bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Preliminary In Vitro and In Vivo Evaluation of Thiirane‐Based Slow‐Binding MMP Inhibitors as Potential Radiotracers for PET Imaging
Authors: Hohn Michael , Chang Mayland , Meisel Jayda E. , Frost Emma , Schwegmann Katrin , Hermann Sven , Schäfers Michael , Riemann Burkhard , Haufe Günter , Breyholz Hans‐Jörg , Wagner Stefan 
Published: November 2018

AbstractMany serious diseases such as cancer, atherosclerosis and arthritis are characterized by upregulation of activated matrix metalloproteinases (MMPs). For this reason imaging and quantification of activated MMPs with the molecular imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) using radiolabeled MMP inhibitors would be a valuable tool for the diagnosis and therapy planning of mentioned diseases. This work aims at the synthesis and preliminary in vitro and in vivo evaluation of positron‐emitter 18F‐fluorine labeled radiotracers based on 2‐{[(4‐phenoxyphenyl)sulfonyl]methyl}thiirane (SB‐3CT), a slow‐binding and mechanism‐based MMP‐2 and −9 inhibitor. Therefore, a library of fluorinated SB‐3CT derivatives were prepared and evaluated in vitro in MMP inhibition assays. From this pool the 18F‐labeled triazole [18F]18d was successfully synthesized in a two‐step procedure. However, this compound was unstable in human and mouse serum and showed a biodistribution behavior in C57BL/6 mice that is not favorable for PET imaging preventing further in vivo evaluations in MMP‐associated mouse models of disease.
Quinic Acid‐Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins
Authors: Xu Jun , Lee Steve Seung‐Young , Seo Howon , Pang Liang , Jun Yearin , Zhang Ruo‐Yu , Zhang Zhong‐Yin , Kim Pilhan , Lee Wooin , Kron Stephen J. , Yeo Yoon 
Published: November 2018

AbstractCurrent nanoparticle (NP) drug carriers mostly depend on the enhanced permeability and retention (EPR) effect for selective drug delivery to solid tumors. However, in the absence of a persistent EPR effect, the peritumoral endothelium can function as an access barrier to tumors and negatively affect the effectiveness of NPs. In recognition of the peritumoral endothelium as a potential barrier in drug delivery to tumors, poly(lactic‐co‐glycolic acid) (PLGA) NPs are modified with a quinic acid (QA) derivative, synthetic mimic of selectin ligands. QA‐decorated NPs (QA‐NP) interact with human umbilical vein endothelial cells expressing E‐/P‐selectins and induce transient increase in endothelial permeability to translocate across the layer. QA‐NP reach selectin‐upregulated tumors, achieving greater tumor accumulation and paclitaxel (PTX) delivery than polyethylene glycol‐decorated NPs (PEG‐NP). PTX‐loaded QA‐NP show greater anticancer efficacy than Taxol or PTX‐loaded PEG‐NP at the equivalent PTX dose in different animal models and dosing regimens. Repeated dosing of PTX‐loaded QA‐NP for two weeks results in complete tumor remission in 40–60% of MDA‐MB‐231 tumor‐bearing mice, while those receiving control treatments succumb to death. QA‐NP can exploit the interaction with selectin‐expressing peritumoral endothelium and deliver anticancer drugs to tumors to a greater extent than the level currently possible with the EPR effect.
Surface Engineering of Nanomaterials for Photo‐Electrochemical Water Splitting
Authors: Yao Bin , Zhang Jing , Fan Xiaoli , He Jianping , Li Yat 
Published: November 2018

AbstractPhoto‐electrochemical water splitting represents a green and environmentally friendly method for producing solar hydrogen. Semiconductor nanomaterials with a highly accessible surface area, reduced charge migration distance, and tunable optical and electronic property are regarded as promising electrode materials to carry out this solar‐to‐hydrogen process. Since most of the photo‐electrochemical reactions take place on the electrode surface or near‐surface region, rational engineering of the surface structures, physical properties, and chemical nature of photoelectrode materials could fundamentally change their performance. Here, the recent advances in surface engineering methods, including the modification of the nanomaterial surface morphology, crystal facet, defect and doping concentrations, as well as the deposition of a functional overlayer of sensitizers, plasmonic metallic structures, and protective and catalytic materials are highlighted. Each surface engineering method and how it affects the structural features and photo‐electrochemical performance of nanomaterials are reviewed and compared. Finally, the current challenges and the opportunities in the field are discussed.
Improving the Sensitivity of Fluorescence‐Based Immunoassays by Photobleaching the Autofluorescence of Magnetic Beads
Authors: Roth Shira , Hadass Orr , Cohen Meir , Verbarg Jasenka , Wilsey Jennifer , Danielli Amos 
Published: November 2018

