bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute kidney injury in heart failure: a population study
Authors: Holgado Jose Luis , Lopez Cristina , Fernandez Antonio , Sauri Inmaculada , Uso Ruth , Trillo Jose Luis , Vela Sara , Nuñez Julio , Redon Josep , Ruiz Adrian
Published: February 2020

Aims

The objective of the present study is to assess the prognostic value of acute kidney injury (AKI) in the evolution of patients with heart failure (HF) using real‐world data.

Methods and results

Patients with a diagnosis of HF and with serial measurements of renal function collected throughout the study period were included. Estimated glomerular filtration rate (GFR) was calculated with the CKD‐EPI (Chronic Kidney Disease Epidemiology Collaboration). AKI was defined when a sudden drop in creatinine with posterior recovery was recorded. According to the Risk, Injury, Failure, Loss, and End‐Stage Renal Disease (RIFLE) scale, AKI severity was graded in three categories: risk [1.5‐fold increase in serum creatinine (sCr)], injury (2.0‐fold increase in sCr), and failure (3.0‐fold increase in sCr or sCr > 4.0 mg/dL). AKI incidence and risk of hospitalization and mortality after the first episode were calculated by adjusting for potential confounders. A total of 30 529 patients with HF were included. During an average follow‐up of 3.2 years, 5294 AKI episodes in 3970 patients (13.0%) and incidence of 3.3/100 HF patients/year were recorded. One episode was observed in 3161 (10.4%), two in 537 (1.8%), and three or more in 272 (0.9%). They were more frequent in women with diabetes and hypertension. The incidence increases across the GFR levels (Stages 1 to 4: risk 7.6%, 6.8%, 11.3%, and 12.5%; injury 2.1%, 2.0%, 3.3%, and 5.5%; and failure 0.9%, 0.6%. 1.4%, and 8.0%). A total of 3817 patients with acute HF admission were recorded during the follow‐up, with incidence of 38.4/100 HF patients/year, 3101 (81.2%) patients without AKI, 545 (14.3%) patients with one episode, and 171 (4.5%) patients with two or more. The number of AKI episodes [one hazard ratio (HR) 1.05 (0.98–1.13); two or more HR 2.01 (1.79–2.25)] and severity [risk HR 1.05 (0.97–1.04); injury HR 1.41 (1.24–1.60); and failure HR 1.90 (1.64–2.20)] increases the risk of hospitalization. A total of 10 560 deaths were recorded, with incidence of 9.3/100 HF patients/year, 8951 (33.7%) of subjects without AKI episodes, 1180 (11.17%) of subjects with one episode, and 429 (4.06%) with two or more episodes. The number of episodes [one HR 1.05 (0.98–1.13); two or more HR 2.01 (1.79–2.25)] and severity [risk 1.05 confidence interval (CI) (0.97–1.14), injury 1.41 (CI 1.24–1.60), and failure 1.90 (CI 1.64–2.20)] increases mortality risk.

Conclusions

The study demonstrated the worse prognostic value of sudden renal function decline in HF patients and pointed to those with more future risk who require review of treatment and closer follow‐up.
A Common, Facile and Eco‐Friendly Method for the Reduction of Nitroarenes, Selective Reduction of Poly‐Nitroarenes and Deoxygenation of N‐Oxide Containing Heteroarenes Using Elemental Sulfur
Authors: Romero Angel H. , Cerecetto Hugo
Published: February 2020

A transition metal‐free, environment‐friendly and practical protocol was developed either for the reduction of nitroarenes or for the deoxygenation of N‐oxide containing heteroarenes. The reaction proceeded with the use of a non‐toxic and cheap feedstock as elemental sulfur in aqueous methanol under relatively mild conditions. Green chemistry credentials were widely favorable compared to traditional and industrial protocols with good E‐factors and a low production of waste. The strategy allowed the efficient reduction of a large variety of substituted‐nitroarenes including various o‐nitroanilines as well as selective reduction of various poly‐nitroarenes in excellent yields with a broad substrate scope. The protocol was successfully extended to the deoxygenation of some N‐oxide containing heteroarenes, like benzofuroxans, phenazine N,N'‐dioxides, pyridine N‐oxides, 2H‐indazole N1‐oxides, quinoxaline N1,N4‐dioxides and benzo[d]imidazole N1,N3‐dioxides. A gram‐scale example for the synthesis of luminol, in green conditions, was reported. A solid mechanism of reaction was proposed from experimental evidences.
Chemical Recycling of Plastics by Microwave‐Assisted High‐Temperature Pyrolysis
Authors: Jiang Haibin , Liu Wenlu , Zhang Xiaohong , Qiao Jinliang
Published: February 2020

Use of plastics faces much criticism because of its shocking and increasing impact on the environment. But banning plastic will not help the environment. Only appropriate recycling of plastic waste can give satisfying solution. A lab‐scale chemical recycling method, in which a mixture of plastic wastes and plant oil is continuously cracked into ethylene, propylene, and other useful chemicals by using microwave‐assisted high‐temperature pyrolysis, is developed. The method has delivered interesting leads that provide the basis for setting up a new process. Based on the encouraging results, a “drop‐in” method for a renewable and circular polymer industry is also proposed. If it is commercially realized, plastic waste and plant oils will be the feedstock for the polymer industry and this industry will become renewable and circular.
Auswirkungen von Strömungen auf lokale hydraulische Sicherheiten – Beispiele mit der FEM
Authors: Karcher Christian , Imposimato Silvia , Herle Ivo
Published: February 2020

