Real-world effectiveness of influenza vaccine over a decade during the 2011-2021 seasons-Implications of vaccine mismatch.

BACKGROUND: Influenza imposes a significant healthcare burden in Korea, leading the government to initiate a national immunization program. Previous studies on vaccine effectiveness (VE) were limited to single-season estimation in Korea. METHODS: This multicenter prospective cohort study enrolled patients with influenza-like illnesses at 10 medical centers in Korea from 2011 to 2021. The demographic and clinical data were collected from questionnaire surveys and electronic medical records. Using a test-negative design, we aimed to investigate the effectiveness of a seasonal influenza vaccine for antigenic matching of the vaccine and circulating viral strains over 10 seasons. RESULTS: Overall, 5322 adults aged ≥65 years were enrolled. Only three (33.3 %) of nine seasons showed >70 % antigenic match between vaccine and circulating strains. Influenza VE was significantly variable by season, ranging from -46.9 % (95 %confidence interval [CI]: -127.6-5.2) in the 2011/12 season to 47.7 % (95 %CI: 22.6-64.7) in the 2016/17 season. A significant difference was observed in the VE depending on whether the vaccine strains matched with epidemic strains: 28.8 % (95 %CI: 8.8-44.8) in matched seasons versus -12.0 % (95 %CI: -30.0-3.7) in mismatched seasons. Across the study period, influenza-related hospitalizations were reduced by 13.6 % (95 %CI: 0.7-24.8) with vaccination. In a subgroup analysis, the VE against influenza-related hospitalization was 48.4 % (95 %CI 29.6-62.2) in A/H3N2 dominant seasons and 53.8 % (95 %CI: -73.4-87.7) in A/H1N1 dominant seasons, respectively. CONCLUSION: Influenza vaccine mismatch was frequent over the study period, leading to negligibly low VE in mismatched seasons. Influenza vaccination reduces the risk of influenza-related hospitalizations.

Epidemiological and Clinical Characteristics of Women Living with HIV in Korea.

BACKGROUND: While Korea maintains a low prevalence of human immunodeficiency virus (HIV), the number of newly diagnosed cases has been steadily rising, reaching approximately 1,000 annually in recent years. The 2022 annual report from the Korea Disease Control and Prevention Agency revealed that women living with HIV (WLWH) constitute 6.4% of the total confirmed people living with the HIV population, totaling 1,219 individuals. Despite this, only a few studies have focused on WLWH in Korea. This study aims to analyze the epidemiological and clinical characteristics of WLWH in Korea. MATERIALS AND METHODS: We retrospectively collected data by reviewing the medical records of all WLWH who visited 10 urban referral hospitals across Korea between January 2005 and May 2023. RESULTS: A total of 443 WLWH were enrolled in this study. The predominant risk exposure was heterosexual contact, with 235 (53%) participants either married or cohabiting with a male partner at their initial clinic visit. Among the participants, 334 (77.7%) were Korean, 27 (6.1%) were Southeast Asian, and 19 (4.3%) were African. Antiretroviral therapy was initiated by 404 WLWH (91.2%). We observed 118 pregnancies in WLWH following their HIV diagnosis, resulting in 78 live births (66.1%), 18 induced abortions (15.2%), 10 pre-viable fetal losses (8.5%), and four stillbirths (3.4%). Over a cumulative follow-up duration of 3,202.1 years, the incidence rates of breast and cervical cancers were both 2.18 per 1,000 person-years. Additionally, the incidence rates of pelvic inflammatory disease, cervical intraepithelial neoplasm (above grade II), and osteoporosis were 4.67, 11.21, and 13.39 per 1,000 patient-years, respectively. CONCLUSION: This is the first multicenter study to investigate the clinical and epidemiological characteristics of WLWH in Korea. The incidence and prevalence of diseases in women, including breast cancer, cervical cancer, and chronic comorbidities, are high in WLWH in Korea; therefore, further research and efforts are needed to manage these diseases.

Estimates of vaccine effectiveness of the updated monovalent XBB.1.5 COVID-19 vaccine against symptomatic SARS-CoV-2 infection, hospitalization, and receipt of oxygen therapy in South Korea - October 26 to December 31, 2023.

OBJECTIVES: We evaluated the vaccine effectiveness of monovalent XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and the need for oxygen therapy in South Korea. DESIGN: This study employed a test-negative case-control design. COVID-19 test results in symptomatic subjects from six university hospitals across South Korea were collected (October 26-December 31, 2023). The adjusted absolute and relative vaccine effectiveness were assessed. RESULTS: In total, 5516 subjects were enrolled: 4,824 were unvaccinated with XBB.1.5, and 692 were vaccinated with XBB.1.5 COVID-19 mRNA vaccines. The absolute vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 65.2% (95% CI, 36.1-81.0), 77.3% (95% CI, 51.1-89.5), and 85.3% (95% CI, 57.8-94.9), respectively. The relative vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no XBB.1.5 vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 57.7% (95% CI, 34.7-72.6), 64.3% (95% CI, 35.9-80.2), and 65.5% (95% CI, 27.0-83.7), respectively. CONCLUSION: The short-term effectiveness of the XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and receipt of oxygen therapy in South Korea was significant. Long-term vaccine effectiveness warrants evaluation, and these assessments should be conducted regularly.

Severe Fever with Thrombocytopenia Syndrome in South Korea, 2016-2021: Clinical Features of Severe Progression and Complications.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection with a high case fatality rate. The serious clinical features need to be further defined. We performed a retrospective analysis among SFTS patients in South Korea during 2016-2021 to update the current status. The basic epidemiology of all reported cases was analyzed, and the detailed clinical data of the subjects were further collected from study hospitals selected in terms of their geographic location and capability of SFTS care. Cases of SFTS were reported across the country and were greatly increased since the initial endemic phase, even under the passive surveillance system. The case fatality rate remained at approximately 16.8%. Coinfections at admission were present in 7.8% of the patients. Major complications included bleeding (15.2%), hemophagocytic lymphohistiocytosis (6.7%), bacteremia or candidemia (4.0%), and invasive pulmonary aspergillosis (1.7%). It took a median 4 days from the onset of illness to hospital admission. Rapid clinical deterioration was observed with a median 1 day for intensive care unit admission, 3 days for mechanical ventilation, 4 days for renal replacement therapy, and 5 days for death, all after the hospitalization. Multivariate analysis showed that the fatality was associated with older age, bacteremia, or candidemia during hospitalization, and the presence of several variables at admission such as fever, altered mentality, aspartate aminotransferase >200 IU/L, serum creatinine level >1.2 mg/dL, and prolonged prothrombin time and activated partial thromboplastin time. Treatment options to improve clinical outcomes are limited, despite best supportive care. Specific treatment is urgently needed to change the fatal course.

Treatment Outcomes Among Patients With a Positive Candida Culture Close to Randomization Receiving Rezafungin or Caspofungin in the ReSTORE Study.

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included day 30 ACM, day 14 global cure rate, and day 5 and 14 mycological response. Adverse events were evaluated. RESULTS: This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively, day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval], 4.6% [-13.7%, 23.5%]), day 14 global response was 55.3% and 50.0% (between-group difference, 5.3% [-16.1%, 26.0%]), and day 5 mycological eradication was 71.1% and 50.0% (between-group difference, 21.1% [-0.2%, 40.2%]). Safety was comparable between treatments. CONCLUSIONS: These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.

Ultrasensitive and Rapid Circulating Tumor DNA Liquid Biopsy Using Surface-Confined Gene Amplification on Dispersible Magnetic Nano-Electrodes.

Circulating tumor DNA (ctDNA) detection has been acknowledged as a promising liquid biopsy approach for cancer diagnosis, with various ctDNA assays used for early detection and treatment monitoring. Dispersible magnetic nanoparticle-based electrochemical detection methods have been proposed as promising candidates for ctDNA detection based on the detection performance and features of the platform material. This study proposes a nanoparticle surface-localized genetic amplification approach by integrating Fe3O4-Au core-shell nanoparticles into polymerase chain reactions (PCR). These highly dispersible and magnetically responsive superparamagnetic nanoparticles act as nano-electrodes that amplify and accumulate target ctDNA in situ on the nanoparticle surface upon PCR amplification. These nanoparticles are subsequently captured and subjected to repetitive electrochemical measurements to induce reconfiguration-mediated signal amplification for ultrasensitive (∼3 aM) and rapid (∼7 min) metastatic breast cancer ctDNA detection in vitro. The detection platform can also detect metastatic biomarkers from in vivo samples, highlighting the potential for clinical applications and further expansion to rapid and ultrasensitive multiplex detection of various cancers.

Impact of Infection Prevention Programs on Catheter-Associated Urinary Tract Infections Analyzed in Multicenter Study.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) account for a large proportion of healthcare-associated infections and have a significant impact on morbidity, length of hospital stay, and mortality. Adherence to the recommended infection prevention practices can effectively reduce the incidence of CAUTIs. This study aimed to assess the characteristics of CAUTIs and the efficacy of prevention programs across hospitals of various sizes. METHODS: Intervention programs, including training, surveillance, and monitoring, were implemented. Data on the microorganisms responsible for CAUTIs, urinary catheter utilization ratio, rate of CAUTIs per 1,000 device days, and factors associated with the use of indwelling catheters were collected from 2017 to 2019. The incidence of CAUTIs and associated data were compared between university hospitals and small- and medium-sized hospitals. RESULTS: Thirty-two hospitals participated in the study, including 21 university hospitals and 11 small- and medium-sized hospitals. The microorganisms responsible for CAUTIs and their resistance rates did not differ between the two groups. In the first quarter of 2018, the incidence rate was 2.05 infections/1,000 device-days in university hospitals and 1.44 infections/1,000 device-days in small- and medium-sized hospitals. After implementing interventions, the rate gradually decreased in the first quarter of 2019, with 1.18 infections/1,000 device-days in university hospitals and 0.79 infections/1,000 device-days in small- and medium-sized hospitals. However, by the end of the study, the infection rate increased to 1.74 infections/1,000 device-days in university hospitals and 1.80 infections/1,000 device-days in small- and medium-sized hospitals. CONCLUSION: We implemented interventions to prevent CAUTIs and evaluated their outcomes. The incidence of these infections decreased in the initial phases of the intervention when adequate support and personnel were present. The rate of these infections may be reduced by implementing active interventions such as consistent monitoring and adherence to guidelines for preventing infections.

Magnetically Stimulated Integrin Binding Alters Cell Polarity and Affects Epithelial-Mesenchymal Plasticity in Metastatic Cancer Cells.

Inorganic nanoparticles (NPs) have been widely recognized for their stability and biocompatibility, leading to their widespread use in biomedical applications. Our study introduces a novel approach that harnesses inorganic magnetic nanoparticles (MNPs) to stimulate apical-basal polarity and induce epithelial traits in cancer cells, targeting the hybrid epithelial/mesenchymal (E/M) state often linked to metastasis. We employed mesocrystalline iron oxide MNPs to apply an external magnetic field, disrupting normal cell polarity and simulating an artificial cellular environment. These led to noticeable changes in the cell shape and function, signaling a shift toward the hybrid E/M state. Our research suggests that apical-basal stimulation in cells through MNPs can effectively modulate key cellular markers associated with both epithelial and mesenchymal states without compromising the structural properties typical of mesenchymal cells. These insights advance our understanding of how cells respond to physical cues and pave the way for novel cancer treatment strategies. We anticipate that further research and validation will be instrumental in exploring the full potential of these findings in clinical applications, ensuring their safety and efficacy.

One-Step Electrochemical Synthesis of Multiyolk-Shell Nanocoils for Exceptional Photocatalytic Performance.

Multiyolk-shell (mYS) nanostructures have garnered significant interest in various photocatalysis applications such as water splitting and waste treatment. Nonetheless, the complexity and rigorous conditions for the synthesis have hindered their widespread implementation. This study presents a one-step electrochemical strategy for synthesizing multiyolk-shell nanocoils (mYSNC), wherein multiple cores of noble metal nanoparticles, such as Au, are embedded within the hollow coil-shaped FePO4 shell structures, mitigating the challenges posed by conventional methods. By capitalizing on the dissimilar dissolution rates of bimetallic alloy nanocoils in an electrochemically programmed solution, nanocoils of different shapes and materials, including two variations of mYSNCs are successfully fabricated. The resulting Au-FePO4 mYSNCs exhibit exceptional photocatalytic performance for environmental remediation, demonstrating up to 99% degradation of methylene blue molecules within 50 min and 95% degradation of tetracycline within 100 min under ultraviolet-visible (UV-vis) light source. This remarkable performance can be attributed to the abundant electrochemical active sites, internal voids facilitating efficient light harvesting with coil morphology, amplified localized surface plasmon resonance (LSPR) at the plasmonic nanoparticle-semiconductor interface, and effective band engineering. The innovative approach utilizing bimetallic alloys demonstrates precise geometric control and design of intricate multicomponent hybrid composites, showcasing the potential for developing versatile hollow nanomaterials for catalytic applications.

Assessment of quality of care for hospitalized non-COVID-19 older adult patients with pneumonia before and after the COVID-19 pandemic.

BACKGROUND: There is limited research into the clinical implications of the coronavirus disease 2019 (COVID-19) pandemic for non-COVID-19 pneumonia in older adults, as well as their quality of care or outcomes. This study aims to assess the process and outcome quality of care for hospitalized older adult patients with pneumonia before and after the pandemic. METHODS: A retrospective cohort of older adult patients (age ≥ 65) hospitalized for non-COVID pneumonia were recruited from five Korean hospitals (January 20, 2019, to January 19, 2021). The quality of care before and after the COVID-19 pandemic was evaluated. RESULTS: A total of 7356 hospitalization episodes of older adult pneumonia were identified, and 978 cases (552 pre-pandemic and 426 during the pandemic) were analyzed. The pneumonia severity score was higher during the pandemic, and the waiting time from the emergency room to admission was also longer. Furthermore, the pneumonia mortality rate during the pandemic was higher than that in the pre-pandemic period (in-hospital mortality: 10.1% vs. 18.1%; 90-day mortality: 11.6% vs. 22.3%). A significantly higher mortality risk was observed during the pandemic than in the period prior (adjusted odds ratio: 1.74, 95% confidence interval: 1.14-2.63). CONCLUSIONS: While the quality of care for hospitalized pneumonia has been maintained during the pandemic, there has been an increase in mortality rates. Further investigations are needed to understand the underlying causes of this increase.

Clinical Characteristics and Risk of Hypoxemia Development in Women Infected with SARS-CoV-2 during Pregnancy.

PURPOSE: There is limited information on the clinical characteristics and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy. The clinical features and risk factors for hypoxemia development were investigated in pregnant women with coronavirus disease-2019 (COVID-19). MATERIALS AND METHODS: From August 2020 to February 2022, we performed a retrospective cohort study of 410 pregnant women with COVID-19. The clinical characteristics and prognoses were compared between pregnant COVID-19 patients requiring oxygen and those who did not. RESULTS: Of 410 patients, 100 (24.4%) required oxygen therapy. Among them, fever [163 (52.6%) vs. 81 (81.0%), p<0.001] and cough [172 (56.4%) vs. 73 (73.0%), p=0.003] were more frequently observed than in non-oxygen group. The proportion of unvaccinated women was higher in oxygen group than in non-oxygen group [264 (85.2%) vs. 98 (98.0%), p=0.003]. During the Omicron wave, patients were more likely to have no oxygen requirement [98 (31.6%) vs. 18 (18.0%), p=0.009]. The risk of hypoxemic respiratory difficulty increased if SARS-CoV-2 infection occurred during the third trimester [adjusted odds ratio (aOR) 5.083, 95% confidence interval (CI): 1.095-23.593, p=0.038] and C-reactive protein (CRP) was elevated (≥1.0 mg/dL) at admission (aOR 5.878, 95% CI: 3.099-11.146, p<0.001). The risk was higher in unvaccinated patients (aOR 5.376, 95% CI: 1.193-24.390, p=0.028). However, the risk was lower in patients during the Omicron wave (aOR 0.498, 95% CI: 0.258-0.961, p=0.038). CONCLUSION: A quarter of SARS-CoV-2-infected women developed hypoxemic respiratory difficulty during pregnancy. SARS-CoV-2 infection during the third trimester, CRP elevation at admission, and no vaccination increased the risk of hypoxemia in pregnant women.

Time-Frequency Multi-Domain 1D Convolutional Neural Network with Channel-Spatial Attention for Noise-Robust Bearing Fault Diagnosis.

This paper proposes a noise-robust and accurate bearing fault diagnosis model based on time-frequency multi-domain 1D convolutional neural networks (CNNs) with attention modules. The proposed model, referred to as the TF-MDA model, is designed for an accurate bearing fault classification model based on vibration sensor signals that can be implemented at industry sites under a high-noise environment. Previous 1D CNN-based bearing diagnosis models are mostly based on either time domain vibration signals or frequency domain spectral signals. In contrast, our model has parallel 1D CNN modules that simultaneously extract features from both the time and frequency domains. These multi-domain features are then fused to capture comprehensive information on bearing fault signals. Additionally, physics-informed preprocessings are incorporated into the frequency-spectral signals to further improve the classification accuracy. Furthermore, a channel and spatial attention module is added to effectively enhance the noise-robustness by focusing more on the fault characteristic features. Experiments were conducted using public bearing datasets, and the results indicated that the proposed model outperformed similar diagnosis models on a range of noise levels ranging from -6 to 6 dB signal-to-noise ratio (SNR).

Coinfection With Severe Fever With Thrombocytopenia Syndrome and Scrub Typhus in Korea.

Background: Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) are the 2 most common tick-borne infectious diseases in Korea. Every year, an increasing number of cases are reported, which is a public health concern. Therefore, we aimed to investigate the prevalence of SFTS-scrub typhus coinfection in patients with SFTS. Methods: Clinical samples were collected from 129 patients with SFTS. One-step reverse-transcription polymerase chain reaction (PCR) was performed to identify the SFTS virus (SFTSV), and real-time PCR followed by nested PCR was performed to detect the Orientia tsutsugamushi gene for scrub typhus. Phylogenetic analysis was conducted to confirm the evolutionary relationships among different species. Results: Among 129 SFTS cases, 2 patients with SFTSV were positive for O. tsutsugamushi with a prevalence of coinfection of 1.6% (95% confidence interval, .001-.06). Phylogenetic analysis confirmed these as O. tsutsugamushi strain Boryong. Conclusions: Our study found that 1.6% of patients were coinfected with SFTS and scrub typhus infection. We believe that this information will add a new dimension to clinical diagnosis, which should be considered for better public health management. Further research is needed to better understand the ecological transmission dynamics and geographical distribution of SFTSV and O. tsutsugamushi in endemic countries.

The Influence of Capping Layers on Tunneling Magnetoresistance and Microstructure in CoFeB/MgO/CoFeB Magnetic Tunnel Junctions upon Annealing.

This study investigates the effects of annealing on the tunnel magnetoresistance (TMR) ratio in CoFeB/MgO/CoFeB-based magnetic tunnel junctions (MTJs) with different capping layers and correlates them with microstructural changes. It is found that the capping layer plays an important role in determining the maximum TMR ratio and the corresponding annealing temperature (Tann). For a Pt capping layer, the TMR reaches ~95% at a Tann of 350 °C, then decreases upon a further increase in Tann. A microstructural analysis reveals that the low TMR is due to severe intermixing in the Pt/CoFeB layers. On the other hand, when introducing a Ta capping layer with suppressed diffusion into the CoFeB layer, the TMR continues to increase with Tann up to 400 °C, reaching ~250%. Our findings indicate that the proper selection of a capping layer can increase the annealing temperature of MTJs so that it becomes compatible with the complementary metal-oxide-semiconductor backend process.

Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trial.

Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18-64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63-3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68-14.32) also satisfied the non-inferiority criterion (95% CI lower limit > -5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Materials Quest for Advanced Interconnect Metallization in Integrated Circuits.

Integrated circuits (ICs) are challenged to deliver historically anticipated performance improvements while increasing the cost and complexity of the technology with each generation. Front-end-of-line (FEOL) processes have provided various solutions to this predicament, whereas the back-end-of-line (BEOL) processes have taken a step back. With continuous IC scaling, the speed of the entire chip has reached a point where its performance is determined by the performance of the interconnect that bridges billions of transistors and other devices. Consequently, the demand for advanced interconnect metallization rises again, and various aspects must be considered. This review explores the quest for new materials for successfully routing nanoscale interconnects. The challenges in the interconnect structures as physical dimensions shrink are first explored. Then, various problem-solving options are considered based on the properties of materials. New materials are also introduced for barriers, such as 2D materials, self-assembled molecular layers, high-entropy alloys, and conductors, such as Co and Ru, intermetallic compounds, and MAX phases. The comprehensive discussion of each material includes state-of-the-art studies ranging from the characteristics of materials by theoretical calculation to process applications to the current interconnect structures. This review intends to provide a materials-based implementation strategy to bridge the gap between academia and industry.

Exploring the Magnetic Properties of Individual Barcode Nanowires using Wide-Field Diamond Microscopy.

A barcode magnetic nanowire typically comprises a multilayer magnetic structure in a single body with more than one segment type. Interestingly, due to selective functionalization and novel interactions between the layers, it has attracted significant attention, particularly in bioengineering. However, analyzing the magnetic properties at the individual nanowire level remains challenging. Herein, the characterization of a single magnetic nanowire is investigated at room temperature under ambient conditions based on magnetic images obtained via wide-field quantum microscopy with nitrogen-vacancy centers in diamond. Consequently, critical magnetic properties of a single nanowire can be extracted, such as saturation magnetization and coercivity, by comparing the experimental result with that of micromagnetic simulation. This study opens up the possibility for a versatile in situ characterization method suited to individual magnetic nanowires.

Clinically differential diagnosis of human granulocytic anaplasmosis and severe fever with thrombocytopenia syndrome.

This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia (< 1500) (OR 41.64, P < 0.001), prolonged activated partial thromboplastin time (OR 80.133, P < 0.001), and normal C-reactive protein concentration (≤ 1.0 mg/dL; OR 166.855, P = 0.001) were significantly associated with SFTS but not with HGA. Each factor, such as meaningful variables, was given 1 point, and a receiver-operating characteristic curve with a cutoff value (> 1) in a 5-point scoring system (0-4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949-0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.

Pregnancy and COVID-19: past, present and future.

Current evidence suggests that severe acute respiratory syndrome coronavirus 2 infection is associated with an increased incidence of adverse severe maternal and perinatal outcomes. However, vertical transmission is rare. The management of pregnant women with coronavirus disease 2019 (COVID-19) is similar to that of non-pregnant women, and effective treatments, including antiviral therapy, dexamethasone, and prophylactic anticoagulation should not be withheld during pregnancy. During the early COVID-19 pandemic period, the management of pregnant women was often delayed until the polymerase chain reaction (PCR) results came out or due to close contact, even among those without symptoms. Out of concern for the spread of infection, cesarean sections were performed instead of vaginal birth, since infection could have led to an increase in maternal and neonatal morbidities. Additionally, if the maternal PCR test was positive, the neonate was quarantined, and despite infectivity decreasing 10 days after symptom onset. It is necessary to ease the strict measures of infection control in the field of obstetrics. The presence or absence of maternal COVID-19 symptoms should be identified to stratify the risk, and vaginal delivery can be attempted in asymptomatic women with low infectivity. With more women being vaccinated safety data about vaccination is rapidly accumulating and no concerns have been detected. Globally, COVID-19 vaccines are recommended even during pregnancy. In order to prepare for future pandemics, it is necessary to apply lessons learned from this pandemic. Policymakers and healthcare leaders must determine efficient and effective strategies for preserving safe maternal care, even during an ongoing global emergency.

Multifunctional Nanoparticle Platform for Surface Accumulative Nucleic Acid Amplification and Rapid Electrochemical Detection: An Application to Pathogenic Coronavirus.

Of various molecular diagnostic assays, the real-time reverse transcription polymerase chain reaction is considered the gold standard for infection diagnosis, despite critical drawbacks that limit rapid detection and accessibility. To confront these issues, several nanoparticle-based molecular detection methods have been developed to a great extent, but still possess several challenges. In this study, a novel nucleic acid amplification method termed nanoparticle-based surface localized amplification (nSLAM) is paired with electrochemical detection (ECD) to develop a nucleic acid biosensor platform that overcomes these limitations. The system uses primer-functionalized Fe3O4-Au core-shell nanoparticles for nucleic acid amplification, which promotes the production of amplicons that accumulate on the nanoparticle surfaces, inducing significantly amplified currents during ECD that identify the presence of target genetic material. The platform, applying to the COVID-19 model, demonstrates an exceptional sensitivity of ∼1 copy/µL for 35 cycles of amplification, enabling the reduction of amplification cycles to 4 cycles (∼7 min runtime) using 1 fM complementary DNA. The nSLAM acts as an accelerator that actively promotes and participates in the nucleic acid amplification process through direct polymerization and binding of amplicons on the nanoparticle surfaces. This ultrasensitive fast-response system is a promising method for detecting emerging pathogens like the coronavirus and can be extended to detect a wider variety of biomolecules.