A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells.

Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.

Study on the diffusion and deposition law of pore slurry in gangue filling zone based on CFD-DEM coupling.

In this study, the slurry diffusion in a cavity filled with coal gangue was studied by combining experimental and numerical simulation methods. By calibrating slurry and particle materials, the grouting process in coal gangue filling area is simulated successfully, and the change of slurry diffusion flow field and particle movement and settling process in different dimensions are deeply analyzed. Both experimental and numerical simulation results show that the particle settlement presents a bell-shaped curve, which is of great significance for understanding the particle movement and settlement behavior in the filling cavity. In addition, it is found that the grouting speed has a significant effect on the particle settlement during the slurry diffusion process. When the grouting speed increases from 0.1m /s to 0.2m /s, the particle settlement and diffusion range increases about twice. In the plane flow field, it is observed that the outward diffusion trend and speed of grouting are more obvious. It is worth noting that in the whole process of grouting, it is observed that with the increase of grouting distance and depth, both the velocity of slurry and particles show a trend of rapid initial decline and gradually slow down, and the flow velocity of slurry near the grouting outlet at a flow rate of 0.2m/s is 2-4 times that of 0.1m/s. This provides important enlightenment for the porous seepage effect at different grouting speeds.

The splicing factor Prpf31 is required for hematopoietic stem and progenitor cell expansion during zebrafish embryogenesis.

Pre-mRNA splicing is a precise regulated process and is crucial for system development and homeostasis maintenance. Mutations in spliceosomal components have been found in various hematopoietic malignancies (HMs) and have been considered as oncogenic derivers of HMs. However, the role of spliceosomal components in normal and malignant hematopoiesis remains largely unknown. Pre-mRNA processing factor 31 (PRPF31) is a constitutive spliceosomal component, which mutations are associated with autosomal dominant retinitis pigmentosa. PRPF31 was found to be mutated in several HMs, but the function of PRPF31 in normal hematopoiesis has not been explored. In our previous study, we generated a prpf31 knockout (KO) zebrafish line and reported that Prpf31 regulates the survival and differentiation of retinal progenitor cells by modulating the alternative splicing of genes involved in mitosis and DNA repair. In this study, by using the prpf31 KO zebrafish line, we discovered that prpf31 KO zebrafish exhibited severe defects in hematopoietic stem and progenitor cell (HSPC) expansion and its sequentially differentiated lineages. Immunofluorescence results showed that Prpf31-deficient HSPCs underwent malformed mitosis and M phase arrest during HSPC expansion. Transcriptome analysis and experimental validations revealed that Prpf31 deficiency extensively perturbed the alternative splicing of mitosis-related genes. Collectively, our findings elucidate a previously undescribed role for Prpf31 in HSPC expansion, through regulating the alternative splicing of mitosis-related genes.

Development of a multi-phase CT-based radiomics model to differentiate heterotopic pancreas from gastrointestinal stromal tumor.

BACKGROUND: To investigate whether CT-based radiomics can effectively differentiate between heterotopic pancreas (HP) and gastrointestinal stromal tumor (GIST), and whether different resampling methods can affect the model's performance. METHODS: Multi-phase CT radiological data were retrospectively collected from 94 patients. Of these, 40 with HP and 54 with GISTs were enrolled between April 2017 and November 2021. One experienced radiologist manually delineated the volume of interest and then resampled the voxel size of the images to 0.5 × 0.5 × 0.5 mm3, 1 × 1 × 1 mm3, and 2 × 2 × 2 mm3, respectively. Radiomics features were extracted using PyRadiomics, resulting in 1218 features from each phase image. The datasets were randomly divided into training set (n = 66) and validation set (n = 28) at a 7:3 ratio. After applying multiple feature selection methods, the optimal features were screened. Radial basis kernel function-based support vector machine (RBF-SVM) was used as the classifier, and model performance was evaluated using the area under the receiver operating curve (AUC) analysis, as well as accuracy, sensitivity, and specificity. RESULTS: The combined phase model performed better than the other phase models, and the resampling method of 0.5 × 0.5 × 0.5 mm3 achieved the highest performance with an AUC of 0.953 (0.881-1), accuracy of 0.929, sensitivity of 0.938, and specificity of 0.917 in the validation set. The Delong test showed no significant difference in AUCs among the three resampling methods, with p > 0.05. CONCLUSIONS: Radiomics can effectively differentiate between HP and GISTs on CT images, and the diagnostic performance of radiomics is minimally affected by different resampling methods.

CTA-Based Radiomics and Area Change Rate Predict Infrarenal Abdominal Aortic Aneurysms Patients Events: A Multicenter Study.

RATIONALE AND OBJECTIVES: Clinical assessment of abdominal aortic aneurysm (AAA) intervention and rupture risk relies primarily on maximum diameter, but studies have shown that sole dependence on diameter has limitations. CTA-based radiomics, aneurysm and lumen area change rates (AACR, LACR) are measured to predict potential AAA events. MATERIALS AND METHODS: Between January 2017 and November 2022, 260 AAA patients from four centers who underwent two preoperative CTA examinations were included in this retrospective study. The endpoint event is defined as AAA rupture or repair. Patients were categorized into event and no-event groups based on the occurrence of endpoint event during follow-up. AACR and LACR were assessed using baseline and follow-up CTA, with radiomics features extracted from the baseline images. C-statistics and the Kaplan-Meier analysis were used to evaluate the predictive performance. RESULTS: A total of 193 eligible infrarenal AAA patients were included, 176 (91.2%) were man and 17 (8.8%) were woman. The median follow-up was 33.4 (14.2, 57.4) months. Seven models were constructed, comprising the aneurysm-based Radscore model, lumen-based Radscore model, intraluminal thrombus (ILT)-based Radscore model, AACR model, LACR model, clinical model (including high-density lipoprotein, D-dimer, and baseline aneurysm diameter), and a merged model. On the external validation set, the C-index of seven models were 0.713 (0.574-0.853), 0.642 (0.499-0.786), 0.727 (0.600-0.854), 0.619 (0.484-0.753), 0.680 (0.530-0.830), 0.690 (0.557-0.824) and 0.760 (0.651-0.869), in that order. In the Kaplan-Meier analysis, the merged model was best-divided patients into high/low-risk groups with Log-rank p < 0.0001. The AARC and LARC between non-event and event groups have significant differences (AACR: 1.4 cm2/y vs. 2.3 cm2/y, p < 0.0001; LACR: 0.3 cm2/y vs. 1.1 cm2/y, p < 0.0001). CONCLUSION: CTA-based radiomics, AACR and LACR have good predictive value for outcome event in infrarenal AAA patients.

Olfactory system structure and function in newly hatched and adult locusts.

An important question in neuroscience is how sensory systems change as animals grow and interact with the environment. Exploring sensory systems in animals as they develop can reveal how networks of neurons process information as the neurons themselves grow and the needs of the animal change. Here we compared the structure and function of peripheral parts of the olfactory pathway in newly hatched and adult locusts. We found that populations of olfactory sensory neurons (OSNs) in hatchlings and adults responded with similar tunings to a panel of odors. The morphologies of local neurons (LNs) and projection neurons (PNs) in the antennal lobes (ALs) were very similar in both age groups, though they were smaller in hatchlings, they were proportional to overall brain size. The odor evoked responses of LNs and PNs were also very similar in both age groups, characterized by complex patterns of activity including oscillatory synchronization. Notably, in hatchlings, spontaneous and odor-evoked firing rates of PNs were lower, and LFP oscillations were lower in frequency, than in the adult. Hatchlings have smaller antennae with fewer OSNs; removing antennal segments from adults also reduced LFP oscillation frequency. Thus, consistent with earlier computational models, the developmental increase in frequency is due to increasing intensity of input to the oscillation circuitry. Overall, our results show that locusts hatch with a fully formed olfactory system that structurally and functionally matches that of the adult, despite its small size and lack of prior experience with olfactory stimuli.

