Pub Date : 2024-11-13DOI: 10.1016/j.jhazmat.2024.136498
Fei Tian, Yuhua Wang, Zhenhe Huang, Aaron M. Qian, Chongjian Wang, Lei Tan, Stephen Edward McMillin, Chad Abresch, Zilong Zhang, Hualiang Lin
Exposure to air pollution has been associated with increased dementia. However, it remains unknown what specific metabolic mechanisms play a role in this relationship. We included 192,300 dementia-free participants from the UK Biobank cohort study. Annual concentrations of air pollution were assessed based on the residential address. Elastic net regression was performed to identify air pollution-related metabolites, and metabolic score was constructed. Cox regression models and covariate balancing generalized propensity scores (CBGPS) regression models were conducted to explore the longitudinal associations between air pollution/metabolic signatures and dementia risk. The underlying mechanisms between air pollution and dementia driven by metabolic signature or specific metabolites were also investigated. A total of 2,592 incident dementia cases were documented. We identified the metabolite profiles in response to air pollution exposure, including 87 metabolites for PM2.5, 65 metabolites for PM10, 76 metabolites for NO2, and 71 metabolites for NOx. The air pollution-related metabolic signatures were associated with increased risk of dementia, with hazard ratios (HR) of 1.17 (95% CI: 1.12, 1.22), 1.06 (95% CI: 1.02, 1.11), 1.16 (95% CI: 1.10, 1.21), and 1.17 (95% CI: 1.12, 1.22) for PM2.5, PM10, NO2 and NOx, respectively. The associations persisted using causal models. Metabolic signatures mediated the associations between air pollution exposure and dementia risk, with mediation proportions ranging from 6.57% to 12.71%. Additionally, we observed that a metabolite known as free cholesterol in medium VLDL (M-VLDL-FC) played a crucial mediating role. Our study provides novel insights into the metabolic mechanisms linking air pollution exposure to dementia risk.
{"title":"Metabolomic profiling identifies signatures and biomarkers linking air pollution to dementia risk: a prospective cohort study","authors":"Fei Tian, Yuhua Wang, Zhenhe Huang, Aaron M. Qian, Chongjian Wang, Lei Tan, Stephen Edward McMillin, Chad Abresch, Zilong Zhang, Hualiang Lin","doi":"10.1016/j.jhazmat.2024.136498","DOIUrl":"https://doi.org/10.1016/j.jhazmat.2024.136498","url":null,"abstract":"Exposure to air pollution has been associated with increased dementia. However, it remains unknown what specific metabolic mechanisms play a role in this relationship. We included 192,300 dementia-free participants from the UK Biobank cohort study. Annual concentrations of air pollution were assessed based on the residential address. Elastic net regression was performed to identify air pollution-related metabolites, and metabolic score was constructed. Cox regression models and covariate balancing generalized propensity scores (CBGPS) regression models were conducted to explore the longitudinal associations between air pollution/metabolic signatures and dementia risk. The underlying mechanisms between air pollution and dementia driven by metabolic signature or specific metabolites were also investigated. A total of 2,592 incident dementia cases were documented. We identified the metabolite profiles in response to air pollution exposure, including 87 metabolites for PM<sub>2.5</sub>, 65 metabolites for PM<sub>10</sub>, 76 metabolites for NO<sub>2</sub>, and 71 metabolites for NO<sub>x</sub>. The air pollution-related metabolic signatures were associated with increased risk of dementia, with hazard ratios (HR) of 1.17 (95% CI: 1.12, 1.22), 1.06 (95% CI: 1.02, 1.11), 1.16 (95% CI: 1.10, 1.21), and 1.17 (95% CI: 1.12, 1.22) for PM<sub>2.5</sub>, PM<sub>10</sub>, NO<sub>2</sub> and NO<sub>x</sub>, respectively. The associations persisted using causal models. Metabolic signatures mediated the associations between air pollution exposure and dementia risk, with mediation proportions ranging from 6.57% to 12.71%. Additionally, we observed that a metabolite known as free cholesterol in medium VLDL (M-VLDL-FC) played a crucial mediating role. Our study provides novel insights into the metabolic mechanisms linking air pollution exposure to dementia risk.","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"35 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chloroquine phosphate (CQ) poses strong biotoxicity on anammox process, and thus detoxifying is essential for the stable operation of anammox in treating CQ-bearing wastewater. Biochar has been proven to simultaneously detoxify pollutant and modulate nitrogen cycle in anammox by its shelter effect and electron exchange capacity (EEC) ability. To further improve the ability of biochar to promote the nitrogen metabolism of anammox, a KOH modification strategy was used to tailor a high-EEC biochar in this work. KOH modified biochar can bind CQ for detoxification driven by hydrogen bond, π–π interaction, and electrostatic interaction. Meanwhile, the EEC of modified biochar increased by 70% than that of pristine biochar, thus improving nitrogen removal efficiency by 55.6% and 9.5% than CQ and BC group, respectively. Besides, the microorganism regulated by modified biochar produced more α-helix configuration, improving EPS barrier ability to CQ and sludge granulation. Lastly, metagenomic analysis revealed that modified biochar can stimulate the Wood-Ljungdahl pathway, increased the relative abundance of CODH from 0.74% in CQ to 1.00% in modified BC group. It favored the proliferation of autotrophic microorganisms, especially increased the relative abundance of anammox bacteria by 86.8% than CQ group. This work will shed the light on integrating high-EEC biochar into anammox to cope with the micropollutants stress.
{"title":"KOH-modified biochar enhances nitrogen metabolism of the chloroquine phosphate-disturbed anammox: physical binding, EPS modulation and versatile metabolic hierarchy","authors":"Rui Hu, Xue Chen, Yule Han, Wanjiang Li, Shuting Zhang, Zhaobin Liu, Jiandong Wang, Xueqin Lu, Gang Luo, Shicheng Zhang, Guangyin Zhen","doi":"10.1016/j.jhazmat.2024.136467","DOIUrl":"https://doi.org/10.1016/j.jhazmat.2024.136467","url":null,"abstract":"Chloroquine phosphate (CQ) poses strong biotoxicity on anammox process, and thus detoxifying is essential for the stable operation of anammox in treating CQ-bearing wastewater. Biochar has been proven to simultaneously detoxify pollutant and modulate nitrogen cycle in anammox by its shelter effect and electron exchange capacity (EEC) ability. To further improve the ability of biochar to promote the nitrogen metabolism of anammox, a KOH modification strategy was used to tailor a high-EEC biochar in this work. KOH modified biochar can bind CQ for detoxification driven by hydrogen bond, π–π interaction, and electrostatic interaction. Meanwhile, the EEC of modified biochar increased by 70% than that of pristine biochar, thus improving nitrogen removal efficiency by 55.6% and 9.5% than CQ and BC group, respectively. Besides, the microorganism regulated by modified biochar produced more α-helix configuration, improving EPS barrier ability to CQ and sludge granulation. Lastly, metagenomic analysis revealed that modified biochar can stimulate the Wood-Ljungdahl pathway, increased the relative abundance of CODH from 0.74% in CQ to 1.00% in modified BC group. It favored the proliferation of autotrophic microorganisms, especially increased the relative abundance of anammox bacteria by 86.8% than CQ group. This work will shed the light on integrating high-EEC biochar into anammox to cope with the micropollutants stress.","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"7 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.jhazmat.2024.136492
Na Qiao, Xueyan Dai, Jing Chen, Huabin Cao, Guoliang Hu, Xiaoquan Guo, Ping Liu, Chenghong Xing, Fan Yang
Vanadium (V) exposure is known to induce renal toxicity, yet its specific effects on renal cell types and molecular mechanisms remain incompletely understood. We used single nucleus RNA sequencing (snRNA-seq) to characterize the impact of V on duck kidney cells at a cellular resolution. Following a 44-day exposure, immunofluorescence analysis revealed a significant increase in α-SMC expression in the renal interstitium, indicative of fibrotic response. SnRNA-seq identified 12 major cell types organized into 19 clusters within the kidney. Significant changes in cell composition were observed, notably an increase in proximal tubule cells (PT2 subtype), glomerular endothelial cells, principal cells, and alterations in immune cell proportions, while collecting duct intercalated cells (CD-IC) and thick ascending limb showed decreased percentages. Differential gene expression analysis highlighted pathways implicated in V toxicity across different cell types. Changes in drug metabolism-cytochrome P450, butanoate metabolism, and actin cytoskeleton regulation were exhibited by PT cells. Alterations in collecting duct secretion, oxidative phosphorylation, and bicarbonate reclamation pathways were shown in CD-IC cells. Furthermore, immune cells displayed changes in T cell receptor and chemokine signaling pathways, indicative of altered immune responses. Taken together, these findings contribute to a better shedding light on the pathogenic mechanisms of V induced renal injury.
