The purposes of the current study were to introduce a Mescher–Garwood (MEGA) semi‐adiabatic spin‐echo full‐intensity localization (MEGA‐sSPECIAL) sequence with macromolecule (MM) subtraction and to ...compare the test–retest reproducibility of γ‐aminobutyric acid (GABA) measurements at 7 T using the sSPECIAL and MEGA‐sSPECIAL sequences. The MEGA‐sSPECIAL editing scheme using asymmetric adiabatic and highly selective Gaussian pulses was used to compare its GABA measurement reproducibility with that of short echo‐time (TE) sSPECIAL. Proton magnetic resonance spectra were acquired in the motor cortex (M1) and medial prefrontal cortex (mPFC) using the sSPECIAL (TR/TE = 4000/16 ms) and MEGA‐sSPECIAL sequences (TR/TE = 4000/80 ms). The metabolites were quantified using LCModel with unsuppressed water spectra. The concentrations are reported in institutional units. The test–retest reproducibility was evaluated by scanning each subject twice. Between‐session reproducibility was assessed using coefficients of variation (CVs), Pearson's r correlation coefficients, and intraclass correlation coefficients (ICCs). Intersequence agreement was evaluated using Pearson's r correlation coefficients and Bland–Altman plots. Regarding GABA measurements by sSPECIAL, the GABA concentrations were 0.92 ± 0.31 (IU) in the M1 and 1.56 ± 0.49 (IU) in the mPFC. This demonstrated strong between‐session correlation across both regions (r = 0.81, p < 0.01; ICC = 0.82). The CVs between the two scans were 21.8% in the M1 and 10.2% in the mPFC. On the other hand, the GABA measurements by MEGA‐sSPECIAL were 0.52 ± 0.04 (IU) in the M1 and 1.04 ± 0.24 (IU) in the mPFC. MEGA‐sSPECIAL demonstrated strong between‐session correlation across the two regions (r = 0.98, p < 0.001; ICC = 0.98) and lower CVs than sSPECIAL, providing 4.1% in the M1 and 5.8% in the mPFC. The MEGA‐editing method showed better reproducibility of GABA measurements in both brain regions compared with the short‐TE sSPECIAL method. Thus it is a more sensitive method with which to detect small changes in areas with low GABA concentrations. In GABA‐rich brain regions, GABA measurements can be achieved reproducibly using both methods.
(A‐D) illustrate overlay spectra from the first and second sessions acquired using sSPECIAL at short‐TE and MEGA‐sSPECIAL in the M1 and mPFC. (E and F) show coefficients of variation of each measurement method depending on the number of averages.
ABSTRACT
Background and objective
PPFE is characterized by fibrosis in the pleura and subpleural lung parenchyma in the upper lobes, while other types of ILD, mainly UIP, can be observed in about ...half of the patients in their lower lobes. The aim of this study was to evaluate the clinical significance of the radiologically defined PPFE in patients with IPF.
Methods
Clinical data and chest CT images were retrospectively analysed in 445 patients with IPF (biopsy‐proven cases, n = 165). The radiological criteria of PPFE were defined as follows: (i) bilateral subpleural dense fibrosis with or without pleural thickening in the upper lobes, (ii) evidence of disease progression and (iii) no clinical evidence of identifiable aetiologies.
Results
The median follow‐up period was 43.0 months. The mean age of the patients was 66.4 years and 76.4% were male. PPFE was identified in 28 patients (6.3%). The PPFE group showed lower BMI and lung function (FVC and TLC) at baseline, more frequent pneumothorax and pneumomediastinum, higher decline rates in lung function and poorer prognosis during follow‐up than the no‐PPFE group. PPFE was an independent risk factor (HR = 2.953, 95% CI: 1.350–6.460, P = 0.007) for pneumothorax or pneumomediastinum, but not for mortality in patients with IPF.
Conclusion
Among patients with IPF, the PPFE group, when compared to the no‐PPFE group, showed lower BMI and lung function and showed more frequent complications and poorer survival during follow‐up.
Radiological PPFE was identified in 6.3% of patients with IPF. Radiological PPFE was associated with low BMI and lung function at baseline, more frequent pneumothorax and pneumomediastinum, higher decline rates in lung function and poorer prognosis during follow‐up in patients with IPF.
γ‐Aminobutyric acid (GABA), as the primary inhibitory neurotransmitter, is extremely important for maintaining healthy brain function, and deviations from GABA homeostasis are related to various ...brain diseases. Short‐echo‐time (short‐TE) proton MR spectroscopy (1H‐MRS) has been employed to measure GABA concentration from various human brain regions at high magnetic fields. The aim of this study was to investigate the effect of spectral linewidth on GABA quantification and explore the application of an optimized basis‐set preparation approach using a spectral‐linewidth‐matched (LM) basis set in LCModel to improve the reproducibility of GABA quantification from short‐TE 1H‐MRS. In contrast to the fixed‐linewidth basis‐set approach, the LM basis‐set preparation approach, where all metabolite basis spectra were simulated with a linewidth 4 Hz narrower than that of water, showed a smaller standard deviation of estimated GABA concentration from synthetic spectra with varying linewidths and lineshapes. The test–retest reproducibility was assessed by the mean within‐subject coefficient of variation, which improved from 19.2% to 12.0% in the thalamus, from 27.9% to 14.9% in the motor cortex, and from 9.7% to 2.8% in the medial prefrontal cortex using LM basis sets at 7 T. We conclude that spectral linewidth has a large effect on GABA quantification from short‐TE 1H‐MRS data and that using LM basis sets in LCModel can improve the reproducibility of GABA quantification.
