The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila.

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity.

Accurate virus identification with interpretable Raman signatures by machine learning.

Rapid identification of newly emerging or circulating viruses is an important first step toward managing the public health response to potential outbreaks. A portable virus capture device, coupled with label-free Raman spectroscopy, holds the promise of fast detection by rapidly obtaining the Raman signature of a virus followed by a machine learning (ML) approach applied to recognize the virus based on its Raman spectrum, which is used as a fingerprint. We present such an ML approach for analyzing Raman spectra of human and avian viruses. A convolutional neural network (CNN) classifier specifically designed for spectral data achieves very high accuracy for a variety of virus type or subtype identification tasks. In particular, it achieves 99% accuracy for classifying influenza virus type A versus type B, 96% accuracy for classifying four subtypes of influenza A, 95% accuracy for differentiating enveloped and nonenveloped viruses, and 99% accuracy for differentiating avian coronavirus (infectious bronchitis virus [IBV]) from other avian viruses. Furthermore, interpretation of neural net responses in the trained CNN model using a full-gradient algorithm highlights Raman spectral ranges that are most important to virus identification. By correlating ML-selected salient Raman ranges with the signature ranges of known biomolecules and chemical functional groups­for example, amide, amino acid, and carboxylic acid­we verify that our ML model effectively recognizes the Raman signatures of proteins, lipids, and other vital functional groups present in different viruses and uses a weighted combination of these signatures to identify viruses.

Association of healthy lifestyle behaviours with incident irritable bowel syndrome: a large population-based prospective cohort study.

OBJECTIVES: To evaluate the association between healthy lifestyle behaviours and the incidence of irritable bowel syndrome (IBS). DESIGN: Population-based prospective cohort study. SETTING: The UK Biobank. PARTICIPANTS: 64 268 adults aged 37 to 73 years who had no IBS diagnosis at baseline were enrolled between 2006 and 2010 and followed up to 2022. MAIN EXPOSURE: The five healthy lifestyle behaviours studied were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality and moderate alcohol intake. MAIN OUTCOME MEASURE: The incidence of IBS. RESULTS: During a mean follow-up of 12.6 years, 961 (1.5%) incident IBS cases were recorded. Among the 64 268 participants (mean age 55.9 years, 35 342 (55.0%) female, 7604 (11.8%) reported none of the five healthy lifestyle behaviours, 20 662 (32.1%) reported 1 behaviour, 21 901 (34.1%) reported 2 behaviours and 14 101 (21.9%) reported 3 to 5 behaviours at baseline. The multivariable adjusted hazard ratios associated with having 1, 2 and 3 to 5 behaviours for IBS incidence were 0.79 (95% confidence intervals 0.65 to 0.96), 0.64 (0.53 to 0.78) and 0.58 (0.46 to 0.72), respectively (P for trend <0.001). Never smoking (0.86, 0.76 to 0.98, P=0.02), high level of vigorous physical activity (0.83, 0.73 to 0.95, P=0.006) and optimal sleep (0.73, 0.60 to 0.88, P=0.001) demonstrated significant independent inverse associations with IBS incidence. No significant interactions were observed between these associations and age, sex, employment status, geographic location, gastrointestinal infection, endometriosis, family history of IBS or lifestyle behaviours. CONCLUSIONS: Adhering to a higher number of healthy lifestyle behaviours is significantly associated with a lower incidence of IBS in the general population. Our findings suggest the potential of lifestyle modifications as a primary prevention strategy for IBS.

Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus.

Cholecystokinin (CCK) has been confirmed to be essential in NMDA-dependent long-term potentiation (LTP) at mouse cortical synapses. This paper has proven that CCK is necessary for LTP induced by high-frequency stimulation of mouse hippocampal synapses projected from the entorhinal cortex. We show that the subunit of the axonal NMDA receptor dominant modulates the activity-induced LTP by triggering pre-synaptic CCK release. A functional pre-synaptic NMDA receptor is required to induce LTP mediated by the axonal Ca2+ elevation and CCK exocytosis at CCK-specific neurons. Genetic depletion of the GluN1 subunit of NMDA receptors on CCK neurons, which projected from the entorhinal cortex largely abolished the axonal Ca2+ elevation and disturbed the secretion of CCK in hippocampus. These results demonstrate that activity-induced LTP at the hippocampal synapse is CCK-dependent, and CCK secretion from the axonal terminal is modulated by pre-synaptic NMDA receptors.