已知钒（V）暴露会诱发肾毒性，但其对肾细胞类型和分子机制的具体影响仍不完全清楚。我们利用单核 RNA 测序（snRNA-seq）从细胞分辨率上描述了钒对鸭肾细胞的影响。暴露 44 天后，免疫荧光分析显示肾间质中 α-SMC 的表达显著增加，表明存在纤维化反应。SnRNA-seq鉴定出了肾脏内分为19个细胞簇的12种主要细胞类型。观察到细胞组成发生了显著变化，特别是近端小管细胞（PT2亚型）、肾小球内皮细胞、主细胞增加，免疫细胞比例发生变化，而集合管夹层细胞（CD-IC）和粗升肢细胞百分比下降。差异基因表达分析强调了不同细胞类型中与 V 毒性有关的通路。PT细胞在药物代谢-细胞色素P450、丁酸代谢和肌动蛋白细胞骨架调节方面发生了变化。CD-IC细胞的集合管分泌、氧化磷酸化和碳酸氢盐回收途径发生了变化。此外，免疫细胞显示出 T 细胞受体和趋化因子信号通路的变化，表明免疫反应发生了改变。总之，这些发现有助于更好地揭示V诱导的肾损伤的致病机制。
{"title":"Single Nucleus RNA Sequencing Reveals Cellular and Molecular Responses to Vanadium Exposure in Duck Kidneys","authors":"Na Qiao, Xueyan Dai, Jing Chen, Huabin Cao, Guoliang Hu, Xiaoquan Guo, Ping Liu, Chenghong Xing, Fan Yang","doi":"10.1016/j.jhazmat.2024.136492","DOIUrl":"https://doi.org/10.1016/j.jhazmat.2024.136492","url":null,"abstract":"Vanadium (V) exposure is known to induce renal toxicity, yet its specific effects on renal cell types and molecular mechanisms remain incompletely understood. We used single nucleus RNA sequencing (snRNA-seq) to characterize the impact of V on duck kidney cells at a cellular resolution. Following a 44-day exposure, immunofluorescence analysis revealed a significant increase in α-SMC expression in the renal interstitium, indicative of fibrotic response. SnRNA-seq identified 12 major cell types organized into 19 clusters within the kidney. Significant changes in cell composition were observed, notably an increase in proximal tubule cells (PT2 subtype), glomerular endothelial cells, principal cells, and alterations in immune cell proportions, while collecting duct intercalated cells (CD-IC) and thick ascending limb showed decreased percentages. Differential gene expression analysis highlighted pathways implicated in V toxicity across different cell types. Changes in drug metabolism-cytochrome P450, butanoate metabolism, and actin cytoskeleton regulation were exhibited by PT cells. Alterations in collecting duct secretion, oxidative phosphorylation, and bicarbonate reclamation pathways were shown in CD-IC cells. Furthermore, immune cells displayed changes in T cell receptor and chemokine signaling pathways, indicative of altered immune responses. Taken together, these findings contribute to a better shedding light on the pathogenic mechanisms of V induced renal injury.","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"8 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1038/s41746-024-01320-4
Mengyan Li, Xiaoou Li, Kevin Pan, Alon Geva, Doris Yang, Sara Morini Sweet, Clara-Lea Bonzel, Vidul Ayakulangara Panickan, Xin Xiong, Kenneth Mandl, Tianxi Cai
Electronic Health Record (EHR) systems are particularly valuable in pediatrics due to high barriers in clinical studies, but pediatric EHR data often suffer from low content density. Existing EHR code embeddings tailored for the general patient population fail to address the unique needs of pediatric patients. To bridge this gap, we introduce a transfer learning approach, MUltisource Graph Synthesis (MUGS), aimed at accurate knowledge extraction and relation detection in pediatric contexts. MUGS integrates graphical data from both pediatric and general EHR systems, along with hierarchical medical ontologies, to create embeddings that adaptively capture both the homogeneity and heterogeneity between hospital systems. These embeddings enable refined EHR feature engineering and nuanced patient profiling, proving particularly effective in identifying pediatric patients similar to specific profiles, with a focus on pulmonary hypertension (PH). MUGS embeddings, resistant to negative transfer, outperform other benchmark methods in multiple applications, advancing evidence-based pediatric research.
由于临床研究的高门槛，电子健康记录（EHR）系统对儿科尤为重要，但儿科 EHR 数据的内容密度往往较低。现有的电子病历代码嵌入是为普通患者量身定制的，无法满足儿科患者的独特需求。为了弥补这一缺陷，我们引入了一种迁移学习方法--MUltisource Graph Synthesis（MUGS），旨在儿科环境中进行准确的知识提取和关系检测。MUGS 整合了来自儿科和普通电子病历系统的图形数据以及分层医疗本体，创建了能自适应捕捉医院系统间同质性和异质性的嵌入。这些嵌入技术可实现完善的电子病历特征工程和细致入微的病人特征描述，在识别与特定特征相似的儿科病人（重点是肺动脉高压（PH））方面尤其有效。MUGS 嵌入抗负转移，在多种应用中优于其他基准方法，推动了循证儿科研究的发展。
{"title":"Multisource representation learning for pediatric knowledge extraction from electronic health records","authors":"Mengyan Li, Xiaoou Li, Kevin Pan, Alon Geva, Doris Yang, Sara Morini Sweet, Clara-Lea Bonzel, Vidul Ayakulangara Panickan, Xin Xiong, Kenneth Mandl, Tianxi Cai","doi":"10.1038/s41746-024-01320-4","DOIUrl":"10.1038/s41746-024-01320-4","url":null,"abstract":"Electronic Health Record (EHR) systems are particularly valuable in pediatrics due to high barriers in clinical studies, but pediatric EHR data often suffer from low content density. Existing EHR code embeddings tailored for the general patient population fail to address the unique needs of pediatric patients. To bridge this gap, we introduce a transfer learning approach, MUltisource Graph Synthesis (MUGS), aimed at accurate knowledge extraction and relation detection in pediatric contexts. MUGS integrates graphical data from both pediatric and general EHR systems, along with hierarchical medical ontologies, to create embeddings that adaptively capture both the homogeneity and heterogeneity between hospital systems. These embeddings enable refined EHR feature engineering and nuanced patient profiling, proving particularly effective in identifying pediatric patients similar to specific profiles, with a focus on pulmonary hypertension (PH). MUGS embeddings, resistant to negative transfer, outperform other benchmark methods in multiple applications, advancing evidence-based pediatric research.","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":" ","pages":"1-15"},"PeriodicalIF":12.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41746-024-01320-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.jhazmat.2024.136479
Guling Xing, Qiong Chen, Yiwen Sun, Jianquan Wang, Junbo Zhou, Lanxuan Sun, Quyu Shu, Jing Zhang, Mei Yan
Phytoremediation is an economical and effective strategy to remove cadmium (Cd) from polluted environments. To improve its efficiency, nanotechnology has been proposed to collaborate with hyperaccumulators in the remediation of Cd-polluted soils. However, the intricate structure-function relationship and the underlying regulatory mechanisms by which nanomaterials regulate Cd migration and conversion within the soil-plant system remained unrevealed. In this study, functional carbon nanodots (FCNs) were modified by doping with nitrogen and (or) sulfur elements. The synthesized nonmetallic atoms-doped FCNs were utilized to investigate their structure-function relationship and the regulatory mechanisms underlying their role in the phytoremediation of Cd-polluted soils by Tagetes patula L. FCNs-based nanomaterials can regulate the migration and bioaccumulation of Cd in the soil-plant system, which exhibits an obvious structural dependency. Specifically, the synergistic application of sulfur doped FCNs and Tagetes patula L. had the highest Cd removal efficiency of 53.2%, which was 20.1% higher than Tagetes patula L. alone. The uptake and migration of Cd in the soil-plant system are regulated by FCNs-based nanomaterials through both direct and indirect mechanisms, involving interfacial reactions, plant physiology regulation and environmental influence. This study not only sheds light on the fate of FCNs-based nanomaterials and Cd in the soil-plant system, but also provides innovative nanotools for reinforcing phytoremediation efficiency in contaminated soils.
{"title":"Synergistic promotion mechanism and structure-function relationship of nonmetallic atoms doped carbon nanodots driving Tagetes patula L. to remediate cadmium-contaminated soils","authors":"Guling Xing, Qiong Chen, Yiwen Sun, Jianquan Wang, Junbo Zhou, Lanxuan Sun, Quyu Shu, Jing Zhang, Mei Yan","doi":"10.1016/j.jhazmat.2024.136479","DOIUrl":"https://doi.org/10.1016/j.jhazmat.2024.136479","url":null,"abstract":"Phytoremediation is an economical and effective strategy to remove cadmium (Cd) from polluted environments. To improve its efficiency, nanotechnology has been proposed to collaborate with hyperaccumulators in the remediation of Cd-polluted soils. However, the intricate structure-function relationship and the underlying regulatory mechanisms by which nanomaterials regulate Cd migration and conversion within the soil-plant system remained unrevealed. In this study, functional carbon nanodots (FCNs) were modified by doping with nitrogen and (or) sulfur elements. The synthesized nonmetallic atoms-doped FCNs were utilized to investigate their structure-function relationship and the regulatory mechanisms underlying their role in the phytoremediation of Cd-polluted soils by <em>Tagetes patula</em> L. FCNs-based nanomaterials can regulate the migration and bioaccumulation of Cd in the soil-plant system, which exhibits an obvious structural dependency. Specifically, the synergistic application of sulfur doped FCNs and <em>Tagetes patula</em> L. had the highest Cd removal efficiency of 53.2%, which was 20.1% higher than <em>Tagetes patula</em> L. alone. The uptake and migration of Cd in the soil-plant system are regulated by FCNs-based nanomaterials through both direct and indirect mechanisms, involving interfacial reactions, plant physiology regulation and environmental influence. This study not only sheds light on the fate of FCNs-based nanomaterials and Cd in the soil-plant system, but also provides innovative nanotools for reinforcing phytoremediation efficiency in contaminated soils.","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"72 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karina D. Véliz, Claudia Pabón‐Pereira, Jeffrey P. Walters, Javiera Fernandez
The construction sector remains a significant contributor to global climate change, accounting for one‐third of global greenhouse gas emissions as well as a substantial portion of solid waste. In response to this pressing crisis, the adoption of circular business models (CBMs) emerges as a way to avoid negative environmental impacts. This study sought to model the interconnected factors influencing future CBM implementation in the Chilean construction industry using a system dynamics modeling approach. By engaging 20 sector experts in a system modeling workshop, it was possible to model and analyze these interconnected factors as a CBM System. The structural analysis of the resulting CBM system model revealed the triumvirate importance of information dissemination, certification of projects and products, and professional training and education. Recommendations for policy and practice that successfully leverage these mechanisms center on a three‐pronged approach of combining effective stakeholder collaboration, technological innovation, and thoughtful product certification frameworks. Overall, a systems thinking and modeling approach, such as the one applied here, is essential for identifying the complex interactions between enablers and barriers that promote or inhibit sustainable transformation in the construction industry in Chile and beyond.
{"title":"Applying circular business models in the Chilean construction sector: A system dynamics perspective","authors":"Karina D. Véliz, Claudia Pabón‐Pereira, Jeffrey P. Walters, Javiera Fernandez","doi":"10.1002/bse.4052","DOIUrl":"https://doi.org/10.1002/bse.4052","url":null,"abstract":"The construction sector remains a significant contributor to global climate change, accounting for one‐third of global greenhouse gas emissions as well as a substantial portion of solid waste. In response to this pressing crisis, the adoption of circular business models (CBMs) emerges as a way to avoid negative environmental impacts. This study sought to model the interconnected factors influencing future CBM implementation in the Chilean construction industry using a system dynamics modeling approach. By engaging 20 sector experts in a system modeling workshop, it was possible to model and analyze these interconnected factors as a CBM System. The structural analysis of the resulting CBM system model revealed the triumvirate importance of information dissemination, certification of projects and products, and professional training and education. Recommendations for policy and practice that successfully leverage these mechanisms center on a three‐pronged approach of combining effective stakeholder collaboration, technological innovation, and thoughtful product certification frameworks. Overall, a systems thinking and modeling approach, such as the one applied here, is essential for identifying the complex interactions between enablers and barriers that promote or inhibit sustainable transformation in the construction industry in Chile and beyond.","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"33 1","pages":""},"PeriodicalIF":13.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1038/s41746-024-01296-1
Courtney J. Lightfoot, Thomas J. Wilkinson, Gurneet K. Sohansoha, Clare L. Gillies, Noemi Vadaszy, Ella C. Ford, Melanie J. Davies, Thomas Yates, Alice C. Smith, Matthew P. M. Graham-Brown, On behalf of SMILE-K collaborators
My Kidneys & Me (MK&M), a digital health intervention delivering specialist health and lifestyle education for people with CKD, was developed and its effects tested (SMILE-K trial, ISRCTN18314195, 18/12/2020). 420 adult patients with CKD stages 3–4 were recruited and randomised 2:1 to intervention (MK&M) (n = 280) or control (n = 140) groups. Outcomes, including Patient Activation Measure (PAM-13), were collected at baseline and 20 weeks. Complete case (CC) and per-protocol (PP) analyses were conducted. 210 (75%) participants used MK&M more than once. PAM-13 increased at 20 weeks compared to control (CC: +3.1 (95%CI: −0.2 to 6.4), P = 0.065; PP: +3.6 (95%CI: 0.2 to 7.0), P = 0.041). In those with low activation at baseline, significant between-group differences were observed (CC: +6.6 (95%CI: 1.3 to 11.9), P = 0.016; PP: +9.2 (95%CI: 4.0 to 14.6), P < 0.001) favouring MK&M group. MK&M improved patient activation in those who used the resource compared to standard care, although the overall effect was non-significant. The greatest benefits were seen in those with low activation.
{"title":"The effects of a digital health intervention on patient activation in chronic kidney disease","authors":"Courtney J. Lightfoot, Thomas J. Wilkinson, Gurneet K. Sohansoha, Clare L. Gillies, Noemi Vadaszy, Ella C. Ford, Melanie J. Davies, Thomas Yates, Alice C. Smith, Matthew P. M. Graham-Brown, On behalf of SMILE-K collaborators","doi":"10.1038/s41746-024-01296-1","DOIUrl":"10.1038/s41746-024-01296-1","url":null,"abstract":"My Kidneys & Me (MK&M), a digital health intervention delivering specialist health and lifestyle education for people with CKD, was developed and its effects tested (SMILE-K trial, ISRCTN18314195, 18/12/2020). 420 adult patients with CKD stages 3–4 were recruited and randomised 2:1 to intervention (MK&M) (n = 280) or control (n = 140) groups. Outcomes, including Patient Activation Measure (PAM-13), were collected at baseline and 20 weeks. Complete case (CC) and per-protocol (PP) analyses were conducted. 210 (75%) participants used MK&M more than once. PAM-13 increased at 20 weeks compared to control (CC: +3.1 (95%CI: −0.2 to 6.4), P = 0.065; PP: +3.6 (95%CI: 0.2 to 7.0), P = 0.041). In those with low activation at baseline, significant between-group differences were observed (CC: +6.6 (95%CI: 1.3 to 11.9), P = 0.016; PP: +9.2 (95%CI: 4.0 to 14.6), P < 0.001) favouring MK&M group. MK&M improved patient activation in those who used the resource compared to standard care, although the overall effect was non-significant. The greatest benefits were seen in those with low activation.","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":" ","pages":"1-13"},"PeriodicalIF":12.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41746-024-01296-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1158/0008-5472.can-24-1142
Tingting Wang, Lingling Liu, Jie Fang, Hongjian Jin, Sivaraman Natarajan, Heather Sheppard, Meifen Lu, Gregory Turner, Thomas Confer, Melissa Johnson, Jeffrey Steinberg, Larry Ha, Nour Yadak, Richa Jain, David J. Picketts, Xiaotu Ma, Andrew Murphy, Andrew M. Davidoff, Evan S. Glazer, John Easton, Xiang Chen, Ruoning Wang, Jun Yang
c-MYC is an important driver of high-risk neuroblastoma. A lack of c-MYC–driven genetically engineered mouse models (GEMM) has hampered the ability to better understand mechanisms of neuroblastoma oncogenesis and to develop effective therapies. Here, we showed that conditional c-MYC induction via Cre recombinase driven by a tyrosine hydroxylase (Th) promoter led to a preponderance of PDX1+ somatostatinoma, a type of pancreatic neuroendocrine tumor (PNET). However, c-MYC activation via an improved Cre recombinase driven by a dopamine β-hydroxylase (Dbh) promoter resulted in neuroblastoma development. The c-MYC murine neuroblastoma tumors recapitulated the pathologic and genetic features of human neuroblastoma and responded to anti-GD2 immunotherapy and DFMO, an FDA-approved inhibitor targeting the MYC transcriptional target ODC1. Thus, c-MYC overexpression results in different but related tumor types depending on the targeted cell. The GEMMs represent valuable tools for testing immunotherapies and targeted therapies for these diseases.
{"title":"Conditional Activation of c-MYC in Distinct Catecholaminergic Cells Drives Development of Neuroblastoma or Somatostatinoma","authors":"Tingting Wang, Lingling Liu, Jie Fang, Hongjian Jin, Sivaraman Natarajan, Heather Sheppard, Meifen Lu, Gregory Turner, Thomas Confer, Melissa Johnson, Jeffrey Steinberg, Larry Ha, Nour Yadak, Richa Jain, David J. Picketts, Xiaotu Ma, Andrew Murphy, Andrew M. Davidoff, Evan S. Glazer, John Easton, Xiang Chen, Ruoning Wang, Jun Yang","doi":"10.1158/0008-5472.can-24-1142","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-1142","url":null,"abstract":"c-MYC is an important driver of high-risk neuroblastoma. A lack of c-MYC–driven genetically engineered mouse models (GEMM) has hampered the ability to better understand mechanisms of neuroblastoma oncogenesis and to develop effective therapies. Here, we showed that conditional c-MYC induction via Cre recombinase driven by a tyrosine hydroxylase (Th) promoter led to a preponderance of PDX1+ somatostatinoma, a type of pancreatic neuroendocrine tumor (PNET). However, c-MYC activation via an improved Cre recombinase driven by a dopamine β-hydroxylase (Dbh) promoter resulted in neuroblastoma development. The c-MYC murine neuroblastoma tumors recapitulated the pathologic and genetic features of human neuroblastoma and responded to anti-GD2 immunotherapy and DFMO, an FDA-approved inhibitor targeting the MYC transcriptional target ODC1. Thus, c-MYC overexpression results in different but related tumor types depending on the targeted cell. The GEMMs represent valuable tools for testing immunotherapies and targeted therapies for these diseases.","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"35 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1038/s41375-024-02466-6
Douglas Tremblay, Clifford Csizmar, Courtney D. DiNardo, Somedeb Ball, Noa Rippel, Danielle Hammond, Tapan M. Kadia, Farhad Ravandi, Kelly Chien, Grace Van Hyfte, Madhu Mazumdar, Antoine Saliba, Abhishek Mangaonkar, Terra Lasho, Aref Al-Kali, Marina Kremyanskaya, Jonathan Feld, Lewis R. Silverman, Rami Komrokji, John Mascarenhas, Eric Padron, Guillermo Garcia-Manero, David A. Sallman, Mrinal M. Patnaik, Guillermo Montalban-Bravo
Chronic myelomonocytic leukemia (CMML) is a rare hematologic malignancy with overlapping features of myelodysplastic neoplasm (MDS) and myeloproliferative neoplasms characterized by peripheral blood monocytosis [1]. There is a predisposition for transformation to acute myeloid leukemia (AML), termed CMML with blast transformation (CMML-BT) [2, 3]. Hypomethylating agents (HMAs) are the sole FDA approved therapy for CMML albeit without established efficacy in terms of prolonging overall survival (OS) and halting disease evolution [4,5,6]. In order to improve response rates, venetoclax (VEN) has been combined with HMAs extrapolating data from AML and MDS [7, 8]. Single centers have offered varied results on the added benefit of VEN to HMA therapy in CMML and CMML-BT [9,10,11], but these studies lack control cohorts and are limited by small sample sizes of patients evaluated in each treatment setting and disease category.
To clarify the role of upfront HMA + VEN in patients with CMML and CMML-BT, we performed a multicenter retrospective cohort study utilizing a propensity score matched (PSM) cohort of patients treated with HMA alone.
{"title":"Venetoclax in combination with hypomethylating agents in chronic myelomonocytic leukemia: a propensity score matched multicenter cohort study","authors":"Douglas Tremblay, Clifford Csizmar, Courtney D. DiNardo, Somedeb Ball, Noa Rippel, Danielle Hammond, Tapan M. Kadia, Farhad Ravandi, Kelly Chien, Grace Van Hyfte, Madhu Mazumdar, Antoine Saliba, Abhishek Mangaonkar, Terra Lasho, Aref Al-Kali, Marina Kremyanskaya, Jonathan Feld, Lewis R. Silverman, Rami Komrokji, John Mascarenhas, Eric Padron, Guillermo Garcia-Manero, David A. Sallman, Mrinal M. Patnaik, Guillermo Montalban-Bravo","doi":"10.1038/s41375-024-02466-6","DOIUrl":"https://doi.org/10.1038/s41375-024-02466-6","url":null,"abstract":"<p>Chronic myelomonocytic leukemia (CMML) is a rare hematologic malignancy with overlapping features of myelodysplastic neoplasm (MDS) and myeloproliferative neoplasms characterized by peripheral blood monocytosis [1]. There is a predisposition for transformation to acute myeloid leukemia (AML), termed CMML with blast transformation (CMML-BT) [2, 3]. Hypomethylating agents (HMAs) are the sole FDA approved therapy for CMML albeit without established efficacy in terms of prolonging overall survival (OS) and halting disease evolution [4,5,6]. In order to improve response rates, venetoclax (VEN) has been combined with HMAs extrapolating data from AML and MDS [7, 8]. Single centers have offered varied results on the added benefit of VEN to HMA therapy in CMML and CMML-BT [9,10,11], but these studies lack control cohorts and are limited by small sample sizes of patients evaluated in each treatment setting and disease category.</p><p>To clarify the role of upfront HMA + VEN in patients with CMML and CMML-BT, we performed a multicenter retrospective cohort study utilizing a propensity score matched (PSM) cohort of patients treated with HMA alone.</p>","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"147 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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