Üblicherweise werden in der Praxis hydraulische Sicherheiten für vordefinierte Versagensmechanismen und ohne Berücksichtigung einer bodenmechanischen Vorgeschichte berechnet. Die mathematische Analyse der durch Strömung reduzierten effektiven Spannungen, verbunden mit lokalen hydraulischen Sicherheiten, lässt Schlussfolgerungen auf den Gesamt‐ und örtlichen Zustand im Untersuchungsgebiet vergleichsweise einfach zu. Dazu werden unter Zuhilfenahme der Finite‐Elemente‐(FE)Methode Porenwasserdruckverteilungen und Effektivspannungen bewertet. Bei FE‐Programmen, die Berechnungen mit Porenwasserdrücken anbieten, genügen für diese Analyse Anpassungen im Post‐Processing.
Comparing the EQ‐5D‐5L crosswalks and value sets for England, the Netherlands and Spain: Exploring their impact on cost‐utility results
Authors: Ben Ângela , Finch Aureliano Paolo , van Dongen Johanna M. , de Wit Maartje , van Dijk Susan E.M. , Snoek Frank J. , Adriaanse Marcel C. , van Tulder Maurits W. , Bosmans Judith E.
Published: February 2020

This study compares the five‐level EuroQol five‐dimension questionnaire (EQ‐5D‐5L) crosswalks and the 5L value sets for England, the Netherlands, and Spain and explores the implication of using one or the other for the results of cost–utility analyses. Data from two randomized controlled trials in depression and diabetes were used. Utility value distributions were compared, and mean differences in utility values between the EQ‐5D‐5L crosswalk and the 5L value set were described by country. Quality‐adjusted life years (QALYs) were calculated using the area‐under‐the‐curve method. Incremental cost‐effectiveness ratios (ICERs) were calculated, and uncertainty around ICERs was estimated using bootstrapping and graphically shown in cost‐effectiveness acceptability curves. For all countries investigated, utility value distributions differed between the EQ‐5D‐5L crosswalk and 5L value set. In both case studies, mean utility values were lower for the EQ‐5D‐5L crosswalk compared with the 5L value set in England and Spain, but higher in the Netherlands. However, these differences in utility values did not translate into relevant differences across utility estimation methods in incremental QALYs and the interventions' probability of cost‐effectiveness. Thus, our results suggest that EQ‐5D‐5L crosswalks and 5L value sets can be used interchangeably in patients affected by mild or moderate conditions. Further research is needed to establish whether these findings are generalizable to economic evaluations among severely ill patients.
Risk of second primary cancer in oral squamous cell carcinoma
Authors: Mroueh Rayan , Nevala Aapeli , Haapaniemi Aaro , Pitkäniemi Janne , Salo Tuula , Mäkitie Antti A.
Published: February 2020

Background

The incidence and survival of oral squamous cell carcinoma (OSCC) patients have increased in recent years. Understanding their long‐term survival aspects is essential for optimal treatment and follow‐up planning. Almost one in five cancers diagnosed occurs nowadays in individuals with a previous diagnosis of cancer.

Methods

Patients diagnosed with primary OSCC during 1953‐2015 were retrieved from the Finnish Cancer Registry. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person‐years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population.

Results

Among 6602 first primary OSCC patients there were 640 (10%) SPCs. The SIR for SPCs was 1.85 (95% CI: 1.71‐1.99, P < .001) corresponding to an EAR of 8.78 (95% CI: 7.29‐10.26).

Conclusions

Health care professionals should be aware of the second primary cancer risk after management of primary OSCC and patients need to be counseled about this phenomenon.
First Principles Investigation of Cold Curves of Metals
Authors: Eidelstein Eitan , Barzilai Shmuel , Curtarolo Stefano , Levy Ohad
Published: February 2020

The rapid development of better high pressure experimental techniques combined with efficient and accurate density functional calculations of the structural properties of materials provide a new avenue to promote the study of materials at high pressures, which is currently based mostly on simple phenomenological modelling. The progress of experimental results into higher‐pressure regimes represents a challenge to the phenomenological approaches, which can be addressed by carefully considered ab initio calculations. We present cold curves of several elements, calculated using different approximations of DFT and compare them with available experimental data. The comparison shows good agreement both in simple single phase and complex multi‐phase cases. It suggests that DFT may be used to extrapolate high pressure behaviour of materials beyond the currently possible pressure range, with a robust estimate of the accuracy of the extrapolation based on various DFT implementations.
Substance use and mothers’ neural responses to infant cues
Authors: Lowell Amanda F. , Maupin Angela N. , Landi Nicole , Potenza Marc N. , Mayes Linda C. , Rutherford Helena J. V.
Published: February 2020

Substance use may influence mothers’ responsiveness to their infants and negatively impact the parent–infant relationship. Maternal substance use may co‐opt neural circuitry involved in caregiving, thus reducing the salience of infant cues and diminishing the sense of reward experienced by caring for infants. Gaps in understanding exist with regard to the mechanisms by which substance use operates to influence mothers’ processing of infant cues and how this translates to caregiving. Therefore, we examined how substance use might relate to maternal neural responses to infant cues using event‐related potentials (ERPs). Substance‐using (n = 29) and nonsubstance‐using (n = 29) mothers viewed photographs of infant faces and heard recordings of infant vocalizations while electroencephalography was recorded simultaneously. Three specific ERP components were used to examine initial processing of infant faces (N170) and cries (N100), and attentional allocation to infant faces and cries (P300). Substance‐using mothers did not discriminate facial affect at early encoding stages (N170), were generally slower to orient to infant cries (N100), showed heightened responses to neutral faces (P300), and failed to adaptively differentiate between high‐distress versus low‐distress cries (P300). These differences may be important to caregiving behaviors associated with the formation of mother–child attachment. Implications are discussed, as are limitations and future directions.
MicroRNA‐34a causes ceramide accumulation and effects insulin signaling pathway by targeting ceramide kinase (CERK) in aging skeletal muscle
Authors: Kukreti Himani , Amuthavalli Kottaiswamy
Published: February 2020

Aging skeletal muscle shows perturbations in metabolic functions. MicroRNAs have been shown to play a critical role in aging and metabolic functions of skeletal muscle. MicroRNA‐34a (miR‐34a) is implicated in the brain and cardiac aging, however, its role in aging muscle is unclear. We analyzed levels of miR‐34a, ceramide kinase (CERK) and other insulin signaling molecules in skeletal muscle from old mice. In addition to in vivo model, levels of these molecules were also analyzed in myoblast derived from insulin resistant (IR) humans and C2C12 myoblasts overexpressing mir‐34a. Our results show that miR‐34a is elevated in the muscles of 2‐year‐old mice and in the myoblasts of IR humans. Overexpression of miR‐34a in C2C12 myoblasts leads to alterations in the insulin signaling pathway, which were rescued by its antagonism. Our analyses revealed that miR‐34a targets CERK resulting in ceramide accumulation, activation of PP2A and the pJNK pathway in muscle and C2C12 myoblasts. Also, myostatin (Mstn) levels were increased in 2‐year‐old mouse muscle and Mstn treatment upregulated miR‐34a in C2C12 myoblasts. In addition, miR‐34a expression and ceramide levels did not increase during aging in Mstn−/− mice muscle. In summary, we, therefore, propose that Mstn levels increase in aging muscle and upregulate miR‐34a, which inhibits CERK resulting in increased ceramide levels. This ceramide accumulation activates PP2A and pJNK causing hypophosphorylation of AKT and hyperphosphorylation of IRS1 (Ser307), respectively, impairing insulin signaling pathway and eventually inhibiting the sarcolemma localization of GLUT4. These changes would result in reduced glucose uptake and insulin resistance. This study is the first to explain the phenomenon of ceramide accrual and impairment of insulin signaling pathway in aging muscle through a miR‐34a based mechanism. In conclusion, our results suggest that Mstn and miR‐34a antagonism can help ameliorate ceramide accumulation and loss of insulin sensitivity in aging skeletal muscle.
Retracted: Kinesin family member 2C aggravates the progression of hepatocellular carcinoma and interacts with competing endogenous RNA
Authors: Zhang Guo‐Pei , Shen Shun‐Li , Yu Yang , Yue Xiao , Hu Wen‐Jie , Li Shao‐Qiang
Published: February 2020

Kinesin family member 2C (KIF2C), a substantial mitotic regulator, has been verified to exert a malignant function in several cancers. However, its function in hepatocellular carcinoma (HCC) remains unclear. In this study, the expression profile of KIF2C in HCC was characterized through the dataset from the TCGA and clinical tissue microarrays containing 220 pairs of resected HCC tissues and adjacent nontumor tissues in our hospital. The results indicated that KIF2C was substantially higher expression in tumor tissues than adjacent nontumor tissues. High expression of KIF2C significantly correlated with large tumor (>5.0 cm) (P = .001) and implied a dismal postoperative overall survival (OS) (hazard ratio [HR] = 1.729; P = .002) in our cohort of patients. Gain and loss of function assays displayed that KIF2C promoted HCC cell proliferation, accelerated cell cycle progression, and impeded apoptosis. By bioinformatic tools and mechanistic investigation, we found that KIF2C interacted with various cell‐cycle‐related proteins and was significantly involved in growth‐promoting pathways. KIF2C upregulated PCNA and CDC20 expression. Subsequently, we investigated the regulation of KIF2C by competing endogenous RNA and elucidated that has‐miR‐6715a‐3p was directly bond to the 3′‐untranslated region of KIF2C through dual luciferase assays, thereby inhibiting KIF2C expression. Furthermore, the long noncoding RNA GS1‐358P8.4 was found to be a candidate of KIF2C for has‐miR‐6715a‐3p binding. HCC patients with high lncRNA‐GS1‐358P8.4 expression had shorter OS and relapse‐free survival compared to those with low expression, which was accordance with the KIF2C. Taken together, KIC2C aggravated HCC progression, it could serve as a prognostic indicator and confer a novel target for clinical treatment.
Efficient implementation of the interacting quantum atoms energy partition of the second‐order Møller–Plesset energy
Authors: Casals‐Sainz José Luis , Guevara‐Vela José Manuel , Francisco Evelio , Rocha‐Rinza Tomás , Martín Pendás Ángel
Published: February 2020

We describe an efficient implementation of the partition of the second‐order Møller–Plesset (MP2) correlation energy within the interacting quantum atoms (IQA) energy decomposition. We simplify the IQA integration bottleneck by considering only the occupied to virtual elements of the second order reduced density matrix, a procedure that reduces substantially the size of the two‐electron matrix, which has to be addressed. The algorithmic improvements described herein allow to perform the decomposition of the MP2 correlation energy for medium size molecular systems using moderate computational resources. We expect that the methods developed in this investigation will prove useful to understand electron correlation effects through a real space perspective.
miR‐22 represses osteoblast viability with ESR1 presenting a direct target and indirectly inactivating p38 MAPK/JNK signaling
Authors: Chen Guang‐Hua , Zhang Xin‐Le , Chen Hang , Lin Hao , Wu Hao‐Jun , Lin Han , Huang Gui‐Zhi
Published: February 2020

Background

MicroRNAs (miRs) hold critical implications in the modulation of osteogenesis. This work was designed to unravel the underlying regulatory mechanism of miR‐22 during osteoblast differentiation.

Methods

Synthetic miR‐22 mimics or inhibitors were transfected into preosteoblast MC3T3‐E1 cells to regulate miR‐22 expression. MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] and flow cytometry analyses were employed to assess cell proliferation and apoptosis. A quantitative real‐time polymerase chain reaction and western blot assays were applied to measure mRNA and protein expression. Alkaline phosphatase activity and alizarin red staining were tested to further analyze cell differentiation. In silico analysis and luciferase reporter assays were utilized to identify the direct binding between miR‐22 and its potential target.

Results

MTT and flow cytometry analyses showed that miR‐22 repressed MC3T3‐E1 cell viability and promoted cell apoptosis. By detecting osteogenic‐specific molecule expression, alkaline phosphatase activity and alizarin red staining, miR‐22 was observed to suppress osteogenic differentiation of MC3T3‐E1 cells. In silico analysis and luciferase reporter assays confirmed that ESR1 is a direct target gene of miR‐22. In addition, miR‐22 expression affected the phosphorylation of p38 mitogen‐activated protein kinase and Jun N‐terminal kinase expression in MC3T3‐E1 cells.

Conclusions

The findings of the present study highlight the functional significance of miR‐22 in osteoblast differentiation and suggest its role as a possible therapeutic target in metabolic bone disorders.
Partial replacement of rock phosphate by sewage sludge ash for the production of superphosphate fertilizers
Authors: Hartmann Tobias Edward , Möller Kurt , Meyer Carsten , Müller Torsten
Published: February 2020

Thermal utilization of sewage sludge through mono‐incineration or gasification results in phosphorus (P) rich sewage sludge ash (SSA) that must be returned to agricultural production systems to fulfill the need for recycling of P resources contained in wastewater streams. As the plant‐availability of P contained in SSA is low, we propose feeding SSA directly into the production of superphosphate fertilizers, thereby opening a further pathway for the recycling of phosphorus (P) from wastewater streams to agricultural production systems by using available technologies. We carried out laboratory‐scale production of superphosphate test‐products, in which rock phosphate (RP) was partially replaced with SSA (gasification) before digestion with concentrated sulfuric acid, and evaluated these products with regard to the solubility of P in H2O and neutral ammoniumcitrate solution. We further carried out a growth‐chamber experiment (28 d) using maize (Zea mays L. cv. Sulano) as a model plant on a low P (0.4 mg PCAL 100g−1), high pH (7.6) substrate to evaluate plant P availability of the test products. Our laboratory‐scale results show that at least 8% of P from RP can be replaced by P from SSA while maintaining both the high solubility of P in the fertilizer product and the growth of maize compared to pure RP digested with concentrated sulfuric acid. Further substitution of RP through SSA decreased the total P concentration of the test products, as well as the relative amounts of P soluble in H2O and neutral ammoniumcitrate solution, which affected early plant development of maize.
Adsorption of toluene‐3,4‐dithiol on silver islands investigated by surface‐enhanced Raman spectroscopy
Authors: Plaickner Julian , Speiser Eugen , Chandola Sandhya , Esser Norbert , Singh Dheeraj K.
Published: February 2020

The adsorbtion of toluene‐3,4‐dithiol (TDT) molecules on Ag islands was investigated with surface‐enhanced Raman spectroscopy (SERS). The SERS spectrum was compared with the ordinary Raman spectrum of TDT, and differences in spectral features were discussed with the support of density functional theory calculations. The disappearance of all the S–H‐related bands in the SERS spectrum indicates that TDT adsorbs on Ag via both thiol groups, as supported by the emergence of a weak band at 223 cm−1 attributed to Ag–S stretching. Signatures of Ag–S–C complexes suggest that the adsorption is partially disordered. The observation of all the vibrational modes involving the methyl group indicates that the methyl group is exposed, offering new functionalization possibilities of the surface.
Enhancement of Fat Oxidation during Submaximal Exercise in Sedentary Persons: Variations by Medium‐Chain Fatty Acid Composition and Age Group
Authors: Nosaka Naohisa , Tsujino Shougo , Honda Kazumitsu , Suemitsu Hiromi , Kato Kazuhiko
Published: February 2020

Previous studies in recreational and trained athletes aged mostly in their 20s have reported that short‐term ingestion of medium‐chain triacylglycerols (MCT) enhances fat oxidation (FAO) during submaximal exercise. However, whether the FAO‐enhancing effect of MCT with a different composition of medium‐chain fatty acids (MCFA) occurs in older sedentary persons is unclear. The present study investigated the effect of MCT ingestion with different proportions of MCFA in sedentary participants in their 40's and 50's. Participants ingested 0 g of MCT (control), 6 g of octanoic acid‐rich MCT (OAR), or 6 g of decanoic acid‐rich MCT (DAR) for 14 days separated by a 14‐day washout period in random order. Cumulative FAO (Fcv) during submaximal, fixed, and incremental exercise was evaluated at workload from 20 W to the appearance of a ventilation threshold (VT). During the 20 W fixed‐load exercise, Fcv was significantly (p < 0.05) higher in the OAR than in the control. At appearance of VT, intervention effect of power output was significantly higher in the OAR and DAR than in the control. In a subgroup analysis by age, intervention effects of maximal FAO rate and oxygen uptake in the upper age subgroup were higher in the OAR and DAR than in the control. In a pooled analysis with age subgroup and diet, the integrated pooled estimate of Fcv during submaximal exercise was significantly higher in 6 g of MCT ingestion than 0 g ingestion. Our data show that the effect of MCT might differ depending on the age group and the proportion of MCFA, while MCT could enhance FAO during submaximal exercise.
Projected increase of the East Asian summer monsoon (Meiyu) in Taiwan by climate models with variable performance
Authors: Tung Yu‐Shiang , Wang S.‐Y. Simon , Chu Jung‐Lien , Wu Chi‐Hua , Chen Yung‐Ming , Cheng Chao‐Tzuen , Lin Lee‐Yaw
Published: February 2020

The active phase of the East Asian summer monsoon (EASM) in Taiwan during May and June, known as Meiyu, produces substantial precipitation for water uses in all sectors of society. Following a companion study that analysed the historical increase in the Meiyu precipitation, the present study conducted model evaluation and diagnosis based on the EASM lifecycle over Taiwan. Higher and lower skill groups were identified from 17 Couple Model Intercomparison Project Phase 5 (CMIP5) models, with five models in each group. Despite the difference in model performance, both groups projected a substantial increase in the Meiyu precipitation over Taiwan. In the higher skill group, weak circulation changes and reduced low‐level convergence point to a synoptically unfavourable condition for precipitation. In the lower skill group, intensified low‐level southwesterly winds associated with a deepened upper level trough enhance moisture pooling. Thus, the projected increase in Meiyu precipitation will likely occur through the combined effects of (1) the extension of a strengthened North Pacific anticyclone enhancing southwesterlies; and (2) more systematically, the Clausius–Clapeyron relationship that increases precipitation intensity in a warmer climate. The overall increase in the Meiyu precipitation projected by climate models of variable performance supports the observed tendency toward more intense rainfall in Taiwan and puts its early June 2017 extreme precipitation events into perspective.
Identification of two compound heterozygous VPS13A large deletions in chorea‐acanthocytosis only by protein and quantitative DNA analysis
Authors: Spieler Derek , Velayos‐Baeza Antonio , Mühlbäck Alžbeta , Castrop Florian , Maegerlein Christian , Slotta‐Huspenina Julia , Bader Benedikt , Haslinger Bernhard , Danek Adrian
Published: February 2020

Background

Chorea‐acanthocytosis (ChAc; OMIM #200150) is a rare autosomal recessive condition with onset in early adulthood that is caused by mutations in the vacuolar protein sorting 13A (VPS13A) gene encoding chorein. Several diagnostic genomic DNA (gDNA) sequencing approaches are widely used. However, their limitations appear not to be acknowledged thoroughly enough.

Methods

Clinically, we deployed magnetic resonance imaging, blood smear analysis, and clinical chemistry for the index patient's characterization. The molecular analysis of the index patient next to his parents covered genomic DNA (gDNA) sequencing approaches, RNA/cDNA sequencing, and chorein specific Western blot.

Results

We report a 33‐year‐old male patient without functional protein due to compound heterozygosity for two VPS13A large deletions of 1168 and 1823 base pairs (bp) affecting, respectively, exons 8 and 9, and exon 13. To our knowledge, this represents the first ChAc case with two compound heterozygous large deletions identified so far. Of note, standard genomic DNA (gDNA) Sanger sequencing approaches alone yielded false negative findings.

Conclusion

Our case demonstrates the need to carry out detection of chorein in patients suspected of having ChAc as a helpful and potentially decisive tool to establish diagnosis. Furthermore, the course of the molecular analysis in this case discloses diagnostic pitfalls in detecting some variations, such as deletions, using only standard genomic DNA (gDNA) Sanger sequencing approaches and exemplifies alternative methods, such as RNA/cDNA sequencing or qRT‐PCR analysis, necessary to avoid false negative results.
Methylation‐based algorithms for diagnosis: experience from neuro‐oncology
Authors: Pickles Jessica C , Stone Thomas J , Jacques Thomas S
Published: February 2020

Brain tumours are the most common tumour‐related cause of death in young people. Survivors are at risk of significant disability, at least in part related to the effects of treatment. Therefore, there is a need for a precise diagnosis that stratifies patients for the most suitable treatment, matched to the underlying biology of their tumour. Although traditional histopathology has been accurate in predicting treatment responses in many cases, molecular profiling has revealed a remarkable, previously unappreciated, level of biological complexity in the classification of these tumours. Among different molecular technologies, DNA methylation profiling has had the most pronounced impact on brain tumour classification. Furthermore, using machine learning‐based algorithms, DNA methylation profiling is changing diagnostic practice. This can be regarded as an exemplar for how molecular pathology can influence diagnostic practice and illustrates some of the unanticipated benefits and risks. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability
Authors: Lim Sin Yin , Sharan Satish , Woo Sukyung
Published: February 2020

Introduction

There is a large variation in cannabidiol (CBD) pharmacokinetics and little information on its bioavailability. This study aims to establish the CBD dose‐exposure relationship and to evaluate the effects of dosage forms, food, and doses on CBD absorption.

Methods

Single‐dose (range: 5–6000 mg) CBD plasma concentration‐time profiles administered as oral solution (OS), oral capsule (OC), or oromucosal spray/drop (OM) from healthy volunteers were extracted from 15 published clinical studies. A dose‐exposure proportionality assessment was performed, and a population‐based meta‐analysis of CBD pharmacokinetics and systemic bioavailability was conducted with a nonlinear mixed‐effects modeling. A three‐compartment model with a Weibull or zero‐order absorption model was used to describe CBD disposition and absorption kinetics. Dosage form, food, and dose were assessed for covariation.

Results

Oral solution CBD exposures increased less than proportionally with doses of 750 mg or greater, and bioavailability (6.5% at 3000 mg) decreased with increasing dose. The bioavailability of OC (5.6%) and fed‐state OM (6.2%) were similar, whereas it was lower in fasted‐state OM (0.9%). The Weibull absorption model best described OS, OC, and fed‐state OM profiles. The slowest absorption rate was observed in OS, resulting in a time of maximum concentration of 4.75 hours, followed by fed‐state OM (3.13 hrs) and OC (2.1 hrs). The absorption kinetics of fasted‐state OM was best described by a zero‐order absorption for the duration of 1.71 hours.

Conclusion

The effects of doses, dosage forms, and feeding status on CBD pharmacokinetics were quantified and should be taken into consideration for dose optimization.
Halogenation effect promoted low bandgap polymers based on asymmetric isoindigo unit with low energy loss
Authors: Shahid Bilal , Zhu Dangqiang , Wang Qian , Yuan Xiyue , Ismail Irfan , Wu Yao , Du Zurong , Yang Renqiang
Published: February 2020

To optimize the energy levels of the structural framework of isoindigo polymers, a series of asymmetric isoindigo based low bandgap polymers with chlorine, fluorine and thiazole substituents was constructed and their optical, electrochemical and photovoltaic properties were comparatively evaluated for the impact of different substitutions. In comparison with the polymer based on 2,2'‐bithiophene and isoindigo unit (PTi) with non‐substituted bithiophene as the donor moiety, the highest occupied molecular orbital energy level for the newly synthesized polymers is significantly decreased, and in turn an improvement of the open‐circuit voltage (VOC) is noted in the corresponding photovoltaic devices. More importantly, combined with a low bandgap of 1.32 eV, the energy losses (Eloss) could be reduced to 0.61 eV for polymer based on chlorinated 2,2'‐bithiophene and isoindigo unit (PCl). In addition, the halogen moieties are observed to be superior in device fabrication and give better values than the thiazole substituent. Both fluorinated and chlorinated polymer donors exhibited improved performance compared with the original polymer PTi. Consequently, this work not only presents the influence of different electron withdrawing substituents on the physicochemical and photovoltaic performance, but also backs the concept of how to reduce the energy loss via the heteroatom effect. © 2020 Society of Chemical Industry
Rapid microwave controlled polyesterification of aconitic acid and ethylene glycol
Authors: Orozco Ferley , Andrade Andrés , Delgado Lina M , Rojas Giovanni
Published: February 2020

Microwave polyesterification of trans‐aconitic acid and ethylene glycol was carried out by controlling two parameters: temperature and exposure to irradiation. A series of crosslinked materials was obtained showing diverse behavior in terms of solubility, glass transition temperature and decomposition temperature. In contrast to heating by convection that could last hours, polyesters obtained by microwave irradiation were obtained after a maximum of 30 min of reaction. More importantly, the polyesterifications were carried out in bulk, with no solvent involved and without the use of any catalyst. © 2020 Society of Chemical Industry
Rosmarinus plants: Key farm concepts towards food applications
Authors: Sharifi‐Rad Javad , Ezzat Shahira M. , El Bishbishy Mahitab H. , Mnayer Dima , Sharopov Farukh , Kılıç Ceyda S. , Neagu Monica , Constantin Carolina , Sharifi‐Rad Mehdi , Atanassova Maria , Nicola Silvana , Pignata Giuseppe , Salehi Bahare , Fokou Patrick V. T. , Martins Natália
Published: February 2020

Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti‐inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications.
Rapid differentiation of graft Citrus sinensis with and without Xylella fastidiosa infection by mass spectrometry
Authors: Soares Márcio Santos , da Silva Danielle Fernandes , Amaral Jéssica Cristina , da Silva Michelli Masaroli , Forim Moacir Rossi , Rodrigues‐Filho Edson , das Graças Fernandes da Silva Maria Fátima , Fernandes João Batista , Machado Marcos Antônio , de Souza Alessandra Alves , Martins Carlos Henrique Gomes
Published: February 2020

Rationale

Xylella fastidiosa causes citrus variegated chlorosis (CVC) in sweet orange trees. A diagnostic method for detecting CVC before the symptoms appear, which would inform citrus producers in advance about when the plant should be removed from the orchard, is essential for reducing pesticide application costs.

Methods

Chemometrics was applied to high‐performance liquid chromatography diode array detector (HPLC‐DAD) data to evaluate the similarities and differences between the chromatographic profiles. A liquid chromatography/atmospheric pressure chemical ionization mass spectrometry selected reaction monitoring (LC/APCI‐MS‐SRM) method was developed to identify the major compounds and to determine their amounts in all samples.

Results

We evaluated the effect of this bacterium on the variation in the chemical profile in citrus plants. The organs of C. sinensis grafted on C. limonia were analyzed. Chemometrics was applied to the obtained data, and two major groups were differentiated. Flavonoids were observed in one group (leaves) and coumarins in the second (roots), both at higher concentrations in the plants with CVC symptoms than in those without the symptoms and those in the negative control. The rootstocks also interfered in the metabolism of the scion.

Conclusions

The developed LC/APCI‐MS‐SRM method for detecting CVC before the symptoms appear is simple and accurate. It is inexpensive, and many samples can be screened per hour using 1 mg of leaves. Knowledge of the influence of the rootstock on the chemical profile of the graft is limited. This study demonstrates the effect of the rootstock in synthesizing flavonoids and increasing its content in all parts of the graft.
Remarkable response to nivolumab in sarcomatoid malignant pleural mesothelioma with high PD‐L1
Authors: Tsubouchi Kazuya , Inoue Shigesato , Ibusuki Ritsu , Iwasaki Takeshi , Harada Taishi
Published: February 2020

We report herein a case of sarcomatoid malignant pleural mesothelioma (MPM) with high PD‐L1 expression who was refractory to standard chemotherapy but had a remarkable and sustained response to nivolumab. A 78‐year‐old man presented with right chest pain. Computed tomography (CT) showed a solid mass extending to the right pleura. Histopathological examination revealed the proliferation of spindle to pleomorphic ovoid shaped tumour cells, which are positive for calretinin and podoplanin. The patient was diagnosed with sarcomatoid MPM. Despite treatment with carboplatin and pemetrexed, the primary lesion rapidly progressed and new multiple pleural metastases were observed. Although his performance status decreased with advancing of symptoms and adverse events, nivolumab was administered. After the nivolumab treatment, CT showed a significant reduction in pleural tumours with a marked improvement in symptoms. In the primary specimens, TPS of PD‐L1 was 80%. The patient has continued this treatment with sustained and remarkable effectiveness with good quality of life (QOL).
Feasibility and necessity of the fourth arm of the da Vinci Si surgical system for robot‐assisted partial nephrectomy
Authors: Kira Satoru , Mitsui Takahiko , Sawada Norifumi , Nakagomi Hiroshi , Ihara Tatsuya , Takahashi Nobuhiro , Takeda Masayuki
Published: February 2020

Background

To investigate the feasibility of the fourth arm of the da Vinci Si system for robot‐assisted partial nephrectomy (RAPN).

Methods

Fifty‐eight consecutive patients underwent RAPN with the same port placements. After reviewing the surgical videos and records, 38 patients showing usefulness of the fourth arm were categorized into Group A and those not showing usefulness into Group B. The background data, tumor characteristics, and perioperative outcomes were compared between the groups.

Results

Group B had a larger proportion of tumors located on the inner side of the kidney, and the console time was significantly longer. Multivariable logistic regression analysis showed that tumors located on the inner side of the kidney were associated with the non‐use of the fourth arm of the da Vinci Si system during RAPN.

Conclusions

Our findings suggested that use of fourth arm in RAPN by da Vinci Si should be considered for each tumor location.
Does information and communication technology affect CO2 mitigation under the pathway of sustainable development during the mode of globalization?
Authors: Ulucak Recep , Danish  , Khan Salah Ud‐Din
Published: February 2020

The rapid developments of globalization promote interaction among countries and people around the globe through the fast mode of information and telecommunication technology (ICT). ICT development also contributes to economic growth through various channels, but it may influence the environment on the other hand. Considering this concern, the present study focuses on examining the relationship between ICT developments and carbon emissions through the globalization channel. The study employs robust panel data estimation methods, continuously updated fully modified, and continuously updated bias corrected estimators, for the data set of Brazil, Russia, India, China, and South Africa (BRICS) economies spanning from 1990 to 2015. Findings of the study are robust against heteroskedasticity, endogeneity, and cross‐sectional dependence issues. The robust panel data estimators reveal that ICT has a favourable effect on carbon emissions in BRICS countries. Also, globalization leads to environmental pollution by contributing to an increase in CO2 emissions. These findings provide new insights to the policymakers in combatting environmental challenges.
MMLT: A mutual multilevel trust framework based on trusted third parties in multicloud environments
Authors: Aghaee Ghazvini Golnaz , Mohsenzadeh Mehran , Nasiri Ramin , Masoud Rahmani Amir
Published: February 2020

In this article, a mutual multilevel trust framework is proposed, which involves managing trust from the perspective of cloud users (CUs) and cloud service providers (CSPs) in a multicloud environment based on a set of trusted third parties (TTPs). These independent agents are trusted by CUs and CSPs and distributed on different clouds. The TTPs evaluate the CUs' trustworthiness based on the accuracy of feedback ratings and assess the CSPs' trustworthiness based on the quality of service monitoring information. They are connected themselves through the trusted release network, which enables a TTP to obtain trust information about CSPs and CUs from other clouds. With the objective of developing an effective trust management framework, a new approach has been provided to improve trust‐based interactions, that is, able to rank the trusted cloud services (CSs) based on CU's priorities via fuzzy logic. Fuzzy logic is applied to manage the different priorities of CUs, all the CUs do not have the same priorities to use trusted CSs. Customizing service ranking allows CUs to apply trusted CSs based on their priorities. Experiments on real datasets well matched the analytical results, indicating that our proposed approach is effective and outperforms the existing approaches.
Fully Automated HTML and JavaScript Rewriting for Constructing a Self‐healing Web Proxy
Authors: Durieux Thomas , Hamadi Youssef , Monperrus Martin
Published: February 2020

Over the last few years, the complexity of web applications has increased to provide more dynamic web applications to users. The drawback of this complexity is the growing number of errors in the front‐end applications. In this paper, we present an approach to provide self‐healing for the web. We implemented this approach in two different tools: (i) BikiniProxy, an HTTP repair proxy, and (ii) BugBlock, a browser extension. They use five self‐healing strategies to rewrite the buggy HTML and JavaScript code to handle errors in web pages. We evaluate BikiniProxy and BugBlock with a new benchmark of 555 reproducible JavaScript errors of which 31.76% can be automatically self‐healed by BikiniProxy and 15.67% by BugBlock.
Erratum zu: Bedeutsame Momente im Coaching
Authors: Wegener Robert
Published: February 2020

R. Wegener,Bedeutsame Momente im Coaching,
Production and clinical evaluation of breast lesion skin markers for automated three-dimensional ultrasonography of the breast: a pilot study
Authors: de Jong Leon , Welleweerd Marcel K. , van Zelst Jan C.M. , Siepel Francoise J. , Stramigioli Stefano , Mann Ritse M. , de Korte Chris L. , Fütterer Jurgen J.
Published: February 2020

Objectives

Automated ultrasound of the breast has the advantage to have the whole breast scanned by technicians. Consequently, feedback to the radiologist about concurrent focal abnormalities (e.g., palpable lesions) is lost. To enable marking of patient- or physician-reported focal abnormalities, we aimed to develop skin markers that can be used without disturbing the interpretability of the image.

Methods

Disk-shaped markers were casted out of silicone. In this IRB-approved prospective study, 16 patients were included with a mean age of 57 (39–85). In all patients, the same volume was imaged twice using an automated breast ultrasound system, once with and once without a marker in place. Nine radiologists from two medical centers filled scoring forms regarding image quality, image interpretation, and confidence in providing a diagnosis based on the images.

Results

Marker adhesion was sufficient for automated scanning. Observer scores showed a significant shift in scores from excellent to good regarding diagnostic yield/image quality (χ2, 15.99, p < 0.01), and image noise (χ2, 21.20, p < 0.01) due to marker presence. In 93% of cases, the median score of observers “agree” with the statement that marker-induced noise did not influence image interpretability. Marker presence did not interfere with confidence in diagnosis (χ2, 6.00, p = 0.20).

Conclusion

Inexpensive, easy producible skin markers can be used for accurate lesion marking in automated ultrasound examinations of the breast while image interpretability is preserved. Any marker-induced noise and decreased image quality did not affect confidence in providing a diagnosis.

Key Points

• The use of a skin marker enables the reporting radiologist to identify a location which a patient is concerned about.

• The developed skin marker can be used for accurate breast lesion marking in ultrasound examinations.
Interpretation of Tonsillectomy Outcome Inventory-14 scores: a prospective matched cohort study
Authors: Laajala Aleksi , Autio Timo J. , Ohtonen Pasi , Alho Olli-Pekka , Koskenkorva Timo J.
Published: February 2020

Purpose

Knowledge of disease-specific instruments enables the evaluation of health- related quality-of-life (QoL) change associated with chronic and recurrent tonsillitis in adults. The main objective was to explore the interpretation of scores according to the throat-related QoL instrument, Tonsillectomy Outcome Inventory-14 (TOI-14), by determining the typical scores in healthy subjects and patients and define the minimum important change (MIC).

Methods

We performed a prospective matched cohort study in a secondary care area of Oulu University Hospital. The surgical cohort consisted of 42 patients referred to tonsillectomy due to recurrent or chronic tonsillitis. The control cohort consisted of 42 age- and sex-matched healthy controls obtained from the escorts of patients in the same hospital. We translated and validated the Finnish TOI-14 instrument and collected TOI-14 scores at entry and at 6 months and compared results to the anchor question.

Results

At entry, the mean TOI-14 scores were significantly higher in the surgical cohort than in the control cohort [mean (95% confidence interval)] 33.0 (27.0–39.1) vs. 5.0 (3.6–6.4), respectively. At 6 months follow-up, the mean TOI-14 scores had improved markedly after tonsillectomy to the level of the control cohort. In the healthy population, the score was in most cases under 15.0 points. In patients, a score of about 20.0 indicated mild symptoms, 30.0 moderate symptoms and 40.0 or higher intense symptoms. The MIC value was 10.0 points.

Conclusions

These results enable the more accurate interpretation of the scores of the only disease-specific QoL instrument for adult throat-related diseases.
Changing phase relationship of the stepping rhythm to neuronal oscillatory theta activity in the septo-hippocampal network of mice
Authors: Joshi Abhilasha , Somogyi Peter
Published: February 2020

Movement-related sensory and motor activity in the brain contributes to cognitive processes. We have observed that the frequency of stepping rhythm in head-fixed mice running on a jetball overlaps with the range of frequencies that characterize hippocampal rhythmic slow activity, including theta (~ 3 to 10 Hz). On average, step-cycle troughs (i.e. when the paw touches the ground) were weakly coupled to hippocampal theta oscillations. This weak coupling was sustained during a range of running speeds. In short temporal windows, step-cycle troughs were synchronous with hippocampal theta oscillatory cycle troughs, while during other periods they led or lagged behind theta cycles. Furthermore, simultaneously recorded theta rhythmic medial septal neurons in the basal forebrain were phase-coupled to both step-cycles and theta-cycles. We propose that the weak overall phase relationship of step-cycles with theta-cycles signifies a distinct mode of information processing. Transient synchronization of the step-cycle with theta may indicate the engagement of septo-hippocampal-entorhinal network with the current heading of the animal.