bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilberry and Sea Buckthorn Leaves and Their Subcritical Water Extracts Prevent Lipid Oxidation in Meat Products
Authors: Mäkinen Sari , Hellström Jarkko , Mäki Maarit , Korpinen Risto , Mattila Pirjo H.
Published: March 2020

The aim of this study was to find new sustainable, Nordic natural antioxidant sources, develop subcritical water extraction (SWE) process for recovering the antioxidant compounds from the most potential raw materials, and to test their antioxidative effects in meat products. The antioxidant capacities of water and 50% ethanol (aq) extracts of 13 berry, grain, and horticultural plant materials as well as hexane/ethanol extracted stilbene fractions from pine heartwood and spruce inner bark were measured in hydrophilic and lipophilic systems. Tree, bilberry leaf (BL), and sea buckthorn leaf (SBL) extracts showed the highest antioxidant capacities. BL and SBL were selected for the development of SWE. The optimal conditions for recovering maximal antioxidative capacities were 110 °C/1 min for SBL and 120 °C/1 min for BL. Dried BL and SBL and the respective optimized subcritical water extracts were applied in chicken slices and pork sausage, and their ability to prevent lipid oxidation was evaluated during 8 and 20 days storage, respectively, at 6 °C. All tested plant ingredients effectively prevented lipid oxidation in the products compared to the control samples. Sensory acceptance of the plant ingredients was good, especially in the chicken product. To our knowledge, this is the first study to assess the antioxidant effects of SW extracted berry leaves in meat products.
Inactivation and Damage of Histamine-Forming Bacteria by Treatment with High Hydrostatic Pressure
Authors: Lee Yi-Chen , Tsai Yung-Hsiang , Chen Shao-Lan , Kung Hsien-Feng , Arakawa Osamu , Wei Cheng-I
Published: March 2020

The inactivation and damage of histamine-forming bacteria (HFB), Enterobacter aerogenes and Staphylococcus capitis, in a 0.1 M potassium phosphate buffer (pH 6.8) and marlin meat slurry by high hydrostatic pressure (HHP) treatments were studied using viability measurement and scanning electron microscopy (SEM). HHP treatments showed first order destruction kinetics to E. aerogenes and S. capitis during the pressure holding period. HFB in marlin meat slurry had higher D values and were more resistant to HHP treatments than in phosphate buffer. In phosphate buffer, E. aerogenes had higher D values than S. capitis at >380 MPa of pressure, whereas the reverse trend was noticed at lower pressures (<380 MPa). In marlin meat slurry, S. capitis had a higher D value than E. aerogenes at the same treatment pressure, indicating that S. capitis was more resistant to HHP treatment. To our knowledge, this is the first report to demonstrate that HHP can be used to inactivate HFB, E. aerogenes, and S. capitis, by causing disruption to bacterial cell membrane and cell wall as demonstrated by SEM micrographs.
Exogenous Spermidine Promotes γ-Aminobutyric Acid Accumulation and Alleviates the Negative Effect of NaCl Stress in Germinating Soybean (Glycine max L.)
Authors: Fang Weiming , Qi Fei , Yin Yongqi , Yang Zhengfei
Published: March 2020

We investigated the effects of exogenous spermidine (Spd) on the physiological status, γ-aminobutyric acid (GABA) synthase activity, and gene expressions in germinating soybeans under NaCl stress. The results show that Spd significantly increases sprout growth and biomass, decreases malonaldehyde and H2O2 contents, and markedly promotes the activities of superoxide dismutase, catalase, peroxidase, and glutathione peroxidase of germinating soybeans. The harmful effect of NaCl stress was alleviated by exogenous Spd. GABA accumulation in germinating soybeans was caused by the activation of diamine oxidase, polyamine oxidase, aminoaldehyde dehydrogenase, and glutamate decarboxylase activities and by up-regulating their gene expression under Spd-NaCl treatment. The GABA content decreased by 57% and 46% in germinating soybeans with the application of aminoguanidine under Spd and Spd-NaCl treatments, respectively. In conclusion, spermidine induces the accumulation of GABA and increases sprouts biomass, thereby enhancing the functional quality of germinating soybeans.
Inhibitory Effect of 1,5-Dimethyl Citrate from Sea Buckthorn (Hippophae rhamnoides) on Lipopolysaccharide-Induced Inflammatory Response in RAW 264.7 Mouse Macrophages
Authors: Baek Su Cheol , Lee Dahae , Jo Mun Seok , Lee Kwang Ho , Lee Yong Hoon , Kang Ki Sung , Yamabe Noriko , Kim Ki Hyun
Published: March 2020

