基因调控网络是基于微阵列基因表达数据,对基因之间表达关系依赖程度的一种仿真或重建。从基因表达数据挖掘基因之间存在的一定程度因果关系,对重构基因调控网络具有十分重要的意义。提出一种基于频繁原子序列关联熵的基因关联分析算法...基因调控网络是基于微阵列基因表达数据,对基因之间表达关系依赖程度的一种仿真或重建。从基因表达数据挖掘基因之间存在的一定程度因果关系,对重构基因调控网络具有十分重要的意义。提出一种基于频繁原子序列关联熵的基因关联分析算法,通过基因关联熵有效识别基因之间的因果关系,并采用启发式搜索策略构建基因关联贝叶斯调控网络(gene association based Bayesian regulatory,GABR)。与基因贝叶斯网络描述基因表达水平值之间依赖关系不同,GABR是一种基因序列贝叶斯网络,基因关联分析对象是生物组织样本的基因表达值排序并置换为基因列下标所形成的序列。算法的优势在于基因变量取值原子序列,该基因为原子序列的结果,基因关联熵以及条件概率分布的计算更符合基因表达数据分析的生物本质特征。ALARM网络模拟数据的实验结果表明,基因关联分析算法性能明显优于同类算法。在酵母菌微阵列基因数据GDS2267和小鼠胚胎基因GSE76118等GEO数据集进行实验,测试结果表明GABR方法重构的基因调控网络具有较高的有效性和鲁棒性。展开更多
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors ...Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.展开更多
Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive te...Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive text data.Their potential integration into clinical settings offers a promising avenue that could transform clinical diagnosis and decision-making processes in the future(Thirunavukarasu et al.,2023).This article aims to provide an in-depth analysis of LLMs’current and potential impact on clinical practices.Their ability to generate differential diagnosis lists underscores their potential as invaluable tools in medical practice and education(Hirosawa et al.,2023;Koga et al.,2023).展开更多
癌症是人类健康的第一杀手。随着测序技术的快速发展,积累了海量的癌症基因表达数据,利用计算方法进行致病基因预测成为癌症研究领域新的热点。然而,目前致病基因预测大多基于基因相互作用网络等,很少考虑网络局部连接与基因差异表达间...癌症是人类健康的第一杀手。随着测序技术的快速发展,积累了海量的癌症基因表达数据,利用计算方法进行致病基因预测成为癌症研究领域新的热点。然而,目前致病基因预测大多基于基因相互作用网络等,很少考虑网络局部连接与基因差异表达间的潜在联系。针对上述问题,首先利用患病前后的基因表达差异数据,通过互信息计算基因间的相关性并构建邻接网络,然后设计特征向量模型用于癌症致病基因预测。向量特征包括候选基因及其近邻的差异表达信息。从TCGA,OMIM和GEO等公共数据库获取癌症相关的致病与非致病基因以及患病前后基因差异表达数据进行实验,利用邻接网络中基因及其近邻的差异表达信息进行癌症致病基因预测(Differential Information of Gene and Nearest Neighbor for Cancer Pathogenic Gene Prediction,DICPG)。实验结果表明,DICPG癌症基因分类模型的生物学意义明显,分类精度和AUC等性能指标优于同类方法。展开更多
BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vom...BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vomiting,and constipation which may delay discharge.Liposomal bupivacaine,ketorolac,and scheduled acetaminophen have all demonstrated efficacy for management of post-operative pain in this population.AIM To assess the efficacy and safety of an opioid-sparing protocol utilizing a multimodal pain management approach in living kidney donors post-nephrectomy.METHODS Single-center,retrospective chart review study examining 52 living kidney donors(26 pre-protocol implementation,26 post-protocol implementation)from May 24th,2019 to September 27th,2023.Patients in the post-protocol group received intraoperative liposomal bupivacaine,hydromorphone PCA(until able to tolerate oral medications),15 mg of intravenous ketorolac every 6 hours for 3 doses,and scheduled oral acetaminophen,in addition to oxycodone as needed for moderate to severe pain.The primary endpoint was oral morphine equivalent(OME)use within 48 hours post-surgery.Secondary endpoints include average daily pain scale within 48 hours post-surgery,length of stay(LOS)(days),and incidence of new acute kidney injury(AKI)or gastrointestinal(GI)bleed during admission per provider.Differences between the pre-and post-protocol implementation groups were compared utilizing the exact Wilcoxon test for continuous variables and either the Fisher’s Exact orχ^(2) test for categorical variables.RESULTS Patients in the pre-protocol implementation group received more OME(mg)within 48 hours post-surgery when compared to the post-protocol group(median:84.5 vs 69.0).The median of total OME over the course of admission was numerically greater the pre-protocol group(105.0 vs 69.0),and was significantly more per LOS(41.3 vs 25.7,P=0.02).Average daily pain score was not