bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractReports 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/HypothesisTo 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 DesignRetrospective database review.MethodsWe 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.ResultsA 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.ConclusionsIt 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 Evidence4Laryngoscope, 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

AbstractA 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

AbstractBackgroundThe 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.MethodsThe 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.ResultsHearing 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.ConclusionInvolvement 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

AbstractBackgroundMultiple 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.MethodsWe 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.ResultsExome 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.ConclusionNewborn 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.
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

ScopeThe 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 resultsAn 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.ConclusionHydrolysis 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

ScopeFerulic 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 ResultsOral 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.ConclusionThe 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

PurposeA 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.MethodsClinically 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.ResultsThe 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.ConclusionClinically 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

AbstractFrameworks 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

AbstractBackgroundEwing 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 methodsSixty‐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.ResultsThe 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.ConclusionsPositive 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

AbstractObjectiveEvaluate the diagnostic yield of prenatal submicroscopic chromosome anomalies using prenatal array comparative genomic hybridisation (aCGH).MethodProspective 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.ResultsOne 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).ConclusionPrenatal 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.