One-hit kill: On the inactivation of RNA viruses by ultraviolet (UV)-C-induced genomic damage.

Large scale outbreaks of infectious respiratory disease have repeatedly plagued the globe over the last 100 years. The scope and strength of the outbreaks are getting worse as pathogenic RNA viruses are rapidly evolving and highly evasive to vaccines and anti-viral drugs. Germicidal UV-C is considered as a robust agent to disinfect RNA viruses regardless of their evolution. While genomic damage by UV-C has been known to be associated with viral inactivation, the precise relationship between the damage and inactivation remains unsettled as genomic damage has been analyzed in small areas, typically under 0.5 kb. In this study, we assessed genomic damage by the reduced efficiency of reverse transcription of regions of up to 7.2 kb. Our data seem to indicate that genomic damage was directly proportional to the size of the genome, and a single hit of damage was sufficient for inactivation of RNA viruses. The high efficacy of UV-C is already effectively adopted to inactivate airborne RNA viruses.

Usefulness of CT Quantification-Based Assessment in Defining Progressive Pulmonary Fibrosis.

RATIONALE AND OBJECTIVES: To establish a quantitative CT threshold for radiological disease progression of progressive pulmonary fibrosis (PPF) and evaluate its feasibility in patients with connective tissue disease-related interstitial lung disease (CTD-ILD). MATERIALS AND METHODS: Between April 2007 and October 2022, patients diagnosed with CTD-ILD retrospectively evaluated. CT quantification was conducted using a commercial software by summing the percentages of ground-glass opacity, consolidation, reticular opacity, and honeycombing. The quantitative threshold for radiological progression was determined based on the highest discrimination on overall survival (OS). Two thoracic radiologists independently evaluated visual radiological progression, and the senior radiologist's assessment was used as the final result. Cox regression was used to assess prognosis of PPF based on the visual assessment and quantitative threshold. RESULTS: 97 patients were included and followed up for a median of 30.3 months (range, 4.7-198.1 months). For defining radiological disease progression, the optimal quantitative CT threshold was 4%. Using this threshold, 12 patients were diagnosed with PPF, while 14 patients were diagnosed with PPF based on the visual assessment, with an agreement rate of 97.9% (95/97). Worsening respiratory symptoms (hazard ratio [HR], 12.73; P < .001), PPF based on the visual assessment (HR, 8.86; P = .002) and based on the quantitative threshold (HR, 6.72; P = .009) were independent risk factors for poor OS. CONCLUSION: The quantitative CT threshold for radiological disease progression (4%) was feasible in defining PPF in terms of its agreement with PPF grouping and prognostic performance when compared to visual assessment.

Clinical Efficacy and Safety of an Automatic Closed-Suction System in Mechanically Ventilated Patients with Pneumonia: A Multicenter, Prospective, Randomized, Non-Inferiority, Investigator-Initiated Trial.

Endotracheal suctioning is an essential but labor-intensive procedure, with the risk of serious complications. A brand new automatic closed-suction device was developed to alleviate the workload of healthcare providers and minimize those complications. We evaluated the clinical efficacy and safety of the automatic suction system in mechanically ventilated patients with pneumonia. In this multicenter, randomized, non-inferiority, investigator-initiated trial, mechanically ventilated patients with pneumonia were randomized to the automatic device (intervention) or conventional manual suctioning (control). The primary efficacy outcome was the change in the modified clinical pulmonary infection score (CPIS) in 3 days. Secondary outcomes were the frequency of additional suctioning and the amount of secretion. Safety outcomes included adverse events or complications. A total of 54 participants, less than the pre-determined number of 102, were enrolled. There was no significant difference in the change in the CPIS over 72 h (-0.13 ± 1.58 in the intervention group, -0.58 ± 1.18 in the control group, p = 0.866), but the non-inferiority margin was not satisfied. There were no significant differences in the secondary outcomes and safety outcomes, with a tendency for more patients with improved tracheal mucosal injury in the intervention group. The novel automatic closed-suction system showed comparable efficacy and safety compared with conventional manual suctioning in mechanically ventilated patients with pneumonia.

Assessment of Treatment Response in Patients With Severe Asthma Using Visual and Quantitative Analysis of Chest CT.

