Altered Gut Microbiome Composition in Dogs with Hyperadrenocorticism: Key Bacterial Genera Analysis.

Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, which is associated with diverse metabolic abnormalities. We hypothesized that elevated cortisol levels in dogs with HAC disrupt the gut microbiome (GM), and this disruption persists even after trilostane treatment. This study explored GM composition in dogs with HAC. We included 24 dogs, 15 with HAC and 9 healthy controls, and followed up with 5 dogs with HAC who received trilostane treatment. The GM analysis revealed significant compositional changes in dogs with HAC, including reduced microbiome diversity compared to healthy controls, particularly in rare taxa, as indicated by the Shannon index (p = 0.0148). Beta diversity analysis further showed a distinct clustering of microbiomes in dogs with HAC, separating them from healthy dogs (p < 0.003). Specifically, an overrepresentation of Proteobacteria (Pseudomonadota), Actinobacteria, Bacteroides, Enterococcus, Corynebacterium, Escherichia, and Proteus populations occurred alongside a decreased Firmicutes (Bacillota) population. Despite trilostane treatment, gut dysbiosis persisted in dogs with HAC at a median of 41 d post treatment, suggesting its potential role in ongoing metabolic issues. We identified GM dysbiosis in dogs with HAC by examining key bacterial genera, offering insights into potential interventions like probiotics or fecal microbiota transplants for better HAC management.

Clinical Significance of Overlap Syndrome of Histologically Confirmed Lupus Nephritis with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objectives: We applied the 2022 American College of Rheumatology/ European Alliance of Association for Rheumatology (ACR/EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients histologically diagnosed with lupus nephritis (LN) to investigate the overall rate of and initial contributing factors to the reclassification of overlap syndrome of LN with AAV (OS-LN-AAV). Methods: We retrospectively reviewed the medical records of 1292 patients with systemic lupus erythematosus (SLE) and included 164 patients with LN in this study. Patient demographics, SLE manifestations, LN classes, and laboratory data, including ANCA levels, were recorded. All-cause mortality and end-stage kidney disease (ESKD) were evaluated as poor outcomes. Results: The median age of the 164 patients was 37.0 years, and 12.2% were men. The overall reclassification rate was 37.8%, of which 34.1% and 3.7% of the patients were reclassified as having OS-LN-microscopic polyangiitis and OS-LN-granulomatosis with polyangiitis (GPA), respectively, but none as having eosinophilic GPA. ANCA positivity and AAV-suggesting lung lesions were major contributors to OS-LN-AAV reclassification. When patients were compared based on OS-LN AAV reclassification, ANCA positivity and myeloperoxidase-ANCA (or P-ANCA) positivity favoured for OS-LN-AAV reclassification, whereas oral ulcers did not. However, OS-LN-AAV reclassification did not affect all-cause mortality or ESKD. Conclusions: This is the first study demonstrating a 37.8% reclassification rate in patients histologically diagnosed with LN using the 2022 ACR/EULAR criteria for AAV. Furthermore, it was also the first to reveal ANCA positivity and AAV-suggesting lung lesions as major contributors to OS-LN-AAV reclassification.

Use of artificial intelligence-powered ECG to differentiate between cardiac and pulmonary pathologies in patients with acute dyspnoea in the emergency department.

BACKGROUND: Acute dyspnoea is common in acute care settings. However, identifying the origin of dyspnoea in the emergency department (ED) is often challenging. We aimed to investigate whether our artificial intelligence (AI)-powered ECG analysis reliably distinguishes between the causes of dyspnoea and evaluate its potential as a clinical triage tool for comparing conventional heart failure diagnostic processes using natriuretic peptides. METHODS: A retrospective analysis was conducted using an AI-based ECG algorithm on patients ≥18 years old presenting with dyspnoea at the ED from February 2006 to September 2023. Patients were categorised into cardiac or pulmonary origin groups based on initial admission. The performance of an AI-ECG using a transformer neural network algorithm was assessed to analyse standard 12-lead ECGs for accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Additionally, we compared the diagnostic efficacy of AI-ECG models with N-terminal probrain natriuretic peptide (NT-proBNP) levels to identify cardiac origins. RESULTS: Among the 3105 patients included in the study, 1197 had cardiac-origin dyspnoea. The AI-ECG model demonstrated an AUC of 0.938 and 88.1% accuracy for cardiac-origin dyspnoea. The sensitivity, specificity and positive and negative predictive values were 93.0%, 79.5%, 89.0% and 86.4%, respectively. The F1 score was 0.828. AI-ECG demonstrated superior diagnostic performance in identifying cardiac-origin dyspnoea compared with NT-proBNP. True cardiac origin was confirmed in 96 patients in a sensitivity analysis of 129 patients with a high probability of cardiac origin initially misdiagnosed as pulmonary origin predicted by AI-ECG. CONCLUSIONS: AI-ECG demonstrated superior diagnostic accuracy over NT-proBNP and showed promise as a clinical triage tool. It is a potentially valuable tool for identifying the origin of dyspnoea in emergency settings and supporting decision-making.

