Chimeric CRISPR-CasX enzymes and guide RNAs for improved genome editing activity.

A compact protein with a size of <1,000 amino acids, the CRISPR-associated protein CasX is a fundamentally distinct RNA-guided nuclease when compared to Cas9 and Cas12a. Although it can induce RNA-guided genome editing in mammalian cells, the activity of CasX is less robust than that of the widely used S. pyogenes Cas9. Here, we show that structural features of two CasX homologs and their guide RNAs affect the R-loop complex assembly and DNA cleavage activity. Cryo-EM-based structural engineering of either the CasX protein or the guide RNA produced two new CasX genome editors (DpbCasX-R3-v2 and PlmCasX-R1-v2) with significantly improved DNA manipulation efficacy. These results advance both the mechanistic understanding of CasX and its application as a genome-editing tool.

Comparative characteristics of early-onset vs. late-onset advanced colorectal cancer: a nationwide study in China.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC, diagnosed in patients under the age of 50 years) has been increasing around the world. Here, we aimed to systematically identify distinctive features of EOCRC. METHODS: From 2020 to 2021, we conducted a nationwide survey in 19 hospitals, collecting data on advanced CRC patients' demographics, clinical features, disease knowledge, medical experiences, expenditures, and health-related quality of life (HRQOL). We compared these features between EOCRC and late-onset colorectal cancer (LOCRC, ≥ 50 years old) groups and analyzed the association between EOCRC and HRQOL using multivariate linear regression. FINDINGS: In total, 991 patients with EOCRC and 3581 patients with LOCRC were included. Compared to the LOCRC group, the EOCRC group had higher levels of education, were more informed about the risk factors for CRC, were more likely to have widespread metastases throughout the body, were more inclined to undergo gene testing, and were more likely to opt for targeted therapy, radiotherapy, and chemotherapy. However, HRQOL in the EOCRC group was similar to that of the LOCRC group, and no significant association was observed between EOCRC and HRQOL (beta: -0.753, P value: 0.307). INTERPRETATION: In Chinese patients, EOCRC patients had more aggressive features. Despite undergoing more intensified treatments and gene testing, they had similar HRQOL compared with LOCRC. These findings advocate for a more tailored approach to treatment, especially for young CRC patients with advanced TNM stages and metastasis.

Effect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne.

AIMS: Previously, retinoids have decreased CYP2D6 mRNA expression in vitro and induced CYP3A4 in vitro and in vivo. This study aimed to determine whether isotretinoin administration changes CYP2D6 and CYP3A activities in patients with severe acne. METHODS: Thirty-three patients (22 females and 11 males, 23.5 ± 6.0 years old) expected to receive isotretinoin treatment completed the study. All participants were genotyped for CYP2D6 and CYP3A5. Participants received dextromethorphan (DM) 30 mg orally as a dual-probe substrate of CYP2D6 and CYP3A activity at two study timepoints: pre-isotretinoin treatment and with isotretinoin for at least 1 week. The concentrations of isotretinoin, DM and their metabolites were measured in 2-h postdose plasma samples and in cumulative 0-4-h urine collections using liquid chromatography-mass spectrometry. RESULTS: In CYP2D6 extensive metabolizers, the urinary dextrorphan (DX)/DM metabolic ratio (MR) (CYP2D6 activity marker) was numerically, but not significantly, lower with isotretinoin administration compared to pre-isotretinoin (geometric mean ratio [GMR] [90% confidence interval (CI)] 0.78 [0.55, 1.11]). The urinary 3-hydroxymorphinan (3HM)/DX MR (CYP3A activity marker) was increased (GMR 1.18 [1.03, 1.35]) and the urinary DX-O-glucuronide/DX MR (proposed UGT2B marker) was increased (GMR 1.22 [1.06, 1.39]) with isotretinoin administration compared to pre-isotretinoin. CONCLUSIONS: Administration of isotretinoin did not significantly reduce CYP2D6 activity in extensive metabolizers, suggesting that the predicted downregulation of CYP2D6 based on in vitro data does not translate into humans. We observed a modest increase in CYP3A activity (predominantly CYP3A4) with isotretinoin treatment. The data also suggest that DX glucuronidation is increased following isotretinoin administration.

Deep learning based automatic internal gross target volume delineation from 4D-CT of hepatocellular carcinoma patients.

