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The Role of Negative Parental Influences and Criminal Thinking in Juvenile Offending Behaviors. 父母的负面影响和犯罪思维在青少年犯罪行为中的作用。
IF 16.4 1区 化学
Accounts of Chemical Research Pub Date : 2025-02-01 Epub Date: 2022-10-31 DOI: 10.1177/0306624X221132998
Branna Humphrey, Bradley D Edwards, Jennifer Pealer
{"title":"The Role of Negative Parental Influences and Criminal Thinking in Juvenile Offending Behaviors.","authors":"Branna Humphrey, Bradley D Edwards, Jennifer Pealer","doi":"10.1177/0306624X221132998","DOIUrl":"10.1177/0306624X221132998","url":null,"abstract":"<p><p>Previous research has established that juveniles who experience negative parental influence are more likely to engage in problem and offending behavior. Less attention has been given to the possibility that criminal thinking styles might partially explain this relationship. This study examined the negative parental influences and criminal thinking styles of 1,354 juvenile offenders to establish that both negative parental influences and criminal thinking are significantly associated with juvenile problem and offending behavior. Further, the analysis showed that juvenile criminal thinking (proactive, reactive, and general) might mediate the relationship between negative parental influences and problem behavior. Implications for such findings are discussed.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"170-183"},"PeriodicalIF":16.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40446315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Huge unrepaired myelocystocele, progressive sac enlargement in later stages of life: a case report. 巨大骨髓囊肿未修复,后期囊肿逐渐增大:病例报告。
IF 16.4 1区 化学
Accounts of Chemical Research Pub Date : 2025-02-01 Epub Date: 2022-09-08 DOI: 10.1080/02688697.2022.2118235
Hosein Safari, Armin Jahangiri Babadi, Pooyan Alizadeh, Reza Ajudani, Soroor Hamidi
{"title":"Huge unrepaired myelocystocele, progressive sac enlargement in later stages of life: a case report.","authors":"Hosein Safari, Armin Jahangiri Babadi, Pooyan Alizadeh, Reza Ajudani, Soroor Hamidi","doi":"10.1080/02688697.2022.2118235","DOIUrl":"10.1080/02688697.2022.2118235","url":null,"abstract":"<p><strong>Background: </strong>Spinal dysraphism is characterized by failure of fusion at dorsal midline structures through the embryonic developmental stages. A terminal myelocystocele consists of a skin-covered lumbosacral spina bifida and meningocele that directly continuous with the spinal subarachnoid space.</p><p><strong>Observation: </strong>A 43-year-old woman who was diagnosed at birth with myelocystocele in the lower segments of the lumbar spine. She was not operated in the early stages of life. At the 43th years of her old, during 9-months, the sac began to progressively increase in size. In our initial examination before surgery, an extremely large skin-covered myelocystocele sac was observed in the thoracolumbar with a diameter of approximately 60 * 70 * 40 cm. patient operated and sac repaired. More than 20 liter of cerebrospinal fluid drainaged from cyst during surgery.</p><p><strong>Lessons: </strong>The mechanism of cyst enlargement is not well understood. Progressive and severe increase in size of unrepaired myelocystocele sac is possible in old ages even without cerebral hydrocephalus.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"84-87"},"PeriodicalIF":16.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33449707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A case of aggressive pituitary neuroendocrine tumour with extremely rapid progression: possible diagnostic value of TERT promoter methylation. 一例进展极快的侵袭性垂体神经内分泌肿瘤:TERT 启动子甲基化的可能诊断价值。
IF 16.4 1区 化学
Accounts of Chemical Research Pub Date : 2025-02-01 Epub Date: 2022-12-05 DOI: 10.1080/02688697.2022.2151564
Masamichi Endo, Jun-Ichi Adachi, Chiaki Murakami, Chie Inomoto, Miyu Komatsu, Shunya Hanakita, Ken-Ichi Oyama, Akira Matsuno, Ryo Nishikawa, Soichi Oya
