Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling.

Human somatic cells can be reprogrammed into neuron cell fate through regulation of a single transcription factor or application of small molecule cocktails. Methods: Here, we report that forskolin efficiently induces the conversion of human somatic cells into induced neurons (FiNs). Results: A large population of neuron-like phenotype cells was observed as early as 24-36 h post-induction. There were >90% TUJ1-, >80% MAP2-, and >80% NEUN-positive neurons at 5 days post-induction. Multiple subtypes of neurons were present among TUJ1-positive cells, including >60% cholinergic, >20% glutamatergic, >10% GABAergic, and >5% dopaminergic neurons. FiNs exhibited typical neural electrophysiological activity in vitro and the ability to survive in vitro and in vivo more than 2 months. Mechanistically, forskolin functions in FiN reprogramming by regulating the cAMP-CREB1-JNK signals, which upregulates cAMP-CREB1 expression and downregulates JNK expression. Conclusion: Overall, our studies identify a safer and efficient single-small-molecule-driven reprogramming approach for induced neuron generation and reveal a novel regulatory mechanism of neuronal cell fate acquisition.

Three-dimensional array of microbubbles sonoporation of cells in microfluidics.

Sonoporation is a popular membrane disruption technique widely applicable in various fields, including cell therapy, drug delivery, and biomanufacturing. In recent years, there has been significant progress in achieving controlled, high-viability, and high-efficiency cell sonoporation in microfluidics. If the microchannels are too small, especially when scaled down to the cellular level, it still remains a challenge to overcome microchannel clogging, and low throughput. Here, we presented a microfluidic device capable of modulating membrane permeability through oscillating three-dimensional array of microbubbles. Simulations were performed to analyze the effective range of action of the oscillating microbubbles to obtain the optimal microchannel size. Utilizing a high-precision light curing 3D printer to fabricate uniformly sized microstructures in a one-step on both the side walls and the top surface for the generation of microbubbles. These microbubbles oscillated with nearly identical amplitudes and frequencies, ensuring efficient and stable sonoporation within the system. Cells were captured and trapped on the bubble surface by the acoustic streaming and secondary acoustic radiation forces induced by the oscillating microbubbles. At a driving voltage of 30 Vpp, the sonoporation efficiency of cells reached 93.9% ± 2.4%.

Edge-Type Hyperintense Intracranial Artery Plaque: A Potential MRI Biomarker of Stroke Recurrence.

BACKGROUND: Identifying patients at high risk of stroke recurrence is important for stroke prevention and treatment. PURPOSE: To explore the characteristics of T1 hyperintense plaques (HIP) and their relationship with stroke recurrence in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). STUDY TYPE: Retrospective. POPULATION: One hundred fifty-seven patients with moderate-to-severe (≥50%) nonocclusive sICAS and MRI studies (42 females and 115 males, mean age 58.69 ± 10.68 years). FIELD STRENGTH/SEQUENCE: 3D higher-resolution black-blood T1-weighted fast-spin-echo sequence at 3.0 T. ASSESSMENT: HIP (signal intensity [SI] of plaque-to-adjacent gray matter >1.0 on non-contrast T1-weighted images) and non-HIP plaques were identified. HIP plaques were categorized as edge type (high SI adjacent to lumen) and non-edge type (high SI within plaque). Clinical and imaging features of different plaque types were compared. Stroke recurrence was assessed through telephone or medical records at 3 and 6 months, and then once a year post-MRI. The relationship between edge type and non-edge types HIP with stroke recurrence was analyzed. STATISTICAL TESTS: Student's t test, Mann-Whitney U-test, chi square test and Fisher's exact test to compare features between plaque types. Kaplan-Meier curves (with log-rank tests) and Cox proportional hazards regression to assess relationship between stroke recurrence and different plaque types. A two-tailed P-value of <0.05 was considered statistically significant. RESULTS: Of 157 culprit lesions, 87 (55%) were HIPs (43 edge type, 44 non-edge type) and 70 (45%) were non-HIPs. Plaque thickness, area, and volume were significantly higher for HIPs than for non-HIPs. Among patients with HIPs, edge type was significantly more likely in the posterior circulation (53.5% vs. 27.3%), and had significantly higher plaque thickness, length, area, volume, plaque burden, and remodeling index than non-edge type. Edge-type HIP was significantly more common than non-edge HIP in patients with diabetes mellitus (51.2% vs. 29.5%) and dyslipidemia (79.1% vs. 54.5%). During median follow-up of 27 months, 33 patients experienced stroke recurrence. Recurrence was associated with edge-type HIP (adjusted hazard ratio = 2.83; 95% confidence interval: 1.40-5.69), both in the overall cohort (34.9% vs. 15.8%) and in patients with HIP (34.9% vs. 9.0%). Age ≥60 years and edge-type HIP had a significant interaction. DATA CONCLUSIONS: Hyperintense plaque may be categorized as edge type or non-edge type. Edge-type HIP may be a potential MRI biomarker of stroke recurrence. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Distinguishing Intracranial Diabetes-Related Atherosclerotic Plaques: A High-Resolution Magnetic Resonance Imaging-Based Radiomics Study.