Altered CD226/TIGIT expressions were associated with NK phenotypes in primary antiphospholipid syndrome and affected by IL-4/JAK pathway.

Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and activating receptor cluster of differentiation 226 (CD226) are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS. We comparatively assessed the changes of CD56brightNK, CD56dimNK, and NK-like cells in 70 pAPS patients compared with control groups, including systemic lupus erythematosus, asymptomatic antiphospholipid antibodies carriers (asymp-aPLs carriers), and healthy controls and their expression diversities of CD226/TIGIT by flow cytometry. CD25, CD69, CD107α expression, and interferon gamma (IFN-γ) secretion levels of NK subsets were detected to determine the potential association of CD226/TIGIT expression with NK subsets phenotypes. CD226/TIGIT expression levels were compared among different subgroups divided by aPLs status. Moreover, in vitro cultures were conducted to explore the potential mechanisms of CD226/TIGIT expression imbalance. CD56brightNK and CD3+CD56+NK-like cells were significantly increased while CD56dimNK cells were obviously decreased in pAPS, and CD56brightNK and NK-like cells exhibited significantly higher CD226 but lower TIGIT expressions. CD226+CD56brightNK and TIGIT-CD56brightNK cells show higher CD69 expression and IFN-γ secretion capacity, and CD226+NK-like and TIGIT-NK-like cells showed higher expressions of CD25 and CD69 but lower apoptosis rate than CD226- and TIGIT+CD56brightNK/NK-like cells, respectively. The imbalanced CD226/TIGIT expressions were most significant in aPLs triple-positive group. Imbalanced expressions of CD226/TIGIT on CD56brightNK and NK-like cells were aggravated after interleukin-4 (IL-4) stimulation and recovered after tofacitinib blocking. Our data revealed significant imbalanced CD226/TIGIT expressions on NK subsets in pAPS, which closely associated with NK subsets phenotypes and more complicated autoantibody status. CD226/TIGIT imbalanced may be affected by IL-4/Janus Kinase (JAK) pathway activation.

Electron microscopic analysis of the influence of iPSC-derived motor neurons on bioengineered human skeletal muscle tissues.

3D bioengineered skeletal muscle macrotissues are increasingly important for studies of cell biology and development of therapeutics. Tissues derived from immortalized cells obtained from patient samples, or from pluripotent stem cells, can be co-cultured with motor-neurons to create models of human neuromuscular junctions in culture. In this study, we present foundational work on 3D cultured muscle ultrastructure, with and without motor neurons, which is enabled by the development of a new co-culture platform. Our results show that tissues from Duchenne muscular dystrophy patients are poorly organized compared to tissues grown from healthy donor and that the presence of motor neurons invariably improves sarcomere organization. Electron micrographs show that in the presence of motor neurons, filament directionality, banding patterns, z-disc continuity, and the appearance of presumptive SSR and T-tubule profiles all improve in healthy, DMD-, and iPSC-derived muscle tissue. Further work to identify the underlying defects of DMD tissue disorganization and the mechanisms by which motor neurons support muscle are likely to yield potential new therapeutic approaches for treating patients suffering from Duchenne muscular dystrophy.

Objective monitoring tools for improved management of childhood asthma.

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients' self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices.

Patterns and factors associated with the prescription of psychotropic medications after diagnosis of cancer in Chinese patients: A population-based cohort study.