Hippophae rhamnoides L. (Elaeagnaceae; commonly known as “sea buckthorn” and “vitamin tree”), is a spiny deciduous shrub whose fruit is used in foods and traditional medicines. The H. rhamnoides fruit (berry) is rich in vitamin C, with a level exceeding that found in lemons and oranges. H. rhamnoides berries are usually washed and pressed to create pomace and juice. Today, the powder of the aqueous extract of H. rhamnoides berries are sold as a functional food in many countries. As part of our ongoing effort to identify bioactive constituents from natural resources, we aimed to isolate and identify those from the fruits of H. rhamnoides. Phytochemical analysis of the extract of H. rhamnoides fruits led to the isolation and identification of six compounds, namely, a citric acid derivative (1), a phenolic (2), flavonoids (3 and 4), and megastigmane compounds (5 and 6). Treatment with compounds 1–6 did not have any impact on the cell viability of RAW 264.7 mouse macrophages. However, pretreatment with these compounds suppressed lipopolysaccharide (LPS)-induced NO production in RAW 264.7 mouse macrophages in a concentration-dependent manner. Among the isolated compounds, compound 1 was identified as the most active, with an IC50 of 39.76 ± 0.16 μM. This value was comparable to that of the NG-methyl-L-arginine acetate salt, a nitric oxide synthase inhibitor with an IC50 of 28.48 ± 0.05 μM. Western blot analysis demonstrated that compound 1 inhibited the LPS-induced expression of IKKα/β (IκB kinase alpha/beta), I-κBα (inhibitor of kappa B alpha), nuclear factor kappa-B (NF-κB) p65, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) in RAW 264.7 cells. Furthermore, LPS-stimulated cytokine production was detected using a sandwich enzyme-linked immunosorbent assay. Compound 1 decreased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) production in LPS-stimulated RAW 264.7 cells. In summary, the mechanism of action of 1 included the suppression of LPS-induced NO production in RAW 264.7 cells by inhibiting IKKα/β, I-κBα, NF-κB p65, iNOS, and COX-2, and the activities of IL-6 and TNF-α.
Effect of Aromatic Amines on the Properties of Formaldehyde-Based Xerogels
Authors: Martin David , Prostredný Martin , Fletcher Ashleigh J.
Published: March 2020

This study investigates the synthesis of formaldehyde-based xerogels using alternative aromatic precursors, with comparison to traditional resorcinol-formaldehyde analogues, in order to alter the chemical composition of the resulting gels. By replacing resorcinol with aromatic amine molecules, i.e., ammeline, melamine and melem, each expected to undergo similar reactions with formaldehyde as the substituted species, we found that for all substituted gels, at low additive contents, the gel structure was compromised and non-porous materials were formed, as opposed to the most abundant monomers, and therefore, these additives seem to act as impurities at low levels. Working towards higher additive contents, melem monomers exhibited low solubility (~5%), even at elevated temperatures, thereby limiting the range to which melem could act as a substitute, while melamine could be incorporated up to ~40% under acidic conditions, with enhanced microporosity over this range. Pure gels were successfully synthesised from ammeline, but their performance was inferior to resorcinol-formaldehyde gels, while melamine-formaldehyde analogues required acidic reaction conditions but shrank considerably on sub-critical drying, adversely affecting the gel properties and demonstrating their lack of potential as sorbents. This demonstrates the potential for the inclusion of aminated aromatics within resorcinol-based gel systems, however, only as partial substitutes and not complete replacements.
Haplotype Analysis of GJB2 Mutations: Founder Effect or Mutational Hot Spot?
Authors: Shinagawa Jun , Moteki Hideaki , Nishio Shin-ya , Noguchi Yoshihiro , Usami Shin-ichi
Published: March 2020

The GJB2 gene is the most frequent cause of congenital or early onset hearing loss worldwide. In this study, we investigated the haplotypes of six GJB2 mutations frequently observed in Japanese hearing loss patients (i.e., c.235delC, p.V37I, p.[G45E; Y136X], p.R143W, c.176_191del, and c.299_300delAT) and analyzed whether the recurring mechanisms for each mutation are due to founder effects or mutational hot spots. Furthermore, regarding the mutations considered to be caused by founder effects, we also calculated the age at which each mutation occurred using the principle of genetic clock analysis. As a result, all six mutations were observed in a specific haplotype and were estimated to derive from founder effects. Our haplotype data together with their distribution patterns indicated that p.R143W and p.V37I may have occurred as multiple events, and suggested that both a founder effect and hot spot may be involved in some mutations. With regard to the founders’ age of frequent GJB2 mutations, each mutation may have occurred at a different time, with the oldest, p.V37I, considered to have occurred around 14,500 years ago, and the most recent, c.176_191del, considered to have occurred around 4000 years ago.
Does DNA Methylation Matter in FSHD?
Authors: Salsi Valentina , Magdinier Frédérique , Tupler Rossella
Published: March 2020

Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the genetic and epigenetic molecular features of the CpG-rich D4Z4 repeat tandem array at 4q35. Reduced DNA methylation of D4Z4 repeats is considered part of the FSHD mechanism and has been proposed as a reliable marker in the FSHD diagnostic procedure. We considered the assessment of D4Z4 DNA methylation status conducted on distinct cohorts using different methodologies. On the basis of the reported results we conclude that the percentage of DNA methylation detected at D4Z4 does not correlate with the disease status. Overall, data suggest that in the case of FSHD1, D4Z4 hypomethylation is a consequence of the chromatin structure present in the contracted allele, rather than a proxy of its function. Besides, CpG methylation at D4Z4 DNA is reduced in patients presenting diseases unrelated to muscle progressive wasting, like Bosma Arhinia and Microphthalmia syndrome, a developmental disorder, as well as ICF syndrome. Consistent with these observations, the analysis of epigenetic reprogramming at the D4Z4 locus in human embryonic and induced pluripotent stem cells indicate that other mechanisms, independent from the repeat number, are involved in the control of the epigenetic structure at D4Z4.
Reliability of the Linear Measurement (Contact) Method Compared with Stereophotogrammetry (Optical Scanning) for the Evaluation of Edema after Surgically Assisted Rapid Maxillary Expansion
Authors: Koçer Gülperi , Sönmez Samed , Findik Yavuz , Yazici Tayfun
Published: March 2020

