Standard Sequence Research Articles

Compressed Sensitivity Encoding Artificial Intelligence Accelerates Brain Metastasis Imaging by Optimizing Image Quality and Reducing Scan Time.

Accelerating the image acquisition speed of MR imaging without compromising the image quality is challenging. This study aimed to evaluate the feasibility of contrast-enhanced (CE) 3D T1WI and CE 3D-FLAIR sequences reconstructed with compressed sensitivity encoding artificial intelligence (CS-AI) for detecting brain metastases (BM) and explore the optimal acceleration factor (AF) for clinical BM imaging. Fifty-one patients with cancer with suspected BM were included. Fifty participants underwent different customized CE 3D-T1WI or CE 3D-FLAIR sequence scans. Compressed SENSE encoding acceleration 6 (CS6), a commercially available standard sequence, was used as the reference standard. Quantitative and qualitative methods were used to evaluate image quality. The SNR and contrast-to-noise ratio (CNR) were calculated, and qualitative evaluations were independently conducted by 2 neuroradiologists. After exploring the optimal AF, sample images were obtained from 1 patient by using both optimized sequences. Quantitatively, the CNR of the CS-AI protocol for CE 3D-T1WI and CE 3D-FLAIR sequences was superior to that of the CS protocol under the same AF (P < .05). Compared with reference CS6, the CS-AI groups had higher CNR values (all P < .05), with the CS-AI10 scan having the highest value. The SNR of the CS-AI group was better than that of the reference for both CE 3D-T1WI and CE 3D-FLAIR sequences (all P < .05). Qualitatively, the CS-AI protocol produced higher image quality scores than did the CS protocol with the same AF (all P < .05). In contrast to the reference CS6, the CS-AI group showed good image quality scores until an AF of up to 10 (all P < .05). The CS-AI10 scan provided the optimal images, improving the delineation of normal gray-white matter boundaries and lesion areas (P < .05). Compared with the reference, CS-AI10 showed reductions in scan time of 39.25% and 39.93% for CE 3D-T1WI and CE 3D-FLAIR sequences, respectively. CE 3D-T1WI and CE 3D-FLAIR sequences reconstructed with CS-AI for the detection of BM may provide a more effective alternative reconstruction approach than CS. CS-AI10 is suitable for clinical applications, providing optimal image quality and a shortened scan time.

Comparison between postcontrast thin-slice T1-weighted 2D spin echo and 3D T1-weighted SPACE sequences in the detection of brain metastases at 1.5 and 3 T

ObjectivesAccurate detection of metastatic brain lesions (MBL) is critical due to advances in radiosurgery. We compared the results of three readers in detecting MBL using T1-weighted 2D spin echo (SE) and sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences with whole-brain coverage at both 1.5 T and 3 T.MethodsFifty-six patients evaluated for MBL were included and underwent a standard protocol (1.5 T, n = 37; 3 T, n = 19), including postcontrast T1-weighted SE and SPACE. The rating was performed by three raters in two sessions > six weeks apart. The true number of MBL was determined using all available imaging including follow-up. Intraclass correlations for intra-rater and inter-rater agreement were calculated. Signal intensity ratios (SIR; enhancing lesion, white matter) were determined on a subset of 46 MBL > 4 mm. A paired t-test was used to evaluate postcontrast sequence order and SIR. Reader accuracy was evaluated by the coefficient of determination.ResultsA total of 135 MBL were identified (mean/subject 2.41, SD 6.4). The intra-rater agreement was excellent for all 3 raters (ICC = 0.97–0.992), as was the inter-rater agreement (ICC = 0.995 SE, 0.99 SPACE). Subjective qualitative ratings were lower for SE images; however, signal intensity ratios were higher in SE sequences. Accuracy was high in all readers for both SE (R2 0.95–0.96) and SPACE (R2 0.91–0.96) sequences.ConclusionsAlthough SE sequences are superior to gradient echo sequences in the detection of small MBL, they have long acquisition times and frequent artifacts. We show that T1-weighted SPACE is not inferior to standard thin-slice SE sequences in the detection of MBL at both imaging fields.Critical relevance statementOur results show the suitability of 3D T1-weighted turbo spin echo (TSE) sequences (SPACE, CUBE, VISTA) in the detection of brain metastases at both 1.5 T and 3 T.Key points• Accurate detection of brain metastases is critical due to advances in radiosurgery.• T1-weighted SE sequences are superior to gradient echo in detecting small metastases.• T1-weighted 3D-TSE sequences may achieve high resolution and relative insensitivity to artifacts.• T1-weighted 3D-TSE sequences have been recommended in imaging brain metastases at 3 T.• We found T1-weighted 3D-TSE equivalent to thin-slice SE at 1.5 T and 3 T.Graphical

Molecular identification and characterization of endophytic bacteria from root of chamaecrista rotundifolia growing on the nigerian air force shooting range, kaduna.

