bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 41-Gene Pair Signature for Predicting the Pathological Response of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiation
Authors: Xue Zhengfa , Yang Shuxin , Luo Yun , Cai Hao , He Ming , Ding Youping , Lei Lei , Peng Wei , Hong Guini , Guo You 
Published: September 2021

Background and Purpose: Pathological response status is a standard reference for the early evaluation of the effect of neoadjuvant chemoradiation (nCRT) on locally advanced rectal cancer (LARC) patients. Various patients respond differently to nCRT, but identifying the pathological response of LARC to nCRT remains a challenge. Therefore, we aimed to identify a signature that can predict the response of LARC to nCRT.Material and Methods: The gene expression profiles of 111 LARC patients receiving fluorouracil-based nCRT were used to obtain gene pairs with within-sample relative expression orderings related to pathological response. These reversal gene pairs were ranked according to the mean decrease Gini index provided by the random forest algorithm to obtain the signature. This signature was verified in two public cohorts of 46 and 42 samples, and a cohort of 33 samples measured at our laboratory. In addition, the signature was used to predict disease-free survival benefits in a series of colorectal cancer datasets.Results: A 41-gene pair signature (41-GPS) was identified in the training cohort with an accuracy of 84.68% and an area under the receiver operating characteristic curve (AUC) of 0.94. In the two public test cohorts, the accuracy was 93.37 and 73.81%, with AUCs of 0.97 and 0.86, respectively. In our dataset, the AUC was 0.80. The results of the survival analysis show that 41-GPS plays an effective role in identifying patients who will respond to nCRT and have a better prognosis.Conclusion: The signature consisting of 41 gene pairs can robustly predict the clinical pathological response of LARC patients to nCRT.
Molecular Brightness Approach for FRET Analysis of Donor-Linker-Acceptor Constructs at the Single Molecule Level: A Concept
Authors: Kay Taryn M. , Aplin Cody P. , Simonet Rowan , Beenken Julie , Miller Robert C. , Libal Christin , Boersma Arnold J. , Sheets Erin D. , Heikal Ahmed A. 
Published: September 2021

In this report, we have developed a simple approach using single-detector fluorescence autocorrelation spectroscopy (FCS) to investigate the Förster resonance energy transfer (FRET) of genetically encoded, freely diffusing crTC2.1 (mTurquoise2.1–linker–mCitrine) at the single molecule level. We hypothesize that the molecular brightness of the freely diffusing donor (mTurquoise2.1) in the presence of the acceptor (mCitrine) is lower than that of the donor alone due to FRET. To test this hypothesis, the fluorescence fluctuation signal and number of molecules of freely diffusing construct were measured using FCS to calculate the molecular brightness of the donor, excited at 405 nm and detected at 475/50 nm, in the presence and absence of the acceptor. Our results indicate that the molecular brightness of cleaved crTC2.1 in a buffer is larger than that of the intact counterpart under 405-nm excitation. The energy transfer efficiency at the single molecule level is larger and more spread in values as compared with the ensemble-averaging time-resolved fluorescence measurements. In contrast, the molecular brightness of the intact crTC2.1, under 488 nm excitation of the acceptor (531/40 nm detection), is the same or slightly larger than that of the cleaved counterpart. These FCS-FRET measurements on freely diffusing donor-acceptor pairs are independent of the precise time constants associated with autocorrelation curves due to the presence of potential photophysical processes. Ultimately, when used in living cells, the proposed approach would only require a low expression level of these genetically encoded constructs, helping to limit potential interference with the cell machinery.
Trajectory of Long-Term Outcome in Severe Pediatric Diffuse Axonal Injury: An Exploratory Study
Authors: Lang Shih-Shan , Kilbaugh Todd , Friess Stuart , Sotardi Susan , Kim Chong Tae , Mazandi Vanessa , Zhang Bingqing , Storm Phillip B. , Heuer Gregory G. , Tucker Alexander , Ampah Steve B. , Griffis Heather , Raghupathi Ramesh , Huh Jimmy W. 
Published: September 2021

Introduction: Pediatric severe traumatic brain injury (TBI) is one of the leading causes of disability and death. One of the classic pathoanatomic brain injury lesions following severe pediatric TBI is diffuse (multifocal) axonal injury (DAI). In this single institution study, our overarching goal was to describe the clinical characteristics and long-term outcome trajectory of severe pediatric TBI patients with DAI.Methods: Pediatric patients (&lt;18 years of age) with severe TBI who had DAI were retrospectively reviewed. We evaluated the effect of age, sex, Glasgow Coma Scale (GCS) score, early fever ≥ 38.5°C during the first day post-injury, the extent of ICP-directed therapy needed with the Pediatric Intensity Level of Therapy (PILOT) score, and MRI within the first week following trauma and analyzed their association with outcome using the Glasgow Outcome Score—Extended (GOS-E) scale at discharge, 6 months, 1, 5, and 10 years following injury.Results: Fifty-six pediatric patients with severe traumatic DAI were analyzed. The majority of the patients were &gt;5 years of age and male. There were 2 mortalities. At discharge, 56% (30/54) of the surviving patients had unfavorable outcome. Sixty five percent (35/54) of surviving children were followed up to 10 years post-injury, and 71% (25/35) of them made a favorable recovery. Early fever and extensive DAI on MRI were associated with worse long-term outcomes.Conclusion: We describe the long-term trajectory outcome of severe pediatric TBI patients with pure DAI. While this was a single institution study with a small sample size, the majority of the children survived. Over one-third of our surviving children were lost to follow-up. Of the surviving children who had follow-up for 10 years after injury, the majority of these children made a favorable recovery.
Postoperative Evaluation of the Quality of Life, Depression, and Anxiety of Temporal Lobe Epilepsy Cohort: A Single Institute Experience in Indonesia
Authors: Bakhtiar Yuriz , Pratama Brilliantika Surya , Bunyamin Jacob , Arifin Muhammad Thohar , Hardian Hardian , Bintoro Aris Catur , Muttaqin Zainal 
Published: September 2021

Background: Besides seizure control, quality of life (QoL) should be considered as an equally important outcome for epilepsy surgery service providers. The paucity of QoL reports from developing countries has enlarged the representation gap between wealthy countries and countries with fewer resources. In this study, we evaluated postoperative QoL in the Indonesian drug-resistant epilepsy cohort where the epilepsy surgery service faces limited resource availability.Methods: We evaluated the QoL in patients with temporal lobe epilepsy who underwent surgery in our epilepsy surgery center in Semarang, Indonesia, from 2001 until 2015. The follow–up period started in 2018 through 2019. Postoperative QoL, depression, and anxiety were evaluated with self-reporting questionnaires including the Quality of Life in Epilepsy Inventory-31, Beck Depression Inventory-II, and Zung Self-Rating Anxiety Scales.Results: Forty returned questionnaires were included in the analysis (male 25, 62.5%; mean age 27.6 ± 9.05 years). The seizure-free cohort (n = 22, 55.0%) reported higher scores in most QoL dimensions particularly adjustment, overall QoL, and seizure worry compared to those with persistent seizures. The overall QoL level was correlated with seizure freedom and surgery type. QoL dimensions were negatively correlated with anxiety and depression levels.Conclusions: Postoperative seizure freedom was a major factor of postoperative QoL level. Besides seizure freedom, anxiety and depression levels were also negatively correlated with QoL levels in the Indonesian population.
Outer Retinal Layer Thickness Changes in White Matter Hyperintensity and Parkinson's Disease
Authors: Zhao Yitian , Zhao Jinyu , Gu Yuanyuan , Chen Bang , Guo Jiaqi , Xie Jianyang , Yan Qifeng , Ma Yuhui , Wu Yufei , Zhang Jiong , Lu Qinkang , Liu Jiang 
Published: September 2021

