A Computed Tomography Analysis of the Success of Spinal Fusion Using Ultra-Low Dose (0.7 mg per Facet) of Recombinant Human Bone Morphogenetic Protein 2 in Multilevel Adult Degenerative Spinal Deformity Surgery

Study Design Retrospective cohort study. Purpose To report on spinal fusion assessment using computed tomography (CT) after adult spinal deformity (ASD) surgery using ultra-low dose recombinant human bone morphogenetic protein 2 (RhBMP-2). Overview of Literature The reported dose of RhBMP-2 needed for successful spinal posterolateral fusion in ASD ranges from 10 to 20 mg per spinal level. This study reports the use of ultra-low dose of RhBMP-2 (0.07 mg per facet) to achieve spinal fusion in multilevel ASD surgery. Methods Consecutive patients who underwent ASD surgery using ultra-low dose RhBMP-2 were recruited. Routine postoperative CT analysis for spinal fusion was performed by two spine surgeons. Inter-observer agreement was calculated for facet fusion (FF) and interbody fusion (IBF) at 6 and 12 months after the procedure. Results Six consecutive ASD patients with a mean age of 62 years (28–72 years) were examined. Each patient received a total dose of 12 mg with an average dose of 0.69±0.2 mg (0.42–1 mg) per single FF and 1.38±0.44 mg (0.85–2 mg) for IBF. Total 131 FF and 15 IBF were examined in the study, with 88 FFs and nine IBFs being analyzed specifically at 6 months after the surgery. FF and IBF reported by surgeons A and B at 6 months were 97.7% vs. 91.9% FF, respectively (κ=0.95) and 100% vs. 100% IBF, respectively (κ=1). Two patients underwent longitudinal follow-up CT at 12 months, and the FF rates reported by surgeons A and B were 100% vs. 95.8%, respectively (κ=0.96). Five out of nine facet (56%) non-unions were identified at the cross-links. The remaining four facet pseudarthrosis were noted at 1–2 spinal levels caudal to the cross-links. At the final clinical follow-up, there was no rod breakage, deformity progression, neurological deficit, or symptom recurrence. The Oswestry Disability Index improved by an average of 32.8±6.3, while the mental component summary of the 36-item Short-Form Health Survey improved by an average of 4.7±2.1, and physical component summary improved by an average of 10.5±2.1. Conclusions To our knowledge, this is the first study to report a CT that defined 92%–98% FF and 100% IBF using the lowest reported dose of RhBMP-2 in multilevel ASD surgery. The use of ultra-low dose RhBMP-2 reduces the RhBMP-2 related complications and healthcare costs

Transmission Roles of Symptomatic and Asymptomatic COVID-19 Cases: A Modelling Study

Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9–80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0–34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks

Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles

BACKGROUND: Cell therapy is a promising strategy for tissue regeneration. Key to this strategy is mobilization and recruitment of exogenous or autologous stem/progenitor cells by cytokines. However, there is no effective cytokine delivery system available for clinic application, in particular for myocardial regeneration. The aim of this study was to develop a novel cytokine delivery system that is stable in solution at physiological pH. METHODS: Four groups of self-assembled chitosan oligosaccharide/heparin (CSO/H) nanoparticles were prepared with various volume ratios of chitosan oligosaccharide to heparin (5:2, 5:4, 4:15, 1:5) and characterized by laser diffraction, particle size analysis, and transmission electron microscopy. The encapsulation efficiency and loading content of two cytokines, ie, stromal cell-derived factor (SDF)-1α and vascular endothelial growth factor (VEGF) were quantified using an enzyme-linked immunosorbent assay. The biological activity of the loaded SDF-1α and VEGF was evaluated using the transwell migration assay and MTT assay. The dispersion profiles for the cytokine-loaded nanoparticles were quantified using fluorescence molecular tomography. RESULTS: CSO/H nanoparticles were prepared successfully in solution with physiological pH. The particle sizes in the four treatment groups were in the range of 96.2–210.5 nm and the zeta potential ranged from −29.4 mV to 24.2 mV. The loading efficiency in the CSO/H nanoparticle groups with the first three ratios was more than 90%. SDF-1α loaded into CSO/H nanoparticles retained its migration activity and VEGF loaded into CSO/H nanoparticles continued to show proliferation activity. The in vivo dispersion test showed that the CSO/H nanoparticles enabled to VEGF to accumulate locally for a longer period of time. CONCLUSION: CSO/H nanoparticles have a high cytokine loading capacity and allow cytokines to maintain their bioactivity for longer, are stable in an environment with physiological pH, and may be a promising cytokine delivery system for tissue regeneration

Residual swin transformer for classifying the types of cotton pests in complex background

BackgroundCotton pests have a major impact on cotton quality and yield during cotton production and cultivation. With the rapid development of agricultural intelligence, the accurate classification of cotton pests is a key factor in realizing the precise application of medicines by utilize unmanned aerial vehicles (UAVs), large application devices and other equipment.MethodsIn this study, a cotton insect pest classification model based on improved Swin Transformer is proposed. The model introduces the residual module, skip connection, into Swin Transformer to improve the problem that pest features are easily confused in complex backgrounds leading to poor classification accuracy, and to enhance the recognition of cotton pests. In this study, 2705 leaf images of cotton insect pests (including three insect pests, cotton aphids, cotton mirids and cotton leaf mites) were collected in the field, and after image preprocessing and data augmentation operations, model training was performed.ResultsThe test results proved that the accuracy of the improved model compared to the original model increased from 94.6% to 97.4%, and the prediction time for a single image was 0.00434s. The improved Swin Transformer model was compared with seven kinds of classification models (VGG11, VGG11-bn, Resnet18, MobilenetV2, VIT, Swin Transformer small, and Swin Transformer base), and the model accuracy was increased respectively by 0.5%, 4.7%, 2.2%, 2.5%, 6.3%, 7.9%, 8.0%.DiscussionTherefore, this study demonstrates that the improved Swin Transformer model significantly improves the accuracy and efficiency of cotton pest detection compared with other classification models, and can be deployed on edge devices such as utilize unmanned aerial vehicles (UAVs), thus providing an important technological support and theoretical basis for cotton pest control and precision drug application

Single-Cell Atlas of the Chinese Tongue Sole (Cynoglossus semilaevis) Ovary Reveals Transcriptional Programs of Oogenesis in Fish

16 pages, 6 figures, supplementary material https://www.frontiersin.org/articles/10.3389/fcell.2022.828124/full#supplementary-material.-- Data Availability Statement: According to national legislation/guidelines, specifically the Administrative Regulations of the People’s Republic of China on Human Genetic Resources (http://www.gov.cn/zhengce/content/2019-06/10/content_5398829.htm, http://english.www.gov.cn/policies/latest_releases/2019/06/10/content_281476708945462.htm), no additional raw data is available at this time. Data of this project can be accessed after an approval application to the China National Genebank (CNGB, https://db.cngb.org/cnsa/). Please refer to https://db.cngb.org/, or email: [email protected] for detailed application guidance. The accession code CNP0002319 should be included in the applicationOogenesis is a highly orchestrated process that depends on regulation by autocrine/paracrine hormones and growth factors. However, many details of the molecular mechanisms that regulate fish oogenesis remain elusive. Here, we performed a single-cell RNA sequencing (scRNA-seq) analysis of the molecular signatures of distinct ovarian cell categories in adult Chinese tongue sole (Cynoglossus semilaevis). We characterized the successive stepwise development of three germ cell subtypes. Notably, we identified the cellular composition of fish follicle walls, including four granulosa cell types and one theca cell type, and we proposed important transcription factors (TFs) showing high activity in the regulation of cell identity. Moreover, we found that the extensive niche–germline bidirectional communications regulate fish oogenesis, whereas ovulation in fish is accompanied by the coordination of simultaneous and tightly sequential processes across different granulosa cells. Additionally, a systems biology analysis of the homologous genes shared by Chinese tongue sole and macaques revealed remarkably conserved biological processes in germ cells and granulosa cells across vertebrates. Our results provide key insights into the cell-type-specific mechanisms underlying fish oogenesis at a single-cell resolution, which offers important clues for exploring fish breeding mechanisms and the evolution of vertebrate reproductive systemsThis work was supported by the National Nature Science Foundation of China (31722058, 31802275 and 31472269); the National Key R&D Program of China (2018YFD0900301); the AoShan Talents Cultivation Program Supported by Qingdao National Laboratory for Marine Science and Technology (2017ASTCP-ES06); the Taishan Scholar Project Fund of Shandong of China to C.S.; the National Ten-Thousands Talents Special Support Program to C.S.; the Central Public-interest Scientific Institution Basal Research Fund, CAFS (No.2020TD19); and the China Agriculture Research System (CARS-47-G03)With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

Single-cell-resolution transcriptome map revealed novel genes involved in testicular germ cell progression and somatic cells specification in Chinese tongue sole with sex reversal

19 pages, 7 figures, supporting information https://doi.org/10.1007/s11427-021-2236-4.-- Data availability: The data reported in this study are available in the CNGB Nucleotide Sequence Archive (CNSA: https://db.cngb.org/cnsa; accession number CNP0002135).Female-to-male sex reversals (pseudomales) are common in lower vertebrates and have been found in natural populations, which is a concern under rapid changes in environmental conditions. Pseudomales can exhibit altered spermatogenesis. However, the regulatory mechanisms underlying pseudomale spermatogenesis remain unclear. Here, we characterized spermatogenesis in Chinese tongue sole (Cynoglossus semilaevis), a species with genetic and environmental sex determination, based on a high-resolution single-cell RNA-seq atlas of cells derived from the testes of genotypic males and pseudomales. We identified five germ cell types and six somatic cell types and obtained a single-cell atlas of dynamic changes in gene expression during spermatogenesis in Chinese tongue sole, including alterations in pseudomales. We detected decreased levels of Ca2+ signaling pathway-related genes in spermatogonia, insufficient meiotic initiation in spermatocytes, and a malfunction of somatic niche cells in pseudomales. However, a cluster of CaSR genes and MAPK signaling factors were upregulated in undifferentiated spermatogonia of pseudomales. Additionally, we revealed that Z chromosome-specific genes, such as piwil2, dhx37, and ehmt1, were important for spermatogenesis. These results improve our understanding of reproduction after female-to-male sex-reversal and provide new insights into the adaptability of reproductive strategies in lower vertebratesThis work was supported by the National Key R&D Program of China (2018YFD0900301), the National Nature Science Foundation of China (31722058, 31802275, 31472269), the AoShan Talents Cultivation Program Supported by Qingdao National Laboratory for Marine Science and Technology (2017ASTCP-ES06), the Taishan Scholar Project Fund of Shandong of China to C.S., the National Ten-Thousands Talents Special Support Program to C.S., the Central Public-interest Scientific Institution Basal Research Fund, CAFS (2020TD19) and the China Agriculture Research System (CARS-47-G03)With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

ImportanceIt is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy.ObjectiveTo assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO.Design, Setting, and ParticipantsThis investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy.Main Outcomes and MeasuresThe primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours.ResultsAmong 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo.Conclusions and RelevanceAmong patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR2100051729</p

Intra-Arterial Tenecteplase Following Endovascular Reperfusion for Large Vessel Occlusion Acute Ischemic Stroke: The POST-TNK Randomized Clinical Trial.

The impact of adjunctive intra-arterial tenecteplase administration following near-complete to complete reperfusion by endovascular thrombectomy (EVT) for acute ischemic stroke is unknown. To assess the efficacy and adverse events of adjunctive intra-arterial tenecteplase in patients with large vessel occlusion stroke who had achieved near-complete to complete reperfusion (defined as a score on the expanded Thrombolysis in Cerebral Infarction [eTICI] scale of 2c to 3) after EVT. Investigator-initiated, randomized, open-label, blinded outcome assessment trial implemented at 34 hospitals in China among 540 patients with stroke due to proximal intracranial large vessel occlusion within 24 hours of the time they were last known to be well, with an eTICI score of 2c to 3 after EVT, and without prior intravenous thrombolysis. Recruitment took place between October 26, 2022, and March 1, 2024, with final follow-up on June 3, 2024. Eligible patients were randomly assigned to receive intra-arterial tenecteplase (n = 269) at 0.0625 mg/kg or no intra-arterial thrombolysis (control group; n = 271). The primary efficacy outcome was freedom from disability, defined as a score of 0 or 1 on the modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) at 90 days. The primary safety outcomes were death at 90 days and symptomatic intracranial hemorrhage within 48 hours. A total of 539 participants (99.8%) completed the trial (median age, 69 years; 221 female [40.9%]). The proportion with a modified Rankin Scale score of 0 or 1 at 90 days was 49.1% (132/269) in the intra-arterial tenecteplase group and 44.1% (119/270) in the control group (adjusted risk ratio, 1.15 [95% CI, 0.97-1.36]; P = .11). Ninety-day mortality was 16.0% and 19.3% (adjusted hazard ratio, 0.75 [95% CI, 0.50-1.13]; P = .16), respectively. The proportions of symptomatic intracranial hemorrhage were 6.3% and 4.4% (adjusted risk ratio, 1.43 [95% CI, 0.68-2.99]; P = .35), respectively. In patients with acute ischemic stroke due to large vessel occlusion presenting within 24 hours of time last known to be well and who had achieved near-complete to complete reperfusion after EVT, adjunctive intra-arterial tenecteplase did not significantly increase the likelihood of freedom from disability at 90 days. ChiCTR.org.cn Identifier: ChiCTR2200064809