bluuebunny/crossref_metadata_2025_split huggingface dataset:
UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment
Authors: Wang Zhan , Liu Xiaoyan , Wang Wenda , Xu Jiyu , Sun Haidan , Wei Jing , Yu Yuncui , Zhao Yang , Wang Xu , Liao Zhangcheng , Sun Wei , Jia Lulu , Zhang Yushi 
Published: February 2023

Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis.Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms.Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism.Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.
Intermuscular coherence of plantar and dorsiflexor muscles in older adults with Parkinson’s disease and age-matched controls during bipedal and unipedal stance
Authors: Smart Rowan R. , Toumi Anis , Harris Owen D. , Cremoux Sylvain , Dalton Brian H. , Wile Daryl J. , Jakobi Jennifer M. 
Published: February 2023

IntroductionPostural instability increases with age and is exacerbated in neurological disorders such as Parkinson’s disease (PD). Reducing the base of support from bipedal to unipedal stance increases center of pressure (CoP) parameters and intermuscular coherence in lower-leg muscles of healthy older adults. To further develop an understanding of postural control in an altered state of neurological impairment, we explored intermuscular coherence in lower-leg muscles and CoP displacement in older adults with PD.MethodsThis study measured surface EMG from the medial (MG) and lateral (LG) gastrocnemii, soleus (SOL), and tibialis anterior (TA), and examined EMG amplitude and intermuscular coherence during bipedal and unipedal stance on a force plate with firm (no foam) and compliant (standing on foam) surface conditions in nine older adults with PD (70±5 years, 6 females) and 8 age-matched non-Parkinsonian older adults (5 females). Intermuscular coherence was analyzed between agonist-agonist and agonist-antagonist muscle pairs in the alpha (8-13 Hz) and beta (15-35 Hz) frequency bands.ResultsCoP parameters increased from bipedal to unipedal stance in both groups (p &lt; 0.01), but did not increase from the firm to compliant surface condition (p &gt; 0.05). During unipedal stance, CoP path length was shorter in older adults with PD (2027.9 ± 1074.1 mm) compared to controls (3128.5 ± 1198.7 mm) (p &lt; 0.01). Alpha and beta agonist-agonist and agonist-antagonist coherence increased by 28% from bipedal to unipedal stance (p &gt; 0.05), but did not differ between older adults with PD (0.09 ± 0.07) and controls (0.08 ± 0.05) (p &gt; 0.05). The older adults with PD also had greater normalized EMG amplitude of the LG (63.5 ± 31.7%) and TA (60.6 ± 38.4%) during the balance tasks (p &gt; 0.05) than the non-Parkinsonian counterparts.DiscussionOlder adults with PD had shorter path lengths during unipedal stance and required greater muscle activation than older adults without PD to perform the tasks, but intermuscular coherence did not differ between the groups. This may be attributable to their early disease stage and high motor function.
mGluR5 in amygdala modulates fear memory generalization
Authors: Xuan Shou-Min , Su Ya-Wen , Liang Yi-Meng , Gao Zhen-Jie , Liu Chun-Yan , Fan Bu-Fang , Shi Yan-Wei , Wang Xiao-Guang , Zhao Hu 
Published: February 2023

IntroductionFear memory generalization is regarded as the core characteristic of posttraumatic stress disorder (PTSD) development. However, the mechanism that contributes to the generalization of conditioned fear memory is still unclear. The generalization is generally considered to be a mismatch that occurs during memory consolidation.MethodsFoot shocks and tones were given as unconditioned stress and conditioned stress, respectively for fear conditioning training. Immunofluorescence staining, western blotting and qPCR were performed to determine the expression of different genes in amygdala of mice after fear conditioning training. Cycloheximide was used as a protein synthesis inhibitor and 2-methyl-6-phenylethynyl-pyridine was injected for mGluR5 inhibition.ResultsFear conditioning using caused incremental generalization, which was clearly observed during training. The density of c-Fos+ cells or the synaptic p-NMDAR expression did not differ with stress intensities. Strong-shock fear conditioning could induce significant mGluR5 de novo synthesis in the amygdala, which was not observed in the weak-shock group. Inhibition of mGluR5 impaired fear memory generalization induced by strong-shock fear conditioning, but the generalization level induced by weak-shock training was enhanced.DiscussionThese results indicated that mGluR5 in the amygdala is critical to the function of inappropriate fear memory generalization and suggested that this may be a potential target for the treatment of PTSD.
Improved space breakdown method – A robust clustering technique for spike sorting
Authors: Ardelean Eugen-Richard , Ichim Ana-Maria , Dînşoreanu Mihaela , Mureşan Raul Cristian 
Published: February 2023

