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Although detecting small objects is critical in various applications, neural network models designed and trained for generic object detection struggle to do so with precision. For example, the popular Single Shot MultiBox Detector (SSD) tends to perform poorly for small objects, and balancing the performance of SSD across different sized objects remains challenging. In this study, we argue that the current IoU-based matching strategy used in SSD reduces the training efficiency for small objects due to improper matches between default boxes and ground truth objects. To address this issue and improve the performance of SSD in detecting small objects, we propose a new matching strategy called aligned matching that considers aspect ratios and center-point distance in addition to IoU. The results of experiments on the TT100K and Pascal VOC datasets show that SSD with aligned matching detected small objects significantly better without sacrificing performance on large objects or requiring extra parameters.

The recent detection of N-nitroso-atenolol, a mutagenic and potentially carcinogenic impurity in atenolol-based pharmaceuticals, has raised serious safety concerns and emphasized the need for stringent analytical control. This study developed and validated a highly sensitive LC-MS/MS method for quantifying N-nitroso-atenolol in both active pharmaceutical ingredients (APIs) and finished products. Quantification was carried out using multiple reaction monitoring (MRM) under positive-mode electrospray ionization (ESI). Separation was performed on a C18 reversed-phase column with a gradient of water and methanol containing 0.1% formic acid. The method was validated to meet a specification limit of 15 ng/mg, with a linear range of 0.5–80 ng/mL, effectively covering 10–400% of the regulatory threshold. The method exhibited an excellent performance in terms of specificity, accuracy, precision, linearity, and robustness. It achieved a limit of detection (LOD) of 0.2 ng/mL (0.30 ng/mg) and a limit of quantification (LOQ) of 0.5 ng/mL (0.75 ng/mg), alongside a comprehensive uncertainty analysis with an expanded uncertainty of ±3.86 mg/kg. Application to commercial atenolol products confirmed the reliability and practical utility of the method. This validated approach offers a critical tool for pharmaceutical manufacturers and regulatory agencies to monitor and control N-nitroso-atenolol, ensuring compliance and enhancing patient safety.

Objectives To investigate the utility of MR findings and texture analysis for predicting the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs). Methods Two hundred forty-eight patients with surgically confirmed IPMNs (106 malignant [invasive carcinoma/high-grade dysplasia] and 142 benign [low/intermediate-grade dysplasia]) and who underwent magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) were included. Two reviewers independently analyzed MR findings as proposed by the 2017 international consensus guidelines. Texture analysis of MRCP was also performed. A multivariate logistic regression analysis was used to identify predictors for malignant IPMNs. Diagnostic performance was also analyzed using receiver operating curve analysis. Results Among MR findings, enhancing mural nodule size ≥ 5 mm, main pancreatic duct (MPD) ≥ 10 mm or MPD of 5 to 9 mm, and abrupt change of MPD were significant predictors for malignant IPMNs ( p  < 0.05). Among texture variables, significant predictors were effective diameter, surface area, sphericity, compactness, entropy, and gray-level co-occurrence matrix entropy ( p  < 0.05). At multivariate analysis, enhancing mural nodule ≥ 5 mm (odds ratios (ORs), 6.697 and 6.968, for reviewers 1 and 2, respectively), MPD ≥ 10 mm or MPD of 5 to 9 mm (ORs, 4.098 and 4.215, and 2.517 and 3.055, respectively), larger entropy (ORs, 1.485 and 1.515), and smaller compactness (ORs, 0.981 and 0.977) were significant predictors for malignant IPMNs ( p  < 0.05). When adding texture variable to MR findings, diagnostic performance for predicting malignant IPMNs improved from 0.80 and 0.78 to 0.85 and 0.85 in both reviewers ( p  < 0.05), respectively. Conclusions MRCP-derived texture features are useful for predicting malignant IPMNs, and the addition of texture analysis to MR features may improve diagnostic performance for predicting malignant IPMNs. Key Points • Among the MR imaging findings, an enhancing mural nodule size ≥ 5 mm and dilated main pancreatic ducts are independent predictors for malignant IPMNs. • Greater entropy and smaller compactness on MR texture analysis are independent predictors for malignant IPMNs. • The addition of MR texture analysis improved the diagnostic performance for predicting malignant IPMNs from 0.80 and 0.78 to 0.85 and 0.85, respectively.

