Sophie de Grouchy's Political Thought in the Letters on Sympathy (1798).

This article proposes a reading of Sophie de Grouchy's moral, political, and economic thought as embedded in the tradition of natural jurisprudence, adapted to the context of the French First Republic. A close reading of her French translation of Adam Smith's Theory of Moral Sentiment and her eight Letters on Sympathy confirms that there are points to be made by reading her works in the context of the language of early modern natural law. This sheds light on the important question of how to read revolutionary republicanism emanating from multiple traditions other than the neo-Roman discourse of non-domination.

Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using MRI indices from diffusion tensor imaging.

OBJECTIVE: The glymphatic system is a glial-based perivascular network that promotes brain metabolic waste clearance. Glymphatic system dysfunction has been observed in both multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), indicating the role of neuroinflammation in the glymphatic system. However, little is known about how the two diseases differently affect the human glymphatic system. The present study aims to evaluate the diffusion MRI-based measures of the glymphatic system by contrasting MS and NMOSD. METHODS: This prospective study included 63 patients with NMOSD (n = 21) and MS (n = 42) who underwent DTI. The fractional volume of extracellular-free water (FW) and an index of diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) were used as indirect indicators of water diffusivity in the interstitial extracellular and perivenous spaces of white matter, respectively. Age and EDSS scores were adjusted. RESULTS: Using Bayesian hypothesis testing, we show that the present data substantially favor the null model of no differences between MS and NMOSD for the diffusion MRI-based measures of the glymphatic system. The inclusion Bayes factor (BF10) of model-averaged probabilities of the group (MS, NMOSD) was 0.280 for FW and 0.236 for the ALPS index. CONCLUSION: Together, these findings suggest that glymphatic alteration associated with MS and NMOSD might be similar and common as an eventual result, albeit the disease etiologies differ. PRACTITIONER POINTS: Previous literature indicates important glymphatic system alteration in MS and NMOSD. We explore the difference between MS and NMOSD using diffusion MRI-based measures of the glymphatic system. We show support for the null hypothesis of no difference between MS and NMOSD. This suggests that glymphatic alteration associated with MS and NMOSD might be similar and common etiology.

Factors associated with the development of exudation in treatment-naive eyes with nonexudative macular neovascularization.

PURPOSE: To identify the predictive factors for development of exudation in patients with treatment-naïve nonexudative macular neovascularization (MNV). METHODS: We retrospectively analyzed 61 treatment-naïve patients with nonexudative MNV who had not received treatment for nonexudative MNV before the exudation developed. Baseline characteristics and changes in MNV were evaluated using multivariate modeling to determine the potential risk factors for exudative conversion. RESULTS: Exudation development was identified in 31.1% (19/61 eyes) of the study eyes during the 46.2 ± 8.2-month mean follow-up period. The mean period of development of exudation from the baseline was 21.5 ± 6.7 months. Multivariate Cox regression analysis identified that older age (hazard ratio [HR] of 1.380, 95% confidence interval [CI] 1.129-1.688, P = 0.008), larger MNV area at baseline (HR of 1.715, CI 1.288-2.308; P = 0.006), increase of MNV area by doubling (HR of 4.992, CI 1.932-9.246; P = 0.002), and retinal pigment epithelium (RPE) elevation more than 100 µm (HR of 1.017, CI 1.006-1.233; P = 0.015) were associated with increased risk of the development of exudation. CONCLUSION: Older age, larger MNV area, increasing MNV area, and higher RPE elevation were associated with an increased risk of exudative conversion in patients with treatment-naïve nonexudative MNV. Identifying these risk factors may be helpful in establishing treatment strategies and monitoring patients.

DNA and Nanomaterials: A Functional Combination for DNA Sensing.