Short‐TE proton MR spectroscopy (1H‐MRS) has been used to measure γ‐aminobutyric acid (GABA) concentration. This study focused on reducing the spectral linewidth effects on GABA quantification by using the spectral‐linewidth‐matched basis sets in LCModel, which enabled improving the reproducibility of GABA measurement.
During October 2022-March 2023, highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b virus caused outbreaks in South Korea, including 174 cases in wild birds. To understand the origin and ...role of wild birds in the evolution and spread of HPAI viruses, we sequenced 113 HPAI isolates from wild birds and performed phylogenetic analysis. We identified 16 different genotypes, indicating extensive genetic reassortment with viruses in wild birds. Phylodynamic analysis showed that the viruses were most likely introduced to the southern Gyeonggi-do/northern Chungcheongnam-do area through whooper swans (Cygnus cygnus) and spread southward. Cross-species transmission occurred between various wild bird species, including waterfowl and raptors, resulting in the persistence of HPAI in wild bird populations and further geographic spread as these birds migrated throughout South Korea. Enhanced genomic surveillance was an integral part of the HPAI outbreak response, aiding in timely understanding of the origin, evolution, and spread of the virus.
Intrinsically disordered proteins rich in cationic amino acid groups can undergo Liquid-Liquid Phase Separation (LLPS) in the presence of charge-balancing anionic counterparts. Arginine and Lysine ...are the two most prevalent cationic amino acids in proteins that undergo LLPS, with arginine-rich proteins observed to undergo LLPS more readily than lysine-rich proteins, a feature commonly attributed to arginine's ability to form stronger cation-π interactions with aromatic groups. Here, we show that arginine's ability to promote LLPS is independent of the presence of aromatic partners, and that arginine-rich peptides, but not lysine-rich peptides, display re-entrant phase behavior at high salt concentrations. We further demonstrate that the hydrophobicity of arginine is the determining factor giving rise to the reentrant phase behavior and tunable viscoelastic properties of the dense LLPS phase. Controlling arginine-induced reentrant LLPS behavior using temperature and salt concentration opens avenues for the bioengineering of stress-triggered biological phenomena and drug delivery systems.
Water-in-oil emulsion droplet microfluidic systems have been extensively developed, and currently, almost all cell handling steps can be conducted in this format. An exception is the cell washing and ...solution exchange step, which is commonly utilized in many conventional cell assays. This paper presents an in-droplet cell washing and solution exchange technology that utilizes dielectrophoretic (DEP) force to move all cells to one side of a droplet, followed by asymmetrical splitting of the droplet to obtain a small daughter droplet that contains all or most of the cells, and then finally merges this cell-concentrated droplet with a new droplet that contains the desired solution. These sequential droplet manipulation steps were integrated into a single platform, where up to 88% of the original solution in the droplet could be exchanged with the new solution while keeping cell loss to less than 5%. Two application examples were demonstrated using the developed technology. In the first example, green microalga Chlamydomonas reinhardtii cells were manipulated using negative DEP force to exchange the regular culture medium with a nitrogen-limited medium to induce lipid production. In the second example, Salmonella enterica cells were manipulated using positive DEP force to replace fluorescent dye that models fluorescent cell stains that contribute to high background noise in fluorescence-based droplet content detection with fresh buffer solution, significantly improving the droplet content detection sensitivity. Since the cell washing step is one of the most frequently utilized steps in many cell biology assays, we expect that the developed technology can significantly broaden the type of assay that can be conducted in droplet microfluidic format.
Summary
Atelectasis occurs in the majority of children undergoing general anaesthesia. Lung ultrasound has shown reliable sensitivity and specificity for diagnosing anaesthesia‐induced atelectasis. ...We assessed the effects of a recruitment manoeuvre on atelectasis using lung ultrasound in infants undergoing general anaesthesia. Forty infants, randomly allocated to either a recruitment manoeuvre group or a control group, received volume‐controlled ventilation with 5 cmH2O positive end‐expiratory pressure. Lung ultrasound examination was performed twice in each patient, the first a minute after starting mechanical ventilation of the lungs and the second at the end of surgery. Patients in the recruitment manoeuvre group received ultrasound‐guided recruitment manoeuvres after each lung ultrasound examination. The incidence of significant anaesthesia‐induced atelectasis at the second lung ultrasound examination was less in the recruitment manoeuvre group compared with the control group (25% vs. 80%; p = 0.001; odds ratio (OR) 0.083; 95% confidence interval (CI): 0.019–0.370). The median (IQR range) lung ultrasound scores for consolidation and B‐lines on the second examination were lower in the recruitment manoeuvre group compared with the control group; 6.0 (3.0–9.3 0.0–14.0) vs. 13.5 (11.0–16.5 8.0–23.0); p < 0.001 and 6.5 (3.0–12.0 0.0–28.0) vs. 15.0 (10.8–20.5 7.0–28.0); p < 0.001, respectively. The lung ultrasound scores for consolidation on the first and second examinations showed a negative correlation with age (r = −0.340, p = 0.008; r = −0.380, p = 0.003). We conclude that ultrasound‐guided recruitment manoeuvres with positive end‐expiratory pressure proved useful in reducing the incidence of anaesthesia‐induced atelectasis in infants, although 5 cmH2O positive end‐expiratory pressure alone was not sufficient to eliminate it. In addition, the younger the patient, the more susceptible they were to atelectasis.
