"Pseudo-pseudogenes" in bacterial genomes: Proteogenomics reveals a wide but low protein expression of pseudogenes in Salmonella enterica.

Pseudogenes (genes disrupted by frameshift or in-frame stop codons) are ubiquitously present in the bacterial genome and considered as nonfunctional fossil. Here, we used RNA-seq and mass-spectrometry technologies to measure the transcriptomes and proteomes of Salmonella enterica serovars Paratyphi A and Typhi. All pseudogenes' mRNA sequences remained disrupted, and were present at comparable levels to their intact homologs. At the protein level, however, 101 out of 161 pseudogenes suggested successful translation, with their low expression regardless of growth conditions, genetic background and pseudogenization causes. The majority of frameshifting detected was compensatory for -1 frameshift mutations. Readthrough of in-frame stop codons primarily involved UAG; and cytosine was the most frequent base adjacent to the codon. Using a fluorescence reporter system, fifteen pseudogenes were confirmed to express successfully in vivo in Escherichia coli. Expression of the intact copy of the fifteen pseudogenes in S. Typhi affected bacterial pathogenesis as revealed in human macrophage and epithelial cell infection models. The above findings suggest the need to revisit the nonstandard translation mechanism as well as the biological role of pseudogenes in the bacterial genome.

Geospatial artificial intelligence for estimating daytime and nighttime nitrogen dioxide concentration variations in Taiwan: A spatial prediction model.

Nitrogen dioxide (NO2) is a major air pollutant primarily emitted from traffic and industrial activities, posing health risks. However, current air pollution models often underestimate exposure risks by neglecting the bimodal pattern of NO2 levels throughout the day. This study aimed to address this gap by developing ensemble mixed spatial models (EMSM) using geo-artificial intelligence (Geo-AI) to examine the spatial and temporal variations of NO2 concentrations at a high resolution of 50m. These EMSMs integrated spatial modelling methods, including kriging, land use regression, machine learning, and ensemble learning. The models utilized 26 years of observed NO2 measurements, meteorological parameters, geospatial layers, and social and season-dependent variables as representative of emission sources. Separate models were developed for daytime and nighttime periods, which achieved high reliability with adjusted R2 values of 0.92 and 0.93, respectively. The study revealed that mean NO2 concentrations were significantly higher at nighttime (9.60 ppb) compared to daytime (5.61 ppb). Additionally, winter exhibited the highest NO2 levels regardless of time period. The developed EMSMs were utilized to generate maps illustrating NO2 levels pre and during COVID restrictions in Taiwan. These findings could aid epidemiological research on exposure risks and support policy-making and environmental planning initiatives.

Toxicity prediction: An application of alternative testing and computational toxicology in contaminated groundwater sites in Taiwan.

Groundwater contamination remains a global threat due to its toxic effects to humans and the environment. The remediation of contaminated groundwater sites can be costly, thus, identifying the priority areas of concern is important to reduce money spent on resources. In this study, we aimed to identify and rank the priority groundwater sites in a contaminated petrochemical district by combining alternative, non-animal approaches - chemical analysis, cell-based high throughput screening (HTS), and Toxicological Priority Index (ToxPi) computational toxicology tool. Groundwater samples collected from ten different sites in a contaminated district showed pollutant levels below the detection limit, however, hepatotoxic bioactivity was demonstrated in human hepatoma HepaRG cells. Integrating the pollutants information (i.e., pollutant characteristics and concentration data) with the bioactivity data of the groundwater samples, an evidence-based ranking of the groundwater sites for future remediation was established using ToxPi analysis. The currently presented combinatorial approach of screening groundwater sites for remediation purposes can further be refined by including relevant parameters, which can boost the utility of this approach for groundwater screening and future remediation.

Examining impacts of information system success and perceived stress on students' self-regulated learning mediated by intrinsic motivation in online learning environments: second-order structural equation modelling analyses.

The unanticipated switch from face-to-face learning to online education caused by the Covid-19 pandemic has led to a lack of familiarization preparation for students, potentially hampering their learning processes in several ways. The success of online learning is primarily based on the quality of the information systems, self-regulated learning, and intrinsic learning motivation. The severe stress amid epidemic lockdowns might trigger negative impacts on students' learning motivation and self-regulated learning. Nevertheless, studies examining the relationship between information system success, self-regulated learning, perceived stress, and intrinsic learning motivation in the context of developing countries are still scarce. The current research aims to address this gap in the literature. Participants were 303 university students. The results of second-order structural equation modelling revealed the positive direct and indirect relationships between information system success, intrinsic learning motivation, and online self-regulated learning. Besides, despite the insignificant relationships between perceived stress, intrinsic learning motivation, and online self-regulated learning, most participants in this study were found to have moderate to high stress levels. Hence, the potential adverse effect of stress on students' learning process should not be ignored. The results provide implications for educators and researchers studying online learning environments and educational psychology.

Aggregating exposures and toxicity equivalence approach into an integrated probabilistic dietary risk assessment for perchlorate, nitrate, and thiocyanate: Results from the National food monitoring study and National Food Consumption Database.

Perchlorate, nitrate, and thiocyanate, namely thyroid disrupting chemicals (TDCs), are found ubiquitously in the environment, leading to broad human exposure and primary uptake through the food web and drinking water. TDCs are all competitive inhibitors of thyroid iodide uptake activity, but limited studies have assessed the cumulative risk of dietary exposure to multiple TDCs. Thus, in this study, we analyzed the individual exposure risk from 310 food samples in 11 categories, and also assessed the cumulative health risks from TDCs for the Taiwanese population using a perchlorate equivalent concentration (PEC) approach. Consequently, this study not only demonstrated the non-carcinogenic health risks from individual exposure but also highlighted that the cumulative exposure to these TDCs may adversely affect human thyroid functioning. Vegetables, livestock, fruits, and dairy products are the most susceptible to PEC exposure. We highlighted nitrate as the main contributor to PEC exposure. Finally, controlling the overall TDC concentrations from vegetables, livestock, fruits, and dairy products is emphasized in this study. This is the first study to conduct a cumulative risk assessment of dietary exposure to TDCs using the PEC approach for the Taiwanese population through probabilistic and sensitivity analyses.

Efficacy and safety of radiofrequency ablation for primary and secondary hyperparathyroidism with or without previous parathyroidectomy: a retrospective study.

INTRODUCTION: This study aimed to investigate and compare the therapeutic efficacy and safety of ultrasound-guided radiofrequency ablation (RFA), between primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT) patients, with or without previous parathyroidectomy (PTX). SUBJECTS AND METHODS: A total of 21 patients (7 PHPT, 14 SHPT) underwent RFA for hyperparathyroidism (HPT) at Kaohsiung Chang Gung Memorial Hospital, Taiwan. Five of the 14 SHPT patients had previously received PTX. The laboratory data, volume change of each parathyroid nodule, symptomatic scores, and complications were analyzed and compared between all groups at 1 and 7 days, and at 1, 3, 6, and 12 months after RFA. RESULTS: After RFA, the volume reduction ratio (VRR) for all patients at the last follow-up was 93.76%, and clinical symptoms significantly improved. At 12 months, all PHPT patients achieved successful treatment of intact PTH (iPTH). In SHPT patients, the mean iPTH value significantly decreased 1-day post-RFA, subsequently exhibiting a transient rebound which proceeded to decrease, with 57.1% reaching successful treatment standards. SHPT patients with PTX showed a lower complication score, shorter ablation time, higher iPTH baseline and outcomes, and lower VRR, compared to patients without PTX. The serum calcium level significantly decreased to normal range in 85.7% of all patients at 12 months. Severe hypocalcemia occurred in 23.8% at 1 week, and all were corrected with calcium supplements. CONCLUSIONS: RFA demonstrates a therapeutic efficacy similar to PTX. It can thus be considered an effective alternative treatment for PHPT, SHPT, or post-PTX patients who are unsuitable for another PTX.

Residual, regrowth, and new growth of radiofrequency ablation for benign thyroid nodules of different volumes: two-year follow-up results.

INTRODUCTION: Radiofrequency ablation (RFA) is recognized as an effective technique for the treatment of benign thyroid nodules (BTNs), although the long-term results are limited. This study aimed to evaluate the residual vital volume increase, regrowth, and new growth over a 2-year period after RFA among different nodule volume groups. SUBJECTS AND METHODS: This retrospective study evaluated 135 patients with 153 BTNs who underwent ultrasound guided RFA. The BTNs were categorized into small (<10 mL), medium (10-30 mL), and large (>30 mL) according to the initial volume of BTNs prior to ablation. The volume changes of each nodule were analyzed at 1, 3, 6, 12 and 24 months after RFA. New growth was defined as the growth in volume not found in the early follow-up on ultrasonography. RESULTS: The initial ablation ratio of all BTNs was 99.67%. The mean volume reduction ratio (VRR) of BTNs was 85.53% after 2-year follow-up. The small nodule group showed a lower VRR compared to the other two groups at the 1-month follow-up, and there was no difference of VRR at the subsequent follow-ups. The incidence of residual vital volume increase was 4.58%. The overall incidence of regrowth was 3.92% and the mean timing of regrowth was 16.71 months. New growth occurred in 18.95% of patients. No further treatment was required in the majority of cases. CONCLUSION: RFA achieved a clinically relevant volume reduction in different sizes of single BTNs which persisted for at least 2 years, thereby preventing the need for retreatment.

Efficacy and safety of single-session radiofrequency ablation for intrathoracic goiter: preliminary results and short-term evaluation.

BACKGROUND: An intrathoracic goiter (ITG) is defined as a thyroid extension below the sternal notch. Compared to cervical goiters, surgery for ITG is more challenging, with a higher risk of an extracervical approach. Ultrasound (US)-guided radiofrequency ablation (RFA) is a minimally invasive treatment modality. The purpose of this study was to prospectively evaluate the safety and efficacy of RFA in patients with ITG. METHODS: From a total of 324 patients who underwent thyroid RFA at a single medical center, 15 patients (mean age 52.2 years; 73.3% female) with 16 ITGs were included and classified into three grades and three types using the cross-section imaging CT system. Clinical features and demographics, degree of extension, RFA details, goiter volume, and complications were analyzed. RESULTS: Mean pre- and post-RFA goiter volumes as measured by US were 106.62 ± 61.82 and 25.09 ± 14.22 mL respectively, with a volume reduction rate (VRR) of 75.5% (p < 0.001) at 6 months. The VRR as measured by CT/MRI was 57.0 ± 10.0% (p < 0.001) at 6 months. The intrathoracic length reduction rate at 6 months was 44.9 ± 39.2% (p = 0.001). In addition, 4 (25%) ITGs had total regression of the intrathoracic extension, with a downgrade from grade 1 to cervical goiter. Mean pre- and post-RFA symptom and cosmetic scores were 1.53 and 0.15 (p = 0.001), and 2.67 and 2.00 (p = 0.001), respectively. One patient had transient vocal cord palsy and another had perithyroidal and mediastinal hemorrhage. CONCLUSION: US-guided RFA is an effective treatment for ITG in terms of both cervical and intrathoracic reductions with an acceptable complication rate.

Nonthermal plasma-activated water: A comprehensive review of this new tool for enhanced food safety and quality.

Nonthermal plasma (NTP) is an advanced technology that has gained extensive attention because of its capacity for decontaminating food from both biological and chemical sources. Plasma-activated water (PAW), a product of NTP's reaction with water containing a rich diversity of highly reactive oxygen species (ROS) and reactive nitrogen species (RNS), is now being considered as the primary reactive chemical component in food decontamination. Despite exciting developments in this field recently, at present there is no comprehensive review specifically focusing on the comprehensive effects of PAW on food safety and quality. Although PAW applications in biological decontamination have been extensively evaluated, a complete analysis of the most recent developments in PAW technology (e.g., PAW combined with other treatments, and PAW applications in chemical degradation and as curing agents) is nevertheless lacking. Therefore, this review focuses on PAW applications for enhanced food safety (both biological and chemical safeties) according to the latest studies. Further, the subsequent effects on food quality (chemical, physical, and sensory properties) are discussed in detail. In addition, several recent trends of PAW developments, such as curing agents, thawing media, preservation of aquatic products, and the synergistic effects of PAW in combination with other traditional treatments, are also presented. Finally, this review outlines several limitations presented by PAW treatment, suggesting several future research directions and challenges that may hinder the translation of these technologies into real-life applications.

Ultrasound-Guided Moving Shot Radiofrequency Ablation of Benign Soft Tissue Neoplasm.