PURPOSE: Patients with cancer may be prescribed psychotropic medications to address their psychiatric symptoms and disorders. This study examined the patterns and factors associated with the prescription of psychotropics after cancer diagnosis using a population-based database in Hong Kong. METHODS: Patients who were diagnosed with malignant cancer and had no documented psychiatric diagnosis or psychotropic medications prior to cancer diagnosis, were included. Multivariable log-binomial models were used to explore the associations between predictive factors and psychotropic medications use. RESULTS: Among 9337 patients, 1868 patients (20.0%) were newly prescribed with psychotropic medications after cancer diagnoses, most commonly hypnotics (50.3%) and antidepressants (32.8%). About one-third (31.4%) were prescribed chronic psychotropics (≥90 days). Approximately 48.3% of patients who were prescribed psychotropic medications received their prescriptions within 1 year after diagnosed with cancer. Only 18.6% of those prescribed psychotropic medications had a registered psychiatric diagnosis. Patients with multiple comorbidities (adjusted risk ratio[aRR] = 2.74; CI = 2.46-3.05) and diagnosed with oral (aRR = 1.89; CI = 1.52-2.35) or respiratory cancers (aRR = 1.62; CI = 1.36-1.93) were more likely to be prescribed psychotropics. CONCLUSIONS: The use of psychotropic medication is common (20%) among patients with cancer. Our findings highlight the importance of identification and documentation of psychiatric needs among patients with cancer.

Simultaneous multi-slice technique for reducing acquisition times in diffusion tensor imaging of the knee: a feasibility study.

OBJECTIVES: To explore the feasibility of simultaneous multi-slice (SMS) technique for reducing acquisition times in readout-segmented echo planar imaging (RESOLVE) for diffusion tensor imaging (DTI) of the knee. MATERIALS AND METHODS: A total of 30 healthy volunteers and 23 patients with knee acute injury (12 cases with anterior ligament (ACL) tears and 16 cases with patellar cartilage (PC) injury) were enrolled in this prospective study. Three DTI protocols were used: conventional RESOLVE-DTI with 12 directions (protocol 1), SMS-RESOLVE-DTI with 12 directions (protocol 2) and 20 directions (protocol 3). DTI parameters of gastrocnemius, ACL and posterior cruciate ligament (PCL), and PC from three protocols were quantitatively assessed. RESULTS: For volunteers, protocol 2 significantly reduced acquisition time by 38.6% and 34.2% compared to protocols 1 and 3 while maintaining similar high-quality images and similar diffusive parameters, except for the fractional anisotropy (FA) and axial diffusivity (AD) of the PC between protocols 2 and 1 (P < 0.05). For injured ACL and PC, protocols 1 and 2 showed similar accurate diffusive parameters (except for AD, P = 0.025) and similar diagnostic efficacy, which demonstrated significantly lower FA and higher radial diffusivity (RD) in protocols 1 and 2 compared to volunteers (P < 0.05). CONCLUSIONS: The 12-direction SMS-RESOLVE-DTI demonstrated a favorable balance between acquisition time and image quality, making it a promising alternative to conventional DTI for evaluating ligament and cartilage injuries. ADVANCES IN KNOWLEDGE: The SMS technique greatly reduces acquisition time while maintaining image quality, which signified the possibility of DTI's clinical application.

Enhancing pneumonia prognosis in the emergency department: a novel machine learning approach using complete blood count and differential leukocyte count combined with CURB-65 score.

BACKGROUND: Pneumonia poses a major global health challenge, necessitating accurate severity assessment tools. However, conventional scoring systems such as CURB-65 have inherent limitations. Machine learning (ML) offers a promising approach for prediction. We previously introduced the Blood Culture Prediction Index (BCPI) model, leveraging solely on complete blood count (CBC) and differential leukocyte count (DC), demonstrating its effectiveness in predicting bacteremia. Nevertheless, its potential in assessing pneumonia remains unexplored. Therefore, this study aims to compare the effectiveness of BCPI and CURB-65 in assessing pneumonia severity in an emergency department (ED) setting and develop an integrated ML model to enhance efficiency. METHODS: This retrospective study was conducted at a 3400-bed tertiary medical center in Taiwan. Data from 9,352 patients with pneumonia in the ED between 2019 and 2021 were analyzed in this study. We utilized the BCPI model, which was trained on CBC/DC data, and computed CURB-65 scores for each patient to compare their prognosis prediction capabilities. Subsequently, we developed a novel Cox regression model to predict in-hospital mortality, integrating the BCPI model and CURB-65 scores, aiming to assess whether this integration enhances predictive performance. RESULTS: The predictive performance of the BCPI model and CURB-65 score for the 30-day mortality rate in ED patients and the in-hospital mortality rate among admitted patients was comparable across all risk categories. However, the Cox regression model demonstrated an improved area under the ROC curve (AUC) of 0.713 than that of CURB-65 (0.668) for in-hospital mortality (p<0.001). In the lowest risk group (CURB-65=0), the Cox regression model outperformed CURB-65, with a significantly lower mortality rate (2.9% vs. 7.7%, p<0.001). CONCLUSIONS: The BCPI model, constructed using CBC/DC data and ML techniques, performs comparably to the widely utilized CURB-65 in predicting outcomes for patients with pneumonia in the ED. Furthermore, by integrating the CURB-65 score and BCPI model into a Cox regression model, we demonstrated improved prediction capabilities, particularly for low-risk patients. Given its simple parameters and easy training process, the Cox regression model may be a more effective prediction tool for classifying patients with pneumonia in the emergency room.

Prognostic value of neutrophil-to-lymphocyte ratio dynamics in patients with septic acute kidney injury: a cohort study.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined. METHODS: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses. RESULTS: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs. 46.6%, p < 0.001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality (p = 0.004), need for renal replacement therapy (p = 0.011), and developing stage-3 AKI (p = 0.040) according to the adjusted models. CONCLUSIONS: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.

The role of postoperative radiotherapy or chemoradiation in pT1-2N1M0 oral squamous cell carcinoma.

BACKGROUND: Postoperative radiotherapy (PORT) and concurrent chemoradiation (CCRT) are indicated for patients with advanced oral cancer. However, the benefits for pT1-2N1 disease without adverse pathological features are controversial. METHODS: This retrospective study using the Taiwan Cancer Registry database included patients with pT1-2N1 oral cancer from January 1, 2011, to December 31, 2017. Overall survival was analyzed in patients receiving surgery alone, PORT, or CCRT. RESULTS: Among the 862 patients, the five-year overall survival rate in patients receiving surgery alone, PORT, and CCRT was 62.2%, 58.7%, and 71.1% (P = 0.03), respectively. CCRT was associated with longer survival than PORT (P = 0.008). Survival in patients with pT2 disease was significantly higher with CCRT than PORT (P = 0.001), but no difference was observed in pT1 disease. CONCLUSION: CCRT demonstrated a favorable impact on survival outcomes in patients diagnosed with pT2N1 oral cancer when compared to PORT. However, no significant survival benefits were observed for patients with pT1 disease.

Mn-Incorporation-Induced Phase Transition in Bottom-Up Synthesized Colloidal Sub-1-nm Ni(OH)2 Nanosheets for Enhanced Oxygen Evolution Catalysis.

Sub-1-nm structures are attractive for diverse applications owing to their unique properties compared to those of conventional nanomaterials. Transition-metal hydroxides are promising catalysts for oxygen evolution reaction (OER), yet there remains difficulty in directly fabricating these materials within the sub-1-nm regime, and the realization of their composition and phase tuning is even more challenging. Here we define a binary-soft-template-mediated colloidal synthesis of phase-selective Ni(OH)2 ultrathin nanosheets (UNSs) with 0.9 nm thickness induced by Mn incorporation. The synergistic interplay between binary components of the soft template is crucial to their formation. The unsaturated coordination environment and favorable electronic structures of these UNSs, together with in situ phase transition and active site evolution confined by the ultrathin framework, enable efficient and robust OER electrocatalysis. They exhibit a low overpotential of 309 mV at 100 mA cm-2 as well as remarkable long-term stability, representing one of the most high-performance noble-metal-free catalysts.

African Suid Genomes Provide Insights into the Local Adaptation to Diverse African Environments.

African wild suids consist of several endemic species that represent ancient members of the family Suidae and have colonized diverse habitats on the African continent. However, limited genomic resources for African wild suids hinder our understanding of their evolution and genetic diversity. In this study, we assembled high-quality genomes of a common warthog (Phacochoerus africanus), a red river hog (Potamochoerus porcus), as well as an East Asian Diannan small-ear pig (Sus scrofa). Phylogenetic analysis showed that common warthog and red river hog diverged from their common ancestor around the Miocene/Pliocene boundary, putatively predating their entry into Africa. We detected species-specific selective signals associated with sensory perception and interferon signaling pathways in common warthog and red river hog, respectively, which contributed to their local adaptation to savannah and tropical rainforest environments, respectively. The structural variation and evolving signals in genes involved in T-cell immunity, viral infection, and lymphoid development were identified in their ancestral lineage. Our results provide new insights into the evolutionary histories and divergent genetic adaptations of African suids.

Synthetic gene circuits for cell state detection and protein tuning in human pluripotent stem cells.

During development, cell state transitions are coordinated through changes in the identity of molecular regulators in a cell type- and dose-specific manner. The ability to rationally engineer such transitions in human pluripotent stem cells (hPSC) will enable numerous applications in regenerative medicine. Herein, we report the generation of synthetic gene circuits that can detect a desired cell state using AND-like logic integration of endogenous miRNAs (classifiers) and, upon detection, produce fine-tuned levels of output proteins using an miRNA-mediated output fine-tuning technology (miSFITs). Specifically, we created an "hPSC ON" circuit using a model-guided miRNA selection and circuit optimization approach. The circuit demonstrates robust PSC-specific detection and graded output protein production. Next, we used an empirical approach to create an "hPSC-Off" circuit. This circuit was applied to regulate the secretion of endogenous BMP4 in a state-specific and fine-tuned manner to control the composition of differentiating hPSCs. Our work provides a platform for customized cell state-specific control of desired physiological factors in hPSC, laying the foundation for programming cell compositions in hPSC-derived tissues and beyond.

Assessment of Prognostic Factors and Molecular Subtypes of Breast Cancer With a Continuous-Time Random-Walk MR Diffusion Model: Using Whole Tumor Histogram Analysis.

BACKGROUND: The continuous-time random-walk (CTRW) diffusion model to evaluate breast cancer prognosis is rarely reported. PURPOSE: To investigate the correlations between apparent diffusion coefficient (ADC) and CTRW-specific parameters with prognostic factors and molecular subtypes of breast cancer. STUDY TYPE: Retrospective. POPULATION: One hundred fifty-seven women (median age, 50 years; range, 26-81 years) with histopathology-confirmed breast cancer. FIELD STRENGTH/SEQUENCE: Simultaneous multi-slice readout-segmented echo-planar imaging at 3.0T. ASSESSMENT: The histogram metrics of ADC, anomalous diffusion coefficient (D), temporal diffusion heterogeneity (α), and spatial diffusion heterogeneity (ß) were calculated for whole-tumor volume. Associations between histogram metrics and prognostic factors (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], and Ki-67 proliferation index), axillary lymph node metastasis (ALNM), and tumor grade were assessed. The performance of histogram metrics, both alone and in combination, for differentiating molecular subtypes (HER2-positive, Luminal or triple negative) was also assessed. STATISTICAL TESTS: Comparisons were made using Mann-Whitney test between different prognostic factor statuses and molecular subtypes. Receiver operating characteristic curve analysis was used to assess the performance of mean and median histogram metrics in differentiating the molecular subtypes. A P value <0.05 was considered statistically significant. RESULTS: The histogram metrics of ADC, D, and α differed significantly between ER-positive and ER-negative status, and between PR-positive and PR-negative status. The histogram metrics of ADC, D, α, and ß were also significantly different between the HER2-positive and HER2-negative subgroups, and between ALNM-positive and ALNM-negative subgroups. The histogram metrics of α and ß significantly differed between high and low Ki-67 proliferation subgroups, and between histological grade subgroups. The combination of αmean and ßmean achieved the highest performance (AUC = 0.702) to discriminate the Luminal and HER2-positive subtypes. DATA CONCLUSION: Whole-tumor histogram analysis of the CTRW model has potential to provide additional information on the prognosis and intrinsic subtyping classification of breast cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Intraobserver and Interobserver Reproducibility of Breast Diffusion-Weighted Imaging Quantitative Parameters: Readout-Segmented vs. Single-Shot Echo-Planar Imaging.

BACKGROUND: The recommended technique for breast diffusion-weighted imaging (DWI) acquisitions is not sufficiently standardized in clinical practice. PURPOSE: To investigate the intraobserver and interobserver reproducibility of DWI measurements, diffusion-kurtosis imaging (DKI) parameters, and image quality evaluation in breast lesions between single-shot echo-planar imaging (ss-EPI) and readout-segmented echo-planar imaging (rs-EPI). STUDY TYPE: Prospective. POPULATION: A total of 295 women with 209 malignant and 86 benign breast lesions. FIELD STRENGTH/SEQUENCE: A 3-T; fat-saturated T2-weighted MR imaging (T2WI); multi-b-value DWI with both ss-EPI and rs-EPI readouts; T1-weighted dynamic contrast-enhanced MRI (DCE-MRI). ASSESSMENT: Mean kurtosis (MK), mean diffusion (MD), and apparent diffusion coefficient (ADC) values were measured for each lesion on ss-EPI and rs-EPI, respectively. Image quality was visually evaluated regarding image sharpness, geometric distortion, lesion conspicuity, visualization of anatomic structures, and overall quality. Quantitative and qualitative analyses were performed twice with a time interval of 2 weeks. STATISTICAL TESTS: Intraobserver and interobserver reproducibility were evaluated using intra-class correlation coefficients (ICC), within-subject coefficient of variation (wCV), and Bland-Altman plots. RESULTS: MK, MD, and ADC quantitative parameters for breast lesions showed excellent intraobserver and interobserver reproducibility, with ICCs >0.75 and wCV values ranging from 2.51% to 7.08% for both sequences. The wCV values in both intraobserver and interobserver measurements were higher in the ss-EPI sequence (3.63%-7.08%) than that of the rs-EPI sequence (2.51%-3.62%). The wCV values differed in subgroups with different histopathological types of lesions, breast density, lesion morphology, and lesion sizes, respectively. Furthermore, rs-EPI (ICCs, 0.76-0.97; wCV values, 2.41%-6.04%) had better intraobserver and interobserver reproducibility than ss-EPI (ICCs, 0.54-0.90; wCV values, 6.18%-13.69%) with regard to image quality. DATA CONCLUSION: Compared to the ss-EPI, the rs-EPI sequence showed higher intraobserver and interobserver reproducibility for quantitative diffusion-related parameters and image quality assessments measured in breast DWI and DKI. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Contrasts Between Diffusion-Weighted Imaging and Dynamic Contrast-Enhanced MR in Diagnosing Malignancies of Breast Nonmass Enhancement Lesions Based on Morphologic Assessment.

BACKGROUND: Nonmass enhancement (NME) breast lesions are considered to be the leading cause of unnecessary biopsies. Diffusion-weighted imaging (DWI) or dynamic contrast-enhanced (DCE) sequences are typically used to differentiate between benign and malignant NMEs. It is important to know which one is more effective and reliable. PURPOSE: To compare the diagnostic performance of DCE curves and DWI in discriminating benign and malignant NME lesions on the basis of morphologic characteristics assessment on contrast-enhanced (CE)-MRI images. STUDY TYPE: Retrospective. SUBJECTS: A total of 180 patients with 184 lesions in the training cohort and 75 patients with 77 lesions in the validation cohort with pathological results. FIELD STRENGTH/SEQUENCE: A 3.0 T/multi-b-value DWI (b values = 0, 50, 1000, and 2000 sec/mm2 ) and time-resolved angiography with stochastic trajectories and volume-interpolated breath-hold examination (TWIST-VIBE) sequence. ASSESSMENT: In the training cohort, a diagnostic model for morphology based on the distribution and internal enhancement characteristics was first constructed. The apparent diffusion coefficient (ADC) model (ADC + morphology) and the time-intensity curves (TIC) model (TIC + morphology) were then established using binary logistic regression with pathological results as the reference standard. Both models were compared for sensitivity, specificity, and area under the curve (AUC) in the training and the validation cohort. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve analysis and two-sample t-tests/Mann-Whitney U-test/Chi-square test were performed. P < 0.05 was considered statistically significant. RESULTS: For the TIC/ADC model in the training cohort, sensitivities were 0.924/0.814, specificities were 0.615/0.615, and AUCs were 0.811 (95%, 0.727, 0.894)/0.769 (95%, 0.681, 0.856). The AUC of the TIC-ADC combined model was significantly higher than ADC model alone, while comparable with the TIC model (P = 0.494). In the validation cohort, the AUCs of TIC/ADC model were 0.799/0.635. DATA CONCLUSION: Based on the morphologic analyses, the performance of the TIC model was found to be superior than the ADC model for differentiating between benign and malignant NME lesions. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Early Identification of Pathologic Complete Response to Neoadjuvant Chemotherapy Using Multiphase DCE-MRI by Siamese Network in Breast Cancer: A Longitudinal Multicenter Study.

BACKGROUND: Siamese network (SN) using longitudinal DCE-MRI for pathologic complete response (pCR) identification lack a unified approach to phases selection. PURPOSE: To identify pCR in early-stage NAC, using SN with longitudinal DCE-MRI and introducing IPS for phases selection. STUDY TYPE: Multicenter, longitudinal. POPULATION: Center A: 162 female patients (50.63 ± 8.41 years) divided 7:3 into training and internal validation cohorts. Center B: 61 female patients (50.08 ± 7.82 years) were used as an external validation cohort. FIELD STRENGTH/SEQUENCE: Center A: single vendor 3.0 T with a compressed-sensing volume interpolated breath-hold examination sequence. Center B: single vendor 1.5 T with volume interpolated breath-hold examination sequence. ASSESSMENT: Patients underwent DCE-MRI before and after two NAC cycles, with tumor regions of interest (ROI) manually delineated. Histopathology was the reference for pCR identification. Models developed included a clinical one, four SN models based on IPS-selected phases, and integrated models combining clinical and SN features. STATISTICAL TESTS: Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The DeLong test was used to compare AUCs. Net reclassification improvement and integrated discrimination improvement (IDI) tests were employed for performance comparison. P < 0.05 was considered significant. RESULTS: In internal and external validation cohorts, the clinical model showed AUCs of 0.760 and 0.718. SN and integrated models, with increasing phases via IPS, achieved AUCs ranging from 0.813 to 0.951 and 0.818 to 0.922. Notably, SN-3 and integrated-3 and integrated-4 outperformed the clinical model. However, input phases beyond 20% did not significantly enhance performance (IDI test: SN-4 vs. SN-3, P = 0.314 and 0.630; integrated-4 vs. integrated-3, P = 0.785 and 0.709). DATA CONCLUSION: The longitudinal multiphase DCE-MRI based on the SN demonstrates promise for identifying pCR in breast cancer. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Clinical, neuroimaging, and behavioural risk factors for neurocognitive impairment in Chinese patients with haemophilia: A multicentre study.

BACKGROUND: Few studies have evaluated the impact of subclinical microstructural changes and psychosocial factors on cognitive function in patients with haemophilia. OBJECTIVES: To determine the prevalence and characteristics of cognitive impairment in patients with haemophilia, and identify associated risk factors. METHODS: We recruited haemophilia A or B patients who were aged ≥10 years old from three public hospitals in Hong Kong. A neurocognitive battery was administered to evaluate their attention, memory, processing speed and cognitive flexibility performances. They also underwent magnetic resonance imaging to identify cerebral microbleeds. Validated self-reported questionnaires were administered to assess their mental health status and adherence to prophylactic treatment. General linear modelling was used to investigate the association of neurocognitive outcomes with risks factors, adjusting for age and education attainment. RESULTS: Forty-two patients were recruited (median age 32.0 years; 78.6% haemophilia A; 80.9% moderate-to-severe disease). Six patients (14.3%) had developed cerebral microbleeds. A subgroup of patients demonstrated impairments in cognitive flexibility (30.9%) and motor processing speed (26.2%). Hemarthrosis in the previous year was associated with worse attention (Estimate = 7.62, 95% CI: 1.92-15.33; p = .049) and cognitive flexibility (Estimate = 8.64, 95% CI: 2.52-13.29; p = .043). Depressive (Estimate = 0.22, 95% CI: 0.10-0.55; p = .023) and anxiety (Estimate = 0.26, 95% CI: 0.19-0.41; p = .0069) symptoms were associated with inattentiveness. Among patients receiving prophylactic treatment (71.4%), medication adherence was positively correlated with cognitive flexibility (p = .037). CONCLUSION: A substantial proportion of patients with haemophilia demonstrated cognitive impairment, particularly higher-order thinking skills. Screening for cognitive deficits should be incorporated into routine care. Future studies should evaluate the association of neurocognitive outcomes with occupational/vocational outcomes.