bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical features and FLAIR radiomics nomogram for predicting functional outcomes after thrombolysis in ischaemic stroke
Authors: Xu Qingqing , Zhu Yan , Zhang Xi , Kong Dan , Duan Shaofeng , Guo Lili , Yin Xindao , Jiang Liang , Liu Zaiyi , Yang Wanqun 
Published: February 2023

ObjectiveWe explored whether radiomics features extracted from diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) images can predict the clinical outcome of patients with acute ischaemic stroke. This study was conducted to investigate and validate a radiomics nomogram for predicting acute ischaemic stroke prognosis.MethodsA total of 257 patients with acute ischaemic stroke from three clinical centres were retrospectively assessed from February 2019 to July 2022. According to the modified Rankin scale (mRS) at 3 months, the patients were divided into a favourable outcome group (mRS of 0–2) and an unfavourable outcome group (mRS of 3−6). The high-throughput features from the regions of interest (ROIs) within the radiologist-drawn contour by AK software were extracted. We used two feature selection methods, minimum redundancy and maximum (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO), to select the features. Three radiomics models (DWI, FLAIR, and DWI-FLAIR) were established. A radiomics nomogram with patient characteristics and radiomics signature was built using a multivariate logistic regression model. The performance of the nomogram was evaluated in the test and validation sets. Ultimately, decision curve analysis was implemented to assess the clinical value of the nomogram.ResultsThe FLAIR, DWI, and DWI-FLAIR radiomics model exhibited good prediction performance, with area under the curve (AUCs) of 0.922 (95% CI: 0.876−0.968), 0.875 (95% CI: 0.815−0.935), and 0.895 (95% CI: 0.840−0.950). The radiomics nomogram with clinical characteristics including the overall cerebral small vessel disease (CSVD) burden score, hemorrhagic transformation (HT) and admission National Institutes of Health Stroke Scale score (NIHSS) score and the FLAIR Radscore presented good discriminatory potential in the training set (AUC = 0.94; 95% CI: 0.90−0.98) and test set (AUC = 0.94; 95% CI: 0.87−1), which was validated in the validation set 1 (AUC = 0.95; 95% CI: 0.88−1) and validation set 2 (AUC = 0.90; 95% CI: 0.768−1). In addition, it demonstrated good calibration, and decision curve analysis confirmed the clinical value of this nomogram.ConclusionThis non-invasive clinical-FLIAR radiomics nomogram shows good performance in predicting ischaemic stroke prognosis after thrombolysis.
Alternations of neuromagnetic activity across neurocognitive core networks among benign childhood epilepsy with centrotemporal spikes: A multi-frequency MEG study
Authors: Wang Siyi , Wang Yingfan , Li Yihan , Sun Jintao , Wang Pengfei , Niu Kai , Xu Yue , Li Yanzhang , Sun Fangling , Chen Qiqi , Wang Xiaoshan 
Published: February 2023

ObjectiveWe aimed to investigate the alternations of neuromagnetic activity across neurocognitive core networks among early untreated children having benign childhood epilepsy with centrotemporal spikes (BECTS).MethodsWe recorded the Magnetoencephalography (MEG) resting-state data from 48 untreated children having BECTS and 24 healthy children. The fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV) was utilized to divide the children with BECTS into two groups: the cognitive impairment (CI) group with a full-scale intelligence quotient (FSIQ) of &lt; 90 and the cognitive non-impairment (CNI) group with an FSIQ of &gt; 90. We selected 26 bilateral cognitive-related regions of interest based on the triple network model. The neurocognitive core network spectral power was estimated using a minimum norm estimate (MNE).ResultsIn the CNI group, the spectral power inside the bilateral anterior cingulate cortex (ACC) and the bilateral caudal middle frontal cortex (CMF) enhanced within the delta band and reduced within the alpha band. Both the CI and the CNI group demonstrated enhanced spectral power inside the bilateral posterior cingulate cortex (PCC), bilateral precuneus (PCu) region, bilateral superior and middle temporal cortex, bilateral inferior parietal lobe (IPL), and bilateral supramarginal cortex (SM) region in the delta band. Moreover, there was decreased spectral power in the alpha band. In addition, there were consistent changes in the high-frequency spectrum (&gt; 90 Hz). The spectral power density within the insula cortex (IC), superior temporal cortex (ST), middle temporal cortex (MT), and parahippocampal cortex (PaH) also decreased. Therefore, studying high-frequency activity could lead to a new understanding of the pathogenesis of BECTS.ConclusionThe alternations of spectral power among neurocognitive core networks could account for CI among early untreated children having BECTS. The dynamic properties of spectral power in different frequency bands could behave as biomarkers for diagnosing new BECTS.
Functional and structural alterations as diagnostic imaging markers for depression in de novo Parkinson’s disease
Authors: Wang Hui , Xu Jianxia , Yu Miao , Zhou Gaiyan , Ren Jingru , Wang Yajie , Zheng Huifen , Sun Yu , Wu Jun , Liu Weiguo 
Published: February 2023

