bluuebunny/crossref_metadata_2025_split huggingface dataset:
In patients undergoing dialysis who require a valve replacement is a bioprosthetic valve superior to a mechanical prosthesis in terms of long-term survival and morbidity?
Authors: Fong Laura S , Ang Zhen Hao , Wolfenden Hugh , Akhunji Zakir 
Published: April 2020

Abstract
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was ‘In [dialysis patients undergoing a valve replacement] is [a bioprosthetic valve superior to a mechanical prosthesis] for [long-term survival and morbidity]’. Altogether more than 501 papers were found using the reported search, of which five represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. There was limited high-quality evidence with all studies being retrospective. One meta-analysis and four cohort studies provided the evidence that there was no significant difference in long-term survival based on prosthesis type. However, the majority of studies demonstrated a significantly higher rate of valve-related complications including bleeding and thromboembolism, and readmission to hospital in the mechanical valve prosthesis group, likely related to the requirement for long-term anticoagulation. We conclude that overall long-term survival in dialysis-dependent patients is poor. While prosthesis type does not play a significant contributing role to long-term survival, bioprosthetic valves were associated with significantly fewer valve-related complications. Based on the available evidence, a bioprosthetic valve may be more suitable in this high-risk group of patients as it may avoid the complications associated with long-term anticoagulation without any reduction in long-term survival.
Application of Design Space, Uncertainty, and Risk Profile Strategies to the Development and Validation of UPLC Method for the Characterization of Four Authorized Phosphodiesterase Type 5 Inhibitors to Combat Counterfeit Drugs
Authors: Benchekroun Yassine Hameda , El Karbane Miloud , Ihssane Bouchaib , Haidara Hasnaa , Azougagh Mohamed , Saffaj Taoufiq 
Published: April 2020

Abstract

Background
Counterfeit medicines are an increasing scourge that are difficult to identify and they have become industrialized and widespread through highly organized illegal channels.

Objective
This research aims to develop a robust method to determine four phosphodiesterase type-5 inhibitors in counterfeit drugs based on ultra-performance liquid chromatography.

Method
Experimental design methodology (DOE) and design space (DS) recommended by ICH Q8 were used side-by-side in the development phase to define the optimal parameters as well as the robustness of the chromatographic method. Moreover, both the uncertainty and risk profile derived from the β-content and γ-confidence tolerance interval were investigated during the validation phase to examine the performance of this method.

Results
Successful chromatographic results, in a high resolution between the four active ingredients and an optimal analysis time of less than 1.6 min, were achieved at the end of the optimization phase. In addition, validation results show a low risk of future measurements outside acceptance limits set at 5%.

Conclusions
Our procedure was successfully applied in the routine phase to identify 23 illicit formulations of an erectile dysfunction drug.

Highlights
An efficient method for the characterization of 4 authorized phosphodiesterase in less than 1.6 min was established. A DS approach was applied to test the performance of this analytical method during analytical development. A risk profile was then carried out to approve the validity of the analytical method through the uncertainty profile approach.
Three cases of follicular pancreatitis: association between radiological findings and pathological features
Authors: Kondo Ryota , Wada Ryuichi , Matsushita Akira , Nakamura Yoshiharu , Yoshioka Masato , Shimizu Tetsuya , Kanda Tomohiro , Kaneya Yohei , Aoki Yuto , Shimizu Michio , Yoshida Hiroshi , Naito Zenya 
Published: April 2020

Abstract
Follicular pancreatitis (FP) is characterized by nodular mass composed of lymphoid hyperplasia and fibrosis. We here present radiological and pathological features of three cases of FP. The three patients were middle- or old-aged men, and nodular mass was pointed out at health examination. Computed tomography failed to demonstrate a mass. Magnetic resonance imaging demonstrated a mass in each case. 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) demonstrated two nodular masses with high standardized uptake value (SUV) in two cases and single mass in one case. The pathological examination disclosed two lesions with fibrosis and hyperplastic lymphoid follicles in two cases and one lesion in one case. Masses with high SUV appeared to correspond with the lesions of FP. Compared with the features of FDG-PET images of pancreatic ductal carcinoma, multiple lesions with high SUV favor a diagnosis of FP rather than pancreatic cancer. FDG-PET is useful for the diagnosis of FP.
Osteosarcoma of the frontal bone: a study of a rare case in a 17-year-old female
Authors: Mohanna Farah , Slaibi Anas , Al-Shehabi Zuheir , Mahfoud Moufid 
Published: April 2020

Abstract
Head and neck osteosarcomas are infrequent and usually present in the third–fourth decades of life. However, they are extremely rare in the pediatric population. Primary involvement of the cranial vault, excluding the mandible and maxilla, is an exceedingly rare phenomenon; thus, the number of clinical studies published in the literature is limited. Because of the anatomy of the head, complete resection may be difficult to achieve. Furthermore, an aggressive surgical approach can cause a significant functional impairment or cosmetic defect. We report the case of a 17-year-old patient with an aggressive recurrence of multiple tumors in the left side of the skull accompanied with a severe headache and complete left-sided vision loss with no metastases at presentation. The recurrence of the tumor was preceded by pregnancy and delivery, which raised the question of whether pregnancy hormones were a provoking factor in the recurrence of the tumor or not.
Treatment with 2-methoxyestradiol increases endothelial nitric oxide synthase activity via scavenger receptor class BI in human umbilical vein endothelial cells
Authors: Dong Tao , Sato Seisuke , Lyu Jingya , Imachi Hitomi , Kobayashi Toshihiro , Fukunaga Kensaku , Saheki Takanobu , Iwama Hisakazu , Zhang Guoxing , Murao Koji 
Published: April 2020

AbstractConcentrations of 2-methoxyestradiol (2ME2), a principal metabolite of estradiol, are significantly lower in women with severe preeclampsia. Nitric oxide (NO) released by endothelial nitric oxide synthase (eNOS) plays an important role in regulating cardiovascular homeostasis. Importantly, high-density lipoprotein (HDL) stimulates eNOS activity via endothelial human scavenger receptor class B type I (hSR-BI/CLA-1). Here, we aimed to determine the effect of 2ME2 on hSR-BI/CLA-1 expression in human umbilical vein endothelial cells (HUVECs). hSR-BI/CLA-1 expression was measured by real-time PCR, western blotting and reporter gene assays; eNOS activity was assessed by the measurement of eNOS phosphorylation. Both the mRNA and protein concentrations of hSR-BI/CLA-1 were significantly increased by 2ME2 in HUVECs. 2ME2 also dose-dependently increased the transcriptional activity of the hSR-BI/CLA-1 promoter. The effect of 2ME2 treatment on the promoter activity of hSR-BI/CLA-1 was abrogated by treatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, as was the increase in HDL-induced eNOS activation. Notably, constitutively active Akt increased the activity of the hSR-BI/CLA-1 promoter, whereas dominant-negative Akt abolished the effect of 2ME2 treatment on hSR-BI/CLA-1 promoter activity. The nuclear Sp1 protein concentration was significantly increased by exposure to 2ME2 and Sp1 overexpression increased the promoter activity of the hSR-BI/CLA gene. Furthermore, knockdown of Sp1 inhibited the effect of 2ME2 treatment on hSR-BI/CLA-1 protein expression. These results indicate that 2ME2 treatment increases HDL-dependent eNOS phosphorylation by upregulating endothelial hSR-BI/CLA-1 expression, suggesting that 2ME2 has a potential therapeutic value in the treatment of preeclampsia.
Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff
Authors: Lunell Erik , Fagerström Karl , Hughes John , Pendrill Robert 
Published: April 2020

Abstract

Introduction
The single-dose pharmacokinetics (PK) of a novel, non-tobacco-based nicotine pouch, ZYN, 3 and 6 mg, were compared with 8 mg General snus (part 1) and ZYN 8 mg was compared with 18 mg Longhorn moist snuff (part 2). The present study demonstrates the characteristics of three strengths of a novel tobacco-free oral snus, ZYN, viz. the extraction of nicotine from the oral cavity and its uptake into the systemic blood circulation. Comparison is made to Swedish General snus and American Longhorn moist snuff and from literature 4 mg Nicorette gum and mean of 13 brands of e-cigarettes.

Aims and Methods
A single-dose randomized crossover design was used. In vivo extraction and PK parameters were determined.

Results
Part 1. The AUCinf of ZYN 3 mg was 27% smaller than that of 8 mg General and the AUCinf of ZYN 6 mg was 34% larger than that of 8 mg General. Less nicotine was extracted from ZYN 3 mg (1.5 mg) and more from ZYN 6 mg (3.5 mg) than from 8 mg General (2.4 mg). The extracted fractions of nicotine for both ZYN products (56% and 59%) were significantly larger than for 8 mg General (32%).

Results
Part 2. Close to identical plasma nicotine curves, AUCinf and Cmax were found for ZYN 8 mg and Longhorn Natural 18 mg moist snuff. The extracted amount of nicotine from ZYN 8 mg (3.8 mg) was larger than the amount extracted from Longhorn Natural 18 mg (3.0 mg), but smaller than the extracted amount of nicotine from General 2 × 8 mg snus pouches (5.0 mg). The extracted fraction of nicotine for ZYN 8 mg (50%) was larger than for Longhorn Natural (19%) and General 2 × 8 mg snus pouches (33%).

Conclusions
The two higher doses of ZYN (6 and 8 mg) deliver nicotine as quickly and to a similar extent as existing smokeless products, with no significant adverse effects.
Do Proxies for Informed Trading Measure Informed Trading? Evidence from Illegal Insider Trades
Authors: Ahern Kenneth R 
Published: April 2020

AbstractThis paper exploits hand-collected data on illegal insider trades to provide new evidence on the ability of a host of standard measures of illiquidity to detect informed trading. Controlling for unobserved cross-sectional and time-series variation, sampling bias, and strategic timing of insider trades, I find that when information is short-lived, only absolute order imbalance and effective spread are statistically and economically robust predictors of illegal insider trading. However, when information is long-lasting, insiders strategically time their trades to avoid illiquidity, and none of the standard measures considered are reliable predictors, including bid-ask spreads, order imbalance, Kyle’s λ, and Amihud illiquidity. (JEL D53D82G12G14K42)Received: March 14, 2019; Editorial decision: February 18, 2020 by Editor Thierry Foucault. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Tn‐MUC1 Glycopeptides as Ligands: Detection of the Effect of Peptide Sequence, Site of Glycosylation, and Glycan Density on MGL Binding in H2O/D2O
Authors: Beckwith Donella M. , FitzGerald Forrest G. , Rodriguez Benavente Maria C. , Gabius Hans-Joachim , Cudic Mare 
Published: April 2020

ObjectiveTo apply synthetic Tn‐MUC1 glycopeptides for characterizing contributions of their structural parameters to affinity for the endogenous lectin MGL.AbstractO‐Glycosylation of mucins is assumed to serve as a versatile signal via recognition by tissue lectins. Human macrophage galactose‐type lectin (hMGL, CD301 or CLEC10A), a C‐type lectin expressed by dendritic cells and macrophages, is a receptor of Ser/Thr‐linked a‐GalNAc (T antigen nouvelle: Tn, CD175) and its a2,6‐sialylated derivative (sTn). The relative contributions of the glycan and the peptide backbone to affinity are not well understood. In this study, the chemical synthesis of the tandem‐repeat sequence of mucin MUC1, i.e. HGVTSAPDTRPAPGSTAPPA, and site‐specific Thr‐based glycopeptides facilitated calorimetric study of lectin binding. First, CD spectroscopy revealed stabilization of the polyproline II (PPII) structure with increasing density of the glycan epitope. Binding is an enthalpy‐driven process, affinity enhancement occurred for glycopeptides relative to free GalNAc. Size of enthalpic gains were associated to valency, the monoglycosylated peptides had ΔH of about −10 kcal mol−1 and the triply glycosylated ligands had ΔH −30.4 kcal mol− 1. Increases in affinity (Kd) by one order of magnitude were determined for mono‐ (5.6 μM) to triglycosylated (588 nM) MUC1 peptides. Analysis of the kinetic profiles of binding of the MUC1 glycopeptides to hMGL appears to support involvement of a “bind and jump” mechanism. The lifetimes (lower koff values) increase as the density of GalNAc increases along the MUC1 20‐mer sequence. In order to assess a role of solvent reorganization to binding to a C‐type lectin, experiments were performed in parallel in D2O. Unlike GalNAc binding, H/D exchange resulted in more favorable enthalpic contributions, for the monoglycosylated analogs accompanied by compensating higher entropic penalty. Peptide backbone presence makes a difference, as glycan density was revealed to do. In summary, our results suggest that contact building of MUC1 glycopeptides with hMGL critically depends on structural characteristics in the vicinity of the glycan and its density.Support or Funding InformationThis work was supported by the National Institutes of Health Grant CA242351 M. C.
Hyperbaric fluorescence microscopy: imaging reactive O2 and N2 species in rat brain slices during exposure to normobaric and hyperbaric hyperoxia
Authors: Hinojo Christopher M. , Stavitzski Nicole , Dean Jay B. 
Published: April 2020

Hyperbaric oxygen (HBO) is breathed in hyperbaric and undersea medicine. Protracted exposure to HBO, however, is toxic to the mammalian brain and results in central nervous system‐O2 toxicity (CNS‐OT; i.e., seizures). Thus, the use of HBO in military diving operations is limited by maximum time at depth; e.g., 10 min at 50 fsw on 100% O2. Our lab is interested in the mechanisms and mitigation of CNS‐OT for safer, longer dives. The present study reports our methods for measuring the rate of reactive species production in real time using fluorescence microscopy as a function of PO2 at normobaric and hyperbaric pressures. Our recent improvements in hyperbaric fluorescence microscopy include the following: 1) quantifying the effect of pressure on focal length of the microscope—during compression the focal length increases and during decompression the focal length shortens (“baro‐blurring”); 2) visual monitoring of the brain slice bath inside a sealed, dark pressure chamber without exciting fluorescent dyes (DHE ex/em: 525/590nm; DAF‐FM ex/em: 495/515nm) by continuous IR illumination (770nm) of the microscope objective and slice bath while imaging with a CCD camera (heat filter removed); 3) an internal pump for recirculating medium containing fluorescent dye; 4) addition of a Lumencor SPECTRA Light Engine; and 5) upgrades in remote controls for x‐y translation of the slice chamber. Experiments using hyperbaric fluorescence microscopy show that while normobaric hyperoxia (NBO; 0.4 – 0.95 ATA O2) and hyperbaric oxygen (HBO; 0.4 – 1.95 ATA O2) increase the rate of superoxide production (2.5uM DHE), not all cells produce superoxide at the same rate. Most DHE‐loaded cSC neurons exhibited varying fluorescence intensities initially in 0.4 ATA O2 that we labeled “Dim cells” (fluorescence intensity units (FIU) < average FIU at t=0) and “Bright cells” (FIU ≥ average FIU at t=0). O2‐ sensitive cells significantly increased superoxide production (by at least 25% ΔFIU/min) in both Dim and Bright cells after exposure to 0.95/1.95 ATA O2. Certain Bright and Dim cells, however, were O2‐insensitive cells (< 25% ΔFIU/min). After measuring the effects of NBO and HBO on superoxide production, we tested the effects of a 1:1 mixture of ketone salts (KS) on ΔFIU/min during increased background oxygenation. The rationale for this is that ketone metabolic therapy delays onset of CNS‐OT seizures. 5mM KS significantly decreased the production superoxide in O2‐sensitive Bright cells at 0.95/1.95 ATA O2. Our findings suggest that cells in the cSC are heterogeneous in their capacity for superoxide production and neuroprotection by ketone bodies during exposure to hyperoxia. Studies are underway to determine the effects of NBO & HBO ±KS on nitric oxide production in cSC cells using 1 uM DAF‐FM.Support or Funding InformationResearch funded by ONR Undersea Medicine Program
A Novel Inhibitor of Epithelial‐to‐Mesenchymal Transition Reduces Pancreatic Cancer Cell Invasion and Tumor Growth in Mice
Authors: Wang Tao , Dong Ruochen , Chen Ping , Chen Qi 
Published: April 2020

ObjectiveEpithelial to Mesenchymal Transition (EMT) has been proposed to contribute importantly to metastasis, cancer stem cell (CSC) generation and drug resistance in many cancers. Targeting EMT may be promising to benefit cancer treatment. Our previous high throughput screening study has identified a potential EMT inhibitor (namely, C150) in pancreatic cancer cells. Here, we sought to investigate the activities of C150 in inhibiting pancreatic cancer cell invasion, migration and tumor growth in mice, as well as its mechanisms of EMT inhibition.MethodsCell viability was detected by MTT assay. Cell migration/invasion was detected by Boyden chamber trans‐well migration‐invasion assay, wound scratch assay and a 3‐dimension (3D) cell invasion assay. MMP zymography assay was used to indicate MMP inhibition. In vivo tumor growth was evaluated in an orthotopic mouse model of pancreatic cancer. EMT marker proteins were examined by western blot.ResultsC150 exhibited a well‐separated cytotoxicity between pancreatic cancer cells and non‐cancerous cells, with IC50 values of 1~2.5 μM in multiple pancreatic cancer cell lines and >25 μM in a noncancerous pancreatic epithelial cell line (hTERT‐HPNE). C150 was found to significantly inhibit PANC‐1 cell invasion in the 3‐dimension (3D) cell invasion model, the wound scratching assay and the Boyden Chamber trans‐well migration‐invasion assay. C150 treatment reduced the expressions of MMP‐2 and MMP‐9 in PANC‐1 cells, and inhibited MMP enzyme activity in zymography assay. In orthotopic pancreatic cancer mouse model, C150 significantly reduced tumor growth at the dose of 15 mg/kg, 3x weekly by IP injection. C150 decreased the mesenchymal markers of N‐cadherin and Snail while increased epithelial markers of ZO‐1 and Claudin‐1. Further studies revealed that C150 treatment significantly increased proteasome activity in the cell without changing the protein expression levels of proteasome subunits.ConclusionThe novel compound C150 inhibited pancreatic cancer cell migration, invasion, and in vivo tumor growth in mice. The compound increased cellular proteasome activity, which enhanced the protein degradation of Snail, resulting in EMT inhibition in the cell. The studies of more detailed mechanisms of C150 induced EMT inhibition and proteasome activation, as well as target identification are currently undergoing.Support or Funding InformationInstitutional Development Award (IDeA) of NIH and State of Kansas Grant # 8P30GM103495, KU Cancer Center Lied Basic Science Grant 2018
Glycophorin B‐A‐B Variant GP.Mur, a Chaperone for Erythroid SLC4A Transporter, Supports Gas Exchange during Exhaustive Exercise
Authors: Hsu Kate 
Published: April 2020

The main function of glycophorin A is to stabilize protein complex expression of SLC4A (band 3) and to facilitate its Cl−/HCO3− antiporter activity across human red blood cell (RBC) membrane. Anion exchange through SLC4A on the RBC surface is physiologically critical for blood CO2 transport. We previously found that glycophorin B‐A‐B hybrid protein GP.Mur, a special blood type unique to people of Southeast Asian origins, further promotes erythroid expression of SLC4A. People with GP.Mur phenotype not only express more band 3 on their RBCs but also exhibit more efficient blood CO2 expiration when challenged with a mild stepping exercise test. We have noticed a disproportional number of elite athletes in Taiwan bearing the GP.Mur phenotype. The goal of this study was thus to verify whether GP.Mur expression could indeed support the respiratory function of elite athletes during exhaustive exercise. Here we recruited GP.Mur+ and GP.Mur‐young elite/professional athletes in Taiwan and challenged them with a graded, exhaustive protocol of cardiopulmonary exercise testing (CPET). As revealed by CPET, compared to the athletes lacking the special blood type, GP.Mur+ athletes showed smaller respiratory quotient (RQ) and lower arterial CO2 tension throughout the graded test before exhaustion. This suggests relative easiness on the respiratory function for athletes with GP.Mur phenotype during exhaustive exercise. We are currently exploring the possibility of utilizing one’s GP.Mur/band 3 expression levels in personalized athletic training.Support or Funding InformationTaiwan Ministry of Science & Technology (MOST 108‐2628‐B‐195‐001)