bluuebunny/crossref_metadata_2025 huggingface dataset:
Can dementia be predicted using olfactory identification test in the elderly? A Bayesian network analysis
Authors: Ding Ding , Liang Xiaoniu , Xiao Zhenxu , Wu Wanqing , Zhao Qianhua , Cao Yang
Published: August 2020

Background

Previous studies suggest that olfactory dysfunction is associated with cognitive decline or dementia.

Objective

To find a potential association between the olfactory identification (OI) and dementia onset, and build a prediction model for dementia screening in the older population.

Methods

Nine hundred and forty‐seven participants from the Shanghai Aging Study were analyzed. The participants were dementia‐free and completed OI test using the Sniffin’ Sticks Screening Test‐12 at baseline. After an average of 4.9‐year follow‐up, 75 (8%) of the participants were diagnosed with incident dementia. Discrete Bayesian network (DBN) and multivariable logistic regression (MLR) models were used to explore the dependencies of the incident dementia on the baseline demographics, lifestyles, and OI test results.

Results

In DBN analysis, odors of orange, cinnamon, peppermint, and pineapple, combined with age and Mini‐mental State Examination (MMSE), achieved a high predictive ability for incident dementia, with an area under the receiver operating characteristic curve (AUC) larger than 0.8. The odor cinnamon showed the highest AUC of 0.838 (95% CI: 0.731–0.946) and a high accuracy of 0.867. The DBN incorporating age, MMSE, and one odor test had an accuracy (0.760–0.872 vs. 0.835) comparable to that of the MLR model and revealed the dependency between the variables.

Conclusion

The DBN using OI test may have predictive ability comparable to MLR analysis and suggest potential causal relationship for further investigation. Identification of odor cinnamon might be a useful indicator for dementia screening and deserve further investigation.
Spectroscopy integration to miniature bioreactors and large scale production bioreactors–Increasing current capabilities and model transfer
Authors: Rowland‐Jones Ruth C. , Graf Alexander , Woodhams Angus , Diaz‐Fernandez Paloma , Warr Steve , Soeldner Robert , Finka Gary , Hoehse Marek
Published: August 2020

Spectroscopy techniques are being implemented within the biopharmaceutical industry due to their non‐destructive ability to measure multiple analytes simultaneously, however, minimal work has been applied focussing on their application at small scale. Miniature bioreactor systems are being applied across the industry for cell line development as they offer a high‐throughput solution for screening and process optimization. The application of small volume, high‐throughput, automated analyses to miniature bioreactors has the potential to significantly augment the type and quality of data from these systems and enhance alignment with large‐scale bioreactors. Here, we present an evaluation of 1. a prototype that fully integrates spectroscopy to a miniature bioreactor system (ambr®15, Sartorius Stedim Biotech) enabling automated Raman spectra acquisition, 2. In 50 L single‐use bioreactor bag (SUB) prototype with an integrated spectral window. OPLS models were developed demonstrating good accuracy for multiple analytes at both scales. Furthermore, the 50 L SUB prototype enabled on‐line monitoring without the need for sterilization of the probe prior to use and minimal light interference was observed. We also demonstrate the ability to build robust models due to induced changes that are hard and costly to perform at large scale and the potential of transferring these models across the scales. The implementation of this technology enables integration of spectroscopy at the small scale for better process understanding and generation of robust models over a large design space while facilitating model transfer throughout the scales enabling continuity throughout process development and utilization and transfer of ever‐increasing data generation from development to manufacturing.
Transcatheter mitral valve in ring, hazards of long anterior mitral leaflet and 3‐dimensional rings
Authors: Sekaran Nishant , Horne Benjamin D. , Doty John R. , Reid Bruce B. , Miner Edward C. , Harkness James R. , Jones Kent W. , Minder Camille Michael , Caine William T. , Clayson Stephen E. , Whisenant Brian K.
Published: August 2020

Objectives

The purpose of this study was to define anterior mitral leaflet (AML) length and mitral ring characteristics associated with LVOT obstruction and PVL following MViR.

Background

Transcatheter Mitral Valve in Ring (MViR) procedural complications including parvalvular leak (PVL) and left ventricular outflow tract (LVOT) obstruction are frequent.

Methods

Clinical records, computer tomographic scans (CTs) and echocardiograms of consecutive MViR patients were retrospectively reviewed for anterior mitral leaflet length, CT‐simulated neoLVOT, and aortomitral angle among patients with and without MViR‐induced LVOT obstruction. Acute and 1‐year outcomes are described.

Results

Twenty‐two patients underwent MViR. Technical success was achieved in 13/22 (57.1%) patients, limited by paravalvular regurgitation requiring second transcatheter heart valves (THVs) in seven patients. Second valves were needed in 6/11 (54.5%) patients with 3‐dimensional rings but 1/11 (9.1%, p = .06) of patients with planar rings. Procedure success at 30 days was achieved in 20/22 (90.9%) patients. There were no procedural, in‐hospital, or 30‐day deaths. Two patients developed significant LVOT obstruction, one managed with urgent surgery and one with elective alcohol septal ablation. Anterior mitral leaflets were longer among the two patients with LVOT obstruction than the 20 patients who did not develop LVOT obstruction when measured by TEE (30 mm vs. 21 mm, p = .009) or by CT (29 mm vs. 22 mm, p = .026).

Conclusions

AML >25 mm increases the risk of MViR induced LVOT obstruction. PVL is common, particularly in 3‐dimensional rings which can be managed with a second THV.
Long‐term clinical outcomes of coronary artery bypass graft surgery compared to those of percutaneous coronary intervention with second generation drug eluting stents in patients with stable angina and an isolated lesion in the proximal left anterior descending artery
Authors: Matsoukis Ioannis L. , Karanasos Antonios , Patsa Chrysoula , Anousakis‐Vlachochristou Nikolaos , Triantafyllou Konstantinos , Kantzanou Maria , Drakopoulou Maria , Tsiamis Eleftherios , Latsios George , Synetos Andreas , Petridou Eleni Th , Tousoulis Dimitris , Toutouzas Konstantinos
Published: August 2020

Objectives

We compared the long‐term outcomes of percutaneous coronary intervention with second‐generation drug‐eluting stents (PCI‐DES) and coronary artery bypass graft surgery (CABG) with the left internal mammary artery in stable angina patients with isolated single‐vessel proximal left anterior descending artery (pLAD) disease.

Background

Long‐term outcomes of second‐generation PCI‐DES and CABG in isolated pLAD lesions have not been extensively studied.

Methods

We included 631 PCI‐DES patients and 379 CABG patients. Unadjusted and adjusted hazard ratios (HRs) were derived for major adverse cardiac events (MACEs), their components (cardiac death, nonfatal myocardial infarction [MI] not attributed to a non‐target vessel, target‐lesion revascularization), and patient‐related outcome (PRO, composed of all‐cause mortality, any MI, any revascularization).

Results

In the unadjusted and adjusted analyses, no significant difference was observed between the two groups at follow‐up (mean:4.6 ± 2.5 years) for MACEs (HR: 1.45, 95% CI: 0.92–2.28, p = .11; HR:1.43, 95% CI: 0.91–2.26, p = .13), PRO (HR: 1.18, 95%CI: 0.86–1.61, p = .30; HR: 1.18, 95% CI: 0.86–1.62, p = .31), cardiac death (HR: 0.97, 95% CI: 0.46–2.05, p = .93; HR: 0.79, 95% CI: 0.36–1.72, p = .56) and MI (HR: 1.43, 95% CI: 0.49–4.13, p = .51; HR: 1.57, 95% CI: 0.53–4.64, p = .42). Compared with CABG, PCI‐DES had a borderline significantly greater risk of repeat revascularization (HR: 1.99, 95% CI: 1.00–3.94, p = .05; HR: 1.95, 95% CI: 0.98–3.9, p = .06). Angina recurred more often after PCI (p < .001), whereas more arrhythmias developed after CABG (p = .02). PCI‐DES resulted in fewer in‐hospital complications (p < .001) and shorter hospitalizations (p < .001).

Conclusions

The long‐term clinical outcomes of second‐generation PCI‐DES and CABG in patients with stable angina and isolated pLAD disease were comparable.
Transcatheter aortic valve implantation for severe pure aortic regurgitation due to active aortitis
Authors: Ruggiero Rossella , Ponticelli Francesco , Giannini Francesco , Galvani Marcello
Published: August 2020

Aortitis is an uncommon systemic inflammatory disease affecting the aorta and its main branches. Severe aortic regurgitation (AR) represents a fearsome complication of aortitis and is associated with an increased mortality rate. Surgical aortic valve replacement represents the only treatment choice for these patients. However, it is associated with a higher risk of medium to long‐term complications such as prosthetic valve detachment. This is the first reported case where severe AR secondary to aortitis was managed with transcatheter aortic valve implantation (TAVI). TAVI was safe and effective in this clinical setting and may be considered a viable alternative to high‐risk surgery in these complex patients.
Variable selection for proportional hazards models with high‐dimensional covariates subject to measurement error
Authors: Chen Baojiang , Yuan Ao , Yi Grace Y.
Published: August 2020

Methods of analyzing survival data with high‐dimensional covariates are often challenged by the presence of measurement error in covariates, a common issue arising from various applications. Conducting naive analysis with measurement‐error effects ignored usually gives biased results. However, relatively little research has been focused on this topic. In this article, we consider this important problem and discuss variable selection for proportional hazards models with high‐dimensional covariates subject to measurement error. We propose a penalized “corrected” likelihood‐based method to simultaneously address the measurement‐error effects and perform variable selection. We establish theoretical results including the consistency, the oracle property and the asymptotic distribution of the proposed estimator. Simulation studies are conducted to assess the finite sample performance of the proposed method. To illustrate the use of our method, we apply the proposed method to analyze a dataset arising from the breast cancer study.
Genetic Manipulation of Corynebacterium diphtheriae and Other Corynebacterium Species
Authors: Chang Chungyu , Nguyen Minh Tan , Ton‐That Hung
Published: August 2020

This article describes several established approaches for genetic manipulation of Corynebacterium diphtheriae, the causative agent of diphtheria that is known to have provided key evidence for Koch's postulates on the germ theory. First, it includes a detailed gene deletion method that generates nonpolar, in‐frame, markerless deletion mutants, utilizing the levansucrase SacB as a counter‐selectable marker. Second, it provides a thorough protocol for rescuing deletion mutants using Escherichia coli–Corynebacterium shuttle vectors. Finally, a Tn5 transposon mutagenesis procedure is described. In principle, these protocols can be used for other Corynebacterium species, including Corynebacterium glutamicum and Corynebacterium matruchotii. © 2020 Wiley Periodicals LLC

Basic Protocol 1: Gene deletion in Corynebacterium diphtheriae

Basic Protocol 2: Complementation of a mutant strain

Basic Protocol 3: Tn5 transposon mutagenesis of Corynebacterium diphtheriae
Simultaneous Assessment of Circadian Rhythms and Sleep in Mice Using Passive Infrared Sensors: A User's Guide
Authors: Brown Laurence A. , Banks Gareth T. , Horner Neil , Wilcox Sian L. , Nolan Patrick M. , Peirson Stuart N.
Published: August 2020

The 24‐hr cycle of activity and sleep provides perhaps the most familiar example of circadian rhythms. In mammals, circadian activity rhythms are generated by a master biological clock located in the hypothalamic suprachiasmatic nuclei (SCN). This clock is synchronized (entrained) to the external light environment via light input from retinal photoreceptors. However, sleep is not a simple circadian output and also is regulated by a homeostatic process whereby extended wakefulness increases the need for subsequent sleep. As such, the amount and distribution of sleep depends upon the interaction between both circadian and homeostatic processes. Moreover, the study of circadian activity and sleep is not confined only to these specialized fields. Sleep and circadian rhythm disruption is common in many conditions, ranging from neurological and metabolic disorders to aging. Such disruption is associated with a range of negative consequences including cognitive impairment and mood disorders, as well as immune and metabolic dysfunction. As circadian activity and sleep are hallmarks of normal healthy physiology, they also provide valuable welfare indicators. However, traditional methods for the monitoring of circadian rhythms and sleep in mice can require separate specialized resources as well as significant expertise. Here, we outline a low‐cost, non‐invasive, and open‐source method for the simultaneous assessment of circadian activity and sleep in mice. This protocol describes both the assembly of the hardware used and the capture and analysis of data without the need for expertise in electronics or data processing. © 2020 Wiley Periodicals LLC.

Basic Protocol: Assembly of a PIR system for basic activity and sleep recordings

Alternate Protocol: Data collection using Raspberry Pi

Support Protocol: Circadian analysis using PIR sensors
Using CRISPR/ttLbCas12a for in planta Gene Targeting in A. thaliana
Authors: Merker Laura , Schindele Patrick , Puchta Holger
Published: August 2020

CRISPR/Cas systems enable gene editing through the induction of site‐specific DNA double‐strand breaks (DSB). However, the nature of the induced modification highly depends on the mechanism used for DNA DSB repair. Non‐homologous end joining (NHEJ)‐mediated targeted mutagenesis induced by CRISPR/Cas is an already standardly applied tool, which can lead to various different kinds of mutations at a specific genomic site. Nevertheless, precise genome modification using homologous donor sequences is still challenging in plants. Applications depending on the less frequent homologous recombination (HR) require further improvements to create an attractive and efficient tool for general application in plants. Focusing on this issue, we developed the in planta gene targeting (ipGT) system, which is based on the simultaneous excision of a stably integrated, homologous donor sequence and the induction of a DSB within the target site. In recent years, several improvements were achieved enhancing gene targeting (GT) frequencies. After the successful application of Streptococcus pyogenes Cas9 (SpCas9) and Staphylococcus aureus Cas9 (SaCas9) for ipGT, we were able to further improve the system using Lachnospiraceae bacterium Cas12a (LbCas12a), which also enables cleavage in T‐rich regions. Most recently, we tested an improved, temperature‐tolerant version of LbCas12a (ttLbCas12a) for ipGT and were able to further increase GT efficiencies. Here, we describe the experimental procedure of the recently published ipGT system using ttLbCas12a in Arabidopsis thaliana in detail. © 2020 The Authors.

Basic Protocol 1: Construction of CRISPR/ttLbCas12a expression vector to analyze ipGT efficiencies

Basic Protocol 2: Achieving heritable GT plants
Luminescent Thermometers: From a Library of Europium(III) β‐Diketonates to a General Model for Predicting the Thermometric Behaviour of Europium‐Based Coordination Systems
Authors: Carlotto Alice , Babetto Luca , Carlotto Silvia , Miozzi Massimo , Seraglia Roberta , Casarin Maurizio , Bottaro Gregorio , Rancan Marzio , Armelao Lidia
Published: August 2020

The front cover artwork is provided by the Functional Molecules and Inorganic Nanosystems Lab at ICMATE‐CNR and University of Padova (Italy). The image shows a europium luminescent molecular thermometer (LMT) with a maze on the background. It symbolizes the dead‐ends behind the design of new Eu‐LMTs for which we propose a predictive tool, named ThesEuS, developed from a library of Eu(III)‐β‐diketonates, in order to get out of the maze. Read the full text of the Article at 10.1002/cptc.2020000116.
Molecular study of drought response in the Mediterranean conifer Pinus pinaster Ait.: Differential transcriptomic profiling reveals constitutive water deficit‐independent drought tolerance mechanisms
Authors: de María Nuria , Guevara María Ángeles , Perdiguero Pedro , Vélez María Dolores , Cabezas José Antonio , López‐Hinojosa Miriam , Li Zhen , Díaz Luís Manuel , Pizarro Alberto , Mancha José Antonio , Sterck Lieven , Sánchez‐Gómez David , Miguel Célia , Collada Carmen , Díaz‐Sala María Carmen , Cervera María Teresa
Published: August 2020

Adaptation of long‐living forest trees to respond to environmental changes is essential to secure their performance under adverse conditions. Water deficit is one of the most significant stress factors determining tree growth and survival. Maritime pine (Pinus pinaster Ait.), the main source of softwood in southwestern Europe, is subjected to recurrent drought periods which, according to climate change predictions for the years to come, will progressively increase in the Mediterranean region. The mechanisms regulating pine adaptive responses to environment are still largely unknown. The aim of this work was to go a step further in understanding the molecular mechanisms underlying maritime pine response to water stress and drought tolerance at the whole plant level. A global transcriptomic profiling of roots, stems, and needles was conducted to analyze the performance of siblings showing contrasted responses to water deficit from an ad hoc designed full‐sib family. Although P. pinaster is considered a recalcitrant species for vegetative propagation in adult phase, the analysis was conducted using vegetatively propagated trees exposed to two treatments: well‐watered and moderate water stress. The comparative analyses led us to identify organ‐specific genes, constitutively expressed as well as differentially expressed when comparing control versus water stress conditions, in drought‐sensitive and drought‐tolerant genotypes. Different response strategies can point out, with tolerant individuals being pre‐adapted for coping with drought by constitutively expressing stress‐related genes that are detected only in latter stages on sensitive individuals subjected to drought.
Major histocompatibility complex variation is similar in little brown bats before and after white‐nose syndrome outbreak
Authors: Yi Xueling , Donner Deahn M. , Marquardt Paula E. , Palmer Jonathan M. , Jusino Michelle A. , Frair Jacqueline , Lindner Daniel L. , Latch Emily K.
Published: August 2020

White‐nose syndrome (WNS), caused by the fungal pathogen Pseudogymnoascus destructans (Pd), has driven alarming declines in North American hibernating bats, such as little brown bat (Myotis lucifugus). During hibernation, infected little brown bats are able to initiate anti‐Pd immune responses, indicating pathogen‐mediated selection on the major histocompatibility complex (MHC) genes. However, such immune responses may not be protective as they interrupt torpor, elevate energy costs, and potentially lead to higher mortality rates. To assess whether WNS drives selection on MHC genes, we compared the MHC DRB gene in little brown bats pre‐ (Wisconsin) and post‐ (Michigan, New York, Vermont, and Pennsylvania) WNS (detection spanning 2014–2015). We genotyped 131 individuals and found 45 nucleotide alleles (27 amino acid alleles) indicating a maximum of 3 loci (1–5 alleles per individual). We observed high allelic admixture and a lack of genetic differentiation both among sampling sites and between pre‐ and post‐WNS populations, indicating no signal of selection on MHC genes. However, post‐WNS populations exhibited decreased allelic richness, reflecting effects from bottleneck and drift following rapid population declines. We propose that mechanisms other than adaptive immunity are more likely driving current persistence of little brown bats in affected regions.
Reconstructing continental‐scale variation in soil δ15N: a machine learning approach in South America
Authors: Sena‐Souza João Paulo , Houlton Benjamin Z. , Martinelli Luiz Antônio , Bielefeld Nardoto Gabriela
Published: August 2020

Soil nitrogen isotope composition (δ15N) is an essential tool for investigating ecosystem nitrogen balances, plant–microbe interactions, ecological niches, animal migration, food origins, and forensics. The advancement of these applications is limited by a lack of robust geospatial models that are capable of capturing variation in soil δ15N (i.e., isotopic landscapes or isoscapes). Due to the complexity of the nitrogen cycle and general scarcity of isotopic information, previous approaches have reconstructed regional to global soil δ15N patterns via highly uncertain linear regression models. Here, we develop a new machine learning approach to ascertain a finer‐scale understanding of geographic differences in soil δ15N, using the South American continent as a test case. We use a robust training set spanning 278 geographic locations across the continent, spanning all major biomes. We tested three different machine learning methods: cubist, random forest (RF), and stochastic gradient boosting (GBM). 10‐fold cross‐validation revealed that the RF method outperformed both the cubist and GBM approaches. Variable importance analysis of the RF framework pointed to biome type as the most crucial auxiliary variable, followed by soil organic carbon content, in determining the model performance. We thereby created a biogeographic boundary map, which predicted an expected multiscale spatial pattern of soil δ15N with a high degree of confidence, performing substantially better than all previous approaches for the continent of South America. Therefore, the RF machine learning framework showed to be a great opportunity to explore a broad array of ecological, biogeochemical, and forensic issues through the lens of soil δ15N.
Comparative Study of Metallocene Modified Gold Nanoparticles Polymer Electrodes for Effective Determination of Dopamine
Authors: Atta Nada F. , Galal Ahmed , Hassan Samar H.
Published: August 2020

Here in we present a gold nanoparticles‐poly (3,4‐ethylenedioxythiophene) (PEDOT) modified with metallocene (ferrocene carboxylic acid (FC1), ferrocene (FC2) or cobaltocene (CC)) composites based electrochemical sensors for sensitive determination of dopamine (DA). Higher electron transfer and electrocatalytic activity towards DA are obtained with FC1. The presence of ferrocenium ions enhances the charge exchange rate and the carboxyl groups enhance the electronic conduction in the composite. DA is determined in presence of uric and ascorbic acids with excellent resolution and sensitivity. DA is determined in urine samples with limit of detection 19.6 nM, in the range of 4 to 160 μM.
Phase II study of de‐intensified intensity‐modulated radiotherapy and concurrent carboplatin/5‐fluorouracil in lateralized p16‐associated oropharyngeal carcinoma
Authors: Bahig Houda , Lambert Louise , Filion Edith , Soulières Denis , Guertin Louis , Ayad Tareck , Christopoulos Apostolos , Bissada Eric , Alizadeh Moein , Bélair Manon , Nguyen‐Tan Phuc Felix
Published: August 2020

Purpose

To assess cancer control and patient‐reported outcomes (PROs) after de‐intensified intensity‐modulated radiotherapy (IMRT) in lateralized p16‐associated oropharyngeal cancer (p16‐OPC).

Methods

Lateralized p16‐OPC treated with radiotherapy and concurrent Carboplatin/5‐fluorouracil between 2011 and 2014 were enrolled. De‐intensified IMRT consisted in elective neck dose of 43.2 Gy/24 fractions and omission of contralateral retropharyngeal/level IV nodes. PROs were assessed using the EORTC QLC‐C30 and QLQ‐HN35 scales.