BACKGROUND: The location and morphology of the liver are significantly affected by respiratory motion. Therefore, delineating the gross target volume (GTV) based on 4D medical images is more accurate than regular 3D-CT with contrast. However, the 4D method is also more time-consuming and laborious. This study proposes a deep learning (DL) framework based on 4D-CT that can achieve automatic delineation of internal GTV. METHODS: The proposed network consists of two encoding paths, one for feature extraction of adjacent slices (spatial slices) in a specific 3D-CT sequence, and one for feature extraction of slices at the same location in three adjacent phase 3D-CT sequences (temporal slices), a feature fusion module based on an attention mechanism was proposed for fusing the temporal and spatial features. Twenty-six patients' 4D-CT, each consisting of 10 respiratory phases, were used as the dataset. The Hausdorff distance (HD95), Dice similarity coefficient (DSC), and volume difference (VD) between the manual and predicted tumor contour were computed to evaluate the model's segmentation accuracy. RESULTS: The predicted GTVs and IGTVs were compared quantitatively and visually with the ground truth. For the test dataset, the proposed method achieved a mean DSC of 0.869 ± 0.089 and an HD95 of 5.14 ± 3.34 mm for all GTVs, with under-segmented GTVs on some CT slices being compensated by GTVs on other slices, resulting in better agreement between the predicted IGTVs and the ground truth, with a mean DSC of 0.882 ± 0.085 and an HD95 of 4.88 ± 2.84 mm. The best GTV results were generally observed at the end-inspiration stage. CONCLUSIONS: Our proposed DL framework for tumor segmentation on 4D-CT datasets shows promise for fully automated delineation in the future. The promising results of this work provide impetus for its integration into the 4DCT treatment planning workflow to improve hepatocellular carcinoma radiotherapy.

The vaginal microbiota among the different status of human papillomavirus infection and bacterial vaginosis.

Although human papillomavirus (HPV) infection plays a decisive role in causing tumors, its infection is insufficient for independently promoting cancer development and other co-factors facilitate the carcinogenic process. The objective of this study was to demonstrate the association between vaginal microbiota and high-risk human papillomavirus (HR-HPV) infection in women with and without bacterial vaginosis (BV). The study included 1015 women aged 21-64 who participated in cervical cancer screening in two areas of China from 2018 to 2019. Women were collected cervical exfoliated cell specimens and reproductive tract secretions samples for HR-HPV, BV and microbial composition testing. From the non-BV & HPV- group (414 HPV-negative women without BV) to the non-BV & HPV+ group (108 HPV-positive women without BV), to the BV & HPV-group (330 HPV-negative women with BV) and then to the BV & HPV+ group (163 HPV positive-women with BV), microbial diversity increased. The relative abundance of 12 genera, including Gardnerella, Prevotella, and Sneathia increased, while Lactobacillus declined. Correlation networks of these genera and host characteristics were disrupted in the non-BV & HPV+ group, and the network trended more disordered in the BV & HPV+ group. Besides, multiple HPV infection, certain HPV genotype infection and cervical intraepithelial neoplasia (CIN) status were associated with some microbes and higher microbial diversity. HPV shifted the composition and diversity of vaginal microbiota, and BV further reinforced the trend. The relative abundance of 12 genera increased and 1 genus decreased on account of BV and HPV infection, and some genera including Lactobacillus, Prevotella, and Sneathia were associated with some specific HPV genotypes infection and CIN.

The features of high-risk human papillomavirus infection in different female genital sites and impacts on HPV-based cervical cancer screening.

BACKGROUND: The causal role of high-risk Human papillomavirus (HR-HPV) in the pathogenesis of anogenital cancers is well established. In contrast, information on HR-HPV distribution of continuous anatomic sites within the female genital tract is limited, and the impact of sample type on the clinical performance in HPV-based cervical cancer screening warrants investigation. METHODS: A total of 2,646 Chinese women were enrolled in the study from May 2006 to April 2007. We analyzed the infection features by infection status and pathological diagnoses of 489 women with complete HR-HPV type and viral load data on the cervix, upper vagina, lower vagina, and perineum samples. Additionally, we assessed the clinical performance for detecting high-grade cervical intraepithelial neoplasia of grade two or worse (≥ CIN2) among these four types of samples. RESULTS: HR-HPV positivity rate was lower in the cervix (51.53%) and perineum (55.83%), higher in the upper (65.64%) and lower vagina (64.42%), and increased with the severity of cervical histological lesions (all P<0.001). Single infection was more dominant than multiple infections at each anatomic site of the female genital tract. The proportion of single HR-HPV infection decreased successively from the cervix (67.05%) to the perineum (50.00%) (Ptrend=0.019) in cervical intraepithelial neoplasia grade 1 (CIN1) and was higher in samples of the cervix (85.11%) and perineum (72.34%) in ≥ CIN2. In addition, the highest viral load was observed in the cervix compared to the other three sites. The overall agreement of the cervical and perineum samples was 79.35% and increased continuously from normal (76.55%) to ≥ CIN2 (91.49%). As for the detection of ≥ CIN2, the sensitivity was 100.00%, 97.87%, 95.74%, and 91.49% for the cervix, upper vagina, lower vagina, and perineum samples, respectively. CONCLUSIONS: Single HR-HPV infection predominated throughout the female genital tract, but the viral load was lower compared to multiple HR-HPV infections. Despite the decreasing viral load from cervix to perineum, the clinical performance for detecting ≥ CIN2 of the perineum sample was comparable to that of the cervix.