Serum Wnt3A levels are significantly associated with cross-sectional vasculitis activity and end-stage kidney disease during follow-up of patients with antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: In this study, we investigated whether serum Wnt3A levels at diagnosis reflected cross-sectional activity and predicted poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: This study included 80 patients who were newly diagnosed with AAV at a tertiary hospital. At diagnosis, whole blood was obtained from patients and sera was immediately isolated and stored at -80℃. Moreover, AAV activity was assessed using the Birmingham Vasculitis Activity Score (BVAS), and a high BVAS was defined as the highest tertile. Poor outcomes including all-cause mortality and end-stage kidney disease (ESKD) were recorded. RESULTS: The patients had a median age of 63.5 years, with 40% being male and 60% female patients. Serum levels of Wnt3A at diagnosis were correlated with the cross-sectional BVAS and serum Wnt3A ≥411.7 pg/mL exhibited an increased risk of high BVAS. In addition, serum Wnt3A levels at diagnosis significantly correlated with cross-sectional acute-phase reactants and serum albumin levels. Furthermore, serum Wnt3A levels at diagnosis were associated with AAV exacerbation, leading to ESKD. Particularly, serum Wnt3A ≥407.1 pg/mL also demonstrated an elevated risk of ESKD (relative risk 3.867). Additionally, patients with serum Wnt3A ≥407.1 pg/mL exhibited a significantly lower cumulative ESKD-free survival rate than those with lower serum Wnt3A levels. CONCLUSIONS: This study is the first to demonstrate the clinical potential of serum Wnt3A levels at diagnosis for estimating cross-sectional activity and partially predicting the advancement to ESKD during follow-up in patients with AAV.

Serum Soluble Receptors for Advanced Glycation End-Products May Predict Mortality in Microscopic Polyangiitis and Granulomatosis with Polyangiitis.

PURPOSE: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). MATERIALS AND METHODS: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. RESULTS: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). CONCLUSION: This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

Serum Glial Fibrillary Acidic Protein Can Predict Cross-Sectional Vasculitis Activity by Reflecting Renal Involvement in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background and Objectives: Glial fibrillary acidic protein (GFAP) is a type III intermediate filament protein primarily produced by cells in the central nervous system (CNS) and other major organs such as the kidneys. This study investigated whether serum GFAP could be used to estimate cross-sectional vasculitis activity presented via the Birmingham vasculitis activity score (BVAS) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 74 patients with AAV. Clinical and laboratory data at diagnosis including BVAS and C-reactive protein (CRP) were reviewed. During follow-up, all-cause mortality and end-stage kidney disease (ESKD) were considered poor outcomes. Serum GFAP was measured from sera collected and stored at diagnosis. Results: The median age of the 74 patients was 63.5 years. Serum GFAP was inversely correlated with the cross-sectional BVAS (r = -0.373) and CRP (r = -0.320). It was also significantly correlated with general (r = -0.237) and renal (r = -0.335) manifestations among BVAS systemic items, and furthermore, among minor items of renal manifestation, correlating with sum scores for proteinuria (r = -0.409) and haematuria (r = -0.305). Additionally, compared with patients with serum GFAP > 194.9 pg/mL, those with serum GFAP ≤ 194.9 pg/mL showed a higher risk for progression to ESKD (relative risk 3.150) and a significantly lower cumulative ESKD-free survival rate. Conclusions: This study demonstrated the clinical potential of serum GFAP at diagnosis for predicting not only cross-sectional vasculitis activity through the anticipation of the extent of renal involvement but also future progression to ESKD in patients with AAV.

Serum syndecan1 has the potential to reflect activity at diagnosis and predict death during follow-up in patients with ANCA-associated vasculitis.

OBJECTIVES: This study investigated whether serum syndecan1 at diagnosis reflects activity at diagnosis and predicts poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: The study included 79 patients with AAV from the cohort of Korean patients diagnosed with AAV. AAV-specific indices, including the Birmingham vasculitis activity score (BVAS), five-factor score (FFS), 36-item short-form survey (SF-36) physical and mental component summary (PCS and MCS), and vasculitis damage index (VDI), were assessed. Laboratory data including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also collected. The highest tertile and upper half of the BVAS were tentatively defined as having high AAV activity. Serum syndecan1 levels were measured in sera stored at diagnosis. RESULTS: Serum syndecan1 at diagnosis was significantly correlated with AAV activity and functional status, as assessed by BVAS, FFS, SF-36 PCS, MCS, and acute-phase reactants, including ESR and CRP. Patients with serum syndecan1 ≥ 76.1 ng/mL at diagnosis, and those with serum syndecan1 ≥ 60.0 ng/mL at diagnosis showed significantly higher risks for the highest tertile and the upper half of BVAS at diagnosis than those without, respectively. Patients with serum syndecan1 ≥ 120.1 ng/mL at diagnosis had a significantly higher risk for all-cause mortality during follow-up than those without, and further, exhibited a significantly lower cumulative patients' survival rate than those without. CONCLUSION: Serum syndecan1 at diagnosis may not only reflect AAV activity at diagnosis but may also be associated with all-cause mortality during follow-up.

Survival of lung cancer patients according to screening eligibility using Korean Lung Cancer Registry 2014-2016.

This study assessed survival for lung cancer patients meeting criteria for the National Lung Cancer Screening Program in Korea launched in 2019 and updated guideline reported by the US Preventive Service Task Force (USPSTF). We assessed all-cause mortality based on the Korean Lung Cancer Registry (KLCR), including lung cancer patients diagnosed in 2014-2016. We compared survival among lung cancer patients eligible for extended USPSTF criteria (age 50-80 years and ≥ 20 pack-years) and those meeting current criteria (age 54-74 years and ≥ 30 pack-years, current or within the past 15 years). The nearest neighbour propensity-score matching was performed to generate a matched set. Kaplan-Meier curves were generated to compare survival among groups; differences in survival were analyzed using the stratified log-rank test. The mortality risk was estimated based on a Cox proportional hazards regression model and the robust standard error was calculated. Of 8110 patients, 37.4% and 24.3% met the extended USPSTF eligibility criteria and National Lung Cancer Screening Program (NLCSP) criteria, respectively. Overall mortality risk was not significantly different between the extended younger age group and the NLCSP group (hazard ratio [HR] [95% confidence interval (CI)]: 0.78 [0.59-1.02]). The extended older age group had a significantly higher mortality risk (HR [95% CI]: 1.41 [1.26-1.58]). Mortality risk was not significantly different between patients who smoked 20-29 pack-years and those who smoked ≥ 30 pack-years (HR [95% CI]: 0.90 [0.79-1.03]). Lung cancer patients aged 50-53 years and those with a 20-29 pack-years smoking history exhibited similar mortality risk to individuals meeting current criteria, while patients aged 75-80 years were at a higher risk of death. Although we verified similar or higher mortality risks in extended subgroups, a careful assessment of the benefits and harms of the screening tests is necessary when contemplating the extension of criteria.

Hypophysitis and central nervous system involvement in association with Sjögren's syndrome along with hypoparathyroidism: a case report.

BACKGROUND: Patients with autoimmune diseases can develop multiple autoimmune diseases over a long period of time, and the presence of more than one autoimmune disease in a single patient is defined as polyautoimmunity. Polyautoimmunity may be clinical evidence that autoimmune diseases share similar immunological mechanisms. CASE PRESENTATION: We report a 30-year-old woman with a unique combination of autoimmune diseases predominantly affecting the central nervous system, with hypoparathyroidism, hypophysitis, medulla involvement, and pons and temporal lobe involvement associated with primary Sjögren's syndrome (pSS), occurring independently over a long period. The patient who had a history of muscle cramps and one seizure incident, presented with vomiting and blurred vision. She was diagnosed with hypophysitis and hypoparathyroidism with calcifications in the basal ganglia and cerebellum. She recovered after four months of corticosteroid treatment for hypophysitis and was started on treatment for hypoparathyroidism. Eight months later, she developed vomiting, hiccups, vertigo, and ataxia with a focal lesion in the medulla. She recovered with immunosuppressive treatment for 2 years. Fifty-eight months after the onset of hypophysitis, she developed diplopia and dry mouth and eyes. MRI showed infiltrative lesions in the left pons and left temporal lobe. Based on positive anti-Sjögren's syndrome-related antigen A antibodies and low unstimulated whole salivary flow rate, pSS was diagnosed. She received corticosteroids and continued mycophenolate mofetil treatment with recovery of neurological symptoms. CONCLUSION: This case highlights the need for long-term follow-up to detect autoimmune disease processes involving various organs.

Cross-Modality Image Translation From Brain 18 F-FDG PET/CT Images to Fluid-Attenuated Inversion Recovery Images Using the CypixGAN Framework.

PURPOSE: PET/CT and MRI can accurately diagnose dementia but are expensive and inconvenient for patients. Therefore, we aimed to generate synthetic fluid-attenuated inversion recovery (FLAIR) images from 18 F-FDG PET and CT images of the human brain using a generative adversarial network (GAN)-based deep learning framework called the CypixGAN, which combined the CycleGAN framework with the L1 loss function of the pix2pix. PATIENTS AND METHODS: Data from 143 patients who underwent PET/CT and MRI were used for training (n = 79), validation (n = 20), and testing (n = 44) the deep learning frameworks. Synthetic FLAIR images were generated using the pix2pix, CycleGAN, and CypixGAN, and white matter hyperintensities (WMHs) were then segmented. The performance of CypixGAN was compared with that of the other frameworks. RESULTS: The CypixGAN outperformed the pix2pix and CycleGAN in generating synthetic FLAIR images with superior visual quality. Peak signal-to-noise ratio and structural similarity index (mean ± standard deviation) estimated using the CypixGAN (20.23 ± 1.31 and 0.80 ± 0.02, respectively) were significantly higher than those estimated using the pix2pix (19.35 ± 1.43 and 0.79 ± 0.02, respectively) and CycleGAN (18.74 ± 1.49 and 0.78 ± 0.02, respectively) ( P < 0.001). WMHs in synthetic FLAIR images generated using the CypixGAN closely resembled those in ground-truth images, as indicated by the low absolute percentage volume differences and high dice similarity coefficients. CONCLUSIONS: The CypixGAN generated high-quality FLAIR images owing to the preservation of spatial information despite using unpaired images. This framework may help improve diagnostic performance and cost-effectiveness of PET/CT when MRI scan is unavailable.

Homogeneously Mixed Cu-Co Bimetallic Catalyst Derived from Hydroxy Double Salt for Industrial-Level High-Rate Nitrate-to-Ammonia Electrosynthesis.

Electrocatalytic nitrate reduction reaction (NO3RR) presents an innovative approach for sustainable NH3 production. However, selective NH3 production is hindered by the multiple intermediates involved in the NO3RR process and the competitive hydrogen evolution reaction. Hence, the development of highly efficient NO3RR catalysts is paramount. Herein, we report highly efficient bimetallic catalysts derived from hydroxy double salt (HDS). Under NO3RR conditions, Cu1Co1-HDS undergoes in situ reconstruction, forming nanocomposites of homogeneously distributed metallic Cu0 and Co(OH)2. Reconstruction-induced Cu0 rapidly converts NO3- to NO2-, which is further hydrogenated to NH3 by Co(OH)2. Homogeneously mixed Cu and Co species maximize this synergistic effect, achieving outstanding NO3RR performance including the highest NH3 yield rate (4.625 mmol h-1 cm-2) reported for powder-type NO3RR catalysts. Integration of Cu1Co1-HDS with a commercial Si solar cell attained 4.53% solar-to-ammonia efficiency from industrial wastewater-level concentrations of NO3- (2000 ppm), demonstrating practical application potential for solar-driven NH3 production. This study provides a strategy for enhancing the NH3 yield rate by optimizing the compositions and distributions of Cu and Co.

