Multipathway regulation induced by 4-(phenylsulfonyl)morpholine derivatives against triple-negative breast cancer.

Phenotypic drug discovery (PDD) is an effective drug discovery approach by observation of therapeutic effects on disease phenotypes, especially in complex disease systems. Triple-negative breast cancer (TNBC) is composed of several complex disease features, including high tumor heterogeneity, high invasive and metastatic potential, and a lack of effective therapeutic targets. Therefore, identifying effective and novel agents through PDD is a current trend in TNBC drug development. In this study, 23 novel small molecules were synthesized using 4-(phenylsulfonyl)morpholine as a pharmacophore. Among these derivatives, GL24 (4m) exhibited the lowest half-maximal inhibitory concentration value (0.90 µM) in MDA-MB-231 cells. To investigate the tumor-suppressive mechanisms of GL24, transcriptomic analyses were used to detect the perturbation for gene expression upon GL24 treatment. Followed by gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, multiple ER stress-dependent tumor suppressive signals were identified, such as unfolded protein response (UPR), p53 pathway, G2/M checkpoint, and E2F targets. Most of the identified pathways triggered by GL24 eventually led to cell-cycle arrest and then to apoptosis. In summary, we developed a novel 4-(phenylsulfonyl)morpholine derivative GL24 with a strong potential for inhibiting TNBC cell growth through ER stress-dependent tumor suppressive signals.

Modular Edge Analysis Reveals Chemotherapy-induced Brain Network Changes in Lung Cancer Patients.

BACKGROUND: Lung cancer patients with post-chemotherapy may have disconnected or weakened function connections within brain networks. OBJECTIVE: This study aimed to explore the abnormality of brain functional networks in lung cancer patients with post-chemotherapy by modular edge analysis. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 40 patients after chemotherapy, 40 patients before chemotherapy and 40 normal controls. Patients in all three groups were age and sex well-matched. Then, modular edge analysis was applied to assess brain functional network alterations. RESULTS: Post-chemotherapy patients had the worst MoCA scores among the three groups (p < 0.001). In intra-modular connections, compared with normal controls, the patients after chemotherapy had decreased connection strengths in the occipital lobe module (p < 0.05). Compared with the nonchemotherapy group, the patients after chemotherapy had decreased connection strengths in the subcortical module (p < 0.05). In inter-modular connections, compared with normal controls, the patients after chemotherapy had decreased connection strength in the frontal-temporal lobe modules (p < 0.05). Compared with the non-chemotherapy group, the patients after chemotherapy had decreased connection strength in the subcortical-temporal lobe modules (p < 0.05). CONCLUSION: The results reveal that chemotherapy can disrupt connections in brain functional networks. As far as we know, the use of modular edge analysis to report changes in brain functional brain networks associated with chemotherapy was rarely reported. Modular edge analysis may play a crucial part in predicting the clinical outcome for the patients after chemotherapy.

Bladder neck incompetence could be an etiology of overactive bladder syndrome in women with stress urinary incontinence after anti-incontinence surgery: insights from transrectal sonography.

PURPOSE: To investigate the prevalence of bladder neck incompetence (BNI) and the anatomic differences between different types of urinary incontinence (UI) and overactive bladder (OAB) by transrectal sonography, and to investigate these differences among those with stress UI (SUI) or mixed UI (MUI) who exhibited de novo or persistent OAB symptoms following anti-incontinence surgery. METHODS: A retrospective analysis was conducted on a total of 184 patients with SUI, MUI, urge UI (UUI), or OAB dry who underwent transrectal ultrasound between 2017 and 2022. The presence of BNI and urethral incompetence assessed by transrectal ultrasound were recorded in all included patients, and recorded preoperatively and postoperatively among patients with SUI and MUI who underwent anti-incontinence surgery. RESULTS: Among the patients, 91%, 84%, 76%, and 71% exhibited BNI in MUI, SUI, UUI, OAB dry group, respectively. Significantly higher rate of patients with BNI were found in MUI than in OAB dry group. Patients with OAB symptoms after anti-incontinence surgery exhibited significantly higher rates of BNI and urethral incompetence than those who did not have postoperative OAB symptoms. Among MUI patients with preoperative BNI, significantly lower rate of postoperative BNI and urethral incompetence was observed in individuals who had improved OAB symptoms after surgery, compared to those without improvement. CONCLUSION: A higher BNI rate was observed in the MUI group. A significantly higher BNI rate was observed in women with OAB symptoms after anti-incontinence surgery. Patients with MUI had improved OAB symptoms if BNI was successfully corrected after anti-incontinence surgery.

Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration.

The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, the mechanism underlying this type of cell migration remains unclear. Here we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo epithelial-mesenchymal transition-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-hijacked RhoA signaling significantly alters cellular morphology and rearranges the actin cytoskeleton involving the depolymerization of robust actin stress fibers, leading-edge protrusion formation, and the rear-edge recontraction, which coordinates VACV-induced cell migration. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses.

Detecting intragenic trans-splicing events from non-co-linearly spliced junctions by hybrid sequencing.

Trans-spliced RNAs (ts-RNAs) are a type of non-co-linear (NCL) transcripts that consist of exons in an order topologically inconsistent with the corresponding DNA template. Detecting ts-RNAs is often interfered by experimental artifacts, circular RNAs (circRNAs) and genetic rearrangements. Particularly, intragenic ts-RNAs, which are derived from separate precursor mRNA molecules of the same gene, are often mistaken for circRNAs through analyses of RNA-seq data. Here we developed a bioinformatics pipeline (NCLscan-hybrid), which integrated short and long RNA-seq reads to minimize false positives and proposed out-of-circle and rolling-circle long reads to distinguish between intragenic ts-RNAs and circRNAs. Combining NCLscan-hybrid screening and multiple experimental validation steps successfully confirmed that four NCL events, which were previously regarded as circRNAs in databases, originated from trans-splicing. CRISPR-based endogenous genome modification experiments further showed that flanking intronic complementary sequences can significantly contribute to ts-RNA formation, providing an efficient/specific method to deplete ts-RNAs. We also experimentally validated that one ts-RNA (ts-ARFGEF1) played an important role for p53-mediated apoptosis through affecting the PERK/eIF2a/ATF4/CHOP signaling pathway in breast cancer cells. This study thus described both bioinformatics procedures and experimental validation steps for rigorous characterization of ts-RNAs, expanding future studies for identification, biogenesis, and function of these important but understudied transcripts.

Lamin A/C and Vimentin as a Coordinated Regulator during Amoeboid Migration in Microscale Confined Microenvironments.

Cell migration occurs in confined microenvironments, which plays a vital role in the process of tumor metastasis. However, it is challenging to study their behaviors in vivo. Here we developed a cell squeeze system that can be scaled down to micrometers to mimic native physical confined microenvironments, wherein degrees of surface adhesion and mechanical constraints could be manipulated in order to investigate cell-migrating behaviors. Based on the microscale cell squeeze system, we found the synergistic role of lamin A/C and vimentin in cell transition and migration under strong confinement. The dynamic variations in lamin A/C and vimentin expression establish a positive feedback loop in response to confinement, effectively promoting amoeboid migration by modulating nuclear deformability while ensuring cell viability. This work shed light on modulating cell response to microenvironments by altering the expression of lamin A/C and/or vimentin, which may be a more efficient way of inhibiting cancer metastasis.

CD4+ T cell calibration of antigen-presenting cells optimizes antiviral CD8+ T cell immunity.

Antiviral CD8+ T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-ß (IFNα/ß)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4+ T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/ß or CD40 alone. These responses are critical for the acquisition of antiviral CD8+ T cell effector function, and their activity in APCs from individuals infected with severe acute respiratory syndrome coronavirus 2 correlates with milder disease. These observations uncover a sequential integration process whereby APCs rely on CD4+ T cells to select the innate circuits that guide antiviral CD8+ T cell responses.

Clinical and CT diagnosis of 50 cases of Chlamydia psittaci pneumonia.

