MRI radiomics model differentiates small hepatic metastases and abscesses in periampullary cancer patients.

This multi-center, retrospective study focused on periampullary cancer patients undergoing MRI for hepatic metastasis and abscess differentiation. T1-weighted, T2-weighted, and arterial phase images were utilized to create radiomics models. In the training-set, 112 lesions in 54 patients (median age [IQR, interquartile range], 73 [63-80]; 38 men) were analyzed, and 123 lesions in 55 patients (72 [66-78]; 34 men) comprised the validation set. The T1-weighted + T2-weighted radiomics model showed the highest AUC (0.82, 95% CI 0.75-0.89) in the validation set. Notably, < 30% T1-T2 size discrepancy in MRI findings predicted metastasis (Ps ≤ 0.037), albeit with AUCs of 0.64-0.68 for hepatic metastasis. The radiomics model enhanced radiologists' performance (AUCs, 0.85-0.87 vs. 0.80-0.84) and significantly increased diagnostic confidence (P < 0.001). Although the performance increase lacked statistical significance (P = 0.104-0.281), the radiomics model proved valuable in differentiating small hepatic lesions and enhancing diagnostic confidence. This study highlights the potential of MRI-based radiomics in improving accuracy and confidence in the diagnosis of periampullary cancer-related hepatic lesions.

Factors affecting the technical outcome of catheter-directed sclerotherapy for ovarian endometriomas.

PURPOSE: To identify factors related to technical outcomes of catheter-directed sclerotherapy (CDS) and suggest selection criteria for CDS in patients with ovarian endometrioma. METHOD: This retrospective study included patients with endometriomas treated with CDS between November 2015 and June 2023. The characteristics of the endometriomas, including diameter, morphology (unilocular or multilocular), and T2 signal intensity were evaluated using pre-procedure magnetic resonance imaging. Moreover, the size of the catheter (7- or 8.5-French) and route of access (transabdominal vs. transvaginal) was also analyzed. Multivariate logistic regression analyses were used to identify factors associated with the technical outcomes of CDS. RESULTS: Technical success was defined as successful completion of the following: 1) insertion of a 7- or 8.5-French catheter into the endometrioma, 2) full aspiration of the internal content, and 3) completion of sclerotherapy without ethanol leakage. Of the 323 women (mean age = 32.2 ± 6.0 years) with 401 endometriomas included in our study, technical success was achieved in 377 endometriomas (94.0 %). No major complications were observed. In the multivariate analysis, a diameter < 3 cm (odds ratio, 25.641; p < 0.001), T2 dark signal intensity (odds ratio, 7.462; p = 0.001), and transvaginal access (odds ratio, 4.016; p = 0.004) were associated with technical failure. CONCLUSIONS: Small endometrioma size (<3cm), T2 dark signal intensity, and transvaginal access were identified as significant risk factors for technical failure during catheter-directed sclerotherapy.

Magneto-Responsive Chiral Optical Materials: Flow-Induced Twisting of Cellulose Nanocrystals in Patterned Magnetic Fields.

Magnetic fields have been used to uniformly align the lyotropic chiral nematic (cholesteric) liquid crystalline (LC) phase of biopolymers to a global orientation and optical appearance. Here, we demonstrate that, in contrast, weak and patterned magnetic field gradients can create a complex optical appearance with the variable spatial local organization of needle-like magnetically decorated cellulose nanocrystals. The formation of optically patterned thin films with left- and right-handed chiral and achiral regions is observed and related to local magnetic gradient-driven vortices during LC suspension flow. We trace the localized flow directions of the magnetically decorated nanocrystals during evaporation-induced assembly, demonstrating how competing evaporation and field-induced localized flow affect the twisted organization within magnetically induced vortices. The simulations suggested that localized twisting inversion originates from the interplay between the direction and strength of the local-depth-related magnetic gradients and the receding front through peripheral magnetic gaps. We propose that this finding will lead to magnetically patterned photonic films.

The Biocompatibility and the Effect of Titanium and PEKK on the Osseointegration of Customized Facial Implants.

