Multimodality Imaging Evaluation of Nasal Rhabdomyosarcoma in Adults: A Case Report and Literature Review.

BACKGROUND: Alveolar rhabdomyosarcoma (ARMS) predominantly affects adolescents aged 10-15 years and is distinguished by its high aggressiveness and adverse prognosis compared with other sarcomas. It exhibits a pronounced tendency for lymphatic and hematogenous metastases at early stages. ARMS commonly manifests in the limbs and genitourinary system, with occurrences in the head and neck region being relatively uncommon. The role of CT, MRI, and 18F-FDG positron emission tomography combined with computed tomography (PET/CT) in the diagnostic process of ARMS is yet to be fully established. CASE REPORT: We report the case of a 49-year-old woman who presented with hematological nasal discharge for one month. CT imaging revealed a soft tissue mass in the left nasal cavity. MRI demonstrated a marginally hypo- to isointense signal on T1-weighted images, a hyperintense signal on T2-weighted images, and heterogeneous enhancement post-contrast. 18F-FDG PET/CT identified a hypermetabolic lesion located within the left nasal cavity. Surgical intervention entailed the excision of the left intranasal mass and the skull base lesion. Postoperative pathological analysis indicated ARMS. CONCLUSION: Sinus ARMS is notably malignant and associated with a dismal prognosis. Accurate diagnosis depends on histopathological and immunohistochemical evaluation, complemented by genetic analysis for specific chromosomal translocations and fusion genes. Imaging techniques, including CT, MRI, and PET/CT, are crucial for assessing lesion extent and metastasis, supporting disease diagnosis, informing treatment choices, facilitating surgical planning, and monitoring response to therapy.

Predicting Microwave Ablation Early Efficacy in Pulmonary Malignancies via Δ Radiomics Models.

OBJECTIVE: This study aimed to explore the value of preoperative and postoperative computed tomography (CT)-based radiomic signatures and Δ radiomic signatures for evaluating the early efficacy of microwave ablation (MWA) for pulmonary malignancies. METHODS: In total, 115 patients with pulmonary malignancies who underwent MWA treatment were categorized into response and nonresponse groups according to relevant guidelines and consensus. Quantitative image features of the largest pulmonary malignancies were extracted from CT noncontrast scan images preoperatively (time point 0, TP0) and immediately postoperatively (time point 1, TP1). Critical features were selected from TP0 and TP1 and as Δ radiomics signatures for building radiomics models. In addition, a combined radiomics model (C-RO) was developed by integrating radiomics parameters with clinical risk factors. Prediction performance was assessed using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: The radiomics model using Δ features outperformed the radiomics model using TP0 and TP1 features, with training and validation AUCs of 0.892, 0.808, and 0.787, and 0.705, 0.825, and 0.778, respectively. By combining the TP0, TP1, and Δ features, the logistic regression model exhibited the best performance, with training and validation AUCs of 0.945 and 0.744, respectively. The DCA confirmed the clinical utility of the Δ radiomics model. CONCLUSIONS: A combined prediction model, including TP0, TP1, and Δ radiometric features, can be used to evaluate the early efficacy of MWA in pulmonary malignancies.

Noninvasive twin genotyping for recessive monogenic disorders by relative haplotype dosage.

OBJECTIVE: To establish a haplotype-based noninvasive prenatal testing (NIPT) workflow for single-gene recessive disorders that adapt to dizygotic (DZ) twin pregnancies. METHOD: Twin pregnancies at risk of Duchenne muscular dystrophy, Becker muscular dystrophy, hemophilia B, spinal muscular atrophy, phenylketonuria, and nonsyndromic hearing loss were recruited. For subsequent analysis, capture sequencing targeting highly heterozygotic single nucleotide polymorphism sites was conducted. Paternal-specific alleles were used to calculate the total and individual fetal fractions and determine zygosity. A two-step Bayes Factor model was applied to clarify the complex genomic landscape in the maternal plasma: the first step involved determining whether the twins inherited the same haplotype, and the second step involved estimating their individual genotypes. NIPT results were subsequently confirmed by invasive diagnosis. RESULTS: Nine twin pregnancies were recruited, including five DZ and four monozygotic (MZ) twins. The earliest gestational age was 8+0 weeks, and the minimum fetal fraction was 4.6%. Three twin pregnancies were reported with one affected fetus, while the remaining six were reported without affected fetuses. Two dichorionic diamniotic twin pregnancies were confirmed to be MZ twins. The NIPT results were 100% consistent with those of invasive procedures or diagnostic genetic testing after birth. CONCLUSION: This study is the first to perform NIPT for single-gene disorders in twin pregnancies and preliminarily confirm its clinical feasibility. Acknowledging the twins' genotypes in the first trimester is valuable as it empowers obstetric care providers and parents to have adequate time for pregnancy management and decision-making.

3D printed osteochondral scaffolds: design strategies, present applications and future perspectives.

Articular osteochondral (OC) defects are a global clinical problem characterized by loss of full-thickness articular cartilage with underlying calcified cartilage through to the subchondral bone. While current surgical treatments can relieve pain, none of them can completely repair all components of the OC unit and restore its original function. With the rapid development of three-dimensional (3D) printing technology, admirable progress has been made in bone and cartilage reconstruction, providing new strategies for restoring joint function. 3D printing has the advantages of fast speed, high precision, and personalized customization to meet the requirements of irregular geometry, differentiated composition, and multi-layered boundary layer structures of joint OC scaffolds. This review captures the original published researches on the application of 3D printing technology to the repair of entire OC units and provides a comprehensive summary of the recent advances in 3D printed OC scaffolds. We first introduce the gradient structure and biological properties of articular OC tissue. The considerations for the development of 3D printed OC scaffolds are emphatically summarized, including material types, fabrication techniques, structural design and seed cells. Especially from the perspective of material composition and structural design, the classification, characteristics and latest research progress of discrete gradient scaffolds (biphasic, triphasic and multiphasic scaffolds) and continuous gradient scaffolds (gradient material and/or structure, and gradient interface) are summarized. Finally, we also describe the important progress and application prospect of 3D printing technology in OC interface regeneration. 3D printing technology for OC reconstruction should simulate the gradient structure of subchondral bone and cartilage. Therefore, we must not only strengthen the basic research on OC structure, but also continue to explore the role of 3D printing technology in OC tissue engineering. This will enable better structural and functional bionics of OC scaffolds, ultimately improving the repair of OC defects.

A systematic review of polycyclic aromatic hydrocarbon pollution: A combined bibliometric and mechanistic analysis of research trend toward an environmentally friendly solution.

Pollution caused by polycyclic aromatic hydrocarbons (PAHs) is a significant concern. This concern has become more problematic given the rapid modification of PAHs in the environment during co-contamination to form substituted PAHs. This review aims to integrate bibliometric analysis with a rigorous study of mechanistic insights, resulting in a more comprehensive knowledge of evolving research trends on PAH remediation. The results show that research in this field has progressed over the years and peaked in 2022, potentially due to the redirection of resources toward emerging pollutants, hinting at the dynamic nature of environmental research priorities. During this year, 158,147 documents were published, representing 7 % of the total publications in the field between 2000 and 2023. The different remediation methods used for PAH remediation were identified and compared. Bioremediation, having >90 % removal efficiency, has been revealed to be the best technique because it is cost-effective and easy to operate at large scale in situ and ex-situ. The current challenges in PAH remediation have been detailed and discussed. Implementing innovative and sustainable technologies that target pollutant removal and valuable compound recovery is necessary to build a more robust future for water management.

A Radiomics-clinical Nomogram based on CT Radiomics to Predict Acquired T790M Mutation Status in Non-small Cell Lung Cancer Patients.

OBJECTIVE: To develop and validate a radiomics-clinical nomogram for the detection of the acquired T790M mutation in patients with advanced non-small cell lung cancer (NSCLC) with resistance after the duration of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: Thoracic CT was collected from 120 advanced NSCLC patients who suffered progression on first- or second-generation TKIs. Radiomics signatures were retrieved from the entire tumor. Pearson correlation and the least absolute shrinkage and selection operator (LASSO) regression method were adopted to choose the most suitable radiomics features. Clinical and radiological factors were assessed using univariate and multivariate analysis. Three Machine Learning (ML) models were constructed according to three classifiers, including Logistic Regression (LR), Support Vector Machine (SVM), and RandomForest (RF), combining clinical and radiomic features. A nomogram combining clinical features and the rad score signature was built. The predictive ability of the nomogram was assessed by the ROC curve, calibration curve, and decision curve analysis (DCA). RESULTS: Multivariate regression analysis showed that two clinicopathological characteristics and two radiological features were highly correlated with the acquired T790M mutation, including the progression-free survival (PFS) of first-line EGFR TKIs (P = 0.029), the initial EGFR profile (P = 0.01), vascular convergence (P = 0.043), and air bronchogram (P = 0.030). The AUCs of clinical, radiomics, and combined models using RF classifiers for T790M mutation detection were 0.951 (95% confidence interval [CI] 0.911,0.991), 0.917 (95%CI 0.856,0.978), and 0.961 (95%CI 0.927,0.995) in the training cohort, respectively, higher than those of other classifier models.The calibration curve and Hosmer-Lemeshow Test showed good calibration power, and the DCA demonstrated a significant net benefit. CONCLUSION: A radiomics-clinical nomogram based on CT radiomics proved valuable in non-invasively and efficiently predicting the acquired T790M mutation in patients who suffered progression on first-line TKIs.

Bladder xanthoma: clinical analysis of 22 cases from multiple centers.

This study aims to outline the clinical and pathological characteristics of bladder xanthoma, alongside its diagnostic and treatment approaches. METHODS: We reviewed bladder xanthoma literature spanning the last 60 years from databases such as PubMed, Web of Science, Embase, and Medline. Additionally, we analyzed clinical data from a singular case of bladder xanthoma treated at our hospital. Patient particulars, including age, gender, symptoms, tumor size, associated neoplasms, imaging results, and pathological findings, were documented. Tumors underwent surgical removal, followed by pathological examination of the excised tissues. Subsequent to surgery, patients underwent cystoscopy follow-up after 3 months. RESULTS: Among the 22 identified cases of bladder xanthoma, 15 were solitary (comprising both single and multiple lesions), while 7 were associated with urinary tract epithelial tumors. There were 6 male patients and 1 female patient concurrently diagnosed with urinary tract epithelial carcinoma. Males exhibited an average onset age of 56.0 years, with an average tumor diameter of 21.57 mm. Females presented an average onset age of 63.00 years, with an average tumor diameter of 20.86 mm. The onset age for females was notably lower than that for males, and their tumor diameter was significantly smaller than that of males (P<0.05). Among the 9 patients with lipid metabolism disorders, 7 were males and 2 were females, indicating a marked male predominance. No instances of recurrence or malignant transformation were observed during follow-up. In this study, we treated a 65-year-old female patient who, during cystoscopy, exhibited a round, hanging lesion measuring about 2.5 × 1 × 1 cm on the left side of the ureteral opening in the bladder trigone. Post-surgery, pathological examination disclosed bladder xanthoma with multiple groups of foam cells. Immunohistochemistry findings were as follows: CD68 (+), CD163 (+), Vimentin (+), CK (-), Desmin (-). A follow-up cystoscopy after 3 months did not reveal any tumor recurrence. CONCLUSION: Bladder xanthoma is an uncommon benign condition predominantly affecting older males. It frequently manifests on the side walls and trigone region of the bladder and may be linked to lipid metabolism disorders. Approximately 50% of patients exhibit concurrent urinary tract epithelial tumors, with diagnosis primarily reliant on microscopic tissue examination. Prolonged post-surgical follow-up is imperative.

Wnt signaling: Modulating tumor-associated macrophages and related immunotherapeutic insights.

Wnt signaling pathways are highly conserved cascades that mediate multiple biological processes through canonical or noncanonical pathways, from embryonic development to tissue maintenance, but they also contribute to the pathogenesis of numerous cancers. Recent studies have revealed that Wnt signaling pathways critically control the interplay between cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) and potentially impact the efficacy of cancer immunotherapy. In this review, we summarize the evidence that Wnt signaling pathways boost the maturation and infiltration of macrophages for immune surveillance in the steady state but also polarize TAMs toward immunosuppressive M2-like phenotypes for immune escape in the TME. Both cancer cells and TAMs utilize Wnt signaling to transmit signals, and this interaction is crucial for the carcinogenesis and progression of common solid cancers, such as colorectal, gastric, hepatocellular, breast, thyroid, prostate, kidney, and lung cancers; osteosarcoma; and glioma. Specifically, compared with those in solid cancers, Wnt signaling pathways play a distinct role in the pathogenesis of leukemia. Efforts to develop Wnt-based drugs for cancer treatment are still ongoing, and some indeed enhance the anticancer immune response. We believe that the combination of Wnt signaling-based therapy with conventional or immune therapies is a promising therapeutic approach and can facilitate personalized treatment for most cancers.

First-trimester noninvasive prenatal diagnosis of seven facioscapulohumeral muscular dystrophy type 1 families using SNP-based amplicon sequencing: An earlier, rapid and safer way.

The study is to explore the feasibility and value of SNP-based noninvasive prenatal diagnosis (NIPD) for facioscapulohumeral muscular dystrophy type 1 (FSHD1) in early pregnancy weeks. We prospectively collected seven FSHD1 families, with an average gestational age of 8+6 . Among these seven couples, there were three affected FSHD1 mothers and four affected fathers. A multiplex-PCR panel comprising 402 amplicons was designed to selective enrich for highly heterozygous SNPs upstream of the DUX4 gene. Risk haplotype was constructed based on familial linkage analysis. Fetal genotypes were accurately inferred through relative haplotype dosage analysis using Bayes Factor. All tests were successfully completed in a single attempt, and no recombination events were detected. NIPD results were provided within a week, which is 4 weeks earlier than karyomapping and 7 weeks earlier than Bionano single-molecule optical mapping (BOM). Ultimately, five FSHD1 fetuses and two normal fetuses were successfully identified, with a 100% concordance rate with karyomapping and BOM. Therefore, SNP-based NIPD for FSHD1 was demonstrated to be feasible and accurate in early weeks of gestation, although the risk of recombination events cannot be completely eliminated. In the future, testing of more cases is still necessary to fully determine the clinical utility.

Correlation of MRI quantitative perfusion parameters with EGFR, VEGF and EGFR gene mutations in non-small cell cancer.

To explore the relationship between quantitative perfusion histogram parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with the expression of tumor tissue epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and EGFR gene mutations in non-small cell lung cancer (NSCLC). A total of 44 consecutive patients with known NSCLC were recruited from March 2018 to August 2021. Histogram parameters (mean, uniformity, skewness, energy, kurtosis, entropy, percentile) of each (Ktrans, Kep, Ve, Vp, Fp) were obtained by Omni Kinetics software. Immunohistochemistry staining was used in the detection of the expression of VEGF and EGFR protein, and the mutation of EGFR gene was detected by PCR. Corresponding statistical test was performed to compare the parameters and protein expression between squamous cell carcinoma (SCC) and adenocarcinoma (AC), as well as EGFR mutations and wild-type. Correlation analysis was used to evaluate the correlation between parameters with the expression of VEGF and EGFR protein. Fp (skewness, kurtosis, energy) were statistically significant between SCC and AC, and the area under the ROC curve were 0.733, 0.700 and 0.675, respectively. The expression of VEGF in AC was higher than in SCC. Fp (skewness, kurtosis, energy) were negatively correlated with VEGF (r = - 0.527, - 0.428, - 0.342); Ktrans (Q50) was positively correlated with VEGF (r = 0.32); Kep (energy), Ktrans (skewness, kurtosis) were positively correlated with EGFR (r = 0.622, r = 0.375, 0.358), some histogram parameters of Kep, Ktrans (uniformity, entropy) and Ve (kurtosis) were negatively correlated with EGFR (r = - 0.312 to - 0.644). Some perfusion histogram parameters were statistically significant between EGFR mutations and wild-type, they were higher in wild-type than mutated (P < 0.05). Quantitative perfusion histogram parameters of DCE-MRI have a certain value in the differential diagnosis of NSCLC, which have the potential to non-invasively evaluate the expression of cell signaling pathway-related protein.

Analysis of the influence of shear-tensile resistance and rock-breaking effect of cutting holes.

In the process of drilling and blasting construction of large-cross-section tunnels, the layout of wedge-shaped cutting holes has a great influence on the effect of blasting. In this study, theoretical analysis and numerical simulation were used to assess the effect of different forms of cutting hole placement on blasting effectiveness. First, the fissure-inducing angle was proposed, a three-dimensional model of wedge-shaped cutting considering the effect of shear-tensile resistance was established, and theoretical analyses of cutting holes with different cutting angles and fissure-inducing angles were carried out. Second, the parameters of the Riedel-Hiermaier-Thoma model were determined based on the experimental data, and verified. Third, three-dimensional numerical models were established, and analyze the influence of different forms of hole deployment on the blasting effect from the perspective of stress wave propagation and dynamic damage to the surrounding rock. Finally, based on the theoretical analysis and numerical simulation results, the wedge-shaped hollowing holes were re-designed, and 20 tunnel blasting tests were carried out using this deployment method for large-section tunnel blasting, which verified the feasibility of this deployment method. The results of the study show that for level III surrounding rock, the angle of wedge-shaped cutting holes should meet 68° ≤ θ ≤ 70° and 70° ≤ ß ≤ 72°. This study provides a kind of refined and efficient blasting for the drilling and blasting excavation process of large section tunnels.

The value of intratumoral and peritumoral radiomics features in differentiating early-stage lung invasive adenocarcinoma (≤3 cm) subtypes.

Background: The identification of different subtypes of early-stage lung invasive adenocarcinoma before surgery contributes to the precision treatment. Radiomics could be one of the effective and noninvasive identification methods. The value of peritumoral radiomics in predicting the subtypes of early-stage lung invasive adenocarcinoma perhaps clinically useful. Methods: This retrospective study included 937 lung adenocarcinomas which were randomly divided into the training set (n=655) and testing set (n=282) with a ratio of 7:3. This study used the univariate and multivariate analysis to choose independent clinical predictors. Radiomics features were extracted from 18 regions of interest (1 intratumoral region and 17 peritumoral regions). Independent and conjoint prediction models were constructed based on radiomics and clinical features. The performance of the models was evaluated using receiver operating characteristic (ROC) curves, accuracy (ACC), sensitivity (SEN), and specificity (SPE). Significant differences between areas under the ROC (AUCs) were estimated using in the Delong test. Results: Patient age, smoking history, carcinoembryonic antigen (CEA), lesion location, length, width and clinic behavior were the independent predictors of differentiating early-stage lung invasive adenocarcinoma (≤3 cm) subtypes. The highest AUC value among the 19 independent models was obtained for the PTV0~+3 radiomics model with 0.849 for the training set and 0.854 for the testing set. As the peritumoral distance increased, the predictive power of the models decreased. The radiomics-clinical conjoint model was statistically significantly different from the other models in the Delong test (P<0.05). Conclusions: The intratumoral and peritumoral regions contained a wealth of clinical information. The diagnostic efficacy of intra-peritumoral radiomics combined clinical model was further improved, which was particularly important for preoperative staging and treatment decision-making.

Prediction of Microwave Ablation Recurrence in Pulmonary Malignancies Using Preoperative Computed Tomography Radiomics Models.

BACKGROUND: Assessing the early efficacy of microwave ablation (MWA) for pulmonary malignancies is a challenge for interventionalists. However, performing an accurate efficacy assessment at an earlier stage can significantly enhance clinical intervention and improve the patient's prognosis. PURPOSE: This research aimed to create and assess non-invasive diagnostic techniques using pre-operative computed tomography (CT) radiomics models to predict the recurrence of MWA in pulmonary malignancies. MATERIALS AND METHODS: We retrospectively enrolled 116 eligible patients with pulmonary malignancies treated with MWA. we separated the patients into two groups: a recurrence group (n = 28) and a non-recurrence group (n = 88), following the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) criteria. We segmented the preoperative tumor area manually. We expanded outward the tumor boundary 4 times, with a width of 3 mm, using the tumor boundary as the baseline. Five groups of radiomics features were extracted and screened using max-relevance and min-redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) regression. Weight coefficients of the aforementioned features were used to calculate the Radscore and construct radiomics models for both tumoral and peritumoral areas. The Radscore from the radiomics model was combined with clinical risk factors to construct a combined model. The performance and clinical usefulness of the combined models were assessed through the evaluation of receiver operating characteristic (ROC) curves, the Delong test, calibration curves, and decision curve analysis (DCA) curves. RESULTS: The clinical risk factor for recurrence after MWA was tumor diameter (P < 0.05). Both tumoral and four peritumoral radiomics models exhibited high diagnostic efficacy. Furthermore, the combined 1 (C1)-RO model and the combined 2 (C2)-RO model showed higher efficacy with area under the curve (AUCs) of 0.89 and 0.89 in the training cohort, and 0.93 and 0.94 in the validation cohort, respectively. Both combined models demonstrated excellent predictive accuracy and clinical benefit. CONCLUSION: Preoperative CT radiomics models for both tumoral and peritumoral regions are capable of accurately predicting the recurrence of pulmonary malignancies after MWA. The combination of both models may lead to better performance and may aid in devising more effective preoperative treatment strategies.

Impact of Running Exercise on Intervertebral Disc: A Systematic Review.

CONTEXT: Running is one of the most popular sports worldwide. However, controversies exist regarding how running affects runner's intervertebral discs (IVD). OBJECTIVE: The purpose of this study was to systematically review studies that evaluated IVD morphology or composition changes in response to running exercise, to determine the impact of running exercise on IVD. DATA SOURCES: A systematic literature search was performed for 4 major databases: PubMed, Cochrane, Embase, and Web of Science. STUDY SELECTION: Inclusion criteria were as follows: (1) healthy people without known IVD disease or major complications such as tuberculosis (IVD degeneration or low back pain are considered as minor complications); (2) subjects performed 1-time or regular running exercises; (3) pre and post comparison of runners or comparison between runners and healthy control subjects; (4) direct or indirect IVD morphology or composition measured; (5) IVD assessed before and after either acute or chronic running exercise, or compared cross-sectionally between runners and controls. Exclusion criteria were as follows: (1) reviews, editorials, letters or abstracts only; (2) animal studies; (3) subjects performed exercise other than running. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 3. DATA EXTRACTION: The extracted data included study design and primary outcomes of the included studies. The Newcastle-Ottawa scale (NOS) was used to evaluate study quality and risk of bias. RESULTS: A total of 13 studies with 632 participants were included in the final analysis; 4 studies measured IVD changes using stature or spinal height, and the other 9 measured IVD changes using magnetic resonance imaging; 6 studies found that running acutely and negatively impacts IVD; 3 out of 5 cross-sectional studies found that IVD parameters are better for runners than controls; 1 longitudinal study found no significant difference in IVD before and after training for marathon in runners; 1 longitudinal study found no significant difference in changes of IVD between runners and controls after 15 years of follow-up. CONCLUSION: Negative changes in IVD exist for a short period of time after running, which may be due to the temporary compression pushing water content out of the disc. Cross-sectional studies suggest that long-term running exerts a mild positive effect on IVD; however, this inference has not been confirmed by high-quality longitudinal studies.

Exploring factors impacting haplotype-based noninvasive prenatal diagnosis for single-gene recessive disorders.

Haplotype-based noninvasive prenatal diagnosis (NIPD) is applicable for various recessive single-gene disorders in proband families. However, a comprehensive exploration of critical factors influencing the assay performance, such as fetal fraction, informative single nucleotide polymorphism (SNP) count, and recombination events, has yet to be performed. It is critical to identify key factors affecting NIPD performance, including its accuracy and success rate, and their impact on clinical diagnostics to guide clinical practice. We conducted a prospective study, recruiting 219 proband families with singleton pregnancies at risk for eight recessive single-gene disorders (Duchenne muscular dystrophy, spinal muscular atrophy, phenylketonuria, methylmalonic acidemia, hemophilia A, hemophilia B, non-syndromic hearing loss, and congenital adrenal hyperplasia) at 7-14 weeks of gestation. Haplotype-based NIPD was performed by evaluating the relative haplotype dosage (RHDO) in maternal circulation, and the results were validated via invasive prenatal diagnosis or newborn follow-ups. Among the 219 families, the median gestational age at first blood draw was 8+5 weeks. Initial testing succeeded for 190 families and failed for 29 due to low fetal fraction (16), insufficient informative SNPs (9), and homologous recombination near pathogenic variation (4). Among low fetal fraction families, successful testing was achieved for 11 cases after a redraw, while 5 remained inconclusive. Test failures linked to insufficient informative SNPs correlated with linkage disequilibrium near the genes, with F8 and MMUT exhibiting the highest associated failure rates (14.3% and 25%, respectively). Homologous recombination was relatively frequent around the DMD and SMN1 genes (8.8% and 4.8%, respectively) but led to detection failure in only 44.4% (4/9) of such cases. All NIPD results from the 201 successful families were consistent with invasive diagnostic findings or newborn follow-up. Fetal fraction, informative SNPs count, and homologous recombination are pivotal to NIPD performance. Redrawing blood effectively improves the success rate for low fetal fraction samples. However, informative SNPs count and homologous recombination rates vary significantly across genes, necessitating careful consideration in clinical practice. We have designed an in silico method based on linkage disequilibrium data to predict the number of informative SNPs. This can identify genomic regions where there might be an insufficient number of SNPs, thereby guiding panel design. With these factors properly accounted for, NIPD is highly accurate and reliable.

Radiogenomics for predicting microsatellite instability status and PD-L1 expression with machine learning in endometrial cancers: A multicenter study.

Purpose: To evaluate the effectiveness of machine learning model based on magnetic resonance imaging (MRI) in identifying microsatellite instability (MSI) status and PD-L1 expression in endometrial cancer (EC). Methods: This retrospective study included 82 EC patients from 2 independent centers. Radiomics features from the intratumoral and peritumoral regions, obtained from four conventional MRI sequences (T2-weighted images; contrast-enhanced T1-weighted images; diffusion-weighted images; apparent diffusion coefficient), were combined with clinicopathologic characteristics to develop machine learning model for predicting MSI status and PD-L1 expression. 60 patients from center 1 were used as the training set for model construction, while 22 patients from center 2 were used as an external validation set for model evaluation. Results: For predicting MSI status, the clinicopathologic model, radscore model, and combination model achieved area under the curves (AUCs) of 0.728, 0.833, and 0.889 in the training set, respectively, and 0.595, 0.790, and 0.848 in the validation set, respectively. For predicting PD-L1 expression, the clinicopathologic model, radscore model, and combination model achieved AUCs of 0.648, 0.814, and 0.834 in the training set, respectively, and 0.660, 0.708, and 0.764 in the validation set, respectively. Calibration curve analysis and decision curve analysis demonstrated good calibration and clinical utility of the combination model. Conclusion: The machine learning model incorporating MRI-based radiomics features and clinicopathologic characteristics could be a potential tool for predicting MSI status and PD-L1 expression in EC. This approach may contribute to precision medicine for EC patients.

Haplotype-based noninvasive prenatal diagnosis of methylmalonic acidemia and the discovery of a recurrent pathogenic haplotype associated with c.609G>A.

BACKGROUND: Early diagnosis and intervention are crucial for the prognosis of methylmalonic acidemia (MMA). However, research focused on early prenatal diagnosis of MMA is limited. METHODS: A 161.89kb capture panel was designed for selectively enriching highly heterozygous SNPs. Fetal genotypes were inferred using relative haplotype dosage (RHDO) and Bayes factor, followed by invasive prenatal diagnosis (IPD) for validation. A core pathogenic haplotype associated with c.609G>A was identified based on the frequency differences between pathogenic and normal haplotypes. RESULTS: We recruited 41 pregnancies at risk of MMA with a median gestational age of 8+2  weeks. The assay success rate of NIPD-MMA for maternal variants was 92.7% (38/41), and after incorporating the paternal result, the overall assay success rate reached 100% (41/41). All NIPD results were concordant with IPD. Notably, a core haplotype (hap_2), comprising 28 SNPs, demonstrates significant enrichment within pathogenic haplotypes bearing the c.609G>A variation. On average, c.609G>A carriers had 22.38 heterozygous loci within these 28 SNPs. CONCLUSION: NIPD-MMA presents a viable choice for early, accurate, and safe prenatal diagnosis. Furthermore, the discovery of the recurrent core pathogenic haplotype provides a novel approach for haplotype phasing and has the potential for realizing proband-independent NIPD in the future.

Potential missed opportunities for diagnosis of lymphoepithelioma-like intrahepatic cholangiocarcinoma: report of a rare case.

Lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-ICC) is a rare distinctive variant of liver cancer with unique epidemiological and pathological characteristics, including dense lymphocyte infiltration. We herein describe a 67-year-old Chinese man with LEL-ICC. The patient had undergone endoscopic extraction of a bile duct stone 1 month prior. Contrast-enhanced abdominal computed tomography (CT) revealed a 2.5- × 2.5- × 1.5-cm low-density mass located in a covert part of the left lateral segment of the liver. Contrast-enhanced magnetic resonance imaging revealed a hyperintense lesion on T2-weighted and diffusion-weighted images of the left lateral liver, with similar size and signal characteristics in the arterial and portal venous phases. The patient subsequently underwent left lateral laparoscopic hepatectomy. The results of postoperative pathology and immunohistochemistry allowed for the definitive diagnosis. In situ hybridization using an Epstein-Barr virus-encoded RNA probe revealed extensive reactivity in the tumor cell nuclei, supporting a diagnosis of LEL-ICC. The patient was recurrence-free at 12 months postoperatively as shown by CT. A literature review indicated that in middle-aged patients with Epstein-Barr virus infection, a liver mass with a well-defined margin and a combination of hypervascularity and delayed intratumoral enhancement on CT and magnetic resonance imaging may suggest a diagnosis of LEL-ICC.

Highly Efficient Electroreduction of CO2 to Ethanol via Asymmetric C-C Coupling by a Metal-Organic Framework with Heterodimetal Dual Sites.

The electroreduction of CO2 into value-added liquid fuels holds great promise for addressing global environmental and energy challenges. However, achieving highly selective yielding of multi-carbon oxygenates through the electrochemical CO2 reduction reaction (eCO2RR) is a formidable task, primarily due to the sluggish asymmetric C-C coupling reaction. In this study, a novel metal-organic framework (CuSn-HAB) with unprecedented heterometallic Sn···Cu dual sites (namely, a pair of SnN2O2 and CuN4 sites bridged by µ-N atoms) was designed to overcome this limitation. CuSn-HAB demonstrated an impressive Faradic efficiency (FE) of 56(2)% for eCO2RR to alcohols, achieving a current density of 68 mA cm-2 at a low potential of -0.57 V (vs RHE). Notably, no significant degradation was observed over a continuous 35 h operation at the specified current density. Mechanistic investigations revealed that, in comparison to the copper site, the SnN2O2 site exhibits a higher affinity for oxygen atoms. This enhanced affinity plays a pivotal role in facilitating the generation of the key intermediate *OCH2. Consequently, compared to homometallic Cu···Cu dual sites (generally yielding ethylene product), the heterometallic dual sites were proved to be more thermodynamically favorable for the asymmetric C-C coupling between *CO and *OCH2, leading to the formation of the key intermediate *CO-*OCH2, which is favorable for yielding ethanol product.

Development and validation of a radiomics nomogram for diagnosis of malignant pleural effusion.

OBJECTIVE: We aimed to develop a radiomics nomogram based on computed tomography (CT) scan features and high-throughput radiomics features for diagnosis of malignant pleural effusion (MPE). METHODS: In this study, 507 eligible patients with PE (207 malignant and 300 benign) were collected retrospectively. Patients were divided into training (n = 355) and validation cohorts (n = 152). Radiomics features were extracted from initial unenhanced CT images. CT scan features of PE were also collected. We used the variance threshold algorithm and least absolute shrinkage and selection operator (LASSO) to select optimal features to build a radiomics model for predicting the nature of PE. Univariate and multivariable logistic regression analyzes were used to identify significant independent factors associated with MPE, which were then included in the radiomics nomogram. RESULTS: A total of four CT features were retained as significant independent factors, including massive PE, obstructive atelectasis or pneumonia, pleural thickening > 10 mm, and pulmonary nodules and/or masses. The radiomics nomogram constructed from 13 radiomics parameters and four CT features showed good predictive efficacy in training cohort [area under the curve (AUC) = 0.926, 95% CI 0.894, 0.951] and validation cohort (AUC = 0.916, 95% CI 0.860, 0.955). The calibration curve and decision curve analysis showed that the nomogram helped differentiate MPE from benign pleural effusion (BPE) in clinical practice. CONCLUSION: This study presents a nomogram model incorporating CT scan features and radiomics features to help physicians differentiate MPE from BPE.