RNA 5-methylcytosine marks mitochondrial double-stranded RNAs for degradation and cytosolic release.

Mitochondria are essential regulators of innate immunity. They generate long mitochondrial double-stranded RNAs (mt-dsRNAs) and release them into the cytosol to trigger an immune response under pathological stress conditions. Yet the regulation of these self-immunogenic RNAs remains largely unknown. Here, we employ CRISPR screening on mitochondrial RNA (mtRNA)-binding proteins and identify NOP2/Sun RNA methyltransferase 4 (NSUN4) as a key regulator of mt-dsRNA expression in human cells. We find that NSUN4 induces 5-methylcytosine (m5C) modification on mtRNAs, especially on the termini of light-strand long noncoding RNAs. These m5C-modified RNAs are recognized by complement C1q-binding protein (C1QBP), which recruits polyribonucleotide nucleotidyltransferase to facilitate RNA turnover. Suppression of NSUN4 or C1QBP results in increased mt-dsRNA expression, while C1QBP deficiency also leads to increased cytosolic mt-dsRNAs and subsequent immune activation. Collectively, our study unveils the mechanism underlying the selective degradation of light-strand mtRNAs and establishes a molecular mark for mtRNA decay and cytosolic release.

Alternative polyadenylation determines the functional landscape of inverted Alu repeats.

Inverted Alu repeats (IRAlus) are abundantly found in the transcriptome, especially in introns and 3' untranslated regions (UTRs). Yet, the biological significance of IRAlus embedded in 3' UTRs remains largely unknown. Here, we find that 3' UTR IRAlus silences genes involved in essential signaling pathways. We utilize J2 antibody to directly capture and map the double-stranded RNA structure of 3' UTR IRAlus in the transcriptome. Bioinformatic analysis reveals alternative polyadenylation as a major axis of IRAlus-mediated gene regulation. Notably, the expression of mouse double minute 2 (MDM2), an inhibitor of p53, is upregulated by the exclusion of IRAlus during UTR shortening, which is exploited to silence p53 during tumorigenesis. Moreover, the transcriptome-wide UTR lengthening in neural progenitor cells results in the global downregulation of genes associated with neurodegenerative diseases, including amyotrophic lateral sclerosis, via IRAlus inclusion. Our study establishes the functional landscape of 3' UTR IRAlus and its role in human pathophysiology.

PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs.

Protein kinase RNA-activated (PKR) induces immune response by sensing viral double-stranded RNAs (dsRNAs). However, growing evidence suggests that PKR can also be activated by endogenously expressed dsRNAs. Here, we capture these dsRNAs by formaldehyde-mediated crosslinking and immunoprecipitation sequencing and find that various noncoding RNAs interact with PKR. Surprisingly, the majority of the PKR-interacting RNA repertoire is occupied by mitochondrial RNAs (mtRNAs). MtRNAs can form intermolecular dsRNAs owing to bidirectional transcription of the mitochondrial genome and regulate PKR and eIF2α phosphorylation to control cell signaling and translation. Moreover, PKR activation by mtRNAs is counteracted by PKR phosphatases, disruption of which causes apoptosis from PKR overactivation even in uninfected cells. Our work unveils dynamic regulation of PKR even without infection and establishes PKR as a sensor for nuclear and mitochondrial signaling cues in regulating cellular metabolism.

Innate immune signatures in the nasopharynx after SARS-CoV-2 infection and links with the clinical outcome of COVID-19 in Omicron-dominant period.

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by impaired induction of interferons (IFNs) and IFN-stimulated genes (ISGs), the IFNs and ISGs in upper airway is essential to restrict the spread of respiratory virus. Here, we identified the prominent IFN and ISG upregulation in the nasopharynx (NP) of mild and even severe coronavirus disease 2019 (COVID-19) patients (CoV2+) in Omicron era and to compare their clinical outcome depending on the level of IFNs and ISGs. Whereas the induction of IFNB was minimal, transcription of IFNA, IFNG, and IFNLs was significantly increased in the NP of CoV2 + patients. IFNs and ISGs may be more upregulated in the NP of CoV2 + patients at early phases of infection according to viral RNA levels and this is observed even in severe cases. IFN-related innate immune response might be characteristic in macrophages and monocytes at the NP and the CoV2 + patients with higher transcription of IFNs and ISGs in the NP showed a correlation with good prognosis of COVID-19. This study presents that IFNs and ISGs may be upregulated in the NP, even in severe CoV2 + patients depending on viral replication during Omicron-dominant period and the unique IFN-responsiveness in the NP links with COVID-19 clinical outcomes.

Comparative outcomes and prognostic indicators in adrenalectomy for adrenal metastasis.

PURPOSE: The indications for adrenalectomy and feasibility of laparoscopic adrenalectomy for adrenal metastasis are controversial. This study aimed to compare the surgical outcomes between open adrenalectomy (OA) and laparoscopic adrenalectomy (LA) and to evaluate the prognostic factors for oncological outcomes of adrenal metastasis. MATERIALS AND METHODS: We conducted a retrospective chart review of 141 consecutive patients who underwent adrenalectomy for adrenal metastasis at Seoul National University Hospital from April 2005 to February 2021. Surgical and oncological outcomes were compared between OA and LA. RESULTS: OA was performed in 95 (67.4%) patients, and 46 (32.6%) patients underwent LA. Among the patients who underwent adrenalectomy without adjacent organ resection for adrenal tumors less than 8 cm, LA was associated with a shorter operation time (100.1 ± 48.8 vs. 158.6 ± 81.2, P = 0.001), less blood loss (94.8 ± 93.8 vs. 566.8 ± 1156.0, P = 0.034), and a shorter hospital stay (3.7 ± 1.3 vs. 6.9 ± 5.8, P = 0.003). For locoregional recurrence-free survival (LRRFS), on multivariate analysis, a positive pathological margin (hazard ratio [HR]: 5.777, P = 0.002), disease activity at the primary site (HR: 6.497, P = 0.005), other metastases (HR: 4.154, P = 0.015), and a relatively larger tumor size (HR: 1.198, P = 0.018) were significantly associated with poor LRRFS. Multivariate analysis indicated that metachronous metastasis (HR: 0.51, P = 0.032) was associated with a longer overall survival (OS), whereas a positive pathological margin (HR: 2.40, P = 0.017), metastases to other organs (HR: 2.08, P = 0.025), and a relatively larger tumor size (HR: 1.11, P = 0.046) were associated with a shorter OS. CONCLUSIONS: LA is a feasible treatment option for adrenal metastasis in selected patients. The pathological margin, metastases to other organs, and tumor size should be considered in adrenalectomy for adrenal metastasis.

Association of Delta Neutrophil Index with the 30-day Mortality in Adult Cardiac Surgical Patients.

Purpose: This study aimed to assess the predictive accuracy of 30-day mortality with delta neutrophil index (DNI) in adult cardiac surgical patients. Methods: This study enrolled patients who underwent cardiac surgery under general anesthesia between March 2016 and May 2022 at a tertiary hospital in the Republic of Korea. DNI was measured preoperatively, on postoperative arrival to the surgical intensive care unit (ICU), and 12, 24, 48, and 72 h postoperatively. Receiver operating characteristic (ROC) analysis was employed to identify the prediction accuracy of DNI. An area under ROC curve (AUROC) ≥0.700 was defined as satisfactory predictive accuracy. An optimal cutoff point for the DNI value to maximize predictive accuracy was revealed in the ROC curve, where [sensitivity + specificity] was maximum. Results: This study included a total of 843 patients in the final analyses. The mean age of the study population was 66.9±12.2 years and 38.4% of them were female patients. The overall 30-day mortality rate was 5.2%. Surgery involving the thoracic aorta, history of prior cardiac surgery, or emergency surgery were associated with a higher mortality rate. The DNI showed satisfactory predictive accuracy at 24 h, 48 h, and 72 h postoperatively, with AUROC of 0.729, 0.711, and 0.755, respectively. The optimal cutoff points of DNI at each time point were 3.2, 3.8, and 2.3, respectively. Conclusions: Postoperative DNI is a good predictor of 30-day mortality after cardiac surgery and has the benefit of no additional financial costs or time.

Disability-related disparities in health outcomes among newly diagnosed diabetic patients: A retrospective cohort.

BACKGROUND: A distinct gap in the literature persists regarding the health outcome of individuals with Type 2 diabetes who also have disabilities. This study aimed to investigate potential disparities in events occurrence among diabetes patients across various disability stages. METHODS: We conducted a retrospective cohort study on patients newly diagnosed with diabetes in 2013 and 2014, aged ≥ 18 years, and followed them until December 2021, using data from the Korean National Health Insurance database. All-cause mortality and hospitalization for diabetes mellitus and cardio-cerebrovascular diseases (CVD) was assessed. RESULTS: The study included 26,085 patients, encompassing individuals without disabilities and those with physical, visual, hearing and speech, intellectual and developmental, and mental disabilities. After adjustment, individuals with disabilities had a higher risk of all-cause death (adjusted hazard ratio [aHR]: 1.25, 95% CI: 1.07-1.48) compared to those without disabilities. In particular, severe disabilities and hearing and speech disabilities showed significantly higher risks of all-cause death (aHR: 1.40, 95% CI: 1.06-1.85 and aHR: 1.58, 95% CI: 1.17-2.15, respectively), with marginal significance for mild disabilities (aHR: 1.20, 95% CI: 0.99-1.45) and mental disorders (aHR: 1.92, 95% CI: 0.98-3.73). Patients with disabilities also had significantly increased risks of CVD-related first admissions (aHR: 1.30, 95% CI: 1.07-1.56) and diabetes-related first admissions (aHR: 1.31, 95% CI: 1.20-1.43) compared to those without disabilities. CONCLUSIONS: This study underscores the urgent need for public health policies to prioritize individuals with disabilities and diabetes, addressing the disparities in health outcome.

Salivary Cortisol and Melatonin, Sleep, and Behavioral Patterns in Older Adults Living With Dementia.

BACKGROUND: Over half of the older adults living with dementia have behavioral and psychological symptoms of dementia (BPSD), including sleep disturbance; however, little is known about physiological markers. Salivary cortisol and melatonin have been identified as potential biomarkers of BPSD, with evidence suggesting a relationship between these biomarkers and various behavioral factors, as well as sleep and activity patterns. OBJECTIVES: The aim of this study was to investigate the time-dependent changes in salivary cortisol and melatonin levels in older adults with dementia, their relationship with the sleep-wake cycle, and their correlation with BPSD symptoms and behavioral factors. METHODS: This observational study conducted in Seoul and Gyeonggi-do, South Korea, used data from 172 older adults with dementia, measuring sleep and activity patterns for 2 weeks using a wearable device, in addition to administering questionnaires for neuropsychiatric and psychological symptoms-the Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory, and Cornell Scale for Depression in Dementia. Salivary cortisol and melatonin levels were measured at four time points and divided into four groups based on a dual-trajectory model. Differences among the groups were analyzed using one-way analysis of variance. RESULTS: The participants showed normal but heterogeneous patterns of salivary cortisol and melatonin levels. Dual-trajectory pattern analysis showed that higher levels of melatonin during the daytime were correlated with poor nighttime sleep efficiency and decreased disinhibited behaviors, and higher levels of cortisol at all four time points were associated with decreased physical activity. DISCUSSION: Measuring and analyzing periodic changes in cortisol and melatonin levels can predict various behavioral symptoms (e.g., sleep disturbances, activity counts, and disinhibition) in older adults with dementia. A study with an experimental design is needed to discover the direct physiological interactions between cortisol, melatonin, and these symptoms.

Demonstration of transverse ligament on 3D SPACE MRI in whiplash-associated disorder and nontraumatic conditions.

PURPOSE: This study aims to delineate the three-dimensional (3D) SPACE MRI findings of the transverse ligament (TL) in whiplash-associated disorder (WAD) patients, and to compare them with those from a nontraumatic group. METHODS: A retrospective analysis was performed on cervical spine MRI scans obtained from 46 patients with WAD and 62 nontraumatic individuals. Clinical features, including the WAD grade and stage, were recorded. The TL's morphological grade and the symmetricity of the lateral atlantodental interval was assessed using axial 3D T2-SPACE images. The morphological grading was evaluated using a four-point scale: 0 = homogeneously low signal intensity with normal thickness, 1 = high signal intensity with normal thickness, 2 = reduced thickness, 3 = full-thickness rupture or indistinguishable from surrounding structures. Additionally, the number of cervical levels exhibiting degeneration was documented. RESULTS: When comparing the WAD and nontraumatic groups, a significant difference was observed in the proportion of high-grade TL changes (grade 2 or 3) and the number of degenerated cervical levels. Logistic regression analysis revealed that high-grade TL changes and a lower number of degenerative levels independently predicted the presence of WAD. Within the WAD group, the subset of patients with high-grade TL changes demonstrated a significantly higher mean age than the low-grade group (grade 0 or 1). CONCLUSION: High-grade morphological changes in the TL can be detected in patients with WAD through the use of 3D SPACE sequences. Clinical relevance statement 3D SPACE MRI could serve as an instrumental tool in the assessment of TL among patients with WAD. Integrating MRI findings with patient history and symptomology could facilitate the identification of potential ligament damage, and may help treatment and follow-up planning.

Efficacy of Mobile App-Based Cognitive Behavioral Therapy for Insomnia: Multicenter, Single-Blind Randomized Clinical Trial.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBTi) is the first-line therapy for chronic insomnia. Mobile app-based CBTi (MCBTi) can enhance the accessibility of CBTi treatment; however, few studies have evaluated the effectiveness of MCBTi using a multicenter, randomized controlled trial design. OBJECTIVE: We aimed to assess the efficacy of Somzz, an MCBTi that provides real-time and tailored feedback to users, through comparison with an active comparator app. METHODS: In our multicenter, single-blind randomized controlled trial study, participants were recruited from 3 university hospitals and randomized into a Somzz group and a sleep hygiene education (SHE) group at a 1:1 ratio. The intervention included 6 sessions for 6 weeks, with follow-up visits over a 4-month period. The Somzz group received audiovisual sleep education, guidance on relaxation therapy, and real-time feedback on sleep behavior. The primary outcome was the Insomnia Severity Index score, and secondary outcomes included sleep diary measures and mental health self-reports. We analyzed the outcomes based on the intention-to-treat principle. RESULTS: A total of 98 participants were randomized into the Somzz (n=49, 50%) and SHE (n=49, 50%) groups. Insomnia Severity Index scores for the Somzz group were significantly lower at the postintervention time point (9.0 vs 12.8; t95=3.85; F2,95=22.76; ηp2=0.13; P<.001) and at the 3-month follow-up visit (11.3 vs 14.7; t68=2.61; F2,68=5.85; ηp2=0.03; P=.01) compared to those of the SHE group. The Somzz group maintained their treatment effect at the postintervention time point and follow-ups, with a moderate to large effect size (Cohen d=-0.62 to -1.35; P<.01 in all cases). Furthermore, the Somzz group showed better sleep efficiency (t95=-3.32; F2,91=69.87; ηp2=0.41; P=.001), wake after sleep onset (t95=2.55; F2,91=51.81; ηp2=0.36; P=.01), satisfaction (t95=-2.05; F2,91=26.63; ηp2=0.20; P=.04) related to sleep, and mental health outcomes, including depression (t95=2.11; F2,94=29.64; ηp2=0.21; P=.04) and quality of life (t95=-3.13; F2,94=54.20; ηp2=0.33; P=.002), compared to the SHE group after the intervention. The attrition rate in the Somzz group was 12% (6/49). CONCLUSIONS: Somzz outperformed SHE in improving insomnia, mental health, and quality of life. The MCBTi can be a highly accessible, time-efficient, and effective treatment option for chronic insomnia, with high compliance. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) KCT0007292; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22214&search_page=L.

Attention-deficit/hyperactivity disorder and subsequent diagnoses of major psychiatric disorders: a nationwide population-based study.

We evaluated the risk of being diagnosed with various psychiatric disorders after an attention-deficit/hyperactivity disorder (ADHD) diagnosis using data from South Korea's National Health Insurance Service from 2002 to 2019, which covers approximately 97% of the country's population. ADHD and control groups were selected after propensity score matching was performed for individuals diagnosed with ADHD and their age- and sex-matched counterparts from the general population. Comorbid psychiatric disorders included depressive disorder, bipolar disorder, tic disorder, and schizophrenia. The incidence of newly diagnosed psychiatric disorders was compared between the groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated and adjusted for ADHD medication prescription. After matching, 353,898 individuals were assigned to each of the two groups. Compared to the control group, the ADHD group showed a significantly higher risk of being subsequently diagnosed with depressive disorder, bipolar disorder, schizophrenia, and tic disorder. The onset age of depressive disorder, bipolar disorder, and schizophrenia in the ADHD group was 16-17 years, approximately 5 years earlier than that in the control group. The risk for depression was the highest in individuals with high income levels, and that for schizophrenia was the highest among rural patients. The median length of the follow-up time until the diagnosis of each comorbid psychiatric disorder was 7.53, 8.43, 8.53, and 8.34 years for depressive disorder, bipolar disorder, schizophrenia, and tic disorder, respectively. Individuals with ADHD had an overall higher risk of being diagnosed with subsequent psychiatric disorders than did the controls. Hence, they should be carefully screened for other psychiatric symptoms from an early age and followed up for an extended duration, along with appropriate interventions for ADHD symptoms, including psychosocial treatments and educational approaches.

Child and adolescent participation measurement tools and their translations: A systematic review.

BACKGROUND: Numerous participation measurement tools targeting children and youth have been developed. Despite the translation of these tools into specific languages and cultures, the reliability and validity of the translated versions remain uncertain. To address this gap in knowledge, this study aims to identify tools for assessing the participation of children aged 5-18 years and to appraise the psychometric properties of their translated versions. METHODS: Four electronic databases were searched for peer-reviewed studies published in English. Preferred Reporting Items for Systematic Reviews guidelines was followed. Study titles and abstracts were screened by four independent reviewers. Data were extracted for both original and translated versions of eligible tools. Instrument quality assessments were performed using the Outcome Measures Rating Form Guidelines. Any discrepancies were resolved by consensus. RESULTS: Out of the 31 measurement tools examined, 18 tools had at least one translated version available, and among those original measurement tools, a total of 58 translated versions were identified. The most widely translated tool was the Physical Activity Questionnaire for Children (12 languages), and the most frequently translated language was Chinese (7 tools). Most translated versions verified internal consistency and content validity. Only three translated versions were verified inter-rater reliability, and seven translated versions were tested criterion validity with the gold standard tools assessing participation of children (e.g., accelerometer, Pediatric Evaluation of Disability Inventory and four 24-h recalls). None of the translated versions were tested for intra-rater reliability and responsiveness. CONCLUSIONS: These findings can support the selection of psychometrically sound tools for children with disabilities, given their culture and language, and tool quality.

Intraplaque hemorrhage volume in patients with carotid atherosclerosis: How informative is it?

BACKGROUND AND PURPOSE: Intraplaque hemorrhage (IPH) of carotid atherosclerosis is an important feature in complex lesions preceding acute stroke events. The current study aimed to determine the role played by IPH volume compared to that of carotid stenosis or maximal wall thickness in patients with carotid IPH. MATERIALS AND METHODS: This retrospective study included 233 patients who presented with carotid IPH on vessel wall imaging (VWI). We divided the patients into symptomatic or asymptomatic groups based on territorial acute focal infarction. The IPH volume, degree of stenosis, and maximal wall thickness on VWI were analyzed. RESULTS: Of the 233 included patients with carotid IPH, 51 (21.9 %) patients showed initial clinical symptoms and positive territorial findings on diffusion-weighted imaging (DWI). Moreover, 154 (66.1 %) patients had low-grade stenosis below 50 % (n = 19: symptomatic groups). Overall, carotid IPH volume, degree of stenosis, and maximal wall thickness were all significantly higher in the symptomatic groups (p = 0.001). The degree of stenosis, in all patients and especially in those with high-grade stenosis above 50 %, was significantly correlated with territorial acute focal infarction on multivariate analysis (p < 0.01). In patients with low-grade stenosis below 50 %, maximal wall thickness was associated with territorial acute focal infarction (p = 0.48). CONCLUSION: Carotid IPH volume was a risk factor for territorial acute focal infarction. However, in patients with high-grade stenosis, the degree of stenosis was significantly linked to acute stroke. By contrast, in patients with low-grade stenosis, maximal wall thickness exhibited a significant association with acute stroke.

Markerless Kinematic Data in the Frontal Plane Contributions to Movement Quality in the Single-Leg Squat Test: A Comparison and Decision Tree Approach.

OBJECTIVE: The aim of this study is to compare kinematic data of the frontal trunk, pelvis, knee, and summated angles (trunk plus knee) among categorized grades using the single-leg squat (SLS) test, to classify the SLS grade, and to investigate the association between the SLS grade and the frontal angles using smartphone-based markerless motion capture. METHODS: Ninety-one participants were categorized into 3 grades (good, reduced, and poor) based on the quality of the SLS test. An automated pose estimation algorithm was employed to assess the frontal joint angles during SLS, which were captured by a single smartphone camera. Analysis of variance and a decision tree model using classification and regression tree analysis were utilized to investigate intergroup differences, classify the SLS grades, and identify associations between the SLS grade and frontal angles, respectively. RESULTS: In the poor group, each frontal trunk, knee, and summated angle was significantly larger than in the good group. Classification and regression tree analysis showed that frontal knee and summated angles could classify the SLS grades with a 76.9% accuracy. Additionally, the classification and regression tree analysis established cutoff points for each frontal knee (11.34°) and summated angles (28.4°), which could be used in clinical practice to identify individuals who have a reduced or poor grade in the SLS test. CONCLUSIONS: The quality of SLS was found to be associated with interactions among frontal knee and summated angles. With an automated pose estimation algorithm, a single smartphone computer vision method can be utilized to compare and distinguish the quality of SLS movement for remote clinical and sports assessments.

Surgical Outcomes in Patients With Low-risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation After Active SurveillanceA Multicenter Prospective Cohort Study.

OBJECTIVE: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. BACKGROUND: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. METHODS: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed. RESULTS: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression. CONCLUSIONS: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02938702.

Keratin 8 mutations in transgenic mice predispose to lung injury.

Keratin 8 (K8) is the cytoskeletal intermediate filament protein of simple-type epithelia. Mutations in K8 predispose the affected individual and transgenic mouse to liver disease. However, the role of K8 in the lung has not been reported in mutant transgenic mouse models. Here, we investigated the susceptibility of two different transgenic mice expressing K8 Gly62-Cys (Gly62 replaced with Cys) or Ser74-Ala (Ser74 replaced with Ala) to lung injury. The mutant transgenic mice were highly susceptible to two independent acute and chronic lung injuries compared with control mice. Both K8 Gly62-Cys mice and K8 Ser74-Ala mice showed markedly increased mouse lethality (∼74% mutant mice versus ∼34% control mice) and more severe lung damage, with increased inflammation and apoptosis, under L-arginine-mediated acute lung injury. Moreover, the K8 Ser74-Ala mice had more severe lung damage, with extensive hemorrhage and prominent fibrosis, under bleomycin-induced chronic lung injury. Our study provides the first direct evidence that K8 mutations predispose to lung injury in transgenic mice.

US Predictors of Papillary Thyroid Microcarcinoma Progression at Active Surveillance.

Background Active surveillance (AS) is an accepted strategy for patients with low-risk papillary thyroid microcarcinoma (PTMC). While previous studies have evaluated the prognostic value of US features, results have been inconsistent. Purpose To determine if US features can help predict tumor progression in patients with low-risk PTMC undergoing AS. Materials and Methods This prospective study enrolled 1177 participants with PTMC from three hospitals between June 2016 and January 2021. Participants were self-assigned to either immediate surgery or AS, and those with two or more US examinations in the absence of surgery were included in the analysis. A χ2 test was used to compare estimated tumor progression rate at 4 years between participants stratified according to US features. Multivariable Cox regression analysis was used to assess the association of clinical and US features with overall tumor progression and specific progression criteria. Results Among 699 participants included in the analysis, 68 (mean age, 49 years ± 12 [SD]; 40 female participants) showed tumor progression (median follow-up, 41.4 months ± 16 [SD]). Tumor progression was associated with the US features of diffuse thyroid disease (DTD) (hazard ratio [HR], 2.3 [95% CI: 1.4, 3.7]; P = .001) and intratumoral vascularity (HR, 1.7 [95% CI: 1.0, 3.0]; P = .04) and the participant characteristics of male sex (HR, 2.8 [95% CI: 1.7, 4.6]; P < .001), age less than 30 years (HR, 2.9 [95% CI: 1.2, 6.8]; P = .01), and thyroid-stimulating hormone level of 7 µU/mL or higher (HR, 6.9 [95% CI: 2.7, 17.4]; P < .001). The risk of tumor progression was higher for participants with DTD (14%, P = .001) or intratumoral vascularity (14%, P = .02) than for participants without these features (6%). DTD and intratumoral vascularity were associated with tumor enlargement (HR, 2.7 [95% CI: 1.4, 5.1]; P = .002) and new lymph node metastasis (HR, 5.0 [95% CI: 1.3, 19.4]; P = .02), respectively. Conclusion DTD and intratumoral vascularity were associated with an increased risk of tumor progression in participants with PTMC undergoing AS. Clinical trial registration no. NCT02938702 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Reuter and the review "International Expert Consensus on US Lexicon for Thyroid Nodules" by Durante et al in this issue.

Trends in HOMA-IR values among South Korean adolescents from 2007-2010 to 2019-2020: a sex-, age-, and weight status-specific analysis.

BACKGROUND/OBJECTIVES: An increase in obesity prevalence may lead to an increase in the HOMA-IR value. This study aimed to investigate changes in age- and sex-specific homeostasis model assessment of insulin resistance (HOMA-IR) values among South Korean adolescents, using data from the Korean National Health and Nutrition Examination Survey (KNHANES) IV, V, and VIII conducted between 2007-2010 and 2019-2020. SUBJECTS/METHODS: Overall, 4621 adolescents aged 10-18 years were evaluated, including 3473 from the 2007-2010 dataset and 1148 from the 2019-2020 dataset. The mean HOMA-IR values and percentile curves were evaluated by age, sex, and weight status. RESULTS: The mean HOMA-IR values peaked at puberty in both sexes and further increased during puberty in the 2019-2020 dataset (boys 5.21, 95% confidence interval [CI] 4.16-6.26; girls 5.21, 95% CI 3.09-7.33) compared with the 2007-2010 dataset (boys 3.25, 95% CI 3.04-3.47; girls 3.58, 95% CI 3.31-3.85). Both groups (with normal-weight and overweight/obesity) exhibited a peak HOMA-IR value during puberty in both sexes and both datasets, although the group with overweight/obesity had a higher and wider peak age range. While the mean HOMA-IR values did not change in adolescents with normal-weight, they increased during puberty and post-puberty in boys with overweight/obesity. CONCLUSIONS: HOMA-IR values should be interpreted considering sex, weight status, and pubertal stages. In particular, during the pubertal period, insulin resistance (IR) can coexist not only due to weight-related factors but also as a result of the distinct hormonal changes characteristic of puberty. Over the 10-year period, the mean HOMA-IR values increased in the group with overweight/obesity during puberty and post-puberty, highlighting the need for active intervention to prevent metabolic complications in adolescents with overweight/obesity.

Effect of Nanoparticles in LiFePO4 Cathode Material Using Organic/Inorganic Composite Solid Electrolyte for All-Solid-State Batteries.

Herein, we report the effect of using nanoparticles of LiFePO4 on the electrochemical properties of all-solid-state batteries (ASSBs) with a solid electrolyte. LiFePO4 (LFP) cathode materials are promising cathode materials in polymer-based composite solid electrolytes because of their limited electrochemical window range. However, LFP cathodes exhibit poor electric conductivity and sluggish lithium ion diffusion. In addition, there is a disadvantage in that the interfacial resistance increases due to poor contact between the LFP cathode material and the solid electrolyte when composing the composite cathode. The nano-sized LFP cathode material increases the contact area between solid electrolyte in the positive electrode and enhances lithium ion diffusion. Therefore, the structural differences and electrochemical performance of these nanoscale LFP cathode materials in the ASSB were studied by X-ray diffraction, scanning electron microscopy, and electrochemical analysis.

MRI evaluation of interconnections between flexor hallucis longus and flexor digitorum longus around the Master knot of Henry.

OBJECTIVES: To demonstrate the magnetic resonance imaging (MRI) findings of interconnections between flexor hallucis longus (FHL) and flexor digitorum longus (FDL) around the Master knot of Henry (MKH). METHODS: Fifty-two MRI scans of adult patients were retrospectively analyzed. The types and subtypes of interconnections between the FHL and FDL were evaluated using the classification suggested by Beger et al based on the direction and number of the tendon slips and contributions to the lesser toes. The layering organization formed by the FDL, quadratus plantae, and tendon slip from the FHL was evaluated. The distance between bony landmarks and the branching site of tendon slips and the cross-sectional area (CSA) of the tendon slips were measured. Descriptive statistics were reported. RESULTS: MRI scans revealed that type 1 interconnection was the most common (81%), followed by type 5 (10%) and types 2 and 4 (4% each). All tendon slips from the FHL contributed to the second toe, and 51% of the tendon slips contributed to the second and third toes. For the layering organization, the two-layered type was the most common (59%), followed by the three-layered (35%) and single-layered (6%) types. The mean distance between the branching site and bony landmarks was longer in the FDL to FHL cases than that in the FHL to FDL cases. The mean CSA of the tendon slips from the FHL to FDL was larger than that of the FDL to FHL. CONCLUSIONS: MRI could provide detailed information about the anatomical variations around the MKH. CLINICAL RELEVANCE STATEMENT: In lower extremity reconstruction surgery, the flexor hallucis longus and flexor digitorum longus tendons serve as donor tendons. A preoperative MRI scan could provide information on anatomical variations around the Master knot of Henry, which can help predict postoperative functional outcomes. KEY POINTS: • Normal anatomical variations around the Master knot of Henry were not extensively studied in the radiology literature before. • MRI identified the various types, sizes, and locations of interconnections between the flexor digitorum longus tendon and the flexor hallucis longus tendon. • MRI is a useful noninvasive tool for evaluating the interconnections between the flexor digitorum longus tendon and the flexor hallucis longus tendon.