INTRODUCTION: Diabetes markedly affects the formation and development of intracranial atherosclerosis. The study was aimed at evaluating whether radiomics features can help distinguish plaques primarily associated with diabetes. MATERIALS AND METHODS: We retrospectively analyzed patients who were admitted to our center because of acute ischemic stroke due to intracranial atherosclerosis between 2016 and 2022. Clinical data, blood biomarkers, conventional plaque features, and plaque radiomics features were collected for all patients. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined from logistic regression models. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to describe diagnostic performance. The DeLong test was used to compare differences between models. RESULTS: Overall, 157 patients (115 men; mean age, 58.7 ± 10.7 years) were enrolled. Multivariate logistic regression analysis showed that plaque length (OR: 1.17; 95% CI: 1.07-1.28) and area (OR: 1.13; 95% CI: 1.02-1.24) were independently associated with diabetes. On combining plaque length and area as a conventional model, the AUCs of the training and validation cohorts for identifying diabetes patients were 0.789 and 0.720, respectively. On combining radiomics features on T1WI and contrast-enhanced T1WI sequences, a better diagnostic value was obtained in the training and validation cohorts (AUC: 0.889 and 0.861). The DeLong test showed the model combining radiomics and conventional plaque features performed better than the conventional model in both cohorts (p < 0.05). CONCLUSIONS: The use of radiomics features of intracranial plaques on high-resolution magnetic resonance imaging can effectively distinguish culprit plaques with diabetes as the primary pathological cause, which will provide new avenues of research into plaque formation and precise treatment.

Evaluating the impact of test-trace-isolate for COVID-19 management and alternative strategies.

There are many contrasting results concerning the effectiveness of Test-Trace-Isolate (TTI) strategies in mitigating SARS-CoV-2 spread. To shed light on this debate, we developed a novel static-temporal multiplex network characterizing both the regular (static) and random (temporal) contact patterns of individuals and a SARS-CoV-2 transmission model calibrated with historical COVID-19 epidemiological data. We estimated that the TTI strategy alone could not control the disease spread: assuming R0 = 2.5, the infection attack rate would be reduced by 24.5%. Increased test capacity and improved contact trace efficiency only slightly improved the effectiveness of the TTI. We thus investigated the effectiveness of the TTI strategy when coupled with reactive social distancing policies. Limiting contacts on the temporal contact layer would be insufficient to control an epidemic and contacts on both layers would need to be limited simultaneously. For example, the infection attack rate would be reduced by 68.1% when the reactive distancing policy disconnects 30% and 50% of contacts on static and temporal layers, respectively. Our findings highlight that, to reduce the overall transmission, it is important to limit contacts regardless of their types in addition to identifying infected individuals through contact tracing, given the substantial proportion of asymptomatic and pre-symptomatic SARS-CoV-2 transmission.

Long-chain noncoding RNA sequencing analysis reveals the molecular profiles of chemically induced mammary epithelial cells.

Long noncoding RNAs (lncRNAs) were important regulators affecting the cellular reprogramming process. Previous studies from our group have demonstrated that small molecule compounds can induce goat ear fibroblasts to reprogram into mammary epithelial cells with lactation function. In this study, we used lncRNA-Sequencing (lncRNA-seq) to analyze the lncRNA expression profile of cells before and after reprogramming (CK vs. 5i8 d). The results showed that a total of 3,970 candidate differential lncRNAs were detected, 1,170 annotated and 2,800 new lncRNAs. Compared to 0 d cells, 738 lncRNAs were significantly upregulated and 550 were significantly downregulated in 8 d cells. Heat maps of lncrnas and target genes with significant differences showed that the fate of cell lineages changed. Functional enrichment analysis revealed that these differently expressed (DE) lncRNAs target genes were mainly involved in signaling pathways related to reprogramming and mammary gland development, such as the Wnt signaling pathway, PI3K-Akt signaling pathway, arginine and proline metabolism, ECM-receptor interaction, and MAPK signaling pathway. The accuracy of sequencing was verified by real-time fluorescence quantification (RT-qPCR) of lncRNAs and key candidate genes, and it was also demonstrated that the phenotype and genes of the cells were changed. Therefore, this study offers a foundation for explaining the molecular mechanisms of lncRNAs in chemically induced mammary epithelial cells.