Unassisted Clinicians Versus Deep Learning-Assisted Clinicians in Image-Based Cancer Diagnostics: Systematic Review With Meta-analysis.

BACKGROUND: A number of publications have demonstrated that deep learning (DL) algorithms matched or outperformed clinicians in image-based cancer diagnostics, but these algorithms are frequently considered as opponents rather than partners. Despite the clinicians-in-the-loop DL approach having great potential, no study has systematically quantified the diagnostic accuracy of clinicians with and without the assistance of DL in image-based cancer identification. OBJECTIVE: We systematically quantified the diagnostic accuracy of clinicians with and without the assistance of DL in image-based cancer identification. METHODS: PubMed, Embase, IEEEXplore, and the Cochrane Library were searched for studies published between January 1, 2012, and December 7, 2021. Any type of study design was permitted that focused on comparing unassisted clinicians and DL-assisted clinicians in cancer identification using medical imaging. Studies using medical waveform-data graphics material and those investigating image segmentation rather than classification were excluded. Studies providing binary diagnostic accuracy data and contingency tables were included for further meta-analysis. Two subgroups were defined and analyzed, including cancer type and imaging modality. RESULTS: In total, 9796 studies were identified, of which 48 were deemed eligible for systematic review. Twenty-five of these studies made comparisons between unassisted clinicians and DL-assisted clinicians and provided sufficient data for statistical synthesis. We found a pooled sensitivity of 83% (95% CI 80%-86%) for unassisted clinicians and 88% (95% CI 86%-90%) for DL-assisted clinicians. Pooled specificity was 86% (95% CI 83%-88%) for unassisted clinicians and 88% (95% CI 85%-90%) for DL-assisted clinicians. The pooled sensitivity and specificity values for DL-assisted clinicians were higher than for unassisted clinicians, at ratios of 1.07 (95% CI 1.05-1.09) and 1.03 (95% CI 1.02-1.05), respectively. Similar diagnostic performance by DL-assisted clinicians was also observed across the predefined subgroups. CONCLUSIONS: The diagnostic performance of DL-assisted clinicians appears better than unassisted clinicians in image-based cancer identification. However, caution should be exercised, because the evidence provided in the reviewed studies does not cover all the minutiae involved in real-world clinical practice. Combining qualitative insights from clinical practice with data-science approaches may improve DL-assisted practice, although further research is required. TRIAL REGISTRATION: PROSPERO CRD42021281372; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=281372.

Correction: Unassisted Clinicians Versus Deep Learning-Assisted Clinicians in Image-Based Cancer Diagnostics: Systematic Review With Meta-analysis.

[This corrects the article DOI: 10.2196/43832.].

The Stress Phase Angle Measurement Using Spectral Domain Optical Coherence Tomography.

The stress phase angle (SPA), defined as the temporal phase angle between circumferential stress (CS) in the arterial wall and wall shear stress (WSS), is utilized to investigate the interactions between CS and WSS. SPA serves as an important parameter for the early diagnosis of cardiovascular disease. In this study, we proposed a novel method for measuring SPA using spectral domain optical coherence tomography (SD-OCT). The multi-M-mode scan strategy is adopted for interference spectrum acquisition. The phases of CS and WSS are extracted from the corresponding structural and flow velocity images of SD-OCT. The method is validated by measuring SPA in the outflow tract (OFT) of chick embryonic hearts and the common carotid artery of mice. To the best of our knowledge, this is the first time that OCT has been used for SPA measurement.

Spectral interference contrast based non-contact photoacoustic microscopy realized by SDOCT.