Chamaecrista rotundifolia is one of the few plant species growing on heavy metal-contaminated Nigerian Air Force shooting range, Kaduna. This microbially unexplored plant species can have microbial association with endophytes. This study was aimed at isolating, identifying and characterizing endophytic bacteria associated with the roots of Chamaecrista rotundifolia growing on the Nigerian Air Force shooting range, Kaduna. The identification of the endophytic bacteria was done using standard biochemical methods and 16S rRNA sequencing analysis. The isolates were then screened for antibiotic resistance, plant growth promoting properties and heavy metal tolerance using standard techniques. Varied concentrations of heavy metal salts (Pb2+, Cr3+, Ni2+ and Mn2+) were used to test the isolates for their heavy metal tolerance. Four endophytic bacteria isolated from the roots of C. rotundifolia were Aerococcus viridans, Peribacillus simplex, Staphylococcus simplex and Pseudomonas aeruginosa. Results on antibiotic sensitivity test revealed that the four isolates were resistant to most of the antibiotics. The isolates possessed plant growth promoting properties by showing positive results for Indole-3-acetic acid (IAA) production, 1-aminocyclopropane-1-carboxylic (ACC) deaminase activity and phosphate solubilizing. Results also revealed that the isolates showed some degree of tolerance to the heavy metals. The tolerance of both A. viridans and P. simplex to chromium and manganese showed significant difference (p&lt;0.05) across all the concentration levels of the metal salts. It is therefore concluded that Chamaecrista rotundifolia growing on Nigerian Air Force shooting range, Kaduna, is associated with endophytic bacteria which could be the reason the plant species thrive in heavy metal-contaminated site.&#x0D; &#x0D;

Genome-wide repeat landscapes in cancer and cell-free DNA.

Genetic changes in repetitive sequences are a hallmark of cancer and other diseases, but characterizing these has been challenging using standard sequencing approaches. We developed a de novo kmer finding approach, called ARTEMIS (Analysis of RepeaT EleMents in dISease), to identify repeat elements from whole-genome sequencing. Using this method, we analyzed 1.2 billion kmers in 2837 tissue and plasma samples from 1975 patients, including those with lung, breast, colorectal, ovarian, liver, gastric, head and neck, bladder, cervical, thyroid, or prostate cancer. We identified tumor-specific changes in these patients in 1280 repeat element types from the LINE, SINE, LTR, transposable element, and human satellite families. These included changes to known repeats and 820 elements that were not previously known to be altered in human cancer. Repeat elements were enriched in regions of driver genes, and their representation was altered by structural changes and epigenetic states. Machine learning analyses of genome-wide repeat landscapes and fragmentation profiles in cfDNA detected patients with early-stage lung or liver cancer in cross-validated and externally validated cohorts. In addition, these repeat landscapes could be used to noninvasively identify the tissue of origin of tumors. These analyses reveal widespread changes in repeat landscapes of human cancers and provide an approach for their detection and characterization that could benefit early detection and disease monitoring of patients with cancer.

Impact of Band‐gap Gradient in Semi‐Transparent and Bifacial Ultra‐Thin Cu(In,Ga)Se2 Solar Cells

AbstractUltra‐thin Cu(In,Ga)Se2 (CIGSe) solar cells on transparent conductive oxide back contact reduce the material consumption of rare indium and gallium and simultaneously exhibit great potential for semi‐transparent bifacial application. For highly efficient CIGSe solar cells, a steep back Ga grading and Na treatment are expected. However, Na will promote the formation of highly resistive GaOx at the rear interface owing to Ga accumulation. In this work, the three‐stage co‐evaporation process is renewed and the effect of the deposition sequence in the first stage on the Ga distribution as well as the cross‐correlated influence of Na is explored. In particular, the standard deposition sequence of Ga+In is altered to start with In. When a thin In layer is pre‐deposited on the back contact, the fill factor and efficiency increase. The deposition of In+Ga+In in the first stage of CIGSe growth leads to efficiencies 28% (on average) higher than for the standard deposition sequence of Ga+In. Additionally, 2.74% efficiency is reached under rear and 9.32% under simultaneous front and rear illumination. Therefore, adapting the deposition sequence in the first stage of CIGSe growth is identified as a key to improving the device performance on transparent back contact.