Upper gastrointestinal tract microbiota with oral origin in relation to oesophageal squamous cell carcinoma.

Introduction: Poor oral hygiene is linked to high risks of many systemic diseases, including cancers. Oral dysbiosis is closely associated with poor oral hygiene, causing tooth loss, gingivitis, and periodontitis. We provide a summary of studies and discuss the risk factors for oesophageal squamous cell carcinoma (ESCC) from a microbial perspective in this review.Methods: A literature search of studies published before December 31, 2022 from PubMed, Web of Science, and The Cochrane Library was performed. The search strategies included the following keywords: (1) oral care, oral health, oral hygiene, dental health, dental hygiene, tooth loss, teeth loss, tooth absence, missing teeth, edentulism, tooth brushing, mouthwash, and tooth cleaning; (2) esophageal, esophagus, oesophagus, and oesophageal; (3) cancer, carcinoma, tumor, and neoplasm.Discussion: Poor oral health, indicated by infrequent tooth brushing, chronic periodontitis, and tooth loss, has been associated with an increased risk of squamous dysplasia and ESCC. Oral microbial diversity and composition are profoundly dysregulated during oesophageal tumorigenesis. Similar to the oral microbiota, the oesophageal microbiota varies distinctly in multiple bacterial taxa in ESCC and gastric cardia adenocarcinoma, both of which have high co-occurrence rates in the "Oesophageal Cancer Belt". In addition, the potential roles of oncogenic viruses in ESCC have also been discussed. We also briefly explore the potential mechanisms underlying the tumor-promoting role of dysregulated microbiota for the development of therapeutic targeting strategies.Conclusion: Poor oral health is an established risk indicator of ESCC. The dysbiosis of microbiota in upper gastrointestinal tract that highly resembles the oral microbial ecosystem but with distinct features at individual sites contributes to the development and progression of ESCC.

The splicing factor DHX38 enables retinal development through safeguarding genome integrity.

DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, we demonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control.

Innate attraction and aversion to odors in locusts.

Many animals display innate preferences for some odors, but the physiological mechanisms underlying these preferences are poorly understood. Here, with behavioral tests, we establish a model system well suited to investigating olfactory mechanisms, the locust Schistocerca americana. We conducted open field tests in an arena designed to provide only olfactory cues to guide navigation choices. We found that newly hatched locusts navigated toward, and spent more time near, the odor of wheat grass than humidified air. In similar tests, we found that hatchlings avoided moderate concentrations of major individual components of the food blend odor, 1-hexanol (1% v/v) and hexanal (0.9% v/v) diluted in mineral oil relative to control presentations of unscented mineral oil. Hatchlings were neither attracted nor repelled by a lower concentration (0.1% v/v) of 1-hexanol but were moderately attracted to a low concentration (0.225% v/v) of hexanal. We quantified the behavior of the animals by tracking their positions with the Argos software toolkit. Our results establish that hatchlings have a strong, innate preference for food odor blend, but the valence of the blend's individual components may be different and may change depending on the concentration. Our results provide a useful entry point for an analysis of physiological mechanisms underlying innate sensory preferences.

Risk prediction of intraoperative pain in percutaneous microwave ablation of lung tumors under CT guidance.

