Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice.

A protective HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted with AS01B was found to induce VRC01-class bnAb precursors in 97% of vaccine recipients in the IAVI G001 phase 1 clinical trial; however, heterologous boost immunizations with antigens more similar to the native glycoprotein will be required to induce bnAbs. Therefore, we designed core-g28v2 60mer, a nanoparticle immunogen to be used as a first boost after eOD-GT8 60mer priming. We found, using a humanized mouse model approximating human conditions of VRC01-class precursor B cell diversity, affinity, and frequency, that both protein- and mRNA-based heterologous prime-boost regimens induced VRC01-class antibodies that gained key mutations and bound to near-native HIV envelope trimers lacking the N276 glycan. We further showed that VRC01-class antibodies induced by mRNA-based regimens could neutralize pseudoviruses lacking the N276 glycan. These results demonstrated that heterologous boosting can drive maturation toward VRC01-class bnAb development and supported the initiation of the IAVI G002 phase 1 trial testing mRNA-encoded nanoparticle prime-boost regimens.

Ethanol Ablation of Ranulas and Risk Factor Analysis for Recurrence.

Importance: Ethanol ablation (EA) was shown to be safe and effective for treating ranula, but few studies have assessed long-term outcomes and recurrence of ranula after EA. Objective: To evaluate the long-term outcomes and the risk factors for recurrence and receipt of subsequent surgery in patients who underwent treatment with EA for ranula. Design, Setting, and Participants: This case-series study was conducted at a single tertiary hospital and assessed patients who were treated with EA between July 2009 and March 2021. Among 70 consecutive patients, those with follow-up loss or who were followed up for less than 24 months were excluded. Exposures: EA for ranula. Main Outcomes and Measures: The primary outcome was recurrence at last follow-up after single or multiple EA sessions. Secondary outcomes included receipt of subsequent surgery and the recurrence-free survival (RFS) rate after initial EA. Factors possibly associated with outcomes included patient age and sex; ranula site, type, diameter, volume, and echogenicity; the presentation-to-EA interval; parapharyngeal space extension; and sublingual gland herniation. Risk factors were identified on logistic regression analyses. Two-year RFS rates were analyzed for the initial cohort using the Kaplan-Meier method and compared by log-rank tests. Results: A total of 57 patients (mean [SD] age, 26.4 [12.1] years; 24 female individuals [42%]) who were followed up for a median of 57 months (range, 24-167 months) were included. The recurrence rate was 33% (n = 19), and 11 (19%) underwent subsequent surgery. Among patients with recurrence, 86% (31 of 36) experienced first recurrence within 12 months after initial EA. A presentation-to-EA interval of 12 months or longer was associated with an increased risk of recurrence (adjusted odds ratio [OR], 3.74; 95% CI, 1.01-13.82). No risk factors were significantly associated with subsequent surgery (highest OR in parapharyngeal space extension: adjusted OR, 4.96; 95% CI, 0.94-26.35). Among the initial cohort of 70 patients, 2-year RFS was lower in a maximum diameter of ranula of 5 cm or greater than less than 5 cm (24% [95% CI, 7%-41%] vs 50% [95% CI, 34%-66%]; difference, 26% [95% CI, -4% to 56%]; log-rank test, P = .02). Conclusions and Relevance: This case-series study found that the recurrence rate of ranula after EA was 33%. A presentation-to-EA interval of 12 months or longer may be a risk factor for recurrence, suggesting that early intervention with EA might minimize recurrence. Most first recurrences occurred within 12 months after EA, with a maximum diameter of ranula of 5 cm or greater being a possible risk factor.

mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies.

Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody-induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan-targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development.

Should we suspect gallbladder cancer if which CT finding is observed in patients with localized gallbladder wall thickening?