Effect of nitrogen fixation enhancing type SEN1 gene on soybean growth

ABSTRACT It is well known that the growth of legumes is greatly affected not only by fertilizer nitrogen but also by fixed nitrogen by symbiosis with rhizobia. We have reported that a polymorphism in SEN1, which is essential for nitrogen fixation in Lotus japonicus, could be used to enhance nitrogen fixation and plant growth. In this study, we examined whether the same strategy could be applied to Glycine max. Sequencing of orthologs of the LjSEN1 gene in 38 soybean cultivars revealed that the polymorphism occurred at Glyma.08g076300. We defined the standard sequence that most of the cultivars retained as Peking type SEN1, and the mutated sequence found in Enrei as Enrei type SEN1. To investigate the effect of genotype differences, we generated near-isogenic lines by crossing Enrei with Fukuyutaka, which has Peking type SEN1, and analyzed their characteristics. The results showed that Enrei type enhanced nitrogen fixation activity and promoted plant growth. Since soybean SEN1 has been reported to be a homolog of vacuolar iron transporter-like protein, we investigated the iron content in the nodules. In the result, the iron content in the nodules of Enrei type was significantly higher than that of Peking type. Iron is known to be present in the active center of nitrogenase, and the high iron content may have contributed to the increased nitrogen fixation activity. These results suggest that Enrei type SEN1 is a nitrogen fixation enhancing gene and that introduction of Enrei type SEN1 may reduce nitrogen fertilizer application and increase yield.

Diffusion tensor imaging within the healthy cervical spinal cord: Within- participants reliability and measurement error

BackgroundDiffusion tensor imaging (DTI) is a promising technique for the visualization of the cervical spinal cord (CSC) in vivo. It provides information about the tissue structure of axonal white matter, and it is thought to be more sensitive than other MR imaging techniques for the evaluation of damage to tracts in the spinal cord. AimThe purpose of this study was to determine the within-participants reliability and error magnitude of measurements of DTI metrics in healthy human CSC. MethodsA total of twenty healthy controls (10 male, mean age: 33.9 ± 3.5 years, 10 females, mean age: 47.5 ± 14.4 years), with no family history of any neurological disorders or a contraindication to MRI scanning were recruited over a period of two months. Each participant was scanned twice with an MRI 3 T scanner using standard DTI sequences. Spinal Cord Toolbox (SCT) software was used for image post-processing. Data were first corrected for motion artefact, then segmented, registered to a template, and then the DTI metrics were computed. The within-participants coefficients of variation (CV%), the single and average within-participants intraclass correlation coefficients (ICC) and Bland-Altman plots for WM, VC, DC and LC fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were determined for the cervical spinal cord (between the 2nd and 5th cervical vertebrae). ResultsDTI metrics showed poor to excellent within-participants reliability for both single and average ICC and moderate to high reproducibility for CV%, all variation dependent on the location of the ROI. The BA plots showed good within-participants agreement between the scan-rescan values. ConclusionResults from this reliability study demonstrate that clinical trials using the DTI technique are feasible and that DTI, in particular regions of the cord is suitable for use for the monitoring of degenerative WM changes.

Quantification of myocardial scar of different etiology using dark- and bright-blood late gadolinium enhancement cardiovascular magnetic resonance