Dissecting the molecular trajectory of fibroblast reprogramming to chemically induced mammary epithelial cells.

Introduction: The plasticity of cell identity allows cellular reprogramming that manipulates the lineage of cells to generate the target cell types, bringing new avenues for disease modeling and autologous tailored cell therapy. Previously, we had already successfully established a technical platform for inducing fibroblast reprogramming to chemically induced mammary epithelial cells (CiMECs) by small-molecule compounds. However, exactly how the molecular mechanism driving the lineage conversion remains unknown. Methods: We employ the RNA-sequencing technology to investigate the transcriptome event during the reprogramming process and reveal the molecular mechanisms for the fate acquisition of mammary lineage. Results: The multi-step reprogramming process first overcomes multiple barriers, including the inhibition of mesenchymal characteristics, pro-inflammatory and cell death signals, and then enters an intermediate plastic state. Subsequently, the hormone and mammary development genes were rapidly activated, leading to the acquisition of the mammary program together with upregulation of the milk protein synthesis signal. Moreover, the gene network analyses reveal the potential relationship between the TGF-ß signaling pathway to mammary lineage activation, and the changes in the expression of these genes may play important roles in coordinating the reprogramming process. Conclusion: Together, these findings provide critical insights into the molecular route and mechanism triggered by small-molecule compounds that induce fibroblast reprogramming into the fate of mammary epithelial cells, and they also laid a foundation for the subsequent research on the development and differentiation of mammary epithelial cells and lactation.

Incremental value of enhanced plaque length for identifying intracranial atherosclerotic culprit plaques: a high-resolution magnetic resonance imaging study.

OBJECTIVES: Besides plaque enhancement grade, the incremental value of enhancement-related high-resolution MRI features in defining culprit plaques needs further evaluation. This study was focused on assessing whether plaque enhancement features contribute to culprit plaque identification and further risk stratification. METHODS: We retrospectively studied patients who experienced an acute ischaemic stroke and transient ischaemic attack due to intracranial atherosclerosis from 2016 to 2022. The enhancement features included enhancement grade, enhanced length, and enhancement quadrant. Associations between plaque enhancement features and culprit plaques, as well as diagnostic value, were investigated using logistic regression and receiver operating characteristic analyses. RESULTS: Overall, 287 plaques were identified, of which 231 (80.5%) and 56 (19.5%) were classified as culprit and non-culprit plaques, respectively. Comparison of the pre- and post-enhancement images revealed enhanced length longer than the plaque length in 46.32% of the culprit plaques. Multivariate logistic regression showed that enhanced length longer than plaque length (OR 6.77; 95% CI 2.47-18.51) and grade II enhancement (OR 7.00; 95% CI 1.69-28.93) were independently associated with culprit plaques. The area under the curve value for the combination of stenosis and plaque enhancement grade for the diagnosis of culprit plaques was 0.787, which increased significantly to 0.825 on the addition of enhanced length longer than the plaque length (p = 0.026 for DeLong's test). CONCLUSIONS: Enhanced length longer than the plaque length and grade II enhancement were independently associated with culprit plaques. The combination of the enhanced plaque features resulted in better culprit plaque identification.

Rapid direct conversion of bovine non-adipogenic fibroblasts into adipocyte-like cells by a small-molecule cocktail.

Introduction: The molecular regulation mechanism of fat deposition in bovine and its improvement on beef quality are important research directions in the livestock industry. The research of molecular mechanisms that govern the regulation and differentiation of adipocytes may conduct to understand the mechanism of obesity, lipid disorders, and fat deposition. In the recent decade, small-molecule compounds have been widely used in reprogramming and transdifferentiation fields, which can promote the induction efficiency, replace exogenous genes, or even induce cell fate conversion alone. Furthermore, small-molecule compound induction is expected to be a novel approach to generate new cell types from somatic cells in vitro and in vivo. Methods: In this study, we established rapid chemically induced platform for transdifferentiation of bovine ear fibroblasts into adipocyte-like cells using a small-molecule cocktail (Repsox, VPA, TTNPB). The chemically induced adipocytes (CiADCs) were characterized by lipid staining, qRT-PCR and WB. Bovine natural adipocytes were used as positive control, and the expression of adipocyte-related marker genes in CiADCs were analyzed. Moreover, RNA-Seq explore the mechanism of RVB in the regulation of Bovine adipocyte transdifferentiation. Results: In this study, the chemically induced adipocytes (CiADCs) could be identified as early as day 6. The CiADCs appeared to be circular and rich of lipid droplets. The adipocyte-specific genes of LPL, PPARγ, IGF1, GPD1, C/EBPδ, ADIPOQ, PCK2, FAS, C/EBPß, PPARGC1A, C/EBPα, and CFD were detected to be significantly upregulated in both CiADCs and natural adipocytes. Western blot analysis also confirmed the increase C/EBPα and PPARγ protein level in induced adipocytes (CiADCs-6d) treated with RVB. In addition, we also found that the signaling pathways (PPAR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, MAPK signaling pathway, and ECM-receptor interaction) regulated by the DEGs played a vital role in adipogenesis. Discussion: In the present study, a combination of small-molecule compounds RVB was used to transdifferentiate bovine ear fibroblasts into the chemically-induced adipocyte cells (CiADCs) that have a large number of lipid droplets. Importantly, the small-molecule cocktail significantly shortened the reprogramming turnaround time. The morphology of CiADCs is close to the "ring type" of natural differentiated adipocytes on sixth day. And, the CiADCs showed similar adipocyte-specific gene expression patterns to natural adipocytes. Furthermore, RVB increased protein expression of PPARγ and C/EBPα in the chemically-induced adipocytes (CiADCs-6d). Our findings reveal that the signaling pathways of C/EBPα and PPARγ play pivotal roles in this transdifferentiation process. In addition, we also found that the signaling pathways (PPAR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, MAPK signaling pathway, and ECM-receptor interaction) regulated by the DEGs played a vital role in adipogenesis. In general, this study provides valuable evidence to deepen our understanding of the molecular mechanism of small molecule cocktails in regulating adipogenesis.

Combined arthroscopic release with corticosteroid hydrodilatation versus corticosteroid hydrodilatation only in treating freezing-phase primary frozen shoulder: a randomized clinical trial.

BACKGROUND: There has been no ideal treatment for freezing-phase frozen shoulder to rapidly relieve pain and improve joint mobility. No any other team directly compared the effectiveness of combination of arthroscopic release and corticosteroid hydrodilatation with corticosteroid hydrodilatation only in treatment of freezing-phase frozen shoulder. METHODS: Seventy-two patients with freezing-phase frozen shoulder were randomly assigned to combined arthroscopic release with corticosteroid hydrodilatation (group A) or corticosteroid hydrodilatation only (group B). Clinical states were examined at baseline and periodically (Weeks 1, 4, 12, 24 and 1 year) after intervention by passive ROM; visual analog scale (VAS); UCLA and Disabilities of the Arm, Shoulder, and Hand (DASH) score. RESULTS: The passive ROM, VAS, UCLA and DASH scores always improved along the time points (all p < 0.01). The passive abduction (pAB), passive forward flexion (pFL), passive external rotation (pER), passive internal rotation (pIR) were better in group A than in group B at Week 1, 4, 12, 24 (all p < 0.01). At 1 year post-operation, the pFL and pIR were better in group A than in group B (all p < 0.01). VAS scores of group A were similar with those of group B (all p > 0.01), the differences between group A and group B were all lower than minimal clinically important difference (MCID). At Week 12, the UCLA sores and DASH scores were 26.8 ± 3.8, 14.2 ± 2.0 in group A versus 22.3 ± 3.4, 22.5 ± 3.1 in group B (all p < 0.01). At Week 24 post-operation, there were 32.7 ± 2.0, 9.8 ± 1.5 in group A versus 26.3 ± 3.6, 17.5 ± 3.5 in group B (all p < 0.01). At 1 year post-operation, there were 34.5 ± 0.8, 1.7 ± 1.5 in group A versus 32.1 ± 2.3, 8.8 ± 2.8 in group B (all p < 0.01), the differences of UCLA scores between group A and group B at Week 24 was higher than the MCID. There were no complications such as infection, nerve or vascular injury. CONCLUSIONS: Combined arthroscopic release with corticosteroid hydrodilatation would yield better results in passive ROM and function than corticosteroid hydrodilatation only. TRIAL REGISTRATION: ChiCTR1900024235, July 2, 2019 (Retrospectively registered).

Comparative Analysis of Acanthopanacis Cortex and Periplocae Cortex Using an Electronic Nose and Gas Chromatography-Mass Spectrometry Coupled with Multivariate Statistical Analysis.

