gebhart/patrepeval huggingface dataset:
Abstract PS17-49: Investigating CDK4/6 inhibition in triple negative breast cancer (2021)

Abstract The purpose of our study is to evaluate the immunological effects of CDK4/6 inhibitors in pre-clinical models of triple negative breast cancer (TNBC). CDK4/6 inhibitors, including abemaciclib, are currently approved to treat patients with metastatic hormone receptor-positive (HR+), Her2-negative breast cancer. We previously reported in our Her2+ model that CDK4/6 inhibitors promote anti-tumor immunity through inducing tumor cell antigen presentation via activating tumor endogenous retroviral elements, which induce type III interferon production and MHC-I upregulation (Goel, DeCristo, et al., Nature, 2017). We also uncovered important anti-tumor effects on the immune system: CDK4/6 inhibitors decrease T regulatory cell proliferation without affecting cytotoxic CD8 T cell numbers. TNBC has been considered a poor candidate for CDK4/6 inhibitor therapy, as tumors often lose retinoblastoma (Rb) protein expression/function, which is critical for CDK4/6 inhibitor-induced cell cycle arrest. However, Rb mutation or loss occurs in only ~20% of TNBC cases and we found Rb expressing murine and human TNBC cell lines decreased proliferation in vitro in response to abemaciclib. In our preclinical model of TNBC, abemaciclib induced tumor regression. Consistent with previous findings, TNBC tumor cells upregulated MHC-I upon abemaciclib treatment, suggesting increased antigen presentation. Tumor cell-surface PD-L1 was also increased with abemaciclib both in vitro and in vivo, as assessed by flow cytometry and RT-qPCR. These results are encouraging, given that αPD-L1 therapy (Atezolizumab) in combination with chemotherapy (nab-paclitaxel) has recently been approved as standard care for metastatic TNBC and the IMpassion130 trial reported enhanced progression-free and overall survival in patients with PD-L1+ tumors. We also found that abemaciclib increased CD8+ and CD4+ T cells and decreased PD1+ CD8 and CD4 cells in the spleen. Furthermore, total numbers of naïve CD8+ and CD4+ T cells increased with abemaciclib treatment, suggesting a favorable anti-tumor systemic immunological effect. Our data suggest the potential efficacy of CDK4/6 inhibitors in combination with αPD-L1 in the treatment of Rb+ TNBC. Deeper analysis of the mechanisms involved in regulating PD-L1 and enhancing naïve T cells should enable us to evaluate combination therapies using CDK4/6 inhibitors for this particularly deadly breast cancer subtype. Citation Format: Qiuchen Guo, Gregory J Goreczny, Milos Spasic, Adam Maynard, Sandra S McAllister. Investigating CDK4/6 inhibition in triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-49.
Cancer in Transgender and Gender-Diverse Persons (2023)

The findings suggest that transgender and gender-diverse peoples' needs in the cancer care continuum are not optimally addressed. Effective solutions are needed to offer the best care to every patient in a person-centric and gender diversity-sensitive environment.
Optimized angle scanning method for array sample detection in surface plasmon resonance biosensor (2012)

An optimized angle scanning method is presented for array sample detection in a surface plasmon resonance biosensor. It provides a way to find the optimal rotation axis in the prism to resolve the drifting problem of the light incidence point on samples in the plane prism-coupling mode. The detection of array samples can be achieved by the translation of the prism along a particular direction. The validity of this method is theoretically analyzed and demonstrated by experiments.
Shock-induced defects in cadmium sulfide (1981)

We report on the explosive shock loading of CdS powders pressed to 50% of theoretical density in a copper recovery capsule, to pressures in the copper of about 3, 13, and 20 GPa, and preservation of the samples for post‐shock study. No residual structural changes were detected via X‐ray diffraction, but large densities (∼1016/cm3) of two types of defects were detected using ESR. One defect had an isotropic spectrum, with g=2.0028, and the other had an axial spectrum with g∥=1.790 and g⊥=1.775. The axial defect seems to be connected with the wurtzite‐rocksalt phase transition in CdS.
Clinical Effectiveness of Incentive Spirometry for the Prevention of Postoperative Pulmonary Complications (2017)

Incentive spirometry (IS) is commonly prescribed to reduce pulmonary complications, despite limited evidence to support its benefits and a lack of consensus on optimal protocols for its use. Although numerous studies and meta-analyses have examined the effects of IS on patient outcomes, there is no clear evidence establishing its benefit to prevent postoperative pulmonary complications. Clinical practice guidelines advise against the routine use of IS in postoperative care. Until evidence of benefit from well-designed clinical trials becomes available, the routine use of IS in postoperative care is not supported by high levels of evidence.
Chinese Grammatical Correction Using BERT-based Pre-trained Model (2020)

In recent years, pre-trained models have been extensively studied, and several downstream tasks have benefited from their utilization. In this study, we verify the effectiveness of two methods that incorporate a BERT-based pre-trained model developed by Cui et al. (2020) into an encoder-decoder model on Chinese grammatical error correction tasks. We also analyze the error type and conclude that sentence-level errors are yet to be addressed.
Real-time polymerase chain reaction assay for endogenous reference gene for specific detection and quantification of common wheat-derived DNA (Triticum aestivum L.). (2007)

A species-specific endogenous reference gene system was developed for polymerase chain reaction (PCR)-based analysis in common wheat (Triticum aestivum L.) by targeting the ALMT1 gene, an aluminium-activated malate transporter. The primers and probe were elaborated for real-time PCR-based qualitative and quantitative assay. The size of amplified product is 95 base pairs. The specificity was assessed on 17 monocot and dicot plant species. The established real-time PCR assay amplified only T. aestivum-derived DNA; no amplification occurred on other phylogenetically related species, including durum wheat (T. durum). The robustness of the system was tested on the DNA of 15 common wheat cultivars using 20 000 genomic copies per PCR the mean cycle threshold (Ct) values of 24.02 +/- 0.251 were obtained. The absolute limits of detection and quantification of the real-time PCR assay were estimated to 2 and 20 haploid genome copies of common wheat, respectively. The linearity was experimentally validated on 2-fold serial dilutions of DNA from 650 to 20 000 haploid genome copies. All these results show that the real-time PCR assay developed on the ALMT1 gene is suitable to be used as an endogenous reference gene for PCR-based specific detection and quantification of T. aestivum-derived DNA in various applications, in particular for the detection and quantification of genetically modified materials in common wheat.
Association between GWAS-Identified Genetic Variations and Disease Prognosis for Patients with Colorectal Cancer (2015)

Genome-wide association studies (GWASs) have already identified at least 22 common susceptibility loci associated with an increased risk of colorectal cancer (CRC). This study examined the relationship between these single nucleotide polymorphisms (SNPs) and the clinical outcomes of patients with colorectal cancer. Seven hundred seventy-six patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. Twenty-two of the GWAS-identified SNPs were genotyped using a Sequenom MassARRAY. Among the 22 SNPs, two (rs1321311G>T in CDKN1A and rs10411210C>T in RHPN2) were significantly associated with the survival outcomes of CRC in a multivariate survival analysis. In a recessive model, the rs1321311 TT genotype (vs. GG + GT) and rs10411210 TT genotype (vs. CC + CT) were associated with a worse prognosis for disease-free survival (adjusted HR = 1.90; 95% confidence interval = 1.00-3.60; P = 0.050, adjusted HR = 1.94; 95% confidence interval = 1.05-3.57; P = 0.034, respectively) and overall survival (adjusted HR = 2.05; 95% confidence interval = 1.00-4.20; P = 0.049, adjusted HR = 2.06; 95% confidence interval = 1.05-4.05; P = 0.036, respectively). None of the other SNPs was significantly associated with any clinicopathologic features or survival. The present results suggest that the genetic variants of the CDKN1A (rs1321311) and RHPN2 (rs10411210) genes can be used as prognostic biomarkers for patients with surgically resected colorectal cancer.
Applicability of the Momentum-Flux-Parameter Closure for the Two-Fluid Model to Slug Flow (2010)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Raad I. Issa, Marco Montini; Applicability of the Momentum‐Flux‐Parameter Closure for the Two‐Fluid Model to Slug Flow. AIP Conference Proceedings 1 March 2010; 1207 (1): 712–722. https://doi.org/10.1063/1.3366452 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioAIP Conference Proceedings Search Advanced Search |Citation Search
Obstetrics, genetics, and litigation (2021)