statistically significantly different between the two groups on postoperative day 1(median:5.3 vs 4.4;P=0.43)and post-operative day 2(median:4.7 vs 5.2;P=0.96).No significant differences were found in provider-identified incidences of AKI or GI bleeding during admission.There was no difference in serum creatinine at the time of discharge between the two groups.CONCLUSION A multimodal,opioid-sparing pain management protocol was as effective for pain control and resulted in significantly less opioid daily exposure over LOS.No adverse events were found related to use of ketorolac in patients undergoing donor nephrectomy.Our findings suggest that an opioid-sparing protocol is both safe and effective at minimizing opioid exposure and managing post-operative pain within the first 48 hours post-surgery.展开更多
Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,mar...Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.展开更多
There is a growing body of clinical research on the utility of synthetic data derivatives,an emerging research tool in medicine.In nephrology,clinicians can use machine learning and artificial intelligence as powerful...There is a growing body of clinical research on the utility of synthetic data derivatives,an emerging research tool in medicine.In nephrology,clinicians can use machine learning and artificial intelligence as powerful aids in their clinical decision-making while also preserving patient privacy.This is especially important given the epidemiology of chronic kidney disease,renal oncology,and hypertension worldwide.However,there remains a need to create a framework for guidance regarding how to better utilize synthetic data as a practical application in this research.展开更多
Background:Early identification of concussion-related vision disorders(CRVDs)may improve outcomes by enabling earlier management,referral,and treatment.Objective eye tracking may provide additional data to support the...Background:Early identification of concussion-related vision disorders(CRVDs)may improve outcomes by enabling earlier management,referral,and treatment.Objective eye tracking may provide additional data to support the diagnose of CRVDs.The purpose of this study was to determine the utility of objective infrared eye tracking in identifying CRVDs among adolescents experiencing persisting post-concussive symptoms(PPCS)more than 28 days after injury.Methods:This was a prospective study of adolescents with PPCS evaluated with visio-vestibular examination(VVE),comprehensive vision examination,and an eye tracking device.Results:Of the 108 adolescents enrolled,67(62%)were diagnosed with a CRVD by comprehensive vision examination.On VVE,the near point of convergence break(5.5±3.2 cm vs.3.9±1.7 cm(mean±SD),p<0.001)and recovery(8.1±3.3 cm vs.6.8±2.3 cm,p=0.02)distinguished between those with and without CRVD.Concussion symptom provocation on VVE with horizontal saccades(35(52%)vs.12(29%),p=0.02)and horizontal vestibulo-ocular reflex testing(37(55%)vs.14(34%),p=0.03),and sway on tandem gait under the forward eyes closed condition(25(37%)vs.6(15%),p=0.01)also identified those with CRVD.From the eye tracking device,the BOX score(8.1±5.8 vs.5.2±4.1,p=0.007)and a metric of the left eye tracking along the bottom of the visual target(0.094±0.500 vs.-0.124±0.410,p=0.02)identified those with CRVD,with a multivariable receiver operating characteristic curve analysis,including the BOX score,achieving an area under the receiver operating characteristic curve of 0.7637.Conclusion:CRVDs are common in those with PPCS,with impact on recovery after concussion.Novel eye-tracking metrics can serve as an aid in the identification of those with CRVDs who would benefit from referral for comprehensive diagnosis and treatment.展开更多
基金supported by the National Natural Science Foundation of China(No.82160051,32100908)the Jiangxi Provincial Natural Science Foundation(No.20232BAB206018)+2 种基金the Science and Technology Research Project in the Education Department of Jiangxi Province,China(No.GJJ2200904)the Ph.D.Start-up Research Fund in Jiangxi University of Chinese Medicine(No.2020BSZR009)the Discipline of Chinese and Western Integrative Medicine in Jiangxi University of Chinese Medicine(No.zxyylxk20220103)。
文摘基因调控网络是基于微阵列基因表达数据,对基因之间表达关系依赖程度的一种仿真或重建。从基因表达数据挖掘基因之间存在的一定程度因果关系,对重构基因调控网络具有十分重要的意义。提出一种基于频繁原子序列关联熵的基因关联分析算法,通过基因关联熵有效识别基因之间的因果关系,并采用启发式搜索策略构建基因关联贝叶斯调控网络(gene association based Bayesian regulatory,GABR)。与基因贝叶斯网络描述基因表达水平值之间依赖关系不同,GABR是一种基因序列贝叶斯网络,基因关联分析对象是生物组织样本的基因表达值排序并置换为基因列下标所形成的序列。算法的优势在于基因变量取值原子序列,该基因为原子序列的结果,基因关联熵以及条件概率分布的计算更符合基因表达数据分析的生物本质特征。ALARM网络模拟数据的实验结果表明,基因关联分析算法性能明显优于同类算法。在酵母菌微阵列基因数据GDS2267和小鼠胚胎基因GSE76118等GEO数据集进行实验,测试结果表明GABR方法重构的基因调控网络具有较高的有效性和鲁棒性。
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
文摘Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.
文摘Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive text data.Their potential integration into clinical settings offers a promising avenue that could transform clinical diagnosis and decision-making processes in the future(Thirunavukarasu et al.,2023).This article aims to provide an in-depth analysis of LLMs’current and potential impact on clinical practices.Their ability to generate differential diagnosis lists underscores their potential as invaluable tools in medical practice and education(Hirosawa et al.,2023;Koga et al.,2023).
文摘癌症是人类健康的第一杀手。随着测序技术的快速发展,积累了海量的癌症基因表达数据,利用计算方法进行致病基因预测成为癌症研究领域新的热点。然而,目前致病基因预测大多基于基因相互作用网络等,很少考虑网络局部连接与基因差异表达间的潜在联系。针对上述问题,首先利用患病前后的基因表达差异数据,通过互信息计算基因间的相关性并构建邻接网络,然后设计特征向量模型用于癌症致病基因预测。向量特征包括候选基因及其近邻的差异表达信息。从TCGA,OMIM和GEO等公共数据库获取癌症相关的致病与非致病基因以及患病前后基因差异表达数据进行实验,利用邻接网络中基因及其近邻的差异表达信息进行癌症致病基因预测(Differential Information of Gene and Nearest Neighbor for Cancer Pathogenic Gene Prediction,DICPG)。实验结果表明,DICPG癌症基因分类模型的生物学意义明显,分类精度和AUC等性能指标优于同类方法。
文摘BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vomiting,and constipation which may delay discharge.Liposomal bupivacaine,ketorolac,and scheduled acetaminophen have all demonstrated efficacy for management of post-operative pain in this population.AIM To assess the efficacy and safety of an opioid-sparing protocol utilizing a multimodal pain management approach in living kidney donors post-nephrectomy.METHODS Single-center,retrospective chart review study examining 52 living kidney donors(26 pre-protocol implementation,26 post-protocol implementation)from May 24th,2019 to September 27th,2023.Patients in the post-protocol group received intraoperative liposomal bupivacaine,hydromorphone PCA(until able to tolerate oral medications),15 mg of intravenous ketorolac every 6 hours for 3 doses,and scheduled oral acetaminophen,in addition to oxycodone as needed for moderate to severe pain.The primary endpoint was oral morphine equivalent(OME)use within 48 hours post-surgery.Secondary endpoints include average daily pain scale within 48 hours post-surgery,length of stay(LOS)(days),and incidence of new acute kidney injury(AKI)or gastrointestinal(GI)bleed during admission per provider.Differences between the pre-and post-protocol implementation groups were compared utilizing the exact Wilcoxon test for continuous variables and either the Fisher’s Exact orχ^(2) test for categorical variables.RESULTS Patients in the pre-protocol implementation group received more OME(mg)within 48 hours post-surgery when compared to the post-protocol group(median:84.5 vs 69.0).The median of total OME over the course of admission was numerically greater the pre-protocol group(105.0 vs 69.0),and was significantly more per LOS(41.3 vs 25.7,P=0.02).Average daily pain score was not statistically significantly different between the two groups on postoperative day 1(median:5.3 vs 4.4;P=0.43)and post-operative day 2(median:4.7 vs 5.2;P=0.96).No significant differences were found in provider-identified incidences of AKI or GI bleeding during admission.There was no difference in serum creatinine at the time of discharge between the two groups.CONCLUSION A multimodal,opioid-sparing pain management protocol was as effective for pain control and resulted in significantly less opioid daily exposure over LOS.No adverse events were found related to use of ketorolac in patients undergoing donor nephrectomy.Our findings suggest that an opioid-sparing protocol is both safe and effective at minimizing opioid exposure and managing post-operative pain within the first 48 hours post-surgery.
基金supported by NIH grants NIH/NIA R01AG069401(to L.Q.)NIH/NHLBI U54HL165442(to K.T.)P30AR069619(to Penn Center for Musculoskeletal Disorders).
文摘Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.
文摘There is a growing body of clinical research on the utility of synthetic data derivatives,an emerging research tool in medicine.In nephrology,clinicians can use machine learning and artificial intelligence as powerful aids in their clinical decision-making while also preserving patient privacy.This is especially important given the epidemiology of chronic kidney disease,renal oncology,and hypertension worldwide.However,there remains a need to create a framework for guidance regarding how to better utilize synthetic data as a practical application in this research.
基金supported by funding from the National Institution of Neurological Disorders and Stroke(1R41NS103698-01A1 to CLM)。
文摘Background:Early identification of concussion-related vision disorders(CRVDs)may improve outcomes by enabling earlier management,referral,and treatment.Objective eye tracking may provide additional data to support the diagnose of CRVDs.The purpose of this study was to determine the utility of objective infrared eye tracking in identifying CRVDs among adolescents experiencing persisting post-concussive symptoms(PPCS)more than 28 days after injury.Methods:This was a prospective study of adolescents with PPCS evaluated with visio-vestibular examination(VVE),comprehensive vision examination,and an eye tracking device.Results:Of the 108 adolescents enrolled,67(62%)were diagnosed with a CRVD by comprehensive vision examination.On VVE,the near point of convergence break(5.5±3.2 cm vs.3.9±1.7 cm(mean±SD),p<0.001)and recovery(8.1±3.3 cm vs.6.8±2.3 cm,p=0.02)distinguished between those with and without CRVD.Concussion symptom provocation on VVE with horizontal saccades(35(52%)vs.12(29%),p=0.02)and horizontal vestibulo-ocular reflex testing(37(55%)vs.14(34%),p=0.03),and sway on tandem gait under the forward eyes closed condition(25(37%)vs.6(15%),p=0.01)also identified those with CRVD.From the eye tracking device,the BOX score(8.1±5.8 vs.5.2±4.1,p=0.007)and a metric of the left eye tracking along the bottom of the visual target(0.094±0.500 vs.-0.124±0.410,p=0.02)identified those with CRVD,with a multivariable receiver operating characteristic curve analysis,including the BOX score,achieving an area under the receiver operating characteristic curve of 0.7637.Conclusion:CRVDs are common in those with PPCS,with impact on recovery after concussion.Novel eye-tracking metrics can serve as an aid in the identification of those with CRVDs who would benefit from referral for comprehensive diagnosis and treatment.