We introduce a method to extract the photoacoustic (PA) signal from a contrast reduction of the interference spectrum acquired by spectral domain optical coherence tomography (SDOCT). This all-optical detection is achieved in a noncontact manner directly on the water surface covered on the sample by using its specular reflection. During SDOCT exposure, the phase of the interference spectrum keeps shaking according to the water surface vibration induced by PA excitation. This results in an interference contrast reduction which is quantified by a fast Fourier transform (FFT) for PA imaging. A tungsten filament, asparagus fern leaf, and mouse auricle are imaged to demonstrate the method.

Main active components of Si-Miao-Yong-An decoction (SMYAD) attenuate autophagy and apoptosis via the PDE5A-AKT and TLR4-NOX4 pathways in isoproterenol (ISO)-induced heart failure models.

Heart failure (HF), the main cause of death in patients with many cardiovascular diseases, has been reported to be closely related to the complicated pathogenesis of autophagy, apoptosis, and inflammation. Notably, Si-Miao-Yong-An decoction (SMYAD) is a traditional Chinese medicine (TCM) used to treat cardiovascular disease; however, the main active components and their relevant mechanisms remain to be discovered. Based on our previous ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) results, we identified angoriside C (AC) and 3,5-dicaffeoylquinic acid (3,5-DiCQA) as the main active components of SMYAD. In vivo results showed that AC and 3,5-DiCQA effectively improved cardiac function, reduced the fibrotic area, and alleviated isoproterenol (ISO)-induced myocarditis in rats. Moreover, AC and 3,5-DiCQA inhibited ISO-induced autophagic cell death by inhibiting the PDE5A/AKT/mTOR/ULK1 pathway and inhibited ISO-induced apoptosis by inhibiting the TLR4/NOX4/BAX pathway. In addition, the autophagy inhibitor 3-MA was shown to reduce ISO-induced apoptosis, indicating that ISO-induced autophagic cell death leads to excess apoptosis. Taken together, the main active components AC and 3,5-DiCQA of SMYAD inhibit the excessive autophagic cell death and apoptosis induced by ISO by inhibiting the PDE5A-AKT and TLR4-NOX4 pathways, thereby reducing myocardial inflammation and improving heart function to alleviate and treat a rat ISO-induced heart failure model and cell heart failure models. More importantly, the main active components of SMYAD will provide new insights into a promising strategy that will promote the discovery of more main active components of SMYAD for therapeutic purposes in the future.

Explainable Prediction of Dacryocystitis From Noninvasive Ocular Indicators Using Deep Stacked Network and The Shapley Additive Explanations Approach.

ABSTRACT: Dacryocystitis diagnosis is important for preventing rapid blurring and vision loss. Existing state-of-the-art methods focus on routine clinical examinations and objective scattering index-based statistical analysis. Such approaches are invasive operations or lack quantitative indicators, and their application is limited. in addition, little attention has been paid to the explainability and clinical utility of models. This paper proposes an explainable dacryocystitis prediction model from noninvasive ocular indicators. The proposed model is based on an deep stacked network with 4 improvements: a multivariable feature extraction module, obtaining comprehensive predictive factors including the quantitative ocular indictors, conventional texture features, and deep learning features from shallow to deep convolutional layers; a multifeature fusion and attribute selection module based on the ReliefF method, guiding the network to focus on useful information at variables; Decision curve analysis the model is introduced into the model to evaluates the risks and benefits; and appending a SHapley Additive exPlanations (SHAP) module to the framework to automatically and efficiently interpret the prediction of the models. By integrating the above improvements in series, the models' performances are gradually enhanced. Real labeled data samples are used to train and test the model, and our model achieves high accuracy and reliability.

Expression Patterns of Key Genes in the Photoperiod and Vernalization Flowering Pathways in Lilium longiflorum with Different Bulb Sizes.

