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.

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.

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.

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.

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.

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.

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.

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.

The Cancer Clinical Library Database (CCLD) from the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) Project.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea's cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

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.

The monocyte-to-high-density lipoprotein-cholesterol ratio at diagnosis is associated with cerebrovascular accident during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Objective: In this study, the association between the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) at diagnosis and poor outcomes of atherosclerosis-related antineutrophil cytoplasmic antibody-associated vasculitis (AAV) during follow-up in patients with AAV was investigated. Methods: This retrospective study included 138 patients diagnosed with AAV. Their comprehensive medical records were meticulously reviewed. All-cause mortality, cerebrovascular accident (CVA), and acute coronary syndrome (ACS) were evaluated as atherosclerosis-related poor outcomes of AAV. MHR was obtained by dividing monocyte counts (/mm3) by high-density lipoprotein cholesterol (mg/dL) levels. Results: The median age of the 138 patients was 58.3 years with 44 being male (31.9%). Among the 138 patients, 11 (8.0%) died, and 11 (8.0%) and 9 (6.5%) had CVA, and ACS, respectively. MHR at diagnosis was significantly correlated with the Birmingham vasculitis activity score, erythrocyte sedimentation rate, and C-reactive protein at diagnosis. Among the three poor outcomes of AAV, only CVA during follow-up was significantly associated with MHR at diagnosis, and thus, only CVA was considered an atherosclerosis-related poor outcome of AAV. In the multivariable Cox hazards model analysis, MHR (hazard ratio [HR] 1.195) and serum albumin (HR 0.203) at diagnosis were independently associated with CVA during follow-up. Additionally, patients with MHR at diagnosis ≥3.0 exhibited a significantly higher risk for CVA and lower cumulative CVA-free survival rate than those with MHR at diagnosis <3.0. Conclusion: This study is the first to demonstrate clinical implications of MHR suggesting that MHR at diagnosis is significantly and independently associated with CVA during follow-up in patients with AAV.

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.

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.

Longitudinal assessment of urinary ALCAM, HPX, and PRDX6 in Korean patients with systemic lupus erythematosus: implications for disease activity monitoring and treatment response.

Introduction: This study aimed to demonstrate the potential of activated leukocyte cell adhesion molecule (ALCAM), hemopexin (HPX), and peroxiredoxin 6 (PRDX6) as urine biomarkers for systemic lupus erythematosus (SLE). Methods: Urine samples were collected from 138 Korean patients with SLE from the Ajou Lupus Cohort and 39 healthy controls (HC). The concentrations of urine biomarkers were analyzed using enzyme-linked immunosorbent assay kits specific for ALCAM, HPX, and PRDX6, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic utility, and Pearson's correlation analysis was conducted to assess the relationships between the disease activity and urine biomarkers. Results: Patients with SLE and patients with lupus nephritis (LN) showed significantly elevated ALCAM, HPX, and PRDX6 levels compared with HCs. ALCAM, HPX, and PRDX6 showed significant diagnostic values, especially for lupus nephritis (LN), with areas under the receiver operating characteristic curve for LN was 0.850 for ALCAM (95% CI, 0.778-0.921), 0.781 for HPX (95% CI, 0.695-0.867), and 0.714 for PRDX6 (95% CI, 0.617-0.812). Correlation analysis revealed that all proteins were significantly associated with anti-double stranded DNA antibody (ALCAM, r = 0.350, p < 0.001; HPX, r = 0.346, p < 0.001; PRDX6, r = 0.191, p = 0.026) and SLEDAI (ALCAM, r = 0.526, p < 0.001; HPX, r = 0.479, p < 0.001; PRDX6, r = 0.262, p = 0.002). Results from the follow-up of the three biomarker levels in these patients revealed a significant decrease, showing a positive correlation with changes in SLEDAI-2k scores (ALCAM, r = 0.502, p < 0.001; HPX, r = 0.475, p < 0.001; PRDX6, r = 0.245, p = 0.026), indicating their potential as indicators for tracking disease activity. Discussions: Urinary ALCAM, HPX, and PRDX6 levels have diagnostic value and reflect disease activity in Korean patients with SLE, emphasizing their potential for non-invasive monitoring and treatment response evaluation.

Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies.

Many growth factors and cytokines signal by binding to the extracellular domains of their receptors and driving association and transphosphorylation of the receptor intracellular tyrosine kinase domains, initiating downstream signaling cascades. To enable systematic exploration of how receptor valency and geometry affect signaling outcomes, we designed cyclic homo-oligomers with up to 8 subunits using repeat protein building blocks that can be modularly extended. By incorporating a de novo-designed fibroblast growth factor receptor (FGFR)-binding module into these scaffolds, we generated a series of synthetic signaling ligands that exhibit potent valency- and geometry-dependent Ca2+ release and mitogen-activated protein kinase (MAPK) pathway activation. The high specificity of the designed agonists reveals distinct roles for two FGFR splice variants in driving arterial endothelium and perivascular cell fates during early vascular development. Our designed modular assemblies should be broadly useful for unraveling the complexities of signaling in key developmental transitions and for developing future therapeutic applications.

Wideband PRM: Highly Accurate and Sensitive Method for High-Throughput Targeted Proteomics.

Targeted mass spectrometry (MS) approaches, which are powerful methods for uniquely and confidently quantifying a specific panel of proteins in complex biological samples, play a crucial role in validating and clinically translating protein biomarkers discovered through global proteomic profiling. Common targeted MS methods, such as multiple reaction monitoring (MRM) and parallel-reaction monitoring (PRM), employ specific mass spectrometric technologies to quantify protein levels by comparing the transitions of surrogate endogenous (ENDO) peptides with those of stable isotope-labeled (SIL) peptide counterparts. These methods utilizing amino acid analyzed (AAA) SIL peptides warrant sensitive and precise measurements required for targeted MS assays. Compared with MRM, PRM provides higher experimental throughput by simultaneously acquiring all transitions of the target peptides and thereby compensates for different ion suppressions among transitions of a target peptide. However, PRM still suffers different ion suppressions between ENDO and SIL peptides due to spray instability, as the ENDO and SIL peptides were monitored at different liquid chromatography (LC) retention times. Here we introduce a new targeted MS method, termed wideband PRM (WBPRM), that is designed for high-throughput targeted MS analysis. WBPRM employs a wide isolation window for simultaneous fragmentation of both ENDO and SIL peptides along with multiplexed single ion monitoring (SIM) scans for enhanced MS sensitivity of the target peptides. Compared with PRM, WBPRM was demonstrated to provide increased sensitivity, precision, and reproducibility of quantitative measurements of target peptides with increased throughput, allowing more target peptide measurements in a shortened experiment time. WBPRM is a straightforward adaptation to a manufacturer-provided MS method, making it an easily implementable technique, particularly in complex biological samples where the demand for higher precision, sensitivity, and efficiency is paramount.

Antimicrobial activity of cell-free supernatant derived from Ligilactobacillus animalis SWLA-1 in a novel ex vivo canine corneal infection model.

Introduction: Canine bacterial keratitis is a corneal infection that causes various symptoms, including visual impairment, and necessitates eye removal in severe cases. Staphylococcus pseudintermedius is a pathogen that causes significant bacterial keratitis in canine patients. Moreover, multi-drug resistant Staphylococcus pseudintermedius (MDRSP) has been reported in both humans and animals. Regarding treatment failure against multi-drug resistant (MDR) pathogens with classic antibiotics, antimicrobial compounds derived from probiotics have been suggested as an alternative approach. Methods: Ligilactobacillus animalis SWLA-1 strain and its cell-free supernatant (CFS) have previously demonstrated potent antimicrobial activity against various MDR pathogenic bacteria. Based on this finding, we evaluated the anti-staphylococcal activity of CFS derived from Ligilactobacillus animalis SWLA-1 against MDRSP in a newly established ex vivo canine corneal infection model using fresh canine corneoscleral rims. Additionally, an in vitro cytotoxicity test using human keratocytes was performed. Results and Discussion: CFS significantly inhibited the growth of MDRSP in the novel ex vivo model and did not exhibit any significant toxicity against keratocytes in vitro. Based on these results, the antimicrobial compounds in CFS show potential as a novel approach for MDR staphylococcal keratitis treatment.

Epidemiology of Respiratory Viruses in Korean Children Before and After the COVID-19 Pandemic: A Prospective Study From National Surveillance System.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to a decrease in the seasonal incidence of many respiratory viruses worldwide due to the impact of nonpharmaceutical interventions (NPIs). However, as NPI measures were relaxed, respiratory viral infections re-emerged. We aimed to characterize the epidemiology of respiratory viruses in Korean children during post-COVID-19 pandemic years compared to that before the pandemic. METHODS: A nationwide prospective ongoing surveillance study has been conducted for detection of respiratory viruses between January 2017 and June 2023. We included data on adenovirus (AdV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus (HMPV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV), which were detected in children and adolescents younger than 20 years. We analyzed the weekly detection frequency of individual viruses and the age distribution of the affected children. The study period was divided into prepandemic (2017-2019) and postpandemic (2021-2023) periods. RESULTS: A total of 19,589 and 14,068 samples were collected in the pre- and postpandemic periods, respectively. The overall detection rate of any virus throughout the study period was 63.1%, with the lowest occurring in the 2nd half of 2020 (50.6%) and the highest occurring in the 2nd half of 2021 (72.3%). Enveloped viruses (HCoV, HMPV, IFV, PIV, and RSV) almost disappeared, but nonenveloped viruses (AdV, HBoV, and HRV) were detected even during the peak of the COVID-19 pandemic. The codetection rate increased from 15.0% prepandemic to 19.1% postpandemic (P < 0.001). During the postpandemic period, a large out-of-season PIV and HMPV epidemic occurred, but the usual seasonality began to be restored in 2023. The mean age of children with each virus detected in 2023 was significantly greater than that in prepandemic years (P = 0.003 and 0.007 for AdV and HCoV, respectively; P < 0.001 for others). The mean age of children with IFV increased in 2022 (11.1 ± 5.2 years) from prepandemic years (7.9 ± 4.6 years) but decreased to 8.7 ± 4.1 years in 2023. CONCLUSION: With the relaxation of NPI measures, several seasonal respiratory viruses cocirculated with unusual seasonal epidemic patterns and were associated with increasing age of infected children.

Titanium Silicide: A Promising Candidate of Recombination Layer for Perovskite/Tunnel Oxide Passivated Contact Silicon Two-Terminal Tandem Solar Cells.

This study proposes a titanium silicide (TiSi2) recombination layer for perovskite/tunnel oxide passivated contact (TOPCon) 2-T tandem solar cells as an alternative to conventional transparent conductive oxide (TCO)-based recombination layers. TiSi2 was formed while TiO2 was made by oxidizing a Ti film deposited on the p+-Si layer. The reaction formation mechanism was proposed based on the diffusion theory supported by experimental results. The optical and electrical properties of the TiSi2 layer were optimized by controlling the initial Ti thicknesses (5-100 nm). With the initial Ti of 50 nm, the lowest reflectance and highly ohmic contact between the TiO2 and p+-Si layers with a contact resistivity of 161.48 mΩ·cm2 were obtained. In contrast, the TCO interlayer shows Schottky behavior with much higher contact resistivities. As the recombination layer of TiSi2 and the electron transport layer of TiO2 are formed simultaneously, the process steps become simpler. Finally, the MAPbI3/TOPCon tandem device yielded an efficiency of 16.23%, marking the first reported efficiency for a device including a silicide-based interlayer.