Many lessons and recommendations emerge in this report. These include the realization that the vast majority of errors in this series involved at least two caregivers, serial ultrasound studies are important, decreased fetal movements may signal a genetic disorder, congenital abnormality, or syndrome, family history and ethnicity are vital, cognitive biases profoundly affect decision-making. Finally, the simplest of errors have the potential for causing life-long grief.
Four‐factor response surface optimization of the enzymatic modification of triolein to structured lipids (1995)

Abstract The ability of an immobilized lipase to modify the fatty acid composition of (88.8% C 18:1 , 4.3% C 16:0 , 3.1% C 18:0 , and 3.8% C 18:2 as determined by gas chromatography, and approximately 90% triolein) in hexane by incorporation of a medium‐chain fatty acid, capric acid (C 10 ), to form structured triacylglycerol was studied. Response surface methodology was used to evaluate the effect of synthesis variables, such as reaction time (12–36 h), temperature (25–65°C), molar substrate ratio of capric acid to triolein (2:1–6:1), and enzyme amount (10–30% wt% of triacylglycerol), on the yield of structured lipid. Optimization of the transesterification was attempted to obtain maximum yield of structured lipid while using the minimum molar substrate ratio and enzyme amount as much as possible. Computer‐generated contour plot interpretation revealed that a relatively high molar substrate ratio (6:1) combined with low enzyme amount (10%) after 30 h of reaction at 25°C gave optimum incorporation of capric acid. A total yield for combined monoand dicaproolein of up to 100% was obtained.
Chelate-free metal ion binding and heat-induced radiolabeling of iron oxide nanoparticles (2014)

A novel reaction for chelate-free, heat-induced metal ion binding and radiolabeling of ultra-small paramagnetic iron oxide nanoparticles (USPIOs) has been established. Radiochemical and non-radioactive labeling studies demonstrated that the reaction has a wide chemical scope and is applicable to p-, d- and f-block metal ions with varying ionic sizes and formal oxidation states from 2+ to 4+. Radiolabeling studies found that <sup>89</sup>Zr-Feraheme (<sup>89</sup>Zr-FH or <sup>89</sup>Zr-ferumoxytol) can be isolated in 93 ± 3% radiochemical yield (RCY) and >98% radiochemical purity using size-exclusion chromatography. <sup>89</sup>Zr-FH was found to be thermodynamically and kinetically stable <i>in vitro</i> using a series of ligand challenge and plasma stability tests, and <i>in vivo</i> using PET/CT imaging and biodistribution studies in mice. Remarkably, ICP-MS and radiochemistry experiments showed that the same reaction conditions used to produce <sup>89</sup>Zr-FH can be employed with different radionuclides to yield <sup>64</sup>Cu-FH (66 ± 6% RCY) and <sup>111</sup>In-FH (91 ± 2% RCY). Electron magnetic resonance studies support a mechanism of binding involving metal ion association with the surface of the magnetite crystal core. Collectively, these data suggest that chelate-free labeling methods can be employed to facilitate clinical translation of a new class of multimodality PET/MRI radiotracers derived from metal-based nanoparticles. Further, this discovery is likely to have broader implications in drug delivery, metal separation science, ecotoxicology of nanoparticles and beyond.
Preserving Statistical Validity in Adaptive Data Analysis (2015)

A great deal of effort has been devoted to reducing the risk of spurious scientific discoveries, from the use of sophisticated validation techniques, to deep statistical methods for controlling the false discovery rate in multiple hypothesis testing. However, there is a fundamental disconnect between the theoretical results and the practice of data analysis: the theory of statistical inference assumes a fixed collection of hypotheses to be tested, or learning algorithms to be applied, selected non-adaptively before the data are gathered, whereas in practice data is shared and reused with hypotheses and new analyses being generated on the basis of data exploration and the outcomes of previous analyses.
An efficient approach to rotation invariant face detection using PCA, generalized regression neural network and Mahalanobis distance by reducing search space (2007)