AbstractIn fluorescence‐based assays, usually a target molecule is captured using a probe conjugated to a capture surface, and then detected using a second fluorescently labeled probe. One of the most common capture surfaces is a magnetic bead. However, magnetic beads exhibit strong autofluorescence, which often overlaps with the emission of the reporter fluorescent dyes and limits the analytical performance of the assay. Here, several widely used magnetic beads are photobleached and their autofluorescence is reduced to 1% of the initial value. Their autofluorescence properties, including their photobleaching decay rates and autofluorescence spectra pre‐ and post‐photobleaching, and the stability of the photobleaching over a period of two months are analyzed. The photobleached beads are stable over time and their surface functionality is retained. In a high‐sensitivity LX‐200 system using photobleached magnetic beads, human interleukin‐8 is detected with a threefold improvement in detection limit and signal‐to‐noise ratio over results achievable with nonbleached beads. Since many contemporary immunoassays rely on magnetic beads as capture surfaces, prebleaching the beads may significantly improve the analytical performance of these assays. Moreover, nonmagnetic beads with low autofluorescence are also successfully photobleached, suggesting that photobleaching can be applied to various capture surfaces used in fluorescence‐based assays.
First occurrence of Rift Valley fever outbreak in Niger, 2016
Authors: Lagare Adamou , Fall Gamou , Ibrahim Alkassoum , Ousmane Sani , Sadio Bacary , Abdoulaye Mariama , Alhassane Abdou , Mahaman Ali Elh , Issaka Bassira , Sidikou Fati , Zaneidou Maman , Bienvenue Baruani , Djingarey Mamoudou Harouna , Bailo Diallo Amadou , Kadadé Goumbi , Testa Jean , Boubacar Mainassara Halima , Faye Ousmane 
Published: November 2018

AbstractRift Valley fever (RVF) is a mosquito‐borne viral zoonosis causing abortions and high mortality among animals, whereas in humans, the disease is usually mild or asymptomatic. In September 2016, the Republic of Niger declared the first RVF outbreak in the northern region of Tahoua near the Malian border. This study describes the outbreak and reports the results of serological and molecular investigations of the human and animal samples collected. Serum samples from both human and animal suspected cases have been confirmed at the Centre de Recherche Médicale et Sanitaire (CERMES) and the Laboratoire Centrale d'Elevage (LABOCEL) public health and animal reference laboratories, respectively. Techniques for biological confirmation were real time reverse transcription polymerase chain reaction (RT‐PCR) and enzyme linked immunosorbent assay (ELISA). Phylogenetic trees were established after genetic sequencing of the small and medium segments of the RVF virus (RVFV) genome. Out of the 399 human samples collected, 17 (4.3%) were confirmed positive for RVFV. Overall, 33 (8.3%) deaths occurred out of which five (29%) were among the 17 confirmed cases. Regarding animals, 45 samples were tested, three of which were RT‐PCR positive and 24 were IgG positive. The phylogenetic analyses showed that the Niger strains clustered with Senegal 2013 and Mauritania 2015 RVFV strains. This first outbreak of RVF was very challenging for public and animal health laboratories in Niger. Besides resulting in human deaths, important loss of cattle has been reported. Therefore, vigilance has to be strengthened emphasising vector control strategies and active surveillance among animals.
Phase 1 study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell carcinoma
Authors: Huijts Charlotte M. , Werter Inge M. , Lougheed Sinéad M. , Goedegebuure Ruben S. , van Herpen Carla M. , Hamberg Paul , Tascilar Metin , Haanen John B. , Verheul Henk M. , de Gruijl Tanja D. , van der Vliet Hans J. ,   for the Dutch WIN-O Consortium
Published: November 2018

Abstract
mTOR inhibitors are frequently used in the treatment of metastatic renal cell cancer (mRCC). mTOR regulates cell growth, proliferation, angiogenesis, and survival, and additionally plays an important role in immune regulation. Since mTOR inhibitors were shown to benefit immunosuppressive regulatory T-cell (Treg) expansion, this might suppress antitumor immune responses. Metronomic cyclophosphamide (CTX) was shown to selectively deplete Tregs. This study was, therefore, designed to determine the optimal dosage and schedule of CTX when combined with everolimus to prevent this potentially detrimental Treg expansion. In this national multi-center phase I study, patients with mRCC progressive on first line anti-angiogenic therapy received 10 mg everolimus once daily and were enrolled into cohorts with different CTX dosages and schedules. Besides immune monitoring, adverse events and survival data were monitored. 40 patients, 39 evaluable, were treated with different doses and schedules of CTX. Combined with 10 mg everolimus once daily, the optimal Treg depleting dose and schedule of CTX was 50 mg CTX once daily. 23 (59%) patients experienced one or more treatment-related ≥ grade 3 toxicity, mostly fatigue, laboratory abnormalities and pneumonitis. The majority of the patients achieved stable disease, two patients a partial response. Median PFS of all cohorts was 3.5 months. In conclusion, the optimal Treg depleting dose and schedule of CTX, when combined with everolimus, is 50 mg once daily. This combination leads to acceptable adverse events in comparison with everolimus alone. Currently, the here selected combination is being evaluated in a phase II clinical trial.

Trial registration
NCT01462214.
Mechanically Induced Periprosthetic Osteolysis: A Systematic Review
Authors: McArthur Benjamin A. , Scully Ryan , Patrick Ross F. , Bostrom Mathias P. G. , Falghren Anna 
Published: November 2018

Background Peri-prosthetic bone loss can result from chemical, biological, and mechanical factors. Mechanical stimulation via fluid pressure and flow at the bone–implant interface may be a significant cause. Evidence supporting mechanically induced osteolysis continues to grow, but there is no synthesis of published clinical and basic science data. Questions/Purposes We sought to review the literature on two questions: (1) What published evidence supports the concept of mechanically induced osteolysis? (2) What is the proposed mechanism of mechanically induced osteolysis, and does it differ from that of particle-induced osteolysis? Methods A systematic review was performed of the PubMed and Web of Science databases. Additional relevant articles were recommended by the senior authors based on their expert opinion. Abstracts were reviewed and the manuscripts pertaining to the study questions were read in full. Studies showing support of mechanically induced osteolysis were quantified and findings summarized. Results We identified 49 articles of experimental design supporting the hypothesis that mechanical stimulation of peri-prosthetic bone from fluid pressure and flow can induce osteolysis. While the molecular mechanisms may overlap with those implicated in particle-induced osteolysis, mechanically induced osteolysis appears to be mediated by distinct and parallel pathways. Conclusions The role of mechanical stimuli is increasingly recognized in the pathogenesis of peri-prosthetic osteolysis. Current research aims to elucidate the molecular mechanisms to better target therapeutic interventions.
Cerebral Oxygenation in the Sitting Position is Not Compromised During Spontaneous or Positive-Pressure Ventilation
Authors: YaDeau Jacques T. , Kahn Richard L. , Lin Yi , Goytizolo Enrique A. , Gordon Michael A. , Gadulov Yuliya , Garvin Sean , Fields Kara , Goon Amanda , Armendi Isabel , Dines David M. , Craig Edward V. 
Published: November 2018

Background General anesthesia with neuromuscular blockade may facilitate total shoulder arthroplasty but appears to increase risk of cerebral oxygen desaturation. Cerebral desaturation is undesirable and is a proxy for risk of stroke. Purposes/Questions This study tested the hypothesis that cerebral oxygen desaturation occurs frequently during general anesthesia with neuromuscular blockade and positive-pressure ventilation but does not occur with spontaneous ventilation. Correlations were sought among cerebral oxygen saturation, blood pressure, and cardiac index. Methods We designed a prospective, observational, cohort study to measure cerebral oxygenation in 25 patients during general anesthesia, both with and without positive-pressure ventilation. Patients undergoing elective shoulder arthroplasty in the sitting position received an arterial catheter, near-infrared spectroscopic measurement of cerebral oxygenation, and non-invasive cardiac output measurement. Moderate hypotension was allowed. Blood pressure was supported as needed with ephedrine or low-dose epinephrine (but avoiding phenylephrine). Hypercapnia (45 to 55 mmHg) was targeted during positive-pressure ventilation. Results No cerebral oxygen desaturations occurred, regardless of ventilation mode. Under positive-pressure ventilation, the median (interquartile range: Q1, Q3) cerebral oxygenation was 110% of baseline (104, 113), the mean arterial pressure was 62% of baseline (59, 69), and the cardiac index was 82% of baseline (71, 104). Cerebral oxygenation did not correlate with blood pressure or cardiac index but had moderate correlation with end-tidal carbon dioxide. No strokes occurred. Conclusions There were no signs of inadequate brain perfusion during general anesthesia using paralytic agents. Positive-pressure ventilation with moderate hypotension in the sitting position does not endanger patients, in the context of moderate hypercapnia and hemodynamic support using ephedrine or epinephrine.
The CESuRa System: Allowing Changes in a Rail Track Profile While Maintaining Full Vertical Support
Authors: Foan Andy , Thonstad Travis , Stanton John F. 
Published: November 2018