OBJECTIVES: To evaluate the effect of intraoperative pain in microwave ablation of lung tumors (MWALT) on local efficacy and establish the pain risk prediction model. METHODS: It was a retrospectively study. Consecutive patients with MWALT from September 2017 to December 2020 were divided into mild and severe pain groups. Local efficacy was evaluated by comparing technical success, technical effectiveness, and local progression-free survival (LPFS) in two groups. All cases were randomly allocated into training and validation cohorts at a ratio of 7:3. A nomogram model was established using predictors identified by logistics regression in training dataset. The calibration curves, C-statistic, and decision curve analysis (DCA) were used to evaluate the accuracy, ability, and clinical value of the nomogram. RESULTS: A total of 263 patients (mild pain group: n = 126; severe pain group: n = 137) were included in the study. Technical success rate and technical effectiveness rate were 100% and 99.2% in the mild pain group and 98.5% and 97.8% in the severe pain group. LPFS rates at 12 and 24 months were 97.6% and 87.6% in the mild pain group and 91.9% and 79.3% in the severe pain group (p = 0.034; HR: 1.90). The nomogram was established based on three predictors: depth of nodule, puncture depth, and multi-antenna. The prediction ability and accuracy were verified by C-statistic and calibration curve. DCA curve suggested the proposed prediction model was clinically useful. CONCLUSIONS: Severe intraoperative pain in MWALT reduced the local efficacy. An established prediction model could accurately predict severe pain and assist physicians in choosing a suitable anesthesia type. CLINICAL RELEVANCE STATEMENT: This study firstly provides a prediction model for the risk of severe intraoperative pain in MWALT. Physicians can choose a suitable anesthesia type based on pain risk, in order to improve patients' tolerance as well as local efficacy of MWALT. KEY POINTS: • The severe intraoperative pain in MWALT reduced the local efficacy. • Predictors of severe intraoperative pain in MWALT were the depth of nodule, puncture depth, and multi-antenna. • The prediction model established in this study can accurately predict the risk of severe pain in MWALT and assist physicians in choosing a suitable anesthesia type.

ECG-based cardiodynamicsgram can reflect anomalous functional information in coronary artery disease.

BACKGROUND: The cardiodynamicsgram (CDG), a novel noninvasive method, extracts dynamic ST-T segment information from an electrocardiogram (ECG) through deterministic learning. HYPOTHESIS: The CDG can reflect anomalous functional information in coronary artery disease (CAD). METHODS: We retrospectively enrolled 456 patients with suspected CAD who underwent coronary computed tomography angiography (CCTA) from January 2020 to 2022, followed immediately by standard 12-lead ECG acquisition. Positivity for CAD were defined as CCTA ≥ 50% or CT-derived fractional flow reserve (CT-FFR) ≤ 0.8. A CDG value <0 was considered negative; otherwise, it was considered positive. We also evaluated the diagnostic performance of the CDG in the ECG-diagnosis-negative subgroup and in patients who had undergone invasive coronary angiography (ICA) after CCTA. RESULTS: Of 362 patients, 168 (46.41%) were positive for CAD, and 178 (49.17%) were men. The median age was 59 (52-66) years. The accuracy of the CDG in the diagnosis of CAD was 79.56%, with a sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) of 75.60%, 82.99%, and 0.836 (95% CI: 0.794-0.878), respectively. Similarly, in the ECG-diagnosis-negative subgroup (n = 223), the accuracy of the CDG was 80.27%, with an AUC of 0.842 (95% CI: 0.790-0.895). Among the 11 patients with CAD confirmed by ICA, 10 were diagnosed positive by the CDG. Furthermore, the CDG values and CT-FFR were correlated (r = -.395; p < .001). CONCLUSIONS: The ECG-based CDG has relatively high specificity and accuracy for the diagnosis of CAD and reflects functional cardiac information to some extent. It has the potential to be used as a screening tool for suspected CAD patients before CCTA.

A Novel Sample-to-Answer Visual Nucleic Acid Detection System for Adenovirus Detection.

Human adenoviruses (HAdVs) are common viruses that can cause local outbreaks in schools, communities and military camps, posing a huge threat to public health. An ideal POCT device for adenovirus detection in resource-limited settings is critical to control the spread of the virus. In this study, we developed an integrated and electricity-independent sample-to-answer system that can complete nucleic acid extraction, amplification, and detection at room temperature. This system is suitable for field and on-site detection because of its rapidity, sensitivity, lack of contamination, and lack of requirements of high-precision instruments and skilled technicians. It consists of two separate modules, ALP FINA (alkaline lysis with the paper-based filtration isolation of nucleic acid) and SV RPA (sealed and visual recombinase polymerase amplification). The extraction efficiency of ALP FINA can reach 48 to 84%, which is close to that of the conventional centrifuge column. The detection sensitivity of SV RPA is close to 10 copies/µL of AdvB and AdvE without aerosol contamination after repeated operations. When SV RPA was applied to the detection of nasopharyngeal swab samples of 19 patients who were infected with AdvB or AdvE as well as 10 healthy volunteers, its sensitivity and specificity reached 100%, respectively. IMPORTANCE HAdV infections are readily transmittable and, in some instances, highly contagious. Early and rapid diagnosis is essential for disease control. In this work, we developed a portable, disposable, and modularized sample-to-answer detection system for AdvB and AdvE, which rendered the entire test to be completely independent of electricity and other laboratory infrastructure. Thus, this detection system can be applied in resource-limited settings, and it has the potential to be further developed as an early diagnosis method in the field.

Ultrasound image-based deep learning to differentiate tubal-ovarian abscess from ovarian endometriosis cyst.

Objectives: We developed ultrasound (US) image-based convolutional neural networks (CNNs) to distinguish between tubal-ovarian abscess (TOA) and ovarian endometriosis cyst (OEC). Methods: A total of 202 patients who underwent US scanning and confirmed tubal-ovarian abscess or ovarian endometriosis cyst by pathology were enrolled in retrospective research, in which 171 patients (from January 2014 to September 2021) were considered the primary cohort (training, validation, and internal test sets) and 31 patients (from September 2021 to December 2021) were considered the independent test cohort. There were 68 tubal-ovarian abscesses and 89 OEC, 4 TOA and 10 OEC, and 10 TOA and 21 OEC patients belonging to training and validation sets, internal sets, and independent test sets, respectively. For the model to gain better generalization, we applied the geometric image and color transformations to augment the dataset, including center crop, random rotation, and random horizontal flip. Three convolutional neural networks, namely, ResNet-152, DenseNet-161, and EfficientNet-B7 were applied to differentiate tubal-ovarian abscess from ovarian endometriosis cyst, and their performance was compared with three US physicians and a clinical indicator of carbohydrate antigen 125 (CA125) on the independent test set. The area under the receiver operating characteristic curves (AUROCs) of accuracy, sensitivity, and specificity were used to evaluate the performance. Results: Among the three convolutional neural networks, the performance of ResNet-152 was the highest, with AUROCs of 0.986 (0.954-1). The AUROCs of the three physicians were 0.781 (0.620-0.942), 0.738 (0.629-848), and 0.683 (0.501-0.865), respectively. The clinical indicator CA125 achieved only 0.564 (0.315-0.813). Conclusion: We demonstrated that the CNN model based on the US image could discriminate tubal-ovarian abscess and ovarian endometriosis cyst better than US physicians and CA125. This method can provide a valuable predictive reference for physicians to screen tubal-ovarian abscesses and ovarian endometriosis cysts in time.

CT-based radiomics nomogram for differentiation of adrenal hyperplasia from lipid-poor adenoma: an exploratory study.

BACKGROUND: To establish and verify a radiomics nomogram for differentiating isolated micronodular adrenal hyperplasia (iMAD) from lipid-poor adenoma (LPA) based on computed tomography (CT)-extracted radiomic features. METHODS: A total of 148 patients with iMAD or LPA were divided into three cohorts: a training cohort (n = 72; 37 iMAD and 35 LPA), a validation cohort (n = 36; 22 iMAD and 14 LPA), and an external validation cohort (n = 40; 20 iMAD and 20 LPA). Radiomics features were extracted from contrast-enhanced and non-contrast CT images. The least absolute shrinkage and selection operator (LASSO) method was applied to develop a triphasic radiomics model and unenhanced radiomics model using reproducible radiomics features. A clinical model was constructed using certain laboratory variables and CT findings. Radiomics nomogram was established by selected radiomics signature and clinical factors. Nomogram performance was assessed by calibration curve, the areas under receiver operating characteristic curves (AUC), and decision curve analysis (DCA). RESULTS: Eleven and eight extracted features were finally selected to construct an unenhanced radiomics model and a triphasic radiomics model, respectively. There was no significant difference in AUC between the two models in the external validation cohort (0.838 vs. 0.843, p = 0.949). The radiomics nomogram inclusive of the unenhanced model, maximum diameter, and aldosterone showed the AUC of 0.951, 0.938, and 0.893 for the training, validation, and external validation cohorts, respectively. The nomogram showed good calibration, and the DCA demonstrated the superiority of the nomogram compared with the clinical factors model alone in terms of clinical usefulness. CONCLUSIONS: A radiomics nomogram based on unenhanced CT images and clinical variables showed favorable performance for distinguishing iMAD from LPA. In addition, an efficient unenhanced model can help avoid extra contrast-enhanced scanning and radiation risk.

Using deep learning to predict survival outcome in non-surgical cervical cancer patients based on pathological images.

PURPOSE: We analyzed clinical features and the representative HE-stained pathologic images to predict 5-year overall survival via the deep-learning approach in cervical cancer patients in order to assist oncologists in designing the optimal treatment strategies. METHODS: The research retrospectively collected 238 non-surgical cervical cancer patients treated with radiochemotherapy from 2014 to 2017. These patients were randomly divided into the training set (n = 165) and test set (n = 73). Then, we extract deep features after segmenting the HE-stained image into patches of size 224 × 224. A Lasso-Cox model was constructed with clinical data to predict 5-year OS. C-index evaluated this model performance with 95% CI, calibration curve, and ROC. RESULTS: Based on multivariate analysis, 2 of 11 clinical characteristics (C-index 0.68) and 2 of 2048 pathomic features (C-index 0.74) and clinical-pathomic model (C-index 0.83) of nomograms predict 5-year survival in the training set, respectively. In test set, compared with the pathomic and clinical characteristics used alone, the clinical-pathomic model had an AUC of 0.750 (95% CI 0.540-0.959), the clinical predictor model had an AUC of 0.729 (95% CI 0.551-0.909), and the pathomic model AUC was 0.703 (95% CI 0.487-0.919). Based on appropriate nomogram scores, we divided patients into high-risk and low-risk groups, and Kaplan-Meier survival probability curves for both groups showed statistical differences. CONCLUSION: We built a clinical-pathomic model to predict 5-year OS in non-surgical cervical cancer patients, which may be a promising method to improve the precision of personalized therapy.

Ultrasound Image-Based Deep Features and Radiomics for the Discrimination of Small Fat-Poor Angiomyolipoma and Small Renal Cell Carcinoma.

We evaluated the performance of ultrasound image-based deep features and radiomics for differentiating small fat-poor angiomyolipoma (sfp-AML) from small renal cell carcinoma (SRCC). This retrospective study included 194 patients with pathologically proven small renal masses (diameter ≤4 cm; 67 in the sfp-AML group and 127 in the SRCC group). We obtained 206 and 364 images from the sfp-AML and SRCC groups with experienced radiologist identification, respectively. We extracted 4024 deep features from the autoencoder neural network and 1497 radiomics features from the Pyradiomics toolbox; the latter included first-order, shape, high-order, Laplacian of Gaussian and Wavelet features. All subjects were allocated to the training and testing sets with a ratio of 3:1 using stratified sampling. The least absolute shrinkage and selection operator (LASSO) regression model was applied to select the most diagnostic features. Support vector machine (SVM) was adopted as the discriminative classifier. An optimal feature subset including 45 deep and 7 radiomics features was screened by the LASSO model. The SVM classifier achieved good performance in discriminating between sfp-AMLs and SRCCs, with areas under the curve (AUCs) of 0.96 and 0.85 in the training and testing sets, respectively. The classifier built using deep and radiomics features can accurately differentiate sfp-AMLs from SRCCs on ultrasound imaging.

Treatment planning computed tomography radiomics for predicting treatment outcomes and haematological toxicities in locally advanced cervical cancer treated with radiotherapy: A retrospective cohort study.

OBJECTIVE: We evaluated whether radiomic features extracted from planning computed tomography (CT) scans predict clinical end points in patients with locally advanced cervical cancer (LACC) undergoing intensity-modulated radiation therapy and brachytherapy. DESIGN: A retrospective cohort study. SETTING: Xiangya Hospital of Central South University, Changsha, Hunan, China. POPULATION: Two hundred and fifty-seven LACC patients who were treated with intensity-modulated radiotherapy from 2014 to 2017. METHODS: Patients were allocated into the training/validation sets (3:1 ratio) using proportional random sampling, resulting in the same proportion of groups in the two sets. We extracted 254 radiomic features from each of the gross target volume, pelvis and sacral vertebrae. The sequentially backward elimination support vector machine algorithm was used for feature selection and end point prediction. MAIN OUTCOMES AND MEASURES: Clinical end points include tumour complete response (CR), 5-year overall survival (OS), anaemia, and leucopenia. RESULTS: A combination of ten clinicopathological parameters and 34 radiomic features performed best for predicting CR (validation balanced accuracy: 80.8%). The validation balanced accuracy of 54 radiomic features was 85.8% for OS, and their scores can stratify patients into the low-risk and high-risk groups (5-year OS: 95.5% versus 36.4%, p < 0.001). The clinical and radiomic models were also predictive of anaemia and leucopenia (validation balanced accuracies: 71.0% and 69.9%). CONCLUSION: This study demonstrated that combining clinicopathological parameters with CT-based radiomics may have value for predicting clinical end points in LACC. If validated, this model may guide therapeutic strategy to optimise the effectiveness and minimise toxicity or treatment for LACC.

Evaluation and countermeasures of contracted services of Chinese family doctors from demanders' point of view - a case study of a city.

BACKGROUND: The "gatekeepers" for residents' health are their family doctors. The implementation of contracted services provided by family doctors is conducive to promoting hierarchical diagnosis and treatment and achieving the objective of providing residents comprehensive and full-cycle health services. Since its implementation in 2016, the contract service system for Chinese family doctors has yielded a number of results while also highlighting a number of issues that require further investigation. Consequently, the purpose of this study is to assess the impact of family doctors' contracted services in a Chinese city from the perspective of demanders (i.e., contracted residents), identify the weak links, and then propose optimization strategies. METHODS: In this study, a city in Shandong Province, China was selected as the sample city. In January 2020, 1098 contracted residents (including 40.5% men and 59.5% women) from 18 primary medical institutions (including township health centers and community health centers) were selected for on-site investigation. Take the PCAT-AS(Adult Short) scale revised in Chinese as the research tool to understand the medical experience of contracted residents in primary medical institutions, and interview some family doctors and residents to obtain more in-depth information. RESULTS: Among the four core dimensions of PCAT-AS, the score of Continuous was the highest (3.44 ± 0.58); The score of Coordinated was the lowest (3.08 ± 0.66); Among the three derived dimensions, the score of Family-centeredness was the highest (3.33 ± 0.65); The score of Culturally-competent was the lowest (2.93 ± 0.77). The types of contracting institutions, residents' age, marital status, occupation, and whether chronic diseases are confirmed are the influencing factors of PCAT scores. CONCLUSION: The family doctors' contracted services in the city has achieved certain results. At the same time, there are still some problems, such as difficult access to outpatient services during non-working hours, incomplete service items, an imperfect referral system, and inadequate utilization of traditional Chinese medicine services, it is recommended that the government continue to enhance and increase its investment in relevant policies and funds. Primary medical institutions should improve the compensation mechanism for family doctors and increase their work enthusiasm, improve and effectively implement the two-way referral system, gradually form an orderly hierarchical pattern of medical treatment, provide diversified health services in accordance with their own service capacity and the actual needs of residents, and improve the utilization rate of traditional Chinese medicine services in primary medical institutions.

CircFOXK2 Promotes the Progression of Osteoarthritis by Regulating the miR-4640-5p/NOTCH2 Axis.

OBJECTIVE: Osteoarthritis (OA) is the most common age-related chronic and disabling joint disease, frequently causing pain and disability in the adult population. Given that there are no proven disease-modifying drugs for OA, it is urgent to gain a deeper understanding of OA pathogenesis. This study intended to uncover the circFOXK2 regulation in OA. METHODS: Firstly, in vitro OA cell model was constructed by treating murine chondrocytes with interleukin (IL)-1ß. Then, a series of functional assays were conducted to evaluate the effect of circFOXK2 on OA progression in murine chondrocytes. Bioinformatics analysis and mechanism investigations were performed to investigate the competitive endogenous RNA (ceRNA) network of circFOXK2 in OA. RESULTS: CircFOXK2 is overexpressed in IL-1ß-treated chondrocyte. We confirmed the cyclic structure and cytoplasmic distribution of circFOXK2. Functionally, circFOXK2 promotes chondrocyte apoptosis and extracellular matrix (ECM) degradation but inhibiting chondrocyte proliferation. Mechanically, circFOXK2 competitively binds to microRNA-4640-5p (miR-4640-5p) to enhance NOTCH2 expression in OA, affecting OA progression. Besides, circFOXK2 could motivate the Notch pathway to accelerate OA progression. CONCLUSION: CircFOXK2/miR-4640-5p/NOTCH2 axis stimulates the Notch pathway to promote the transcription of inflammatory cytokines (IL33, IL17F and IL6), consequently facilitating OA progression in murine chondrocytes.

Tulp1 deficiency causes early-onset retinal degeneration through affecting ciliogenesis and activating ferroptosis in zebrafish.

Mutations in TUB-like protein 1 (TULP1) are associated with severe early-onset retinal degeneration in humans. However, the pathogenesis remains largely unknown. There are two homologous genes of TULP1 in zebrafish, namely tulp1a and tulp1b. Here, we generated the single knockout (tulp1a-/- and tulp1b-/-) and double knockout (tulp1-dKO) models in zebrafish. Knockout of tulp1a resulted in the mislocalization of UV cone opsins and the degeneration of UV cones specifically, while knockout of tulp1b resulted in mislocalization of rod opsins and rod-cone degeneration. In the tulp1-dKO zebrafish, mislocalization of opsins was present in all types of photoreceptors, and severe degeneration was observed at a very early age, mimicking the clinical manifestations of TULP1 patients. Photoreceptor cilium length was significantly reduced in the tulp1-dKO retinas. RNA-seq analysis showed that the expression of tektin2 (tekt2), a ciliary and flagellar microtubule structural component, was downregulated in the tulp1-dKO zebrafish. Dual-luciferase reporter assay suggested that Tulp1a and Tulp1b transcriptionally activate the promoter of tekt2. In addition, ferroptosis might be activated in the tulp1-dKO zebrafish, as suggested by the up-regulation of genes related to the ferroptosis pathway, the shrinkage of mitochondria, reduction or disappearance of mitochondria cristae, and the iron and lipid droplet deposition in the retina of tulp1-dKO zebrafish. In conclusion, our study establishes an appropriate zebrafish model for TULP1-associated retinal degeneration and proposes that loss of TULP1 causes defects in cilia structure and opsin trafficking through the downregulation of tekt2, which further increases the death of photoreceptors via ferroptosis. These findings offer insight into the pathogenesis and clinical treatment of early-onset retinal degeneration.