This paper introduces a new effective method for human face recognition, which employs Mahalanobis distance, a color segment method, to reduce the search space for a face in an image. The color segment method is used to detect the area where a face may exist and searching for a face by the network is localized in that area. The face, with its orientation, is recognized using principle components analysis (PCA), generalized regression neural networks (GRNN) and Mahalanobis distance. The idea behind PCA is to reduce the dimension of the input vectors and extracting a feature vector. GRNN used as a function approximation network to detect whether the input image contains a face or not and if exists then reports about its orientation. The proposed system shows how GRNN can perform better than back-propagation algorithm and give some solution for better regularization. The proposed classifier system demonstrates advantages in: 1) better capability of approximation to underlying functions, 2) faster learning speed and 3) high robustness to outliers. The proposed technique overcomes one of the main problems for searching method reducing the computing time in two ways; firstly reducing the area to be searched and secondly reducing the scaling factor of the selected area of the image.
Unexpected course of olefin loss from some alkylcyclopentanone ions. Gaseous ion structure by ion cyclotron resonance spectrometry, mass‐analyzed ion kinetic energy spectrometry and collision‐induced dissociation (1976)

Abstract Ion cyclotron resonance results show that the ions formed by single and by double McLafferty rearrangement in 2‐ethyl‐5‐propylcyclopentanone have neither keto nor enol structures. Collision‐induced dissociations confirm that these ions are structurally distinct from the keto ions formed directly by electron impact upon the corresponding neutral molecules. It is suggested that the major reaction path for olefin loss from 2‐ethyl‐5‐propylcyclopentanone and from 2‐ethylcyclopentanone involves ring opening followed by hydrogen transfer to carbon in the alkene elimination step. Only in metastable ions is there evidence for the occurrence of the normal McLafferty rearrangement. The techniques mentioned in the title, together with conventional low and high resolution mass spectrometry, have been used to characterize the sometimes complex mixtures of cyclic and acyclic ions formed from cyclopentanone and some of its alkyl derivatives. Use of a number of different techniques of ion structure characterization allowed corroboration of particular results by quite distinct methods and it also allowed the effects of ion internal energy and lifetime upon structure to be partly elucidated.
Clinical implications of the tiotropium/olodaterol inhaler for patients with chronic obstructive pulmonary disease (2018)

Oral inhalation is the recommended delivery method of medications for the treatment of patients with chronic obstructive pulmonary disease (COPD). However, patients may struggle when using the various available inhaler platforms, and, as a result, may fail to achieve the benefit of the prescribed medication. Propellant-based, pressurized metered-dose inhaler and powder-based, dry powder inhaler devices are currently the most commonly prescribed delivery systems. Each of these devices has its own advantages and challenges. The Respimat® Soft Mist™ inhaler (SMI) (Boehringer Ingelheim) is a delivery system that incorporates features intended to improve orally inhaled drug delivery to these patients. These features include simple device actuation, patient inspiratory effort-independent aerosol generation, and a slower spray emission with a longer spray duration, helping to mitigate issues with precise aerosol release and breath coordination. We review the clinical trials assessing lung deposition, efficacy, and safety, and patient satisfaction for the Respimat® SMI. These data indicate that the Respimat® SMI is a device capable of delivering a consistent, clinically effective dose of medication that patients can use and prefer, which may provide significant clinical benefits for patients with COPD.
Evaluating the Effector Function of Individual CD19-Specific T Cells to Assess the Therapeutic Impact of a Manufactured Product (2014)

Adoptive cell therapy, based on the adoptive transfer of T cells genetically modified to enforce expression of a chimeric antigen receptor (CAR) has shown considerable promise in clinical trials, such as with CD19+ malignancies refractory to conventional treatments. However, efficiently predicting which patient may benefit from a given CAR design remains a challenge and undermines the therapeutic potential of such genetically modified T cells. Our approach to manufacturing CD19-specific T cells is based on electro-transfer of DNA plasmids from the Sleeping Beauty transposon/transposase system and selective outgrowth of CAR+ T cells on irradiated artificial antigen presenting cells (aAPC). The clinical-grade T cells prepared for infusion comprise a heterogeneous mixture and likely only a fraction of the genetically modified product contributes to therapeutic efficacy. Thus, we are developing an approach whereby the therapeutic potential of individual CAR+ T cell can be assessed. T cells are capable of different anti-tumor effector functions including cytotoxicity, cytokine secretion, and homing to target tissues, and currently no methodologies exist that can inform on all of these functions for a given (single) cell. Therefore, we have implemented an approach to interrogate the complexity of bulk populations of manufactured CAR+ T cells, so that the contribution of individual cells to the overall anti-tumor effect can be ascertained. CD19-specific CAR+ T cells currently being used in clinical trials were analyzed at a single cell level using technology that combines functional screening (cytotoxicity, cytokine production) with their molecular profiles. Bulk T cells which lysed tumor targets at 28% (1:1; effector:target ratio) in a standard 4 hour chromium lysis assay were observed at the single level to lyse multiple targets and function as serial killers (Figure). There was no correlation between IFN-g production and cytolysis. T cells that participated in killing and/or cytokine secretion were more susceptible to apoptosis than lymphocytes that did not participate in effector function. These data highlight that deconstructing the heterogeneity of a bulk population into individual cells can be used to determine whether subsets of T cells can participate in serial killing. The ability to serially image T-cell killing in massively parallel arrays will enable investigators to design CAR molecules that can support multi-hit kill kinetics. This lays the ground work for more complex studies evaluating cytokine production and genetic signatures of individual T cells bearing CAR species that comprise the infusion product.
From Gestational Hypertension and Preeclampsia to Atypical Hemolytic Uremic Syndrome (2016)

This case illustrates the importance of distinguishing atypical hemolytic uremic syndrome from preeclampsia.
Glomerular filtration and tubular secretion of MAG-3 in the rat kidney. (1989)

Technetium-99m mercaptoacetyltriglycine (MAG-3) has recently been introduced as a new radiopharmaceutical for dynamic renal scintigraphy. To elucidate the mechanism of renal excretion, micropuncture experiments were performed in rat kidneys for direct measurements of glomerular filtration and tubular secretory capacity. Fluid of Bowman space was collected from superficial glomeruli and analyzed for its contents of [99mTc]MAG-3, [125I]hippurate and [3H]inulin during constant infusion of these compounds. The ratio of activity of ultrafiltrate to that of arterial plasma was 0.23 for MAG-3, 0.68 for hippurate and 1.04 for inulin which demonstrates that the filtrated amount of MAG-3 is only 23% of that of inulin, presumably because of higher plasma protein binding which was also measured in vitro and found to be 80 +/- 1.5% for MAG-3 and 32 +/- 2% for [125I]hippurate. Proximal and distal tubules were also micropunctured and their tubular fluid as well as the final urine analyzed for the activity of hippurate and MAG-3. The tubular fluid to plasma ratio values along the nephron and in the final urine were all lower for MAG-3 than for hippurate, indicating a lower secretory capacity. From measurements of whole renal clearance, GFR and plasma protein binding the filtered amount of MAG-3 was 0.26 and of hippurate 0.87 ml/min.g kidney weight (p less than 0.001) and the secreted amount 2.01 and 2.38 ml/min.g kidney weight (p less than 0.05), respectively. We conclude that MAG-3 is predominantly excreted by tubular secretion and that the lower renal clearance of MAG-3 as compared with that of hippurate is a result both of a substantially decreased glomerular filtration and of a lower tubular secretion.
3D Co-culture System of Mouse Prostatic Wild-type Fibroblasts with Human Prostate Cancer Epithelial Cells (2019)

Heterogeneous prostatic carcinoma-associated fibroblasts (CAF) contribute to tumor progression. This was established using transgenic mouse models. Paracrine interactions between fibroblasts and epithelial cells were further interrogated using isolated 2D cell culture systems, but 3D culture systems currently being developed can better mimic reciprocal interactions potentially found in the native tissue. To understand paracrine and juxtacrine signaling among fibroblasts and epithelia, 3D co-cultures with species differences allows for further subsequent analysis of the cultures. The use of mouse and human cells, for example, in one system allows for species-specific FACS or quantitative PCR analysis. This protocol describes the use of a 3D Co-culture System of Mouse Prostatic Wild-type Fibroblasts with Human Prostate Cancer Epithelial Cells.