Chinese Herbal Medicines (CHMs) can be identified by experts according to their odors. However, the identification of these medicines is subjective and requires long-term experience. The samples of Acanthopanacis Cortex and Periplocae Cortex used were dried cortexes, which are often confused in the market due to their similar appearance, but their chemical composition and odor are different. The clinical use of the two herbs is different, but the phenomenon of being confused with each other often occurs. Therefore, we used an electronic nose (E-nose) to explore the differences in odor information between the two species for fast and robust discrimination, in order to provide a scientific basis for avoiding confusion and misuse in the process of production, circulation and clinical use. In this study, the odor and volatile components of these two medicinal materials were detected by the E-nose and by gas chromatography-mass spectrometry (GC-MS), respectively. An E-nose combined with pattern analysis methods such as principal component analysis (PCA) and partial least squares (PLS) was used to discriminate the cortex samples. The E-nose was used to determine the odors of the samples and enable rapid differentiation of Acanthopanacis Cortex and Periplocae Cortex. GC-MS was utilized to reveal the differences between the volatile constituents of Acanthopanacis Cortex and Periplocae Cortex. In all, 82 components including 9 co-contained components were extracted by chromatographic peak integration and matching, and 24 constituents could be used as chemical markers to distinguish these two species. The E-nose detection technology is able to discriminate between Acanthopanacis Cortex and Periplocae Cortex, with GC-MS providing support to determine the material basis of the E-nose sensors' response. The proposed method is rapid, simple, eco-friendly and can successfully differentiate these two medicinal materials by their odors. It can be applied to quality control links such as online detection, and also provide reference for the establishment of other rapid detection methods. The further development and utilization of this technology is conducive to the further supervision of the quality of CHMs and the healthy development of the industry.

What is the role of aerosol transmission in SARS-Cov-2 Omicron spread in Shanghai?

The Omicron transmission has infected nearly 600,000 people in Shanghai from March 26 to May 31, 2022. Combined with different control measures taken by the government in different periods, a dynamic model was constructed to investigate the impact of medical resources, shelter hospitals and aerosol transmission generated by clustered nucleic acid testing on the spread of Omicron. The parameters of the model were estimated by least square method and MCMC method, and the accuracy of the model was verified by the cumulative number of asymptomatic infected persons and confirmed cases in Shanghai from March 26 to May 31, 2022. The result of numerical simulation demonstrated that the aerosol transmission figured prominently in the transmission of Omicron in Shanghai from March 28 to April 30. Without aerosol transmission, the number of asymptomatic subjects and symptomatic cases would be reduced to 130,000 and 11,730 by May 31, respectively. Without the expansion of shelter hospitals in the second phase, the final size of asymptomatic subjects and symptomatic cases might reach 23.2 million and 4.88 million by May 31, respectively. Our results also revealed that expanded vaccination played a vital role in controlling the spread of Omicron. However, even if the vaccination rate were 100%, the transmission of Omicron should not be completely blocked. Therefore, other control measures should be taken to curb the spread of Omicron, such as widespread antiviral therapies, enhanced testing and strict tracking quarantine measures. This perspective could be utilized as a reference for the transmission and prevention of Omicron in other large cities with a population of 10 million like Shanghai.

Parabolic relationship between SMAD3 expression level and the reprogramming efficiency of goat induced mammary epithelial cells.

Mammary epithelial cells are the only cells of mammary glands with lactation capacity. They are closely related to mammary development and milk yield. Our earlier studies showed that the transformation of goat fibroblasts into induced mammary epithelial cells (iMECs) was closely correlated with SMAD3 overexpression. Therefore, we further explored the role of SMAD3 on iMECs reprogramming in this study. The SMAD3 gene was overexpressed in goat ear fibroblasts using the tetracycline-induced expression method. The outcomes demonstrated that goat ear fibroblasts can be converted into iMECs by overexpressing the SMAD3 gene. In contrast, it was discovered that SMAD3 downregulation by RNA interference significantly decrease the reprogramming efficiency of iMECs. These results show that SMAD3 plays a key regulatory role in the reprogramming of iMECs. Surprisingly, we also found a parabolic relationship between SMAD3 expression level and iMECs reprogramming efficiency, and that the reprogramming efficiency was maximum when the addition of doxycycline concentration was 5 µg/ml. In light of this, our findings may offer new perspectives on the regulatory mechanism governing mammary epithelial cell fate in goats as well as a fresh approach to studying mammary development and differentiation in vitro.

Identification of high-risk intracranial plaques with 3D high-resolution magnetic resonance imaging-based radiomics and machine learning.

BACKGROUND: Identifying high-risk intracranial plaques is significant for the treatment and prevention of stroke. OBJECTIVE: To develop a high-risk plaque model using three-dimensional (3D) high-resolution magnetic resonance imaging (HRMRI) based radiomics features and machine learning. METHODS: 136 patients with documented symptomatic intracranial artery stenosis and available HRMRI data were included. Among these patients, 136 and 92 plaques were identified as symptomatic and asymptomatic plaques, respectively. A conventional model was developed by recording and quantifying the radiological plaque characteristics. Radiomics features from T1-weighted images (T1WI) and contrast-enhanced T1WI (CE-T1WI) were used to construct a high-risk plaque model with linear support vector classification (linear SVC). The radiological and radiomics features were combined to build a combined model. Receiver operating characteristic (ROC) curves were used to evaluate these models. RESULTS: Plaque length, burden, and enhancement were independently associated with clinical symptoms and were included in the conventional model, which had an AUC of 0.853 vs. 0.837 in the training and test sets. While the radiomics and the combined model showed an improved AUC: 0.923 vs. 0.925 for the training sets and 0.906 vs. 0.903 in the test sets. Both the radiomics model (p = 0.024, p = 0.018) and combined model (p = 0.042, p = 0.049) outperformed the conventional model in the two sets, whereas the performance of the combined model was not significantly different from that of the radiomics model in the two sets (p = 0.583 and p = 0.606). CONCLUSION: The radiomics model based on 3D HRMRI can accurately differentiate symptomatic from asymptomatic intracranial arterial plaques and significantly outperforms the conventional model.

[Measurement of external deviation angle of patellar tendon and its application on diagnosis of recurrent patellar dislocation].

OBJECTIVE: To compare computed tomography (CT) measurement results of external deviation angle of patellar tendon and tibia tubercle-trochlea groove (TT-TG), as well as the diagnostic ability and pathology in recurrent patellar dislocation threshold. METHODS: From January 2015 to March 2020, 46 patients with recurrent patella dislocation and 112 patients with non-patella dislocation were retrospectively analyzed. Forty-six patients with recurrent patella dislocation were divived into 2 groups according to TT-TG value, 11 patients with patellar dislocation with TT-TG≥20 mm(group A), including 7 males and 4 females, aged from 16 to 27 years old with an average of(21.00±3.98) years old; 35 patients with patellar dislocation with TT-TG<20 mm(group B), including 14 males and 21 females, aged from 16 to 37 years old with an average of(22.83±6.09) years old. While 112 patients with non-patella dislocation(group C) included 63 males and 49 females, aged 16 to 36 years old with an average of(22.87±5.69) years old. The measurement data of external deviation angle of patellar tendon and TT-TG value among three groups were compared. Spearman analysis was used to analyze correlation among them. Intraclass correlation coefficient (ICC) was used to determine repeatability within group. Receiver operating characteristic (ROC) area under the curve was used to evaluate diagnostic ability of parameters, and calculate osteotomy parameters of external deviation angle of patellar tendon, as well as external deviation angle of patellar tendon and TT-TG value in the diagnosis of recurrent patella diagnostic parameters of dislocation. RESULTS: External deviation angle of patellar tendon in group A, B and C was (22.04±3.09)°, (17.20±4.43)°and (10.22±3.45)° respectively;while TT-TG value was(21.15±0.71) mm, (15.97±2.69) mm and (11.12±3.77) mm, there were significance among three groups (P<0.01), and had difference between group A and B(P<0.01). There was strong positive correlation between external deviation angle of patellar tendon and TT-TG value (r=0.735, P<0.000 1). The intra-group ICC value(0.980, 0.982) of external deviation angle of patellar tendon in group A and B have better repeatability than TT-TG value (0.594, 0.775). The external deviation angle of patellar tendon in group C(0.956) and repeatability of TT-TG value(0.906) was very good. In the diagnosis of recurrent patellar dislocation, the area under ROC curve of external deviation angle of patellar tendon (0.916) was greater than TT-TG value(0.886), and diagnostic parameters were 13.84°and 14.69 mm, respectively;in tibial osteotomy, the area under ROC curve of external deviation angle of patellar tendon was 0.821, and osteotomy parameter was 20.15°. CONCLUSION: CT imaging could reliably measure external deviation angle of patellar tendon.There is a strong positive correlation between external deviation angle of patellar tendon and value of TT-TG, which could be used to determine pathological state of recurrent patellar dislocation, and external deviation angle of patellar tendon is superior to the TT-TG value in the diagnosis of recurrent patellar dislocation. The external deviation angle of patellar tendon could also be used to guide the formulation of the tibial osteotomy plan for recurrent patellar dislocation.