Results

Twenty‐nine patients were included. Median follow‐up was 44 months. As per AJCC 7th Ed, 7%, 83% and 10% of patients had stage III, IVa and IVb. 5‐year locoregional control and overall survival rates were 100% and 100%, respectively. Rates of acute were 52% and 35%, respectively. At 2 years post‐treatment, 50% and 14% of patients had grade 1 xerostomia and dysgueusia, respectively. Most PROs scores returned to baseline within 8 months post‐treatment.

Conclusion

De‐intensified IMRT was associated with excellent cancer outcomes, and rapid recovery of PROs in lateralized p16‐OPC.
Pharyngocutaneous fistulas after total laryngectomy or pharyngolaryngectomy: Place of video‐fluoroscopic swallowing study
Authors: Carsuzaa Florent , Capitaine Anne‐Laure , Ferrié Jean‐Claude , Apert Vincent , Tonnerre Denis , Frasca Denis , Dufour Xavier
Published: August 2020

Background

Specify place of video‐fluoroscopic swallowing study (VFS) in the decision of oral refeeding after total pharyngolaryngectomy.

Methods

At postoperative day 7, a blue dye testing was performed. If negative, a VFS was performed looking for a blind fistula. If this exam was negative, oral refeeding was started, but if a blind fistula was observed, cervical compression bandage was performed.

Results

In 186 patients, a VFS was performed for 142 patients with negative blue dye testing. It was negative for 98 patients (69%) and positive for 44 patients (31%) (blind fistula). Patients had a probability of 7.1% to have a secondary pharyngocutaneous fistula (PCF) if the VFS was negative, and 15.9% if it was positive. No risk factor for the development of a secondary PCF or a blind fistula emerged from our analysis.

Conclusion

VFS should be performed before any oral refeeding in all patients operated with a total pharyngolaryngectomy.
Evaluation of in vitro corrosion behavior of zinc–hydroxyapatite and zinc–hydroxyapatite–iron as biodegradable composites
Authors: Pathak Dayanidhi Krishana , Pandey Pulak Mohan
Published: August 2020

Zinc (Zn) based biomaterials have been emerged as one of the capable biodegradable materials for biomedical applications because of the ideal degradation properties. In the present work, corrosion kinetics of Zn–hydroxyapatite (HA), and Zn–HA–iron (Fe) materials developed using microwave sintering process were investigated. The effect of the inclusion of HA and Fe in Zn on corrosion properties have been evaluated in the simulated body fluid solution. Further, the wettability test of the developed composites was performed to confirm the hydrophilic nature of the surface of all samples. Zn‐3HA was found to have better hydrophilicity as compared to other samples. Increased corrosion rate and pH of Zn‐5HA‐2Fe samples were attributed to the addition of HA and Fe in the Zn matrix. The corrosion rate and weight loss rate from electrochemical and immersion testing of all samples were found in the order from highest to lowest: Zn‐5HA‐2Fe > Zn‐3HA > Zn‐3HA‐2Fe > Zn. The highest cell viability nearly 100% was obtained for Zn‐3HA samples, whereas other samples also showed sufficient biocompatibility to be utilized for biomedical applications.
Novel three‐dimensional bioglass functionalized gelatin nanofibrous scaffolds for bone regeneration
Authors: Zheng Xiao , Liu Yu , Liu Yangxi , Pan Yining , Yao Qingqing
Published: August 2020

The clinical use of FDA‐approved bone morphogenetic proteins (BMPs) are impeded by high costs, super‐high dosage requirement, short half‐life, and other undesirable side effects. Therefore, designing a biomaterial that can promote new bone formation without using exogenous BMPs is highly desirable in clinical applications. In the present work, a new kind of nanofibrous scaffold composed of gelatin and 45S5 bioglass (GF/45S5 BG) was prepared through thermally induced phase separation method together with the particle leach technique (TIPS&P). In addition to the significantly higher mechanical strength, the composite scaffolds (GF/45S5 BG) significantly increased osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro compared with the neat scaffold (GF) without adding other biological agents, for example, BMPs or hormones. Most importantly, our in vivo studies also indicated that GF/45S5 BG scaffolds could directly promote ectopic bone regeneration in SD rats without exogenous BMP2. In summary, both in vitro and in vivo results indicated that the novel 45S5 bioglass functionalized GF nanofibrous scaffold is a promising alternative for bone tissue engineering.
Rutin treats myocardial damage caused by pirarubicin via regulating miR‐22‐5p‐regulated RAP1/ERK signaling pathway
Authors: Qin Meng , Li Qi , Wang Yadi , Li Tengteng , Gu Zehui , Huang Peng , Ren Liqun
Published: August 2020

Our experiments have previously demonstrated that rutin (RUT) can improve myocardial damage caused by pirarubicin (THP). However, the underlying molecular mechanisms remain uncertain. In this study, we developed an microRNA (miRNA) chip by replicating the rat model of THP‐induced myocardial injury and identified miR‐22‐5p and the RAP1‐member of RAS oncogene family/extracellular regulated protein kinases (RAP1/ERK) signaling pathway as an object of study. Also, in vivo experiments demonstrated that THP caused abnormal changes in the electrocardiogram, cardiac function, and histomorphology in rats (P < .01). THP also reduces the expression of miR‐22‐5p (P < .01) and increases the levels of RAP1/ERK signaling pathway‐related proteins (P < .01, P < .05). RUT significantly improved THP‐induced myocardial damage (P < .01), increased the expression of miR‐22‐5p (P < .01), and decreased the levels of RAP1/ERK signaling pathway‐related proteins (P < .01, P < .05). In vitro studies confirmed that Rap1a is one of the target genes of miR‐22‐5p. miR‐22‐5p overexpression in cardiomyocytes can affect the RAP1/ERK pathway and reduce reactive oxygen species production and cardiomyocyte apoptosis caused by THP (P < .01), which is consistent with the effect of RUT. Our results indicate that RUT treats THP‐induced myocardial damage, which may be achieved by upregulating miR‐22‐5p, causing changes in its target gene Rap1a and the RAP1/ERK pathway.
Toward universal substituent constants: Model chemistry sensitivity of descriptors from the quantum theory of atoms in molecules
Authors: Lefrancois‐Gagnon Kevin M. , Mawhinney Robert C.
Published: August 2020

The quantum theory of atoms in molecules (QTAIM) provides a theoretical foundation to determine the properties of functional groups through additive atomic contributions. Many studies have used QTAIM in their analyses with a variety of electronic structure methods, but it is unknown if the properties measured using one model chemistry, the combination of the electronic structure method and basis set, can be compared to those measured by another. Here, we evaluate the sensitivity of QTAIM functional group and bond critical point properties using six functionals and seven basis sets. High‐level B2PLYPD3‐BJ/aug‐cc‐pV5Z reference values are provided for 116 functional groups and the property sensitivity with respect to these values are evaluated based on absolute deviations and by assessing linear relationships. Functional group properties, including charges, dipoles, quadrupoles and volumes, were found to be mostly insensitive to choice of computational model chemistry. However, due to structural and topological inconsistencies, the 6‐31G(d) basis set is not recommended for use. Bond critical point properties varied with choice of model chemistry, but models incorporating hybrid functionals and triple‐ζ basis sets provided values suitable for use in regression studies.
A nanoscale Ni/ZrO2 catalyst coated with Al2O3 for carbon dioxide reforming of methane
Authors: Wang Xiaorui , Bai Xiaoli , Guo Yu , Liu Qirui , Ji Shengfu , Wang Zhou‐jun
Published: August 2020

BACKGROUND

CO2 reforming of methane, also known as dry reforming of methane, has received significant attention because this technology can convert notorious greenhouse gases (CH4/CO2) into useful syngas (H2/CO). However, this technology still has not been commercialized, primarily due to the lack of feasible catalysts.

RESULTS

Based on zirconia (ZrO2) nanoparticles with pure monoclinic (m) or tetragonal (t) crystal phase, three nickel catalysts (Ni/m‐ZrO2, Ni/t‐ZrO2 and Ni/m‐ZrO2@Al2O3) have been synthesized for CO2 reforming of methane. The Ni/t‐ZrO2 catalyst exhibited the lowest reforming activity with CH4 conversion of 15.5% at 700 °C under 1 atm with a gas hourly space velocity of 96 000 mL (h gcat)−1. The Ni/m‐ZrO2 catalyst showed much higher initial activity but underwent severe deactivation, during which CH4 conversion decreased from 56.1% to 33.4% after 300 min of reaction. The nanocomposite Ni/m‐ZrO2@Al2O3 catalyst with confinement effect exhibited the best activity and good stability. Specifically, its CH4 conversion decreased merely from 60.2% to 55.3% after 24 h of reaction.

CONCLUSIONS

Structural characterizations demonstrate that limited specific surface area and weak metal–support interactions existed on the Ni/t‐ZrO2 catalyst, which led to large nickel nanoparticles and thus poor reforming activity. Both Ni/m‐ZrO2 and Ni/m‐ZrO2@Al2O3 catalysts had high specific surface area and very small nickel nanoparticles, which may rationalize the high reforming activity. The improved stability of the Ni/m‐ZrO2@Al2O3 catalyst was mainly related to the alleviated carbon deposition resulting from enriched surface basicity and strengthened metal–support interactions. © 2020 Society of Chemical Industry (SCI)
AI‐Enhanced Diagnosis of Challenging Lesions in Breast MRI: A Methodology and Application Primer
Authors: Meyer‐Base Anke , Morra Lia , Tahmassebi Amirhessam , Lobbes Marc , Meyer‐Base Uwe , Pinker Katja
Published: August 2020

Computer‐aided diagnosis (CAD) systems have become an important tool in the assessment of breast tumors with magnetic resonance imaging (MRI). CAD systems can be used for the detection and diagnosis of breast tumors as a “second opinion” review complementing the radiologist's review. CAD systems have many common parts, such as image preprocessing, tumor feature extraction, and data classification that are mostly based on machine‐learning (ML) techniques. In this review article, we describe applications of ML‐based CAD systems in MRI covering the detection of diagnostically challenging lesions of the breast such as nonmass enhancing (NME) lesions, and furthermore discuss how multiparametric MRI and radiomics can be applied to the study of NME, including prediction of response to neoadjuvant chemotherapy (NAC). Since ML has been widely used in the medical imaging community, we provide an overview about the state‐of‐the‐art and novel techniques applied as classifiers to CAD systems. The differences in the CAD systems in MRI of the breast for several standard and novel applications for NME are explained in detail to provide important examples, illustrating: 1) CAD for detection and diagnosis, 2) CAD in multiparametric imaging, 3) CAD in NAC, and 4) breast cancer radiomics. We aim to provide a comparison between these CAD applications and to illustrate a global view on intelligent CAD systems based on machine and deep learning in MRI of the breast.

Level of Evidence

2

Technical Efficacy Stage

2
The regional MiKlip decadal prediction system for Europe: Hindcast skill for extremes and user‐oriented variables
Authors: Moemken Julia , Feldmann Hendrik , Pinto Joaquim G. , Buldmann Benjamin , Laube Natalie , Kadow Christopher , Paxian Andreas , Tiedje Bente , Kottmeier Christoph , Marotzke Jochem
Published: August 2020

Regional climate predictions for the next decade are gaining importance, as this period falls within the planning horizon of politics, economy, and society. The potential predictability of climate indices or extremes at the regional scale is of particular interest. The German MiKlip project (“mid‐term climate forecast”) developed the first regional decadal prediction system for Europe at 0.44° resolution, based on the regional model COSMO‐CLM using global MPI‐ESM simulations as boundary conditions. We analyse the skill of this regional system focussing on extremes and user‐oriented variables. The considered quantities are related to temperature extremes, heavy precipitation, wind impacts, and the agronomy sector. Variables related to temperature (e.g., frost days, heat wave days) show high predictive skill (anomaly correlation up to 0.9) with very little dependence on lead‐time, and the skill patterns are spatially robust. The skill patterns for precipitation‐related variables (e.g., heavy precipitation days) and wind‐based indices (like storm days) are less skilful and more heterogeneous, particularly for the latter. Quantities related to the agronomy sector (e.g., growing degree days) show high predictive skill, comparable to temperature. Overall, we provide evidence that decadal predictive skill can be generally found at the regional scale also for extremes and user‐oriented variables, demonstrating how the utility of decadal predictions can be substantially enhanced. This is a very promising first step towards impact‐related modelling at the regional scale and the development of individual user‐oriented products for stakeholders.
Pharmacokinetic comparison of nine bioactive components in rat plasma following oral administration of raw and wine‐processed Ligustri Lucidi Fructus by ultra‐high‐performance liquid chromatography coupled with triple quadrupole mass spectrometry
Authors: Zhang Danjie , Sun Linlin , Li Huifen , Cui Yueli , Liu Shuai , Wu Peng , Zhao Dongsheng , Zhao Pan , Zhang Xuelan
Published: August 2020

An accurate and sensitive ultra‐high‐performance liquid chromatography coupled with triple quadrupole mass spectrometry method was established and validated for the determination of nine bioactive compounds of Ligustri Lucidi Fructus in rat plasma. Separation was performed on Halo® C18 column with a mobile phase of acetonitrile and 0.1% formic acid in water. The eluate was detected by multiple reaction monitoring scanning operating in the negative ionization mode. This assay method was validated for selectivity, linearity, intra‐ and interday precision, accuracy, recovery, matrix effect, and stability, and all methodological parameters fulfilled the Food and Drug Administration criteria for bioanalytical validation. The established method was successfully applied to a comparative pharmacokinetic study of raw and wine‐processed Ligustri Lucidi Fructus in rats for the first time. It was found that the AUC0‐24 and Cmax value of salidroside, hydroxytyrosol, and nuezhenidic acid were increased significantly after processing, while the AUC0‐24 and Cmax value of oleoside 11‐methyl ester, 1′''‐O‐β‐d‐glucosylformoside, specnuezhenide, G13, oleonuezhenide, and oleanolic acid were decreased, which suggested that processing affects the absorption and bioavailability of Ligustri Lucidi Fructus. The results might be valuable for the clinical reasonable application and understanding the processing mechanism of Ligustri Lucidi Fructus.
Fetal Lung Echo Texture in Pregnancies at Risk for Pulmonary Hypoplasia
Authors: Blitz Matthew J. , Ghorayeb Sleiman R. , Solmonovich Rachel , Glykos Stella , Jauhari Arushi , Rochelson Burton , Bracero Luis A.
Published: August 2020

Pulmonary hypoplasia is associated with severe respiratory distress immediately after birth and frequently leads to neonatal death. In this study, we compared the fetal lung echo texture in pregnancies at high and low risk for pulmonary hypoplasia. Ultrasonic tissue heterogeneity was determined by a dynamic range calculation. This quantification uses a dithering technique based on the Floyd‐Steinberg algorithm, in which the pixels are transformed into a binary map. Pregnancies at high risk for pulmonary hypoplasia showed decreased fetal lung heterogeneity on ultrasound imaging. This image‐processing technique may allow improved risk stratification, patient counseling, and treatment approaches for pulmonary hypoplasia.
Variability of benthic methane‐derived carbon along seasonal, biological, and sedimentary gradients in a polymictic lake
Authors: Tsuchiya Kenji , Komatsu Kazuhiro , Shinohara Ryuichiro , Imai Akio , Matsuzaki Shin‐ichiro S. , Ueno Ryuhei , Kuwahara Victor S. , Kohzu Ayato
Published: August 2020

The spatial and seasonal variations of methane‐derived carbon contributions to Chironomus plumosus larvae and oligochaetes biomass at four stations in a polymictic, eutrophic lake were examined to determine which factors (CH4 and/or dissolved oxygen) affect the methane‐derived carbon contributions, and quantify impacts of benthic methane‐derived carbon on the lake food web. Methane‐derived carbon contributions were estimated by a two‐source mixing model using δ13C values of monthly particulate organic matter ( −29.5 to −20.8‰) and methane‐oxidizing bacteria (−85.7‰). Large spatial and seasonal variability of methane‐derived carbon contributions to C. plumosus and oligochaetes within the lake (0–38% and 0–32%, respectively) were observed, where contributions varied spatially along a gradient of sediment CH4 concentration, but not dissolved oxygen. The results suggest that for both C. plumosus and oligochaetes, spatial variabilities of the methane‐derived carbon contributions are regulated by CH4. Seasonal variability of methane‐derived carbon contributions to C. plumosus revealed increases in summer and autumn following increases in CH4. Methane‐derived biomass (methane‐derived carbon% × biomass) of C. plumosus were also higher in summer and autumn, suggesting transfer of methane‐derived carbon to higher trophic organisms may be larger during those seasons, and limited in winter and spring. Although oligochaetes did not show seasonal variability of methane‐derived carbon contributions, they provided a consistent source of methane‐derived biomass to higher trophic levels throughout the year. Our study demonstrates that two major macroinvertebrates complementarily contribute to fueling methane‐derived carbon cycling through trophic transfer in a polymictic lake.
Cell‐Membrane‐Targeted Drug Delivery System Based on Choline‐Phosphate‐Functionalized β‐Cyclodextrin
Authors: Feng Ying , Xin Qiangwei , Zhang Wanlin , Wang Zuxin , Gao Shan , Chen Xin , Chen Xingyu , Li Jianshu
Published: August 2020

In this study, a novel cyclodextrin derivative, i.e., zwitterionic choline phosphate (CP)‐functionalized β‐cyclodextrin (CP‐β‐CD) is successfully synthesized by click chemistry reaction. CP‐β‐CD has excellent cell‐membrane‐targeted ability because of the CP group can bind to phosphate choline (PC) in the cell membrane and promote the cellular uptake. Due to the introduction of CP group on β‐CD, it disrupts the hydrogen network between natural β‐CD molecules. Meanwhile, the water solubility of CP‐β‐CD is improved dramatically to 816 mg mL−1, which is 440 times as that of unmodified β‐CD. Apatinib, a small molecular inhibitor, is used as a model of hydrophobic drug and loaded into CP‐β‐CD to study the solubilization effect and the anti‐angiogenisis activity. In addition, the cytotoxicity of CP‐β‐CD is also studied, and it is demonstrated that CP‐β‐CD is nontoxic. These results indicate that the apatinib can be transported into cell interior and play an excellent anti‐angiogenisis activity after being loaded into CP‐β‐CD drug delivery system. This work suggests that the water soluble CP‐β‐CD with excellent cell internalization efficiency has a potential application prospect in the field of drug delivery.
Dual characterization of fractional capacity via solution of fractional p‐Laplace equation
Authors: Shi Shaoguang , Zhang Lei
Published: August 2020

In terms of weak solutions of the fractional p‐Laplace equation with measure data, this paper offers a dual characterization for the fractional Sobolev capacity on bounded domain. In addition, two further results are given: one is an equivalent estimate for the fractional Sobolev capacity; the other is the removability of sets of zero capacity and its relation to solutions of the fractional p‐Laplace equation.
Coaggregation properties of trimeric autotransporter adhesins
Authors: Khalil Hawzeen S. , Øgaard Jonas , Leo Jack C.
Published: August 2020

Trimeric autotransporter adhesins (TAAs) comprise a group of virulence‐related proteins in Gram‐negative bacteria. Members of this family bind to extracellular matrix components such as collagen and fibronectin, but also they exhibit several other functions, such as conferring serum resistance and autoaggregation. Autoaggregation promoted by TAAs is homotypic and mediated by the sticky, globular head domains of these lollipop‐like molecules. However, whether TAAs mediate heterotypic interactions (i.e., coaggregation) has not been studied. To address this question, we investigated the coaggregation of two model TAA groups: YadA from the enteropathogenic Yersiniae and the immunoglobulin‐binding Eib proteins from Escherichia coli. To study TAA coaggregation, we coexpressed a fluorescent label together with a particular TAA and followed the aggregative interactions using fluorescence microscopy and quantified the interactions using a novel script implemented in Fiji. Our results show that there is coaggregation between some populations expressing different TAAs, which can be explained by relatively high sequence similarity between the interacting TAAs. Generally, the level of coaggregation correlated with the sequence similarity. However, some TAAs did not interact despite high sequence similarity, showing exclusion of bacteria producing a noncompatible TAA. These data demonstrate that TAAs can mediate bacterial coaggregation, but in some cases prevent coaggregation of bacteria with disparate TAAs. Our results have implications for the ecology of TAA‐producing bacteria, where coaggregation may promote co‐operation whereas exclusion might be an indication of competition.
Women with Fragile X–associated Tremor/Ataxia Syndrome
Authors: Schneider Andrea , Summers Scott , Tassone Flora , Seritan Andreea , Hessl David , Hagerman Paul , Hagerman Randi
Published: August 2020

Background

Fragile X–associated tremor and ataxia syndrome (FXTAS) is a late‐onset neurodegenerative disorder linked to the FMR1 premutation.

Objectives

FXTAS in women is far less common than in men, and this study represents the largest sample reported to date.

Methods

A total of 53 female premutation carriers with FXTAS (meanage, 66.83 years; FXTAS stages 2–5) and 55 age‐matched and demographic background–matched control participants (meanage, 61.94 years) underwent a comprehensive molecular, physiological, neuropsychological, and psychiatric assessment.

Results

The large sample of female premutation carriers showed a wide range of variability of clinical signs and symptom progression. The imaging results showed a middle cerebellar peduncles sign in only 6 patients; another symptom included high‐signal intensity in the splenium of the corpus callosum, and diffuse cerebral deep white matter changes (e.g., in the pons) are more common. The rate of psychiatric disorders, especially depression, is higher than in the general population. There is a clear impairment in executive functioning and fine motor skills in connection with a higher FXTAS stage.

Conclusions

The manifestation of FXTAS symptoms in female carriers can be diverse with a milder phenotype and a lower penetrance than those observed in male premutation carriers. The middle cerebellar peduncles sign is present in only a small percentage of the sample, and we propose that the imaging criteria for FXTAS in women need to be expanded.