Dark-blood late gadolinium enhancement (LGE) has been shown to improve the visualization and quantification of areas of ischemic scar compared to standard bright-blood LGE. Recently, the performance of various semi-automated quantification methods has been evaluated for the assessment of infarct size using both dark-blood LGE and conventional bright-blood LGE with histopathology as a reference standard. However, the impact of this sequence on different quantification strategies in vivo remains uncertain. In this study, various semi-automated scar quantification methods were evaluated for a range of different ischemic and non-ischemic pathologies encountered in clinical practice. A total of 62 patients referred for clinical cardiovascular magnetic resonance (CMR) were retrospectively included. All patients had a confirmed diagnosis of either ischemic heart disease (IHD; n = 21), dilated/non-ischemic cardiomyopathy (NICM; n = 21), or hypertrophic cardiomyopathy (HCM; n = 20) and underwent CMR on a 1.5 T scanner including both bright- and dark-blood LGE using a standard PSIR sequence. Both methods used identical sequence settings as per clinical protocol, apart from the inversion time parameter, which was set differently. All short-axis LGE images with scar were manually segmented for epicardial and endocardial borders. The extent of LGE was then measured visually by manual signal thresholding, and semi-automatically by signal thresholding using the standard deviation (SD) and the full width at half maximum (FWHM) methods. For all quantification methods in the IHD group, except the 6 SD method, dark-blood LGE detected significantly more enhancement compared to bright-blood LGE (p < 0.05 for all methods). For both bright-blood and dark-blood LGE, the 6 SD method correlated best with manual thresholding (16.9% vs. 17.1% and 20.1% vs. 20.4%, respectively). For the NICM group, no significant differences between LGE methods were found. For bright-blood LGE, the 5 SD method agreed best with manual thresholding (9.3% vs. 11.0%), while for dark-blood LGE the 4 SD method agreed best (12.6% vs. 11.5%). Similarly, for the HCM group no significant differences between LGE methods were found. For bright-blood LGE, the 6 SD method agreed best with manual thresholding (10.9% vs. 12.2%), while for dark-blood LGE the 5 SD method agreed best (13.2% vs. 11.5%). Semi-automated LGE quantification using dark-blood LGE images is feasible in both patients with ischemic and non-ischemic scar patterns. Given the advantage in detecting scar in patients with ischemic heart disease and no disadvantage in patients with non-ischemic scar, dark-blood LGE can be readily and widely adopted into clinical practice without compromising on quantification.

A rapid improvement event: progesterone prescribing in prevention of miscarriage

A rapid improvement event (RIE) is a standard operational excellence technique that uses team-based problem solving to improve processes. In this study, a RIE was undertaken to improve progesterone prescribing...

Evaluation of Upscaling the Selective Electrophoretic Deposition of Reduced Graphene Oxide on Miniaturized Au Interdigital Electrodes from Chip-to Wafer-Level

Today’s novel materials challenge the research industry to enhance the performance and to reduce the power consumption of microchips as well as to develop new sensor principles. All this applies pressure on the investigation of new economical mass production technologies for the integration into standard process sequences or on top of state-of-the-art CMOS devices. Since the discovery of graphene in 2004, many different variations have been investigated, thus the number of publications of graphene-based content grew from a few in 2004 exponential to 1.2 million only in 2019, according to Google Scholar analysis. The deposition of graphene-based materials at wafer-level is still difficult to do economically on standard SEMI wafers up to 8” diameter. In this publication, the selective electrophoretic deposition (EPD) of reduced graphene oxide flakes (rGO) will be shown. This technique is a very promising deposition method for large scale fabrication. The EPD of rGO particles is the only known way to create 3D surface topologies for an enhanced sensing area of electrochemical sensor applications e.g. biosensors. The electrical and chemical properties of this novel material provides a broad range of applications for possible sensor solutions [1, 2]. Firstly, the deposition will be shown on chip scale to gain optimum parameters in suspension preparation and EPD deposition time/voltage for a uniform particle deposition over the sensor area. Shortcuts from particles between the transmission lines or co-deposition on reference electrodes have to be avoided. This leads to a high selectivity in rGO particle deposition on Au-structures. Afterwards designs and experiments have been made on array level and a proof of concept wafer-level deposition with a low volume suspension is demonstrated. In previous work, the adhesion of rGO on Au structures in electrochemical sensors with a liquid flow, showed a migration of the deposited particles with the friction of the liquid [3]. Therefore, standard separation of particle agglomeration or splitting of primary particles with ultra sonic sonotrodes are not sufficient to gain highly concentrated suspensions with homogenous target particle distributions (&lt; 0,5µm ≤ 1µm ≥ 5µm). For this reason, a novel particle crushing preparation by ball milling is introduced and enhanced selectivity with an improved adhesion is demonstrated. A full process of the preparation of the colloidal suspension with the definition of target particle sizes with an optimum zeta potential will be provided and the cathodic electrophoretic deposition shown [4, 5]. For the evaluation of the deposition experiments, stereo microscopy is used to reveal the selectivity on the interdigital electrode (IDE) structures (sensor area) and scanning electron microscopy (SEM) analysis is used to characterize particle sizes and 3D topography, in terms of primary and secondary particles (agglomerates). For this study, IDE structures with 15 different geometry variations (3µm to 15µm lines and spaces) are used that were manufactured [6] to evaluate the rGO deposition on chip level. A novel multisensory array design with eight sensing areas are presented, combined with wafer-level deposition as a proof of concept on a 200mm wafer.

