bluuebunny/crossref_metadata_2025 huggingface dataset:
Long noncoding RNA MEG3 silencing protects against hypoxia‐induced pheochromocytoma‐12 cell injury through inhibition of TIMP2 promoter methylation
Authors: Zheng Xiu‐Yuan , Lei Bing‐Xi , Lin Yang‐Yang , Sui Ming‐Hong , Zhang Ma‐Lan , Zhuang Zhi‐Qiang , Dong Jun‐Tao , Jin Dong‐Mei , Yan Tie‐Bin
Published: August 2019

Hypoxia is a common pathological process caused by insufficient oxygen. Long noncoding RNAs (lncRNAs) have been proven to participate in this pathology. Hypoxia is reported to significantly reduce the secretion of tissue inhibitor of metalloproteinase 2 (TIMP2) and TIMP2 induces pheochromocytoma‐12 (PC12) cell cycle arrest. Thus, our study aimed to explore the mechanism by which lncRNA maternally expressed gene 3 (MEG3) was implicated in hypoxia‐induced PC12 cell injury through TIMP2 promoter methylation. To elucidate the potential biological significance of MEG3 and the regulatory mechanism between MEG3 and TIMP2, a hypoxia‐induced PC12 cell injury model was generated. The hypoxia‐exposed cells were subjected to a series of overexpression plasmids and short hairpin RNAs, followed by the measurement of levels of MEG3, TIMP2, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), Bcl‐2‐associated X protein, B‐cell lymphoma‐2, and caspase‐3, as well as the changes in MMP, cell proliferation, apoptosis, and cell cycle progression. On the basis of the findings, MEG3 was upregulated in hypoxia‐injured PC12 cells. MEG3 recruited methylation proteins DNMT3a, DNMT3b, and MBD1 and accelerated TIMP2 promoter methylation, which in turn inhibited its expression. Moreover, PC12 cells following MEG3 silencing and TIMP2 overexpression exhibited significantly decreased levels of LDH, MDA, and ROS along with cell apoptosis, yet increased SOD and MMP levels, as well as cell cycle entry to the S phase and cell proliferation. In conclusion, MEG3 silencing suppresses hypoxia‐induced PC12 cell injury by inhibiting TIMP2 promoter methylation. This study may provide novel therapeutic targets for hypoxia‐induced injury.
Industrial separation of oxygen isotopes by oxygen distillation
Authors: Igarashi Takehiro , Kambe Takashi , Kihara Hitoshi
Published: August 2019

18O‐labeled water (Water‐18O) is a widely used starting material of 18F‐labeled diagnostic agents in positron emission tomography (PET). Conventionally, Water‐18O has been separated from other stable oxygen isotope species (16O, 17O) by water distillation or nitric oxide distillation. However, conventional methods are costly and may have safety issues. In 2004, we developed the first unit of our novel oxygen isotope separation process by cryogenic oxygen distillation to overcome these issues. To meet the needs of the market, we built a second unit in 2013 and a third in 2016. We are now operating three commercially viable separation units with a total capacity of 600 kg of Water‐18O per year.
Do BDNF and NT‐4/5 exert synergistic or occlusive effects on corticostriatal transmission in a male mouse model of Huntington's disease?
Authors: Torres‐Cruz Francisco M. , Mendoza Ernesto , Vivar‐Cortés Israel C. , García‐Sierra Francisco , Hernández‐Echeagaray Elizabeth
Published: August 2019

Brain‐derived neurotrophic factor (BDNF) and neurotrophin‐4/5 (NT‐4/5) are trophic factors belonging to the neurotrophin family; in addition to their trophic role, both neurotrophins play an important role in modulating corticostriatal synaptic transmission. Failures in BDNF supply and mitochondrial dysfunction are among the factors involved in the striatal degeneration that occurs in Huntington's disease (HD). While the effects of BDNF have been widely studied in striatal degeneration, the role of NT‐4/5 has been less addressed. NT‐4/5 does not appear to exert effects similar to those of BDNF in HD. The physiological roles of these molecules in corticostriatal transmission have been evaluated separately, and we have demonstrated that sequential exposure to both neurotrophins results in different modulatory effects on corticostriatal transmission depending on the exposure order. In the present study, we evaluated the effects of BDNF followed by NT‐4/5 or NT‐4/5 followed by BDNF on corticostriatal synaptic transmission with field recordings in a male mouse model of HD produced by in vivo treatment with the mitochondrial toxin 3‐nitropropionic acid. Here, we show that these neurotrophins elicit an antagonistic or synergistic effect that depends on the activation of the truncated isoform or the stimulation of the full‐length isoform of the tropomyosin receptor kinase B.
Can reanalysis products with only surface variables assimilated capture Madden–Julian oscillation characteristics?
Authors: Cui Jingxuan , Wang Lu , Li Tim , Wu Bo
Published: August 2019

The Madden–Julian Oscillation (MJO), as a dominant mode of tropical intraseasonal oscillation, plays an important role in the variability of global weather and climate. However, current state‐of‐the‐art atmospheric circulation models have difficulty in reproducing observed MJO characteristics when forced by observed daily sea surface temperature alone. An important practical question is how much data a model needs in assimilation to reproduce real MJO events? By analysing ERA‐20C and NOAA‐20CR reanalysis data, the authors tried to figure out whether a model could reproduce observed MJO events by assimilating the observed surface signal alone. The phase propagation and vertical structure associated with MJO were compared between the reanalysis data and observations during 1979–2010. A total skill score considering both temporal correlation and spatial standard deviation were defined. The result showed that both ERA‐20C and NOAA‐20CR could reproduce the observed MJO characteristics very well, with the former superior to the latter, regardless of MJO intensity. Thus, a minimum requirement for an operational atmospheric model for MJO prediction is the assimilation of the observed surface signals.
Modulation of agronomic and nutritional response of Pleurotus eryngii strains by utilizing glycine betaine enriched cotton waste
Authors: Khan Asif Ali , Muhammad Muzammil Jahangir , Muhammad Idrees , Jan Ibadullah , Samin Ghufrana , Zahid Anam , Fozia  , Muhammad Ishaq , Wang Peng , Lu Lixin , Fang Ming , Yao Fang Jie
Published: August 2019