PURPOSE: To identify high-risk computed tomography (CT) features for predicting gallbladder (GB) cancer in patients presenting with localized GB wall thickening. METHODS: This retrospective analysis included 120 patients (mean age: 63.9 ± 10.0 years; 51 men) exhibiting localized GB wall thickening on CT scans obtained between January 2008 and May 2017. Two radiologists independently evaluated CT imaging features for predicting GB cancer. The diagnostic performance of significant imaging features and their combinations was evaluated. High-risk CT features ranked by accuracy were delineated for predicting GB cancer. RESULTS: This study included 55 patients with GB cancer and 65 with benign GB conditions. The top-four most accurate CT imaging features for predicting GB cancer were identified: heterogeneously enhancing single layer or strongly enhancing thick inner layer; GB wall thickness > 6.5 mm; hyperenhancement on arterial phase; and absence of intramural small cystic lesions (accuracies of 90.0 %, 88.3 %, 85.0 %, and 85.0 %, respectively). The combination of any three high-risk features exhibited the highest accuracy (94.2 %). The presence of any high-risk feature yielded a sensitivity of 100 %, whereas that of all high-risk features indicated a specificity of 100 %. CONCLUSION: CT imaging features, whether alone or in combination, could effectively and accurately predict GB cancer among patients with localized GB wall thickening. This finding holds significance in guiding decisions regarding further diagnostic tests and treatment planning.

Vaccination induces broadly neutralizing antibody precursors to HIV gp41.

A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.

Prognostic significance of MRI features in patients with solitary large hepatocellular carcinoma following surgical resection.

OBJECTIVE: To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection. MATERIAL AND METHODS: This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors. RESULTS: Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019). CONCLUSION: MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies. CLINICAL RELEVANCE STATEMENT: Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies. KEY POINTS: MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes.

Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates.

Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

Collagen Meniscal Scaffold Implantation Can Provide Meniscal Regeneration in Asian Patients with Partial Meniscal Defects: A Prospective Randomized Controlled Study with Three-Dimensional Volume Analysis of the Meniscus.

Background: To date, the efficiency of collagen meniscal scaffold implantation in Asian patients with partial meniscal defects has not been evaluated. In addition, no study has quantitatively analyzed meniscal regeneration using three-dimensional (3D) volume analysis after collagen scaffold implantation. We aimed to compare meniscal regeneration using 3D volume analysis between Asian patients undergoing collagen-based meniscal scaffold implantation after partial meniscectomy and those undergoing only partial meniscectomy. Methods: Nineteen patients who underwent collagen-based meniscal scaffold implantation and 14 who underwent partial meniscectomy were analyzed with a prospective randomized control design for 12 months postoperatively. The demographic characteristics, Kellgren-Lawrence grade, and location of the injury lesion (medial or lateral meniscus) were not significantly different between the groups. Using 3D volume analysis with magnetic resonance imaging (MRI), the meniscus-removing ratio during the operative procedure and the meniscus defect-filling ratio were measured during the 12-month postoperative period. Clinically, the visual analog scale, International Knee Documentation Committee score, and Knee Injury and Osteoarthritis Outcome Score were evaluated. The Whole-Organ Magnetic Resonance Imaging Score (WORMS) and Genovese grade were also evaluated using MRI. Results: In the 3D volume analysis, the average meniscus-removing ratio during surgery was not significantly different between the groups (-9.3% vs. -9.2%, p = 0.984). The average meniscus defect-filling ratio during the postoperative 12-month period was 7.5% in the scaffold group and -0.4% in the meniscectomy group (p < 0.001). None of the clinical results were significantly different between the scaffold and meniscectomy groups at 12 months postoperatively. The average change in the total WORMS score was not significantly different between the groups (0 vs. 1.9, p = 0.399). The Genovese grade of the implanted collagen scaffold did not significantly change during the follow-up period in terms of morphology and size (p = 0.063); however, the grade significantly improved in terms of signal intensity (p = 0.001). Conclusions: Definite meniscal regeneration and stable scaffold incorporation were observed after collagen-based meniscal scaffold implantation in Asian patients during 12 months of follow-up. A long-term follow-up study with a larger cohort is required to determine the advantages of collagenous meniscal scaffold implantation in Asian patients.

Using GPT-4 for LI-RADS feature extraction and categorization with multilingual free-text reports.

BACKGROUND AND AIMS: The Liver Imaging Reporting and Data System (LI-RADS) offers a standardized approach for imaging hepatocellular carcinoma. However, the diverse styles and structures of radiology reports complicate automatic data extraction. Large language models hold the potential for structured data extraction from free-text reports. Our objective was to evaluate the performance of Generative Pre-trained Transformer (GPT)-4 in extracting LI-RADS features and categories from free-text liver magnetic resonance imaging (MRI) reports. METHODS: Three radiologists generated 160 fictitious free-text liver MRI reports written in Korean and English, simulating real-world practice. Of these, 20 were used for prompt engineering, and 140 formed the internal test cohort. Seventy-two genuine reports, authored by 17 radiologists were collected and de-identified for the external test cohort. LI-RADS features were extracted using GPT-4, with a Python script calculating categories. Accuracies in each test cohort were compared. RESULTS: On the external test, the accuracy for the extraction of major LI-RADS features, which encompass size, nonrim arterial phase hyperenhancement, nonperipheral 'washout', enhancing 'capsule' and threshold growth, ranged from .92 to .99. For the rest of the LI-RADS features, the accuracy ranged from .86 to .97. For the LI-RADS category, the model showed an accuracy of .85 (95% CI: .76, .93). CONCLUSIONS: GPT-4 shows promise in extracting LI-RADS features, yet further refinement of its prompting strategy and advancements in its neural network architecture are crucial for reliable use in processing complex real-world MRI reports.

Mechanism of Action and Translational Potential of (S)-Meclizine in Preemptive Prophylaxis Against Stroke.

BACKGROUND: Mild chemical inhibition of mitochondrial respiration can confer resilience against a subsequent stroke or myocardial infarction, also known as preconditioning. However, the lack of chemicals that can safely inhibit mitochondrial respiration has impeded the clinical translation of the preconditioning concept. We previously showed that meclizine, an over-the-counter antivertigo drug, can toggle metabolism from mitochondrial respiration toward glycolysis and protect against ischemia-reperfusion injury in the brain, heart, and kidney. Here, we examine the mechanism of action of meclizine and report the efficacy and improved safety of the (S) enantiomer. METHODS: We determined the anoxic depolarization latency, tissue and neurological outcomes, and glucose uptake using micro-positron emission tomography after transient middle cerebral artery occlusion in mice pretreated (-17 and -3 hours) with either vehicle or meclizine. To exclude a direct effect on tissue excitability, we also examined spreading depression susceptibility. Furthermore, we accomplished the chiral synthesis of (R)- and (S)-meclizine and compared their effects on oxygen consumption and histamine H1 receptor binding along with their brain concentrations. RESULTS: Micro-positron emission tomography showed meclizine increases glucose uptake in the ischemic penumbra, providing the first in vivo evidence that the neuroprotective effect of meclizine indeed stems from its ability to toggle metabolism toward glycolysis. Consistent with reduced reliance on oxidative phosphorylation to sustain the metabolism, meclizine delayed anoxic depolarization onset after middle cerebral artery occlusion. Moreover, the (S) enantiomer showed reduced H1 receptor binding, a dose-limiting side effect for the racemate, but retained its effect on mitochondrial respiration. (S)-meclizine was at least as efficacious as the racemate in delaying anoxic depolarization onset and decreasing infarct volumes after middle cerebral artery occlusion. CONCLUSIONS: Our data identify (S)-meclizine as a promising new drug candidate with high translational potential as a chemical preconditioning agent for preemptive prophylaxis in patients with high imminent stroke or myocardial infarction risk.

Comparison of Nasal Dimensions According to the Facial and Nasal Indices Using Cone-Beam Computed Tomography.

The nasal cavity constitutes the foremost portion of the respiratory system, composed of the anterior nasal aperture, nostrils, and choanae. It has an intricate anatomical structure since it has various functions, such as heat exchange, humidification, and filtration. Accordingly, clinical symptoms related to the nose, such as nasal congestion, snoring, and nasal septal deviation, are closely linked to the complex anatomical structure of the nasal cavity. Thus, the nasal cavity stands as a paramount structure in both forensic and clinical contexts. The majority of relevant studies have performed comparisons between sexes, with studies making comparisons according to the FI and NI only and examining relative percentages. Furthermore, the nasal cavity was measured in 2D, and not 3D, in most cases. In this study, we conducted a 3D modeling and anthropometric assessment of the nasal cavity using a 3D analysis software. Furthermore, we aimed to investigate whether the size of the nasal cavity differs according to sex, facial index (FI), and nasal index (NI). We retrospectively reviewed the cone-beam computed tomography (CBCT) data of 100 participants (50 males, 50 females) aged 20-29 years who visited the dental hospital of Dankook University (IRB approval no. DKUDH IRB 2020-01-007). Our findings showed that nasal cavity sizes generally differed according to sex, FI, and NI. These findings provide implications for performing patient-tailored surgeries in clinical practice and conducting further research on the nasal cavity. Therefore, we believe that our study makes a significant contribution to the literature.

N-(2,3-dihydroxypropyl) carbamoyl side chain: a potentially significant factor for recurrent iodinated contrast medium-related adverse drug reactions.

PURPOSE: To determine whether switching to contrast media based on the sharing of N-(2,3-dihydroxypropyl) carbamoyl side chain reduces the recurrence of iodinated contrast media (ICM)-associated adverse drug reactions (ADRs). MATERIALS AND METHODS: This single-center retrospective study included 2133 consecutive patients (mean age ± SD, 56.1 ± 11.4 years; male, 1052 [49.3%]) who had a history of ICM-associated ADRs and underwent contrast-enhanced CT examinations. The per-patient and per-exam-based recurrence ADR rates were compared between cases of switching and non-switching the ICM from ICMs that caused the previous ADRs, and between cases that used ICMs with common and different carbamoyl side chains from ICMs that caused the previous ADRs. Downgrade rates (no recurrence or the occurrence of ADR less severe than index ADRs) were also compared. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were additionally performed. RESULTS: In per-patient analysis, switching of ICM showed a lower recurrence rate (switching, 10.4% [100/965] vs. non-switching, 28.4% [332/1168]), with the adjusted odds ratio (OR) of 0.27 (95% CI: 0.21, 0.34; p < 0.001). The result was consistent in PSM (OR, 0.29 [95% CI: 0.22, 0.39]; p < 0.001), IPTW (OR, 0.28 [95% CI: 0.22, 0.36]; p < 0.001), and in per-exam analysis (5.5% vs. 13.8%; OR, 0.32 [95% CI: 0.27, 0.37]; p < 0.001). There was lower per-exam recurrence (5.0% [195/3938] vs. 7.8% [79/1017]; OR, 0.63 [95% CI: 0.47, 0.83]; p = 0.001) and higher downgrade rates (95.6% [3764/3938] vs. 93.3% [949/1017]; OR, 1.51 [95% CI: 1.12, 2.03]; p = 0.006) when using different side chain groups. CONCLUSION: Switching to an ICM with a different carbamoyl side chain reduced the recurrent ADRs and their severity during subsequent examinations. CLINICAL RELEVANCE STATEMENT: Switching to an iodinated contrast media with a different carbamoyl side chain reduced the recurrent adverse drug reactions and their severity during subsequent examinations.

Volumetric assessment of ulnar nerves in cubital tunnel syndrome with 3D modeling of the MRI and its relationship with electrodiagnostic findings.

BACKGROUND: Thickened nerve cross-sectional areas (CSA) have been investigated in compressive neuropathy, but the longitudinal extent of nerve swelling has yet to be evaluated. We did a volumetric assessment of the ulnar nerve in cubital tunnel syndrome (CuTS) with three-dimensional (3D) magnetic resonance imaging (MRI) modeling and investigated this relationship with clinical and electrodiagnostic parameters. METHODS: We compared 40 CuTS patient elbow MRIs to 46 patient elbow MRIs with lateral elbow epicondylitis as controls. The ulnar nerve was modeled with Mimics software and was assessed qualitatively and quantitatively. The CSA and ulnar nerve volumes were recorded, and the area under the receiver operating characteristic (ROC) curve was calculated for diagnostic performance. We analyzed clinical and electrodiagnostic parameters to investigate their relationship with the 3D ulnar nerve parameters. RESULTS: For the diagnosis of CuTS, the area under the curve value was 0.915 for the largest CSA and 0.910 for the volume in the ROC curve. The optimal cut-off was 14.53 mm2 and 529 mm3 respectively. When electrodiagnostic parameters were investigated, the 3D ulnar nerve volume was significantly inversely associated with motor conduction velocity, although there was no association between the largest CSA and any of the electrodiagnostic parameters. CONCLUSIONS: The 3D ulnar nerve volume, which is an integration or multilevel measurement of CSAs, showed diagnostic usefulness similar to CSA, but it correlated better with conduction velocity, indicating demyelination or early-to-moderate nerve damage in CuTS.

Magnetic resonance elastography as a preoperative assessment for predicting intrahepatic recurrence in patients with hepatocellular carcinoma.

PURPOSE: Magnetic resonance elastography (MRE) is a noninvasive tool for diagnosing hepatic fibrosis with high accuracy. We investigated the preoperative clinical and imaging predictors of intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC), and evaluated MRE as a predictor of intrahepatic recurrence. METHODS: We retrospectively evaluated 80 patients who underwent preoperative contrast-enhanced magnetic resonance imaging (MRI) with two-dimensional MRE and curative resection for treatment-naïve HCC between May 2019 and December 2021. Liver stiffness (LS) was measured on the elastograms, and the optimal cutoff of LS for predicting intrahepatic recurrence was obtained using receiver operating characteristic (ROC) analysis. An LS above this cutoff was defined as MRE-recurrence. Preoperative imaging features of the tumor were assessed on MRI, including features in the Liver Imaging Reporting and Data System and microvascular invasion (MVI). Recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method, and differences were compared using the log-rank test. Using a Cox proportional hazards model, we conducted a multivariable analysis to investigate the factors affecting recurrence-free survival. RESULTS: During a median follow-up period of 32 months (range, 4-52 months), thirteen patients (16.3%) developed intrahepatic recurrence. ROC analysis determined an LS cutoff of ≥4.35 kPa to define MRE-recurrence. The 4-year RFS rate was significantly higher in patients without MRE-recurrence than in those with MRE-recurrence (93.4% vs. 48.9%; p = 0.001). In multivariable analysis, MRE-recurrence (Hazard ratio [HR], 5.9; 95% confidence interval [CI], 1.5-23.1) and MVI (HR, 3.4; 95% CI, 1.0-11.3) were independent predictors of intrahepatic recurrence. CONCLUSIONS: Patients without MRE-recurrence had significantly higher RFS rates than those with MRE-recurrence. MRE-recurrence and MVI were independent predictors of intrahepatic recurrence in patients after curative resection for HCC.

Prolonged viral shedding in an immunocompromised Korean patient infected with hMPXV, sub-lineage B.1.3, with acquired drug resistant mutations during tecovirimat treatment.

Following the worldwide surge in mpox (monkeypox) in 2022, cases have persisted in Asia, including South Korea, and sexual contact is presumed as the predominant mode of transmission, with a discernible surge in prevalence among immunocompromised patients. Drugs such as tecovirimat can result in drug-resistant mutations, presenting obstacles to treatment. This study aimed to ascertain the presence of tecovirimat-related resistant mutations through genomic analysis of the monkeypox virus isolated from a reported case involving prolonged viral shedding in South Korea. Here, tecovirimat-resistant mutations, previously identified in the B.1 clade, were observed in the B.1.3 clade, predominant in South Korea. These mutations exhibited diverse patterns across different samples from the same patient and reflected the varied distribution of viral subpopulations in different anatomical regions. The A290V and A288P mutant strains we isolated hold promise for elucidating these mechanisms, enabling a comprehensive analysis of viral pathogenesis, replication strategies, and host interactions. Our findings imply that acquired drug-resistant mutations, may present a challenge to individual patient treatment. Moreover, they have the potential to give rise to transmitted drug-resistant mutations, thereby imposing a burden on the public health system. Consequently, the meticulous genomic surveillance among immunocompromised patients, conducted in this research, assumes paramount importance.

Knot-and-ear sign: a pathognomonic ultrasonographic feature of suture granuloma after thyroid surgery.

PURPOSE: This study investigated the clinical and ultrasonographic (US) findings of suture granulomas and recurrent tumors, and aimed to identify specific characteristics of suture granulomas through an experimental study. METHODS: This retrospective study included 20 pathologically confirmed suture granulomas and 40 recurrent tumors between January 2010 and December 2020. The clinical findings included suture material, surgery, and initial TNM stage. The US findings included shape, size, margin, echogenicity, heterogeneity, vascularity, and internal echogenic foci. The distribution, paired appearance, and "knot-and-ear" appearance of internal echogenic foci were assessed. An experiment using pork meat investigated the US configuration of suture knots. RESULTS: Eighteen patients with 20 suture granulomas (15 women; mean age, 52±13 years) and 37 patients with 40 recurrent tumors (24 women; 54±18 years) were included. Patients with suture granulomas exhibited earlier initial T and N stages than those with recurrent tumors. The knot-and-ear appearance, defined as an echogenic dot accompanied by two adjacent echogenic dots or lines based on experimental findings, was observed in 50% of suture granulomas, but not in recurrent tumors (P<0.001). Central internal echogenic foci (68.8%, P=0.023) and paired appearance (75.0%, P<0.001) were more frequent in suture granulomas. During follow-up, 94.1% of suture granulomas shrunk. CONCLUSION: The knot-and-ear appearance is a potential pathognomonic finding of suture granuloma, and central internal echogenic foci with paired appearance were typical US features. Clinically, suture granulomas showed early T and N stages and size reduction during follow-up. Understanding these features can prevent unnecessary biopsy or diagnostic surgery.

nnU-Net-Based Pancreas Segmentation and Volume Measurement on CT Imaging in Patients with Pancreatic Cancer.

RATIONALE AND OBJECTIVES: To develop and validate a deep learning (DL)-based method for pancreas segmentation on CT and automatic measurement of pancreatic volume in pancreatic cancer. MATERIALS AND METHODS: This retrospective study used 3D nnU-net architecture for fully automated pancreatic segmentation in patients with pancreatic cancer. The study used 851 portal venous phase CT images (499 pancreatic cancer and 352 normal pancreas). This dataset was divided into training (n = 506), internal validation (n = 126), and external test set (n = 219). For the external test set, the pancreas was manually segmented by two abdominal radiologists (R1 and R2) to obtain the ground truth. In addition, the consensus segmentation was obtained using Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm. Segmentation performance was assessed using the Dice similarity coefficient (DSC). Next, the pancreatic volumes determined by automatic segmentation were compared to those determined by manual segmentation by two radiologists. RESULTS: The DL-based model for pancreatic segmentation showed a mean DSC of 0.764 in the internal validation dataset and DSC of 0.807, 0.805, and 0.803 using R1, R2, and STAPLE as references in the external test dataset. The pancreas parenchymal volume measured by automatic and manual segmentations were similar (DL-based model: 65.5 ± 19.3 cm3 and STAPLE: 65.1 ± 21.4 cm3; p = 0.486). The pancreatic parenchymal volume difference between the DL-based model predictions and the manual segmentation by STAPLE was 0.5 cm3, with correlation coefficients of 0.88. CONCLUSION: The DL-based model efficiently generates automatic segmentation of the pancreas and measures the pancreatic volume in patients with pancreatic cancer.

The Diagnostic Role of Repeated Biopsy of Thyroid Nodules with Atypia of Undetermined Significance with Architectural Atypia on Core-Needle Biopsy.

BACKGRUOUND: We aimed to evaluate the utility of repeat biopsy of thyroid nodules classified as atypia of undetermined significance with architectural atypia (IIIB) on core-needle biopsy (CNB). METHODS: This retrospective study evaluated patients with thyroid nodules categorized as IIIB on CNB between 2013 and 2015. Demographic characteristics, subsequent biopsy results, and ultrasound (US) images were evaluated. The malignancy rates of nodules according to number of CNBs and the number of IIIB diagnoses was compared. Demographic and US features were evaluated to determine factors predictive of malignancy. RESULTS: Of 1,003 IIIB nodules on CNB, the final diagnosis was determined for 328 (32.7%) nodules, with 121 of them confirmed as malignant, resulting in a malignancy rate of 36.9% (95% confidence interval, 31.7% to 42.1%). Repeat CNB was performed in 248 nodules (24.7%), with 75 (30.2%), 131 (52.8%), 13 (5.2%), 26 (10.5%), one (0.4%), and two (0.8%) reclassified into categories II, IIIB, IIIA, IV, V, and VI, respectively. Malignancy rates were not significantly affected by the number of CNBs (P=0.291) or the number of IIIB diagnoses (P=0.473). None of the nodules confirmed as category II on repeat CNB was malignant. US features significantly associated with malignancy (P<0.003) included solid composition, irregular margins, microcalcifications, and high suspicion on the US risk stratification system. CONCLUSION: Repeat biopsy of nodules diagnosed with IIIB on CNB did not increase the detection of malignancy but can potentially reduce unnecessary surgery. Repeat biopsy should be performed selectively, with US features guiding the choice between repeat biopsy and diagnostic surgery.

Preoperative prediction of early recurrence in resectable pancreatic cancer integrating clinical, radiologic, and CT radiomics features.

OBJECTIVES: To use clinical, radiographic, and CT radiomics features to develop and validate a preoperative prediction model for the early recurrence of pancreatic cancer. METHODS: We retrospectively analyzed 190 patients (150 and 40 in the development and test cohort from different centers) with pancreatic cancer who underwent pancreatectomy between January 2018 and June 2021. Radiomics, clinical-radiologic (CR), and clinical-radiologic-radiomics (CRR) models were developed for the prediction of recurrence within 12 months after surgery. Performance was evaluated using the area under the curve (AUC), Brier score, sensitivity, and specificity. RESULTS: Early recurrence occurred in 36.7% and 42.5% of the development and test cohorts, respectively (P = 0.62). The features for the CR model included carbohydrate antigen 19-9 > 500 U/mL (odds ratio [OR], 3.60; P = 0.01), abutment to the portal and/or superior mesenteric vein (OR, 2.54; P = 0.054), and adjacent organ invasion (OR, 2.91; P = 0.03). The CRR model demonstrated significantly higher AUCs than the radiomics model in the internal (0.77 vs. 0.73; P = 0.048) and external (0.83 vs. 0.69; P = 0.038) validations. Although we found no significant difference between AUCs of the CR and CRR models (0.83 vs. 0.76; P = 0.17), CRR models showed more balanced sensitivity and specificity (0.65 and 0.87) than CR model (0.41 and 0.91) in the test cohort. CONCLUSIONS: The CRR model outperformed the radiomics and CR models in predicting the early recurrence of pancreatic cancer, providing valuable information for risk stratification and treatment guidance.