Lilium longiflorum is a wild Lilium, and its flowering transition requires a long period of cold exposure to meet the demand of vernalization. The responses of different sized bulbs to cold exposure and photoperiod are different, and the floral transition pathways of small and large bulbs are different. In this study, small and large bulbs were placed in cold storage for different weeks and then cultured at a constant ambient temperature of 25 °C under long day (LD) and short day (SD) conditions. Then, the flowering characteristics and expression patterns of key genes related to the vernalization and photoperiod pathways in different groups were calculated and analyzed. The results showed that the floral transition of Lilium longiflorum was influenced by both vernalization and photoperiod, that vernalization and LD conditions can significantly improve the flowering rate of Lilium longiflorum, and that the time from planting to visible flowering buds' appearance was decreased. The flowering time and rate of large bulbs were greatly influenced by cold exposure, and the vernalization pathway acted more actively at the floral transition stage. The floral transition of small bulbs was affected more by the photoperiod pathway. Moreover, it was speculated that cold exposure may promote greater sensitivity of the small bulbs to LD conditions. In addition, the expression of LlVRN1, LlFKF1, LlGI, LlCO5, LlCO7, LlCO16, LlFT1, LlFT3 and LlSOC1 was high during the process of floral transition, and LlCO13, LlCO14 and LlCO15 were highly expressed in the vegetative stage. The expression of LlCO13 and LlCO14 was different under different lighting conditions, and the flowering induction function of LlCO9 and LlFT3 was related to vernalization. Moreover, LlFKF1, LlGI, LlCO5, LlCO16, LlSOC1 and LlFT2 were involved in the entire growth process of plants, while LlCO6, LlCO16 and LlFT1 are involved in the differentiation and formation of small bulblets of plants after the inflorescence stage, and this process is also closely related to LD conditions. This study has great significance for understanding the molecular mechanisms of the vernalization and photoperiod flowering pathways of Lilium longiflorum.

Evaluation of triage strategies for high-risk human papillomavirus-positive women in cervical cancer screening: A multicenter randomized controlled trial in different resource settings in China.

Objective: We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus (hrHPV)-positive women in primary healthcare settings in China. Methods: This study was undertaken in 11 rural and 9 urban sites. Women aged 35-64 years old were enrolled. HrHPV-positive women were randomly allocated to liquid-based cytology (LBC), visual inspection with acetic acid and Lugol's iodine (VIA/VILI) (rural only) triage, or directly referred to colposcopy (direct COLP). At 24 months, hrHPV testing, LBC and VIA/VILI were conducted for combined screening. Results: In rural sites, 1,949 hrHPV-positive women were analyzed. A total of 852, 218 and 480 women were randomly assigned to direct COLP, LBC and VIA/VILI. At baseline, colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%. LBC (n=3 and n=7) or VIA/VILI (n=8 and n=26) could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia (CIN) 2 or worse and CIN3+ compared with direct COLP (n=14 and n=23). For the 24-month cumulative detection rate of CIN2+, VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP. When stratified by age, baseline LBC triage+ performed best (P<0.001), peaking among women aged 35-44 years (Ptrend=0.002). In urban sites, 1,728 women were hrHPV genotyping test positive. A total of 408, 571 and 568 women were randomly assigned to direct COLP for HPV16/18+, direct COLP for other hrHPV subtypes+, and LBC triage for other hrHPV subtypes+. LBC (n=12 and n=31) significantly decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ compared with direct COLP (n=14 and n=44). HPV16/18+ increased the 24-month cumulative detection rate of CIN2+ (17.89%, P<0.001). Conclusions: LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+ women and LBC triage for other hrHPV subtype+ women in urban settings might be feasible strategies.

BRS1 mediates plant redox regulation and cold responses.

BACKGROUND: Brassinosteroid-insensitive 1 suppressor 1 (BRS1) is a serine carboxypeptidase that mediates brassinosteroid signaling and participates in multiple developmental processes in Arabidopsis. However, little is known about the precise role of BRS1 in this context. RESULTS: In this study, we analyzed transcriptional and proteomic profiles of Arabidopsis seedlings overexpressing BRS1 and found that this gene was involved in both cold stress responses and redox regulation. Further proteomic evidence showed that BRS1 regulated cell redox by indirectly interacting with cytosolic NADP + -dependent isocitrate dehydrogenase (cICDH). One novel alternative splice form of BRS1 was identified in over-expression mutants brs1-1D, which may confer a new role in plant development and stress responses. CONCLUSIONS: This study highlights the role of BRS1 in plant redox regulation and stress responses, which extends our understanding of extracellular serine carboxypeptidases.

Analysis of miRNA-mediated regulation of flowering induction in Lilium × formolongi.