Space Breakdown Method (SBM) is a clustering algorithm that was developed specifically for low-dimensional neuronal spike sorting. Cluster overlap and imbalance are common characteristics of neuronal data that produce difficulties for clustering methods. SBM is able to identify overlapping clusters through its design of cluster centre identification and the expansion of these centres. SBM’s approach is to divide the distribution of values of each feature into chunks of equal size. In each of these chunks, the number of points is counted and based on this number the centres of clusters are found and expanded. SBM has been shown to be a contender for other well-known clustering algorithms especially for the particular case of two dimensions while being too computationally expensive for high-dimensional data. Here, we present two main improvements to the original algorithm in order to increase its ability to deal with high-dimensional data while preserving its performance: the initial array structure was substituted with a graph structure and the number of partitions has been made feature-dependent, denominating this improved version as the Improved Space Breakdown Method (ISBM). In addition, we propose a clustering validation metric that does not punish overclustering and such obtains more suitable evaluations of clustering for spike sorting. Extracellular data recorded from the brain is unlabelled, therefore we have chosen simulated neural data, to which we have the ground truth, to evaluate more accurately the performance. Evaluations conducted on synthetic data indicate that the proposed improvements reduce the space and time complexity of the original algorithm, while simultaneously leading to an increased performance on neural data when compared with other state-of-the-art algorithms.Code available athttps://github.com/ArdeleanRichard/Space-Breakdown-Method.
Potential association among posterior fossa bony volume and crowdedness, tonsillar hernia, syringomyelia, and CSF dynamics at the craniocervical junction in Chiari malformation type I
Authors: Wang Shengxi , Zhang Dongao , Wu Kun , Fan Wayne , Fan Tao 
Published: February 2023

ObjectiveThe characteristic morphological parameters (bony posterior fossa volume (bony-PFV), posterior fossa crowdness, cerebellar tonsillar hernia, and syringomyelia) and CSF dynamics parameters at the craniocervical junction (CVJ) in Chiari malformation type I (CMI) were measured. The potential association between these characteristic morphologies and CSF dynamics at CVJ was analyzed.MethodsA total of 46 cases of control subjects and 48 patients with CMI underwent computed tomography and phase-contrast magnetic resonance imaging. Seven morphovolumetric measures and four CSF dynamics at CVJ measures were performed. The CMI cohort was further divided into “syringomyelia” and “non-syringomyelia” subgroups. All the measured parameters were analyzed by the Pearson correlation.ResultsCompared with the control, the posterior cranial fossa (PCF) area, bony-PFV, and CSF net flow were significantly smaller (P &lt; 0.001) in the CMI group. Otherwise, the PCF crowdedness index (PCF CI, P &lt; 0.001) and the peak velocity of CSF (P &lt; 0.05) were significantly larger in the CMI cohort. The mean velocity (MV) was faster in patients with CMI with syringomyelia (P &lt; 0.05). In the correlation analysis, the degree of cerebellar tonsillar hernia was correlated with PCF CI (R = 0.319, P &lt; 0.05), MV (R = −0.303, P &lt; 0.05), and the net flow of CSF (R = −0.300, P &lt; 0.05). The Vaquero index was well correlated with the bony-PFV (R= −0.384, P &lt; 0.05), MV (R = 0.326, P &lt; 0.05), and the net flow of CSF (R = 0.505, P &lt; 0.05).ConclusionThe bony-PFV in patients with CMI was smaller, and the MV was faster in CMI with syringomyelia. Cerebellar subtonsillar hernia and syringomyelia are independent indicators for evaluating CMI. Subcerebellar tonsillar hernia was associated with PCF crowdedness, MV, and the net flow of CSF at CVJ, while syringomyelia was associated with bony-PFV, MV, and the net flow of CSF at the CVJ. Thus, the bony-PFV, PCF crowdedness, and the degree of CSF patency should also be one of the indicators of CMI evaluation.
Risk factors of hemorrhagic transformation in acute ischaemic stroke: A systematic review and meta-analysis
Authors: Sun Jiacheng , Lam Christina , Christie Lauren , Blair Christopher , Li Xingjuan , Werdiger Freda , Yang Qing , Bivard Andrew , Lin Longting , Parsons Mark 
Published: February 2023

BackgroundHemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)].MethodsElectronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated.ResultsA total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212–5.599, I2 = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041–1.272, I2 = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970–7.591, I2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060–1.105, I2 = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001–1.005, I2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565–0.833, I2 =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012–1.866, I2 = 86.4%) were predictors of sICH after EVT.ConclusionSeveral predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927.
Association between sarcopenia and survival in patients with gynecologic cancer: A systematic review and meta-analysis
Authors: Lin Wen-Li , Nguyen Thi-Hoang-Yen , Lin Cheng-Yao , Wu Li-Min , Huang Wen-Tsung , Guo How-Ran 
Published: February 2023

BackgroundDespite prior attempts to evaluate the effects of sarcopenia on survival among patients with gynecologic cancer, the results of these studies have not been consistent. The present study evaluated the association between sarcopenia and survival among patients with gynecologic cancer by aggregating multiple studies.MethodsWe performed a literature search using computerized databases and identified additional studies included in the bibliographies of retrieved articles. The quality of each study was evaluated using the Newcastle–Ottawa Scale, and meta-analyses were performed to evaluate overall survival (OS) and progression-free survival (PFS). We constructed a forest plot for each outcome and assessed publication bias using Begg’s test. Heterogeneity was assessed using I2 statistics.ResultsFrom the 5,933 initially identified articles, 16 studies describing 2,031 participants with a mean age of 60.34 years were included in the meta-analysis. We found that compared with patients with gynecologic cancer but without sarcopenia, patients with sarcopenia had worse OS, with a pooled hazard ratio (HR) of 2.61 (95% confidence interval [CI]:1.52–4.46), and worse PFS (HR: 1.37, 95% CI: 1.09–1.73). The quality of studies was generally good, and no publication bias was detected among studies for either OS or PFS. Although 4 of 12 studies were of fair quality, we conducted a sensitivity analysis excluding studies or fair quality and obtained similar results.ConclusionsThese meta-analysis results suggest that sarcopenia is associated with worse OS and PFS among patients with gynecologic cancer. The use of different case definitions appeared to be a major source of heterogeneity among the studies. Further studies remain necessary to confirm our findings, especially those examining OS and PFS, because publication bias was identified.
Proteomic quantification of receptor tyrosine kinases involved in the development and progression of colorectal cancer liver metastasis
Authors: Vasilogianni Areti-Maria , Al-Majdoub Zubida M. , Achour Brahim , Peters Sheila Annie , Rostami-Hodjegan Amin , Barber Jill 
Published: February 2023

IntroductionAlterations in expression and activity of human receptor tyrosine kinases (RTKs) are associated with cancer progression and in response to therapeutic intervention.MethodsThus, protein abundance of 21 RTKs was assessed in 15 healthy and 18 cancerous liver samples [2 primary and 16 colorectal cancer liver metastasis (CRLM)] matched with non-tumorous (histologically normal) tissue, by a validated QconCAT-based targeted proteomic approach.ResultsIt was demonstrated, for the first time, that the abundance of EGFR, INSR, VGFR3 and AXL, is lower in tumours relative to livers from healthy individuals whilst the opposite is true for IGF1R. EPHA2 was upregulated in tumour compared with histologically normal tissue surrounding it. PGFRB levels were higher in tumours relative to both histologically normal tissue surrounding tumour and tissues taken from healthy individuals. The abundances of VGFR1/2, PGFRA, KIT, CSF1R, FLT3, FGFR1/3, ERBB2, NTRK2, TIE2, RET, and MET were, however, comparable in all samples. Statistically significant, but moderate correlations were observed (Rs &gt; 0.50, p &lt; 0.05) for EGFR with INSR and KIT. FGFR2 correlated with PGFRA and VGFR1 with NTRK2 in healthy livers. In non-tumorous (histologically normal) tissues from cancer patients, there were correlations between TIE2 and FGFR1, EPHA2 and VGFR3, FGFR3 and PGFRA (p &lt; 0.05). EGFR correlated with INSR, ERBB2, KIT and EGFR, and KIT with AXL and FGFR2. In tumours, CSF1R correlated with AXL, EPHA2 with PGFRA, and NTRK2 with PGFRB and AXL. Sex, liver lobe and body mass index of donors had no impact on the abundance of RTKs, although donor age showed some correlations. RET was the most abundant of these kinases in non-tumorous tissues (~35%), while PGFRB was the most abundant RTK in tumours (~47%). Several correlations were also observed between the abundance of RTKs and proteins relevant to drug pharmacokinetics (enzymes and transporters).DiscussionDiscussionThis study quantified perturbation to the abundance of several RTKs in cancer and the value generated in this study can be used as input to systems biology models defining liver cancer metastases and biomarkers of its progression.
Endoscopic surveillance of Lynch syndrome at a highly specialized center in Sweden: An observational study of interval colorectal cancer and individual risk factors
Authors: Jamizadeh Nigin , Walton Bernstedt Sophie , Haxhijaj Adrianna , Andreasson Anna , Björk Jan , Forsberg Anna , Backman Ann-Sofie 
Published: February 2023

IntroductionLynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC). In order to detect CRCs amongst LS patients, regular colonoscopies are recommended. However, an international agreement on an optimal surveillance interval has not yet been reached. In addition, few studies have investigated factors that could potentially increase the CRC risk amongst LS patients.AimsThe primary aim was to describe the frequency of CRCs detected during endoscopic surveillance and to estimate the interval from a clean colonoscopy to CRC detection amongst LS patients. The secondary aim was to investigate individual risk factors, including sex, LS genotype, smoking, aspirin use and body mass index (BMI), on CRC risk amongst patients that develop CRC before and during surveillance.Material and methodsClinical data and colonoscopy findings from 366 LS patients’ 1437 surveillance colonoscopies were collected from medical records and patient protocols. Logistic regression and Fisher’s exact test were used to investigate associations between individual risk factors and CRC development. Mann-Whitney U test was used to compare the distribution of TNM stages of CRC detected before surveillance and after index.ResultsCRC was detected in 80 patients before surveillance and in 28 patients during surveillance (10 at index and 18 after index). During the surveillance programme, CRC was detected within 24 months in 65% of the patients, and after 24 months within 35% of the patients. CRC was more common amongst men, previous and current smokers, and the odds of developing CRC also increased with an increasing BMI. CRCs were more often detected amongst MLH1 and MSH2 carriers during surveillance, compared to the other genotypes.ConclusionsWe found that 35% of the CRC cases detected during surveillance were found after 24 months. MLH1 and MSH2 carriers were at higher risk of developing CRC during surveillance. Additionally, men, current or previous smokers, and patients with a higher BMI were at higher risk of developing CRC. Currently, LS patients are recommended a “one-size-fits-all” surveillance program. The results support the development of a risk-score whereby individual risk factors should be taken into consideration when deciding on an optimal surveillance interval.
Corona enhancement combined with microvascular invasion for prognosis prediction of macrotrabecular-massive hepatocellular carcinoma subtype
Authors: Yang Lili , Wang Meng , Zhu Yanyan , Zhang Jiahui , Pan Junhan , Zhao Yanci , Sun Ke , Chen Feng 
Published: February 2023

ObjectivesThe macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) is aggressive and associated with an unfavorable prognosis. This study aimed to characterize MTM-HCC features based on contrast−enhanced MRI and to evaluate the prognosis of imaging characteristics combined with pathology for predicting early recurrence and overall survival after surgery.MethodsThis retrospective study included 123 patients with HCC that underwent preoperative contrast−enhanced MRI and surgery, between July 2020 and October 2021. Multivariable logistic regression was performed to investigate factors associated with MTM-HCC. Predictors of early recurrence were determined with a Cox proportional hazards model and validated in a separate retrospective cohort.ResultsThe primary cohort included 53 patients with MTM-HCC (median age 59 years; 46 male and 7 females; median BMI 23.5 kg/m2) and 70 subjects with non-MTM HCC (median age 61.5 years; 55 male and 15 females; median BMI 22.6 kg/m2) (All P&gt;0.05). The multivariate analysis identified corona enhancement (odds ratio [OR]=2.52, 95% CI: 1.02–6.24; P=0.045) as an independent predictor of the MTM-HCC subtype. The multiple Cox regression analysis identified corona enhancement (hazard ratio [HR]=2.56, 95% CI: 1.08–6.08; P=0.033) and MVI (HR=2.45, 95% CI: 1.40–4.30; P=0.002) as independent predictors of early recurrence (area under the curve=0.790, P&lt;0.001). The prognostic significance of these markers was confirmed by comparing results in the validation cohort to those from the primary cohort. Corona enhancement combined with MVI was significantly associated with poor outcomes after surgery.ConclusionsA nomogram for predicting early recurrence based on corona enhancement and MVI could be used to characterize patients with MTM-HCC and predict their prognosis for early recurrence and overall survival after surgery.