{"title":"A case of aggressive pituitary neuroendocrine tumour with extremely rapid progression: possible diagnostic value of <i>TERT</i> promoter methylation.","authors":"Masamichi Endo, Jun-Ichi Adachi, Chiaki Murakami, Chie Inomoto, Miyu Komatsu, Shunya Hanakita, Ken-Ichi Oyama, Akira Matsuno, Ryo Nishikawa, Soichi Oya","doi":"10.1080/02688697.2022.2151564","DOIUrl":"10.1080/02688697.2022.2151564","url":null,"abstract":"<p><p>Most pituitary adenoma/neuroendocrine tumours (PitNET) are histologically benign and grow slowly; however, a subset of these tumours exhibit a more aggressive clinical course characterized by local invasiveness and early recurrence. These high-risk PitNETs often require multiple surgeries and radiation over several years and may eventually acquire carcinomatous characteristics, such as metastasis in some cases. Herein, we report a rare case of PitNET causing oculomotor paresis with extremely rapid recurrence only 3 months after initial surgery, followed by lethal liver metastasis. Preoperative magnetic resonance imaging and intraoperative findings were consistent with typical PitNETs, other than moderate invasion of the cavernous sinus. Pathological examination of the specimen obtained from the initial transsphenoidal surgery revealed increased mitosis and elevated rates of cells positive for Ki-67 and p53. Based on the immunohistochemical assessment for transcription factors and pituitary hormones, the diagnosis was determined to be a silent sparsely granulated corticotroph PitNET with focal malignant transformation. Aggressive features represented by Ki-67 and p53 positivity were more robust in recurrent and metastatic specimens, but hormone immunostaining was decreased. Epigenetic analysis revealed methylation of the telomerase reverse transcriptase (<i>TERT</i>) promoter in the tumour, resulting in TERT upregulation. Despite extensive research, markers for distinguishing extremely aggressive PitNETs have not been determined. Although further analysis is needed, our case demonstrates the possible usefulness of assessing <i>TERT</i> promoter methylation status in the stratification of recurrence risk in extremely high-risk variants of PitNET.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"93-99"},"PeriodicalIF":16.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35348694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Management of lymphocele following anterior lumbar interbody fusion, case report and review of literature. 前路腰椎椎间融合术后淋巴囊的处理,病例报告和文献综述。
IF 16.4 1区 化学
Accounts of Chemical Research Pub Date : 2025-02-01 Epub Date: 2022-09-14 DOI: 10.1080/02688697.2022.2120962
Madhav R Patel, Kevin C Jacob, Timothy J Hartman, James W Nie, Jonathan A Myers
{"title":"Management of lymphocele following anterior lumbar interbody fusion, case report and review of literature.","authors":"Madhav R Patel, Kevin C Jacob, Timothy J Hartman, James W Nie, Jonathan A Myers","doi":"10.1080/02688697.2022.2120962","DOIUrl":"10.1080/02688697.2022.2120962","url":null,"abstract":"<p><p>While anterior lumbar interbody fusion (ALIF) is known as an established and safe procedure for treatment of degenerative disc disease, albeit rare, the development of postoperative intra-abdominal or retroperitoneal collection of lymph warrants timely diagnosis and management. This study presents the case of a 62-year-old male who underwent L4-L5 and L5-S1 ALIF and developed a persistent left-sided fluid collection, resulting in a symptomatic retroperitoneal lymphocele confirmed by computed tomography (CT). After percutaneous drainage by interventional radiology (IR), output remained high at 1 liter (L) per day, necessitating sclerotherapy with doxycycline and ethanol. In the absence of improvement, a lymphangiogram demonstrating a persistent lymph leak and glue embolization was performed. Due to refractory symptoms, retroperitoneal exploration with methylene blue dye was utilized for lymphatic mapping, and a lymphatic capillary leak in proximity to the left iliac artery was identified and successfully ligated with resolution of symptoms. With suspected fluid collections following ALIF, confirmation with CT or ultrasound (US) imaging followed by percutaneous drainage and testing of fluid is necessary. In mild cases, drainage alone or nonsurgical chemical sclerotherapy may suffice. In symptomatic refractory cases, localization of the site with lymphangiogram or US-guided injection of methylene blue dye allows for easier identification and definitive management with either transabdominal laparoscopic fenestration or retroperitoneal surgical exploration and ligation.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"88-92"},"PeriodicalIF":16.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40356795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dropped head syndrome in a patient with Parkinson's disease and inflammatory myopathy, treated with sternocleidomastoid release and circumferential cervical fusion. 一名患有帕金森病和炎性肌病的患者在接受胸锁乳突肌松解术和颈椎环形融合术治疗后出现低头综合征。
IF 16.4 1区 化学
Accounts of Chemical Research Pub Date : 2025-02-01 Epub Date: 2022-09-15 DOI: 10.1080/02688697.2022.2123892
Yingda Li, Gregory Basil, Steven Vanni