BACKGROUND: MicroRNAs play pivotal roles in plant vegetative phase change and flowering induction via integrating into multiple flowering pathways. Lilium × formolongi is an important ornamental lily cultivar that can flower within one year after sowing. However, it remains unresolved how miRNA-mediated regulation networks contribute to the L. × formolongi characteristics of a short vegetative growth period and rapid flowering. RESULTS: In this study, the small RNA libraries and one degradome library were constructed for L. × formolongi during vegetative growth and flowering initiation, and 366 conserved miRNAs and 32 novel miRNAs were identified. Additionally, 84 miRNAs were significantly differentially expressed during development. A total of 396 targets of 185 miRNAs were identified and validated through degradome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that functions of the targets were top enriched in the cold and cadmium ion responses, pentose phosphate pathway and carbon fixation in photosynthetic organisms. Furthermore, among 23 differentially expressed miRNA-target pairs, the miR156s-LfSPL2, miR172a-LfAP2 and miR164a-LfNAC pairs as well as miR159a-LfSPL2 were found to be relevant to flowering based on the correlation analysis of expression profiles in the miRNA libraries, degradome and transcriptome. A coexpression regulatory network focused on differentially expressed pairs was also constructed by WGCNA, and 14 miRNAs were considered putative key miRNAs during vegetative development and flowering induction. miR156a/ d/ e showed particularly strong relationships with other miRNAs in the coexpression network. CONCLUSIONS: This study provides cues for the further exploration of the regulatory mechanisms of short vegetative development and flowering in L. × formolongi.

Extensive-dynamic-range and high-resolution surface profiling with phase-sensitive spectral-domain white-light interferometry.

We demonstrate a Fourier-transform-based method for extensive-dynamic-range and high-resolution surface profiling using phase-sensitive spectral-domain white-light interferometry. By combining the frequency and phase of interference fringes, this method is capable of displacement measurement with nanometer-scale resolution and a dynamic range up to several millimeters. The performance of the method is demonstrated by surface profiling of a coin, gauge blocks, and a cell-phone circuit board.

lncRNA SNHG14 Plays a Role in Sepsis-Induced Acute Kidney Injury by Regulating miR-93.

Acute kidney injury (AKI) is a common organ injury in sepsis, which leads to poor prognosis. Long noncoding RNA (lncRNA) small nucleolus RNA host gene 14 (SNHG14) was recognized to induce cell injury in LPS-induced acute lung injury and Parkinson's disease. We want to investigate the functions and mechanisms of SNHG14 in sepsis-induced AKI. Increased expression of SNHG14 was observed in LPS-induced HK-2 cells, and this was due to the activation of the TLR4/NF-κB pathway. In vitro studies showed that SNHG14 was involved in the oxidative stress, inflammation, and apoptosis of LPS-induced HK-2 cells. Further investigations confirmed that SNHG14 exerted the functions via miR-93 which could regulate the activation of NF-κB and STAT3 signaling by targeting IRAK4 and IL-6R. We also found that silencing SNHG14 also alleviated cellular injury processes of IL-1ß and IL-6 in HK-2 cells via miR-93. We demonstrate that SNHG14 accelerates cellular injury in sepsis-induced AKI by activating IRAK4/NF-κB and IL-6R/STAT3 signaling via miR-93.

An Unsupervised Learning-Based Multi-Organ Registration Method for 3D Abdominal CT Images.

Medical image registration is an essential technique to achieve spatial consistency geometric positions of different medical images obtained from single- or multi-sensor, such as computed tomography (CT), magnetic resonance (MR), and ultrasound (US) images. In this paper, an improved unsupervised learning-based framework is proposed for multi-organ registration on 3D abdominal CT images. First, the explored coarse-to-fine recursive cascaded network (RCN) modules are embedded into a basic U-net framework to achieve more accurate multi-organ registration results from 3D abdominal CT images. Then, a topology-preserving loss is added in the total loss function to avoid a distortion of the predicted transformation field. Four public databases are selected to validate the registration performances of the proposed method. The experimental results show that the proposed method is superior to some existing traditional and deep learning-based methods and is promising to meet the real-time and high-precision clinical registration requirements of 3D abdominal CT images.

Development and validation of an artificial intelligence system for grading colposcopic impressions and guiding biopsies.

BACKGROUND: Colposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies. METHODS: Anonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance. RESULTS: The agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516, p < 0.001). For detecting pathological high-grade squamous intraepithelial lesion or worse (HSIL+), CAIADS showed higher sensitivity than the use of colposcopies interpreted by colposcopists at either biopsy threshold (low-grade or worse 90.5%, 95% CI 88.9-91.4% versus 83.5%, 81.5-85.3%; high-grade or worse 71.9%, 69.5-74.2% versus 60.4%, 57.9-62.9%; all p < 0.001), whereas the specificities were similar (low-grade or worse 51.8%, 49.8-53.8% versus 52.0%, 50.0-54.1%; high-grade or worse 93.9%, 92.9-94.9% versus 94.9%, 93.9-95.7%; all p > 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758. CONCLUSIONS: The CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer.