bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-Vivo Retention of 5-Fluorouracil Using 19F Magnetic Resonance Chemical Shift Imaging in Colorectal Cancer in a Murine Model
Authors: Shepelytskyi Yurii , Fox Matthew S. , Davenport Karen , Li Tao , Albert Mitchell S. , Davenport Eric 
Published: September 2019

AbstractColorectal cancer is the third leading cause of cancer death worldwide. 5-Fluorouracil (5-FU) is one of the most commonly used chemotherapies for treatment of solid tumours, including colorectal cancer. The efficacy of treatment is dependent on tumour type and can only be determined six weeks after beginning chemotherapy, with only 40–50% of patients responding positively to the 5-FU therapy. In this paper, we demonstrate the potential of using Magnetic Resonance (MR) Chemical Shift Imaging (CSI) for in-vivo monitoring of 5-FU tumor-retention in two different colorectal tumour types (HT-29 & H-508). Time curves for 5-FU signals from the liver and bladder were also acquired. We observed significant differences (p < 0.01) in 5-FU signal time dependencies for the HT-29 and H-508 tumours. Retention of 5-FU occurred in the H-508 tumour, whereas the HT-29 tumour is not expected to retain 5FU due to the observation of the negative b time constant indicating a decline in 5FU within the tumour. This study successfully demonstrates that CSI may be a useful tool for early identification of 5-FU responsive tumours based on observed tumour retention of the 5-FU.
Blood pressure change across pregnancy in white British and Pakistani women: analysis of data from the Born in Bradford cohort
Authors: Farrar Diane , Santorelli Gillian , Lawlor Debbie A. , Tuffnell Derek , Sheldon Trevor A. , West Jane , Macdonald-Wallis Corrie 
Published: September 2019

AbstractThe incidence of gestational hypertension (GH) and pre-eclampsia (PE) is increasing. Use of blood pressure (BP) change patterns may improve early detection of BP abnormalities. We used Linear spline random-effects models to estimate BP patterns across pregnancy for white British and Pakistani women. Pakistani women compared to white British women had lower BP during the first two trimesters of pregnancy, irrespective of the development of GH or PE or presence of a risk factor. Pakistani compared to white British women with GH and PE showed steeper BP increases towards the end of pregnancy. Pakistani women were half as likely to develop GH, but as likely to develop PE than white British women. To conclude; BP trajectories differ by ethnicity. Because GH developed evenly from 20 weeks gestation, and PE occurred more commonly after 36 weeks in both ethnic groups, the lower BP up to the third trimester in Pakistani women resulted in a lower GH rate, whereas PE rates, influenced by the steep third trimester BP increase were similar. Criteria for diagnosing GH and PE may benefit from considering ethnic differences in BP change across pregnancy.
Plasmon-Activated Water Reduces Amyloid Burden and Improves
Memory in Animals with Alzheimer’s Disease
Authors: Cheng Chia-Hsiung , Lin Kun-Ju , Hong Chien-Tai , Wu Dean , Chang Hung-Ming , Liu Cheng-Huan , Hsiao Ing-Tsung , Yang Chih-Ping , Liu Yu-Chuan , Hu Chaur-Jong 
Published: September 2019