Background: This is a retrospective cross-sectional study aiming to explore the clinical and imaging manifestations of Chlamydia psittaci pneumonia (CPP), thus improving its diagnosis, guiding its early clinical treatment, and reducing its mortality rate. Methods: Fifty cases of CPP diagnosed by hospitals across the country with metagenomics next-generation sequencing (mNGS) from January 2019 to March 2021 were collected. Its clinical symptoms, laboratory test results, and computed tomography (CT) features were discussed. Results: Forty patients had a history of poultry exposure; 37 experienced respiratory symptoms, 48 had a fever, 14 experienced gastrointestinal symptoms, and 12 experienced neurological symptoms; 34 patients had normal blood cell counts, 49 patients had elevated C-reactive protein, and 24 showed decreased serum sodium. Imaging manifestations: (I) Distribution: lesions were limited to a single lung in 31 patients, lesions were distributed in bilateral lungs in 19 patients; (II) Signs: 37 patients developed the "fine mesh sign". Necrosis, cavity and "tree-in-bud" were not observed. Pleural effusion occurred in 33 patients, mediastinal lymphadenopathy in 18, and splenomegaly in 15 patients. Conclusions: Patients with CPP often have a history of poultry exposure and present with fever and increased C-reactive protein. White blood cells may be slightly increased or completely normal. Hyponatremia may occur in some patients, and multiple systems may be clinically involved. The imaging can show lesions with unilateral or bilateral lung distribution and a rapid progression. Both the lung parenchyma and the interstitium are involved. Fine mesh sign is the most common sign. Necrosis, cavitation, and tree-in-bud signs are not observed. In conclusion, imaging examinations are helpful for the early diagnosis of this disease and the evaluation of the treatment effect.

Additional single dose GnRH agonist during luteal phase support may improve live birth rate in GnRHa-HRT frozen-thawed embryo transfer cycle: a retrospective cohort study.

BACKGROUND: GnRH agonist (GnRHa) has been reported to have direct effects and functional roles in the endometrium and embryos. Several meta-analyses have shown that GnRHa administration in the luteal phase improved the live birth rate or pregnancy rate in both fresh and frozen embryo transfer (FET) cycles. The aim of this study was to investigate whether luteal GnRHa administration could also improve in vitro fertilization (IVF) outcomes in patients undergoing hormone replacement therapy (HRT) cycles with GnRHa suppression. METHODS: The retrospective cohort study included a total of 350 patients undergoing GnRHa-HRT FET cycles. The study group included 179 patients receiving an additional single dose of GnRHa in the luteal phase following embryo transfer. A total of 171 patients in the control group did not receive luteal GnRHa. The baseline and cycle characteristics and reproductive outcomes were compared between the two groups. RESULTS: Baseline and cycle characteristics were similar between the two groups, except lower AMH levels were found in the luteal GnRHa group than in the control group. The luteal GnRHa group had a significantly higher ongoing pregnancy rate and live birth rate than the control group. The multivariate analysis revealed that luteal GnRHa administration was positively associated with ongoing pregnancy (OR 2.04, 95% CI 1.20-3.47, P = 0.008) and live birth (OR 2.03, 95% CI 1.20-3.45, P = 0.009). When the subgroup of patients with recurrent implantation failure was analyzed, the multivariate analysis also showed that luteal GnRHa administration had beneficial effects on ongoing pregnancy (OR 4.55, 95% CI 1.69-12.30, P = 0.003) and live birth (OR 4.30, 95% CI 1.59-11.65, P = 0.004). CONCLUSIONS: Our data suggest that the addition of one luteal dose of GnRHa may improve the live birth rate in patients undergoing the GnRHa-HRT protocol.

Recent Advances in Metal-Based NanoEnhancers for Particle Therapy.

Radiotherapy is one of the most common therapeutic regimens for cancer treatment. Over the past decade, proton therapy (PT) has emerged as an advanced type of radiotherapy (RT) that uses proton beams instead of conventional photon RT. Both PT and carbon-ion beam therapy (CIBT) exhibit excellent therapeutic results because of the physical characteristics of the resulting Bragg peaks, which has been exploited for cancer treatment in medical centers worldwide. Although particle therapies show significant advantages to photon RT by minimizing the radiation damage to normal tissue after the tumors, they still cause damage to normal tissue before the tumor. Since the physical mechanisms are different from particle therapy and photon RT, efforts have been made to ameliorate these effects by combining nanomaterials and particle therapies to improve tumor targeting by concentrating the radiation effects. Metallic nanoparticles (MNPs) exhibit many unique properties, such as strong X-ray absorption cross-sections and catalytic activity, and they are considered nano-radioenhancers (NREs) for RT. In this review, we systematically summarize the putative mechanisms involved in NRE-induced radioenhancement in particle therapy and the experimental results in in vitro and in vivo models. We also discuss the potential of translating preclinical metal-based NP-enhanced particle therapy studies into clinical practice using examples of several metal-based NREs, such as SPION, Abraxane, AGuIX, and NBTXR3. Furthermore, the future challenges and development of NREs for PT are presented for clinical translation. Finally, we propose a roadmap to pursue future studies to strengthen the interplay of particle therapy and nanomedicine.

Multisystem Sarcoidosis Combined with Sjögren's Syndrome: A Case Report and Literature Review.

BACKGROUND: Sarcoidosis is a systemic non-caseous necrotizing granulomatous disease with unknown etiology. It can involve multiple organs throughout the body, most commonly affecting lungs and/or bilateral hilar lymph nodes. Sjögren's syndrome is a multi-system autoimmune disease. The main clinical symptoms include dry mouth and dry eyes. The combination of the two diseases with the involvement of multiple systems is very rare, and the final diagnosis is mainly based on the comprehensive judgment of clinical history, imaging manifestations and pathological examination. CASE PRESENTATION: We report a case of multiple sarcoidosis (lung, hilar, mediastinal, inguinal, liver, and spleen) with Sjögren syndrome. The patient had a dry mouth, dry eyes, and bilateral parotid gland enlargement. The first computed tomography (CT) scan of the chest and abdomen showed multiple nodules in the lungs, multiple enlarged lymph nodes, and low-density shadows in the liver and spleen. After a one-year interval, the re-examination showed that the lung lesions increased with bead-like changes, and the lymph nodes shrunk. Through pathological puncture and comprehensive judgment, considering the coexistence of the two diseases, the patient improved after hormone therapy and was finally diagnosed. CONCLUSION: Multisystem sarcoidosis combined with Sjögren's syndrome has rarely been reported in the literature. This case has multiple imaging examinations, pathological data and a follow-up review after treatment. The dynamic changes in different periods will help us to better understand the situation of sarcoidosis and explore the connection between the two diseases so as to reduce misdiagnosis.

Functional-structural large-scale brain networks are correlated with neurocognitive impairment in acute mild traumatic brain injury.

Background: This study was conducted to investigate topological changes in large-scale functional connectivity (FC) and structural connectivity (SC) networks in acute mild traumatic brain injury (mTBI) and determine their potential relevance to cognitive impairment. Methods: Seventy-one patients with acute mTBI (29 males, 42 females, mean age 43.54 years) from Nanjing First Hospital and 57 matched healthy controls (HC) (33 males, 24 females, mean age 46.16 years) from the local community were recruited in this prospective study. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were acquired within 14 days (mean 3.29 days) after the onset of mTBI. Then, large-scale FC and SC networks with 116 regions from the automated anatomical labeling (AAL) brain atlas were constructed. Graph theory analysis was used to analyze global and nodal metrics. Finally, correlations were assessed between topological properties and neurocognitive performances evaluated by the Montreal Cognitive Assessment (MoCA). Bonferroni correction was performed out for multiple comparisons in all involved analyses. Results: Compared with HC, acute mTBI patients had a higher normalized clustering coefficient (γ) for FC (Cohen's d=4.076), and higher γ and small worldness (σ) for SC (Cohen's d=0.390 and Cohen's d=0.395). The mTBI group showed aberrant nodal degree (Dc), nodal efficiency (Ne), and nodal local efficiency (Nloc) for FC and aberrant Dc, nodal betweenness (Bc), nodal clustering coefficient (NCp) and Ne for SC mainly in the frontal and temporal, cerebellum, and subcortical areas. Acute mTBI patients also had higher functional-structural coupling strength at both the group and individual levels (Cohen's d=0.415). These aberrant global and nodal topological properties at functional and structural levels were associated with attention, orientation, memory, and naming performances (all P<0.05). Conclusions: Our findings suggested that large-scale FC and SC network changes, higher correlation between FC and SC and cognitive impairment can be detected in the acute stage of mTBI. These network aberrances may be a compensatory mechanism for cognitive impairment in acute mTBI patients.

Minute pulmonary meningothelial-like nodules: associations between computed tomography and pathology features.

Background: Increased use of multislice computed tomography (CT) scans has revealed that minute pulmonary meningothelial-like nodules (MPMNs) showed as ground-glass nodules (GGNs) are frequent in patients. However, little is known about the incidence and fate of nodules. By using a cross-sectional design, this study compared the multislice CT signs and pathological results of MPMNs, and further used pathological results to explain the formation mechanism of the CT signs of MPMNs to improve the clinical understanding of the disease. Methods: The clinicopathological data of 93 cases diagnosed as MPMNs in the Jiangsu Province Hospital from January 2016 to September 2019 and the Nanjing First Hospital from January 2017 to December 2019 were examined. The related literature was reviewed, and each case's age, gender, medical history, and preoperative CT examinations were classified. Based on CT signs, this study analyzed the imaging features, including size, shape, boundary, distribution, opacity, and their relationship with pulmonary blood vessels. Results: A total of 13 cases had immunohistochemistry results among which the lesions showed consistent positive expression of vimentin (100%), followed by epithelial cell membrane antigen (92.3%) and progesterone (8%). The MPMNs mainly occurred in individuals aged 50-59 years (32.6%). Most patients (82.6%) had neoplastic disease. All nodules (100%) manifested with a round shape and well-demarcated borders on images. The size of the nodules on CT scans ranged from 2.5 to 5.0 mm, with an average size of 3.04±1.12 mm. Most nodules were subpleural (89.1%) and showed ground-glass opacity (97.8%). The follow-up results of postoperative clinical manifestations and chest CT examination were negative in 12 patients. Conclusions: This study suggested that the pathological findings of MPMNs could explain the formation mechanism of the CT signs. The results can provide guidance for the diagnosis of the disease in the future.

Efficacy of Tailor-Made Notched Music Training Versus Tinnitus Retraining Therapy in Adults With Chronic Subjective Tinnitus: A Randomized Controlled Clinical Trial.

OBJECTIVES: Chronic subjective tinnitus can have a serious effect on daily life, even causing serious psychological disorders. Currently there are no specific effective solutions or cures. Tailor-made notched music training (TMNMT) is a recently proposed sound therapy that has simpler processes and a higher compliance rate than tinnitus retraining therapy (TRT), a widely used treatment for chronic subjective tinnitus. This study explores the therapeutic effect of TMNMT in comparison to TRT to highlight its clinical value. DESIGN: The study was a randomized controlled, single-blinded clinical trial. One hundred twenty eligible participants were randomly assigned to receive TMNMT (n = 60) or TRT (n = 60) for 3 mo with concurrent follow-up. It should be noted that the duration of sound treatment in TRT was modified to 2 hr per day for better feasibility in practice. The primary outcome was mean change in tinnitus handicap inventory (THI) measured at baseline ( T0 ), 1 mo ( T1 ) and 3 mo ( T2 ) after intervention. Change in visual analog scale (VAS) was measured as a secondary outcome. A comparison of therapeutic effectiveness between TMNMT and TRT was evaluated by repeated measure analysis of variance. RESULTS: One hundred and twelve (93%) of participants took part in the study, of which 64 were men and 48 women. Mean (SD) age was 42.80 (12.91) years. Fifty-eight were allocated to receive TMNMT and 54 to receive TRT. The between-group difference in primary outcome was -6.90 points (95% confidence interval [CI], -13.53 to -0.27) at T1 and -6.17 points (95% CI, -13.04 to 0.71) at T2 . These results closely reached to clinical significance of tinnitus-related effective relief. For the secondary outcome, the mean value in the TMNMT group was 0.83 points (95% CI, 0.12 to 1.54), significantly lower than the mean value of the TRT group. The differences in THI and VAS between the two groups were statistically significant after intervention. Further analysis showed that age and baseline THI and VAS scores were associated with change in THI and VAS scores after interventions. CONCLUSIONS: Both TMNMT and TRT were able to alleviate chronic subjective tinnitus effectively after a 3 month intervention. When the two forms of therapy were compared TMNMT appeared to be more effective and consequently potentially superior to TRT for reducing tinnitus loudness and functional and emotional disturbance associated with chronic subjective tinnitus.