This paper presents a microfluidic device for electrical discrimination of circulating tumor cells (CTCs) using graphene nanoplates (GNPs) as a highly conductive material bound to the cell surface. ...For two-step cascade discrimination, the microfluidic device is composed of a CTC-enrichment device and an impedance cytometry. Using lateral magnetophoresis, the CTC-enrichment device enriches rare CTCs from millions of background blood cells. Then, the impedance cytometry electrically identifies CTCs from the enriched sample, containing CTCs and persistent residual blood cells, based on the electrical impedance of CTCs modified by the GNPs. GNPs were used as a highly conductive material for modifying surface conductivity of CTCs, thereby improving the accuracy of electrical discrimination. The experimental results showed that a colorectal cancer cell line (DLD-1) spiked into peripheral blood was enriched by nearly 500-fold by the CTC-enrichment device. The phase of the electrical signal measured from DLD-1 cells covered by GNPs shifted by about 100° in comparison with that from normal blood cells, which allows the impedance cytometry to identify CTCs at a rate of 94% from the enriched samples.
Concentrating cells or adjusting the concentration of cells are one of the most fundamental steps in cell biology experiments, and are typically achieved through centrifugation. However this step is ...challenging to implement in droplet microfluidics. Here we present an in-droplet cell concentrator that operates by first gradually focusing cells inside a droplet to one side of the droplet using negative dielectrophoresis (nDEP), followed by asymmetric droplet splitting using a Y-shaped junction, resulting in two daughter droplets, one of which containing all or most of the cells. The developed platform was first characterized using droplets containing different number of polystyrene (PS) particles and by varying the applied voltages, flow rates, and the width ratios of the droplet splitting microchannels. Using this platform, the volume of one daughter droplet could be reduced up to 84% compared to that of the mother droplet, which resulted in the PS particle concentration to increase by 5.6-fold, with an average recovery rate of 90%. When testing with cells (Chlamydomonas reinhardtii), recovery rates as high as 98% could be achieved while increasing the cell concentration by 5-fold. This technology adds a new capability to droplet microfluidics operation, and can be used for adjusting concentrations of cells in droplets, exchanging solutions in which cells are suspended in droplets (including cell washing steps), and separating cells of different dielectric properties inside droplets, all of which are common steps in conventional cell assays but have been so far difficult to achieve in droplet format.
•DEP-based in-droplet cell concentrator overcomes the limitation of cell manipulation within a droplet.•Particles/ cells can be focused to one side of a droplet using a pair of angled electrodes.•Downstream asymmetric droplet splitting results in two daughter droplets.•One of daughter droplets contains all or most of the particles/ cells.•Particle/ cell concentration within the droplet can be achieved with high recovery rate.
The Taiwan Biobank (TWB) aims to build a nationwide research database that integrates genomic/epigenomic profiles, lifestyle patterns, dietary habits, environmental exposure history and long-term ...health outcomes of 300,000 residents of Taiwan. We describe here an investigation of the population structure of Han Chinese on this Pacific island using genotype data of 591,048 SNPs in an initial freeze of 10,801 unrelated TWB participants. In addition to the North-South cline reported in other Han Chinese populations, we find the Taiwanese Han Chinese clustered into three cline groups: 5% were of northern Han Chinese ancestry, 79.9% were of southern Han Chinese ancestry, and 14.5% belonged to a third (T) group. We also find that this T group is genetically distinct from neighbouring Southeast Asians and Austronesian tribes but similar to other southern Han Chinese. Interestingly, high degree of LD between HLA haplotype A*33:03-B*58:01, an MHC allele being of pathological relevance, and SNPs across the MHC region was observed in subjects with T origin, but not in other Han Chinese. This suggested the T group individuals may have experienced evolutionary events independent from the other southern Han Chinese. Based on the newly-discovered population structure, we detect different loci susceptible to type II diabetes in individuals with southern and northern Han Chinese ancestries. Finally, as one of the largest dataset currently available for the Chinese population, genome-wide statistics for the 10,810 subjects are made publicly accessible through Taiwan View (https://taiwanview.twbiobank.org.tw/index; date last accessed October 14, 2016) to encourage future genetic research and collaborations with the island Taiwan.
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