BACKGROUND

This study aimed to evaluate the possibility of cotton waste enrichment with glycine betaine (GB) for production of two strains (P9, P10) of king oyster (Pleurotus eryngii). Cotton waste was used as (100%) control (T0 = cotton waste) and augmented with various combinations of GB, (T1 = 2 mmol L−1, T2 = 4 mmol L−1, T3 = 6 mmol L−1, T4 = 8 mmol L−1 and T5 = 10 mmol L−1). The response of king oyster to GB was evaluated by earliness, yield, biological efficiency (BE), minerals (nitrogen, phosphorus, potassium, zinc (Zn), copper (Cu), magnesium (Mg), manganese (Mn), iron (Fe), sodium (Na), calcium (Ca)), total sugars, total soluble solids, reducing sugars, non‐reducing sugars, ascorbic acid, proximate (crude protein, carbohydrates, crude fibers, ash, fats) content of fruiting body and Fourier‐transform infrared (FTIR) spectroscopy analysis compared with the control substrate (cotton waste).

RESULTS

The earliness, yield, and BE were higher as compared to control substrate and increased with an augmentation in the concentration of GB within the cotton waste. Two strains showed (on dry weight basis) 33.9–54.9 mg g−1 nitrogen, 6.8–12.5 mg g−1 phosphorus, 16.9–25.1 mg g−1 potassium, 40.5–64.2 mg kg−1 Zn, 17.1–37.3 mg kg−1 Cu, 1174–1325 mg kg−1 Mg, 20.1–29.1 mg kg−1 Mn, 129–265 mg kg−1 Fe, 779–835 mg kg−1 Ca), 6.3%–11.3% total sugars, 7.3–14.9 °Brix total soluble solids, 2.1–7.3% reducing sugars, 10.4–18.1% crude protein, 3.6–4.4% crude fiber and 5.6–16.7 mg (100 g)‐1 on various concentration of GB enrich cotton waste. Cotton waste enriched with GB significantly affected nutritional profile of king oyster mushroom.

CONCLUSION

The results revealed that GB enriched cotton waste can be used as an innovative substrate to enhance the yield and quality of king oyster mushroom. © 2019 Society of Chemical Industry
Preventive effects of a synthetic absorbable antiadhesive film (seprafilm) on small bowel obstruction in patients who underwent elective surgery for colon cancer: A randomized controlled trial
Authors: Saito Gota , Sadahiro Sotaro , Ogimi Takashi , Miyakita Hiroshi , Okada Kazutake , Tanaka Akira , Suzuki Toshiyuki
Published: August 2019

Background

Seprafilm did not decrease small bowel obstruction (SBO), but significantly decreased reoperation in patients with inflammatory bowel disease. However, the preventive effect in colon cancer remains unclear.

Methods

We conducted a randomized controlled trial in patients with colon cancer. The study group comprised 345 patients with colon cancer. In the seprafilm group (n = 166), two sheets of seprafilm were inserted under a midline incision. Patients who were admitted and required decompression were considered to have SBO.

Results

The median follow‐up was 61.9 months. Patient characteristics were well balanced. There was no significant difference in the incidence of SBO between the seprafilm group (7.8%) and the control group (10.6%) (P = .46). In patients who underwent reoperation, SBO occurred in a midline incision in one patient and at other sites in four patients in the seprafilm group as compared with two patients and five patients, respectively, in the control group. Multivariate analysis showed that only a history of laparotomy was an independent risk factor for SBO.

Conclusions

Seprafilm did not decrease SBO or reoperation in colon cancer. The incidence of SBO caused by adhesion to the midline incision was relatively low as compared with that caused by adhesion to other sites.
Quantification of metal‐induced susceptibility artifacts associated with ultrahigh‐field magnetic resonance imaging of spinal implants
Authors: Chiba Yusuke , Murakami Hideki , Sasaki Makoto , Endo Hirooki , Yamabe Daisuke , Kinno Daichi , Doita Minoru
Published: August 2019

Reports on spinal‐implant metallic artifacts in 7‐T magnetic resonance imaging (MRI) are lacking. Thus, we investigated the magnitude of metal artifacts derived from spinal implants in 7‐T MRI and analyzed the differences obtained with spinal rods manufactured from pure titanium, titanium alloy, and cobalt‐chrome (5.5‐mm and 6.0‐mm diameters and 50‐mm length). Following the American Society for Testing and Materials guidelines, we measured the artifact size and artifact volume ratio of each rod during image acquisition using 7‐T MRI scanners with three‐dimensional (3D) T1‐weighted and 3D T2* spoiled gradient echo (GRE), 3D T2‐weighted fast spin echo, zero echo time (ZTE), and diffusion‐weighted imaging sequences. Pure titanium and titanium alloy rods yielded significantly smaller artifacts than did cobalt‐chrome rods, with no significant difference between pure titanium and titanium alloy rods. The artifact sizes of the 5.5‐mm and 6.0‐mm diameter rods were similar. The artifact magnitude increased in the following sequence order: ZTE, 3D T2 fast spin echo, 3D T1 spoiled GRE, 3D T2* spoiled GRE, and diffusion‐weighted imaging. Artifacts obtained using the spin echo method were smaller than those obtained with the GRE method. Because the echo time in ZTE is extremely short, the occurrence of artifacts because of image distortion and signal loss caused by differences in magnetic susceptibility is minimal, resulting in the smallest artifacts. ZTE can be a clinically useful method for the postoperative evaluation of patients after instrumentation surgery, even with 7‐T MRI.
The natural progression of low‐frequency hearing loss in patients who meet hybrid implant system candidacy criteria
Authors: Okada Masahiro , Quinkert Amy , Franck Kevin H. , Welling D. Bradley
Published: August 2019