Anti-TCP1 Antibody Is a Potential Biomarker for Diagnosing Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease caused by autoantibodies. Serum samples from patients with SLE (n = 10) were compared with those from normal controls (NCs, n = 5) using 21K protein chip analysis to identify a biomarker for SLE, revealing 63 SLE-specific autoantibodies. The anti-chaperonin-containing t-complex polypeptide-1 (TCP1) antibody exhibited higher expression in patients with SLE than in NCs. To validate the specificity of the anti-TCP1 antibody in SLE, dot blot analysis was conducted using sera from patients with SLE (n = 100), rheumatoid arthritis (RA; n = 25), Behçet's disease (BD; n = 28), and systemic sclerosis (SSc; n = 30) and NCs (n = 50). The results confirmed the detection of anti-TCP1 antibodies in 79 of 100 patients with SLE, with substantially elevated expression compared to both NCs and patients with other autoimmune diseases. We performed an enzyme-linked immunosorbent assay to determine the relative amounts of anti-TCP1 antibodies; markedly elevated anti-TCP1 antibody levels were detected in the sera of patients with SLE (50.1 ± 17.3 arbitrary unit (AU), n = 251) compared to those in NCs (33.9 ± 9.3 AU), RA (35 ± 8.7 AU), BD (37.5 ± 11.6 AU), and SSc (43 ± 11.9 AU). These data suggest that the anti-TCP1 antibody is a potential diagnostic biomarker for SLE.

Intranasal Administration of Recombinant Newcastle Disease Virus Expressing SARS-CoV-2 Spike Protein Protects hACE2 TG Mice against Lethal SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged as a global outbreak in 2019, profoundly affecting both human health and the global economy. Various vaccine modalities were developed and commercialized to overcome this challenge, including inactivated vaccines, mRNA vaccines, adenovirus vector-based vaccines, and subunit vaccines. While intramuscular vaccines induce high IgG levels, they often fail to stimulate significant mucosal immunity in the respiratory system. We employed the Newcastle disease virus (NDV) vector expressing the spike protein of the SARS-CoV-2 Beta variant (rK148/beta-S), and evaluated the efficacy of intranasal vaccination with rK148/beta-S in K18-hACE2 transgenic mice. Intranasal vaccination with a low dose (106.0 EID50) resulted in an 86% survival rate after challenge with the SARS-CoV-2 Beta variant. Administration at a high dose (107.0 EID50) led to a reduction in lung viral load and 100% survival against the SARS-CoV-2 Beta and Delta variants. A high level of the SARS-CoV-2 spike-specific IgA was also induced in vaccinated mice lungs following the SARS-CoV-2 challenge. Our findings suggest that rK148/beta-S holds promise as an intranasal vaccine candidate that effectively induces mucosal immunity against SARS-CoV-2.

The Clinical Utility of Serum Alpha-1-Acid Glycoprotein in Reflecting the Cross-Sectional Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Centre Retrospective Study.

Background and Objectives: This study investigated whether serum alpha-1-acid glycoprotein (AGP) at diagnosis could reflect the cross-sectional activity represented by the Birmingham vasculitis activity score (BVAS) and further predict poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 70 patients with AAV. Clinical data at diagnosis, including AAV-specific indices and acute-phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were reviewed. All-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident, and acute coronary syndrome were evaluated as poor outcomes of AAV. Serum AGP was measured using the sera obtained and stored at diagnosis. Results: The median age of the patients was 63.0 years, with 29 male and 41 female patients. The median serum AGP was 150.9 µg/mL. At diagnosis, serum AGP was significantly correlated with BVAS and ESR but not CRP or serum albumin. Additionally, serum AGP showed significant correlations with the sum scores of ear-nose-throat and pulmonary manifestations; however, no significant differences in serum AGP according to each poor outcome were observed. Although serum AGP at diagnosis tended to be associated with ESKD occurrence during follow-up, serum AGP at AAV diagnosis was not significantly useful in predicting the future occurrence of poor outcomes of AAV during follow-up. Conclusions: In this study, we demonstrated the clinical utility of serum AGP at AAV diagnosis in assessing the cross-sectional activity represented by BVAS in patients with AAV for the first time.