The purpose of this study was to investigate the optimization of computer-aided design/computer-aided manufacturing (CAD/CAM) patient-specific implants for mandibular facial bone defects and compare the biocompatibility and osseointegration of machined titanium (Ma), Sandblasted/Large-grit/Acid-etched (SLA) titanium, and polyetherketoneketone (PEKK) facial implants. We hypothesized that the facial implants made of SLA titanium had superior osseointegration when applied to the gonial angle defect and prevented the senile atrophy of the bone. Histologic findings of the soft-tissue reaction, hard-tissue reaction, and bone-implant contact (BIC (%) of 24 Ma, SLA, and PEKK facial implants at 8 and 12 weeks were investigated. There was no statistical difference in the soft tissue reaction. Bone was formed below the periosteum in all facial implants at 12 weeks and the BIC values were significantly different at both 8 and 12 weeks (p < 0.05). Ma, SLA, and PEKK facial implants are biocompatible with osseointegration properties. SLA can enhance osseointegration and provoke minimal soft tissue reactions, making them the most suitable choice. They provide an excellent environment for bone regeneration and, over the long term, may prevent atrophy caused by an aging mandible. The bone formation between the lateral surface of the facial implant and periosteum may assist in osseointegration and stabilization.

Stability Evaluation and Pharmacokinetic Profiling of Vepdegestrant in Rodents Using Liquid Chromatography-Tandem Mass Spectrometry.

Vepdegestrant (formerly ARV-471), a novel proteolysis-targeting chimera (PROTAC), targets estrogen receptor alpha (ERα) for degradation, offering a promising option to treat advanced ER-positive breast cancer. We developed and validated a sensitive and rapid liquid chromatography-tandem mass spectrometry method to quantify vepdegestrant in rodent plasma using bavdegalutamide (formerly ARV-110) as an internal standard. Plasma samples were prepared with protein precipitation using acetonitrile and analyzed using reverse-phase C18 columns and a mobile phase of 10 mM ammonium formate in distilled water and acetonitrile. The method demonstrated linearity from 1 to 1000 ng/mL in mouse and rat plasma, meeting all validation criteria, and successfully applied to in vivo and in vitro studies. Pharmacokinetic analysis revealed low-to-moderate clearance (313.3, 1053 mL/h/kg) and oral bioavailability (17.91, 24.12%) of vepdegestrant in mice and rats, respectively. It was unstable in buffer solutions across pH 2-10 and in phosphate-buffered saline (pH 7.4), likely due to adsorption, but remained stable in mouse and rat plasma at varying temperatures. In liver microsomes, vepdegestrant exhibited moderate stability in rats but was stable in mice, dogs, and humans. These findings enhance the understanding of pharmacokinetic properties of vepdegestrant supporting further development of PROTAC drugs.

Resorbable Microspheres versus Trisacryl Gelatin Microspheres for Uterine Artery Embolization: A Randomized Controlled Trial.

Background There are insufficient data comparing resorbable microspheres (RMs) with permanent trisacryl gelatin microspheres (TAGMs) for uterine artery embolization (UAE). Purpose To compare therapeutic efficacy and clinical outcomes in participants with symptomatic fibroids after UAE with RMs or TAGMs. Materials and Methods This randomized controlled trial included participants undergoing UAE for symptomatic fibroids at a single institution (from May 2021 to May 2023). Participants were randomized one-to-one to undergo UAE with either RMs or TAGMs. Numeric rating scale pain scores and cumulative fentanyl consumption were assessed for 24 hours after undergoing UAE. Anti-Mullerian hormone was measured to assess effects of UAE on ovarian function. MRI was performed before and 3 months after UAE to evaluate fibroid necrosis and uterine artery recanalization. Repeated variables such as pain were analyzed using Mann-Whitney U test with post hoc Bonferroni correction. Results Sixty female participants (mean age, 45.7 years ± 3.6 [SD]) completed the study, with 30 in each group. No evidence of a difference in pain scores was observed between groups (P > .99). Moreover, there was no evidence of a difference in the total fentanyl consumption at 24 hours after UAE between groups (median: RMs, 423 [IQR, 330-530] vs TAGMs, 562 [IQR, 437-780]; P = .15). Serum anti-Mullerian hormone 3 months after UAE showed no evidence of a difference between groups (RMs vs TAGMs, 0.71 ng/mL ± 0.73 vs 0.49 ng/mL ± 0.45, respectively; P = .09). No evidence of a difference in the rate of complete necrosis of the dominant fibroid was observed between groups (97% [29 of 30] for both groups; P > .99). The rate of uterine artery recanalization was higher in RM versus TAGM groups (70% [21 of 30] vs 17% [five of 30], respectively; P < .001). Conclusion UAE with RMs, compared with UAE with TAGMs, showed no evidence of a difference in terms of therapeutic effectiveness or postprocedural pain scores in participants with symptomatic fibroids. Clinical trial registration no. NCT05086770 © RSNA, 2024 See also the editorial by Spies in this issue.