Imaging Manifestation and Pathological Comparison of the Peritoneal Loose Body: A Case Report and Review of the Literature.

BACKGROUND: Peritoneal loose body (PLB) which is also called "peritoneal mouse" is a rare disease, with only a few cases reported. PLB is mostly found due to unplanned examination, surgery, or autopsy. With the increase in abdominal imaging examinations, it was gradually recognized by us. The diagnosis of PLB has three major characteristics: free movement, no blood supply, and pathological exclusion of other tumors. CASE PRESENTATION: We reported a 66-year-old male patient with an asymptomatic freely moving peritoneal loose body. The size of the lesion was about 4*4cm. The imaging data were complete including Ultrasound, Magnetic resonance (MR), Computed tomography (CT) plain scan and enhancement. Interestingly, changes in the location of the lesion were found on follow-up CT. The lesion showed concentric circles changes on CT without obvious enhancement. MR also appeared as a multi-layer signal of concentric circles. In addition, the imaging manifestations were compared with histological pathology in this article to explain imaging characteristics. CONCLUSION: PLB is an uncommon disease. Through the complete imaging examination of this case, we can further understand the mobility of the lesion by changing the position. The CT and MR have characteristic concentric circle changes without obvious enhancement. The diagnosis could be confirmed before surgery, which prompted the clinical early diagnosis of the disease, and an appropriate choice between surgery and conservative treatment.

Radiomics Analysis of Diffusion-Weighted Imaging and Long-Term Unfavorable Outcomes Risk for Acute Stroke.

BACKGROUND: Diffusion-weighted imaging radiomics could be used as prognostic biomarkers in acute ischemic stroke. We aimed to identify a clinical and diffusion-weighted imaging radiomics model for individual unfavorable outcomes risk assessment in acute ischemic stroke. METHODS: A total of 1716 patients with acute ischemic stroke from 2 centers were divided into a training cohort and a validation cohort. Patient outcomes were measured with the modified Rankin Scale score. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2. The primary end point was all-cause mortality or outcomes 1 year after stroke. The MRI-DRAGON score was calculated based on previous publications. We extracted and selected the infarct features on diffusion-weighted imaging to construct a radiomic signature. The clinic-radiomics signature was built by measuring the Cox proportional risk regression score (CrrScore) and compared with the MRI-DRAGON score and the ClinicScore. CrrScore model performance was estimated by 1-year unfavorable outcomes prediction. RESULTS: A high radiomic signature predicted a higher probability of unfavorable outcomes than a low radiomic signature in the training (hazard ratio, 3.19 [95% CI, 2.51-4.05]; P<0.0001) and validation (hazard ratio, 3.25 [95% CI, 2.20-4.80]; P<0.0001) cohorts. The diffusion-weighted imaging Alberta Stroke Program Early CT Score, age, glucose level before therapy, National Institutes of Health Stroke Scale score on admission, glycated hemoglobin' radiomic signature, hemorrhagic infarction, and malignant cerebral edema were associated with an unfavorable outcomes risk after multivariable adjustment. A CrrScore nomogram was developed to predict outcomes and had the best performance in the training (area under the curve, 0.862) and validation cohorts (area under the curve, 0.858). The CrrScore model time-dependent areas under the curve of the probability of unfavorable outcomes at 1 year in the training and validation cohorts were 0.811 and 0.801, respectively. CONCLUSIONS: The CrrScore model allows the accurate prediction of patients with acute ischemic stroke outcomes and can potentially guide rehabilitation therapies for patients with different risks of unfavorable outcomes.

Successful treatment of giant Bowen's disease with photodynamic therapy and subsequent imiquimod in a case with chronic arsenic exposure.

Multiple large lesions of Bowen's disease (BD) often appear in patients who have been under chronic exposure to arsenic. The treatment of such lesions is very challenging. Photodynamic therapy (PDT) has been considered a first-line effective treatment for BD. However, lesions larger than 2 cm are less responsive to PDT. We reported two giant BD lesions (> 10 cm in diameter), that were on a chronic arsenicosis patient's back, to be successfully treated with PDT and subsequent imiquimod occlusion overnight twice a week on the week after PDT. No recurrence was noted during the 12-month follow-up.

Correction: Green sweet potato leaves increase Nrf2-mediated antioxidant activity and facilitate benzo[a]pyrene metabolism in the liver by increasing phase II detoxifying enzyme activities in rats.

Correction for 'Green sweet potato leaves increase Nrf2-mediated antioxidant activity and facilitate benzo[a]pyrene metabolism in the liver by increasing phase II detoxifying enzyme activities in rats' by Ray-Yu Yang et al., Food Funct., 2022, https://doi.org/10.1039/d2fo01049f.

A Novel Deep Learning Model to Distinguish Malignant Versus Benign Solid Lung Nodules.

BACKGROUND In this study we aimed to establish a new transfer learning model based on noncontrast and thin-layer computed tomography (CT) scans to distinguish between malignant and benign solid lung nodules. MATERIAL AND METHODS CT images from 202 patients with 210 lesions (malignant: 127, benign: 83) manifesting as solid lung nodules from January 2016 to December 2020 from 3 institutions were retrospectively collected, and each nodule was histopathologically confirmed. Two experienced thoracic radiologists reviewed all images and determined the regions of interest (ROIs) in the three-dimensional (3D) images layer-by-layer. We divided the lesions and images into training and testing sets at a ratio of 7: 3. The Inception V3 model was pretrained by the training dataset. Five-fold cross-validation was used to choose the optimal model. Receiver operator characteristic curves (ROC curves) for methods to evaluate the performance of the models were drafted. RESULTS In the validation set, the AUC, accuracy, sensitivity, and specificity of Inception V3 model (lesion-level) were 0.999, 0.989, 0.983, and 1.0, respectively, which is higher than the image-level (0.997, 0.933, 0.922, and 0.948, respectively). The Inception V3 model (lesion-level) performed better than the image-level but there was no significant difference between the models (P>0.05). The ResNet50 model based on image level achieved AUC, accuracy, sensitivity, and specificity of 0.963, 0.926, 0.916, and 0.944, respectively, which is lower than that of Inception V3. CONCLUSIONS Our study developed a novel deep learning model based on noncontrast and thin-layer CT scans to classify benign vs malignant lung nodules, and the Inception V3 model greatly improved the differentiation accuracy and specificity.

Rich-club reorganization of functional brain networks in acute mild traumatic brain injury with cognitive impairment.

Background: Mild traumatic brain injury (mTBI) is typically characterized by temporally limited cognitive impairment and regarded as a brain connectome disorder. Recent findings have suggested that a higher level of organization named the "rich-club" may play a central role in enabling the integration of information and efficient communication across different systems of the brain. However, the alterations in rich-club organization and hub topology in mTBI and its relationship with cognitive impairment after mTBI have been scarcely elucidated. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 88 patients with mTBI and 85 matched healthy controls (HCs). Large-scale functional brain networks were established for each participant. Rich-club organizations and network properties were assessed and analyzed between groups. Finally, we analyzed the correlations between the cognitive performance and changes in rich-club organization and network properties. Results: Both mTBI and HCs groups showed significant rich-club organization. Meanwhile, the rich-club organization was aberrant, with enhanced functional connectivity (FC) among rich-club nodes and peripheral regions in acute mTBI. In addition, significant differences in partial global and local network topological property measures were found between mTBI patients and HCs (P<0.01). In patients with mTBI, changes in rich-club organization and network properties were found to be related to early cognitive impairment after mTBI (P<0.05). Conclusions: Our findings suggest that such patterns of disruption and reorganization will provide the basic functional architecture for cognitive function, which may subsequently be used as an earlier biomarker for cognitive impairment after mTBI.