Abstract
A light rail passenger transportation system is being built in Seattle, WA, USA, that traverses Lake Washington over an existing pontoon bridge. The water level in Lake Washington changes throughout the year. This causes rotations of the transition spans, which are needed at each end of the bridge to carry traffic between the fixed, land-based structure, and the floating structure. This paper explains a novel method, the Curved Element Supported Rail (CESuRa) system, that provides rails with the ability to undergo joint rotations at the ends of the transitions spans without risk of damage, while maintaining full vertical support of the track across the joint. The geometric characteristics on which it depends for proper operation, considerations that must be accounted for when using the system for other applications in the future, and an overview of the implementation of the system on the floating bridge are discussed.
Prevalence and Risk Factors for Sexual Problems and Distress in Chinese Unmarried Young Women: An Observational Study
Authors: Lo Sue Seen-Tsing , Kok Wai-ming 
Published: November 2018

Abstract

Introduction
Research conducted in the West has shown that sexual function and distress was common in white women from younger to older adulthood; however, little research attention to date has been given to Chinese young women.

Aim
Our primary aim is to assess the prevalence and factors associated with sexual problems and distress in Chinese unmarried young women.

Methods
Between November 2015 and June 2017, 431 young women who visited 3 sexual health clinics completed an anonymous questionnaire detailing their demographics, sexual behavior, current sexual relationship, sexual function, and sexual distress. Descriptive bivariate analysis and logistic regression analyses were performed.

Main Outcome Measures
Sexual function and distress were assessed by the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R), respectively.

Results
Overall, 76 young women (17.6%) obtained total FSFI score ≤23.45 (Chinese cut-off), 47 of whom scored 11 or above for FSDS-R. Individual domain and total FSFI scores were significantly correlated with FSDS-R score (P &lt; .001). Based on domain scores, 35.5%, 18.8%, 12.8%, and 10.7% of them were at risk for orgasmic, pain, arousal, and desire problems, respectively. Arousal and lubrication problems were strongly associated with distress. Sexual problems were associated with not initiating sex (odds ratio [OR] 2.50, P = .001), often had sexual fantasy (OR 0.55, P = .036), and willingness for vaginal sex (OR 0.49, P &lt; .001). Sexual distress was associated with having life stressors (OR 1.88, P = .012) and willingness for vaginal sex (OR 0.61, P = .003). Self-perception of body being unattractive to boyfriend (OR 3.33, P = .015), not initiating sex (OR 3.21, P = .001), willingness for vaginal sex (OR 0.39, P &lt; .001), and no life stressors (OR 0.46, P = .036) were associated with both sexual problem and distress.

Clinical Implications
Physicians should be alerted to sexual problems in young women and encourage those with distress to seek help.

Strengths & Limitations
Using validated psychometric tools to assess sexual problems and distress provides reference for future comparison. Admission and recall biases are unavoidable in observational questionnaire study. Depression was not evaluated and might bias the estimation of distress.

Conclusion
About 11% of Chinese young women had sexual problems and were distressed (ie, sexual dysfunction). They were characterized by having a self-perception that their body was unattractive to their boyfriend, not initiating sex, unwilling for vaginal sex, and having life stressors.
Hepatocyte Nuclear Factor-4α P2 Promoter Variants Are Associated With the Risk of Metabolic Syndrome and Testosterone Deficiency in Aging Taiwanese Men
Authors: Liu Chia-Chu , Lee Yung-Chin , Huang Shu-Pin , Cheng Kai-Hung , Hsieh Tusty-Jiuan , Huang Tsung-Yi , Lee Cheng-Hsueh , Geng Jiun-Hung , Li Ching-Chia , Wu Wen-Jeng 
Published: November 2018

Abstract

Background
Hepatocyte nuclear factor-4α (HNF4A) can influence the risk of insulin resistance that is postulated to be an important link between metabolic syndrome (MetS) and testosterone deficiency (TD) in men.

Aim
To investigate the relationship between single-nucleotide polymorphisms (SNPs) of HNF4A and the risk of developing MetS and TD in a population of aging Taiwanese men.

Methods
A free health screening of men over 40 years of age was conducted in a medical center in Kaohsiung City, Taiwan. All participants underwent a physical examination, answered a questionnaire on demographics and medical history, completed the Androgen Deficiency in The Aging Male questionnaire to assess clinical symptoms of TD, and provided 20-mL whole blood samples for biochemical, hormonal, and genetic evaluation.

Main Outcome Measure
3 common SNPs (rs11574736, rs1884613, and rs2144908) of HNF4A were selected and identified using a TaqMan 5’ allelic discrimination assay.

Results
559 men were enrolled for this study (mean age, 55.8± 4.9 years). Prevalence of TD was significantly higher (P = .031) in subjects with MetS (16.8%) than those without MetS (10.1%). In SNP rs1884613 of HNF4A, subjects with the C allele carried a 1.31- and 1.50-times higher risk of developing MetS and TD, respectively, compared to those with the G allele, after adjusting for potential covariates. In addition, subjects with the CC genotype were exposed to a 1.91- and 2.20-times higher risk of developing MetS and TD, respectively, compared to those with the GG genotype.

Clinical Implications
Our findings may point to the importance of the role played by insulin resistance in the link between MetS and TD.

Strength & Limitations
Our current work is the first report with adequate sample size to evaluate the role of genetic variants of HNF4A on the risk of both MetS and TD in men. The limitations included subjects enrolled from a free health screening and single measurement of serum testosterone levels.

Conclusion
The rs1884613 SNP marker of HNF4A is significantly associated with an increased risk for developing both MetS and TD in aging Taiwanese men. Further population-based studies utilizing larger samples of different ethnicities may be needed to confirm these preliminary results.
Androgen Receptor Polymorphism and Female Sexual Function and Desire
Authors: Wåhlin-Jacobsen Sarah , Flanagan John N. , Pedersen Anette T. , Kristensen Ellids , Arver Stefan , Giraldi Annamaria 
Published: November 2018

Abstract

Introduction
The effect of testosterone depends on the exposure of and the sensitivity of the androgen receptor (AR). It has been shown that a cytosine–adenine–guanine (CAG) trinucleotide repeat polymorphism in the AR gene has an impact on AR functional capacity in men. However, large studies are lacking on the impact of this polymorphism on female sexual function.

Aim
To determine whether the CAG repeat length was associated with different aspects of women’s sexual function and dysfunction, including desire, arousal, lubrication, orgasm, satisfaction, sexual pain, and sexually related personal distress.

Methods
This cross-sectional study included 529 healthy women, aged 19–65 years. Participants completed a questionnaire to provide demographic and sexual data. The CAG repeat length was analyzed in a blood sample. The correlations between CAG repeat lengths and different aspects of sexual function were calculated. Independent Student t-tests were performed to evaluate differences in the mean number of CAG repeats in the short and long allele and of the biallelic mean length determined by simple calculation and X-inactivation analysis, respectively, between women with sexual problems and women without sexual problems. P values &lt;.05 were considered statistically significant.

Main Outcome Measure
We used the Female Sexual Function Index, with 6 subdomains, to distinguish between women without and women with impaired sexual function; low sexual desire; impaired arousal, lubrication, or orgasm; diminished satisfaction; or pain during sex. The Female Sexual Distress Scale was used to measure sexually related personal distress.

Results
Overall, we found that increasing numbers of CAG repeats were correlated to increased sexual function. We found that women with problems achieving orgasm had a significantly lower number of CAG repeats than women that reported no problems reaching orgasm. We found no associations between CAG repeat lengths and other aspects of female sexual dysfunction, including hypoactive sexual desire disorder.

Clinical Implications
The results could indicate an impact of the AR on women’s sexual function, including the ability to reach orgasm.

Strength & Limitations
This is a large study using validated sexual questionnaires. A limitation is the cross-sectional design. Owing to the study design, this study is explorative and hypothesis generating.

Conclusion
In this large cross-sectional study, we demonstrated that CAG repeat length is positively correlated to sexual function and that women with a reduced ability to reach orgasm had smaller numbers of CAG repeats in the AR gene than women with no orgasmic problems. These findings indicated that androgens and ARs might play a role in women’s sexual function.