The usefulness of 3-dimensional (3D)-printed disease models has been recognized in various medical fields. This study aims to introduce a production platform for patient-specific 3D-printed brain tumor model in clinical practice and evaluate its effectiveness. A full-cycle platform was created for the clinical application of a 3D-printed brain tumor model (3D-printed model) production system. Essential elements included automated segmentation software, cloud-based interactive communication tools, customized brain models with exquisite expression of brain anatomy in transparent material, adjunctive devices for surgical simulation, and swift process cycles to meet practical needs. A simulated clinical usefulness validation was conducted in which neurosurgeons assessed the usefulness of the 3D-printed models in 10 cases. We successfully produced clinically applicable patient-specific models within 4 days using the established platform. The simulated clinical usefulness validation results revealed the significant superiority of the 3D-printed models in surgical planning regarding surgical posture ( p  = 0.0147) and craniotomy design ( p  = 0.0072) compared to conventional magnetic resonance images. The benefit was more noticeable for neurosurgeons with less experience. We established a 3D-printed brain tumor model production system that is ready to use in daily clinical practice for neurosurgery.

Skeletal muscle is the most abundant tissue and constitutes about 40% of total body mass. Herein, we report that crude water extract (CWE) of G. uralensis enhanced myoblast proliferation and differentiation. Pretreatment of mice with the CWE of G. uralensis prior to cardiotoxin-induced muscle injury was found to enhance muscle regeneration by inducing myogenic gene expression and downregulating myostatin expression. Furthermore, this extract reduced nitrotyrosine protein levels and atrophy-related gene expression. Of the five different fractions of the CWE of G. uralensis obtained, the ethyl acetate (EtOAc) fraction more significantly enhanced myoblast proliferation and differentiation than the other fractions. Ten bioactive compounds were isolated from the EtOAc fraction and characterized by GC-MS and NMR. Of these compounds (4-hydroxybenzoic acid, liquiritigenin, (R)-(-)-vestitol, isoliquiritigenin, medicarpin, tetrahydroxymethoxychalcone, licochalcone B, liquiritin, liquiritinapioside, and ononin), liquiritigenin, tetrahydroxymethoxychalcone, and licochalcone B were found to enhance myoblast proliferation and differentiation, and myofiber diameters in injured muscles were wider with the liquiritigenin than the non-treated one. Computational analysis showed these compounds are non-toxic and possess good drug-likeness properties. These findings suggest that G. uralensis-extracted components might be useful therapeutic agents for the management of muscle-associated diseases.

ObjectivesTo assess important features for risk stratification of gallbladder (GB) polyps >10 mm using high-resolution ultrasonography (HRUS) and texture analysis.MethodsWe included 136 patients with GB polyps (>10 mm) who underwent both HRUS and cholecystectomy (non-neoplastic, n = 58; adenomatous, n = 32; and carcinoma, n = 46). Two radiologists retrospectively assessed HRUS findings and texture analysis. Multivariate analysis was performed to identify significant predictors for neoplastic polyps and carcinomas.ResultsSingle polyp (OR, 3.680–3.856) and larger size (OR, 1.450–1.477) were independently associated with neoplastic polyps (p < 0.05). In a single or polyp >14 mm, sensitivity for differentiating neoplastic from non-neoplastic polyps was 92.3%. To differentiate carcinoma from adenoma, sessile shape (OR, 9.485–41.257), larger size (OR, 1.267–1.303), higher skewness (OR, 6.382) and lower grey-level co-occurrence matrices (GLCM) contrast (OR, 0.963) were significant predictors (p < 0.05). In a polyp >22 mm or sessile, sensitivity for differentiating carcinomas from adenomas was 93.5–95.7%. If a polyp demonstrated at least one HRUS finding and at least one texture feature, the specificity for diagnosing carcinoma was increased to 90.6–93.8%.ConclusionIn a GB polyp >10 mm, single and diameter >14 mm were useful for predicting neoplastic polyps. In neoplastic polyps, sessile shape, diameter >22 mm, higher skewness and lower GLCM contrast were useful for predicting carcinoma.Key Points• Risk of neoplastic polyp is low in <14 mm and multiple polyps• A sessile polyp or >22 mm has increased risk for GB carcinomas• Higher skewness and lower GLCM contrast are predictors of GB carcinoma• HRUS is useful for risk stratification of GB polyps >1 cm

Background Most extramedullary plasmacytomas (EMPs) aresolitary and located in the head and neck region. They may also occur in the visceral parts of the body. Objectives Here, we report a case of oral EMP followed by neoplastic plasma cell metastasis to both kidneys in a neutered male Pomeranian. Methods Oral plasmacytoma recurred 11 months aftersurgical removal of an oral mass and partial maxillectomy was performed. Eighteen months after partial maxillectomy, neoplastic masses were detected in both kidneys on computed tomography. The dog died 12 months after detection of bilateral kidney neoplasms. The resected neoplastic masses were routinely processed for histopathological observation and immunohistochemistry against pan‐cytokeratin, desmin, CD3, and MUM‐1. Results The recurred mass mainly consisted of well‐differentiated plasma cells and contained a small portion of aggressive cells with malignant features. Monoclonal gammopathy was not observed on serumelectrophoresis performed to exclude multiple myeloma. The mass was composed of plasma cells with high nuclear pleomorphism and abundant mitotic figures. The neoplasm stained positive for MUM‐1 with a more aggressive morphology than in oral EMP. Conclusion Based on serum biomarker and pathological observations, a diagnosis of recurrence and metastasis of oral‐to‐renal EMP was established. To the best of our knowledge, metastasis of oral EMP into the bilateral kidneys, as described in the current case, has not been previously reported in dogs. This report describes a rare case of oral plasmacytoma metastasising to both kidneys. No bone lytic lesions nor other signs of multiple myeloma were observed.

We investigated the dynamics of the bacterial composition and metabolic function within Akashiwo sanguinea bloom using a 100-L indoor microcosm and metagenomic next-generation sequencing. We found that the bacterial community was classified into three groups at 54% similarity. Group I was associated with “during the A. sanguinea bloom stage” and mainly consisted of Alphaproteobacteria, Flavobacteriia and Gammaproteobacteria. Meanwhile, groups II and III were associated with the “late bloom/decline stage to post-bloom stage” with decreased Flavobacteriia and Gammaproteobacteria in these stages. Upon the termination of the A. sanguinea bloom, the concentrations of inorganic nutrients (particularly PO 4 3− , NH 4 + and dissolved organic carbon) increased rapidly and then decreased. From the network analysis, we found that the A. sanguinea node is associated with certain bacteria. After the bloom, the specific increases in NH 4 + and PO 4 3− nodes are associated with other bacterial taxa. The changes in the functional groups of the bacterial community from chemoheterotrophy to nitrogen association metabolisms were consistent with the environmental impacts during and after A. sanguinea bloom. Consequently, certain bacterial communities and the environments dynamically changed during and after harmful algal blooms and a rapid turnover within the bacterial community and their function can respond to ecological interactions.

The purpose of the study was to compare clinical characteristics and mortality among adults infected with human coronaviruses (HCoV) 229E and OC43. We conducted a retrospective cohort study of adults (≥ 18 years) admitted to the ward of a university teaching hospital for suspected viral infection from October 2012 to December 2017. Multiplex real-time polymerase chain reaction (PCR) was used to test for respiratory viruses. Multivariate logistic regression was used to compare mortality among patients with HCoV 229E and HCoV OC43 infections. The main outcome was 30-day all-cause mortality. Of 8071 patients tested, 1689 were found to have a respiratory virus infection. Of these patients, 133 had HCoV infection, including 12 mixed infections, 44 HCoV 229E infections, and 77 HCoV OC43 infections. HCoV 229E infections peaked in January and February, while HCoV OC43 infections occurred throughout the year. The 30-day all-cause mortality was 25.0% among patients with HCoV 229E infection, and 9.1% among patients with HCoV OC43 infection (adjusted odds ratio: 3.58, 95% confidence interval: 1.19–10.75). Infections with HCoVs 229E and OC43 appear to have different seasonal patterns, and HCoV 229E might be more virulent than HCoV OC43.

The Ras effector NORE1 is frequently silenced in primary adenocarcinomas, although the significance of this silencing for tumorigenesis is unclear. Here we show that NORE1 induces polyubiquitination and proteasomal degradation of oncoprotein HIPK1 by facilitating its interaction with the Mdm2 E3 ubiquitin ligase. Endogenous HIPK1 is stabilized in Nore1 ‐deficient mouse embryonic fibroblasts, and depletion of HIPK1 in NORE1 ‐silenced lung adenocarcinoma cells inhibits anchorage‐independent cell growth and tumour formation in nude mice. These findings indicate that the control of HIPK1 stability by Mdm2–NORE1 has a major effect on cell behaviour, and epigenetic inactivation of NORE1 enables adenocarcinoma formation in vivo through HIPK1 stabilization. NORE1 induces ubiquitin‐mediated degradation of oncoprotein HIPK1 by facilitating its interaction with Mdm2. Depletion of HIPK1 in NORE1‐silenced lung adenocarcinoma cells inhibits tumour formation in vivo , suggesting this pathway has a major impact in tumorigenesis.