Recent decades have experienced tough situations due to the lack of reliable diagnostic facilities. The most recent cases occurred during the pandemic, where researchers observed the lack of diagnostic facilities with precision. Microorganisms and viral disease's ability to escape diagnosis has been a global challenge. DNA always has been a unique moiety with a strong and precise base-paired structure. DNA in human and foreign particles makes identification possible through base pairing. Since then, researchers have focused heavily on designing diagnostic assays targeting DNA in particular. Moreover, DNA nanotechnology has contributed vastly to designing composite nanomaterials by combining DNA/nucleic acids with functional nanomaterials and inorganic nanoparticles exploiting their physicochemical properties. These nanomaterials often exhibit unique or enhanced properties due to the synergistic activity of the many components. The capabilities of DNA and additional nanomaterials have shown the combination of robust and advanced tailoring of biosensors. Preceding findings state that the conventional strategies have exhibited certain limitations such as a low range of target detection, less biodegradability, subordinate half-life, and high susceptibility to microenvironments; however, a DNA-nanomaterial-based biosensor has overcome these limitations meaningfully. Additionally, the unique properties of nucleic acids have been studied extensively due to their high signal conduction abilities. Here, we review recent studies on DNA-nanomaterial-based biosensors, their mechanism of action, and improved/updated strategies in vivo and in situ. Furthermore, this review highlights the recent methodologies on DNA utilization to exploit the interfacial properties of nanomaterials in DNA sensing. Lastly, the review concludes with the limitations/challenges and future directions.

Cytokine and Chemokine Profiles in Acute Severe Fever with Thrombocytopenia Syndrome and Scrub Typhus in South Korea.

In East Asia, severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus, which are common endemic tick- and mite-mediated diseases sharing common clinical manifestations, are becoming public health concerns. However, there are limited data on the comparative immunopathogenesis between the two diseases. We compared the cytokine profiles of SFTS and scrub typhus to further elucidate immune responses that occur during the disease courses. We prospectively enrolled 44 patients with confirmed SFTS and 49 patients with scrub typhus from July 2015 to December 2020. In addition, 10 healthy volunteers were enrolled as healthy controls. A cytometric bead array was used to analyze plasma samples for 16 cytokines. A total of 68 plasma samples, including 31 (45.6%) from patients with SFTS and 37 (54.4%) from patients with scrub typhus, were available for cytokine measurement. There were three cytokine expression patterns: increased levels in both SFTS and scrub typhus (interleukin 6 [IL-6], IL-10, interferon gamma induced protein 10 [IP-10], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), highest levels in SFTS (interferon alpha [IFN-α], IFN-γ, granulocyte-CSF [G-CSF], monocyte chemotactic protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], and IL-8), and distinct levels in scrub typhus (IL-12p40, tumor necrosis factor alpha [TNFα], IL-1ß, regulated on activation and normally T-cell expressed and secreted [RANTES], IL-17A, and vascular endothelial growth factor [VEGF]). Although patients with acute SFTS and scrub typhus exhibited partly shared expression patterns of cytokines related to disease severity, the different profiles of cytokines and chemokines might contribute to higher mortality in SFTS than in scrub typhus. Discrete patterns of helper T cell-related cytokines and VEGF might reflect differences in CD4 T-cell responses and vascular damage between these diseases.

Bidirectional connectivity alterations in schizophrenia: a multivariate, machine-learning approach.

Objective: It is well known that altered functional connectivity is a robust neuroimaging marker of schizophrenia. However, there is inconsistency in the direction of alterations, i.e., increased or decreased connectivity. In this study, we aimed to determine the direction of the connectivity alteration associated with schizophrenia using a multivariate, data-driven approach. Methods: Resting-state functional magnetic resonance imaging data were acquired from 109 individuals with schizophrenia and 120 controls across two openly available datasets. A whole-brain resting-state functional connectivity (rsFC) matrix was computed for each individual. A modified connectome-based predictive model (CPM) with a support vector machine (SVM) was used to classify patients and controls. We conducted a series of multivariate classification analyses using three different feature sets, increased, decreased, and both increased and decreased rsFC. Results: For both datasets, combining information from both increased and decreased rsFC substantially improved prediction accuracy (Dataset 1: accuracy = 70.2%, permutation p = 0.001; Dataset 2: accuracy = 64.4%, permutation p = 0.003). When tested across datasets, the prediction model using decreased rsFC performed best. The identified predictive features of decreased rsFC were distributed mostly in the motor network for both datasets. Conclusion: These findings suggest that bidirectional alterations in rsFC are distributed in schizophrenia patients, with the pattern of decreased rsFC being more similar across different populations.

Gender differences in patient experience in idiopathic inflammatory myopathies: Sub analysis from the COVAD dataset.

OBJECTIVES: We aimed to investigate gender-based differences in idiopathic inflammatory myopathies (IIMs), with a particular focus on patient-reported outcomes, utilizing data obtained through the international COVID-19 vaccination in autoimmune disease (COVAD) e-survey. METHODS: Patient-reported outcomes including fatigue, pain, and physical function were extracted from the COVAD database and compared between genders, adjusting for demographics and IIM subgroups by multivariable analysis. Inclusion body myositis (IBM) was analysed separately because of substantial differences in outcomes. RESULTS: 1197 complete responses from patients with IIMs as of 31 August 2021 were analysed. Seventy percent were women. Women were younger (58 [48-68] vs. 69 [58-75] years old, median [IQR], p < 0.001) and more likely to suffer from autoimmune multimorbidity, defined as three or more autoimmune diseases in an individual patient (11.4% vs. 2.8%, p < 0.001). In non-IBM IIMs, fatigue visual analogue scale scores were higher in women (5 [3-7] vs. 4 [2-6], median [IQR], p = 0.004), whereas no significant gender-based differences were noted in IBM. Multivariable analysis in non-IBM IIMs revealed women, residence in high-income countries, overlap myositis, and autoimmune multimorbidity were independently associated with increased fatigue. CONCLUSIONS: Women with IIMs suffer from autoimmune multimorbidity and experience increased fatigue compared to men.

Structural disconnection is associated with disability in the neuromyelitis optica spectrum disorder.

OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system. Accumulating evidence suggests there is a distinct pattern of brain lesions characteristic of NMOSD, and brain MRI has potential prognostic implications. However, the question of how the brain lesions in NMOSD are associated with its distinct clinical course remains incompletely understood. Here, we aimed to investigate the association between neurological impairment and brain lesions via brain structural disconnection. METHODS: Twenty patients were diagnosed with NMOSD according to the 2015 International Panel for NMO Diagnosis criteria. The white matter lesions were manually drawn section by section. Whole-brain structural disconnection was estimated, and connectome-based predictive modeling (CPM) was used to estimate the patient's Expanded Disability Status Scale score (EDSS) from their disconnection severity matrix. Furthermore, correlational tractography was performed to assess the fractional anisotropy (FA) and axial diffusivity (AD) of white matter fibers, which negatively correlated with the EDSS score. RESULTS: CPM successfully predicted the EDSS using the disconnection severity matrix (r = 0.506, p = 0.028; q2 = 0.274). Among the important edges in the prediction process, the majority of edges connected the motor to the frontoparietal network. Correlational tractography identified a decreased FA and AD value according to EDSS scores in periependymal white matter tracts. DISCUSSION: Structural disconnection-based predictive modeling and local connectome analysis showed that frontoparietal and periependymal white matter disconnection is predictive and associated with the EDSS score of NMOSD patients.

Progressive reduction in basal ganglia explains and predicts cerebral structural alteration in type 2 diabetes.