Quantifying human mixing patterns in Chinese provinces outside Hubei after the 2020 lockdown was lifted.

BACKGROUND: Contact patterns play a key role in the spread of respiratory infectious diseases in human populations. During the COVID-19 pandemic, the regular contact patterns of the population have been disrupted due to social distancing both imposed by the authorities and individual choices. Many studies have focused on age-mixing patterns before the COVID-19 pandemic, but they provide very little information about the mixing patterns in the COVID-19 era. In this study, we aim at quantifying human heterogeneous mixing patterns immediately after lockdowns implemented to contain COVID-19 spread in China were lifted. We also provide an illustrative example of how the collected mixing patterns can be used in a simulation study of SARS-CoV-2 transmission. METHODS AND RESULTS: In this work, a contact survey was conducted in Chinese provinces outside Hubei in March 2020, right after lockdowns were lifted. We then leveraged the estimated mixing patterns to calibrate a mathematical model of SARS-CoV-2 transmission. Study participants reported 2.3 contacts per day (IQR: 1.0-3.0) and the mean per-contact duration was 7.0 h (IQR: 1.0-10.0). No significant differences in average contact number and contact duration were observed between provinces, the number of recorded contacts did not show a clear trend by age, and most of the recorded contacts occurred with family members (about 78%). The simulation study highlights the importance of considering age-specific contact patterns to estimate the COVID-19 burden. CONCLUSIONS: Our findings suggest that, despite lockdowns were no longer in place at the time of the survey, people were still heavily limiting their contacts as compared to the pre-pandemic situation.

Radiomics versus Conventional Assessment to Identify Symptomatic Participants at Carotid Computed Tomography Angiography.

INTRODUCTION: Carotid computed tomography angiography (CTA) is routinely used for evaluating the atherosclerotic process. Radiomics allows the extraction of imaging markers of lesion heterogeneity and spatial complexity. These quantitative features can be used as the input for machine learning (ML). Therefore, in this study, we aimed to evaluate the diagnostic performance of radiomics-based ML assessment of carotid CTA data to identify symptomatic patients with carotid artery atherosclerosis. METHODS: In this retrospective study, participants with carotid artery atherosclerosis who underwent carotid CTA and brain magnetic resonance imaging from May 2010 to December 2017 were studied. The participants were grouped into symptomatic and asymptomatic groups according to their recent symptoms (determination of ipsilateral ischemic stroke). Eight conventional plaque features and 2,107 radiomics parameters were extracted from carotid CTA images. A radiomics-based ML model was fitted on the training set, and the radiomics-based ML model and conventional assessment were compared using the area under the curve (AUC) to identify symptomatic participants. RESULTS: After excluding participants with other stroke sources, 120 patients with 148 carotid arteries were analyzed. Of these 148 carotid arteries, 34 (22.97%) were classified into the symptomatic group. Plaque ulceration (odds ratio [OR] = 0.257; 95% confidence interval [CI], 0.094-0.698) and plaque enhancement (OR = 0.305; 95% CI, 0.094-0.988) were associated with the symptomatic status. Twenty radiomics parameters were chosen to be inputs in the radiomics-based ML model. In the identification of symptomatic participants, the discriminatory value of the radiomics-based ML model was significantly higher than that of the conventional assessment (AUC = 0.858 vs. AUC = 0.706, p = 0.021). CONCLUSION: Radiomics-based ML analysis improves the discriminatory power of carotid CTA in the identification of recent ischemic symptoms in patients with carotid artery atherosclerosis.

Automated quantitative lesion water uptake in acute stroke is a predictor of malignant cerebral edema.