OBJECTIVE: To evaluate the role of visual and quantitative chest CT parameters in assessing treatment response in patients with severe asthma. MATERIALS AND METHODS: Korean participants enrolled in a prospective multicenter study, named the Precision Medicine Intervention in Severe Asthma study, from May 2020 to August 2021, underwent baseline and follow-up chest CT scans (inspiration/expiration) 10-12 months apart, before and after biologic treatment. Two radiologists scored bronchiectasis severity and mucus plugging extent. Quantitative parameters were obtained from each CT scan as follows: normal lung area (normal), air trapping without emphysema (AT without emph), air trapping with emphysema (AT with emph), and airway (total branch count, Pi10). Clinical parameters, including pulmonary function tests (forced expiratory volume in 1 s [FEV1] and FEV1/forced vital capacity [FVC]), sputum and blood eosinophil count, were assessed at initial and follow-up stages. Changes in CT parameters were correlated with changes in clinical parameters using Pearson or Spearman correlation. RESULTS: Thirty-four participants (female:male, 20:14; median age, 50.5 years) diagnosed with severe asthma from three centers were included. Changes in the bronchiectasis and mucus plugging extent scores were negatively correlated with changes in FEV1 and FEV1/FVC (ρ = from -0.544 to -0.368, all P < 0.05). Changes in quantitative CT parameters were correlated with changes in FEV1 (normal, r = 0.373 [P = 0.030], AT without emph, r = -0.351 [P = 0.042]), FEV1/FVC (normal, r = 0.390 [P = 0.022], AT without emph, r = -0.370 [P = 0.031]). Changes in total branch count were positively correlated with changes in FEV1 (r = 0.349 [P = 0.043]). There was no correlation between changes in Pi10 and the clinical parameters (P > 0.05). CONCLUSION: Visual and quantitative CT parameters of normal, AT without emph, and total branch count may be effective for evaluating treatment response in patients with severe asthma.

Diffusion-Weighted MR Neurography with Unidirectional Motion-Probing Gradient to Evaluate Lumbar Nerve Roots at 1.5T MR.

Purpose: Recent studies have demonstrated the usefulness of diffusion-weighted MR neurography (DW MRN) for assessing nerve roots. This study aimed to evaluate the utility of DW MRN with a unidirectional motion-probing gradient (MPG) for the lumbar nerve roots at 1.5T MR. Materials and Methods: Sixty-four lumbar spine MRI scans with DW MRN using anteroposterior unidirectional MPG were retrospectively analyzed. Any changes in the 512 lumbar spinal nerve roots from L3 to S1 were evaluated using T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CE T1WI), and DW MRN, with agreement and correlation analysis. Results: T2WI revealed compression of 78 nerve roots, and CE T1WI revealed 52 instances of nerve root enhancement. Sixty-seven nerve roots showed swelling and hyperintensity on DW MRN. A total of 42 nerve roots showed changes in the CE T1WI and DW MRN sequences. Moderate to substantial agreement and moderate positive correlation were observed between DW MRN and CE T1WI, as well as DW MRN and T2WI (κ = 0.59-0.65, ρ = 0.600-0.653). Conclusion: DW MRN with unidirectional anteroposterior MPG can help evaluate neuritis-related changes in spinal nerve roots and could serve as a sequence capable of complementing or substituting gadolinium CE imaging.

Identifying factors related to delayed neck metastasis after surgical treatment in patients with oral squamous cell carcinoma.

BACKGROUND: General treatment of oral squamous cell carcinoma (OSCC) is surgical treatment with or without neck dissection. Although the incidence of delayed neck metastasis is rare, it may occur after the surgery and is known to be the most important factor in the prognosis. The purpose of is study is to evaluate the clinical and histopathological factors associated with delayed neck metastasis case among patients. METHODS: A total of 195 patients who underwent surgical treatment for OSCC from 2016 to 2022 were investigated. Among them, delayed neck metastasis (DNM) was analyzed. The criterion for delayed neck metastasis was a newly developed neck lesion after the primary operation without neck dissection in cN0 necks. To identify the correlation between prognostic factors and the incidence of delayed neck metastasis, χ2 analysis with phi correlation and Cramer's V test was performed. Cumulative survival rates (CRS) were compared between the groups with the incidence of DNM and without DNM. Also, the log rank test for CSR and Cox proportional hazard model was analyzed to estimate the significance of the CSR and confirm the correlations between prognostic factors and DNM. RESULT: Among 195 patients, 14 were discovered to have DNM. The primary tumor locations were the tongue (n = 5), floor of the mouth (n = 2), mandibular gingiva (n = 1), maxillary gingiva (n = 4), retromolartrigone (n = 1), and buccal mucosa (n = 2) each. The cases consisted of TNM stage I (n = 1), stage II (n = 3), stage III (n = 3), and stage IV (n = 8), respectively. The result of the χ2 analysis identified a correlation between positive neck (p = 0.01), depth of invasion (p = 0.09), radiation therapy (p = 0.003), and DNM. Groups without DNM showed better prognosis compared to groups with DNM. Regarding positive neck, depth of invasion, and radiation therapy, only depth of invasion showed significance in CSR analysis. CONCLUSION: DNM after surgical treatment of OSCC is a rare event, and few were found in a review of the literature. Also, many prognostic factors have been suggested but controversial. However, in our study, some prognostic factors have been identified to have a significant correlation with the incidence of DNM, and analysis of such factors provides important information predicting neck metastasis and the prognosis.

Acquired Acromion Compromise, Including Thinning and Fragmentation, Is Not Associated With Poor Outcomes After Reverse Shoulder Arthroplasty.

BACKGROUND: Acquired acromial compromise, including thinning (less than 30% of the normal acromion) or fragmentation resulting from acromiohumeral impingement or previous acromioplasty, is a concern in reverse shoulder arthroplasty (RSA). This condition may lead to shoulder pain and difficulties in arm elevation because of acromial insufficiency fracture. QUESTIONS/PURPOSES: (1) Do patients with acromial compromise (thinning less than 30% of normal acromion or fragmentation) have worse functional outcome scores, ROM, and strength after RSA compared with patients without acromial compromise? (2) Are patients with acromial compromise at a higher risk of complications such as acromial insufficiency fracture after RSA? (3) Do patients who develop acromial insufficiency fracture have predisposing associated factors and worse clinical outcomes? METHODS: Between January 1, 2016, and December 31, 2020, we treated 398 patients with RSA, and all patients were considered potentially eligible for this study. Our clinic is part of the orthopaedic department within a tertiary general hospital, serving patients from across the country. Among them, 49% (197 of 398) of patients were excluded for the following reasons: 8% (31 of 398) because of proximal humerus fracture, 5% (19 of 398) because of osteonecrosis, 9% (35 of 398) because of previous infective arthritis, 5% (18 of 398) because of a deformed shoulder, 4% (14 of 398) because of poor general condition after surgery, 3% (12 of 398) because of death, and another 17% (68 of 398) were lost before the minimum study follow-up, leaving 51% (201 of 398) for analysis. A preoperative acromial compromise was defined as follows: (1) thinning of the acromion (< 3 mm), which means a thickness of less than 30% of the normal acromion thickness (8 to 9 mm), and (2) acromial fragmentation. Acromial thickness was measured using a CT scan. The middle portion of the anterolateral acromion, situated lateral to the distal end of the clavicle, was crosschecked using the axial view. Measurements were subsequently performed from both coronal and sagittal views. In all, 29 patients with acromion compromise and 172 without acromion compromise met the inclusion and exclusion criteria. There was no differential loss to follow-up before 2 years between patients with and without acromial compromise in this study (36% [16 of 45] versus 23% [52 of 224]; p = 0.12). We matched patients using propensity score, pairing them in a 1:3 ratio based on gender, age, bone mineral density, diagnosis, previous rotator cuff repair surgery, subscapularis repair or latissimus dorsi transfer performed during surgery, the type of prosthesis used, and follow-up duration. Twenty-three patients with acromial compromise (acromion compromised group) and 69 patients without acromial compromise (normal control group) were matched; the mean ± SD duration of follow-up was 40 ± 22 months in those with acromial compromise and 43 ± 19 months the in normal control group. Pre- and postoperative functional outcome scores, ROM, and shoulder strength were compared. Shoulder scaption refers to lifting the arm in the scapular plane, and scaption strength was measured by applying upward force with the arm at 90° while seated, pushing it as far as possible and measured using a handheld myometer. Complications, including acromial insufficiency fracture, scapular notching, dislocation, periprosthetic infection, and overall risk of complication, were analyzed. Acromial insufficiency fracture was diagnosed based on clinical and radiological findings. Clinically, sudden pain and tenderness at the acromion along with reduced shoulder elevation raised acromial insufficiency fracture suspicion. Radiologically, acromion tilt on plain radiograph or fracture line on coronal CT view confirmed diagnosis of acromial insufficiency fracture. RESULTS: Comparing both groups, patients with a compromised acromion had no difference in American Shoulder and Elbow Surgeons scores (60 ± 12 versus 64 ± 12; mean difference -4 [95% CI -11 to 2]; p = 0.16), Constant scores (48 ± 10 versus 54 ± 12; mean difference -6 [95% CI -13 to 0]; p = 0.06), forward flexion degree (125 ± 24 versus 130 ± 21; mean difference -5 [95% CI -16 to 6]; p = 0.36), and scaption strength (5 ± 3 versus 6 ± 3; mean difference -1 [95% CI -3 to 0]; p = 0.13). Having acromial compromise was not associated with increased risk of overall complications (30% [7 of 23] versus 19% [13 of 69], relative risk 2 [95% CI 1 to 4]; p = 0.26). However, the only complication that was higher in the acromial compromised group was infection (13% [3 of 23] versus 0% [0 of 69], relative risk not available; p = 0.01). Only the lateralized glenoid prosthesis demonstrated negative association with the acromial insufficiency fracture occurrence; no other factors showed an association. The use of lateralized glenoid prostheses was not observed in patients with acromial insufficiency fracture (0% [0 of 7] acromial insufficiency fracture versus 39% [33 of 85] no acromial insufficiency fracture, relative risk 0 [95% CI 0]; p = 0.047). CONCLUSION: In patients with acquired acromial compromise-such as thinning or fragmented acromion because of advanced cuff tear arthropathy or previous acromioplasty-primary RSA resulted in no different functional outcome score, ROM, shoulder strength, and overall complications compared with patients without acromial compromise. Our findings suggest that a thin or fragmented acromion may not necessarily be exclusion criteria for RSA, potentially aiding surgeons in their decision-making process when treating these patients. However, one of the major complications, postoperative infection, is more frequently observed in patients with acquired acromial compromise. Pre- and postoperative caution would be necessary to prevent and detect infection even when short-term outcomes are favorable in this study. Further studies with large cohorts and long-term follow-up durations are needed. LEVEL OF EVIDENCE: Level III, therapeutic study.

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.

W-DRAG: A joint framework of WGAN with data random augmentation optimized for generative networks for bone marrow edema detection in dual energy CT.

Dual-energy computed tomography (CT) is an excellent substitute for identifying bone marrow edema in magnetic resonance imaging. However, it is rarely used in practice owing to its low contrast. To overcome this problem, we constructed a framework based on deep learning techniques to screen for diseases using axial bone images and to identify the local positions of bone lesions. To address the limited availability of labeled samples, we developed a new generative adversarial network (GAN) that extends expressions beyond conventional augmentation (CA) methods based on geometric transformations. We theoretically and experimentally determined that combining the concepts of data augmentation optimized for GAN training (DAG) and Wasserstein GAN yields a considerably stable generation of synthetic images and effectively aligns their distribution with that of real images, thereby achieving a high degree of similarity. The classification model was trained using real and synthetic samples. Consequently, the GAN technique used in the diagnostic test had an improved F1 score of approximately 7.8% compared with CA. The final F1 score was 80.24%, and the recall and precision were 84.3% and 88.7%, respectively. The results obtained using the augmented samples outperformed those obtained using pure real samples without augmentation. In addition, we adopted explainable AI techniques that leverage a class activation map (CAM) and principal component analysis to facilitate visual analysis of the network's results. The framework was designed to suggest an attention map and scattering plot to visually explain the disease predictions of the network.

Effect of recombinant human bone morphogenetic protein-2 and osteoprotegerin-Fc in MC3T3-E1 cells.

Objective: We compared the osteoblastogenesis by serially administrating recombinant human bone morphogenetic protein-2 (rhBMP-2) and osteoprotegerin-immunoglobulin Fc segment complex (OPG-Fc). Methods: The MC3T3-E1 preosteoblast cell line was differentiated for 1, 3, and 7 days with a treatment of OPG-Fc in 10~200 ng/mL concentration and the cell viability was evaluated by Cell Counting Kit-8 analysis. The level of differentiation from MC3T3-E1 cells to osteoblasts was determined by alkaline phosphatase activity. The level of runt domain-containing transcription factor 2 (Runx2) and osteopontin (OPN) manifestation, involved in osteoblast differentiation, was examined by real-time polymerase chain reaction and western blotting. Results: During MC3T3-E1 cell differentiation, the differentiation level was high with 1-day treatment using 100 ng/mL OPG-Fc. The treatment with 50 ng/mL rhBMP-2 for 7 days, followed by 1-day treatment with 100 ng/mL OPG-Fc produced the highest differentiation level, which was approximately 5.3 times that of the control group (p<0.05). The expression of Runx2 mRNA significantly increased, reaching 2.5 times the level of the control group under the condition of 7-day treatment with rhBMP-2 and 1-day treatment with OPG-Fc (p<0.001). The expression of Runx2 protein significantly increased to approximately 5.7 times that of the control group under the condition of 7-day treatment with rhBMP-2, followed by 1-day treatment with OPG-Fc (p<0.01). The expression of OPN protein showed no change from that of the control group under various conditions of rhBMP-2 and OPG-Fc combinations. Conclusion: These results imply that the treating preosteoblasts with rhBMP-2 first and then with OPG-Fc increased osteoblast differentiation efficacy.

Effect of Meniscal Tear Patterns and Preoperative Cartilage Status on Joint Space Width After Medial Opening-Wedge High Tibial Osteotomy.

BACKGROUND: Medial opening-wedge high tibial osteotomy (MOWHTO) is performed to treat young adults with medial compartment knee osteoarthritis associated with varus deformity. However, factors influencing joint space width (JSW) vary according to the type of medial meniscal tear and have not yet been completely elucidated. PURPOSE: To examine changes in JSW according to the type of medial meniscal tear after MOWHTO and analyze the influencing factors. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study was conducted on 134 patients who underwent MOWHTO for medial osteoarthritis and were followed up for >2 years. The patients were classified into 3 groups based on medial meniscal status: intact, nonroot tear, and root tear. The authors then measured the JSW preoperatively and at 3 months, 6 months, 1 year, and >2 years postoperatively; analyzed whether the change in JSW varied according to meniscal status; and determined the association of these changes with the preoperative cartilage grade of the medial femoral condyle (MFC) and medial tibial plateau (MTP). International Knee Documentation Committee (IKDC) scores were used to evaluate clinical function. RESULTS: Of the 134 patients, the medial meniscus was intact in 29 patients, a nonroot tear was observed in 58 patients, and a root tear was observed in 47 patients. Postoperatively, JSW increased for all groups, but the timing of the increase varied between the groups (P < .001). JSW increased the most 6 months postoperatively in the intact group and 3 months postoperatively in the nonroot tear and root tear groups (P < .001). Additionally, the increase in JSW was the greatest in the root tear group. Preoperatively, MFC and MTP cartilage status differed among the groups; MTP status did not affect the JSW, but MFC status did (P < .001). The IKDC score increased from the preoperative to postoperative time point in all groups, but there was no significant difference between groups. CONCLUSION: The authors observed that the amount and timing of increase in JSW were dependent on the pattern of medial meniscal tear observed when MOWHTO was performed. In addition, the cartilage grade of MFC before surgery was associated with changes in JSW. The IKDC score was not significantly different between groups. However, a longer follow-up period is needed to analyze the correlation with the meniscal tear pattern and JSW.

Risk factors for progressing to critical illness in patients with hospital-acquired COVID-19.

BACKGROUND/AIMS: Risk factors for progression to critical illness in hospital-acquired coronavirus disease 2019 (COVID-19) remain unknown. Here, we assessed the incidence and risk factors for progression to critical illness and determined their effects on clinical outcomes in patients with hospital-acquired COVID-19. METHODS: This retrospective cohort study analyzed patients admitted to the tertiary hospital between January 2020 and June 2022 with confirmed hospital-acquired COVID-19. The primary outcome was the progression to critical illness of hospital- acquired COVID-19. Patients were stratified into high-, intermediate-, or low-risk groups by the number of risk factors for progression to critical illness. RESULTS: In total, 204 patients were included and 37 (18.1%) progressed to critical illness. In the multivariable logistic analysis, patients with preexisting respiratory disease (OR, 3.90; 95% CI, 1.04-15.18), preexisting cardiovascular disease (OR, 3.49; 95% CI, 1.11-11.27), immunocompromised status (OR, 3.18; 95% CI, 1.11-9.16), higher sequential organ failure assessment (SOFA) score (OR, 1.56; 95% CI, 1.28-1.96), and higher clinical frailty scale (OR, 2.49; 95% CI, 1.62-4.13) showed significantly increased risk of progression to critical illness. As the risk of the groups increased, patients were significantly more likely to progress to critical illness and had higher 28-day mortality. CONCLUSION: Among patients with hospital-acquired COVID-19, preexisting respiratory disease, preexisting cardiovascular disease, immunocompromised status, and higher clinical frailty scale and SOFA scores at baseline were risk factors for progression to critical illness. Patients with these risk factors must be prioritized and appropriately isolated or treated in a timely manner, especially in pandemic settings.

A genome-wide association study on growth traits of Korean commercial pig breeds using Bayesian methods.

OBJECTIVE: This study aims to identify the significant regions and candidate genes of growth-related traits (adjusted backfat thickness [ABF], average daily gain [ADG], and days to 90 kg [DAYS90]) in Korean commercial GGP pig (Duroc, Landrace, and Yorkshire) populations. METHODS: A genome-wide association study (GWAS) was performed using single-nucleotide polymorphism (SNP) markers for imputation to Illumina PorcineSNP60. The BayesB method was applied to calculate thresholds for the significance of SNP markers. The identified windows were considered significant if they explained ≥1% genetic variance. RESULTS: A total of 28 window regions were related to genetic growth effects. Bayesian GWAS revealed 28 significant genetic regions including 52 informative SNPs associated with growth traits (ABF, ADG, DAYS90) in Duroc, Landrace, and Yorkshire pigs, with genetic variance ranging from 1.00% to 5.46%. Additionally, 14 candidate genes with previous functional validation were identified for these traits. CONCLUSION: The identified SNPs within these regions hold potential value for future markerassisted or genomic selection in pig breeding programs. Consequently, they contribute to an improved understanding of genetic architecture and our ability to genetically enhance pigs. SNPs within the identified regions could prove valuable for future marker-assisted or genomic selection in pig breeding programs.

Pharmacokinetic and Pharmacodynamic Modeling Analysis of Delpazolid (LCB01-0371) in Adult Patients with Pulmonary Tuberculosis.

Delpazolid (LCB01-0371) is a novel oxazolidinone derivative with a good safety profile for treating gram-positive pathogenic infections such as Mycobacterium abscessus, a highly pathogenic drug-resistant Mycobacterium. In this study, we evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of delpazolid after 14 days of multiple oral administration, using data from adult patients with pulmonary tuberculosis. 800 mg once a day, 400 mg twice a day, 800 mg twice a day, and 1200 mg once a day delpazolid for 14 days were tested in 63 patients with pulmonary tuberculosis. For PK blood collection, inpatient and outpatient scheduling were separately implemented. Plasma concentrations of delpazolid were measured at visits 2, 4, 6, and 8 in outpatients, and four sparse blood samples were measured in inpatients. PD models were sequentially fitted using individual PK parameter estimates obtained from PK compartmental models. For PK modeling, 180 plasma concentrations of delpazolid from 56 patients were included. A two-compartment mixed first- and zero-order absorption model best described the time course of plasma concentration. For the PD model, 448 bacterial titer data from 60 patients were used. The time course of bacterial titers (log10 CFU/mL) was described by a model that consists of the growth and killing rate of bacteria with the sigmoid Emax model. The PK-PD simulation suggested that the bacterial titers are the lowest on the 800 mg bid regimen among the four, consistent with observed data, as all regimens substantially decrease. In the dose-response relationship, the effectiveness of delpazolid was suggested.

High-κ Dielectric (HfO2)/2D Semiconductor (HfSe2) Gate Stack for Low-Power Steep-Switching Computing Devices.

Herein, a high-quality gate stack (native HfO2 formed on 2D HfSe2) fabricated via plasma oxidation is reported, realizing an atomically sharp interface with a suppressed interface trap density (Dit ≈ 5 × 1010 cm-2 eV-1). The chemically converted HfO2 exhibits dielectric constant, κ ≈ 23, resulting in low gate leakage current (≈10-3 A cm-2) at equivalent oxide thickness ≈0.5 nm. Density functional calculations indicate that the atomistic mechanism for achieving a high-quality interface is the possibility of O atoms replacing the Se atoms of the interfacial HfSe2 layer without a substitution energy barrier, allowing layer-by-layer oxidation to proceed. The field-effect-transistor-fabricated HfO2/HfSe2 gate stack demonstrates an almost ideal subthreshold slope (SS) of ≈61 mV dec-1 (over four orders of IDS) at room temperature (300 K), along with a high Ion/Ioff ratio of ≈108 and a small hysteresis of ≈10 mV. Furthermore, by utilizing a device architecture with separately controlled HfO2/HfSe2 gate stack and channel structures, an impact ionization field-effect transistor is fabricated that exhibits n-type steep-switching characteristics with a SS value of 3.43 mV dec-1 at room temperature, overcoming the Boltzmann limit. These results provide a significant step toward the realization of post-Si semiconducting devices for future energy-efficient data-centric computing electronics.

PK Modeling of L-4-Boronophenylalanine and Development of Bayesian Predictive Platform for L-4-Boronophenylalanine PKs for Boron Neutron Capture Therapy.

L-4-[(10B)]Boronophenylalanine (BPA) is an amino acid analogue with a boron-10 moiety. It is most widely used as a boron carrier in boron neutron capture therapy. In this study, a Bayesian predictive platform of blood boron concentration based on a BPA pharmacokinetic (PK) model was developed. This platform is user-friendly and can predict the individual boron PK and optimal time window for boron neutron capture therapy in a simple way. The present study aimed to establish a PK model of L-4-boronophenylalanine and develop a Bayesian predictive platform for blood boron PKs for user-friendly estimation of boron concentration during neutron irradiation of neutron capture therapy. Whole blood boron concentrations from seven previous reports were graphically extracted and analyzed using the nonlinear mixed-effects modeling (NONMEM) approach. Model robustness was assessed using nonparametric bootstrap and visual predictive check approaches. The visual predictive check indicated that the final PK model is able to adequately predict observed concentrations. The Shiny package was used to input real-time blood boron concentration data, and during the following irradiation session blood boron was estimated with an acceptably short calculation time for the determination of irradiation time. Finally, a user-friendly Bayesian estimation platform for BPA PKs was developed to optimize individualized therapy for patients undergoing BNCT.

Atelocollagen Injection During Arthroscopic Rotator Cuff Repair for Small- to Medium-Sized Subacute or Chronic Rotator Cuff Tears Enhances Radiographic Tendon Integrity: A Propensity Score-Matched Comparative Study.

PURPOSE: To evaluate the clinical and structural outcomes of using injectable atelocollagen during arthroscopic rotator cuff repair (ARCR) for small- to medium-sized rotator cuff tears. METHODS: This retrospective study reviewed patients with small- to medium-sized full-thickness tears who underwent ARCR from 2016 to 2022 with a minimum 1-year follow-up. Propensity score (PS) matching was used to reduce bias. Tendon integrity was evaluated using magnetic resonance imaging (MRI) at postoperative 6 months. Clinical and structural outcomes were compared between the 2 groups. RESULTS: After PS matching, this study included 181 pairs of patients comparing ARCR with atelocollagen injection and without atelocollagen injection. Range of motion, muscle strength, and functional outcomes were significantly improved in both the atelocollagen group and the control group. Forward elevation and external rotation were significantly worse in the atelocollagen group compared with the control group at 2, 6, and 12 months postoperatively and at the final follow-up. In total, 125 patients (69.1%) in the atelocollagen group and 130 patients (71.8%) in the control group exceeded the minimal clinically important difference in the American Shoulder and Elbow Surgeons score without a significant difference between the 2 groups (P = .509). The mean value of Sugaya grade on postoperative MRI evaluation was 2.03 ± 0.81 for the atelocollagen group and 2.24 ± 0.97 for the control group, with a significant difference between the 2 groups (P = .027). Tendon healing failure was observed in 12 patients (6.6%) in the atelocollagen group and 19 patients (10.5%) in the control group, with no statistical difference between the 2 groups (P = .189). CONCLUSIONS: Atelocollagen injection during ARCR for small- to medium-sized subacute or chronic rotator cuff tears did not show a benefit in clinical outcomes. However, postoperative MRI showed significantly lower Sugaya grade compared with the control group, with no significant difference in retear rate. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Pre-Sepsis Length of Hospital Stay and Mortality: A Nationwide Multicenter Cohort Study.

BACKGROUND: Prolonged length of hospital stay (LOS) is associated with an increased risk of hospital-acquired conditions and worse outcomes. We conducted a nationwide, multicenter, retrospective cohort study to determine whether prolonged hospitalization before developing sepsis has a negative impact on its prognosis. METHODS: We analyzed data from 19 tertiary referral or university-affiliated hospitals between September 2019 and December 2020. Adult patients with confirmed sepsis during hospitalization were included. In-hospital mortality was the primary outcome. The patients were divided into two groups according to their LOS before the diagnosis of sepsis: early- (< 5 days) and late-onset groups (≥ 5 days). Conditional multivariable logistic regression for propensity score matched-pair analysis was employed to assess the association between late-onset sepsis and the primary outcome. RESULTS: A total of 1,395 patients were included (median age, 68.0 years; women, 36.3%). The early- and late-onset sepsis groups comprised 668 (47.9%) and 727 (52.1%) patients. Propensity score-matched analysis showed an increased risk of in-hospital mortality in the late-onset group (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.69-5.34). The same trend was observed in the entire study population (aOR, 1.85; 95% CI, 1.37-2.50). When patients were divided into LOS quartile groups, an increasing trend of mortality risk was observed in the higher quartiles (P for trend < 0.001). CONCLUSION: Extended LOS before developing sepsis is associated with higher in-hospital mortality. More careful management is required when sepsis occurs in patients hospitalized for ≥ 5 days.

Risk Factors for the Mortality of Patients With Coronavirus Disease 2019 Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study.

BACKGROUND: Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. METHODS: We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan-Meier (KM) method. RESULTS: Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010-1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312-7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). CONCLUSION: Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.

Comparison of Long-Term Postoperative Outcomes of the Subtypes of Chronic Rhinosinusitis with Nasal Polyps.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition that significantly impacts the health-related quality of life (HRQOL) of patients. This study aims to investigate the disparities in preoperative examination findings, postoperative HRQOL, and disease control status based on CRSwNP subtypes. (2) Methods: A retrospective analysis was conducted on 202 patients who underwent endoscopic sinus surgery for CRSwNP. The study assessed clinical characteristics, blood eosinophil and immunoglobulin E (IgE) levels, modified Lund-Kennedy and Lund-Mackay scores, and Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scores. HRQOL was evaluated using the Sino-nasal Outcome Test (SNOT-22) scores, and disease control status was assessed based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 guidelines. (3) Results: Of the 202 patients, Eosinophilic CRSwNP patients exhibited significantly higher preoperative peripheral blood eosinophil ratios and IgE levels, and JESREC scores (p < 0.05). Two years postoperatively, patients in the non-eosinophilic group showed significantly improved SNOT-22 scores compared to preoperative scores (p = 0.007). Notably, the proportion of patients with uncontrolled disease was significantly higher in the eosinophilic group (p = 0.035). Logistic regression analyses identified preoperative SNOT-22 scores and eosinophilic CRSwNP subtype as influential factors on disease control status (p < 0.05). (4) Conclusions: Patients with more severe preoperative symptoms and eosinophilic CRSwNP demonstrated poorer long-term treatment outcomes.