bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of compound causing yellow bone discoloration following alpha-glycosyl isoquercitrin exposure in Sprague–Dawley rats
Authors: Davis Jeffrey P. , Koyanagi Mihoko , Maronpot Robert R. , Recio Leslie , Hayashi Shim-mo 
Published: May 2020

AbstractPrevious rat toxicity studies of alpha-glycosyl isoquercitrin (AGIQ), a water-soluble flavonol glycoside derived from rutin, revealed systemic yellow bone discoloration. This investigative study was conducted to determine the AGIQ metabolite(s) responsible for the discoloration. Female Sprague–Dawley rats were administered dietary AGIQ at doses of 0%, 1.5%, 3.0%, or 5.0% (0, 1735.0, 3480.8, and 5873.7 mg/kg/day, respectively) for 14 days, followed by a 14- or 28-day recovery period. Measurements of quercetin in urine and quercetin, quercetin 3-O-glucuronide, kaempferol, and 3-o-methylquercetin metabolites of AGIQ in bone (femur), white and brown fat, and cerebrum samples were conducted following the exposure period and each recovery period. Gross examination of the femur revealed yellow discoloration that increased in intensity with dose and was still present in a dose-related manner following both recovery periods. Quercetin, at levels correlating with AGIQ dose, was measured in the urine following the 14-day exposure period and, at lower concentrations, 14 or 28 days following cessation of AGIQ exposure. All four metabolites were present in a dose-dependent manner in the femur following 14 days of dietary exposure; only quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were present during the recovery periods. Quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were detected in white fat (along with kaempferol), brown fat (excluding quercetin due to analytical interference), and cerebrum samples, indicating systemic availability of the metabolites. Collectively, these data implicate quercetin, quercetin 3-O-glucuronide, or 3-o-methylquercetin (or a combination thereof) as the most likely metabolite of AGIQ causing the yellow discoloration of bone in rats administered dietary AGIQ.
Artificial neural networks for quantitative online NMR spectroscopy
Authors: Kern Simon , Liehr Sascha , Wander Lukas , Bornemann-Pfeiffer Martin , Müller Simon , Maiwald Michael , Kowarik Stefan 
Published: May 2020

AbstractIndustry 4.0 is all about interconnectivity, sensor-enhanced process control, and data-driven systems. Process analytical technology (PAT) such as online nuclear magnetic resonance (NMR) spectroscopy is gaining in importance, as it increasingly contributes to automation and digitalization in production. In many cases up to now, however, a classical evaluation of process data and their transformation into knowledge is not possible or not economical due to the insufficiently large datasets available. When developing an automated method applicable in process control, sometimes only the basic data of a limited number of batch tests from typical product and process development campaigns are available. However, these datasets are not large enough for training machine-supported procedures. In this work, to overcome this limitation, a new procedure was developed, which allows physically motivated multiplication of the available reference data in order to obtain a sufficiently large dataset for training machine learning algorithms. The underlying example chemical synthesis was measured and analyzed with both application-relevant low-field NMR and high-field NMR spectroscopy as reference method. Artificial neural networks (ANNs) have the potential to infer valuable process information already from relatively limited input data. However, in order to predict the concentration at complex conditions (many reactants and wide concentration ranges), larger ANNs and, therefore, a larger training dataset are required. We demonstrate that a moderately complex problem with four reactants can be addressed using ANNs in combination with the presented PAT method (low-field NMR) and with the proposed approach to generate meaningful training data.
Exercise Field Testing in Children: A New Approach for Age-Appropriate Evaluation of Cardiopulmonary Function
Authors: Schöffl Isabelle , Ehrlich Benedikt , Stanger Simon , Rottermann Kathrin , Dittrich Sven , Schöffl Volker 
Published: May 2020

AbstractBased on the wide range of problems to effectively perform cardiopulmonary testing in young children, this study strives to develop a new cardiopulmonary exercise test for children using a mobile testing device worn in a backpack in order to test children during their natural movement habits, namely, running outdoors. A standard cardiopulmonary exercise ramp test on a cycle ergometer was performed by a group of twenty 7–10-year-old children. The results were compared with a self-paced incremental running test performed using a mobile cardiopulmonary exercise measuring device in an outdoor park. The children were able to reach significantly higher values for most of the cardiopulmonary exercise variables during the outdoor test and higher. Whereas a plateau in$${\dot{\text{V}}\text{O}}_{{2}}$$V˙O2was reached by 25% of the children during the outdoor test, only 75% were able to reach a reasonable VT2, let alone$${\dot{\text{V}}\text{O}}_{{{\text{2peak}}}}$$V˙O2peak, during the bicycle test. The heart rate at VT1, the O2-pulse, and the OUES were comparable between both tests. OUES was also positively correlated with$${\dot{\text{V}}\text{O}}_{{{\text{2peak}}}}$$V˙O2peakin both tests. Testing children outdoors using a mobile cardiopulmonary exercise unit represents an alternative to standard exercise testing, but without the added problems of exercise equipment like treadmills or bicycles. It allows for individualized exercise testing with the aim of standardized testing durations instead of standardized testing protocols. The running speeds determined during the outdoor tests may then be used to develop age-adapted testing protocols for treadmill testing.
Longitudinal effects of rTMS on neuroplasticity in chronic treatment-resistant depression
Authors: Dalhuisen Iris , Ackermans Eveline , Martens Lieke , Mulders Peter , Bartholomeus Joey , de Bruijn Alex , Spijker Jan , van Eijndhoven Philip , Tendolkar Indira 
Published: May 2020

AbstractMajor depressive disorder (MDD) is amongst the most prevalent of psychiatric disorders. Unfortunately, a third of patients will not respond to conventional treatments and suffer from treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) has been proven effective in treating TRD. The research suggests that rTMS acts via neuroplastic effects on the brain, which can be measured by changes in hippocampal and amygdala volume as well as cortical thickness. This sham-controlled study investigates longitudinal effects of rTMS on the volumes of the hippocampus and amygdala and cortical thickness in patients with chronic TRD. 31 patients received 20 sessions of high-frequency rTMS (N = 15) or sham treatment (N = 16) over the left dorsolateral prefrontal cortex during 4 consecutive weeks. Using structural magnetic resonance imaging, we investigated longitudinal treatment effects on hippocampus and amygdala volume as well as thickness of the paralimbic cortex. We found no clinical differences between the active and sham rTMS group. Longitudinal changes in hippocampal and amygdala volume did not differ significantly, although males showed a significant decrease in left amygdala volume, irrespective of treatment group. Changes in cortical thickness of the paralimbic cortex differed significantly between the active and sham groups. Most notably, the increase in cortical thickness of the isthmus of the left cingulate gyrus was greater in the active as compared to the sham rTMS group. Our data suggest that rTMS can induce neuroplastic changes, particularly in cortical thickness, independent of treatment response. We also found longitudinal changes in amygdala volume in males. For clinical effects to follow these neuroplastic effects, more intensive rTMS treatment might be needed in chronically depressed patients.Trial registration number: ISRCTN 15535800, registered on 29-06-2017.
The differential expression of micro-RNAs 21, 200c, 204, 205, and 211 in benign, dysplastic and malignant melanocytic lesions and critical evaluation of their role as diagnostic biomarkers
Authors: Quiohilag Katherine , Caie Peter , Oniscu Anca , Brenn Thomas , Harrison David 
Published: May 2020

AbstractOverlapping histological features between benign and malignant lesions and a lack of firm diagnostic criteria for malignancy result in high rates of inter-observer variation in the diagnosis of melanocytic lesions. We aimed to investigate the differential expression of five miRNAs (21, 200c, 204, 205, and 211) in benign naevi (n = 42), dysplastic naevi (n = 41), melanoma in situ (n = 42), and melanoma (n = 42) and evaluate their potential as diagnostic biomarkers of melanocytic lesions. Real-time PCR showed differential miRNA expression profiles between benign naevi; dysplastic naevi and melanoma in situ; and invasive melanoma. We applied a random forest machine learning algorithm to classify cases based on their miRNA expression profiles, which resulted in a ROC curve analysis of 0.99 for malignant melanoma and greater than 0.9 for all other groups. This indicates an overall very high accuracy of our panel of miRNAs as a diagnostic biomarker of benign, dysplastic, and malignant melanocytic lesions. However, the impact of variable lesion percentage and spatial expression patterns of miRNAs on these real-time PCR results was also considered. In situ hybridisation confirmed the expression of miRNA 21 and 211 in melanocytes, while demonstrating expression of miRNA 205 only in keratinocytes, thus calling into question its value as a biomarker of melanocytic lesions. In conclusion, we have validated some miRNAs, including miRNA 21 and 211, as potential diagnostic biomarkers of benign, dysplastic, and malignant melanocytic lesions. However, we also highlight the crucial importance of considering tissue morphology and spatial expression patterns when using molecular techniques for the discovery and validation of new biomarkers.
Obesity, metabolic syndrome, and primary hypertension
Authors: Litwin Mieczysław , Kułaga Zbigniew 
Published: May 2020

AbstractPrimary hypertension is the dominant form of arterial hypertension in adolescents. Disturbed body composition with, among other things, increased visceral fat deposition, accelerated biological maturation, metabolic abnormalities typical for metabolic syndrome, and increased adrenergic drive constitutes the intermediary phenotype of primary hypertension. Metabolic syndrome is observed in 15–20% of adolescents with primary hypertension. These features are also typical of obesity-related hypertension. Metabolic abnormalities and metabolic syndrome are closely associated with both the severity of hypertension and the risk of target organ damage. However, even though increased body mass index is the main determinant of blood pressure in the general population, not every hypertensive adolescent is obese and not every obese patient suffers from hypertension or metabolic abnormalities typical for metabolic syndrome. Thus, the concepts of metabolically healthy obesity, normal weight metabolically unhealthy, and metabolically unhealthy obese phenotypes have been developed. The risk of hypertension and hypertensive target organ damage increases with exposure to metabolic risk factors which are determined by disturbed body composition and visceral obesity. Due to the fact that both primary hypertension and obesity-related hypertension present similar pathogenesis, the principles of treatment are the same and are focused not only on lowering blood pressure, but also on normalizing body composition and metabolic abnormalities.
Building an efficient OCR system for historical documents with little training data
Authors: Martínek Jiří , Lenc Ladislav , Král Pavel 
Published: May 2020

AbstractAs the number of digitized historical documents has increased rapidly during the last a few decades, it is necessary to provide efficient methods of information retrieval and knowledge extraction to make the data accessible. Such methods are dependent on optical character recognition (OCR) which converts the document images into textual representations. Nowadays, OCR methods are often not adapted to the historical domain; moreover, they usually need a significant amount of annotated documents. Therefore, this paper introduces a set of methods that allows performing an OCR on historical document images using only a small amount of real, manually annotated training data. The presented complete OCR system includes two main tasks: page layout analysis including text block and line segmentation and OCR. Our segmentation methods are based on fully convolutional networks, and the OCR approach utilizes recurrent neural networks. Both approaches are state of the art in the relevant fields. We have created a novel real dataset for OCR from Porta fontium portal. This corpus is freely available for research, and all proposed methods are evaluated on these data. We show that both the segmentation and OCR tasks are feasible with only a few annotated real data samples. The experiments aim at determining the best way how to achieve good performance with the given small set of data. We also demonstrate that obtained scores are comparable or even better than the scores of several state-of-the-art systems. To sum up, this paper shows a way how to create an efficient OCR system for historical documents with a need for only a little annotated training data.
Existence, iteration procedures and directional differentiability for parabolic QVIs
Authors: Alphonse Amal , Hintermüller Michael , Rautenberg Carlos N. 
Published: May 2020

AbstractWe study parabolic quasi-variational inequalities (QVIs) of obstacle type. Under appropriate assumptions on the obstacle mapping, we prove the existence of solutions of such QVIs by two methods: one by time discretisation through elliptic QVIs and the second by iteration through parabolic variational inequalities. Using these results, we show the directional differentiability (in a certain sense) of the solution map which takes the source term of a parabolic QVI into the set of solutions, and we relate this result to the contingent derivative of the aforementioned map. We finish with an example where the obstacle mapping is given by the inverse of a parabolic differential operator.
Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study)
Authors: Sakaida Isao , Terai Shuji , Kurosaki Masayuki , Okada Mitsuru , Hirano Takahiro , Fukuta Yasuhiko 
Published: May 2020

AbstractBackgroundThis large-scale post-marketing surveillance study (START study) evaluated the effectiveness and safety of tolvaptan in Japanese liver cirrhosis patients with hepatic edema in real-world clinical settings. Here, we present the final analysis outcomes.MethodsA prospective, multicenter, non-interventional study involving patients who received tolvaptan for the treatment of liver cirrhosis with hepatic edema with an insufficient response to conventional diuretics. The observation period was up to 6 months. Effectiveness evaluation included changes in body weight and clinical symptoms. Safety analysis included evaluation of adverse drug reactions (ADRs).ResultsCase reports of 1111 patients were collected. Of these, 1109 were included in the safety analysis and 1098 in the effectiveness analysis. The mean age was 69.4 ± 11.5 years and 695 (62.7%) patients were male. After tolvaptan treatment, a decrease in body weight from baseline was − 2.6 ± 2.7 kg on day 7 and − 3.8 ± 4.1 kg on day 14. Moreover, clinical symptoms significantly improved over the 14-day treatment. Frequently reported ADRs were thirst (6.6%), hepatic encephalopathy (2.3%), dehydration (1.5%), and hypernatremia (1.2%). A serum sodium level of ≥ 150 mEq/L was reported in five patients (0.5%). Multivariate analyses showed that the baseline blood urea nitrogen (BUN) level (cut-off value: 22.4 mg/dL) was the predictive factor for tolvaptan treatment response.ConclusionsThe results suggest that tolvaptan was effective and well-tolerated in liver cirrhosis patients with hepatic edema. In the real-world clinical setting, tolvaptan provides a useful option for the treatment of hepatic edema.
Genetic and epigenetic analyses of panic disorder in the post-GWAS era
Authors: Morimoto Yoshiro , Ono Shinji , Kurotaki Naohiro , Imamura Akira , Ozawa Hiroki 
Published: May 2020

AbstractPanic disorder (PD) is a common and debilitating neuropsychiatric disorder characterized by panic attacks coupled with excessive anxiety. Both genetic factors and environmental factors play an important role in PD pathogenesis and response to treatment. However, PD is clinically heterogeneous and genetically complex, and the exact genetic or environmental causes of this disorder remain unclear. Various approaches for detecting disease-causing genes have recently been made available. In particular, genome-wide association studies (GWAS) have attracted attention for the identification of disease-associated loci of multifactorial disorders. This review introduces GWAS of PD, followed by a discussion about the limitations of GWAS and the major challenges facing geneticists in the post-GWAS era. Alternative strategies to address these challenges are then proposed, such as epigenome-wide association studies (EWAS) and rare variant association studies (RVAS) using next-generation sequencing. To date, however, few reports have described these analyses, and the evidence remains insufficient to confidently identify or exclude rare variants or epigenetic changes in PD. Further analyses are therefore required, using sample sizes in the tens of thousands, extensive functional annotations, and highly targeted hypothesis testing.
Carbon monoxide-dependent transcriptional changes in a thermophilic, carbon monoxide-utilizing, hydrogen-evolving bacterium Calderihabitans maritimus KKC1 revealed by transcriptomic analysis
Authors: Inoue Masao , Izumihara Hikaru , Fukuyama Yuto , Omae Kimiho , Yoshida Takashi , Sako Yoshihiko 
Published: May 2020

AbstractCalderihabitans maritimus KKC1 is a thermophilic, carbon monoxide (CO)-utilizing, hydrogen-evolving bacterium that harbors seven cooS genes for anaerobic CO dehydrogenases and six hyd genes for [NiFe] hydrogenases and capable of using a variety of electron acceptors coupled to CO oxidation. To understand the relationships among these unique features and the transcriptional adaptation of the organism to CO, we performed a transcriptome analysis of C. maritimus KKC1 grown under 100% CO and N2 conditions. Of its 3114 genes, 58 and 32 genes were significantly upregulated and downregulated in the presence of CO, respectively. A cooS–ech gene cluster, an “orphan” cooS gene, and bidirectional hyd genes were upregulated under CO, whereas hydrogen-uptake hyd genes were downregulated. Transcriptional changes in anaerobic respiratory genes supported the broad usage of electron acceptors in C. maritimus KKC1 under CO metabolism. Overall, the majority of the differentially expressed genes were oxidoreductase-like genes, suggesting metabolic adaptation to the cellular redox change upon CO oxidation. Moreover, our results suggest a transcriptional response mechanism to CO that involves multiple transcription factors, as well as a CO-responsive transcriptional activator (CooA). Our findings shed light on the diverse mechanisms for transcriptional and metabolic adaptations to CO in CO-utilizing and hydrogen-evolving bacteria.
Groundwater characterization and monitoring at a complex industrial waste site using electrical resistivity imaging
Authors: Rockhold M. L. , Robinson J. L. , Parajuli K. , Song X. , Zhang Z. F. , Johnson T. C. 
Published: May 2020

AbstractA contaminated industrial waste site in Washington State (USA) containing buried, metallic-waste storage tanks, pipes, and wells, was evaluated to determine the feasibility of monitoring groundwater remediation activities associated with an underlying perched aquifer system using electrical resistivity tomography. The perched aquifer, located ~65 m below ground surface and ~10 m above the regional water table, contains high concentrations of nitrate, uranium, and other contaminants of concern from past tank leaks and intentional releases of wastes to surface disposal sites. The extent of the perched water aquifer is not well known, and the effectiveness of groundwater extraction for contaminant removal is uncertain, so supplemental characterization and monitoring technologies are being evaluated. Numerical simulations of subsurface flow and contaminant transport were performed with a highly resolved model of the hydrogeologic system and waste site infrastructure, and these simulations were used as the physical basis for electrical resistivity tomography modeling. The modeling explicitly accounted for metallic infrastructure at the site. The effectiveness of using surface electrodes versus surface and horizontal subsurface electrodes, for imaging groundwater extraction from the perched water aquifer, was investigated. Although directional drilling is a mature technology, its use for electrode emplacement in the deep subsurface under a complex industrial waste site via horizontal wells has not yet been demonstrated. Results from this study indicate that using horizontal subsurface electrode arrays could significantly improve the ability of electrical resistivity tomography to image deep subsurface features and monitor remediation activities under complex industrial waste sites.
Visual timing abilities of a harbour seal (Phoca vitulina) and a South African fur seal (Arctocephalus pusillus pusillus) for sub- and supra-second time intervals
Authors: Heinrich Tamara , Ravignani Andrea , Hanke Frederike D. 
Published: May 2020

AbstractTiming is an essential parameter influencing many behaviours. A previous study demonstrated a high sensitivity of a phocid, the harbour seal (Phoca vitulina), in discriminating time intervals. In the present study, we compared the harbour seal’s timing abilities with the timing abilities of an otariid, the South African fur seal (Arctocephalus pusillus pusillus). This comparison seemed essential as phocids and otariids differ in many respects and might, thus, also differ regarding their timing abilities. We determined time difference thresholds for sub- and suprasecond time intervals marked by a white circle on a black background displayed for a specific time interval on a monitor using a staircase method. Contrary to our expectation, the timing abilities of the fur seal and the harbour seal were comparable. Over a broad range of time intervals, 0.8–7 s in the fur seal and 0.8–30 s in the harbour seal, the difference thresholds followed Weber’s law. In this range, both animals could discriminate time intervals differing only by 12 % and 14 % on average. Timing might, thus be a fundamental cue for pinnipeds in general to be used in various contexts, thereby complementing information provided by classical sensory systems. Future studies will help to clarify if timing is indeed involved in foraging decisions or the estimation of travel speed or distance.