Advances in Understanding Hepatocellular Carcinoma Vasculature: Implications for Diagnosis, Prognostication, and Treatment.

Hepatocellular carcinoma (HCC) progresses through multiple stages of hepatocarcinogenesis, with each stage characterized by specific changes in vascular supply, drainage, and microvascular structure. These vascular changes significantly influence the imaging findings of HCC, enabling non-invasive diagnosis. Vascular changes in HCC are closely related to aggressive histological characteristics and treatment responses. Venous drainage from the tumor toward the portal vein in the surrounding liver facilitates vascular invasion, and the unique microvascular pattern of vessels that encapsulate the tumor cluster (known as a VETC pattern) promotes vascular invasion and metastasis. Systemic treatments for HCC, which are increasingly being used, primarily target angiogenesis and immune checkpoint pathways, which are closely intertwined. By understanding the complex relationship between histopathological vascular changes in hepatocarcinogenesis and their implications for imaging findings, radiologists can enhance the accuracy of imaging diagnosis and improve the prediction of prognosis and treatment response. This, in turn, will ultimately lead to better patient care.

Bacteria, Fungi, and Scalp Psoriasis: Understanding the Role of the Microbiome in Disease Severity.

Background: Psoriasis is a chronic skin condition affected by genetic and environmental factors. Changes in the skin microbiome may affect the immune system and skin barrier functions, thereby contributing to the development and progression of psoriasis. The scalp, which is a common site for psoriasis, is often resistant to therapy. Although several studies have investigated the scalp microbiome, analyses focusing on both bacteria and fungi remain scarce. Methods: We examined the scalp microbiomes of 11 patients with psoriasis complicated with scalp lesions and categorized them according to their Psoriasis Area Severity Index (PASI) scores. The bacterial and fungal data were analyzed using QIIME2 pipeline version 2021.04 and the UNITE database version 8.3, respectively. Results: The Shannon indices for mild (2 patients), moderate (4 patients), and severe (5 patients) groups were 0.97, 1.38, and 1.88, respectively. A significant correlation was observed between increased mycobiome diversity and disease severity (p = 4.07 × 10-5, Spearman's correlation: 0.9269). Compared with the mild and moderate groups, the severe group exhibited a higher abundance of Malassezia globosa. Pseudomonas and Staphylococcus were, respectively, more prevalent in the moderate and severe groups than in the mild group. Conclusions: This study highlights the potential role of increased fungal diversity and specific microbial compositions in the severity of scalp psoriasis, suggesting a possible avenue for targeted therapeutic interventions.

Intraindividual comparison of prognostic imaging features of HCCs between MRIs with extracellular and hepatobiliary contrast agents.

BACKGROUND & AIMS: Accumulating evidence suggests that certain imaging features of hepatocellular carcinoma (HCC) may have prognostic implications. This study aimed to intraindividually compare MRIs with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (HBA-MRI) for prognostic imaging features of HCC and to compare the prediction of microvascular invasion (MVI) and early recurrence between the two MRIs. METHODS: The present study included 102 prospectively enrolled at-risk patients (median age, 61.0 years; 83 men) with surgically resected single HCC with both preoperative ECA-MRI and HBA-MRI between July 2019 and June 2023. The McNemar test was used to compare each prognostic imaging feature between the two MRIs. Significant imaging features associated with MVI were identified by multivariable logistic regression analysis, and early recurrence rates (<2 years) were compared between the two MRIs. RESULTS: The frequencies of prognostic imaging features were not significantly different between the two MRIs (p = .07 to >.99). Non-smooth tumour margin (ECA-MRI, odds ratio [OR] = 5.30; HBA-MRI, OR = 7.07) and peritumoral arterial phase hyperenhancement (ECA-MRI, OR = 4.26; HBA-MRI, OR = 4.43) were independent factors significantly associated with MVI on both MRIs. Two-trait predictor of venous invasion (presence of internal arteries and absence of hypoattenuating halo) on ECA-MRI (OR = 11.24) and peritumoral HBP hypointensity on HBA-MRI (OR = 20.42) were other predictors of MVI. Early recurrence rates of any two or more significant imaging features (49.8% on ECA-MRI vs 51.3% on HBA-MRI, p = .75) were not significantly different between the two MRIs. CONCLUSION: Prognostic imaging features of HCC may be comparable between ECA-MRI and HBA-MRI.