{"title":"Dropped head syndrome in a patient with Parkinson's disease and inflammatory myopathy, treated with sternocleidomastoid release and circumferential cervical fusion.","authors":"Yingda Li, Gregory Basil, Steven Vanni","doi":"10.1080/02688697.2022.2123892","DOIUrl":"10.1080/02688697.2022.2123892","url":null,"abstract":"<p><strong>Background: </strong>Dropped head syndrome (DHS) is a recently recognised cause of cervical spinal deformity and disability. The combination of Parkinson's disease (PD) and inflammatory myopathy in the genesis of DHS has not been previously reported. Furthermore, the optimal surgical treatment of progressive DHS remains undefined.</p><p><strong>Case description: </strong>We report the case of a 64-year-old patient with severe DHS and coronal plane deformity secondary to underlying PD, precipitated by a focal paraspinal myositis, successfully corrected using asymmetric sternocleidomastoid (SCM) release and circumferential cervical fusion. The nuances of decision-making in this challenging patient population are highlighted, including the benefits of intraoperative traction, anterior column reconstruction and bicortical screw fixation. Postoperatively, significant reductions in pain and disability were achieved, along with restoration of cervical lordosis (CL), C2-7 sagittal vertical axis (CSVA) and chin-brow vertical angle (CBVA).</p><p><strong>Conclusions: </strong>Circumferential cervical fusion with concomitant SCM release is a useful option in the treatment of recalcitrant DHS with biplanar deformity, addressing the unique biomechanical and endocrinological challenges posed by patients with underlying PD.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"104-109"},"PeriodicalIF":16.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40360223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An Empirical Comparison of the Profiles of Security Threat Group Offenders with General Offenders. 安全威胁集团罪犯与一般罪犯的特征实证比较。
IF 16.4 1区 化学
Accounts of Chemical Research Pub Date : 2025-02-01 Epub Date: 2022-09-29 DOI: 10.1177/0306624X221124830
Christian Leuprecht, David B Skillicorn, David Bright
{"title":"An Empirical Comparison of the Profiles of Security Threat Group Offenders with General Offenders.","authors":"Christian Leuprecht, David B Skillicorn, David Bright","doi":"10.1177/0306624X221124830","DOIUrl":"10.1177/0306624X221124830","url":null,"abstract":"<p><p>Datasets of offender attributes, both pre-custody and in-custody, were provided by the Correctional Service of Canada with the goal of exploring whether Security Threat Group (STG) offenders (informally, gang members of various kinds) differ in any systematic way from other offenders. For pre-custody attributes, we show that the entire offender population varies along two almost independent axes, one associated with affinity for violence, and the other with affinity for substance abuse. Within this structure, STG offenders are characteristically less extreme, in either direction, than the general offender population. For approximately two dozen attributes, STG offenders, as a group, tend to have higher values; for a few, they tend to have lower values. For in-custody attributes, the entire offender population forms a triangular structure whose vertices represent: passivity; violence and troublemaking; and involvement in programs leading to partial release. The differences between the STG offender population and the general offender population are small. An offender who is placed at the high end of the propensity for violence axis and/or the high end of the substance abuse axis based on pre-custody attributes is much more likely to be involved in incidents, grievances, and violence while in custody. This may have implications for risk stratification of incoming offenders.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"147-169"},"PeriodicalIF":16.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40379261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of 5-HT in the enteric nervous system and enteroendocrine cells. 5-HT 在肠神经系统和肠内分泌细胞中的作用。
IF 5.3 2区 材料科学
ACS Applied Nano Materials Pub Date : 2025-02-01 Epub Date: 2022-08-17 DOI: 10.1111/bph.15930
Nick J Spencer, Damien J Keating
{"title":"Role of 5-HT in the enteric nervous system and enteroendocrine cells.","authors":"Nick J Spencer, Damien J Keating","doi":"10.1111/bph.15930","DOIUrl":"10.1111/bph.15930","url":null,"abstract":"<p><p>Since the 1950s, considerable circumstantial evidence had been presented that endogenous 5-HT (serotonin) synthesized from within the wall of the gastrointestinal (GI) tract played an important role in GI motility and transit. However, identifying the precise functional role of gut-derived 5-HT has been difficult to ascertain, for a number of reasons. Over the past decade, as recording techniques have advanced significantly and access to new genetically modified animals improved, there have been major new insights and major changes in our understanding of the functional role of endogenous 5-HT in the GI tract. Data from many different laboratories have shown that major patterns of GI motility and transit still occur with minor or no, change when all endogenous 5-HT is pharmacologically or genetically ablated from the gut. Furthermore, antagonists of 5-HT<sub>3</sub> receptors are equally, or more potent at inhibiting GI motility in segments of intestine that are completely depleted of endogenous 5-HT. Here, the most recent findings are discussed with regard to the functional role of endogenous 5-HT in enterochromaffin cells and enteric neurons in gut motility and more broadly in some major homeostatic pathways.</p>","PeriodicalId":6,"journal":{"name":"ACS Applied Nano Materials","volume":" ","pages":"471-483"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40525099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Improving dental student confidence through the use of simulated patient cases. 通过使用模拟病例提高牙科学生的自信心。
IF 16.4 1区 化学
Accounts of Chemical Research Pub Date : 2025-02-01 Epub Date: 2022-11-07 DOI: 10.1111/eje.12867
Jonathan E Marsden, Stephen P Deboo, Matt Cripps, Nicholas N Longridge, Michael Aspden, Kathryn Fox
{"title":"Improving dental student confidence through the use of simulated patient cases.","authors":"Jonathan E Marsden, Stephen P Deboo, Matt Cripps, Nicholas N Longridge, Michael Aspden, Kathryn Fox","doi":"10.1111/eje.12867","DOIUrl":"10.1111/eje.12867","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates whether student confidence could be improved through the use of simulated patient case-based scenarios.</p><p><strong>Materials and methods: </strong>Students in their 4th and 5th year of undergraduate study completed an online e-portfolio workbook consisting of activities related to five simulated patient cases. Following completion of the relevant learning activities within the e-portfolio, students then viewed a tutor case presentation video and attended simulated clinic sessions to complete corresponding exercises involving 3D-printed teeth related to the case. Subsequently, students undertook online self-reflection and goal-setting activities to aid their development. An anonymous questionnaire was distributed to all participants to gain insight into the themes of student confidence and learning support. The Cronbach's Alpha coefficient was calculated for both sections of the student questionnaire. The values for \"student confidence\" and \"learning support\" were α = 0.91 and α = 0.87, respectively.</p><p><strong>Results: </strong>There was a total of 89 valid student responses to the questionnaire (65%). A Spearman's correlation of r<sub>s</sub> = 0.50 (p < .001) suggests a tentative causative correlation between the learning support offered through the simulated patient cases and student confidence. There was a positive directional relationship between engagement with the learning support of the simulated patient cases and student confidence scores.</p><p><strong>Conclusion: </strong>Student confidence increased following the completion of simulated patient cases and students found the learning support offered beneficial to their development. This learning intervention has the potential to improve student self-efficacy, develop contextual competency and facilitate reflective practice. Simulated patient cases may be a useful precursor or adjunct to traditional patient clinics.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"104-115"},"PeriodicalIF":16.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40650001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neurosurgery inpatient outcome prediction for discharge planning with deep learning and transfer learning. 利用深度学习和迁移学习预测神经外科住院病人的出院规划结果。
IF 16.4 1区 化学
Accounts of Chemical Research Pub Date : 2025-02-01 Epub Date: 2022-12-02 DOI: 10.1080/02688697.2022.2151565
Lydia Lam, Antoinette Lam, Stephen Bacchi, Amal Abou-Hamden
{"title":"Neurosurgery inpatient outcome prediction for discharge planning with deep learning and transfer learning.","authors":"Lydia Lam, Antoinette Lam, Stephen Bacchi, Amal Abou-Hamden","doi":"10.1080/02688697.2022.2151565","DOIUrl":"10.1080/02688697.2022.2151565","url":null,"abstract":"<p><strong>Introduction: </strong>Deep learning may be able to assist with the prediction of neurosurgical inpatient outcomes. The aims of this study were to investigate deep learning and transfer learning in the prediction of several inpatient outcomes including timing of discharge and discharge destination.</p><p><strong>Method: </strong>Data were collected on consecutive neurosurgical admissions from existing databases over a 15-month period. Following pre-processing artificial neural networks were applied to admission notes and ward round notes to predict four inpatient outcomes. Models were developed on the training dataset, before being tested on a hold-out test dataset and a validation dataset.</p><p><strong>Results: </strong>1341 individual admissions were included in the study. Using transfer learning and an artificial neural network an area under the receiver operator curve (AUC) of 0.81 and 0.80 on the derivation and validation datasets was able to be achieved for the prediction of discharge within the next 48 hours using daily ward round notes. This result is in comparison to an AUC of 0.71 and 0.68 using an artificial neural network without transfer learning for the same outcome. When the artificial neural network with transfer learning was applied to the other outcomes AUC of 0.72, 0.93 and 0.83 was achieved on the validation datasets for predicting discharge within the next 7 days, survival to discharge and discharge to home as a destination.</p><p><strong>Conclusions: </strong>Deep learning may predict inpatient neurosurgery outcomes from free-text medical data. Recurrent predictions with ward round notes enable the use of information obtained throughout hospital admissions in these estimates.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"110-114"},"PeriodicalIF":16.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40570482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction of Proteolysis-Targeting Chimeras Retention Time Using XGBoost Model Incorporated with Chromatographic Conditions. 结合色谱条件的XGBoost模型预测蛋白水解靶向嵌合体保留时间。
IF 5.6 2区 化学
Journal of Chemical Information and Modeling Pub Date : 2025-01-27 Epub Date: 2025-01-09 DOI: 10.1021/acs.jcim.4c01732
Xinhao Qu, Chen Jiang, Mengyi Shan, Wenhao Ke, Jing Chen, Qiming Zhao, Youhong Hu, Jia Liu, Lu-Ping Qin, Gang Cheng
{"title":"Prediction of Proteolysis-Targeting Chimeras Retention Time Using XGBoost Model Incorporated with Chromatographic Conditions.","authors":"Xinhao Qu, Chen Jiang, Mengyi Shan, Wenhao Ke, Jing Chen, Qiming Zhao, Youhong Hu, Jia Liu, Lu-Ping Qin, Gang Cheng","doi":"10.1021/acs.jcim.4c01732","DOIUrl":"10.1021/acs.jcim.4c01732","url":null,"abstract":"<p><p>Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that target undruggable proteins, enhance selectivity and prevent target accumulation through catalytic activity. The unique structure of PROTACs presents challenges in structural identification and drug design. Liquid chromatography (LC), combined with mass spectrometry (MS), enhances compound annotation by providing essential retention time (RT) data, especially when MS alone is insufficient. However, predicting RT for PROTACs remains challenging. To address this, we compiled the PROTAC-RT data set from literature and evaluated the performance of four machine learning algorithms─extreme gradient boosting (XGBoost), random forest (RF), K-nearest neighbor (KNN) and support vector machines (SVM)─and a deep learning model, fully connected neural network (FCNN), using 24 molecular fingerprints and descriptors. Through screening combinations of molecular fingerprints, descriptors and chromatographic condition descriptors (CCs), we developed an optimized XGBoost model (XGBoost + moe206+Path + Charge + CCs) that achieved an <i>R</i><sup>2</sup> of 0.958 ± 0.027 and an RMSE of 0.934 ± 0.412. After hyperparameter tuning, the model's <i>R</i><sup>2</sup> improved to 0.963 ± 0.023, with an RMSE of 0.896 ± 0.374. The model showed strong predictive accuracy under new chromatographic separation conditions and was validated using six experimentally determined compounds. SHapley Additive exPlanations (SHAP) not only highlights the advantages of XGBoost but also emphasizes the importance of CCs and molecular features, such as bond variability, van der Waals surface area, and atomic charge states. The optimized XGBoost model combines moe206, path, charge descriptors, and CCs, providing a fast and precise method for predicting the RT of PROTACs compounds, thus facilitating their annotation.</p>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":" ","pages":"613-625"},"PeriodicalIF":5.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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