Persons Experiencing Homelessness during Extreme Temperatures: Lessons for Promoting Socially Inclusive Adaptive Capacity.

Climate change and increasing extreme temperatures present unique challenges to persons experiencing homelessness (PEH), including heightened physical and psychological harm. While green and urban infrastructure has emerged as one possible mitigation strategy, homeless populations are rarely included in municipal disaster planning or infrastructure research. This study used in-depth interviews with PEH (N = 42) during the summers of 2022 and 2023. Questions were designed around phenomenological methods to explore the individuals' firsthand descriptions of the lived experience of coping during extreme temperatures within a mid-size city in the Southeastern United States. Our findings highlight how social exclusion within the built environment reduces PEH's adaptive capacity and increases the physical and psychological risks of extreme temperatures, namely through limiting and policing scarce resources and restricting the mobility of PEH. In contrast, public transit provided relief from extreme temperatures. Implications from our findings include the need for attention on inclusive green urban infrastructure, including increased placement and access to shade, public water, mixed-use daytime sheltering models, and the installation of lockers to increase capacity to maintain supplies and gear necessary for enduring extreme temperatures. Findings also highlight the challenges of designing inclusive green infrastructure and the importance of de-stigmatizing homelessness and building more housing and income support to increase adaptive capacity for an entire community in the context of a rapidly warming climate.

Assessing Post-Marketing Requirements for Orphan Drugs: A Cross-Sectional Analysis of FDA and EMA Oversight.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) oversee pharmaceutical regulations, including orphan drugs targeting rare diseases with limited patient populations. Post-marketing studies are crucial for monitoring safety and efficacy, with post-marketing requirements (PMRs) mandated by the regulatory agencies to ensure compliance. This study aims to compare PMR statuses, objectives, and pivotal trial characteristics of orphan drugs approved by the FDA (n = 154) and EMA (n = 79) from 2008 to 2018, shedding light on regulatory differences and their impact on drug development. Contrary to expectations, our analysis found no significant disparity in the proportion of orphan drugs with and without PMRs approved by both the FDA (48.1%) and EMA (55.7%). Safety concerns surrounding orphan drugs post-approval, attributed partly to pivotal trial design, underscore the need for robust post-marketing surveillance. While the FDA primarily focuses on post-marketing safety (36.1%), the EMA places a higher emphasis on both efficacy and safety (47.1%), reflecting distinct approaches to PMR management between the two regulatory bodies. The observed trend of delayed PMRs at the EMA (47.1%) highlights the importance of effective cooperation between regulators and pharmaceutical companies to ensure the timely completion of PMRs and enhance drug safety.

Application of the 2022 ACR/EULAR criteria for Takayasu arteritis to previously diagnosed patients based on the 1990 ACR criteria.

OBJECTIVES: Recently, a joint group of the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) proposed new criteria for Takayasu arteritis (TAK) (the 2022 ACR/EULAR criteria). This study applied the 2022 ACR/EULAR criteria to patients with previously diagnosed TAK based on the 1990 ACR criteria and investigated the concordance rate between the two criteria according to the four imaging modalities. METHODS: This study reviewed the medical records of 179 patients who met the 1990 ACR criteria for TAK. The imaging modalities included conventional angiography, computed tomography angiography, fluorodeoxyglucose-positron emission tomography, and magnetic resonance angiography. RESULTS: Regardless of the imaging modalities, the concordance rate between the two criteria was 85.5% when including all patients, whereas it increased to 98.1% when only patients aged ≤60 years were included. Among the four imaging modalities, computed tomography angiography exhibited the highest concordance rate between the two criteria (85.6%). The concordance rate among patients aged >60 years was 95.7%. Only one patient aged 50-60 years was reclassified as having both TAK and giant cell arteritis. CONCLUSIONS: The concordance rate was 85.5% regardless of the imaging modalities and increased to 86.9% on simultaneous computed tomography angiography and fluorodeoxyglucose-positron emission tomography imaging.

Circulating Malondialdehyde Is a Potential Biomarker for Predicting All-Cause Mortality during Follow-Up by Reflecting Comprehensive Inflammation at Diagnosis in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background and Objectives: To investigate whether circulating malondialdehyde (cMDA) at diagnosis could contribute to reflecting cross-sectional comprehensive inflammation or vasculitis activity and further predicting all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 78 patients with AAV. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected as indices reflecting cross-sectional comprehensive inflammation, whereas the Birmingham vasculitis activity score (bVAS), and the five-factor score (FFS) were reviewed as AAV-specific indices. All-cause mortality was considered to be a poor outcome during follow-up. cMDA was measured from stored sera. Results: The median age of the 78 patients (32 men and 46 women) was 63.0 years. The median BVAS, FFS, ESR, and CRP were 5.0, 0, 24.5 mm/h, and 3.4 mg/L, respectively. Six patients died during the median follow-up duration based on all-cause mortality at 26.7 months. At diagnosis, cMDA was significantly correlated with cross-sectional ESR but not with BVAS or FFS. Compared to patients with cMDA < 221.7 ng/mL, those with cMDA ≥ 221.7 ng/mL at diagnosis exhibited an increased relative risk (RR 12.4) for all-cause mortality and further showed a decreased cumulative patient survival rate. Cox analyses revealed that cMDA ≥ 221.7 ng/mL (hazard ratio 24.076, p = 0.007) exhibited an independent association with all-cause mortality during follow-up in patients with AAV. Conclusions: cMDA at diagnosis may be a potential biomarker for predicting all-cause mortality during follow-up by reflecting comprehensive inflammation at diagnosis in patients with AAV.

Spike-Based Neuromorphic Hardware for Dynamic Tactile Perception with a Self-Powered Mechanoreceptor Array.

A self-powered mechanoreceptor array is demonstrated using four mechanoreceptor cells for recognition of dynamic touch gestures. Each cell consists of a triboelectric nanogenerator (TENG) for touch sensing and a bi-stable resistor (biristor) for spike encoding. It produces informative spike signals by sensing a force of an external touch and encoding the force into the number of spikes. An array of the mechanoreceptor cells is utilized to monitor various touch gestures and it successfully generated spike signals corresponding to all the gestures. To validate the practicality of the mechanoreceptor array, a spiking neural network (SNN), highly attractive for power consumption compared to the conventional von Neumann architecture, is used for the identification of touch gestures. The measured spiking signals are reflected as inputs for the SNN simulations. Consequently, touch gestures are classified with a high accuracy rate of 92.5%. The proposed mechanoreceptor array emerges as a promising candidate for a building block of tactile in-sensor computing in the era of the Internet of Things (IoT), due to the low cost and high manufacturability of the TENG. This eliminates the need for a power supply, coupled with the intrinsic high throughput of the Si-based biristor employing complementary metal-oxide-semiconductor (CMOS) technology.

Increased Trend of Adenovirus Activity After the COVID-19 Pandemic in South Korea: Analysis of National Surveillance Data.

The adenovirus detection rate is <10% throughout the year in South Korea; however, during the summer of 2023, it showed an unusual increase. We analyzed the adenovirus detection rate using data from the Korea Respiratory Integrated Surveillance System before and after coronavirus disease (COVID-19) collected from 2019 to week 36 of 2023. Before the COVID-19 outbreak in 2019, the mean detection rate was 8.2%, which decreased to 6.1% during the COVID-19 pandemic from 2020 to 2022. In 2023, the mean detection rate was 14.3% in week 36 and the highest in week 34, at 42.2%, and adenovirus was predominantly detected in the summer. The detection rate by age group showed substantially high activity among 0-12-yr-olds after the pandemic. This age group had a steady mean rate of 9.5% during the pandemic, without seasonality. In 2023, the detection rate surged in the 0-6-yr and 7-12-yr age groups, peaking at 61.6% and 57.1%, respectively. The dominant epidemic serotypes were HAdV-1 and HAdV-2 during and HAdV-3 after the pandemic. The multifaceted non-pharmaceutical interventions during the COVID-19 pandemic considerably impacted the prevalence of common respiratory viruses and complicated respiratory virus patterns after the pandemic. Constant surveillance is crucial for epidemic preparedness to monitor the possible surge of certain respiratory viruses.