mathijssen
Journal: Journal of Clinical Oncology (2013)

4580 Background: Sunitinib is approved as systemic therapy for mRCC, GIST and pNET. Interpatient variability in the pharmacokinetics (PK) of sunitinib is high, which may have serious consequences for efficacy and toxicity of the drug. The objective of this study was to evaluate whether polymorphisms in candidate genes involved in sunitinib metabolism are related to the PK of sunitinib and its active metabolite SU12662. Methods: In this multicenter study, steady state sunitinib plasma concentrations and genotypes were prospectively obtained from 115 patients. Single nucleotide polymorphisms (SNPs) and haplotypes in 8 genes encoding CYP1A1, CYP3A4, CYP3A5, ABCB1, ABCG2, NR1I2, NR1I3, and PORwere evaluated as covariates in a population pharmacokinetic model describing both sunitinib and SU12662 PK using NONMEM. First, candidate genotypes/haplotypes were individually tested for a potential association with sunitinib or SU12662 clearance. Next, potential significant SNPs (p&lt;0.05) were simultaneously included in a multivariate model and tested by backward elimination with a significance threshold of p&lt;0.0005. Results: Four out of 37 screened genotypes (from 14 different SNPs) were related to sunitinib clearance (CYP3A4*22 CC and CT, CYP3A5*3 GG, and ABCB1 (2677 TT)). CYP3A5*3 AG genotype was associated with clearance of SU12662. In the multivariate analysis, none of the SNPs reached the predefined significance threshold of p&lt;0.0005. Nevertheless, CYP3A4*22T allele carriers showed a 22.5% decreased clearance of sunitinib (p&lt;0.01). Conclusions: Our data suggest that individual SNPs or haplotypes in CYP1A1, CYP3A4, CYP3A5, ABCB1, ABCG2, NR1I2, NR1I3 and POR are not clearly associated with sunitinib or SU12662 clearance. Several (environmental) factors may also influence the PK of sunitinib. Interestingly, the recently identified CYP3A4*22 SNP potentially has an impact on drug exposure. Replication studies in larger groups of patients are needed to verify the role of CYP3A4*22 for sunitinib clearance.
Correlation between anthropometric, pathologic data, and 21-gene recurrence score assay in early-stage breast cancer.
Authors: Keith Ian Quintyne, Bernie Woulfe, Linda Coate, Rajnish K. Gupta
Journal: Journal of Clinical Oncology (2013)

1591 Background: Obesity or body mass index (BMI) &gt; 30kg/m 2 is a grave public health concern. Poorer outcome has been documented in obese breast cancer patients. We report the use of the Oncotype Dx Recurrence Score (RS) assay and its correlation with BMI and pathologic data. Methods: Study period: 01/09/08 – 31/05/12. Data was derived from: MWCC database; pathology reports; patient files; RS reports. Statistical analysis was carried out using R. Results: 89 patients were found. Median follow-up: 21.4 months. See Table for data. Conclusions: For this cohort: A skewed pattern in RS assay scores was observed in obese patients, where there were more intermediate and high scores, although this was not significant in multivariate model; tumour size and grade were shown to correlate with the RS assay results; these findings are thought-provoking and certainly can augment to the accruing energy balance data that has been increasingly of interest in oncological research. [Table: see text]
Prevalence and outcomes of cancers in Ekiti State, southwest Nigeria.
Authors: Oluwole Adeyemi Babatunde, Olusegun Elijah Elegbede, Majekodunmi Lawrence Ayodele, Sunday David Abidoye
Journal: Journal of Clinical Oncology (2013)

e12553 Background: There is an increase in the prevalence of cancer in Nigeria with a change in disease pattern from predominantly infectious to one with both communicable and non-communicable diseases. This study was carried out to determine the prevalence and outcomes of cancers in Ekiti State, Nigeria. Methods: This was a review of the data on patients diagnosed with cancers in Ekiti State as recorded in the database of the Cancer Registry of the Federal Medical Centre, Ido Ekiti between 2007 and 2012. The data was obtained from the cancer registry of the hospital and analysed with SPSS version 15 using descriptive statistics. Results: There were 612 diagnosed cancer patients on record in the cancer registry within the five-year period under review. Most (67.6%) were females, 97.1% belonged to the Yoruba ethnic group, 93.5% were Christians, and 86.6% were married while 13.2% were single and 0.2% were separated. The site most commonly affected was the breast (14.6%) followed by the prostate gland (14.1%), cervix (6.9%), ovary (6.8%), uterus (3.1%) and the stomach (1%). Also, the commonest morphological type of cancer seen was adenocarcinoma (8.5%). The highest levels of education were tertiary, secondary and primary education for 47.4%, 30.2% and 15.2% of the patients respectively while 7.2% had no formal education. Of all the patients seen, 85.3% were symptomatic and 14.7% were not while 79.7% were alive, 2.1% dead and the outcome for 7.6% of the patients was unknown at the time of this survey. Conclusions: The prevalence of cancer is increasing with many of the patients not being able to afford the drugs for treatment. More needs to be done by all stakeholders to encourage early screening and diagnostic measures, reduce exposure to risk factors for cancers and subsidize or waive treatment costs for patients.
Association Between Heart Failure and Postoperative Mortality Among Patients Undergoing Ambulatory Noncardiac Surgery
Authors: Benjamin J. Lerman, Rita A. Popat, Themistocles L. Assimes, Paul A. Heidenreich, Sherry M. Wren
Journal: JAMA Surgery (2019)