Arthroscopic reduction and rigid fixation of the anteriorly displaced temporomandibular joint disc without reduction using titanium screw: a case series.

To evaluate the effectiveness of arthroscopic reduction and rigid fixation (ARRF) using a suture-free titanium screw as a treatment approach to temporomandibular joint's (TMJ) anterior disc displacement without reduction (ADDwoR) and assess its impact on clinical outcomes, including improvements in symptoms related to TMJ disorders. A series of twenty patients presented to the Department of Orthognathic and Temporomandibular Surgery at West China Hospital of Stomatology between September 2022 and January 2023, complaining of symptoms such as pain, clicking, and limited mouth opening. Standard magnetic resonance image (MRI) imaging T1 and T2 sequences in both sagittal and coronal views study with closed and maximal open mouth positions were taken preoperatively to assess the disc's position, integrity, and shape. Also, cone-beam computed tomography (CBCT) scans images to find any degenerative changes and evaluate the condylar bone's features and volume. Additionally, the clinical examination assesses limited oral opening, mechanical pain, and the presence of any noises such as clicking and crepitus. All cases were treated under general anesthesia using the arthroscopic release, reduction, and rigid fixation of the TMJ's ADDwoR to establish a normal disc-condyle relationship and to restore the functional position. Patients' symptoms, such as pain and mouth opening, improved significantly following the arthroscopic treatment. Postoperative MRI and CBCT imaging follow-up conducted at 6 months demonstrated the stable position of the reduced TMJ disc and the fixation screw. Notably, none of the patients exhibited signs of relapse during this follow-up period. Overall, the ARRF of TMJ's ADDwoR using a suture-free titanium screw proved to be safe and provides satisfactory results, in addition to the several advantages of using suture-free titanium screws, such as biocompatibility, strong fixation, and durability. However, it is a technically demanding procedure requiring extensive, long-term training. ARRF using a cost-effective fixation titanium screw to treat ADDwoR emerges as a clinically effective minimally invasive approach.

Assessing the efficacy of target adaptive sampling long-read sequencing through hereditary cancer patient genomes

Innovations in sequencing technology have led to the discovery of novel mutations that cause inherited diseases. However, many patients with suspected genetic diseases remain undiagnosed. Long-read sequencing technologies are expected to significantly improve the diagnostic rate by overcoming the limitations of short-read sequencing. In addition, Oxford Nanopore Technologies (ONT) offers adaptive sampling and computationally driven target enrichment technology. This enables more affordable intensive analysis of target gene regions compared to standard non-selective long-read sequencing. In this study, we developed an efficient computational workflow for target adaptive sampling long-read sequencing (TAS-LRS) and evaluated it through application to 33 genomes collected from suspected hereditary cancer patients. Our workflow can identify single nucleotide variants with nearly the same accuracy as the short-read platform and elucidate complex forms of structural variations. We also newly identified several SINE-R/VNTR/Alu (SVA) elements affecting the APC gene in two patients with familial adenomatous polyposis, as well as their sites of origin. In addition, we demonstrated that off-target reads from adaptive sampling, which is typically discarded, can be effectively used to accurately genotype common single-nucleotide polymorphisms (SNPs) across the entire genome, enabling the calculation of a polygenic risk score. Furthermore, we identified allele-specific MLH1 promoter hypermethylation in a Lynch syndrome patient. In summary, our workflow with TAS-LRS can simultaneously capture monogenic risk variants including complex structural variations, polygenic background as well as epigenetic alterations, and will be an efficient platform for genetic disease research and diagnosis.

Putaminal T1/T2-weighted ratio is increased in PSP compared to PD and healthy controls, a multi-cohort study

IntroductionDifferentiating Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is a common clinical problem. We aimed to apply the T1-/T2-weighted ratio imaging technique, based on standard clinical MRI, to reveal differences in neurodegeneration in three large cohorts. MethodsThree cohorts, with a total of 405 participants (269 PD, 44 PSP, 38 MSA, 54 controls), were combined and T1/T2-weighted ratio image analyses were carried out. A combination of automatic segmentation and atlas-based ROI were used in this study. The cohorts were combined using the ComBat batch correction procedure. ResultsGroup differences were found in the putamen (p = 0.040), with higher T1/T2-weighted ratio in this region in PSP compared to PD and healthy controls (p-values 0.010 and 0.007 respectively). Using putaminal T1/T2-weighted ratio for diagnostic separation, a fair performance was found in separating PSP from healthy controls, with an area under the receiver operating characteristic curve of 0.701. ConclusionDifferent patterns of T1/T2-weighted ratio, reflecting differences in underlying pathophysiology, were found between the groups. Since T1/T2-weighted ratio can be applied to standard clinical MRI sequences to allow more quantitative analyses, this seems to be a promising biomarker for diagnostics and treatment evaluation of parkinsonian disorders for clinical trials.

Prospective Comparison of Free-Breathing Accelerated Cine Deep Learning Reconstruction Versus Standard Breath-Hold Cardiac MRI Sequences in Patients With Ischemic Heart Disease.

BACKGROUND. Cine cardiac MRI sequences require repeated breath-holds, which can be difficult for patients with ischemic heart disease (IHD). OBJECTIVE. The purpose of the study was to compare a free-breathing accelerated cine sequence using deep learning (DL) reconstruction and a standard breath-hold cine sequence in terms of image quality and left ventricular (LV) measurements in patients with IHD undergoing cardiac MRI. METHODS. This prospective study included patients undergoing 1.5- or 3-T cardiac MRI for evaluation of IHD between March 15, 2023, and June 21, 2023. Examinations included an investigational free-breathing cine short-axis sequence with DL reconstruction (hereafter, cine-DL sequence). Two radiologists (reader 1 [R1] and reader 2 [R2]), in blinded fashion, independently assessed left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and subjective image quality for the cine-DL sequence and a standard breath-hold balanced SSFP sequence; R1 assessed artifacts. RESULTS. The analysis included 26 patients (mean age, 64.3 ± 11.7 [SD] years; 14 men, 12 women). Acquisition was shorter for the cine-DL sequence than the standard sequence (mean ± SD, 0.6 ± 0.1 vs 2.4 ± 0.6 minutes; p < .001). The cine-DL sequence, in comparison with the standard sequence, showed no significant difference for LVEF for R1 (mean ± SD, 51.7% ± 14.3% vs 51.3% ± 14.7%; p = .56) or R2 (53.4% ± 14.9% vs 52.8% ± 14.6%; p = .53); significantly greater LVEDV for R2 (mean ± SD, 171.9 ± 51.9 vs 160.6 ± 49.4 mL; p = .01) but not R1 (171.8 ± 53.7 vs 165.5 ± 52.4 mL; p = .16); and no significant difference in LVESV for R1 (mean ± SD, 88.1 ± 49.3 vs 86.0 ± 50.5 mL; p = .45) or R2 (85.2 ± 48.1 vs 81.3 ± 48.2 mL; p = .10). The mean bias between the cine-DL and standard sequences by LV measurement was as follows: LVEF, 0.4% for R1 and 0.7% for R2; LVEDV, 6.3 mL for R1 and 11.3 mL for R2; and LVESV, 2.1 mL for R1 and 3.9 mL for R2. Subjective image quality was better for cine-DL sequence than the standard sequence for R1 (mean ± SD, 2.3 ± 0.5 vs 1.9 ± 0.8; p = .02) and R2 (2.2 ± 0.4 vs 1.9 ± 0.7; p = .02). R1 reported no significant difference between the cine-DL and standard sequences for off-resonance artifacts (3.8% vs 23.1% examinations; p = .10) and parallel imaging artifacts (3.8% vs 19.2%; p = .19); blurring artifacts were more frequent for the cine-DL sequence than the standard sequence (42.3% vs 7.7% examinations; p = .008). CONCLUSION. A free-breathing cine-DL sequence, in comparison with a standard breath-hold cine sequence, showed very small bias for LVEF measurements and better subjective quality. The cine-DL sequence yielded greater LV volumes than the standard sequence. CLINICAL IMPACT. A free-breathing cine-DL sequence may yield reliable LVEF measurements in patients with IHD unable to repeatedly breath-hold. TRIAL REGISTRATION. ClinicalTrials.gov NCT05105984.

Rare subclonal sequencing of breast cancers indicates putative metastatic driver mutations are predominately acquired after dissemination

BackgroundEvolutionary models of breast cancer progression differ on the extent to which metastatic potential is pre-encoded within primary tumors. Although metastatic recurrences often harbor putative driver mutations that are not detected in their antecedent primary tumor using standard sequencing technologies, whether these mutations were acquired before or after dissemination remains unclear.MethodsTo ascertain whether putative metastatic driver mutations initially deemed specific to the metastasis by whole exome sequencing were, in actuality, present within rare ancestral subclones of the primary tumors from which they arose, we employed error-controlled ultra-deep sequencing (UDS-UMI) coupled with FFPE artifact mitigation by uracil-DNA glycosylase (UDG) to assess the presence of 132 “metastasis-specific” mutations within antecedent primary tumors from 21 patients. Maximum mutation detection sensitivity was ~1% of primary tumor cells. A conceptual framework was developed to estimate relative likelihoods of alternative models of mutation acquisition.ResultsThe ancestral primary tumor subclone responsible for seeding the metastasis was identified in 29% of patients, implicating several putative drivers in metastatic seeding including LRP5 A65V and PEAK1 K140Q. Despite this, 93% of metastasis-specific mutations in putative metastatic driver genes remained undetected within primary tumors, as did 96% of metastasis-specific mutations in known breast cancer drivers, including ERRB2 V777L, ESR1 D538G, and AKT1 D323H. Strikingly, even in those cases in which the rare ancestral subclone was identified, 87% of metastasis-specific putative driver mutations remained undetected. Modeling indicated that the sequential acquisition of multiple metastasis-specific driver or passenger mutations within the same rare subclonal lineage of the primary tumor was highly improbable.ConclusionsOur results strongly suggest that metastatic driver mutations are sequentially acquired and selected within the same clonal lineage both before, but more commonly after, dissemination from the primary tumor, and that these mutations are biologically consequential. Despite inherent limitations in sampling archival primary tumors, our findings indicate that tumor cells in most patients continue to undergo clinically relevant genomic evolution after their dissemination from the primary tumor. This provides further evidence that metastatic recurrence is a multi-step, mutation-driven process that extends beyond primary tumor dissemination and underscores the importance of longitudinal tumor assessment to help guide clinical decisions.

Exploratory genetic analysis in children with autism spectrum disorder and other developmental disorders using whole exome sequencing.

Developmental disorders (DDs), such as autism spectrum disorder (ASD), incorporate various conditions; once identified, further diagnostics are necessary to specify their type and severity. The aim of this exploratory study was to identify genetic variants that can help differentiate ASD early from other DDs. We selected 36 children (mean age 60.1 months) with DDs using Developmental Behavioral Scales (DBS) through "EDUS-Education for All", an organization providing services for children with developmental disorders in Bosnia and Herzegovina. We further rated children's autistic traits with the preschool version of the Childhood Autism Rating Scale, second edition (CARS-II). We defined ASD if scores were >25.5 and other DDs if scores were <25.5. Diagnosis of ASD and DD were independently confirmed by child psychiatrists. Whole exome sequencing (WES) was performed by Veritas Genetics, USA, using Illumina NovaSeq 6000 (Illumina Inc., San Diego, CA, USA) next-generation sequencing (NGS) apparatus. We tested genetic association by applying SKAT-O, which optimally combines the standard Sequence Kernel Association Test (SKAT) and burden tests to identify rare variants associated with complex traits in samples of limited power. The analysis yielded seven genes (DSE, COL10A1, DLK2, CSMD1, FAM47E, PPIA, PYDC2) to potentially differentiate observed phenotypic characteristics between our cohort participants with ASD and other DDs. Our exploratory study in a small sample of participants with ASD and other DDs contributed to gene discovery in differentiating ASD from DDs. A replication study is needed in a larger sample to confirm our results.

Impact of the Order of Movement on the Median Nerve Root Function: A Neurophysiological Study with Implications for Neurodynamic Exercise Sequencing

Background: Neurodynamic exercise is a common clinical practice used to restore neural dynamic balance. The order in which movements are performed during these exercises is believed to play a crucial role in their effectiveness. This study aimed to investigate the impact of different sequences of neurodynamic exercise on nerve root function, with a specific focus on the median nerve. Methods: Participants were assigned randomly to three experimental groups, each undergoing a different test sequence: standard, proximal-to-distal, and distal-to-proximal. Dermatomal somatosensory evoked potentials (DSSEPs) were recorded at key levels (C6, C7, C8, and T1). Results: The findings revealed a significant influence of the movement sequence on DSSEP amplitudes. The execution of neurodynamic exercise in the proximal-to-distal sequence was associated with a notable reduction in amplitudes (p &lt; 0.05). Conversely, the distal-to-proximal sequence resulted in increased amplitudes compared to the standard sequence (p &lt; 0.05). Conclusions: This study underscores the importance of carefully considering the order of movements during neurodynamic exercising, particularly when evaluating nerve roots that lack the protective perineurium. The choice of sequence appears to have a substantial impact on nerve function, with implications for optimizing clinical neurodynamic exercise techniques.

Polyphasic molecular approach to the characterization of methanogens in the saliva of Tunisian adults

ObjectivesMethanogenic archaea are a minor component of human oral microbiota. Due to their relatively low abundance, the detection of these neglected microorganisms is challenging. This study concerns the presence of methanogens in salivary samples collected from Tunisian adults to evaluate their prevalence and burden using a polyphasic molecular approach. MethodsA total of 43 saliva samples were included. Metagenomic and standard 16S rRNA sequencing were performed as an initial screening to detect the presence of methanogens in the oral microbiota of Tunisian adults. Further investigations were performed using specific quantitative real-time PCR targeting Methanobrevibacter oralis and Methanobrevibacter smithii. ResultsMethanobrevibacter was detected in 5/43 (11.62 %) saliva samples after metagenomic 16S rRNA data analysis. The presence of M. oralis was confirmed in 6/43 samples by standard 16S rRNA sequencing. Using real-time PCR, methanogens were detected in 35/43 (81.39 %) samples, including 62.79 % positive for M. oralis and 76.74 % positive for M. smithii. These findings reflect the high prevalence of both methanogens, revealed by the high sensitivity of the real-time PCR approach. Interestingly, we also noted a significant statistical association between the detection of M. smithii and poor adherence to a Mediterranean diet, indicating the impact of diet on M. smithii prevalence. ConclusionOur study showed the presence of methanogens in the oral microbiota of Tunisian adults with an unprecedented relatively high prevalence. Choice of methodology is also central to picturing the real prevalence and diversity of such minor taxa in the oral microbiota.

Mitofusin 2 Variant Presenting With a Phenotype of Multiple System Atrophy of Cerebellar Subtype.

To investigate the etiology of cerebellar ataxia in an adult male patient. We performed standard neurologic assessment and genome sequencing of a 62-year-old man with rapidly progressive balance and gait abnormalities. The propositus exhibited cognitive dysfunction, mild appendicular bradykinesia, prominent appendicular ataxia, dysarthria, and hypomimia with minimal dysautonomic symptoms. Nerve conduction studies showed mild peripheral sensory neuropathy and normal motor nerve conduction velocities. Brain imaging showed progressive cerebellar atrophy and gliosis of the olivopontocerebellar fibers, characterized by T2 hyperintensity within the pons. Genetic testing revealed a likely pathogenic germline variant in MFN2 (NM_014874: c.[838C>T];[=], p.(R280C)) in the GTPase domain (G) interface; pathogenic variants of MFN2 typically cause hereditary sensory and motor neuropathy VI or Charcot-Marie-Tooth disease 2A. The presence of progressive ataxia, "hot cross bun" sign, and dysautonomia has been associated with multiple system atrophy, cerebellar type (MSA-C). We describe progressive cerebellar ataxia in an individual with a deleterious variant in MFN2. Our findings suggest that pathogenic variants in MFN2 can result in a spectrum of phenotypes including cerebellar ataxia with cerebellar-pontine atrophy in the absence of significant neuropathy and in a manner closely resembling MSA-C.

Evaluation Of Surrogate Markers to Define H3 G34R/V-Mutant Gliomas

Background: H3 G34-mutant glioma was a new high-grade glioma, characterized by mutation of histone3.3 codon34. Currently, standard gene sequencing methods are helping in tumor diagnosis, but less expensive and faster H3 G34R/V staining method has not been studied yet in Thailand. Objectives: The purpose of this research is to find surrogate makers for diagnosing this tumor by uncomplicated immunohistochemical method. Methods: Formalin-fixed and paraffin-embedded tissue samples of 30 diffuse hemispheric gliomas were collected H3 G34R, H3 G34V, Olig2, p53 were evaluated using immunohistochemistry. Comparisons of immunohistochemical method and sequencing standard technique were made. Cost-effectiveness was analyzed. Results: Two cases of H3 G34-mutant gliomas were confirmed by mutation analysis. One case was positive for H3 G34V antibody (1/1) while another case was negative for H3 G34R (0/1). The cost-effectiveness showed that the sequencing technique prolonged turnaround time but gave a cost saving 23 USD (17%). Conclusions: G34R and G34V antibodies are not sensitive surrogate markers for diagnosing H3.3 G34-mutant gliomas. However, more samplings are yet to be tested in the future.