Many techniques have been developed to evaluate facial swelling after maxillofacial surgeries. Patients who undergo surgically assisted rapid maxillary expansion (SARME) develop facial edema more often than those who undergo minor oral surgeries. Reliable systems to assess soft tissue dimensions offer many advantages for documentation and treatment planning across surgical fields. (1) Background: The objective assessment of facial swelling is advantageous as it allows the evaluation of the effect of anti-inflammatory drugs. Therefore, this study aimed to compare the reliabilities of linear measurement method and optical scanning for the objective assessment of facial swelling after SARME. (2) Methods: Sixteen (12 women and 4 men) patients were enrolled. Linear measurements between guide points and facial scans were obtained for the left and right sides preoperatively and 1, 2, and 5 days after SARME. Preoperative values were subtracted from each post-operative value and the differences were compared between the two measurement methods. (3) Results: There were no statistically significant differences between the right and left sides at any time point in the measurements with either method. (4) Conclusions: Recently, stereophotogrammetry has been considered the first choice method for evaluating facial swelling. Furthermore, we found a strong correlation between volumetric analysis and linear measurement at all time points and for both sides.
Spatial Prediction of Landslide Susceptibility Based on GIS and Discriminant Functions
Authors: Wang Guirong , Chen Xi , Chen Wei
Published: March 2020

The areas where landslides occur frequently pose severe threats to the local population, which necessitates conducting regional landslide susceptibility mapping (LSM). In this study, four models including weight-of-evidence (WoE) and three WoE-based models, which were linear discriminant analysis (LDA), Fisher’s linear discriminant analysis (FLDA), and quadratic discriminant analysis (QDA), were used to obtain the LSM in the Nanchuan region of Chongqing, China. Firstly, a dataset was prepared from sixteen landslide causative factors, including eight topographic factors, three distance-related factors, and five environmental factors. A landslide inventory map including 298 landslide locations was also constructed and randomly divided with a ratio of 70:30 as training and validation data. Subsequently, the WoE method was used to estimate the relationship between landslides and the landslide causative factors, which assign a weight value to each class of causative factors. Finally, four models were applied using the training dataset, and the predictive performance of each model was compared using the validation datasets. The results showed that FLDA had a higher performance than the other three models according to the success rate curve (SRC) and prediction rate curve (PRC), illustrating that it could be considered a promising approach for landslide susceptibility mapping in the study area.
M2 Receptor Activation Counteracts the Glioblastoma Cancer Stem Cell Response to Hypoxia Condition
Authors: Cristofaro Ilaria , Limongi Chiara , Piscopo Paola , Crestini Alessio , Guerriero Claudia , Fiore Mario , Conti Luciano , Confaloni Annamaria , Tata Ada Maria
Published: March 2020

Glioblastoma multiforme (GBM) is the most malignant brain tumor. Hypoxic condition is a predominant feature of the GBM contributing to tumor growth and resistance to conventional therapies. Hence, the identification of drugs able to impair GBM malignancy and aggressiveness is considered of great clinical relevance. Previously, we demonstrated that the activation of M2 muscarinic receptors, through the agonist arecaidine propargyl ester (Ape), arrests cell proliferation in GBM cancer stem cells (GSCs). In the present work, we have characterized the response of GSCs to hypoxic condition showing an upregulation of hypoxia-inducible factors and factors involved in the regulation of GSCs survival and proliferation. Ape treatment in hypoxic conditions is however able to inhibit cell cycle progression, causing a significant increase of aberrant mitosis with consequent decreased cell survival. Additionally, qRT-PCR analysis suggest that Ape downregulates the expression of stemness markers and miR-210 levels, one of the main regulators of the responses to hypoxic condition in different tumor types. Our data demonstrate that Ape impairs the GSCs proliferation and survival also in hypoxic condition, negatively modulating the adaptive response of GSCs to hypoxia.
Benzene Derivatives from Ink Lead to False Positive Results in Neonatal Hyperphenylalaninemia Screening with Ninhydrin Fluorometric Method
Authors: Feng Shuren , Mei Joanne , Yang Lu , Luo Ping , Wang Xiaonan , Wang Yuan , Yao Jingyi , Cui Lan , Pan Lei , Wang Zefang , Xin Li
Published: March 2020

Ninhydrin-based fluorometric quantification of phenylalanine is one of the most widely used methods for hyperphenylalaninemia (HPA) screening in neonates due to its high sensitivity, high accuracy, and low cost. Here we report an increase of false positive cases in neonatal HPA screening with this method, caused by contamination of blood specimen collection devices during the printing process. Through multiple steps of verification, the contaminants were identified from ink circles printed on the collection devices to indicate the positions and sizes of blood drops. Blood specimens from HPA-negative persons collected on these contaminated collection devices showed positive results in the fluorometric tests, but negative results in tandem mass spectroscopy (MS/MS) experiments. Contaminants on the collection devices could be extracted by 80% ethanol and showed an absorption peak around 245 nm, suggesting that these contaminants may contain benzene derivatives with similar structure to phenylalanine. High-performance liquid chromatography (HPLC) analysis of the ethanol extracts from contaminated collection devices identified two prominent peaks specifically from the devices. Methyl-2-benzoylbenzoate (MBB, CAS#606-28-0) was found as one of the major chemicals from contaminated collection devices. This report aims to remind colleagues in the field of this potential contamination and call for tighter regulation and quality control of specimen collection devices.
A Responsible Machine Learning Workflow with Focus on Interpretable Models, Post-hoc Explanation, and Discrimination Testing
Authors: Gill Navdeep , Hall Patrick , Montgomery Kim , Schmidt Nicholas
Published: March 2020