Background and Objective: To evaluate the effectiveness of radiofrequency ablation (RFA) using the moving-shot technique for benign soft tissue neoplasm. Materials and Methods: This retrospective study reviewed eight patients with benign soft tissue neoplasm presenting with cosmetic concerns and/or symptomatic issues who refused surgery. Six patients had vascular malformation, including four with venous malformation and two with congenital hemangioma. The other two patients had neurofibroma. All patients underwent RFA using the moving-shot technique. Imaging and clinical follow-up were performed in all patients. Follow-up image modalities included ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging. The volume reduction ratio (VRR), cosmetic scale (CS), and complications were evaluated. Results: Among the seven patients having received single-stage RFA, there were significant volume reductions between baseline (33.3 ± 21.2 cm3), midterm follow-up (5.1 ± 3.8 cm3, p = 0.020), and final follow-up (3.6 ± 1.4 cm3, p = 0.022) volumes. The VRR was 84.5 ± 9.2% at final follow-up. There were also significant improvements in the CS (from 3.71 to 1.57, p = 0.017). The remaining patient, in the process of a scheduled two-stage RFA, had a 33.8% VRR after the first RFA. The overall VRR among the eight patients was 77.5%. No complications or re-growth of the targeted lesions were noted during the follow-up period. Of the eight patients, two received RFA under local anesthesia, while the other six patients were under general anesthesia. Conclusions: RFA using the moving-shot technique is an effective, safe, and minimally invasive treatment for benign soft tissue neoplasms, achieving mass volume reduction within 6 months and significant esthetic improvement, either with local anesthesia or with general anesthesia under certain conditions.

Hyperexpression of type III secretion system of Salmonella Typhi linked to a higher cytotoxic effect to monocyte-derived macrophages by activating inflammasome.

Inflammasome activation is an important host response to infectious diseases, but the difference in inflammasome activation between typhoid fever and non-typhoidal Salmonella infection has been rarely studied. To determine whether inflammasome activation in macrophages after S. Typhi and S. Typhimurium infection is different, we measured pyroptosis, caspase-1 activation, and IL-1ß secretion in monocyte-derived macrophages infected with S. Typhi or S. Typhimurium both in vitro and ex vivo. The role of Vi capsule and virulence genes in Salmonella pathogenicity island-1 (SPI-1), belonging to type III secretion system, was also examined. S. Typhi caused more pyroptosis, caspase-1 activation, and IL-1ß production than S. Typhimurium did, predominantly within 2 h of infection, in the context of high number of infecting bacteria. Mutagenesis and complementation experiments confirmed that SPI-1 effectors but not Vi were associated with greater inflammasome activation. The expression levels of invA and hilA were significantly higher in S. Typhi than in S. Typhimurium at early log phase in SPI-1 environment. Thus, S. Typhi, relative to its non-typhoidal counterpart, S. Typhimurium, induces greater SPI-1-dependent inflammasome activation in monocyte-derived macrophages. This finding may explain why S. Typhi causes a hyperinflammatory state at bacteremic stage in typhoid fever.

Efficacy and safety of single-session radiofrequency ablation for benign thyroid nodules of different sizes: a retrospective study.

PURPOSE: To compare the effectiveness of radiofrequency ablation (RFA) for benign thyroid nodules (BTNs) among groups presenting with different nodule volumes. MATERIALS AND METHODS: This retrospective study evaluated 186 patients with BTNs who underwent ultrasound guided RFA treatment. The BTNs were categorized into small (≤10 ml); medium (10-30 ml); and large (>30 ml) according to the initial volume of BTNs before ablation. The RFA procedures were performed using the moving shot technique. The volume reduction ratio (VRR) of each nodule, cosmetic score, symptomatic score, and complications were analyzed at 1, 3, and 6 months after RFA treatment and the three groups compared. RESULTS: At 1-month follow-up, the large nodules group showed significantly greater VRR compared to the other two groups (small, 31.88% ± 37.91; medium, 38.9% ± 19.18; large, 48.7% ± 20.43, p = .03). At 6-month follow-up, there was no significant difference of VRR among the three groups (small, 74.6% ± 20.92; medium, 68.1% ± 17.07; large, 75.0% ± 11.88). The most common presented complication was temporary vocal palsy (6 patients; small, n = 1; medium, n = 1; large, n = 3). Additionally, one skin burn, one hematoma, and one nodular rupture of BTNs occurred after the procedures. The complication rate of the large nodules group was highest among the three groups and showed a considerable difference (8 patients; small, n = 1, 2.1%; medium, n = 2, 4.5%; large, n = 5, 11.4%, p = .061). CONCLUSIONS: RFA was confirmed as effective in patients with large thyroid nodule (>30ml), with therapeutic efficacy similar to patients with smaller thyroid nodules.

Alteration of brain temperature and systemic inflammation in Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) is known to be related to various factors, including neuroinflammation, increased oxidative stress, and brain temperature alteration. We aimed to evaluate the correlation between these factors using diffusion-weighted imaging (DWI) thermometry and blood tests of systemic inflammation. METHODS: From July 2012 to Jun 2017, 103 patients with PD (44 men and 59 women; mean age, 60.43 ± 9.12 years) and 106 sex- and age-matched healthy volunteers (48 men and 58 women; mean age, 58.16 ± 8.45 years) retrospectively underwent magnetic resonance DWI thermometry to estimate brain intraventricular temperature (Tv). Subjects were divided into three subgroups in light of their ages. The tested inflammatory markers included plasma nuclear DNA, mitochondrial DNA, apoptotic leukocytes, and serum adhesion molecules. The correlations among the Tv values, clinical severity, and systemic inflammatory markers were then calculated. RESULTS: The PD patients did not show a natural trend of decline in Tv with age. Comparisons among the different age groups revealed that the younger PD subjects had significantly lower Tv values than the younger controls, but the older subjects had no significant group differences. Overall, the PD patients exhibited lower Tv values than the controls, as well as increased oxidative stress. The brain temperature showed positive correlations with inflammatory markers, including plasma nuclear DNA and L-selectin levels, in all the subjects. CONCLUSIONS: Possible pathophysiological correlations between systemic inflammation and brain temperature were indicated by the results of this study, a finding which may aid us in investigating the underlying pathogenesis of PD.

Reduced lateral occipital gray matter volume is associated with physical frailty and cognitive impairment in Parkinson's disease.

INTRODUCTION: To investigate the structural changes of the brain that correlate with physical frailty and cognitive impairments in Parkinson's disease (PD) patients. METHODS: Sixty-one PD patients and 59 age- and sex-matched healthy controls were enrolled. For each participant, a frailty assessment using Fried's criteria and comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted, and structural brain MR images were acquired for voxel-based morphometric analysis. The neuropsychological testing includes various tests in these five domains: attention, executive, memory, speech and language, and visuospatial functions. Exploratory group-wise comparisons of gray matter volume (GMV) in the PD patients and controls were conducted. Voxel-wise multiple linear regression analyses were conducted for physical frailty-related and cognitive impairment-related GMV changes in the PD patients. Voxel-wise multiple linear regressions were also performed with the five cognitive domains separated using the same model. RESULTS: The PD patients exhibited diffuse GMV reductions in comparison to the controls. In the PD patients, physical frailty-related decreases in GMV were observed in the bilateral frontal and occipital cortices, while cognitive impairment-related decreases in GMV were observed in the bilateral frontal, occipital, and temporal cortices. These regions overlap in the lateral occipital cortex. After the five domains of cognitive functions were analyzed separately, physical frailty-related decreases in GMV still overlap in lateral occipital cortices with every domain of cognitive impairment-related decreases in GMV. CONCLUSION: Reduced GMV in the lateral occipital cortex is associated with cognitive impairment and physical frailty in PD patients. KEY POINTS: • Physical frailty in PD was associated with decreased GMV in the frontal and occipital cortices, while cognitive impairment was associated with decreased GMV in the frontal, temporal, and occipital cortices. • Physical frailty and cognitive impairment were both associated with decreased GMV in the lateral occipital cortex, which is part of the ventral object-based visual pathway. • Decreased GMV in the lateral occipital cortex may serve as a potential imaging biomarker for physical frailty and cognitive impairment in PD.

Evaluation of Outcomes following Radiofrequency Ablation for Treatment of Parotid Tail Warthin Tumors.

PURPOSE: To evaluate efficacy and safety of radiofrequency (RF) ablation for parotid Warthin tumor. MATERIALS AND METHODS: From September 2016 to August 2017, 7 consecutive patients with biopsy-proven parotid Warthin tumors who did not undergo surgery presented with symptoms or cosmetic concerns and underwent US-guided percutaneous RF ablation treatment. RF ablation procedures were performed using the moving shot technique. US, contrast-enhanced CT, or MR imaging was performed 6-12 months after each procedure. Complications and cosmetic scale improvement after RF ablation were also evaluated. RESULTS: There was a significant reduction in mean tumor volume from 14.6 cm3 ± 13.1 (range, 1.9-35.5 cm3) to 0.8 cm3 ± 0.5 (range, 0.2-1.54 cm3) and a mean cosmetic scale improvement (from 4 to 1) on imaging studies 6-12 months after RF ablation compared with before RF ablation (P < .05). Volume reduction ratios at 1-2 months, 5-6 months, and 10-12 months after RF ablation were 51.2% ± 18.1%, 87.8% ± 10.6%, and 94.3% ± 2.0%. There was no facial nerve injury. One patient with parotitis and hematoma recovered in 1 week. CONCLUSIONS: RF ablation using the moving shot technique could be an effective and safe alternative treatment for parotid tail Warthin tumors in patients unsuitable for or unwilling to undergo surgical resection.

Interaction of systemic oxidative stress and mesial temporal network degeneration in Parkinson's disease with and without cognitive impairment.

BACKGROUND: To identify the vulnerable areas associated with systemic oxidative stress and further disruption of these vulnerable areas by measuring the associated morphology and functional network alterations in Parkinson's disease (PD) patients with and without cognitive impairment. METHODS: This prospective study was approved by the institutional review board of KCGMH, and written informed consent was obtained. Between December 2010 and May 2015, 41 PD patients with different levels of cognitive functions and 29 healthy volunteers underwent peripheral blood sampling to quantify systemic oxidative stress, as well as T1W volumetric and resting state functional MRI (rs-fMRI) scans. Rs-fMRI was used to derive the healthy intrinsic connectivity patterns seeded by the vulnerable areas associated with any of the significant oxidative stress markers. The two groups were compared in terms of the functional connectivity correlation coefficient (fc-CC) and gray matter volume (GMV) of the network seeded by the vulnerable areas. RESULTS: The levels of oxidative stress markers, including leukocyte apoptosis and adhesion molecules, were significantly higher in the PD group. Using whole-brain VBM-based correlation analysis, the bilateral mesial temporal lobes (MTLs) were identified as the most vulnerable areas associated with lymphocyte apoptosis (P < 0.005). We found that the MTL network of healthy subjects resembled the PD-associated atrophy pattern. Furthermore, reduced fc-CC and GMV were further associated with the aggravated cognitive impairment. CONCLUSION: The MTLs are the vulnerable areas associated with peripheral lymphocyte infiltration, and disruptions of the MTL functional network in both architecture and functional connectivity might result in cognitive impairments in Parkinson's disease.

Site-Selective Functionalization of Flagellin by Steric Self-Protection: A Strategy To Facilitate Flagellin as a Self-Adjuvanting Carrier in Conjugate Vaccine.

Flagellin (FliC) can act as a carrier protein in the preparation of conjugate vaccines to elicit a T-cell-dependent immune response and as an intrinsic adjuvant to activate the toll-like receptor 5 (TLR5) to enhance vaccine potency. To enable the use of FliC as a self-adjuvanting carrier, an effective method for site-selective modification (SSM) of pertinent amino-acid residues in the D2 and D3 domains of FliC is explored without excessive modification of the D0 and D1 domains, which are responsible for activating and binding with TLR5. In highly concentrated Na2 SO4 solution, FliC monomers form flagellar filaments, in which the D0 and D1 domains are situated inside the tubular structure. Thus, the lysine residues (K219, K224, K324, and K331) in the D2 and D3 domains of flagellin are selectively modified by a diazo-transfer reaction with imidazole-1-sulfonyl azide. The sites with azido modification are confirmed by MALDI-TOF-MS, ESI-TOF-MS, and LC-MS/MS analyses along with label-free quantitation. The azido-modified filament dissolves to give FliC monomers, which can conjugate with alkyne-hinged saccharides by the click reaction. Transmission electron microscopy imaging, dynamic light scattering measurements, and the secreted embryonic alkaline phosphatase reporter assay indicate that the modified FliC monomers retain the ability either to bind with TLR5 or to reassemble into filaments. Overall, this study establishes a feasible method for the SSM of FliC by steric self-protection of the D0 and D1 domains.

Extraction of large-scale structural covariance networks from grey matter volume for Parkinson's disease classification.

OBJECTIVES: To identify disease-related spatial covariance patterns of grey matter volume as an aid in the classification of Parkinson's disease (PD). METHODS: Seventy structural covariance networks (SCNs) based on grey matter volume covariance patterns were defined using independent component analysis with T1-weighted structural MRI scans (discovery sample, 70 PD patients and 70 healthy controls). An image-based classifier was constructed from SCNs using a multiple logistic regression analysis with a leave-one-out cross-validation-based feature selection scheme. A validation sample (26 PD patients and 26 healthy controls) was further collected to evaluate the generalization ability of the constructed classifier. RESULTS: In the discovery sample, 13 SCNs, including the cerebellum, anterior temporal poles, parahippocampal gyrus, parietal operculum, occipital lobes, supramarginal gyri, superior parietal lobes, paracingulate gyri and precentral gyri, had higher classification performance for PD. In the validation sample, the classifier had moderate generalization ability, with a mean sensitivity of 81%, specificity of 69% and overall accuracy of 75%. Furthermore, certain individual SCNs were also associated with disease severity. CONCLUSIONS: Although not applicable for routine care at present, our results provide empirical evidence that disease-specific, large-scale structural networks can provide a foundation for the further improvement of diagnostic MRI in movement disorders. KEY POINTS: • Disease-specific, large-scale SCNs can be identified from structural MRI. • A new network-based framework for PD classification is proposed. • An SCN-based classifier had moderate generalization ability in PD classification. • The selected SCNs provide valuable functional information regarding PD patients.

Reduced gray matter volume and respiratory dysfunction in Parkinson's disease: a voxel-based morphometry study.

BACKGROUND: The respiratory dysfunction of patients with Parkinson's disease (PD) has drawn increasing attention. This study evaluated the relationship between gray matter volume (GMV), as determined by voxel-based morphometry (VBM), and respiratory dysfunction in patients with PD and correlated it with systemic inflammatory markers. METHODS: Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 25 PD patients with abnormal pulmonary function (13 men, 12 women; mean age: 62.9 ± 10.8 years) and, for comparison, on 25 sex- and age-matched PD patients with normal pulmonary function (14 men, 11 women; mean age: 62.3 ± 6.9 years). Inflammatory markers were determined by flow cytometry. The differences and correlations in regional GMV, clinical severity and inflammatory markers were determined after adjusting for age, gender and total intracranial volume (TIV). RESULTS: Compared with the normal pulmonary function group, the abnormal pulmonary function group had smaller GMV in several brain regions, including the left parahippocampal formation, right fusiform gyrus, right cerebellum crus, and left postcentral gyri. Forced expiratory volume in 1 s (FEV1) and maximal expiratory flow after expiration of 50% of forced vital capacity (MEF50) were positively correlated with regional GMV. There were no significant differences in the level of serum inflammatory markers between two groups. CONCLUSION: Our findings suggested that involvement of the central autonomic network and GM loss may underlie the respiratory dysfunction in PD patients.

White matter damage and systemic inflammation in Parkinson's disease.

BACKGROUND: Systemic inflammation and white matter (WM) alterations have been noted as effects of Parkinson's disease (PD). This study sought to evaluate WM integrity in PD patients using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation. METHODS: Sixty-six patients with PD (23 men and 43 women) and 67 healthy volunteers (29 men and 38 women) underwent blood sampling to quantify inflammatory markers and DTI scans to determine fiber integrity. The inflammatory markers included leukocyte apoptosis, as well as cellular and serum adhesion molecules, in each peripheral blood sample. DTI-related indices [including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] were derived from DTI scans. The resulting FA maps were compared using voxel-based statistics to determine differences between the PD and control groups. The differences in the DTI indices, clinical severity, and inflammatory markers were correlated. RESULTS: Exploratory group-wise comparison between the two groups revealed that the PD patients exhibited extensive DTI index differences. Low FA accompanied by high RD and MD, without significant differences in AD, suggesting a demyelination process, were found in the parietal, occipital, cerebellar, and insular WM of the PD patients. The declined DTI indices were significantly correlated with increased clinical disease severity, adhesion molecules, and leukocyte apoptosis. CONCLUSIONS: Patients with PD experience WM integrity damage in vulnerable regions, and these impairments are associated with increased disease severity and systemic inflammation. The possible interactions among them may represent variant neuronal injuries and their consequent processes in PD.