OBJECTIVES: Net water uptake (NWU) has been shown to have a linear relationship with brain edema. Based on an automated-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) technique, we automatically derived NWU from baseline multimodal computed tomography (CT), namely ASPECTS-NWU. We aimed to determine if ASPECTS-NWU can predict the development of malignant cerebral edema (MCE). METHODS: One hundred and forty-six patients with large-vessel occlusion were retrospectively enrolled. Quantitative NWU based on automated-ASPECTS was measured both on nonenhanced CT (NECT) and CT angiography (CTA), namely NECT-ASPECT-NWU and CTA-ASPECTS-NWU. The correlation between ASPECTS-NWU and cerebral edema (CED) grades was calculated using Spearman rank correlation. Univariate logistic regression was used to assess the effect of radiological and clinical features on MCE, and a multivariable model with significant factors from the univariate regression analysis was built. Receiver operating characteristic (ROC) was obtained and area under curve (AUC) was compared. RESULTS: CTA-ASPECTS-NWU had a moderate positive correlation with CED grades (r = 0.62; 95% confidence interval [CI], 0.51-0.71; p < 0.001). The CTA-ASPECTS-NWU performed better than the NECT-ASPECTS-NWU with AUC: 0.88 vs. 0.71 (p < 0.001). Multivariable logistic regression model integrating CTA-ASPECTS-NWU, collateral score, and age showed the CTA-ASPECTS-NWU was an independent predictor of MCE with an AUC of 0.94 (95% CI: 0.90-0.98; p < 0.001). CONCLUSIONS: This study demonstrates that ASPECTS-NWU is a quantitative predictor of MCE after large-vessel occlusion of the middle cerebral artery territory. The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment. KEY POINTS: • The automated-ASPECTS technique can automatically detect the affected regions with early ischemic changes and NWU could be manually calculated. • The CTA-ASPECTS-NWU performs better than the NECT-ASPECTS-NWU on predicting the development of MCE. • The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment.

Model-based evaluation of alternative reactive class closure strategies against COVID-19.

There are contrasting results concerning the effect of reactive school closure on SARS-CoV-2 transmission. To shed light on this controversy, we developed a data-driven computational model of SARS-CoV-2 transmission. We found that by reactively closing classes based on syndromic surveillance, SARS-CoV-2 infections are reduced by no more than 17.3% (95%CI: 8.0-26.8%), due to the low probability of timely identification of infections in the young population. We thus investigated an alternative triggering mechanism based on repeated screening of students using antigen tests. Depending on the contribution of schools to transmission, this strategy can greatly reduce COVID-19 burden even when school contribution to transmission and immunity in the population is low. Moving forward, the adoption of antigen-based screenings in schools could be instrumental to limit COVID-19 burden while vaccines continue to be rolled out.

ASPECTS-Based Attenuation Changes on CT Angiography as an Imaging Biomarker to Predict Hemorrhagic Transformation in Acute Ischemic Stroke.

INTRODUCTION: Imaging-based early warning indicators and feasible stratification of acute ischemic stroke (AIS) patients with hemorrhagic transformation (HT), especially high-risk patients with parenchymal hematoma (PH), are crucial in determining subsequent treatment strategies. This study combined automated ASPECTS software with noncontrast CT (NCCT) and CTA source image (CTASI) attenuation changes using Hounsfield unit (HU) values to predict HT and PH in patients with AIS. MATERIALS AND METHODS: We retrospectively enrolled 172 consecutive patients with anterior circulation large-vessel occlusion between 2016 and 2020. Univariate and multivariate logistic regression and receiver operating characteristic (ROC) analyses were used to investigate the relationship between NCCT and CTASI-ASPECTS-HU, as well as other clinical and radiological parameters of HT and PH. Univariate and multivariate logistic regression analyses were performed to explore risk factors for HT or PH, and an ROC curve was used to evaluate their diagnostic values. RESULTS: A multivariate analysis showed that CTASI-ASPECTS-HU and NIHSS score were independent predictors of HT (CTASI-ASPECTS-HU: odds ratio (OR), 2.22; 95% CI, 1.01-4.92; NIHSS: OR, 1.07; 95% CI, 1.02-1.13) and PH (CTASI-ASPECTS-HU: OR, 6.51; 95% CI, 2.29-18.50; NIHSS: OR, 1.07; 95% CI, 1.01-1.13). According to ROC analysis, CTASI-ASPECTS-HU >0.09 identified HT (area under the curve, 0.70; sensitivity, 70.15%; specificity, 61.90%), and CTASI-ASPECTS-HU >0.10 identified PH (area under the curve, 0.79; sensitivity, 76.19%; specificity, 73.33%). The area under the curve for predicting HT or PH increased when CTASI-ASPECTS-HU was combined with NIHSS score (HT: area under the curve, 0.74; sensitivity, 73.13%; specificity, 70.48%; PH: area under the curve, 0.81; sensitivity, 85.71%; specificity, 72.38%). CONCLUSION: CTASI-ASPECTS-HU is a reliable radiological predictor of HT and PH in patients with AIS. Its predictive efficacy is moderately improved when combined with NIHSS score.