This manuscript outlines a viable approach for training and evaluating machine learning systems for high-stakes, human-centered, or regulated applications using common Python programming tools. The accuracy and intrinsic interpretability of two types of constrained models, monotonic gradient boosting machines and explainable neural networks, a deep learning architecture well-suited for structured data, are assessed on simulated data and publicly available mortgage data. For maximum transparency and the potential generation of personalized adverse action notices, the constrained models are analyzed using post-hoc explanation techniques including plots of partial dependence and individual conditional expectation and with global and local Shapley feature importance. The constrained model predictions are also tested for disparate impact and other types of discrimination using measures with long-standing legal precedents, adverse impact ratio, marginal effect, and standardized mean difference, along with straightforward group fairness measures. By combining interpretable models, post-hoc explanations, and discrimination testing with accessible software tools, this text aims to provide a template workflow for machine learning applications that require high accuracy and interpretability and that mitigate risks of discrimination.
Alternate Method of Pavement Assessment Using Geophones and Accelerometers for Measuring the Pavement Response
Authors: Bahrani Natasha , Blanc Juliette , Hornych Pierre , Menant Fabien
Published: March 2020

Pavement instrumentation with embeddable in-situ sensors has been a feasible approach to determine pavement deteriorations. Determining pavement deflections during the passage of the load is a promising strategy to determine the overall performance of the pavement. There are different devices that apply loads to the pavements and measure the deflection basin, these include static, vibratory, or impulse loadings. Most commonly used are the static loading like Benkelman beam and impulse loading like the Falling Weight Deflectometer (FWD). However, these techniques are costly and the measurements are recorded infrequently, i.e., once per year or two years. This study focuses on the use of geophones and accelerometers to measure the surface deflections under traffic loading. To develop a method to measure pavement deflections, the sensors were submitted first to laboratory tests, and then tested in situ, in a full scale accelerated pavement test. In the laboratory, the sensors were submitted to different types of loading using a vibrating table. These tests were used to determine the noise and sensitivity of the sensors, and then to evaluate their response to signals simulating pavement deflections under heavy vehicles. The sensor response was compared with measurements of a reference displacement sensor. Different processing techniques were proposed to correct the measurements from geophones and accelerometers, in order to obtain reliable deflection values. Then, the sensors were evaluated in a full scale accelerated test, under real heavy axle loads. Tests were performed at different loads and speeds, and the deflection measurements were compared with a reference anchored deflection sensor. The main advantage of using accelerometers or geophones embedded in the pavement is to enable continuous pavement monitoring, under real traffic. The sensor measurements could also be used to determine the type of vehicles and their corresponding speeds. The study describes in detail the signal analysis needed to measure the pavement deflections accurately. The measurements of pavement deflection can be then used to analyze the pavement behavior in the field, and its evolution with time, and to back-calculate pavement layer properties.
Autonomous Mobile Ground Control Point Improves Accuracy of Agricultural Remote Sensing through Collaboration with UAV
Authors: Han Xiongzhe , Thomasson J. Alex , Wang Tianyi , Swaminathan Vaishali
Published: March 2020

Ground control points (GCPs) are critical for agricultural remote sensing that require georeferencing and calibration of images collected from an unmanned aerial vehicles (UAV) at different times. However, the conventional stationary GCPs are time-consuming and labor-intensive to measure, distribute, and collect their information in a large field setup. An autonomous mobile GCP and a collaboration strategy to communicate with the UAV were developed to improve the efficiency and accuracy of the UAV-based data collection process. Prior to actual field testing, preliminary tests were conducted using the system to show the capability of automatic path tracking by reducing the root mean square error (RMSE) for lateral deviation from 34.3 cm to 15.6 cm based on the proposed look-ahead tracking method. The tests also indicated the feasibility of moving reflectance reference panels successively along all the waypoints without having detrimental effects on pixel values in the mosaicked images, with the percentage errors in digital number values ranging from −1.1% to 0.1%. In the actual field testing, the autonomous mobile GCP was able to successfully cooperate with the UAV in real-time without any interruption, showing superior performances for georeferencing, radiometric calibration, height calibration, and temperature calibration, compared to the conventional calibration method that has stationary GCPs.
Secondary Hyperparathyroidism and Hypertension: An Intriguing Couple
Authors: Simeoni Mariadelina , Perna Alessandra F. , Fuiano Giorgio
Published: March 2020

Secondary hyperparathyroidism (SHPTH) is a major complication in patients on maintenance hemodialysis burdened with high cardiovascular risk. Hypertension is also a high prevalence complication contributing to an increase in the mortality rate in hemodialysis patients. A possible association between SHPTH and hypertension has been widely reported in the literature and several pathogenetic mechanisms have been described. There is evidence that the decrease of plasma iPTH levels are correlated with hypertension correction in hemodialysis patients undergoing parathyroidectomy and oral calcimimetics administration. We have observed a similar behaviour also in a patient on chronic hemodialysis treated with Etelcalcetide. Even if this is an isolated observation, it could stimulate future investigation, possibly in dedicated clinical trials.
Do Knee Pain Phenotypes Have Different Risks of Total Knee Replacement?
Authors: Pan Feng , Tian Jing , Munugoda Ishanka P. , Graves Stephen , Lorimer Michelle , Cicuttini Flavia , Jones Graeme
Published: March 2020

Pain is the main impetus for osteoarthritis (OA) patients to seek healthcare including joint replacement. The pain experience in OA is heterogeneous and affected by factors across multiple domains—peripheral, psychological, and neurological. This indicates the existence of homogenous subgroups/phenotypes within OA patients with pain. We recently identified three pain phenotypes using a wide spectrum of pain-related factors, including structural damage on magnetic resonance imaging (MRI), emotional problems, number of painful sites, sex, body mass index, education level and comorbidities (i.e., Class 1: high prevalence of emotional problems and low prevalence of structural damage (25%); Class 2: low prevalence of emotional problems and high prevalence of structural damage (20%); Class 3: low prevalence of emotional problems and low prevalence of structural damage (55%)). This study was to examine whether the total knee replacement (TKR) risk over 12 years was different among these three pain phenotypes. Data on 963 participants (mean age 62.8 ± 7.4 years) from a population-based cohort study were utilised. Data on socio-demographic, psychological and comorbidities were collected. MRI of the right knee structural pathology was performed. TKR history was ascertained by linking to the Australian Orthopedic Association National Joint Replacement Registry. Latent class analysis and the Cox proportional hazards model were applied for the analysis. During the follow-up period, 41 right and 44 left TKRs in 67 participants were identified. In multivariable analyses, participants in Class 1 and 2 had a higher risk of having a TKR (Class 1 vs. Class 3, HR (hazard ratio) 4.81, 95%CI (confidence interval) 2.33–9.93; Class 2 vs. Class 3, HR 9.23, 95%CI 4.66–18.30). These associations were stronger in the imaged right knee but were also significant in the left knee. Participants within distinct pain phenotypes have different risks of TKR, suggesting that the identified phenotypes reflect distinct clinical subgroups with different prognoses. The risk for TKR was higher in Class 1 than that in Class 3, suggesting that pain/emotional status is a stronger driver for TKR than structural damage, and that selecting patients for TKR needs to be optimized in clinical practice.
Functional Outcome at Short and Middle Term of the Extracorporeal Shockwave Therapy Treatment in Lateral Epicondylitis: A Case-Series Study
Authors: Testa Gianluca , Vescio Andrea , Perez Stefano , Petrantoni Vincenzo , Mazzarella Giulio , Costarella Luciano , Pavone Vito
Published: March 2020

Lateral epicondylitis (LE) of the humerus is a chronic degeneration of wrist extensor tendons at their attachments to the lateral epicondyle of the humerus. There is not a common consensus on a specific therapeutic algorithm, but Extracorporeal Shockwave Therapy (ESWT) is widely used. The purpose of this study is to evaluate the clinical benefits of low dose ESWT in LE-affected patients in short and medium follow-up. Between January 2015 and December 2017, 60 patients (38 male, mean age 52.2 ± 10.1 years, the duration of the disease was 3.6 ± 1.3 months) were clinically evaluated using visual analog scale (VAS) and Patient Rated Tennis Elbow Evaluation Test (PRTEE-I) scores before treatment, at one, three, six and 12 months after treatment. According to the VAS and PRTEE-I scoring systems, all patients achieved an improvement of pain and functional outcome comparing the baseline results with one, six and 12 months values. Low dose ESWT is a safe and effective treatment of LE in the short and middle term. In elderly subjects, patients with a long disease history, or those with occupational and sportive risk factors, a longer persistence of the symptomatology could be observed.
Gla-Rich Protein (GRP) as an Early and Novel Marker of Vascular Calcification and Kidney Dysfunction in Diabetic Patients with CKD: A Pilot Cross-Sectional Study
Authors: Silva Ana P. , Viegas Carla S.B. , Mendes Filipa , Macedo Ana , Guilherme Patrícia , Tavares Nelson , Dias Carolina , Rato Fátima , Santos Nélio , Faísca Marília , Almeida Edgar de , Neves Pedro L. , Simes Dina C.
Published: March 2020

Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2–4). Spearman’s correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD.
Epidemiological Identification of A Novel Pathogen in Real Time: Analysis of the Atypical Pneumonia Outbreak in Wuhan, China, 2019–2020
Authors: Jung Sung-mok , Kinoshita Ryo , Thompson Robin N. , Linton Natalie M. , Yang Yichi , Akhmetzhanov Andrei R. , Nishiura Hiroshi
Published: March 2020

Virological tests have now shown conclusively that a novel coronavirus is causing the 2019–2020 atypical pneumonia outbreak in Wuhan, China. We demonstrate that non-virological descriptive characteristics could have determined that the outbreak is caused by a novel pathogen in advance of virological testing. Characteristics of the ongoing outbreak were collected in real time from two medical social media sites. These were compared against characteristics of eleven pathogens that have previously caused cases of atypical pneumonia. The probability that the current outbreak is due to “Disease X” (i.e., previously unknown etiology) as opposed to one of the known pathogens was inferred, and this estimate was updated as the outbreak continued. The probability (expressed as a percentage) that Disease X is driving the outbreak was assessed as over 29% on 31 December 2019, one week before virus identification. After some specific pathogens were ruled out by laboratory tests on 5 January 2020, the inferred probability of Disease X was over 49%. We showed quantitatively that the emerging outbreak of atypical pneumonia cases is consistent with causation by a novel pathogen. The proposed approach, which uses only routinely observed non-virological data, can aid ongoing risk assessments in advance of virological test results becoming available.
The Dynamics of Respiratory Microbiota during Mechanical Ventilation in Patients with Pneumonia
Authors: Woo Seongji , Park So-Yeong , Kim Youngmi , Jeon Jin Pyeong , Lee Jae Jun , Hong Ji Young
Published: March 2020

Bacterial pneumonia is a major cause of mechanical ventilation in intensive care units. We hypothesized that the presence of particular microbiota in endotracheal tube aspirates during the course of intubation was associated with clinical outcomes such as extubation failure or 28-day mortality. Sixty mechanically ventilated ICU (intensive care unit) patients (41 patients with pneumonia and 19 patients without pneumonia) were included, and tracheal aspirates were obtained on days 1, 3, and 7. Gene sequencing of 16S rRNA was used to measure the composition of the respiratory microbiome. A total of 216 endotracheal aspirates were obtained from 60 patients. A total of 22 patients were successfully extubatedwithin3 weeks, and 12 patients died within 28days. Microbiota profiles differed significantly between the pneumonia group and the non-pneumonia group (Adonis, p < 0.01). While α diversity (Shannon index) significantly decreased between day 1 and day 7 in the successful extubation group, it did not decrease in the failed extubation group among intubated patients with pneumonia. There was a significant difference in the change of βdiversity between the successful extubation group and the failed extubation group for Bray-Curtis distances (p < 0.001). At the genus level, Rothia, Streptococcus, and Prevotella correlated with the change of β diversity. A low relative abundance of Streptococci at the time of intubation was strongly associated with 28-day mortality. The dynamics of respiratory microbiome were associated with clinical outcomes such as extubation failure and mortality. Further large prospective studies are needed to test the predictive value of endotracheal aspirates in intubated patients.
Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development
Authors: Benetó Noelia , Cozar Monica , Castilla-Vallmanya Laura , Zetterdahl Oskar G. , Sacultanu Madalina , Segur-Bailach Eulalia , García-Morant María , Ribes Antonia , Ahlenius Henrik , Grinberg Daniel , Vilageliu Lluïsa , Canals Isaac
Published: March 2020

Sanfilippo syndrome type C (mucopolysaccharidosis IIIC) is an early-onset neurodegenerative lysosomal storage disorder, which is currently untreatable. The vast majority of studies focusing on disease mechanisms of Sanfilippo syndrome were performed on non-neural cells or mouse models, which present obvious limitations. Induced pluripotent stem cells (iPSCs) are an efficient way to model human diseases in vitro. Recently developed transcription factor-based differentiation protocols allow fast and efficient conversion of iPSCs into the cell type of interest. By applying these protocols, we have generated new neuronal and astrocytic models of Sanfilippo syndrome using our previously established disease iPSC lines. Moreover, our neuronal model exhibits disease-specific molecular phenotypes, such as increase in lysosomes and heparan sulfate. Lastly, we tested an experimental, siRNA-based treatment previously shown to be successful in patients’ fibroblasts and demonstrated its lack of efficacy in neurons. Our findings highlight the need to use relevant human cellular models to test therapeutic interventions and shows the applicability of our neuronal and astrocytic models of Sanfilippo syndrome for future studies on disease mechanisms and drug development.
Specialized Management of Oral Anticoagulation Therapy Improves Outcome in Patients with Chronic Renal Insufficiency
Authors: Lauterbach Michael , Uhrich Eduard , Eggebrecht Lisa , Göbel Sebastian , Panova-Noeva Marina , Nagler Markus , ten Cate Vincent , Bickel Christoph , Espinola-Klein Christine , Münzel Thomas , S. Wild Philipp , H. Prochaska Jürgen
Published: March 2020

Oral anticoagulation (OAC) is effective at preventing and treating thromboses and thromboembolism in patients with normal renal function. We aimed to research the impact of severe renal failure (RF) on patient outcome and to determine the potential benefit of caring for these patients in a specialized coagulation service (CS). A total of 1516 usual medical care patients and 756 CS-managed patients of the thrombEVAL multicenter (21 centers), prospective, cohort study (NCT01809015) were analyzed in a 3-year follow-up. Patients with RF (serum creatinine >3 mg/dL, no renal replacement therapy) were compared to patients without RF in usual care and a CS. The fluctuations in the international normalized ratios were significantly lower in CS-managed patients, and regardless of treatment in usual care or a CS, the time in therapeutic range was significantly lower in RF patients. Cox regression-adjusted hazard ratios for long-term outcome (1.5, 95% CI: 1.22–1.83, p < 0.001), death (1.62, CI: 1.27–2.08, p < 0.001), and hospitalization (1.21, CI: 1.02–1.44, p = 0.032) were significantly higher in RF patients in usual care. Furthermore, there was a trend of more bleeding events in RF patients. CS-treated patients had significantly lower adjusted hazard ratios for death (0.24, CI: 0.14–0.39, p < 0.001), hospitalizations (0.41, CI: 0.34–0.5, p < 0.001), clinically relevant bleeding (0.29, CI: 0.18–0.47, p < 0.001), and major bleeding (0.33, CI: 0.18–0.59, p < 0.001). Thus, patients who required oral anticoagulation therapy benefitted significantly from being managed in a specialized coagulation service, regardless of their renal function.
A New Treatment for Mammillary Fistulas Using Ultrasound-Guided Percutaneous Needle Electrolysis
Authors: Berná-Serna Juan de Dios , García-Vidal José A. , Escolar-Reina María P. , Medina-Mirapeix Francesc , Guzmán-Aroca Florentina , Piñero-Madrona Antonio , Berná-Mestre Juan de Dios
Published: March 2020

The aim of this study was to investigate the efficacy of ultrasound-guided percutaneous needle electrolysis (PNE) in mammillary fistulas (MFs). A prospective study was performed in 18 patients with MF who were treated with the PNE technique. The technique was repeated in the case of no response or recurrence. The results obtained show that MFs revealing an elongated appearance with the ultrasound (US) are generally resolved with two sessions of PNE, whereas ovoid MFs require several sessions of PNE for complete resolution and they tend to recur. Success of the treatment with PNE was observed in 88.8% of the patients (16/18), and failure, after five or six sessions in two cases (11.2%), which were referred for surgery. Conclusions: To the best of our knowledge this is the first study to reveal that the PNE technique is safe, effective, quick, and well-tolerated by patients.
Rapid and Efficient Isolation of Exosomes by Clustering and Scattering
Authors: Kim Jinhyun , Lee Hoyoon , Park KyongHwa , Shin Sehyun
Published: March 2020

Tumor-derived extracellular vesicles (EVs) have become important biomarkers of liquid biopsies for precision medicine. However, the clinical application of EVs has been limited due to the lack of EV isolation practical technology applicable to clinical environments. Here, we report an innovative EV isolation method, which is quick and simple, and facilitates high-yield and high-purity EV isolation from blood. Introducing a cationic polymer in plasma resulted in rapid clustering of anionic EVs and a chaotropic agent can separate EVs from these clusters. Isolated EVs were characterized in terms of size distribution, morphology, surface protein markers, and exosomal RNA. Through performance comparison with various methods, including ultracentrifugation (UC), the present method delivered the highest recovery rate (~20 folds that of UC) and purity ratio (3.5 folds that of UC) of EVs in a short period of time (<20 min). The proposed method is expected to be used in basic and applied research on EV isolation and in clinical applications.
Role of Biomarkers in the Prediction of Serious Adverse Events after Syncope in Prehospital Assessment: A Multi-Center Observational Study
Authors: Martín-Rodríguez Francisco , Del Pozo Vegas Carlos , Mohedano-Moriano Alicia , Polonio-López Begoña , Maestre Miquel Clara , Viñuela Antonio , Durantez Fernández Carlos , Gómez Correas Jesús , López-Izquierdo Raúl , Martín-Conty José Luis
Published: March 2020

Syncope is defined as the nontraumatic, transient loss of awareness of rapid onset, short duration and with complete spontaneous recovery, and accounts for 1%–3% of all visits to the emergency department. The objective of this study was to evaluate the predictive capacity of the National Early Warning Score 2 (NEWS2) and prehospital lactate (pLA), individually and combined, at the prehospital level to detect patients with syncope at risk of early mortality (within 48 h) in the hospital environment. A prospective, multicenter cohort study without intervention was carried out on syncope patients aged over 18 who were given advanced life support and taken to the hospital. Our study included a total of 361 cases. Early mortality affected 21 patients (5.8%). The combined score formed by the NEWS2 and the pLA (NEWS2-L) obtained an AUC of 0.948 (95% CI: 0.88–1) and an odds ratio of 86.25 (95% CI: 11.36–645.57), which is significantly higher than that obtained by the NEWS2 or pLA in isolation (p = 0.018). The NEWS2-L can help stratify the risk in patients with syncope treated in the prehospital setting, with only the standard measurement of physiological parameters and pLA.
Efficacy and Safety of Long-Term and Short-Term Dual Antiplatelet Therapy: A Meta-Analysis of Comparison between Asians and Non-Asians
Authors: Ki You-Jeong , Kang Jeehoon , Park Jiesuck , Han Jung-Kyu , Yang Han-Mo , Park Kyung Woo , Kang Hyun-Jae , Koo Bon-Kwon , Kim Hyo-Soo
Published: March 2020

While dual antiplatelet therapy (DAPT) is essential after percutaneous coronary intervention (PCI), the optimal duration is affected by various factors. However, the effect of ethnicity on DAPT duration has not been fully evaluated. In this study, we evaluated the different effect of DAPT duration by ethnicity. We searched Pubmed, Embase, Cochrane library, and relevant websites to search for randomized clinical trials (RCT) assessing the clinical impact of long term DAPT (L-DAPT) and short term DAPT (S-DAPT). Studies were divided by ethnicity, and we compared the efficacy and safety of DAPT duration in each ethnic group. Thirteen RCTs including 38,255 patients (five East Asian studies and eight non–East Asian studies) were eligible for analysis. For the primary outcome, L-DAPT showed a significantly lower rate of primary outcome only in non–East Asians (S-DAPT vs. L-DAPT, odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.02–1.32, p = 0.02), while in East Asians, the effect of S-DAPT and L-DAPT were comparable. S-DAPT significantly increased ischemic events only in non–East Asians (S-DAPT vs. L-DAPT, OR = 1.24, 95% CI: 1.09–1.42, p <0.01), while bleeding events were decreased by S-DAPT in both ethnicities. These results demonstrate that the adequate DAPT duration after PCI may be different in East Asians.
Does Previous Pelvic Organ Prolapse Surgery Influence the Effectiveness of the Sub-Urethral Sling Procedure
Authors: Horosz Edyta , Pomian Andrzej , Zwierzchowska Aneta , Majkusiak Wojciech , Tomasik Paweł , Barcz Ewa
Published: March 2020

Pelvic organ prolapse (POP) often co-occurs with stress urinary incontinence. There is no consensus on whether prolapse repair and anti-incontinence surgery should be performed concomitantly or separately, in a two-step manner. The present study evaluated the effects of the tension-free vaginal tape (TVT) procedure in patients who had previously undergone pelvic floor repair (study group), compared to women who underwent TVT insertion only (control group). The study group comprised 84 patients who underwent the TVT procedure but had previously also undergone surgical POP repair. The control group consisted of 250 women in whom the TVT was inserted. The primary objective was to compare the objective cure rate and the secondary objective was to compare the subjective cure rate in both groups. Negative pad test was achieved in over 91% in both groups. Objective and subjective cure rates were compared, as well as complication rates. Significant improvement was observed in the postoperative 1-h pad test in all patients. In all patients, we observed significant improvement in the quality of life, with no differences between the groups. No differences were found in the occurrence of postoperative urinary retention, urgency and frequency of daytime micturition, or vaginal erosion between the groups. The current results demonstrate that the two-step approach to pelvic reconstruction and anti-incontinence surgery is as safe and effective as primary TVT implantation.
Effects of Caloric Intake and Aerobic Activity in Individuals with Prehypertension and Hypertension on Levels of Inflammatory, Adhesion and Prothrombotic Biomarkers—Secondary Analysis of a Randomized Controlled Trial
Authors: Wagner En-Young N. , Hong Suzi , Wilson Kathleen L. , Calfas Karen J. , Rock Cheryl L. , Redwine Laura S. , von Känel Roland , Mills Paul J.
Published: March 2020

Background: Cardiopulmonary fitness and low calorie diets have been shown to reduce inflammation but few studies have been conducted in individuals with elevated blood pressure (BP) in a randomized intervention setting. Thereby, adhesion biomarkers, e.g., soluble intercellular adhesion molecule (sICAM)-3, have not been examined so far. Methods: Sixty-eight sedentary prehypertensive and mildly hypertensive individuals (mean age ± SEM: 45 ± 1 years; mean BP: 141/84 ± 1/1 mmHg) were randomized to one of three 12-week intervention groups: cardio training and caloric reduction, cardio training alone, or wait-list control group. Plasma levels of inflammatory, adhesion and prothrombotic biomarkers were assessed. In a second step, intervention groups were combined to one sample and multivariate regression analyses were applied in order to account for exercise and diet behavior changes. Results: There were no significant differences among the intervention groups. In the combined sample, greater caloric reduction was associated with a larger increase of sICAM-3 (p = 0.026) and decrease of C-reactive protein (p = 0.018) as a result of the interventions. More cardio training was associated with increases of sICAM-3 (p = 0.046) as well as interleukin-6 (p = 0.004) and a decrease of tumor necrosis factor-α (p = 0.017) levels. Higher BP predicted higher plasminogen activator inhibitor (PAI)-1 (p = 0.001), and greater fitness predicted lower PAI-1 levels (p = 0.006) after the intervention. Conclusions: In prehypertensive and hypertensive patients, plasma levels of the adhesion molecule sICAM-3 and inflammatory biomarkers have different response patterns to cardio training with and without caloric reduction. Such anti-inflammatory and anti-thrombotic effects may have implications for the prevention of atherothrombotic cardiovascular disease among individuals at increased risk.
Prophylactic Anti-Cytomegalovirus Hyperimmunoglobulin in Critically Ill Liver Transplant Patients: Impact on Early Immunology and Survival
Authors: Kornberg Arno , Witt Ulrike , Kornberg Jennifer , Müller Katharina , Friess Helmut , Thrum Katharina
Published: March 2020

Background: Anti-cytomegalovirus hyperimmunoglobulin (CMVIg) was shown to provide beneficial immunodulatory properties beyond antiviral efficacies. The aim of this retrospective study was to assess the impact of prophylactic CMVIg treatment on early outcome following liver transplantation (LT) in critically ill patients. Methods: Forty-three cirrhotic patients requiring pre-LT intensive care due to multiorgan failure were analyzed. Twenty-eight patients with enhanced CMV risk (D+/R+; D+/R−; D−/R+) received prophylactic CMVIg for a minimum of 7 days, while 15 patients (D−/R−) did not. Results: Post-transplantation rates of intra-abdominal infections (28% vs. 61.1%; p = 0.03), Epstein–Barr virus infections (0% vs. 33.3%; p = 0.034), allograft rejections (0% vs. 22.2%; p = 0.013) and sepsis-related mortality (4% vs. 27.8%; p = 0.026) were significantly lower, whereas incidence of CMV infections (4% vs. 22.2%; p = 0.066) tended to be lower in the CMVIg subset. In multivariate analysis, only pretransplant elevated serum lactate level (hazard ratio = 34.63; p = 0.009) and absence of CMVIg therapy (hazard ratio = 21.76; p = 0.023) were identified as independent promoters of 3-month mortality. Conclusion: Prophylactic treatment with CMVIg reduces predisposition for severe immunological and septic events and, thereby, early mortality in critically ill liver recipients.