BackgroundDepression in Parkinson’s disease (PD) is identified and diagnosed with behavioral observations and neuropsychological measurements. Due to the large overlaps of depression and PD symptoms in clinical manifestations, it is challenging for neurologists to distinguish and diagnose depression in PD (DPD) in the early clinical stage of PD. The advancement in magnetic resonance imaging (MRI) technology provides potential clinical utility in the diagnosis of DPD. This study aimed to explore the alterations of functional and structural MRI in DPD to produce neuroimaging markers in discriminating DPD from non-depressed PD (NDPD) and healthy controls (HC).MethodsWe recruited 20 DPD, 37 NDPD, and 41 HC matched in age, gender, and education years. The patients’ diagnosis with PD was de novo. The differences in regional homogeneity (ReHo), voxel-wise degree centrality (DC), cortical thickness, cortical gray matter (GM) volumes, and subcortical GM volumes among these groups were detected, and the relationship between altered indicators and depression was analyzed. Moreover, the receiver operating characteristic (ROC) analysis was performed to assess the diagnostic efficacy of altered indicators for DPD.ResultsCompared to NDPD and HC, DPD showed significantly increased ReHo in left dorsolateral superior frontal gyrus (DSFG) and DC in left inferior temporal gyrus (ITG), and decreased GM volumes in left temporal lobe and right Amygdala. Among these altered indicators, ReHo value in left DSFG and DC values in left ITG and left DSFG were significantly correlated with the severity of depression in PD patients. Comparing DPD and NDPD, the ROC analysis revealed a better area under the curve value for the combination of ReHo value in left DSFG and DC value in left ITG, followed by each independent indicator. However, the difference is not statistically significant.ConclusionThis study demonstrates that both functional and structural impairments are present in DPD. Among them, ReHo value of left DSFG and DC value of left ITG are equally well suited for the diagnosis and differential diagnosis of DPD, with a combination of them being slightly preferable. The multimodal MRI technique represents a promising approach for the classification of subjects with PD.
Population level multimodal neuroimaging correlates of attention-deficit hyperactivity disorder among children
Authors: Lin Huang , Haider Stefan P. , Kaltenhauser Simone , Mozayan Ali , Malhotra Ajay , Constable R. Todd , Scheinost Dustin , Ment Laura R. , Konrad Kerstin , Payabvash Seyedmehdi 
Published: February 2023