Excision of a gastrointestinal stromal tumour in a dog using short-wave infrared fluorescence imaging and indocyanine green.

A 7-year-old castrated male Golden Retriever weighing 36.8 kg presented to the Veterinary Teaching Hospital with vomiting, anorexia and depression. After blood tests, radiographic, ultrasound and computed tomography examinations, a 7.85 × 5.90 × 8.75 cm mass was identified in the caecum. To visualise the tumour margin and improve the accuracy of tumour resection, intraoperative short-wave infrared imaging using indocyanine green was performed during surgery. An indocyanine green solution was injected intravenously as a bolus of 5 mg/kg 24 h before surgery. Tumour resection was performed with a 0.5 cm margin from the fluorescent-marked tissues. Histopathological examination revealed a diagnosis of a gastrointestinal stromal tumour (GIST) and the absence of neoplastic cells in the surgical margin, indicating a successful surgery. To our knowledge, this is the first case of a GIST resection in a dog using intraoperative short-wave infrared imaging.

Comparison between Nivolumab and Regorafenib as Second-line Systemic Therapies after Sorafenib Failure in Patients with Hepatocellular Carcinoma.

PURPOSE: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. MATERIALS AND METHODS: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. RESULTS: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). CONCLUSION: Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.

Successful post-incomplete resection management of gastrointestinal stromal tumor using imatinib based on adenosine triphosphate-based tumor sensitivity assay in a dog.

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.

Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).

Human Joint Angle Estimation Using Deep Learning-Based Three-Dimensional Human Pose Estimation for Application in a Real Environment.

Human pose estimation (HPE) is a technique used in computer vision and artificial intelligence to detect and track human body parts and poses using images or videos. Widely used in augmented reality, animation, fitness applications, and surveillance, HPE methods that employ monocular cameras are highly versatile and applicable to standard videos and CCTV footage. These methods have evolved from two-dimensional (2D) to three-dimensional (3D) pose estimation. However, in real-world environments, current 3D HPE methods trained on laboratory-based motion capture data encounter challenges, such as limited training data, depth ambiguity, left/right switching, and issues with occlusions. In this study, four 3D HPE methods were compared based on their strengths and weaknesses using real-world videos. Joint position correction techniques were proposed to eliminate and correct anomalies such as left/right inversion and false detections of joint positions in daily life motions. Joint angle trajectories were obtained for intuitive and informative human activity recognition using an optimization method based on a 3D humanoid simulator, with the joint position corrected by the proposed technique as the input. The efficacy of the proposed method was verified by applying it to three types of freehand gymnastic exercises and comparing the joint angle trajectories during motion.

Comparison of Four Diagnostic Guidelines for Hepatocellular Carcinoma Using Gadoxetic Acid-enhanced Liver MRI.

Background Noninvasive diagnostic guidelines for hepatocellular carcinoma (HCC) vary across different global geographic areas, especially regarding criteria about gadoxetic acid-enhanced MRI. Purpose To compare the diagnostic performance of four different international HCC diagnosis guidelines and readers' judgment in diagnosing HCC using gadoxetic acid-enhanced MRI in patients at high risk for HCC. Materials and Methods This retrospective study included patients who had not undergone treatment, were at risk for HCC, and who underwent gadoxetic acid-enhanced MRI from January 2015 to June 2018 from 11 tertiary hospitals in South Korea. Four radiologists independently reviewed focal liver lesions (FLLs) according to four guidelines: American Association for the Study of Liver Diseases (AASLD)/Liver Imaging Reporting and Data System (LI-RADS), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). Reader judgment (HCC or not HCC) was also recorded. Malignant FLLs were confirmed at pathology, and histologic and clinical follow-up data were used for benign FLLs. The guidelines' diagnostic performance was compared using generalized estimating equations. Additionally, the diagnostic odds ratio was assessed. Results A total of 2445 FLLs (median size, 27.4 mm) were analyzed in 2237 patients (mean age, 59 years ± 11 [SD]; 1666 male patients); 69.3% (1694 of 2445) were HCCs. KLCA-NCC showed the highest accuracy (80.0%; 95% CI: 78.7, 81.2; P = .001), with high sensitivity in Eastern guidelines (APASL, 89.1% [95% CI: 87.8, 90.3]; KLCA-NCC, 78.2% [95% CI: 76.6, 79.7]) and high specificity in Western guidelines (AASLD/LI-RADS, 89.6% [95% CI: 87.8, 91.2]; EASL, 88.1% [95% CI: 86.2, 89.9]) (P = .001). The diagnostic odds ratios were 20.7 (95% CI: 17.0, 25.3) for AASLD/LI-RADS, 18.9 (95% CI: 15.8, 22.6) for KLCA-NCC, 16.8 (95% CI: 13.8, 20.4) for EASL, and 8.9 (95% CI: 7.4, 10.7) for APASL. The readers' judgment demonstrated higher accuracy than that of the guidelines (accuracy, 86.0%; 95% CI: 84.9, 86.9; P = .001). Conclusion Among four different international HCC diagnosis guidelines, Eastern guidelines demonstrated higher sensitivity, whereas Western guidelines displayed higher specificity. KLCA-NCC achieved the highest accuracy, and AASLD/LI-RADS exhibited the highest diagnostic odds ratio. © RSNA, 2024 Supplemental material is available for this article.

Recent Advances in Environmentally Friendly Dual-crosslinking Polymer Networks.

Environmentally friendly crosslinked polymer networks feature degradable covalent or non-covalent bonds, with many of them manifesting dynamic characteristics. These attributes enable convenient degradation, facile reprocessibility, and self-healing capabilities. However, the inherent instability of these crosslinking bonds often compromises the mechanical properties of polymer networks, limiting their practical applications. In this context, environmentally friendly dual-crosslinking polymer networks (denoted EF-DCPNs) have emerged as promising alternatives to address this challenge. These materials effectively balance the need for high mechanical properties with the ability to degrade, recycle, and/or self-heal. Despite their promising potential, investigations into EF-DCPNs remain in their nascent stages, and several gaps and limitations persist. This Review provides a comprehensive overview of the synthesis, properties, and applications of recent progress in EF-DCPNs. Firstly, synthetic routes to a rich variety of EF-DCPNs possessing two distinct types of dynamic bonds (i.e., imine, disulfide, ester, hydrogen bond, coordination bond, and other bonds) are introduced. Subsequently, complex structure- and dynamic nature-dependent mechanical, thermal, and electrical properties of EF-DCPNs are discussed, followed by their exemplary applications in electronics and biotechnology. Finally, future research directions in this rapidly evolving field are outlined.

Safety and efficacy of the novel Alpha stent for the treatment of intracranial wide-necked aneurysm.

The Alpha stent is an intracranial closed-cell stent with a unique mesh design to enhance wall apposition. It recently underwent structural modifications to facilitate easier stent deployment. This study aimed to evaluate the safety and efficacy of stent-assisted coil embolization for unruptured intracranial aneurysms using the Alpha stent. Between January 2021 and November 2021, 35 adult patients with 35 unruptured intracranial aneurysms in the distal internal carotid artery were prospectively enrolled. For efficacy outcomes, magnetic resonance angiography at the 6-month follow-up was evaluated using the Raymond-Roy occlusion classification (RROC). The safety outcome evaluated the occurrence of symptomatic procedure-related neurological complications up to 6 months postoperatively. Technical success was achieved in 34/35 (97.1%). Six months postoperatively, aneurysm occlusion showed RROC I in 32/35 (91.4%) and RROC II in 3/35 (8.6%) patients. Procedure-related neurologic complications occurred in one patient (2.9%) who experienced hemiparesis due to acute lacunar infarction, which resulted in a 6-month mRS score of 1. The Alpha stent demonstrated excellent efficacy and safety outcomes in stent-assisted coil embolization of unruptured distal ICA aneurysms. The recent structural modifications allowed for easier stent delivery and deployment.Clinical trial registration number: KCT0005841; registration date: 28/01/2021.

PECI-Net: Bolus segmentation from video fluoroscopic swallowing study images using preprocessing ensemble and cascaded inference.

Bolus segmentation is crucial for the automated detection of swallowing disorders in videofluoroscopic swallowing studies (VFSS). However, it is difficult for the model to accurately segment a bolus region in a VFSS image because VFSS images are translucent, have low contrast and unclear region boundaries, and lack color information. To overcome these challenges, we propose PECI-Net, a network architecture for VFSS image analysis that combines two novel techniques: the preprocessing ensemble network (PEN) and the cascaded inference network (CIN). PEN enhances the sharpness and contrast of the VFSS image by combining multiple preprocessing algorithms in a learnable way. CIN reduces ambiguity in bolus segmentation by using context from other regions through cascaded inference. Moreover, CIN prevents undesirable side effects from unreliably segmented regions by referring to the context in an asymmetric way. In experiments, PECI-Net exhibited higher performance than four recently developed baseline models, outperforming TernausNet, the best among the baseline models, by 4.54% and the widely used UNet by 10.83%. The results of the ablation studies confirm that CIN and PEN are effective in improving bolus segmentation performance.

Rat Pharmacokinetics and In Vitro Metabolite Identification of KM-819, a Parkinson's Disease Candidate, Using LC-MS/MS and LC-HRMS.

FAF1 (FAS-associated factor 1) is involved in the activation of Fas cell surface death receptors and plays a role in apoptosis and necrosis. In patients with Parkinson's disease, FAF1 is overexpressed in dopaminergic neurons in the substantia nigra. KM-819, an FAF1 inhibitor, has shown potential for preventing dopaminergic neuronal cell death, promoting the degradation of α-synuclein and preventing its accumulation. This study aimed to develop and validate a quantitative analytical method for determining KM-819 levels in rat plasma using liquid chromatography-tandem mass spectrometry. This method was then applied to pharmacokinetic (PK) studies in rats. The metabolic stability of KM-819 was assessed in rat, dog, and human hepatocytes. In vitro metabolite identification and metabolic pathways were investigated in rat, dog, and human hepatocytes. The structural analog of KM-819, namely N-[1-(4-bromobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-2-(phenylsulfanyl) acetamide, served as the internal standard (IS). Proteins were precipitated from plasma samples using acetonitrile. Analysis was carried out using a reverse-phase C18 column with a mobile phase consisting of 0.1% formic acid in distilled water and 0.1% formic acid in acetonitrile. The analytical method developed for KM-819 exhibited linearity within the concentration range of 0.002-10 µg/mL in rat plasma. The precision and accuracy of the intra- and inter-day measurements were <15% for the lower limit of quantification (LLOQ) and all quality control samples. KM-819 demonstrated stability under various sample storage conditions (6 h at room temperature (25 °C), four weeks at -20 °C, three freeze-thaw cycles, and pretreated samples in the autosampler). The matrix effect and dilution integrity met the criteria set by the Food and Drug Administration and the European Medicines Agency. This sensitive, rapid, and reliable analytical method was successfully applied in pharmacokinetic studies in rats. Pharmacokinetic analysis revealed the dose-independent kinetics of KM-819 at 0.5-5 mg/kg, with a moderate oral bioavailability of ~20% in rats. The metabolic stability of KM-819 was also found to be moderate in rat, dog, and human hepatocytes. Metabolite identification in rat, dog, and human hepatocytes resulted in the discovery of six, six, and eight metabolites, respectively. Glucuronidation and mono-oxidation have been proposed as the major metabolic pathways. Overall, these findings contribute to a better understanding of the pharmacokinetic characteristics of KM-819, thereby aiding future clinical studies.

Double-wire woven nitinol stent for treating dogs with refractory tracheal collapse: A case series.

This retrospective case series describes the signalments, clinical signs, diagnostic test results, and postoperative complications obtained from the medical records of 10 client-owned dogs that underwent treatment for grade IV tracheal collapse using double-wire woven nitinol stents between October 2017 and September 2021. Respiratory signs resolved in all dogs immediately after tracheal stent placement. Mild to moderate stent fractures were identified in five dogs, of which two showed concurrent respiratory distress necessitating re-stenting after several months. Minor complications, such as stent migration, were absent. The double-wire woven nitinol stent optimised for the canine trachea showed favourable outcomes and minimal complications.