<h3>Importance</h3> Heart failure is an established risk factor for postoperative mortality, but how heart failure is associated with operative outcomes specifically in the ambulatory surgical setting is not well characterized. <h3>Objective</h3> To assess the risk of postoperative mortality and complications in patients with vs without heart failure at various levels of echocardiographic (left ventricular systolic dysfunction) and clinical (symptoms) severity who were undergoing ambulatory surgery. <h3>Design, Setting, and Participants</h3> In this US multisite retrospective cohort study of all adult patients undergoing ambulatory, elective, noncardiac surgery in the Veterans Affairs Surgical Quality Improvement Project database during fiscal years 2009 to 2016, a total of 355 121 patient records were identified and analyzed with 1 year of follow-up after surgery (final date of follow-up September 1, 2017). <h3>Exposures</h3> Heart failure, left ventricular ejection fraction, and presence of signs or symptoms of heart failure within 30 days of surgery. <h3>Main Outcomes and Measures</h3> The primary outcomes were postoperative mortality at 90 days and any postoperative complication at 30 days. <h3>Results</h3> Among 355 121 total patients, outcome data from 19 353 patients with heart failure (5.5%; mean [SD] age, 67.9 [10.1] years; 18 841 [96.9%] male) and 334 768 patients without heart failure (94.5%; mean [SD] age, 57.2 [14.0] years; 301 198 [90.0%] male) were analyzed. Compared with patients without heart failure, patients with heart failure had a higher risk of 90-day postoperative mortality (crude mortality risk, 2.00% vs 0.39%; adjusted odds ratio [aOR], 1.95; 95% CI, 1.69-2.44), and risk of mortality progressively increased with decreasing systolic function. Compared with patients without heart failure, symptomatic patients with heart failure had a greater risk of mortality (crude mortality risk, 3.57%; aOR, 2.76; 95% CI, 2.07-3.70), as did asymptomatic patients with heart failure (crude mortality risk, 1.85%; aOR, 1.85; 95% CI, 1.60-2.15). Patients with heart failure had a higher risk of experiencing a 30-day postoperative complication than did patients without heart failure (crude risk, 5.65% vs 2.65%; aOR, 1.10; 95% CI, 1.02-1.19). <h3>Conclusions and Relevance</h3> In this study, among patients undergoing elective, ambulatory surgery, heart failure with or without symptoms was significantly associated with 90-day mortality and 30-day postoperative complications. These data may be helpful in preoperative discussions with patients with heart failure undergoing ambulatory surgery.
Impact of oncology drug shortages on patient treatment.
Authors: Daniel Jacob Becker, Sumit Talwar, Benjamin Levy, Molly Thorn, Janna Roitman, Ronald H. Blum, Louis Benjamin Harrison, Michael L. Grossbard
Journal: Journal of Clinical Oncology (2012)

6114 Background: Cancer drug shortages increased considerably over the past 5 years, but quantitative analyses of the scope and effects are limited. We assessed the effects of drug shortages on outpatient medication use in a single New York City university hospital. Methods: We examined pharmacy records for drug shortages, defined by the ASHP as supply issues that affect “how the pharmacy prepares or dispenses a drug product or influences patient care when prescribers must use an alternative agent.” We examined outpatient records for all cancer patients treated with infusional antineoplastic and/or supportive medications from 4/2010-9/2010 and from 4/2011-9/2011, and performed subgroup analysis on Aug/Sept 2011, the peak of medication availability problems at our hospital. We compared proportions of patients treated with specific medications in 2010 and 2011 with Pearson’s chi-square test. Results: Twelve medications were in shortage during the study period in 2010 and 22 in 2011. Between 4/1/10 and 9/30/10, 335 cancer patients were treated, and 379 patients were treated between 4/1/11 and 9/30/11. Median patient age was 60 years. Cancer site of origin was comparable between years: breast (40%), GI (15%), lymphoma (10%), GU (8%), and lung (7%). Drugs considered in shortage were used for 170 (50.8%) patients in 2010 and 241 (63.6%) patients in 2011 (p=0.0005). Of 235 patients treated in Aug/Sept 2011, there were 23 (9.8%) documented therapy changes due to shortages, compared with 0 changes among 211 patients treated in Aug/Sept 2010 (p&lt;0.0001). Among patients treated in Aug/Sept 2010 24 (11.4%) patients received paclitaxel and 19 (9.0%) received docetaxel. Among patients treated in Aug/Sept 2011, 11 (4.7%) received paclitaxel and 38 received docetaxel (16.2%), a 69% decrease for paclitaxel and 80% increase for docetaxel from 1 year prior (p=0.009, and p=0.024, respectively). The estimated cost of a single treatment with paclitaxel for 1 patient with BSA 1.75 was $47.59 versus $858.39 for docetaxel, a 1704% increase. Conclusions: Oncology drug shortages affected the majority of patients in our center and increased at an alarming rate. Drug shortages have substantial economic costs and mandate treatment changes that may affect efficacy and toxicity.
The Renin-Angiotensin System
Authors: Suzanne Oparil, Edgar Haber
Journal: New England Journal of Medicine (1974)

Plasma Renin Activity as a Screening Procedure in HypertensionTwo approaches to the use of peripheral plasma renin activity as a screening test for hypertensive disease have been taken: to hospitalize the patient and impose strict control of dietary sodium in an effort to be able to relate his response to a rigidly defined set of normal criteria; and to allow the patient to remain ambulatory and on an ad lib sodium intake and rely on his 24-hour urinary sodium excretion to normalize his response. Stimulation or suppression tests give more information about the patient's renin reserve and the responsiveness . . .
Reply - Re: van Dijk et al.: Half-dose photodynamic therapy versus high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy: the PLACE trial (Ophthalmology. 2018;125:1547-1555)
Authors: E.H.C. van Dijk, S. Fauser, M.B. Breukink, R. Blanco-Garavito, J.M.M. Groenewoud, J.E.E. Keunen, P.J.H. Peters, G. Dijkman, E.H. Souied, R.E. Maclaren, G. Querques, S.M. Downes, C.B. Hoyng, C.J.F. Boon
Journal: Ophthalmology (2019)
Serum NY-ESO-1 and XAGE1 antibodies as predictive biomarkers in anti-PD-1 therapy for non-small-cell lung cancer.
Authors: Mikio Oka, Yoshihiro Ohue, Koji Kurose, Takahiro Karasaki, Takeshi Masuda, Masaaki Fukuda, Akitoshi Kinoshita, Katsuhiko Shimizu, Masao Nakata, Noboru Hattori, Kazuhiro Kakimi, Hiroyuki Yamaguchi, Minoru Fukuda
Journal: Journal of Clinical Oncology (2019)

106 Background: Programmed death-1 (PD-1) inhibitors effectively treat non-small-cell lung cancer (NSCLC) and prolong survival, but the clinical benefits are limited in a small population. However, robust biomarkers for predicting clinical benefits with anti-PD-1 therapy have yet to be identified, therefore, predictive biomarkers are needed to select patients with benefits. On the other hand, NSCLC expresses NY-ESO-1 and XAGE1 cancer-testis antigens, which elicit spontaneous immune responses in NSCLC patients. Methods: We conducted a prospective multicenter study to investigate whether serum antibody against NY-ESO-1 and/or XAGE1 antigens was a predictive biomarker in anti-PD-1 therapy for NSCLC. Serum antibody was serially detected by ELISA, and antibody titers were monitored during anti-PD-1 therapy. Tumor tissues were analyzed by immunohistochemistry and whole exome sequencing. Objective response rate (ORR) and survival were the primary and secondary endpoint, respectively. Results: In the discovery cohort (n = 13), six antibody-positive NSCLC responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC did not. Antibody positivity was associated with good response and survival, regardless of tumor PD-ligand1 expression, mutation burden, and CD8 T-cell infiltration. In the independent validation cohort (n = 40), ten antibody-positive NSCLC obtained the significant clinical benefits with anti-PD-1 therapy as compared with 30 negative NSCLC (ORR 50% vs 6.7%, P = 0.006). In the multivariate analysis, only antibody positivity was a significantly better predictive biomarker of progression free survival (HR 0.04, 95% CI 0.0 to 0.3) and overall survival (HR 0.2, 95% CI 0.0 to 0.9) after anti-PD-1 therapy. Antibody titers in responders transiently increased with spikes and gradually decreased with tumor shrinkage after anti-PD-1 therapy, and strongly correlated with tumor reduction rates and tumor burden. Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits and monitoring tumor burden in anti-PD-1 therapy for NSCLC.