Type 2 diabetes is consistently reported to be associated with reduced gray matter, mainly in the cortical-striatal-limbic networks. However, little is known about how the progression of diabetes affects cerebral gray matter. To investigate, we collected 543 age- and sex-matched participants of nondiabetes, prediabetes, and diabetes. Voxel-based morphometry using a linear trend model was performed to reveal brain regions associated with disease progression. The Granger causal network of structural covariance was used to assess the causal relationships of brain structural alterations according to disease progression. Multivariate pattern analysis was applied for the stage-specific predictions of hyperglycemia. We detected a linear trend of gray matter volume reduction in the basal ganglia with disease progression (P < 0.05, FWER corrected), which caused a reduction in bilateral temporal gyri, frontal pole, parahippocampus, and bilateral posterior cingulate/precuneus volumes. In addition, the gray matter pattern of the basal ganglia could predict patients with diabetes (accuracy 60.12%, p = 0.002). In conclusion, the basal ganglia is the brain area with progressive gray matter reduction as diabetes progress. The reduced volume in the basal ganglia causes widespread gray matter reductions throughout diabetes progression. These findings indicate that the basal ganglia play a key role in diabetes by affecting the cortical-striatal-limbic network.

Cost-effectiveness analysis of 3 radiation treatment strategies for patients with multiple brain metastases.

Background: Patients diagnosed with multiple brain metastases often survive for less than 2 years, and clinicians must carefully evaluate the impact of interventions on quality of life. Three types of radiation treatment are widely accepted for patients with multiple brain metastases: Whole brain radiation therapy (WBRT), hippocampal avoidance whole-brain radiation therapy (HA-WBRT), and stereotactic radiosurgery (SRS). WBRT, the standard option, is less costly than its newer alternatives but causes more severe adverse effects such as memory loss. To determine whether the cost-effectiveness ratio of HA-WBRT and SRS are superior to WBRT, we used published data to simulate cases of multiple brain metastases. Methods: We designed a Markov model using data from previously published studies to simulate the disease course of patients with 5 to 15 brain metastases and determine the cost-effectiveness of HA-WBRT and SRS relative to WBRT. Incremental cost-effectiveness ratios (ICERs) were calculated and compared against a willingness-to-pay threshold of $100 000 per quality-adjusted life year. Results: SRS met the threshold for cost-effectiveness, with ICERs ranging $41 198-$54 852 for patients with 5 to 15 brain metastases; however, HA-WBRT was not cost-effective, with an ICER of $163 915 for all simulated patients. Model results were robust to sensitivity analyses. Conclusions: We propose that SRS, but not HA-WBRT, should be offered to patients with multiple brain metastases as a treatment alternative to standard WBRT. Incorporating these findings into clinical practice will help promote patient-centered care and decrease national healthcare expenditures, thereby addressing issues around health equity and access to care.

Growth Increase in the Herbaceous Plant Centella asiatica by the Plant Growth-Promoting Rhizobacteria Priestia megaterium HyangYak-01.

Centella asiatica is a traditional herbaceous plant with numerous beneficial effects, widely known for its medicinal and cosmetic applications. Maximizing its growth can lead to beneficial effects, by focusing on the use of its active compounds. The use of plant growth-promoting rhizobacteria (PGPR) is known to be an alternative to chemical fertilizers. In this study, we used the PGPR Priestia megaterium HY-01 to increase the yield of C. asiatica. In vitro assays showed that HY-01 exhibited plant growth-promoting activities (IAA production, denitrification, phosphate solubilization, and urease activity). Genomic analyses also showed that the strain has plant growth-promoting-related genes that corroborate with the different PGP activities found in the assays. This strain was subsequently used in field experiments to test its effectiveness on the growth of C. asiatica. After four months of application, leaf and root samples were collected to measure the plant growth rate. Moreover, we checked the rhizosphere microbiome between the treated and non-treated plots. Our results suggest that treatment with Hyang-yak-01 not only improved the growth of C. asiatica (leaf length, leaf weight, leaf width, root length, root width, and chlorophyll content) but also influenced the rhizosphere microbiome. Biodiversity was higher in the treated group, and the bacterial composition was also different from the control group.

High fatigue scores in patients with idiopathic inflammatory myopathies: a multigroup comparative study from the COVAD e-survey.

Idiopathic inflammatory myopathies (IIMs) confer a significant risk of disability and poor quality of life, though fatigue, an important contributing factor, remains under-reported in these individuals. We aimed to compare and analyze differences in visual analog scale (VAS) scores (0-10 cm) for fatigue (VAS-F) in patients with IIMs, non-IIM systemic autoimmune diseases (SAIDs), and healthy controls (HCs). We performed a cross-sectional analysis of the data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) international patient self-reported e-survey. The COVAD survey was circulated from December 2020 to August 2021, and details including demographics, COVID-19 history, vaccination details, SAID details, global health, and functional status were collected from adult patients having received at least one COVID-19 vaccine dose. Fatigue experienced 1 week prior to survey completion was assessed using a single-item 10 cm VAS. Determinants of fatigue were analyzed in regression models. Six thousand nine hundred and eighty-eight respondents (mean age 43.8 years, 72% female; 55% White) were included in the analysis. The overall VAS-F score was 3 (IQR 1-6). Patients with IIMs had similar fatigue scores (5, IQR 3-7) to non-IIM SAIDs [5 (IQR 2-7)], but higher compared to HCs (2, IQR 1-5; P < 0.001), regardless of disease activity. In adjusted analysis, higher VAS-F scores were seen in females (reference female; coefficient -0.17; 95%CI -0.21 to -13; P < 0.001) and Caucasians (reference Caucasians; coefficient -0.22; 95%CI -0.30 to -0.14; P < 0.001 for Asians and coefficient -0.08; 95%CI -0.13 to 0.30; P = 0.003 for Hispanics) in our cohort. Our study found that patients with IIMs exhibit considerable fatigue, similar to other SAIDs and higher than healthy individuals. Women and Caucasians experience greater fatigue scores, allowing identification of stratified groups for optimized multidisciplinary care and improve outcomes such as quality of life.

Ecoinformatic Analysis of the Gut Ecological Diversity of Wild and Captive Long-Tailed Gorals Using Improved ITS2 Region Primers to Support Their Conservation.

Ex situ conservation is used to protect endangered wildlife. As captive and wild long-tailed gorals are known to be similar, individuals under ex situ conservation can be reintroduced into nature. However, there is no appropriate indicator to evaluate them. Here, we amplified the internal transcribed spacer 2 (ITS2) region and compared the gut ecological information (eco-information) of captive and wild long-tailed gorals. We validated the existing ITS86F and ITS4 universal primers using reference sequences of the National Center for Biotechnology Information (NCBI) and improved their matching rates. We compared the gut eco-information of captive and wild long-tailed gorals obtained through experiments using the improved primer pair and found that the gut ecological diversity of captive gorals was low. Based on this, we suggested that the gut eco-information can be used as an evaluation index before reintroducing captive long-tailed gorals. Furthermore, we identified four plant types from the gut eco-information of wild long-tailed gorals, which can be the additional food sources to enhance the reduced intestinal ecological diversity of the captive animals.

Association Between Pulmonary Hypertension and Its Effect on 30-Day Mortality, Readmission, and Cost After Transcatheter Aortic Valve Replacement: A Multicenter Study.

Background Pulmonary hypertension (PH) is commonly seen in patients with severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) has been shown to improve PH, however, its impact on clinical outcomes and cost remains unclear. Methods We did a multicenter, retrospective analysis of patients undergoing TAVR in our system between December 2012 to November 2020. The initial sample size was 1356. We excluded patients with prior history of heart failure, with a left ventricular ejection fraction of 40% or less, and patients who had active symptoms of heart failure within two weeks of the procedure. Patients were divided into four groups based on their pulmonary pressures, using right ventricular systolic pressure (RVSP) as a surrogate for PH. Groups included patients with normal pulmonary pressures (<35mmHg), mild (35-45mmHg) moderate (46-60mmHg), and severe PH (>60mmHg). Primary outcomes included 30-day mortality and readmission. Secondary outcomes included length of ICU stay and cost of admission. We used Chi-square and T-tests for demographic analysis of categorical continuous variables respectively. Adjusted regression was used for the reliability of correlation between variables. Multivariate analysis was used for final outcomes. Results Final sample size was 474. Average age was 78.9 years (SD: 8.2, 53% Male). Thirty-one percent (n=150) had normal pulmonary pressures, 33% (n=156) had mild PH, 25% (n=122) had moderate and 10% (n=46) had severe PH. Patients with history of hypertension (p-value<0.001), diabetes (p-value<0.001), chronic lung disease (p-value=0.006) and those on supplemental oxygen (p-value=0.046), had significantly higher proportion of patients with moderate and severe PH. We found significantly higher odds of 30-day mortality in patients with severe PH (OR: 6.77, CI: 1.09-41.98: p-value 0.04) compared with normal or mild PH. There was no significant difference in 30-day readmission (p-value=0.859) between the four groups. Cost did not change with severity of PH (Avg: $261,075: p-value=0.810). Patients with severe PH spent a significantly higher number of hours in ICU, compared with the other three groups (Mean: 18.2, p=value <0.001). Conclusions Severe pulmonary hypertension significantly increased the odds of 30-day mortality and ICU stay in TAVR patients. We did not see any significant difference in 30-day readmission and cost of admission, based on PH severity.

Multivariate prediction of long COVID headache in adolescents using gray matter structural MRI features.

Objective: Headache is among the most frequent symptoms after coronavirus disease 2019 (COVID-19), so-called long COVID syndrome. Although distinct brain changes have been reported in patients with long COVID, such reported brain changes have not been used for predictions and interpretations in a multivariate manner. In this study, we applied machine learning to assess whether individual adolescents with long COVID can be accurately distinguished from those with primary headaches. Methods: Twenty-three adolescents with long COVID headaches with the persistence of headache for at least 3 months and 23 age- and sex-matched adolescents with primary headaches (migraine, new daily persistent headache, and tension-type headache) were enrolled. Multivoxel pattern analysis (MVPA) was applied for disorder-specific predictions of headache etiology based on individual brain structural MRI. In addition, connectome-based predictive modeling (CPM) was also performed using a structural covariance network. Results: MVPA correctly classified long COVID patients from primary headache patients, with an area under the curve of 0.73 (accuracy = 63.4%; permutation p = 0.001). The discriminating GM patterns exhibited lower classification weights for long COVID in the orbitofrontal and medial temporal lobes. The CPM using the structural covariance network achieved an area under the curve of 0.81 (accuracy = 69.5%; permutation p = 0.005). The edges that classified long COVID patients from primary headache were mainly comprising thalamic connections. Conclusion: The results suggest the potential value of structural MRI-based features for classifying long COVID headaches from primary headaches. The identified features suggest that the distinct gray matter changes in the orbitofrontal and medial temporal lobes occurring after COVID, as well as altered thalamic connectivity, are predictive of headache etiology.

Immune Responses After Vaccination With Primary 2-Dose ChAdOx1 Plus a Booster of BNT162b2 or Vaccination With Primary 2-Dose BNT162b2 Plus a Booster of BNT162b2 and the Occurrence of Omicron Breakthrough Infection.

BACKGROUND: Before the omicron era, health care workers were usually vaccinated with either the primary 2-dose ChAdOx1 nCoV-19 (Oxford-AstraZeneca) series plus a booster dose of BNT162b2 (Pfizer-BioNTech) (CCB group) or the primary 2-dose BNT162b2 series plus a booster dose of BNT162b2 (BBB group) in Korea. METHODS: The two groups were compared using quantification of the surrogate virus neutralization test for wild type severe acute respiratory syndrome coronavirus 2 (SVNT-WT), the omicron variant (SVNT-O), spike-specific IgG, and interferon-gamma (IFN-γ), as well as the omicron breakthrough infection cases. RESULTS: There were 113 participants enrolled in the CCB group and 51 enrolled in the BBB group. Before and after booster vaccination, the median SVNT-WT and SVNT-O values were lower in the CCB (SVNT-WT [before-after]: 72.02-97.61%, SVNT-O: 15.18-42.29%) group than in the BBB group (SVNT-WT: 89.19-98.11%, SVNT-O: 23.58-68.56%; all P < 0.001). Although the median IgG concentrations were different between the CCB and BBB groups after the primary series (2.677 vs. 4.700 AU/mL, respectively, P < 0.001), they were not different between the two groups after the booster vaccination (7.246 vs. 7.979 AU/mL, respectively, P = 0.108). In addition, the median IFN-γ concentration was higher in the BBB group than in the CCB group (550.5 and 387.5 mIU/mL, respectively, P = 0.014). There was also a difference in the cumulative incidence curves over time (CCB group 50.0% vs. BBB group 41.8%; P = 0.045), indicating that breakthrough infection occurred faster in the CCB group. CONCLUSION: The cellular and humoral immune responses were low in the CCB group so that the breakthrough infection occurred faster in the CCB group than in the BBB group.

Hypoalbuminemia and Albumin Replacement during Extracorporeal Membrane Oxygenation in Patients with Cardiogenic Shock.

Background: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with cardiorespiratory failure. The serum albumin level is an important prognostic marker in critically ill patients. We evaluated the efficacy of using pre-ECMO serum albumin levels to predict 30-day mortality in patients with cardiogenic shock (CS) who underwent venoarterial (VA) ECMO. Methods: We reviewed the medical records of 114 adult patients who underwent VA-ECMO between March 2021 and September 2022. The patients were divided into survivors and non-survivors. Clinical data before and during ECMO were compared. Results: Patients' mean age was 67.8±13.6 years, and 36 (31.6%) were female. The proportion of survival to discharge was 48.6% (n=56). Cox regression analysis showed that the pre-ECMO albumin level independently predicted 30-day mortality (hazard ratio, 0.25; 95% confidence interval [CI], 0.11-0.59; p=0.002). The area under the receiver operating characteristic curve of albumin levels (pre-ECMO) was 0.73 (standard error [SE], 0.05; 95% CI, 0.63-0.81; p<0.001; cut-off value=3.4 g/dL). Kaplan-Meier survival analysis showed that the cumulative 30-day mortality was significantly higher in patients with a pre-ECMO albumin level ≤3.4 g/dL than in those with a level >3.4 g/dL (68.9% vs. 23.8%, p<0.001). As the adjusted amount of albumin infused increased, the possibility of 30-day mortality also increased (coefficient=0.140; SE, 0.037; p<0.001). Conclusion: Hypoalbuminemia during ECMO was associated with higher mortality, even with higher amounts of albumin replacement, in patients with CS who underwent VA-ECMO. Further studies are needed to predict the timing of albumin replacement during ECMO.

Pain in individuals with idiopathic inflammatory myopathies, other systemic autoimmune rheumatic diseases, and without rheumatic diseases: A report from the COVAD study.

OBJECTIVES: To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs). METHODS: Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores. RESULTS: Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0-5.0), 3.0 (IQR = 1.0-6.0), and 1.0 (IQR = 0-2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5-4.5, and NRS = 3.6, 95% CI = 3.1-4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios. CONCLUSION: Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status.

Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody.

N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. To evaluate the recombinant PRRSV, in vivo experiments were performed in piglets. The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. On the 42 dpi, both groups were challenged with the wild-type virus. The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. Taken together, this study confirmed that N44S substitution can create an infectious PRRSV that strongly induces neutralizing antibodies. In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs.

Molecular characterization of the intact mouse muscle spindle using a multi-omics approach.

The proprioceptive system is essential for the control of coordinated movement, posture, and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle isolated from the murine deep masseter muscle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development. Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease.