bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proof-of-concept study for the design of a VLP-based combinatorial HPV and placental malaria vaccine
Authors: Janitzek Christoph M. , Peabody Julianne , Thrane Susan , H. R. Carlsen Philip , G. Theander Thor , Salanti Ali , Chackerian Bryce , A. Nielsen Morten , Sander Adam F. 
Published: March 2019

AbstractIn Africa, cervical cancer and placental malaria (PM) are a major public health concern. There is currently no available PM vaccine and the marketed Human Papillomavirus (HPV) vaccines are prohibitively expensive. The idea of a combinatorial HPV and PM vaccine is attractive because the target population for vaccination against both diseases, adolescent girls, would be overlapping in Sub-Saharan Africa. Here we demonstrate proof-of-concept for a combinatorial vaccine utilizing the AP205 capsid-based virus-like particle (VLP) designed to simultaneously display two clinically relevant antigens (the HPV RG1 epitope and the VAR2CSA PM antigen). Three distinct combinatorial VLPs were produced displaying one, two or five concatenated RG1 epitopes without obstructing the VLP’s capacity to form. Co-display of VAR2CSA was achieved through a split-protein Tag/Catcher interaction without hampering the vaccine stability. Vaccination with the combinatorial vaccine(s) was able to reduce HPV infection in vivo and induce anti-VAR2CSA IgG antibodies, which inhibited binding between native VAR2CSA expressed on infected red blood cells and chondroitin sulfate A in an in vitro binding-inhibition assay. These results show that the Tag/Catcher AP205 VLP system can be exploited to make a combinatorial vaccine capable of eliciting antibodies with dual specificity.
Hybrid 3D ranging and velocity tracking system combining multi-view cameras and simple LiDAR
Authors: Radwell Neal , Selyem Adam , Mertens Lena , Edgar Matthew P. , Padgett Miles J. 
Published: March 2019

AbstractScanning our surroundings has become one of the key challenges in automation. Effective and efficient position, distance and velocity sensing is key to accurate decision making in automated applications from robotics to driverless cars. Light detection and ranging (LiDAR) has become a key tool in these 3D sensing applications, where the time-of-flight (TOF) of photons is used to recover distance information. These systems typically rely on scanning of a laser spot to recover position information. Here we demonstrate a hybrid LiDAR approach which combines a multi-view camera system for position and distance information, and a simple (scanless) LiDAR system for velocity tracking and depth accuracy. We show that we are able to combine data from the two component systems to provide a compound image of a scene with position, depth and velocity data at more than 1 frame per second with depth accuracy of 2.5 cm or better. This hybrid approach avoids the bulk and expense of scanning systems while adding velocity information. We hope that this approach will offer a simpler, more robust alternative to 3D scanning systems for autonomous vehicles.
Modulation of the p75 neurotrophin receptor suppresses age-related basal forebrain cholinergic neuron degeneration
Authors: Xie Youmei , Meeker Rick B. , Massa Stephen M. , Longo Frank M. 
Published: March 2019

AbstractAge-related degeneration of basal forebrain cholinergic neurons (BFCNs) is linked to cognitive impairment. The p75 neurotrophin receptor (p75NTR) has been proposed to mediate neuronal degeneration in aging. Therefore, we tested the hypothesis that modifying p75NTR function would prevent or reverse aging-related neuronal degeneration using LM11A-31, a small molecule p75NTR modulator that downregulates degenerative and upregulates trophic receptor-associated signaling. Morphological analysis in mice showed loss of BFCN area detectable by 18 months of age. Oral administration of LM11A-31 from age 15 to 18 months resulted in a dose-related preservation of BFCN area and one month of treatment from 17 to 18 months also preserved cell area. To evaluate reversal of established neuronal atrophy, animals were treated from 21 to 25 months of age. Treatment was associated with an increase of cell size to a mean area larger than that observed at 18 months, accompanied by increases in mean MS/VDB neurite length, as well as increased cholinergic fiber density and synaptophysin pre-synaptic marker levels in the hippocampus. These findings support the idea that modulation of p75NTR activity can prevent and potentially reverse age-associated BFCN degeneration. Moreover, this may be achieved therapeutically with orally bioavailable agents such as LM11A-31.
The ups and downs of a canopy-forming seaweed over a span of more than one century
Authors: Blanfuné Aurélie , Boudouresque Charles François , Verlaque Marc , Thibaut Thierry 
Published: March 2019

AbstractCanopy-forming seaweeds constitute marine forests that deliver ecosystem services. The worldwide range shift, sharp decline or loss of many of these forests, caused by the cumulative impact of increasing human pressure and climate change, have been widely documented. Contrasting examples, reflecting higher than expected resilience, have been more rarely reported. Here, we took the opportunity of having at our disposal a two-century suite of documents (herbarium vouchers, articles) and a ~120-year observation period, dealing with a long-lived brown seaweed, Cystoseira mediterranea, along a well-explored Mediterranean coastline in the Gulf of Lions, to depict the fate of its populations. In addition, we provided baselines for future surveys, with a high degree of accuracy. The northernmost population, scattered on rare suitable substrates, gradually declined and has been extinct since the 1980s. The length of shore occupied by the southern population showed a long-term decline trend, with two sharp minima followed by partial recovery. The causes of the decline differ between sites and periods: coastal development, pollution, competition with mussels, heatwaves and exceptional storms. Overall, the Gulf of Lions populations reflects long-lasting resilience, higher than expected, and a health status that is better than that reported for many other canopy-forming seaweeds.
Influence of p53 Isoform Expression on Survival in High-Grade Serous Ovarian Cancers
Authors: Bischof Katharina , Knappskog Stian , Hjelle Sigrun M. , Stefansson Ingunn , Woie Kathrine , Salvesen Helga B. , Gjertsen Bjorn T. , Bjorge Line 
Published: March 2019

AbstractHigh-grade serous ovarian carcinoma (HGSOC) is characterised by alterations in the p53 pathway. The expression levels of p53 isoforms have been shown to be associated with patient survival in several cancers. This study examined the predictive and prognostic effects of the expression levels of TP53 pre-mRNA splicing isoforms and TP53 mutations in tumour tissues in 40 chemotherapy responders and 29 non-responders with HGSOC. The mRNA expression levels from total p53, and total Δ133p53, p53β, p53γ isoforms were determined by RT-qPCR, and TP53 mutation status by targeted massive parallel sequencing. The results from these analyses were correlated with the clinical outcome parameters. No differential expression of p53 isoforms could be detected between the chemosensitive and chemoresistant subgroups. In a multivariate Cox regression model, high levels of total Δ133p53 were found to be an independent prognosticator for improved overall survival (HR = 0.422, p = 0.018, 95% CI: 0.207–0.861) and reached borderline significance for progression-free survival (HR = 0.569, p = 0.061, 95% CI: 0.315–1.027). TP53 mutations resulting in loss of function or located at known hotspots were predictive of tumour characteristics and disease progression. These findings suggest that total Δ133p53 mRNA can be a biomarker for survival in HGSOC.
Effects of propofol on the inflammatory response during robot-assisted laparoscopic radical prostatectomy: a prospective randomized controlled study
Authors: Roh Go Un , Song Young , Park Junbeom , Ki Yu Min , Han Dong Woo 
Published: March 2019

AbstractRobot-assisted laparoscopic radical prostatectomy (RALRP) is a minimally invasive procedure; however, some amount of surgical trauma that can trigger systemic inflammation remains. Moreover, pneumoperitoneum during RALRP induces ischemia–reperfusion injury (IRI). Propofol, an anesthetic, is known to have anti-inflammatory and antioxidant properties. In the present study, we compared the effects of propofol with those of desflurane on inflammation and IRI during RALRP via measurements of different biomarkers and evaluation of perioperative renal function. Fifty patients were randomized to receive either desflurane (n = 25) or propofol (n = 25) with remifentanil during RALRP. Serum levels of interleukin (IL)-6 (IL-6), tumor necrosis factor alpha, C-reactive protein, and nitric oxide were measured 10 min after anesthesia induction (T1), 100 min after carbon dioxide (CO2) insufflation (T2), and 10 min after CO2 deflation (T3). Perioperative urine outputs and the serum creatinine level at 24 h after surgery were also recorded. We found that IL-6 levels at T2 and T3 were higher than those at T1 in both groups, although the increases were significant attenuated only in the propofol group. The other parameters showed no differences among the three time points in both groups. The intraoperative urine output was significantly higher in the propofol group than in the desflurane group, while the creatinine level showed no significant changes in either group. Our findings suggest that propofol can not only attenuate the inflammatory response during and after pneumoperitoneum in patients undergoing RALRP but also prevent oliguria during pneumoperitoneum.
FOXS1 is regulated by GLI1 and miR-125a-5p and promotes cell proliferation and EMT in gastric cancer
Authors: Wang Sen , Ran Longke , Zhang Wanfeng , Leng Xue , Wang Kexin , Liu Geli , Song Jing , Wang Yujing , Zhang Xianqin , Wang Yitao , Zhang Lian , Ma Yan , Liu Kun , Li Haiyu , Zhang Wei , Qin Guijun , Song Fangzhou 
Published: March 2019

AbstractGastric cancer (GC) is the fourth most common malignant neoplasm and the second leading cause of cancer death. Identification of key molecular signaling pathways involved in gastric carcinogenesis and progression facilitates early GC diagnosis and the development of targeted therapies for advanced GC patients. Emerging evidence has revealed a close correlation between forkhead box (FOX) proteins and cancer development. However, the prognostic significance of forkhead box S1 (FOXS1) in patients with GC and the function of FOXS1 in GC progression remain undefined. In this study, we found that upregulation of FOXS1 was frequently detected in GC tissues and strongly correlated with an aggressive phenotype and poor prognosis. Functional assays confirmed that FOXS1 knockdown suppressed cell proliferation and colony numbers, with induction of cell arrest in the G0/G1 phase of the cell cycle, whereas forced expression of FOXS1 had the opposite effect. Additionally, forced expression of FOXS1 accelerated tumor growth in vivo and increased cell migration and invasion through promoting epithelial–mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, the core promoter region of FOXS1 was identified at nucleotides −660~ +1, and NFKB1 indirectly bind the motif on FOXS1 promoters and inhibit FOXS1 expression. Gene set enrichment analysis revealed that the FOXS1 gene was most abundantly enriched in the hedgehog signaling pathway and that GLI1 expression was significantly correlated with FOXS1 expression in GC. GLI1 directly bound to the promoter motif of FOXS1 and significantly decreased FOXS1 expression. Finally, we found that miR-125a-5p repressed FOXS1 expression at the translational level by binding to the 3′ untranslated region (UTR) of FOXS1. Together, these results suggest that FOXS1 can promote GC development and could be exploited as a diagnostic and prognostic biomarker for GC.
Capturing spontaneous activity in the medial prefrontal cortex using near-infrared spectroscopy and its application to schizophrenia
Authors: Hosomi Fumiharu , Yanagi Masaya , Kawakubo Yoshihiro , Tsujii Noa , Ozaki Satoshi , Shirakawa Osamu 
Published: March 2019

AbstractNear-infrared spectroscopy (NIRS) is an optimal imaging modality used to examine spontaneous brain activity because it can quietly measure blood flow changes with less physical restriction during the resting state. Here, NIRS was used at rest to measure spontaneous activity in the medial prefrontal cortex (mPFC), a main locus of default mode network. Consistent with previous fMRI studies, magnitude of the spontaneous activity in this region declined with increasing age in healthy subjects. The magnitude reduced in the mPFC of patients with schizophrenia. Additionally, in the mPFC of patients with schizophrenia, the spontaneous activity did not show any age-related decline; the activity was already low in younger patients. Further analysis using fractional amplitude of low-frequency fluctuations confirmed the reduction of spontaneous activity in the mPFC of patients with schizophrenia, consistent with the findings of fMRI studies. Our findings demonstrate the ability of NIRS to evaluate the spontaneous activity in the mPFC of patients with schizophrenia, particularly younger patients. Considering the safety and ease of the NIRS measurements, the current NIRS study of the resting-state activity indicates its utility for clinical applications to schizophrenia, which may facilitate chronological assessment of larger cohorts of patients with schizophrenia in further studies.
Renal size and cardiovascular risk in prepubertal children
Authors: Lizarraga-Mollinedo Esther , Martínez-Calcerrada Jose-Maria , Padrós-Fornieles Cristina , Mas-Pares Berta , Xargay-Torrent Silvia , Riera-Pérez Elena , Prats-Puig Anna , Carreras-Badosa Gemma , de Zegher Francis , Ibáñez Lourdes , Bassols Judit , López-Bermejo Abel 
Published: March 2019

AbstractRenal size is an important parameter for the evaluation and diagnosis of kidney disease and has been associated with several cardiovascular risk factors in patients with kidney failure. These results are however discordant and studies in healthy children are lacking. We aimed to study the association between renal size (length and volume) and cardiovascular risk parameters in healthy children. Clinical, analytical and ultrasound parameters [renal length, renal volume, perirenal fat and carotid intima-media thickness (cIMT)] were determined in 515 healthy prepubertal children (176 lean, 208 overweight and 131 obese). Renal length and volume associated significantly and positively with several anthropometric and cardiovascular risk parameters including cIMT and systolic blood pressure (SBP) (all p < 0.001). Renal length and volume associated with cIMT and SBP in all study subgroups, but these associations were predominant in obese children, in whom these associations were independent after adjusting for age, gender and BSA (all p < 0.05). In multivariate analyses in the study subjects as a whole, renal length was an independent predictor of cIMT (β = 0.310, p < 0.0001) and SBP (β = 0.116, p = 0.03). Renal size associates with cIMT and SBP, independent of other well-established cardiovascular risk factors, and may represent helpful parameters for the early assessment of cardiovascular risk in children.
Megahertz non-contact luminescence decay time cryothermometry by means of ultrafast PbI2 scintillator
Authors: Mykhaylyk V. B. , Kraus H. , Bobb L. , Gamernyk R. , Koronski K. 
Published: March 2019

AbstractRealtime in situ temperature monitoring in difficult experimental conditions or inaccessible environments is critical for many applications. Non-contact luminescence decay time thermometry is often the method of choice for such applications due to a favorable combination of sensitivity, accuracy and robustness. In this work, we demonstrate the feasibility of an ultrafast PbI2 scintillator for temperature determination, using the time structure of X-ray radiation, produced by a synchrotron. The decay kinetics of the scintillations was measured over the 8–107 K temperature range using monochromatic pulsed X-ray excitation. It is found that lead iodide exhibits a very fast and intense scintillation response due to excitons and donor-acceptor pairs, with the fast decay component varying between 0.08 and 0.5 ns – a feature that can be readily exploited for temperature monitoring. The observed temperature dependence of the decay time is discussed in terms of two possible mechanisms of thermal quenching – transition over activation barrier and phonon-assisted escape. It is concluded that the latter provides a better fit to the experimental results and is consistent with the model of luminescence processes in PbI2. We evaluated the sensitivity and estimated the accuracy of the temperature determination as ca. ±6 K at 107 K, improving to ±1.4 K at 8 K. The results of this study prove the feasibility of temperature monitoring, using ultrafast scintillation of PbI2 excited by X-ray pulses from a synchrotron, thus enabling non-contact in-situ cryothermometry with megahertz sampling rate.
Single injection of sustained-release prostacyclin analog ONO-1301-MS ameliorates hypoxic toxicity in the murine model of amyotrophic lateral sclerosis
Authors: Tada Satoru , Okuno Tatsusada , Shimizu Mikito , Sakai Yoshiki , Sumi-Akamaru Hisae , Kinoshita Makoto , Yamashita Kazuya , Sanda Eri , Choong Chi-Jing , Namba Akiko , Sasaki Tsutomu , Koda Toru , Takata Kazushiro , Miyagawa Shigeru , Sawa Yoshiki , Nakatsuji Yuji , Mochizuki Hideki 
Published: March 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by several pathologies including oxidative stress, apoptosis, neuroinflammation, and glutamate toxicity. Although multiple reports suggest that ischemia and hypoxia in the spinal cord plays a pivotal role in the pathogenesis of ALS, the precise role of hypoxia in disease progression remains unknown. In this study, we detected higher expression levels of Hypoxia-inducible factor 1-alpha (HIF-1α), a key regulator of cellular responses to hypoxia, in the spinal cord of ALS patients and in the transgenic mice overexpressing the familial ALS-associated G93A SOD1 mutation (mSOD1G93A mice) compared to controls. Single subcutaneous administration of sustained-release prostacyclin analog ONO-1301-MS to mSOD1G93A mice abrogated the expression of HIF-1α in their spinal cords, as well as erythropoietin (EPO) and vascular endothelial growth factor (VEGF), both of which are downstream to HIF-1α. Furthermore, ONO-1301-MS increased the level of mature brain-derived neurotrophic factor (BDNF) and ATP production in the spinal cords of mSOD1G93A mice. At late disease stages, the motor function and the survival of motor neurons of ONO-1301-MS-treated mSOD1G93A mice was significantly improved compared to vehicle-treated mSOD1G93A mice. Our data suggest that vasodilator therapy modulating local blood flow in the spinal cord has beneficial effects against ALS disease progression.
Mendelian randomisation analyses find pulmonary factors mediate the effect of height on coronary artery disease
Authors: Marouli Eirini , Del Greco M. Fabiola , Astley Christina M. , Yang Jian , Ahmad Shafqat , Berndt Sonja I. , Caulfield Mark J. , Evangelou Evangelos , McKnight Barbara , Medina-Gomez Carolina , van Vliet-Ostaptchouk Jana V. , Warren Helen R. , Zhu Zhihong , Hirschhorn Joel N. , Loos Ruth J. F. , Kutalik Zoltan , Deloukas Panos 
Published: March 2019

AbstractThere is evidence that lower height is associated with a higher risk of coronary artery disease (CAD) and increased risk of type 2 diabetes (T2D). It is not clear though whether these associations are causal, direct or mediated by other factors. Here we show that one standard deviation higher genetically determined height (~6.5 cm) is causally associated with a 16% decrease in CAD risk (OR = 0.84, 95% CI 0.80–0.87). This causal association remains after performing sensitivity analyses relaxing pleiotropy assumptions. The causal effect of height on CAD risk is reduced by 1–3% after adjustment for potential mediators (lipids, blood pressure, glycaemic traits, body mass index, socio-economic status). In contrast, our data suggest that lung function (measured by forced expiratory volume [FEV1] and forced vital capacity [FVC]) is a mediator of the effect of height on CAD. We observe no direct causal effect of height on the risk of T2D.
Unraveling the role of the MOV10 RNA helicase during influenza A virus infection
Authors: Villalón-Letelier Fernando , Reading Patrick C. 
Published: March 2019

Abstract
Moloney leukemia virus 10 (MOV10) is an interferon-inducible RNA helicase that has been implicated in a broad range of cellular functions, including modulating the replication of a diverse range of viruses. However, the mechanisms by which MOV10 promotes or inhibits the replication of particular viruses have not been well defined. A recent paper published in the Biochemical Journal by Li et al. [Biochem. J. (2019) 476, 467–481] provides insight regarding the mechanisms by which MOV10 restricts influenza A virus (IAV) infection in host cells. First, the authors confirm that MOV10 binds to the viral nucleoprotein (NP) and sequesters the viral ribonucleoprotein complex in cytoplasmic granules called processing (P)-bodies, thus inhibiting IAV replication. Second, they demonstrate that the non-structural (NS)1 protein of IAV can act as an antagonist of MOV10, inhibiting the association of MOV10 with NP and promoting MOV10 degradation through the lysosomal pathway. Further research will determine if cellular RNA helicases such as MOV10 represent suitable targets for the development of novel anti-IAV therapies.
Research Subjects and Research Trends in Medical Informatics
Authors: Gülkesen Kemal Hakan , Haux Reinhold 
Published: March 2019

Objectives To identify major research subjects and trends in medical informatics research based on the current set of core medical informatics journals.
Methods Analyzing journals in the Web of Science (WoS) medical informatics category together with related categories from the years 2013 to 2017 by using a smart local moving algorithm as a clustering method for identifying the core set of journals. Text mining analysis with binary counting of abstracts from these journals published in the years 2006 to 2017 for identifying major research subjects. Building clusters based on these terms for the complete time period as well as for the periods 2006–2008, 2009–2011, 2012–2014, and 2015–2017 for identifying trends.
Results The identified cluster includes 17 core medical informatics journals. By text mining of these journals, 224,992 different terms in 14,414 articles were identified covering 550 specific key terms. Based on these key terms five clusters were identified: “Biomedical Data Analysis,” “Clinical Informatics,” “EHR and Knowledge Representation,” “Mobile Health,” and “Organizational Aspects of Health Information Systems.” No shifts in the clusters were observed between the first two 3-year periods. In the third period, some terms like “mobile phone,” “mobile apps,” and “message” appear. Also, in the third period, a “Clinical Informatics” cluster appears and persists in the fourth period. In the fourth period, a rearrangement of clusters was observed.
Conclusions Beside classical subjects of medical informatics on organizing, representing, and analyzing data, we observed new developments in the context of mobile health and clinical informatics. These subjects tended to grow over the past years, and we can expect this trend to continue.