AbstractWith the great extension of the human lifespan in recent times, many
aging diseases have inevitably followed. Dementia is one of the most-commom
neurodegenerative aging diseases, in which inflammation-related Alzheimer’s disease
(AD) is the most prevalent cause of dementia. Amyloid accumulation in the brain,
which occurs before any clinical presentations, might be the first and key step in
the development of AD. However, many clinical trials have attempted to remove
amyloid from brains of AD patients, but none has so far been successful. Negatively
charged plasmon-activated water (PAW) is created by resonantly illuminated gold (Au)
nanoparticles (NPs), which reduce the hydrogen-bonded (HB) structure of water. PAW
was found to possess anti-oxidative and anti-inflammatory effects. Herein, we report
on an innovative strategy to retard the progression of AD by the daily consumption
of PAW instead of normal deionized (DI) water. APPswe/PS1dE9 transgenic mice were
treated with PAW or DI water from the age of 5 months for the next 9 months.
Encouragingly, compared to DI water-treated mice, mice treated with PAW presented
better memory performance on a test of novel object recognition and had a
significantly lower amyloid burden according to 18F-florbetapir amyloid-PET and
phosphorylated (p)-tau burden according to Western blotting and immunohistochemistry
measurements. There were no obvious side effects in PAW-treated mice. Collectively,
our findings support that PAW was able to reduce the amyloid and p-tau burden and
improve memory in an AD mouse model. However, the protein levels of molecules
involved in amyloid metabolism and oligomeric amyloid did not change. We propose
that the effects of PAW of reducing the amyloid burden and improving memory function
cannot be attributed to synthesis/degradation of amyloid-βprotein but probably in
preventing aggregation of amyloid-β proteins or other mechanisms, including
anti-inflammation. Further applications of PAW in clinical trials to prevent the
progression of AD are being designed.
A thyroid hormone network exists in synovial fibroblasts of rheumatoid arthritis and osteoarthritis patients
Authors: Pörings Anna-Sophia , Lowin Torsten , Dufner Bianca , Grifka Joachim , Straub Rainer H. 
Published: September 2019

AbstractWhile patients with rheumatoid arthritis (RA) sometimes demonstrate thyroidal illness, the role of thyroid hormones in inflamed synovial tissue is unknown. This is relevant because thyroid hormones stimulate immunity, and local cells can regulate thyroid hormone levels by deiodinases (DIO). The study followed the hypothesis that elements of a thyroid hormone network exist in synovial tissue. In 12 patients with RA and 32 with osteoarthritis (OA), we used serum, synovial fluid, synovial tissue, and synovial fibroblasts (SF) in order to characterize the local thyroid hormone network using ELISAs, immunohistochemistry, imaging methods, tissue superfusion studies, cell-based ELISAs, flow cytometry, and whole genome expression profiling. Serum/synovial fluid thyroid hormone levels were similar in RA and OA (inclusion criteria: no thyroidal illness). The degradation product termed reverse triiodothyronine (reverse T3) was much lower in serum compared to synovial fluid indicating biodegradation of thyroid hormones in the synovial environment. Superfusion experiments with synovial tissue also demonstrated biodegradation, particularly in RA. Cellular membrane transporters of thyroid hormones, DIOs, and thyroid hormone receptors were present in tissue and SF. Density of cells positive for degrading DIOs were higher in RA than OA. TNF increased protein expression of degrading DIOs in RASF and OASF. Gene expression studies of RASF revealed insignificant gene regulation by bioactive T3. RA and OA synovial tissue/SF show a local thyroid hormone network. Thyroid hormones undergo strong biodegradation in synovium. While bioactive T3 does not influence SF gene expression, SF seem to have a relay function for thyroid hormones.
Increase in the Population of Patients with Neovascular Age-Related Macular Degeneration Who Underwent Long-Term Active Treatment
Authors: Baek Seung Kook , Kim Jae Hui , Kim Jong Woo , Kim Chul Gu 
Published: September 2019

AbstractTo investigate changes in the size of the population of patients who are receiving long-term, active treatment for neovascular age-related macular degeneration (AMD). This retrospective, observational study included 3,380 patients who received anti-vascular endothelial growth factor injections (3,974 eyes). The injections performed were divided into the following three groups: group 1, injections performed right after the initial diagnosis; group 2, injections performed <24 months; and group 3, injection performed ≥24 months. Time-dependent changes in the proportion of injections in each group were analyzed. The total number of injections markedly increased from 431 in the 1st quarter of 2014 to 1,323 in the 4th quarter of 2018. There were significant changes in the proportion of injections in each group over time (P < 0.001). The proportions of group 1, group 2, and group 3 in the 1st quarter of 2014 were 17.4%, 65.4%, and 17.2%, respectively. The proportions changed to 10.6%, 50.2%, and 39.5% in the 4th quarter of 2018, respectively. The marked increase in the proportions of group 3 may suggest an increase in the patient population that underwent long-term active treatment. The socioeconomic influence of this trend should be considered when establishing future strategies for neovascular AMD.
Risk-based eradication as a control measure to limit the spread of LA-MRSA among Danish pig herds – a simulation study
Authors: Schulz Jana , Boklund Anette , Toft Nils , Halasa Tariq 
Published: September 2019

AbstractA national screening in 2016 identified 88% of Danish pig herds positive for livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA). This highlights the importance of evaluating potential control measures that could reduce the prevalence of LA-MRSA among Danish pig herds. In addition to describing the effects of (1) reduced within-herd transmission, (2) increased biosecurity, and (3) movement restrictions, the eradication of LA-MRSA as a potential control measure was investigated using a simulation model mimicking the spread of LA-MRSA among pig herds between 2006 and 2015. The latter strategy was simulated either as eradication of a random selection of herds for surveillance or as a risk-based selection of herds based on their potential to spread LA-MRSA via pig movements in four different scenarios: low- vs. high-prevalence scenarios with control measures starting in 2007 and in 2010. Almost all control measures showed the potential to reduce the spread of LA-MRSA among pig herds, especially when implemented intensively and when control measures were combined. Risk-based selection of herds for eradication led to a greater relative reduction compared to random selection. In the high-prevalence scenario in particular, combinations including risk-based eradication led to the greatest relative reduction.
Association of circulating exosomal miR-122 levels with BAT activity in healthy humans
Authors: Okamatsu-Ogura Yuko , Matsushita Mami , Bariuan Jussiaea Valente , Nagaya Kazuki , Tsubota Ayumi , Saito Masayuki 
Published: September 2019

AbstractBrown adipose tissue (BAT) plays an important role in body fat accumulation and the regulation of energy expenditure. Since the role of miRNAs in the pathogenesis of obesity and related metabolic diseases is contentious, we analyzed exosomal miRNAs in serum of healthy subjects with special references to BAT activity and body fat level. Forty male volunteers aged 20–30 years were recruited. Their BAT activity was assessed by fluorodeoxyglucose positron emission tomography and computed tomography after 2 h of cold exposure and expressed as a maximal standardized uptake value (SUVmax). Exosomal miRNA levels was analyzed using microarray and real-time PCR analyses. The miR-122-5p level in the high BAT activity group (SUV ≧ 3) was 53% lower than in the low BAT activity group (SUVmax <3). Pearson’s correlation analysis revealed that the serum miR-122-5p level correlated negatively with BAT activity and the serum HDL-cholesterol, and it correlated positively with age, BMI, body fat mass, and total cholesterol and triglyceride serum levels. Multivariate regression analysis revealed that BAT activity was associated with the serum miR-122-5p level independently of the other parameters. These results reveal the serum exosomal miR-122-5p level is negatively associated with BAT activity independently of obesity.
Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts
Authors: Stafman Laura L. , Williams Adele P. , Marayati Raoud , Aye Jamie M. , Markert Hooper R. , Garner Evan F. , Quinn Colin H. , Lallani Shoeb B. , Stewart Jerry E. , Yoon Karina J. , Whelan Kimberly , Beierle Elizabeth A. 
Published: September 2019

AbstractPatient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.
Mechanical properties of plasma membrane vesicles correlate with lipid order, viscosity and cell density
Authors: Steinkühler Jan , Sezgin Erdinc , Urbančič Iztok , Eggeling Christian , Dimova Rumiana 
Published: September 2019

AbstractRegulation of plasma membrane curvature and composition governs essential cellular processes. The material property of bending rigidity describes the energetic cost of membrane deformations and depends on the plasma membrane molecular composition. Because of compositional fluctuations and active processes, it is challenging to measure it in intact cells. Here, we study the plasma membrane using giant plasma membrane vesicles (GPMVs), which largely preserve the plasma membrane lipidome and proteome. We show that the bending rigidity of plasma membranes under varied conditions is correlated to readout from environment-sensitive dyes, which are indicative of membrane order and microviscosity. This correlation holds across different cell lines, upon cholesterol depletion or enrichment of the plasma membrane, and variations in cell density. Thus, polarity- and viscosity-sensitive probes represent a promising indicator of membrane mechanical properties. Additionally, our results allow for identifying synthetic membranes with a few well defined lipids as optimal plasma membrane mimetics.
Supramolecular fluorescence sensor for liquefied petroleum gas
Authors: Zhan Yi-Yang , Liao Jingyuan , Kajita Mizuho , Kojima Tatsuo , Takahashi Satoshi , Takaya Tomohisa , Iwata Koichi , Hiraoka Shuichi 
Published: September 2019

AbstractSensing systems of nonpolar gas molecules without functional groups such as natural gas and liquefied petroleum gas (LPG) remain difficult to develop because of lacking selective detection of such molecules over other gas molecules. Here we report a supramolecular fluorescence sensor for LPG using a 2-nm-sized cube-shaped molecular container i.e. a nanocube self-assembled from six molecules of gear-shaped amphiphiles (GSA) in water. The nanocube selectively encapsulates LPG, while it does not bind other gas molecules. Upon encapsulation of LPG in the nanocube, the fluorescence from the nanocube is enhanced by 3.9 times, which is caused by the restricted motion of the aromatic rings of GSA in the nanocube based on aggregation-induced emission. Besides the high selectivity, high sensitivity, quick response, high stability of the nanocube for LPG, and easy preparation of GSA satisfy the requirement for its practical use for an LPG sensor.
MiR-182 regulates cell proliferation and apoptosis in laryngeal squamous cell carcinoma by targeting the CRR9
Authors: Lv Yuan , Ye Dong , Qiu Shijie , Zhang Jian , Shen Zhisen , Shen Yi , Deng Hongxia 
Published: September 2019

Abstract
Background: The effect of miR-182 on the expressions of CRR9 in laryngeal squamous cell carcinoma (LSCC) cells, and the impact on invasion and metastasis of LSCC were investigated in the present paper.
Methods: The expressions of miR-182 in LSCC tissue and cell line were detected by RT-qPCR. MTT assay and Annexin V staining were used to detect the effects of miR-182 on tumor cells proliferation. Target gene prediction and screening, and luciferase reporter assay were designed to verify downstream target genes of miR-182. The mRNA and protein expressions of CRR9 were detected by qRT-PCR and Western blot. Finally, the expressions of CRR9 were measured by transfecting cells with miR-182 in mice.
Results: Compared with normal tissue and cell, the expressions of miR-182 in tumor tissues and cells were much lower. Over-expressions of miR-182 can increase apoptosis rate. Luciferase reporter assay revealed that CRR9 was a downstream gene of miR-182. Reintroduction of CRR9 abolished miR-182-induced LSCC cell growth inhibition. In animal models, over-expressions of miR-182 can reduce tumor weight and promote apoptosis.
Conclusion: miR-182 can inhibit the proliferation of LSCC cells by directly inhibiting the expressions of CRR9, thereby suppressing the occurrences and developments of LSCC.
Homology-directed repair in mouse cells increased by CasRx-mediated knockdown or co-expressing Kaposi’s sarcoma-associated herpesvirus ORF52
Authors: Pan Hong , Yu Weina , Zhang Ming 
Published: September 2019

Abstract
Precise genome editing with directed base insertion or targeted point mutations can be achieved by CRISPR/Cas9-mediated homology-directed repair (HDR) and is of great significance in clinical disease therapy. However, HDR efficiency, compared with non-homologous end-joining (NHEJ), is inherently low. To enhance HDR, enabling the insertion of precise genetic modifications, we compared two strategies during surrogate reporter assays in mouse N2A cells: the suppression of DNA ligase IV, a key molecule in NHEJ, using the CasRx (Ruminococcus flavefaciens Cas13d) system, and co-expression of Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF52 proteins. We found that suppression of DNA ligase IV promotes HDR efficiency by 1.4-fold. When co-expressed with the Cas9 system, ORF52 improved HDR efficiency by up to 2.1-fold. In addition, we used ORF52 co-expression to modify the ACTB and Tubb3 genes of mouse N2A and E14 cells, which further increased HDR efficiency by approximately two- to four-fold. In conclusion, our data suggest that ORF52 co-expression is effective for enhancing CRISPR/Cas9-mediated HDR, which may be useful for future studies involving precise genome editing.
aPKC in neuronal differentiation, maturation and function
Authors: Hapak Sophie M. , Rothlin Carla V. , Ghosh Sourav 
Published: September 2019

AbstractThe atypical Protein Kinase Cs (aPKCs)—PRKCI, PRKCZ and PKMζ—form a subfamily within the Protein Kinase C (PKC) family. These kinases are expressed in the nervous system, including during its development and in adulthood. One of the aPKCs, PKMζ, appears to be restricted to the nervous system. aPKCs are known to play a role in a variety of cellular responses such as proliferation, differentiation, polarity, migration, survival and key metabolic functions such as glucose uptake, that are critical for nervous system development and function. Therefore, these kinases have garnered a lot of interest in terms of their functional role in the nervous system. Here we review the expression and function of aPKCs in neural development and in neuronal maturation and function. Despite seemingly paradoxical findings with genetic deletion versus gene silencing approaches, we posit that aPKCs are likely candidates for regulating many important neurodevelopmental and neuronal functions, and may be associated with a number of human neuropsychiatric diseases.
Effects of Early Acoustic Hearing on Speech Perception and Language for Pediatric Cochlear Implant Recipients
Authors: Davidson Lisa S. , Geers Ann E. , Uchanski Rosalie M. , Firszt Jill B. 
Published: September 2019

Purpose
The overall goal of the current study was to identify an optimal level and duration of acoustic experience that facilitates language development for pediatric cochlear implant (CI) recipients—specifically, to determine whether there is an optimal duration of hearing aid (HA) use and unaided threshold levels that should be considered before proceeding to bilateral CIs.

Method
A total of 117 pediatric CI recipients (ages 5–9 years) were given speech perception and standardized tests of receptive vocabulary and language. The speech perception battery included tests of segmental perception (e.g., word recognition in quiet and noise, and vowels and consonants in quiet) and of suprasegmental perception (e.g., talker and stress discrimination, and emotion identification). Hierarchical regression analyses were used to determine the effects of speech perception on language scores, and the effects of residual hearing level (unaided pure-tone average [PTA]) and duration of HA use on speech perception.

Results
A continuum of residual hearing levels and the length of HA use were represented by calculating the unaided PTA of the ear with the longest duration of HA use for each child. All children wore 2 devices: Some wore bimodal devices, while others received their 2nd CI either simultaneously or sequentially, representing a wide range of HA use (0.03–9.05 years). Regression analyses indicate that suprasegmental perception contributes unique variance to receptive language scores and that both segmental and suprasegmental skills each contribute independently to receptive vocabulary scores. Also, analyses revealed an optimal duration of HA use for each of 3 ranges of hearing loss severity (with mean PTAs of 73, 92, and 111 dB HL) that maximizes suprasegmental perception.

Conclusions
For children with the most profound losses, early bilateral CIs provide the greatest opportunity for developing good spoken language skills. For those with moderate-to-severe losses, however, a prescribed period of bimodal use may be more advantageous for developing good spoken language skills.