ObjectivesLeveraging a large population-level morphologic, microstructural, and functional neuroimaging dataset, we aimed to elucidate the underlying neurobiology of attention-deficit hyperactivity disorder (ADHD) in children. In addition, we evaluated the applicability of machine learning classifiers to predict ADHD diagnosis based on imaging and clinical information.MethodsFrom the Adolescents Behavior Cognitive Development (ABCD) database, we included 1,798 children with ADHD diagnosis and 6,007 without ADHD. In multivariate logistic regression adjusted for age and sex, we examined the association of ADHD with different neuroimaging metrics. The neuroimaging metrics included fractional anisotropy (FA), neurite density (ND), mean-(MD), radial-(RD), and axial diffusivity (AD) of white matter (WM) tracts, cortical region thickness and surface areas from T1-MPRAGE series, and functional network connectivity correlations from resting-state fMRI.ResultsChildren with ADHD showed markers of pervasive reduced microstructural integrity in white matter (WM) with diminished neural density and fiber-tracks volumes – most notable in the frontal and parietal lobes. In addition, ADHD diagnosis was associated with reduced cortical volume and surface area, especially in the temporal and frontal regions. In functional MRI studies, ADHD children had reduced connectivity among default-mode network and the central and dorsal attention networks, which are implicated in concentration and attention function. The best performing combination of feature selection and machine learning classifier could achieve a receiver operating characteristics area under curve of 0.613 (95% confidence interval = 0.580–0.645) to predict ADHD diagnosis in independent validation, using a combination of multimodal imaging metrics and clinical variables.ConclusionOur study highlights the neurobiological implication of frontal lobe cortex and associate WM tracts in pathogenesis of childhood ADHD. We also demonstrated possible potentials and limitations of machine learning models to assist with ADHD diagnosis in a general population cohort based on multimodal neuroimaging metrics.
Long non-coding RNA rhabdomyosarcoma 2-associated transcript contributes to neuropathic pain by recruiting HuR to stabilize DNA methyltransferase 3 alpha mRNA expression in dorsal root ganglion neuron
Authors: Guo Xinying , Zhang Gaolong , Cai Weihua , Huang Fa , Qin Jingwen , Song Xingrong 
Published: February 2023

IntroductionLong non-coding RNAs (lncRNAs) act as key regulators in multiple human diseases. In particular, the dysfunction of lncRNAs in dorsal root ganglion (DRG) contributes to the pathogenesis of neuropathic pain (NP). Nevertheless, the role and mechanism of most lncRNAs in NP remain unclear.MethodsTwo classic chronic NP models, including L4 spinal nerve ligation (SNL) model and chronic constriction injury (CCI) of the sciatic nerve, were performed. Mechanical allodynia and heat hyperalgesia were used to evaluate neuropathic pain. DRG microinjection was used to deliver agents into DRG. qRT-PCR, immunofluorescence, immunoprecipitation, western blotting, siRNA transfection, AAV transduction were performed to investigate the phenotypes and molecular basis.ResultsHere, we discovered that Rmst as a lncRNA was specifically expressed in Atf3+ injured DRG neurons and significantly upregulated following peripheral nerve damage. Rmst overexpression by direct DRG injection of AAV5-Rmst causes neuropathic symptoms in the absence of nerve damage. Conversely, blocking Rmst expression in injured DRGs alleviated nerve injury-induced pain hypersensitivities and downregulated Dnmt3a expression. Furthermore, we found peripheral nerve damage induced Rmst increase could interact with RNA-binding protein HuR to stabilize the Dnmt3a mRNA.ConclusionOur findings reveal a crucial role of Rmst in damaged DRG neurons under NP condition and provide a novel target for drug development against NP.
Associations of body mass index with severe outcomes of COVID-19 among critically ill elderly patients: A prospective study
Authors: Gholi Zahra , Vahdat Shariatpanahi Zahra , Yadegarynia Davood , Eini-Zinab Hassan 
Published: February 2023

Background and AimFew studies assessed the associations of overweight and obesity with severe outcomes of coronavirus disease 2019 (COVID-19) among elderly patients. This study was conducted to assess overweight and obesity in relation to risk of mortality, delirium, invasive mechanical ventilation (IMV) requirement during treatment, re-hospitalization, prolonged hospitalization, and ICU admission among elderly patients with COVID-19.MethodsThis was a single-center prospective study that was done on 310 elderly patients with COVID-19 hospitalized in the intensive care unit (ICU). We collected data on demographic characteristics, laboratory parameters, nutritional status, blood pressure, comorbidities, medications, and types of mechanical ventilation at baseline. Patients were followed up during ICU admission and until 45 days after the first visit, and data on delirium incidence, mortality, need for a form of mechanical ventilation, discharge day from ICU and hospital, and re-hospitalization were recorded for each patient.ResultsDuring the follow-up period, we recorded 190 deaths, 217 cases of delirium, and 35 patients who required IMV during treatment. After controlling for potential confounders, a significant association was found between obesity and delirium such that obese patients with COVID-19 had a 62% higher risk of delirium compared with normal-weight patients (HR: 1.62, 95% CI: 1.02–2.57). This association was not observed for overweight. In terms of other outcomes including ICU/45-day mortality, IMV therapy during treatment, re-hospitalization, prolonged hospitalization, and ICU admission, we found no significant association with overweight and obesity either before or after controlling for potential confounders.ConclusionWe found that obesity may be a risk factor for delirium among critically ill elderly patients with COVID-19.
PARP inhibitors in the treatment of ARID1A mutant ovarian clear cell cancer: PI3K/Akt1-dependent mechanism of synthetic lethality
Authors: Yakovlev Vasily A. , Sullivan Stephanie A. , Fields Emma C. , Temkin Sarah M. 
Published: February 2023

IntroductionPoly(ADP-ribose) polymerase (PARP) is a nuclear enzyme involved in the repair of DNA single-strand breaks (SSB). The recent development of poly(ADP-ribose) polymerase inhibitors (PARPi) results from over 45 years of studies. When the activity of PARP1 or PARP2 is compromised, DNA SSB lesions are unresolved and can be converted to DNA double-strand breaks (DSBs) by the cellular transcription mechanisms. ARID1A (also called BAF250a) is an important component of the mammalian Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex. ARID1A gene demonstrates &gt;50% of mutation rate in ovarian clear-cell carcinomas (OCCC). Mutated or downregulated ARID1A significantly compromises the Homologous Recombination Repair (HRR) of DNA DSB.ResultsThe present study demonstrated that downregulated or mutated ARID1A attenuates DNA HRR through stimulation of the PI3K/Akt1 pathway and makes tumor cells highly sensitive to PARPi and PARPi/ionizing radiation (IR) combination. We showed that PI3K/Akt1 pathway plays an important role in the sensitization of cancer cell lines with compromised function of ARID1A to PARPi treatment.DiscussionWe believe that using of PARPi monotherapy or in combination with radiation therapy is an appealing strategy for treating ARID1A-mutated cancers, as well as many other types of PI3K/Akt1-driven cancers.
The efficacies and biomarker investigations of antiangiogenic agents and PD-1 inhibitors for metastatic soft tissue sarcoma: A multicenter retrospective study
Authors: Liu Zhiyong , Wang Xin , Wang Jiaqiang , Zhang Peng , Li Chao , Wang Bangmin , Gao Songtao , Liu Oufei , Yao Weitao 
Published: February 2023

ObjectiveTo investigate the efficacy and safety of antiangiogenesis-immunotherapy in patients with advanced STS in China, and to explore the potential factors of prognosis.Patients and MethodsThis retrospective study was conducted at three hospitals in China, and the patients with metastatic STS who were ineligible for or declined anthracycline-based chemotherapy received antiangiogenic agents (anlotinib or apatinib) plus programmed death-1 (PD‐1) inhibitors (camrelizumab or sintilimab) between June 2019 and May 2022. The primary endpoint was progression-free survival rate at 6 months (6-month PFSR), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) and toxicity. Biomarkers that might affect the prognosis were explored.ResultsThirty-nine patients were included: five patients with alveolar soft tissue sarcoma (ASPS) and 34 with non-ASPS. With a median follow-up of 18.2 months, the 6-month PFSR was 51.3%, with the ORR of 20.5% and DCR of 76.9%. The median PFS and OS were 7.0 months and 17.2 months. The 6-month PFSR for patients with ASPS and non-ASPS was 80.0% and 47.1%, respectively. The most common adverse events were hypothyroidism (56.4%), followed by fatigue (46.2%), and hypertriglyceridemia (43.6%). No treatment-related deaths were observed. Patients with low baseline NLR (NLR &lt; 4) had better 6-month PFSR than those with high NLR (NLR ≥ 4) (82.4% vs. 31.6%).ConclusionAntiangiogenic agents plus PD-1 inhibitors showed acceptable toxicity and promising efficacy in patients with advanced STS, especially patients with ASPS, and a low NLR might serve as a reliable biomarker for 6-month PFSR, PFS, and OS. It provides a reference for randomized controlled trials.
Elucidating factors contributing to disparities in pain-related experiences among adults with or at risk for knee osteoarthritis
Authors: Mickle Angela M. , Domenico Lisa H. , Tanner Jared J. , Terry Ellen L. , Cardoso Josue , Glover Toni L. , Booker Staja , Addison Adriana , Gonzalez Cesar E. , Garvan Cynthia S. , Redden David , Staud Roland , Goodin Burel R. , Fillingim Roger B. , Sibille Kimberly T. 
Published: February 2023

Background and purposeWe and others have reported ethnic/race group differences in clinical pain, physical function, and experimental pain sensitivity. However, recent research indicates that with consideration for socioenvironmental factors, ethnicity/race differences become less or non-significant. Understanding of factors contributing to pain inequities are needed. Guided by the NIA and NIMHD Health Disparities Research Frameworks, we evaluate the contributions of environmental and behavioral factors on previously reported ethnic/race group differences in: (1) clinical pain, (2) physical function, and (3) experimental pain in individuals with knee pain.MethodsBaseline data from Understanding of Pain and Limitations in Osteoarthritis Disease (UPLOAD) and UPLOAD-2 studies were analyzed. Participants were adults 45 to 85 years old who self-reported as non-Hispanic white (NHW) or black (NHB) with knee pain. A health assessment and quantitative sensory testing were completed. Sociodemographics, environmental, health, clinical and experimental pain, and physical functioning measures were included in nested regressions.ResultsPooled data from 468 individuals, 57 ± 8 years of age, 63% women, and 53% NHB adults. As NHB adults were younger and reported greater socioenvironmental risk than the NHW adults, the term sociodemographic groups is used. With inclusion of recognized environmental and behavioral variables, sociodemographic groups remained a significant predictor accounting for &lt;5% of the variance in clinical pain and physical function and &lt;10% of variance in experimental pain.ConclusionThe incorporation of environmental and behavioral factors reduced relationships between sociodemographic groups and pain-related outcomes. Pain sites, BMI, and income were significant predictors across multiple models. The current study adds to a body of research on the complex array of factors contributing to disparities in pain-related outcomes.
Efficacy and safety of canakinumab as a second line biologic after tocilizumab treatment failure in children with systemic juvenile idiopathic arthritis: A single-centre cohort study using routinely collected health data
Authors: Alexeeva Ekaterina , Krekhova Elizaveta , Dvoryakovskaya Tatyana , Isaeva Ksenia , Chomakhidze Aleksandra , Chistyakova Evgeniya , Lomakina Olga , Denisova Rina , Mamutova Anna , Fetisova Anna , Gautier Marina , Vankova Dariya , Kriulin Ivan , Saygitov Ruslan 
Published: February 2023

BackgroundA significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (bDMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required.MethodsPatients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the paediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS-71 = 0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up from time first canakinumab dose administered was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from electronic outpatient medical records.ResultsDuring the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at baseline was 8.2 [interquartile range (IQR) 4.0–12.9] years, with the median sJIA duration being 1.8 (IQR 0.8–5.8) years; 37 (80%) patients received at least one conventional DMARD (cDMARD; oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (IQR 282–404) days. During the follow-up, 1 patient discontinued canakinumab due to tuberculosis detection and the dose was reduced or the injection interval increased in 4 (9%) patients. In total, 27 (60%) patients continued to receive at least one cDMARD. Improvement according to the ACR30 criteria was achieved in 43 patients [96%; 95% confidence interval (CI) 85–99], inactive disease in 42 (93%; 95%CI 82–98), and remission in 37 (82%; 95% CI 69-91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 AEs (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases.ConclusionsOne-year canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA.