Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN domain.

The enzymatic activity of the SARS-CoV-2 nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain is essential for viral propagation, with three distinct activities associated with modification of the nsp9 N terminus, NMPylation, RNAylation, and deRNAylation/capping via a GDP-polyribonucleotidyltransferase reaction. The latter two activities comprise an unconventional mechanism for initiating viral RNA 5' cap formation, while the role of NMPylation is unclear. The structural mechanisms for these diverse enzymatic activities have not been properly delineated. Here, we determine high-resolution cryoelectron microscopy (cryo-EM) structures of catalytic intermediates for the NMPylation and deRNAylation/capping reactions, revealing diverse nucleotide binding poses and divalent metal ion coordination sites to promote its repertoire of activities. The deRNAylation/capping structure explains why GDP is a preferred substrate for the capping reaction over GTP. Altogether, these findings enhance our understanding of the promiscuous coronaviral NiRAN domain, a therapeutic target, and provide an accurate structural platform for drug development.

Observation of the orbital Hall effect in a light metal Ti.

The orbital Hall effect1 refers to the generation of electron orbital angular momentum flow transverse to an external electric field. Contrary to the common belief that the orbital angular momentum is quenched in solids, theoretical studies2,3 predict that the orbital Hall effect can be strong and is a fundamental origin of the spin Hall effect4-7 in many transition metals. Despite the growing circumstantial evidence8-11, its direct detection remains elusive. Here we report the magneto-optical observation of the orbital Hall effect in the light metal titanium (Ti). The Kerr rotation by the orbital magnetic moment accumulated at Ti surfaces owing to the orbital Hall current is measured, and the result agrees with theoretical calculations semi-quantitatively and is supported by the orbital torque12 measurement in Ti-based magnetic heterostructures. This result confirms the orbital Hall effect and indicates that the orbital angular momentum is an important dynamic degree of freedom in solids. Moreover, this calls for renewed studies of the orbital effect on other degrees of freedom such as spin2,3,13,14, valley15,16, phonon17-19 and magnon20,21 dynamics.

Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity.

The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a depot system that regulates non-translational cellular functions. Here we found that the MSC component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at Ser990 induced its dissociation from the MSC, after which it was guided to the antiviral signaling pathway, where it interacted with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. This interaction blocked PCBP2-mediated ubiquitination of MAVS and ultimately suppressed viral replication. EPRS-haploid (Eprs+/-) mice showed enhanced viremia and inflammation and delayed viral clearance. This stimulus-inducible activation of MAVS by EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection.

Inflammasome diversity: exploring novel frontiers in the innate immune response.

Pathogens elicit complex mammalian immune responses by activating multiple sensors within inflammasomes, which recognize diverse pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This simultaneous activation induces the formation of protein complexes referred to as multiple inflammasomes, that orchestrate a spectrum of programmed cell death pathways, including pyroptosis, apoptosis, and necroptosis. This concept is crucial for comprehending the complexity of the innate immune system's response to diverse pathogens and its implications for various diseases. Novel contributions here include emphasizing simultaneous sensor activation by pathogens, proposing the existence of multiple inflammasome complexes, and advocating for further exploration of their structural basis. Understanding these mechanisms may offer insights into disease pathogenesis, paving the way for potential therapeutic interventions targeting inflammasome-mediated immune responses.

Structural basis of dual activation of cell division by the actinobacterial transcription factors WhiA and WhiB.

Studies of transcriptional initiation in different bacterial clades reveal diverse molecular mechanisms regulating this first step in gene expression. The WhiA and WhiB factors are both required to express cell division genes in Actinobacteria and are essential in notable pathogens such as Mycobacterium tuberculosis. The WhiA/B regulons and binding sites have been elucidated in Streptomyces venezuelae (Sven), where they coordinate to activate sporulation septation. However, how these factors cooperate at the molecular level is not understood. Here we present cryoelectron microscopy structures of Sven transcriptional regulatory complexes comprising RNA polymerase (RNAP) σA-holoenzyme and WhiA and WhiB, in complex with the WhiA/B target promoter sepX. These structures reveal that WhiB binds to domain 4 of σA (σA4) of the σA-holoenzyme, bridging an interaction with WhiA while making non-specific contacts with the DNA upstream of the -35 core promoter element. The N-terminal homing endonuclease-like domain of WhiA interacts with WhiB, while the WhiA C-terminal domain (WhiA-CTD) makes base-specific contacts with the conserved WhiA GACAC motif. Notably, the structure of the WhiA-CTD and its interactions with the WhiA motif are strikingly similar to those observed between σA4 housekeeping σ-factors and the -35 promoter element, suggesting an evolutionary relationship. Structure-guided mutagenesis designed to disrupt these protein-DNA interactions reduces or abolishes developmental cell division in Sven, confirming their significance. Finally, we compare the architecture of the WhiA/B σA-holoenzyme promoter complex with the unrelated but model CAP Class I and Class II complexes, showing that WhiA/WhiB represent a new mechanism in bacterial transcriptional activation.

The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy.

Recently, viruses have been shown to regulate selective autophagy for productive infections. For instance, human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), activates selective autophagy of mitochondria, termed mitophagy, thereby inhibiting antiviral innate immune responses during lytic infection in host cells. We previously demonstrated that HHV-8 viral interferon regulatory factor 1 (vIRF-1) plays a crucial role in lytic replication-activated mitophagy by interacting with cellular mitophagic proteins, including NIX and TUFM. However, the precise molecular mechanisms by which these interactions lead to mitophagy activation remain to be determined. Here, we show that vIRF-1 binds directly to mammalian autophagy-related gene 8 (ATG8) proteins, preferentially GABARAPL1 in infected cells, in an LC3-interacting region (LIR)-independent manner. Accordingly, we identified key residues in vIRF-1 and GABARAPL1 required for mutual interaction and demonstrated that the interaction is essential for mitophagy activation and HHV-8 productive replication. Interestingly, the mitophagy receptor NIX promotes vIRF-1-GABARAPL1 interaction, and NIX/vIRF-1-induced mitophagy is significantly inhibited in GABARAPL1-deficient cells. Moreover, a vIRF-1 variant defective in GABARAPL1 binding substantially loses the ability to induce vIRF-1/NIX-induced mitophagy. These results suggest that NIX supports vIRF-1 activity as a mitophagy mediator. In addition, we found that NIX promotes vIRF-1 aggregation and stabilizes aggregated vIRF-1. Together, these findings indicate that vIRF-1 plays a role as a viral mitophagy mediator that can be activated by a cellular mitophagy receptor.

Charity begins at home: non-coding RNA functions in DNA repair.

During the past decade, evolutionarily conserved microRNAs (miRNAs) have been characterized as regulators of almost every cellular process and signalling pathway. There is now emerging evidence that this new class of regulators also impinges on the DNA damage response (DDR). Both miRNAs and other small non-coding RNAs (ncRNAs) are induced at DNA breaks and mediate the repair process. These intriguing observations raise the possibility that crosstalk between ncRNAs and the DDR might provide a means of efficient and accurate DNA repair and facilitate the maintenance of genomic stability.

Capturing Coherent Magnons by Tip-Assisted Terahertz Spectroscopy.

Our study highlights the versatility of tip-assisted terahertz spectroscopy in probing coherent magnons, the elementary quanta of spin waves in magnetic materials. We identify two distinct coherent magnon types in canted antiferromagnet YFeO3. The remarkable consistency with far-field terahertz spectroscopy in crucial magnon parameters, such as coherence time and resonance frequency, firmly establishes the credibility of tip-assisted terahertz spectroscopy. Notably, we capture more coherent ferromagnetic magnons near the sample surface, underscoring the strength of the technique. This approach paves the way for local, free-standing, and real-space investigations of spin waves in solid magnets.

The Association Between Antibody Responses and Prolonged Viable Severe Acute Respiratory Syndrome Coronavirus 2 Shedding in Immunocompromised Patients: A Prospective Cohort Study.

Immunocompromised patients with coronavirus disease 2019 were prospectively enrolled from March to November 2022 to understand the association between antibody responses and severe acute respiratory syndrome coronavirus 2 shedding. A total of 62 patients were analyzed, and the results indicated a faster decline in genomic and subgenomic viral RNA in patients with higher neutralizing and S1-specific immunoglobulin G (IgG) antibodies (both P < .001). Notably, high neutralizing antibody levels were associated with a significantly faster decrease in viable virus cultures (P = .04). Our observations suggest the role of neutralizing antibodies in prolonged virus shedding in immunocompromised patients, highlighting the potential benefits of enhancing their humoral immune response through vaccination or monoclonal antibody treatments.

Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial.

BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.

Safety of Gadoxetate Disodium for Hepatobiliary MRI in Children and Adolescents.

Background Despite a proven role in the characterization of liver lesions, use of the gadolinium-based contrast agent (GBCA) gadoxetate disodium at MRI is limited in children due to a lack of comparative safety data. Purpose To evaluate the safety of the GBCA gadoxetate disodium (a linear ionic hepatobiliary contrast agent [HBA]) in children and adolescents, compared with extracellular contrast agents (ECA). Materials and Methods A retrospective analysis was conducted in children and adolescents aged 18 years or younger who underwent HBA-enhanced MRI at one of three tertiary hospitals from January 2010 to December 2022. The incidence of GBCA-associated acute adverse events was compared between MRI examinations with a HBA and those with ECA. Severity was categorized according to American College of Radiology guidelines (mild, moderate, or severe). (a) Propensity score matching using multivariable logistic regression models and (b) inverse probability of treatment weighting analysis based on nine covariates (age, sex, asthma, allergic rhinitis, chronic urticaria or atopy, food allergy, drug allergy, premedication, and history of GBCA-associated adverse events) were used for confounder adjustment. Results A total of 1629 MRI examinations (ECA, n = 1256; HBA, n = 373) in 1079 patients were included (mean age, 8.6 years ± 6.5; 566 girls). The per-examination incidence of GBCA-associated acute adverse events showed no evidence of a difference, with rates of 0.9% (11 of 1256 examinations) for ECA and 1.3% (five of 373 examinations) for HBA (odds ratio [OR], 1.55 [95% CI: 0.54, 4.46]; P = .42). Acute adverse events were all mild with ECA, whereas with HBA, they were mild for four patients and moderate for one patient. There was no evidence of a difference in the incidence of acute adverse events, even in propensity score matching (OR, 1.33 [95% CI: 0.30, 5.96]; P = .71) and inverse probability of treatment weighting analysis (OR, 0.84 [95% CI: 0.25, 2.86]; P = .78). Conclusion Gadoxetate disodium showed no difference in acute adverse events compared with ECA in children and adolescents, with further large-scale pediatric studies required to confirm its safety. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Otero in this issue.

Differential beta-coronavirus infection dynamics in human bronchial epithelial organoids.

The lower respiratory system serves as the target and barrier for beta-coronavirus (beta-CoV) infections. In this study, we explored beta-CoV infection dynamics in human bronchial epithelial (HBE) organoids, focusing on HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2. Utilizing advanced organoid culture techniques, we observed robust replication for all beta-CoVs, particularly noting that SARS-CoV-2 reached peak viral RNA levels at 72 h postinfection. Through comprehensive transcriptomic analysis, we identified significant shifts in cell population dynamics, marked by an increase in goblet cells and a concurrent decrease in ciliated cells. Furthermore, our cell tropism analysis unveiled distinct preferences in viral targeting: HCoV-OC43 predominantly infected club cells, while SARS-CoV had a dual tropism for goblet and ciliated cells. In contrast, SARS-CoV-2 primarily infected ciliated cells, and MERS-CoV showed a marked affinity for goblet cells. Host factor analysis revealed the upregulation of genes encoding viral receptors and proteases. Notably, HCoV-OC43 induced the unfolded protein response pathway, which may facilitate viral replication. Our study also reveals a complex interplay between inflammatory pathways and the suppression of interferon responses during beta-CoV infections. These findings provide insights into host-virus interactions and antiviral defense mechanisms, contributing to our understanding of beta-CoV infections in the respiratory tract.

Adolescents diagnosed with polycystic ovary syndrome under the Rotterdam criteria but not meeting the diagnosis under the updated guideline.

STUDY QUESTION: What are the characteristics of adolescents diagnosed with polycystic ovary syndrome (PCOS) based on the 2003 Rotterdam criteria, but who do not meet the diagnosis according to the international evidence-based guideline? SUMMARY ANSWER: Adolescents who had features of PCOS but did not meet the evidence-based guideline adolescent criteria exhibited unfavorable metabolic profiles compared to controls and shared considerable metabolic and hormonal features with adolescents who did meet the adolescent criteria. WHAT IS KNOWN ALREADY: The international evidence-based PCOS guideline recommended that ultrasound should not be used for the diagnosis of PCOS in girls with a gynecological age of <8 years. Thus far, few studies have evaluated the clinical characteristics of the girls diagnosed with PCOS based on the Rotterdam criteria but who do not meet the diagnosis according to the updated guideline. STUDY DESIGN, SIZE, DURATION: This is a retrospective study, and subjects attended for care from 2004 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Adolescent girls with PCOS diagnosed according to the 2003 Rotterdam criteria and healthy controls. All participants were between 2 and 8 years since menarche. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 315 girls diagnosed with PCOS according to the Rotterdam criteria, those with irregular menstruation (IM)/hyperandrogenism (HA)/polycystic ovary (PCO), IM/HA, HA/PCO, and IM/PCO phenotypes accounted for 206 (65.4%), 30 (9.5%), 12 (3.8%), and 67 (21.3%) participants, respectively. According to the evidence-based guideline, 79 girls (25.1%) with the HA/PCO or IM/PCO phenotypes were not diagnosed with PCOS, and aligned to the international guideline; they were designated as the 'at-risk' group. As expected, the girls meeting the evidence-based guideline adolescent criteria showed the worst metabolic profiles (degree of generalized or central obesity, frequency of insulin resistance, prediabetes or diabetes, and metabolic syndrome) and higher hirsutism scores than the at-risk group or controls. Approximately 90% of the at-risk group were not overweight or obese, which was similar to the controls. However, they showed worse metabolic profiles, with higher blood pressure, triglyceride, and insulin resistance parameters than controls; furthermore, these profiles were similar to those of the girls meeting the adolescent criteria. The at-risk group showed similarly elevated serum LH levels and LH/FSH ratio with the girls meeting adolescent criteria. LIMITATIONS, REASONS FOR CAUTION: We could not evaluate hormonal or ultrasound parameters in controls. WIDER IMPLICATIONS OF THE FINDINGS: Compared to the conventional Rotterdam criteria, the recent international evidence-based guideline-avoiding ultrasound in PCOS diagnosis in adolescents-still gives the opportunity to identify young girls at risk, aligned to the findings in this study. A practical approach to this adolescent population would involve establishing IM or HA (with ultrasound not indicated) and designating 'at-risk' PCOS status with regular check-ups for newly developed or worsening PCOS-related symptoms or metabolic abnormalities, with subsequent reassessment including ultrasound or anti-Müllerian hormone, once 8 years post-menarche. STUDY FUNDING/COMPETING INTEREST(S): No funding was received in support of this study. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

The Upper Common Pathway in Atrioventricular Nodal Reentrant Tachycardia: A Comprehensive Review of Evidence and Current Perspectives.

Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common form of paroxysmal supraventricular tachycardia, and its diagnostic and therapeutic approaches have been well-established. Traditionally, AVNRT is understood to be an intranodal reentry having two bystander pathways; the upper common pathway (UCP) which connects to the atrium and the lower common pathway which connects to the ventricle. However, the existence of the UCP remains a subject of ongoing debate. The assertion of the UCP's presence is supported by electrophysiological evidence suggesting that the atrium is not essential for the perpetuation of AVNRT. Nonetheless, numerous anatomical studies have failed to identify any structure that could be conclusively designated as the UCP. The histological and electrophysiological characteristics of the slow and fast pathways, which are the core components of AVNRT, suggest the inclusion of atrial myocardium in the reentry circuit. While clear interpretation of these discrepancies remains elusive, potential explanations may be derived from existing evidence and recent research findings concerning the actual AVNRT circuit.

Emergent Quantum Phenomena of a Noncentrosymmetric Charge Density Wave in 1T-Transition Metal Dichalcogenides.

1T-transition metal dichalcogenides (TMDs) have been an exciting platform for exploring the intertwinement of charge density waves and strong correlation phenomena. While the David star structure has been conventionally considered as the underlying charge order in the literature, recent scanning tunneling probe experiments on several monolayer 1T-TMD materials have motivated a new, alternative structure, namely, the anion-centered David star structure. In this Letter, we show that this novel anion-centered David star structure manifestly breaks inversion symmetry, resulting in flat bands with pronounced Rashba spin-orbit couplings. These distinctive features unlock novel possibilities and functionalities for 1T-TMDs, including the giant spin Hall effect, the emergence of Chern bands, and spin liquid that spontaneously breaks crystalline rotational symmetry. Our findings establish promising avenues for exploring emerging quantum phenomena of monolayer 1T-TMDs with this novel noncentrosymmetric structure.

Combination of [18F]FDG and [18F]PSMA-1007 PET/CT predicts tumour aggressiveness at staging and biochemical failure postoperatively in patients with prostate cancer.

PURPOSE: [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limitations in prostate cancer (PCa) detection owing to low glycolysis in the primary tumour. Recently, prostate-specific membrane antigen (PSMA) PET/CT has been useful for biochemical failure detection and radioligand therapy (RLT) guidance. However, few studies have evaluated its use in primary prostate tumours using PSMA and [18F]FDG PET/CT. This study aimed to evaluate [18F]PSMA-1007 and [18F]FDG PET/CT for primary tumour detection and understand the association of metabolic heterogeneity with clinicopathological characteristics at staging and postoperatively. METHOD: This prospective study included 42 index tumours (27 acinar and 15 ductal-dominant) in 42 patients who underwent [18F]PSMA-1007 and [18F]FDG PET/CT and subsequent radical prostatectomy. All patients were followed for a median of 26 mo, and serum prostate-specific antigen levels were measured every 3 mo to evaluate biochemical failure. One-way analysis of variance, Tukey's multiple comparison test, and Fisher's exact test were performed. RESULTS: All 42 index tumours were detected on [18F]PSMA-1007 PET/CT, whereas only 15 were detected on [18F]FDG PET/CT (62.3% vs. 37.7%, p < 0.0001). A high SUVmax for [18F]PSMA-1007 was observed in tumours with high Gleason scores (GS 6-7 vs. GS 8-10; 12.1 vs. 20.1, p < 0.05). Tumours with [18F]FDG uptake were mostly ductal dominant (acinar-dominant 4/27; ductal-dominant; 11/15, p < 0.001), with lower [18F]PSMA-1007 uptake than tumours without [18F]FDG uptake (SUVmax 16.58 vs. 11.19, p < 0.001). There were 16.6% (7/42) of patients with pStage IV in whom the primary tumours were [18F]FDG positive. Biochemical failure was observed in 14.8% (4/27) of patients with [18F]FDG negative tumours but in 53.3% (8/15) of patients with [18F]FDG positive tumours (p = 0.013). CONCLUSIONS: [18F]PSMA-1007 PET/CT was superior to [18F]FDG PET/CT in detecting primary PCa. In contrast, tumours with [18F]FDG uptake are associated with larger size, a ductal-dominant type, and likely to undergo metastasis at staging and biochemical failure postoperatively.

Effect of smoking cessation on psoriasis vulgaris, palmoplantar pustulosis and generalized pustular psoriasis.

BACKGROUND: Smoking is a known risk factor for psoriasis; however, the impact of smoking cessation on psoriasis has seldom been evaluated. OBJECTIVES: We aimed to examine the effects of smoking cessation on the development of psoriasis vulgaris (PsV), palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP). METHODS: Using the Korean National Health Insurance Service database, we retrospectively compiled a cohort of 5 784 973 participants without psoriasis, analysed their changes in smoking status from 2004 to 2007 and followed up new cases of psoriasis until 2021. The psoriasis risks were compared with those of sustained smokers, smoking quitters, sustained ex-smokers and never smokers using multivariate Cox proportional hazard models. RESULTS: The mean age of the participants was 47.1 years (SD 13.5) and 3 092 426 (53.5%) were male. During 77 990 688 person-years, 67 364 psoriasis cases were identified. Compared with sustained smokers, smoking quitters showed a reduced risk of developing psoriasis [adjusted hazard ratio (aHR) 0.91; 95% confidence interval (CI) 0.87-0.95], specifically PsV (aHR 0.92; 95% CI 0.88-0.97) and PPP (aHR 0.71; 95% CI 0.63-0.79). The reduction in risk due to smoking cessation was more prominent in sustained ex-smokers (psoriasis: aHR 0.77, 95% CI 0.74-0.79; PsV: aHR 0.76, 95% CI 0.73-0.79; PPP: aHR 0.56, 95% CI 0.51-0.61; GPP: aHR 0.64; 95% CI 0.52-0.78). When conducting sensitivity analyses to address the potential for changes in smoking habits after 2007, the results and trends were consistent with the main findings, and a more pronounced significance was observed. CONCLUSIONS: Compared with continuous smoking, smoking cessation was associated with a decreased risk of developing psoriasis. The risk-reducing effect of smoking cessation was more pronounced in those maintaining a smoke-free status. Smoking cessation and the maintenance of a smoke-free status should be encouraged to prevent the development of psoriasis and all other smoking-related diseases.

Psoriasis vulgaris (PsV) is a chronic inflammatory skin condition that causes scaly plaques on the body. Pustular psoriasis [including palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP)] is a variant characterized by sterile pustules. Limited evidence exists on how quitting smoking affects psoriasis and its subtypes. In this study conducted in South Korea, we aimed to investigate how changes in smoking habits, especially quitting smoking, could impact the development of psoriasis. We used medical claims records from the Korean National Health Insurance Service database, which included data from over 5.7 million people participating in health checkups between 2004 and 2007. We divided people into four groups based on their smoking habits: sustained smokers, smoking quitters, sustained ex-smokers and never smokers. We found that smoking quitters had a lower risk of developing psoriasis, especially PsV and PPP. Even people who had quit smoking and remained smoke-free for an extended period (sustained ex-smokers) showed a more pronounced reduction in the risk of psoriasis, including PsV, PPP and GPP. Our findings remained consistent across various groups of people, considering factors such as age, sex, weight and overall health. The results suggest that encouraging people to quit smoking and maintain a smoke-free lifestyle may help to prevent the onset of psoriasis. In conclusion, this large-scale study from South Korea provides real-world evidence to suggest that quitting smoking could reduce the risk of developing psoriasis. These findings are valuable for public health initiatives, emphasizing the benefits of quitting smoking for skin health.

Evaluation of renovated double J stents using ureter models with and without stenosis.

PURPOSE: Commercial double J stents (DJS) have a uniform shape regardless of the specific nature of various ureteral diseases. We tested renovated DJS and compared them with conventional DJS using ureter models. METHODS: One straight ureter model included stenosis at the distal ureter near the ureterovesical junction and the other did not. We used conventional DJS and renovated 5- and 6-Fr soft DJS for ureter stones and 6-, 7-, and 8.5-Fr hard DJS for tumors. The DJS comprised holes in the upper, middle, or lower one-third of the shaft (length, 24 cm; 2-cm-diameter coils at both ends). More holes were created along the shaft based on the ureteral disease location. Conventional DJS had holes spaced 1 cm apart along the shaft. Renovated DJS had holes spaced 1 cm apart along the shaft with 0.5-cm intervals on the upper, middle, or lower one-third of the shaft. Urine flow was evaluated. RESULTS: As the DJS diameter increased, the flow rate decreased. The flow rates of DJS with holes in the lower shaft were relatively lower than those of conventional DJS and DJS with holes in the upper and middle shafts. In the ureter model without stenosis, 6-, 7-, and 8.5-Fr renovated stents exhibited significantly higher flow rates than conventional stents. In the ureter model with stenosis, 5-, 6-, 7-, and 8.5-Fr renovated stents did not exhibit significantly higher flow rates than conventional stents. CONCLUSION: Renovated stents and conventional stents did not exhibit significant differences in urine flow with stenosis.

Effectiveness of microvascular flow imaging for radiofrequency ablation in recurrent thyroid cancer: comparison with power Doppler imaging.

OBJECTIVES: To compare microvascular flow imaging (MVFI) and power Doppler ultrasonography imaging (PDUS) for detecting intratumoral vascularity in recurrent thyroid cancer both before and after radiofrequency ablation (RFA). METHODS: This retrospective study included 80 patients (age, 57 ± 12 years; 54 women) with 110 recurrent tumors who underwent RFA between January 2021 and June 2023. A total of 151 PDUS and MVFI image sets were analyzed (85 pre-RFA, 66 post-RFA). Two readers assessed vascularity on the images using a four-point scale with a 2-week interval between PDUS and MVFI to estimate inter-reader agreement. Intra-reader agreement was determined by reinterpreting images in reverse order (MVFI-PDUS) after a 1-month gap. Additionally, diagnostic performance for identifying viable tumors after RFA was assessed in 44 lesions using thyroid-protocol CT as a reference standard. RESULTS: MVFI demonstrated higher vascular grades than PDUS, both before (reader 1: 3.04 ± 1.15 vs. 1.93 ± 1.07, p < 0.001; reader 2: 3.20 ± 0.96 vs. 2.12 ± 1.07, p < 0.001) and after RFA (reader 1: 2.44 ± 1.28 vs. 1.67 ± 1.06, p < 0.001; reader 2: 2.62 ± 1.23 vs. 1.83 ± 0.99, p < 0.001). Inter-reader agreement was substantial (κ = 0.743) and intra-reader agreement was almost perfect (κ = 0.840). MVFI showed higher sensitivity (81.5%-88.9%) and accuracy (84.1%-86.4%) than PDUS (sensitivity: 51.9%, p < 0.01; accuracy: 63.6-70.5%, p < 0.04), without sacrificing specificity. CONCLUSION: MVFI was superior to PDUS for assessing intratumoral vascularity and showed good inter- and intra-reader agreement, highlighting its clinical value for assessing pre-RFA vascularity and accurately identifying post-RFA viable tumors in recurrent thyroid cancer. CLINICAL RELEVANCE STATEMENT: Microvascular flow imaging (MVFI) is superior to power-Doppler US for assessing intratumoral vascularity; therefore, MVFI can be a valuable tool for assessing vascularity before radiofrequency ablation (RFA) and for identifying viable tumors after RFA in patients with recurrent thyroid cancer. KEY POINTS: The value of microvascular flow imaging (MVFI) for evaluating intratumoral vascularity is unexplored. MVFI demonstrated higher vascular grades than power Doppler US before and after ablation. Microvascular flow imaging showed higher sensitivity and accuracy than power Doppler US without sacrificing specificity.

Enhancement on CT for preoperative diagnosis of metastatic lymph nodes in thyroid cancer: a comparison across experience levels.

OBJECTIVES: To investigate the diagnostic performance and interobserver agreement of quantitative CT parameters indicating strong lymph node (LN) enhancement in differentiated thyroid cancer (DTC), comparing them with qualitative analysis by radiologists of varying experience. MATERIALS AND METHODS: This study included 463 LNs from 399 patients with DTC. Three radiologists independently analyzed strong LN enhancement on CT. Qualitative analysis of strong enhancement was defined as LN cortex showing greater enhancement than adjacent muscles on the arterial phase. Quantitative analysis included the mean attenuation value (MAV) of LN on arterial phase (LNA) and venous phase (LNV), LNA normalized to the common carotid artery (NAVCCA), internal jugular vein (NAVIJV), and sternocleidomastoid muscle (NAVSCM), attenuation difference [AD; (LNA - MAVSCM)], and relative washout ratio [((LNA - LNV)/LNA) × 100]. The interobserver agreement and diagnostic performance of the quantitative and qualitative analyses were evaluated. RESULTS: Interobserver agreement was excellent for all quantitative CT parameters (ICC, 0.83-0.94) and substantial for qualitative assessment (κ = 0.61). All CT parameters except for LNV showed good diagnostic performance for metastatic LNs (AUC, 0.81-0.85). NAVCCA (0.85, 95% CI: 0.8-0.9) and AD (0.85, 95% CI: 0.81-0.89) had the highest AUCs. All quantitative parameters except for NAVIJV had significantly higher AUCs than qualitative assessments by inexperienced radiologists, with no significant difference from assessments by an experienced radiologist. CONCLUSION: Quantitative assessment of LN enhancement on arterial phase CT showed higher interobserver agreement and AUC values than qualitative analysis by inexperienced radiologists, supporting the need for a standardized quantitative CT parameter-based model for determining strong LN enhancement. CLINICAL RELEVANCE STATEMENT: When assessing strong LN enhancement in DTC, quantitative CT parameters indicating strong enhancement can improve interobserver agreement, regardless of experience level. Therefore, the development of a standardized diagnostic model based on quantitative CT parameters might be necessary. KEY POINTS: Accurate preoperative assessment of LN metastasis in thyroid cancer is crucial. Quantitative CT parameters indicating strong LN enhancement demonstrated excellent interobserver agreement and good diagnostic performance. Quantitative assessment of contrast enhancement offers a more objective model for the identification of metastatic LNs.