Advances in optical molecular imaging for neural visualization

Iatrogenic nerve injury is a significant complication in surgery, which can negatively impact patients’ quality of life. Currently, the main clinical neuroimaging methods, such as computed tomography, magnetic resonance imaging, and high-resolution ultrasonography, do not offer precise real-time positioning images for doctors during surgery. The clinical application of optical molecular imaging technology has led to the emergence of new concepts such as optical molecular imaging surgery, targeted surgery, and molecular-guided surgery. These advancements have made it possible to directly visualize surgical target areas, thereby providing a novel method for real-time identification of nerves during surgery planning. Unlike traditional white light imaging, optical molecular imaging technology enables precise positioning and identifies the cation of intraoperative nerves through the presentation of color images. Although a large number of experiments and data support its development, there are few reports on its actual clinical application. This paper summarizes the research results of optical molecular imaging technology and its ability to realize neural visualization. Additionally, it discusses the challenges neural visualization recognition faces and future development opportunities

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding Information: GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file : Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Research on the Dynamic Damage Properties and Determination of the Holmquist–Johnson–Cook Model Parameters for Sandstone

During blasting in engineering construction, the surrounding rock becomes unstable and is damaged under the impacts of multiple low-amplitude stress waves. It is of great practical significance to understand the damage evolution characteristics and the attenuation of the mechanical properties of rocks subjected to multiple stress waves. Single impact and repeated impact tests for sandstone were carried out using a split Hopkinson pressure bar (SHPB) loading system. The single impact test results showed that the sandstone materials were strain-rate-dependent, and the dynamic constitutive curve could be divided into four stages, namely the linear elastic stage, the new crack formation stage, the plastic strengthening stage and the unloading stage. The failure pattern mostly indicated splitting tensile failure, and the impact damage threshold was 45 J. The relationship between the damage and stress wave amplitude was D = 0.0029·exp${\boxed{f_{()}}}$(5.4127•σ/76.13) − 0.0504. The repeated impact test results showed that the dynamic compressive strength and the dynamic elastic modulus decreased, while the failure strain increased gradually as the number of impacts (n) increased. The sandstone specimen under repeated impacts had only one fracture surface compared with the single impact failure pattern. The cumulative damage presented the development form of ‘rapid rise–steady development–rapid rise’, and the damage evolution law could be expressed by D = 0.265 − 0.328·ln⁡⁡⁡${\boxed{f_{()}}}$(ln13.989/n). Finally, a set of methods to determine the Holmquist–Johnson–Cook (HJC) model parameters for sandstone was proposed based on a single impact test, repeated impact test, uniaxial compression test and triaxial compression test. The numerical simulation results of the SHPB test showed that the dynamic constitutive curves of sandstone were in good agreement with the experimental results

Research on the Dynamic Damage Properties and Determination of the Holmquist–Johnson–Cook Model Parameters for Sandstone

During blasting in engineering construction, the surrounding rock becomes unstable and is damaged under the impacts of multiple low-amplitude stress waves. It is of great practical significance to understand the damage evolution characteristics and the attenuation of the mechanical properties of rocks subjected to multiple stress waves. Single impact and repeated impact tests for sandstone were carried out using a split Hopkinson pressure bar (SHPB) loading system. The single impact test results showed that the sandstone materials were strain-rate-dependent, and the dynamic constitutive curve could be divided into four stages, namely the linear elastic stage, the new crack formation stage, the plastic strengthening stage and the unloading stage. The failure pattern mostly indicated splitting tensile failure, and the impact damage threshold was 45 J. The relationship between the damage and stress wave amplitude was D = 0.0029·exp({boxed{f_{()}}})(5.4127•σ/76.13) − 0.0504. The repeated impact test results showed that the dynamic compressive strength and the dynamic elastic modulus decreased, while the failure strain increased gradually as the number of impacts (n) increased. The sandstone specimen under repeated impacts had only one fracture surface compared with the single impact failure pattern. The cumulative damage presented the development form of ‘rapid rise–steady development–rapid rise’, and the damage evolution law could be expressed by D = 0.265 − 0.328·ln⁡⁡⁡({boxed{f_{()}}})(ln13.989/n). Finally, a set of methods to determine the Holmquist–Johnson–Cook (HJC) model parameters for sandstone was proposed based on a single impact test, repeated impact test, uniaxial compression test and triaxial compression test. The numerical simulation results of the SHPB test showed that the dynamic constitutive curves of sandstone were in good agreement with the experimental results

Effects of Blasting Vibrations on an Arch in the Jiaohuayu Tunnel Described by Energy Response Spectrum Analysis

The vibrations caused by tunnel blasting strongly affects the construction safety and progress of the tunnel itself. The arch vibration attenuation law, structural energy response, and safety criterion were systematically investigated using blasting vibration monitoring in the Jiaohuayu Tunnel. The peak particle velocity (PPV) at the vault was always larger than that at the arch waist and was greater than that at the sidewall, regardless of the direction. The arch waist was where the initial lining had the highest risk of damage. Existing safety criteria can be supplemented and improved using the maximum instantaneous input energy to measure the first passage damage, the hysteretic energy consumption to measure the cumulative damage, and the input-hysteretic energy criterion to judge the structural failure. The energy threshold of the first passage damage of the initial lining structure was 200 J, and the plastic cumulative damage was 3000 J of the test section. This study is important when evaluating the safety of a tunnel’s initial lining structure

Impact of postmaneuver sleep position on recurrence of benign paroxysmal positional vertigo.

BACKGROUND: The necessity of postural restriction to patients suffering from benign paroxysmal positional vertigo is controversial. OBJECTIVE: To investigate the impact of the sleep position after the repositioning maneuver on BPPV recurrence. METHODS: 150 unilateral BPPV patients who were treated by repositioning maneuver were distributed into two groups. The patients in group A were instructed to sleep in a semi-sitting position at an angle of approximately 30 degrees and refrain from sleeping on their BPPV affected side for one week. The patients in group B were told to sleep in any preferred position. The comparison of recurrence rates according to different actual sleep positions in one week and one month was performed. RESULTS: There was a statistically significant correlation between the sleeping side and the side affected by BPPV. Without instructions on postural restriction, most patients (82.9%, 73/88) avoided sleeping on their affected side. The patients sleeping on their affected side had a higher recurrence rate (35.3%) than ones sleeping in other positions in the first week after the repositioning maneuver (p<0.05, Chi-square test and Fisher's exact test). The patients sleeping randomly in following 3 weeks had a lower recurrence rate than ones sleeping in other position (p<0.05, Fisher's exact test). CONCLUSIONS: BPPV patients had a poor compliance to postural instructions. The habitual sleep side was associated with the side affected by BPPV. The patients sleeping on their affected side had a higher recurrence rate than those sleeping in other positions in first week after the repositioning maneuver

Effects of Blasting Vibrations on an Arch in the Jiaohuayu Tunnel Described by Energy Response Spectrum Analysis

The vibrations caused by tunnel blasting strongly affects the construction safety and progress of the tunnel itself. The arch vibration attenuation law, structural energy response, and safety criterion were systematically investigated using blasting vibration monitoring in the Jiaohuayu Tunnel. The peak particle velocity (PPV) at the vault was always larger than that at the arch waist and was greater than that at the sidewall, regardless of the direction. The arch waist was where the initial lining had the highest risk of damage. Existing safety criteria can be supplemented and improved using the maximum instantaneous input energy to measure the first passage damage, the hysteretic energy consumption to measure the cumulative damage, and the input-hysteretic energy criterion to judge the structural failure. The energy threshold of the first passage damage of the initial lining structure was 200 J, and the plastic cumulative damage was 3000 J of the test section. This study is important when evaluating the safety of a tunnel’s initial lining structure