Objectives/Hypothesis

To investigate the natural progression of hearing loss in patients with high‐frequency hearing loss whose audiograms met the criteria for a hybrid cochlear implant (CI).

Study Design

Retrospective database review.

Methods

We retrospectively identified patients who met the criteria for a hybrid CI from our audiometric database. We also recorded the etiology of hearing loss in each patient and excluded patients with retrocochlear etiologies, those age <6 years, duration of observation <1 year, or those with a mixed or conductive hearing loss. We calculated the pre‐CI progression of residual low‐frequency (LF) hearing level in decibels per year and investigated the risk factor of the progression of hearing loss.

Results

A total of 1,083 ears of 944 patients were included in this study. The average rate of hearing loss progression for all etiologies was 1.70 ± 0.10 dB/yr at an average of 250 Hz, 500 Hz, and 1 kHz in the affected ear(s). The progression of hearing loss was 5.0 ± 0.93 dB/yr in patients with Meniere's disease and 3.5 ± 0.76 dB/yr in those with autoimmune disease, both of which were significantly faster than progression rates in other etiologies. In patients with idiopathic, genetic/hereditary, and congenital hearing loss, the progression of hearing loss was 1.46 ± 0.10 dB/yr. Patients with steeply sloping hearing loss experienced significantly faster progression in the ipsilateral ear compared to patients with another audiometric type.

Conclusions

It is suggested that Meniere's disease, autoimmune‐mediated inner ear disease, and steeply sloping hearing loss in the ipsilateral ear are risk factors for faster progression of residual LF hearing level.

Level of Evidence

4

Laryngoscope, 130:1299–1303, 2020
Cardiac glycoside sensitized hepatocellular carcinoma cells to TRAIL via ROS generation, p38MAPK, mitochondrial transition, and autophagy mediation
Authors: Rasheduzzaman Mohammad , Yin Honghua , Park Sang‐Youel
Published: August 2019

A major concern in the clinical application of tumor necrosis factor related apoptosis‐inducing ligand (TRAIL) in tumors is the development of resistance. Therefore, agents that can potentially restore TRAIL sensitivity are important therapeutic targets for cancer treatment. Herein, we evaluated lanatoside c and digoxin, both of which are widely used cardiac glycosides (CGs), for their ability to sensitize human hepatocellular carcinoma cells (Huh‐7 and HepG2) through TRAIL‐induced apoptosis. CGs functionalize TRAIL as shown by its effect on intracellular reactive oxygen species (ROS) generation, which damages mitochondrial integrity and thereby confers intrinsic apoptotic caspase cascade during combined treatment. Caspase activation is dependent on ROS as shown by the ability of CGs to generate ROS and the ROS‐N‐acetylcysteine (NAC) relationship, which inhibits apoptosis during cotreatment by preventing the formation of caspase‐8 and ‐3. Furthermore, CGs triggered p38MAPK phosphorylation and NAC pre‐exposure blocked p38MAPK phosphorylation, which demonstrated that p38MAPK was dependent upon ROS generation. Additionally, CGs were found to be potent inducers of AMPK‐mediated protective autophagy as pharmacological and genetic autophagy inhibition reached the higher threshold of TRAIL‐mediated apoptosis. Finally, CGs downregulated the expression of the antiapoptotic protein Bcl‐2 and increased the translocation of proapoptotic protein cytochrome c, thereby inducing apoptosis. Collectively, these results indicate that CGs potentiate the enhanced cytotoxic capacity to TRAIL through ROS generation, p38MAPK phosphorylation, cell survival protein downregulation, and protective autophagy inhibition.
Hearing loss in inherited peripheral neuropathies: Molecular diagnosis by NGS in a French series
Authors: Lerat Justine , Magdelaine Corinne , Roux Anne‐Françoise , Darnaud Léa , Beauvais‐Dzugan Hélène , Naud Steven , Richard Laurence , Derouault Paco , Ghorab Karima , Magy Laurent , Vallat Jean‐Michel , Cintas Pascal , Bieth Eric , Arne‐Bes Marie‐Christine , Goizet Cyril , Espil‐Taris Caroline , Journel Hubert , Toutain Annick , Urtizberea Jon Andoni , Boespflug‐Tanguy Odile , Laffargue Fanny , Corcia Philippe , Pasquier Laurent , Fradin Mélanie , Napuri Sylva , Ciron Jonathan , Boulesteix Jean‐Marc , Sturtz Franck , Lia Anne‐Sophie
Published: August 2019

Background

The most common inherited peripheral neuropathy is Charcot‐Marie‐Tooth disease (CMT), with a prevalence of 1/2500. Other symptoms can be associated to the condition, such as hearing loss. Currently, no global hearing impairment assessment has been determined, and the physiopathology is not well known.

Methods

The aim of the study was to analyze among a French series of 3,412 patients with inherited peripheral neuropathy (IPN), the ones who also suffer from hearing loss, to establish phenotype‐genotype correlations. An NGS strategy for IPN one side and nonsyndromic hearing loss (NSHL) on the other side, were performed.

Results

Hearing loss (HL) was present in only 44 patients (1.30%). The clinical data of 27 patients were usable. Demyelinating neuropathy was diagnosed in 15 cases and axonal neuropathy in 12 cases. HL varied from mild to profound. Five cases of auditory neuropathy were noticed. Diagnosis was made for 60% of these patients. Seven novel pathogenic variants were discovered in five different genes: PRPS1; MPZ; SH3TC2; NEFL; and ABHD12. Two patients with PMP22 variant, had also an additional variant in COCH and MYH14 respectively. No pathogenic variant was found at the DFNB1 locus. Genotype‐phenotype correlations do exist, especially with SH3TC2, PRPS1, ABHD12, NEFL, and TRPV4.

Conclusion

Involvement of PMP22 is not enough to explain hearing loss in patients suffering from IPN. HL can be due to cochlear impairment and/or auditory nerve dysfunction. HL is certainly underdiagnosed, and should be evaluated in every patient suffering from IPN.
FLAD1‐associated multiple acyl‐CoA dehydrogenase deficiency identified by newborn screening
Authors: Muru Kai , Reinson Karit , Künnapas Kadi , Lilleväli Hardo , Nochi Zahra , Mosegaard Signe , Pajusalu Sander , Olsen Rikke K. J. , Õunap Katrin
Published: August 2019

Background

Multiple acyl‐CoA dehydrogenase deficiency (MADD), also known as glutaric aciduria type II, is a mitochondrial fatty acid oxidation disorder caused by variants in ETFA, ETFB, and ETFDH. Recently, riboflavin transporter genes and the mitochondrial FAD transporter gene have also been associated with MADD‐like phenotype.

Methods

We present a case of MADD identified by newborn biochemical screening in a full‐term infant suggestive of both medium‐chain acyl‐CoA dehydrogenase deficiency and MADD. Urine organic acid GC/MS analysis was also concerning for both disorders. However, panel sequencing of ETFA, ETFB, ETFDH, and ACADM was unrevealing. Ultimately, a variant in the FAD synthase gene, FLAD1 was found explaining the clinical presentation.

Results

Exome sequencing identified compound heterozygous variants in FLAD1: NM_025207.4: c.[442C>T];[1588C>T], p.[Arg148*];[Arg530Cys]. The protein damaging effects were confirmed by Western blot. The patient remained asymptomatic and there was no clinical decompensation during the first year of life. Plasma acylcarnitine and urinary organic acid analyses normalized without any treatment. Riboflavin supplementation was started at 15 months.

Conclusion

Newborn screening, designed to screen for specific treatable congenital metabolic diseases, may also lead to the diagnosis of additional, very rare metabolic disorders such as FLAD1 deficiency. The case further illustrates that even milder forms of FLAD1 deficiency are detectable in the asymptomatic state by newborn screening.
New center in Delaware health system prioritizes patients' social needs
Authors: Enos Gary
Published: August 2019

A Delaware health system's painstaking experience in stabilizing individuals affected by mental illness, a medical issue and a social need such as lack of housing or transportation has given rise to a new service delivery model for coordinated care.
Interpolants for sixth‐order Numerov‐type methods
Authors: Alolyan Ibraheem , Simos T.E. , Tsitouras Ch.
Published: August 2019

The classical four‐stage family of explicit sixth‐order Numerov‐type method is considered. We provide two kinds of interpolants: (a) a three‐step interpolation based on all available data at mesh points and (b) a local interpolant (ie, two steps) that is constructed after solving scaled equations of condition. These latter equations are explained and provided here. Applying these interpolants in a set of tests, we conclude that they produce global errors of the same magnitude with the underlying method.
Transport Versus Hydrolysis: Reassessing Intestinal Assimilation of Di‐ and Tripeptides by LC–MS/MS Analysis
Authors: Rohm Florian , Daniel Hannelore , Spanier Britta
Published: August 2019

Scope

The role of PEPT1 in the uptake of intact peptides as compared to hydrolysis prior to uptake of their constituents is unknown. Here, dipeptides, tripeptides, and amino acids are quantified to study the fate of selected peptides in different intestinal models.

Methods and results

An LC–MS/MS‐based method is applied for the simultaneous assessment of rates of hydrolysis and transport of a peptide panel in Caco‐2 transwell cell culture, in vitro and in vivo in mice expressing or lacking PEPT1, and in hydrolysis studies in vitro using human intestinal samples. It is shown that susceptibility to hydrolysis of peptides at the brush border membrane or within epithelial cells is practically identical in all tested models and strictly structure‐dependent. Peptides with high luminal disappearance show substantial hydrolysis and low basolateral appearance, while peptides with low disappearance show strong PEPT1 dependency and high basolateral appearance in intact form in Caco‐2 transwell culture.

Conclusion

Hydrolysis and transport of intact peptides are highly variable and structure‐dependent. For peptides possessing less polar N‐terminal residues, hydrolysis usually dominates over transport via PEPT1. For other peptides with high intrinsic hydrolysis resistance, including anserine, carnosine, ɣ‐glutamyl‐dipeptides, and aminocephalosporins, PEPT1 is the main determinant for appearance in peripheral blood.
Antidepressant‐Like Effect of Ferulic Acid via Promotion of Energy Metabolism Activity
Authors: Sasaki Kazunori , Iwata Nozomu , Ferdousi Farhana , Isoda Hiroko
Published: August 2019

Scope

Ferulic acid (FA), a natural phenolic phytochemical abundantly present in whole grains, herbs, and dried fruits, exhibits anti‐inflammatory, antioxidant, and neuroprotective effects. In the present study, the antidepressant‐like effects of FA in male ICR mice using tail suspension test (TST) are investigated and its molecular mechanisms are explored.

Methods and Results

Oral administration of FA at a dose of 5 mg kg–1 for 7 days significantly reduces immobility of mice compared to vehicle‐administered control group. Microarray and real‐time PCR analyses reveal that FA upregulates the expression of several genes associated with cell survival and proliferation, energy metabolism, and dopamine synthesis in mice limbic system of brain. Interestingly, it is found that FA, unlike antidepressant drug bupropion, strongly promotes energy metabolism. Additionally, FA increases catecholamine (dopamine and noradrenaline), brain‐derived neurotrophic factor, and ATP levels, and decreases glycogen levels in the limbic system of the mice brain.

Conclusion

The research provides the first evidence that FA enhances energy production, which can be the underlying mechanism of the antidepressant‐like effects of FA observed in this study.
Effects of different macromolecular models on reproducibility of FID‐MRSI at 7T
Authors: Heckova Eva , Považan Michal , Strasser Bernhard , Motyka Stanislav , Hangel Gilbert , Hingerl Lukas , Moser Philipp , Lipka Alexandra , Gruber Stephan , Trattnig Siegfried , Bogner Wolfgang
Published: August 2019

Purpose

A properly characterized macromolecular (MM) contribution is essential for accurate metabolite quantification in FID‐MRSI. MM information can be included into the fitting model as a single component or parameterized and included over several individual MM resonances, which adds flexibility when pathologic changes are present but is prone to potential overfitting. This study investigates the effects of different MM models on MRSI reproducibility.

Methods

Clinically feasible, high‐resolution FID‐MRSI data were collected in ~5 min at 7 Tesla from 10 healthy volunteers and quantified via LCModel (version 6.3) with 3 basis sets, each with a different approach for how the MM signal was handled: averaged measured whole spectrum (full MM), 9 parameterized components (param MM) with soft constraints to avoid overparameterization, or without any MM information included in the fitting prior knowledge. The test–retest reproducibility of MRSI scans was assessed voxel‐wise using metabolite coefficients of variation and intraclass correlation coefficients and compared between the basis sets. Correlations of concentration estimates were investigated for the param MM fitting model.

Results

The full MM model provided the most reproducible quantification of total NAA, total Cho, myo‐inositol, and glutamate + glutamine ratios to total Cr (coefficients of variations ≤ 8%, intraclass correlation coefficients ≥ 0.76). Using the param MM model resulted in slightly lower reproducibility (up to +3% higher coefficients of variations, up to −0.1 decreased intraclass correlation coefficients). The quantification of the parameterized macromolecules did not affect quantification of the overlapping metabolites.

Conclusion

Clinically feasible FID‐MRSI with an experimentally acquired MM spectrum included in prior knowledge provides highly reproducible quantification for the most common neurometabolites in healthy volunteers. Parameterization of the MM spectrum may be preferred as a compromise between quantification accuracy and reproducibility when the MM content is expected to be pathologically altered.
Regional T1 mapping of the whole cervical spinal cord using an optimized MP2RAGE sequence
Authors: Rasoanandrianina Henitsoa , Massire Aurélien , Taso Manuel , Guye Maxime , Ranjeva Jean‐Philippe , Kober Tobias , Callot Virginie
Published: August 2019

While T1 measurements present multiple challenges (robustness, acquisition time), the recently proposed MP2RAGE sequence (magnetization‐prepared two rapid acquisition gradient echoes) has opened new perspectives to characterize tissue microstructure changes occurring in a pathological or developmental context. Extensively used for brain studies, it was herein adapted to investigate the cervical spinal cord (SC) at 3 T.

By integrating Bloch equations, the MP2RAGE sequence parameters were chosen to optimize SC gray matter/white matter (GM/WM) T1 contrast with sub‐millimetric resolution, a scan time less than 10 min and a reliable T1 determination with minimal B1+ variation effect, within a range of values compatible with different pathologies and surrounding structures. The residual B1+ effect on T1 values was corrected using a look‐up‐table approach and B1+ mapping. The accuracy of B1+‐corrected T1 measurements was assessed on a phantom with respect to conventional inversion recovery. In vivo MP2RAGE acquisitions were performed on five young (28.8 ± 4.3 years old) and five elderly (60.2 ± 2.9 years old) volunteers and analyzed using a template‐based approach.

Phantom experiments led to high agreements between inversion‐recovery spin‐echo and MP2RAGE‐based T1 values (R2 = 0.997). In vivo T1 values for cervical WM, anterior GM (aGM), posterior sensory tracts (PSTs) and lateral motor tracts (LMTs) were 917 ± 29 s, 934 ± 33 ms, 920 ± 37 ms and 877 ± 35 ms, respectively, with all subjects and cervical levels considered. Significant differences were observed between aGM and LMTs, and between LMTs and PSTs, in agreement with the literature. Repeated T1 measurements demonstrated high reproducibility of the MP2RAGE in the SC (variation coefficient < 5% in all regions of interest). Finally, preliminary assessment of age‐related SC tissue microstructure variation additionally showed evidence of SC atrophy and slight trends of T1 decrease with age in all regions.

Overall, this study shows that fast, robust and accurate sub‐millimetric resolution T1 mapping in the cervical SC using the MP2RAGE sequence is possible, paving the way for future multi‐centric and longitudinal clinical studies investigating the pathological cord.
An approach to revising mHealth interventions for children and families: A case example in sickle cell disease
Authors: Phillips Shannon , Kanter Julie , Ruggiero Kenneth J. , Mueller Martina , Johnson Mary A. , Kelechi Teresa J.
Published: August 2019

Frameworks for developing mHealth interventions that are informed by the end‐user and improve accessibility are necessary to ensure interventions meet the needs of the intended population and advance the science of health behavior change. The approach described in this paper addresses a gap in the mHealth development literature by describing a step‐by‐step method for evaluating and revising the mHealth interventions for health behavior change in child–parent dyads. Furthermore, this approach introduces the Website Analysis and MeasureMent Inventory framework as an initial coding structure for analyzing qualitative data to gauge appeal and enhance engagement of intervention for end‐users. This method uses specific considerations for child–parent dyads and details an example in the development and refinement of a mobile application for self‐management in children with sickle cell disease. This approach is translatable to populations of children with other chronic conditions and to other health behaviors.
Treatment and outcome of patients with thoracic tumors of the Ewing sarcoma family: A report from the Cooperative Weichteilsarkom Studiengruppe CWS‐81, ‐86, ‐91, ‐96, and ‐2002P trials
Authors: Seitz Guido , Urla Cristian , Sparber‐Sauer Monika , Schuck Andreas , Vokuhl Christian , Blank Bernd , Klingebiel Thomas , Kazanowska Bernarda , Fuchs Jörg , Koscielniak Ewa
Published: August 2019

Background

Ewing tumors are the most frequent malignant tumors of the chest wall in children and young adults. Surgical management of these tumors can be challenging. Optimal local control remains controversial. The aim of this study was to analyze treatment, outcome, and surgical procedures in patients with thoracic tumors of the Ewing sarcoma family (TES) treated within four Cooperative Soft‐Tissue Sarcoma (CWS) trials and one registry.

Patients and methods

Sixty‐two patients from 0 to 21 years treated between 1981 and 2014 were selected for this analysis. A retrospective chart analysis was carried out. Institutional review board approval was obtained for all trials.

Results

The median age of the patients was 7 years. The 5‐year overall (OS) and event‐free survival (EFS) rates were 58.7% (52.7–64.7) and 52.8% (46.8–58.8). Patients with intrathoracic tumor localization (n = 24) had a worse outcome (EFS: 37.5%; 27.5–37.5) compared with those with chest wall tumors (n = 38; EFS: 62.3%; 54.3–70.3, P = 0.008). Patients ≤10 years (n = 38) had a better survival compared with those > 10 years (EFS: 65.7%; 57.7–73.7 vs 31.3%; 21.3–41.3, P = 0.01). Tumor size ≤5 cm (n = 15) was associated with significantly better survival compared with a size > 5 cm (n = 47, EFS: 93.3%; 87.3–99.3 vs 40%; 33‐47, P = 0.002). Primary resections were carried out in 36 patients, of which 75% were incomplete resulting in inferior EFS (P = 0.006). Complete secondary resections were performed in 22 of 40.

Conclusions

Positive predictive factors for outcome are age ≤10 years, size ≤5 cm, and localization at the chest wall. Diverse IRS groups require individual treatment.
Prenatal chromosomal microarray testing of fetuses with ultrasound structural anomalies: A prospective cohort study of over 1000 consecutive cases
Authors: Chong Hsu P. , Hamilton Susan , Mone Fionnuala , Cheung Ka Wang , Togneri Fiona S. , Morris Rachel K. , Quinlan‐Jones Elizabeth , Williams Denise , Allen Stephanie , McMullan Dominic J. , Kilby Mark D.
Published: August 2019

Objective

Evaluate the diagnostic yield of prenatal submicroscopic chromosome anomalies using prenatal array comparative genomic hybridisation (aCGH).

Method

Prospective cohort study conducted between March 2013 and June 2017 including fetuses where an elevated nuchal translucency (NT) or structural anomaly was identified on ultrasound and common aneuploidy testing was negative. aCGH was performed using an 8‐plex oligonucleotide platform with a genome wide backbone resolution of greater than 200 kb and interpretation in line with American College of Medical Genetics guidance.

Results

One thousand one hundred twenty‐nine fetuses were included; 371 fetuses with an increased NT (32.9%) and 758 with a structural anomaly (67.1%). The rate of pathogenic copy number variants (CNVs) and variant of uncertain significance (VUS) was 5.9% (n = 22) and 0.5% (n = 2) in the elevated NT group and 7.3% (n = 55) and 0.8% (n = 6) in the mid‐trimester anomaly group. No pathogenic CNVs were identified in fetuses with an NT less than 4.0 mm. Multisystem and cardiac anomalies had the greatest yield of pathogenic CNV with a 22q11.2 microdeletion present in 40% (12/30).

Conclusion

Prenatal aCGH is a useful diagnostic tool in the investigation of fetuses with a significantly elevated NT or structural anomaly. With time and experience, rates of pathogenic CNVs have increased, and VUS have reduced, supporting the prenatal application of increasingly high resolution aCGH platforms.
Long‐term morbidity of respiratory viral infections during chemotherapy in children with leukaemia
Authors: Lin Beryl , Kennedy Brendan , McBride Jamie , Dalla‐Pozza Luciano , Trahair Toby , McCowage Geoffrey , Coward Emma , Plush Leanne , Robinson Paul D. , Hardaker Kate , Widger John , Ng Anthea , Jaffe Adam , Selvadurai Hiran
Published: August 2019

Background

Respiratory viruses are a common cause of infection in immunosuppressed children undergoing cancer therapy. Pulmonary sequelae have been documented following respiratory viral infections (RVIs) in hematopoietic stem cell transplant (HSCT) recipients; however potential late effects in children undergoing nonmyeloablative chemotherapy have not been investigated.

Aim

To evaluate the long‐term pulmonary morbidity of respiratory viral infections during chemotherapy in children with acute lymphoblastic leukemia (ALL).

Methods

Childhood ALL survivors, aged 7 to 18 years, greater than 6 months posttreatment were recruited. Exclusion criteria included HSCT or proven bacterial/fungal respiratory infection during treatment. Subjects were classified into “viral” or “control” groups according to retrospective medical records that documented the presence of laboratory‐proven RVIs during chemotherapy. Symptom questionnaires (Liverpool, ISAAC) and lung function testing (spirometry, plethysmography, diffusing capacity, forced oscillation technique to ATS/ERS standards) were then performed cross‐sectionally at the time of recruitment.

Results

Fifty‐four patients (31 viral, 23 control) were recruited: median (range) age 11.2 (7.2‐18.1) years, and at 4.9 (0.5‐13) years posttherapy. Abnormalities were detected in 17 (31%) individuals (8 viral, 9 control), with the most common being DLCO impairment (3 viral, 4 control) and reduced respiratory reactance at 5 Hz (5 viral, 6 control). Children with RVIs during chemotherapy reported more current respiratory symptoms, particularly wheeze (odds ratio [OR], 3.0; 95% confidence interval [CI]: 0.9‐10.0; P = .09) and cough (OR, 2.7; 95% CI: 0.8‐9.5; P = .11). No differences in lung function tests were observed between the two groups.

Conclusions

Our study found children with RVIs during chemotherapy developed more long‐term respiratory symptoms than controls; however, differences did not reach statistical significance. No differences in static lung function were found between the two groups. Overall, pulmonary abnormalities and/or significant ongoing respiratory symptoms were detected in nearly a third of ALL survivors treated without HSCT. Larger, prospective studies are warranted to evaluate the etiology and clinical significance of these findings.
SimpleDSFviewer: A tool to analyze and view differential scanning fluorimetry data for characterizing protein thermal stability and interactions
Authors: Sun Changye , Li Yong , Yates Edwin A. , Fernig David G.
Published: August 2019

Differential scanning fluorimetry (DSF) is a widely used thermal shift assay for measuring protein stability and protein–ligand interactions that are simple, cheap, and amenable to high throughput. However, data analysis remains a challenge, requiring improved methods. Here, the program SimpleDSFviewer, a user‐friendly interface, is described to help the researchers who apply DSF technique in their studies. SimpleDSFviewer integrates melting curve (MC) normalization, smoothing, and melting temperature (Tm) analysis and directly previews analyzed data, providing an efficient analysis tool for DSF. SimpleDSFviewer is developed in Matlab, and it is freely available for all users to use in Matlab workspace or with Matlab Runtime. It is easy to use and an efficient tool for researchers to preview and analyze their data in a very short time.
Disruption of an adenylate‐forming reductase required for conidiation, increases virulence of the insect pathogenic fungus Metarhizium acridum by enhancing cuticle invasion
Authors: Guo Haoyu , Wang Hongjuan , Keyhani Nemat O , Xia Yuxian , Peng Guoxiong
Published: August 2019

BACKGROUND

Metarhizium acridum, is a specific acridid pathogen developed for use against the migratory locust (Locusta migratoria manilensis). Adenylate‐forming reductases (AFRs) include enzymes that are involved in natural product biosynthesis. Here, we genetically characterize the functions of a class IV AFR in M. acridum (MaAfrIV) on fungal development and virulence.

RESULTS

Gene expression analyses indicated MaAfrIV was induced on locust wings early during the infection process. Surprisingly, loss of MaAfrIV increased virulence (25.20% decrease in the median lethal time) against the locust in topical bioassays but was no different than the wild type when the cuticle was bypassed by direct infection of conidia into the insect hemocoel. Virulence markers including protease (Pr1) expression and appressorial turgor pressure were higher in the mutant than the parent strain. No difference was seen in the expression of host immune genes (Toll pathway) or in polyphenol oxidase (PPO) activity in locusts infected by the ΔMaAfrIV or wild type strains. However, the ΔMaAfrIV strain was unable to successfully sporulate on dead cadavers.

CONCLUSION

Disruption of MaAfrIV increased fungal virulence by promoting insect cuticle invasion without altering host immune response or fungal immune evasion. Although loss of MaAfrIV conferred an apparent benefit to the fungus in terms of enhanced virulence, a significant trade‐off was seen in the inability of the fungus to sporulate on the cadaver. As conidiation on the cadaver is essential for subsequent propagation in the environment, loss of MaAfrIV can reduce the engineering strains survivability in the field and improve the safety. © 2019 Society of Chemical Industry
Implication of human drug transporters to toxicokinetics and toxicity of pesticides
Authors: Guéniche Nelly , Bruyere Arnaud , Le Vée Marc , Fardel Olivier
Published: August 2019

Human membrane drug transporters are recognized as major actors of pharmacokinetics. Pesticides also interact with human drug transporters, which may have consequences for pesticide toxicokinetics and toxicity. The present review summarizes key findings about this topic.In vitroassays have demonstrated that some pesticides, belonging to various chemical classes, modulate drug transporter activity, regulate transporter expression and/or are substrates, thus bringing the proof of concept for pesticide‐transporter relationships. The expected low human concentration of pesticides in response to environmental exposure constitutes a key‐parameter to be kept in mind for judging thein vivorelevance of such pesticide‐transporter interactions and their consequences for human health. Existing data about interactions of pesticides with drug transporters remain, however, rather sparse; more extensive and systematic characterization of pesticide‐transporter relationships, through the use of high throughputin vitroassays and/orin silicomethods, is, therefore, required. In addition, consideration of transporter polymorphisms, pesticide mixture effects and physiological and pathological factors governing drug transporter expression may help to better define thein vivorelevance of pesticide‐transporter interactions in terms of toxicokinetics and toxicity for humans. © 2019 Society of Chemical Industry
Fungal volatile organic compounds show promise as potent molluscicides
Authors: Khoja Salim , Eltayef Khalifa M , Baxter Ian , Bull James C , Loveridge Edric Joel , Butt Tariq
Published: August 2019

BACKGROUND

Slugs and snails constitute major crop pests. Withdrawal of metaldehyde has prompted a search for more environmentally friendly yet fast acting molluscicides. This study investigated the response of representative molluscs to conidia and volatile organic compounds (VOCs) of the insect pathogenic fungus Metarhizium brunneum Petch.

RESULTS

Conidia of M. brunneum had antifeedant/repellent properties with repellency being dependent upon the fungal strain and conidia concentration. Three commonly produced fungal VOCs, 1‐octene, 3‐octanone and 1‐octen‐3‐ol, were repellent at low doses (1–5 μL) but could kill slugs and snails on contact or fumigation. At the highest dose tested (10 μL), 100% mortality was achieved for Cornu aspersum Muller (garden snail) and Derocerus reticulatum Muller (grey field slug) within 1 h post‐treatment with the first deaths being recorded in <11 min. Aqueous formulations (20% v/v) of the most potent VOCs, 3‐octanone and 1‐octen‐3‐ol, could be sprayed onto plants to kill or drive the pest of the crop with no phytotoxic effects.

CONCLUSION

The sensitivity of terrestrial molluscs to 3‐octanone and 1‐octen‐3‐ol and the ephemeral nature of these compounds makes these excellent candidates for development as mollusc repellents or molluscicides. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Extreme precipitation events over northern Italy. Part I: A systematic classification with machine‐learning techniques
Authors: Grazzini Federico , Craig George C. , Keil Christian , Antolini Gabriele , Pavan Valentina
Published: August 2019

Extreme precipitation events (EPEs) are meteorological phenomena of major concern for society. They can have different characteristics depending on the physical mechanisms responsible for their generation, which in turn depend on the large and mesoscale conditions. This work provides a systematic classification of EPEs over northern–central Italy, one of the regions in Europe with the highest frequency of these events. The EPE statistics have been deduced using the new high‐resolution precipitation dataset ArCIS (Climatological Archive for Central–Northern Italy), that gathers together a very high number of daily, quality‐controlled and homogenized observations from different networks of 11 Italian regions. Gridded precipitation is aggregated over Italian operational warning‐area units (WA). EPEs are defined as events in which daily average precipitation in at least one of the 94 WAs exceeds the 99th percentile with respect to the climate reference 1979–2015. A list of 887 events is compiled, significantly enlarging the database compared to any previous study of EPEs. EPEs are separated into three different dynamical classes: Cat1, events mainly attributable to frontal/orographic uplift; Cat2, events due to frontal uplift with (equilibrium) deep convection embedded; Cat3, events mainly generated by non‐equilibrium deep convection. A preliminary version of this classification is based on fixed thresholds of environmental parameters, but the final version is obtained using a more robust machine‐learning unsupervised K‐means clustering and random forest algorithm. All events are characterized by anomalously high integrated water vapour transport (IVT). This confirms IVT as an important large‐scale predictor, especially for Cat2 events, which is shown to be the most important category in terms of impacts and EPE area extension. Large IVT values are caused by upper‐level waves associated with remotely triggered Rossby wave packets, as shown for two example Cat2 events.
Context and Implications Document for: Do schools matter? An exploration of the determinants of lower secondary school subject choices under the Scottish Curriculum for Excellence
Authors: Shapira Marina , Priestley Mark
Published: August 2019

This guide accompanies the following article: Shapira, M. & Priestley, M. (2019). Do schools matter? An exploration of the determinants of lower secondary school subject choices under the Scottish Curriculum for Excellence. Review of Education, https://doi.org/10.1002/rev3.3180.
The Plasma Environment of Comets
Authors: GOMBOSI TAMAS I.
Published: August 2019

This review concentrates on US research activities in the area of cometary plasma physics during the four year period from 1987 to 1990. This quadrennium immediately followed the historic “traffic jam” on the dusty roads of Giacobini‐Zinner and Halley; during this period there has been a substantial increase of activity in the area of cometary science. During these years the “comet rush” resulted in a better understanding of the major physical and chemical processes controlling cometary environments. The quantitative and qualitative leap of available information paved the road to a new generation of comprehensive models synthesizing our knowledge about the ionosphere, magnetosphere, and solar wind interaction. In spite of these major advances cometary plasma physics is still a rapidly changing ‐ and sometimes controversial — subject, and one can can expect significant progress during the next quadrennium.
An overview of non‐native species invasions in urban river corridors
Authors: Francis Robert A. , Chadwick Michael A. , Turbelin Anna J.
Published: August 2019

Recent studies have highlighted cities as prime locations for the introduction, establishment, and spread of non‐native and invasive species. As the hydrological arteries of cities, urban river corridors have an important role to play in influencing species invasions. This overview examines existing literature to consider (a) how the landscape functions of urban river corridors (habitat, conduit, barrier/filter, sink, and source) relate to species invasions; (b) the organismal and geographical foci of research into non‐native species invasions along urban rivers; and (c) the need to more fully consider the roles that non‐native species may play in the recombinant communities of novel urban river ecosystems. The review ends with an identification of research priorities at the intersection of urban river corridor function and invasion biology.