Purpose: To investigate the thickness changes of outer retinal layers in subjects with white matter hyperintensities (WMH) and Parkinson's Disease (PD).Methods: 56 eyes from 31 patients with WMH, 11 eyes from 6 PD patients, and 58 eyes from 32 healthy controls (HC) were enrolled in this study. A macular-centered scan was conducted on each participant using a spectral-domain optical coherence tomography (SD-OCT) device. After speckle noise reduction, a state-of-the-art deep learning method (i.e., a context encoder network) was employed to segment the outer retinal layers from OCT B-scans. Thickness quantification of the outer retinal layers was conducted on the basis of the segmentation results.Results: WMH patients had significantly thinner Henle fiber layers, outer nuclear layers (HFL+ONL) and photoreceptor outer segments (OS) than HC (p = 0.031, and p = 0.005), while PD patients showed a significant increase of mean thickness in the interdigitation zone and the retinal pigment epithelium/Bruch complex (IZ+RPE) (19.619 ± 4.626) compared to HC (17.434 ± 1.664). There were no significant differences in the thickness of the outer plexiform layer (OPL), the myoid and ellipsoid zone (MEZ), and the IZ+RPE layer between WMH and HC subjects. Similarly, there were also no obvious differences in the thickness of the OPL, HFL+ONL, MEZ and the OS layer between PD and HC subjects.Conclusion: Thickness changes in HFL+ONL, OS, and IZ+RPE layers may correlate with brain-related diseases such as WMH and PD. Further longitudinal study is needed to confirm HFL+ONL/OS/IZ+RPE layer thickness as potential biomarkers for detecting certain brain-related diseases.
Preoperative Metastatic Brain Tumor-Associated Intracerebral Hemorrhage Is Associated With Dismal Prognosis
Authors: Hamed Motaz , Schäfer Niklas , Bode Christian , Borger Valeri , Potthoff Anna-Laura , Eichhorn Lars , Giordano Frank A. , Güresir Erdem , Heimann Muriel , Ko Yon-Dschun , Landsberg Jennifer , Lehmann Felix , Radbruch Alexander , Scharnböck Elisa , Schaub Christina , Schwab Katjana S. , Weller Johannes , Herrlinger Ulrich , Vatter Hartmut , Schuss Patrick , Schneider Matthias 
Published: September 2021

ObjectIntra-tumoral hemorrhage is considered an imaging characteristic of advanced cancer disease. However, data on the influence of intra-tumoral hemorrhage in patients with brain metastases (BM) remains scarce. We aimed at investigating patients with BM who underwent neurosurgical resection of the metastatic lesion for a potential impact of preoperative hemorrhagic transformation on overall survival (OS).MethodsBetween 2013 and 2018, 357 patients with BM were surgically treated at the authors’ neuro-oncological center. Preoperative magnetic resonance imaging (MRI) examinations were assessed for the occurrence of malignant hemorrhagic transformation.Results122 of 375 patients (34%) with BM revealed preoperative intra-tumoral hemorrhage. Patients with hemorrhagic transformed BM exhibited a median OS of 5 months compared to 12 months for patients without intra-tumoral hemorrhage. Multivariate analysis revealed preoperative hemorrhagic transformation as an independent and significant predictor for worsened OS.ConclusionsThe present study identifies preoperative intra-tumoral hemorrhage as an indicator variable for poor prognosis in patients with BM undergoing neurosurgical treatment.
AGTRAP Is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma
Authors: Liu Shanshan , Zhao Wei , Li Xuemei , Zhang La , Gao Yu , Peng Qiling , Du Chengyou , Jiang Ning 
Published: September 2021

BackgroundRecently, it has been reported that angiotensin II receptor-associated protein (AGTRAP) plays a substantial role in tumor progression. Nevertheless, the possible role of AGTRAP in hepatocellular carcinoma (HCC) remains unrecognized.MethodsThe metabolic gene rapid visualizer, Cancer Cell Line Encyclopedia, Human Protein Atlas, and Hepatocellular Carcinoma Database were used to analyze the expression of AGTRAP in HCC tissues and normal liver tissues or adjacent tissues. Kaplan-Meier plotter and UALCAN analysis were used to assess the prognostic and diagnostic value of AGTRAP. LinkedOmics and cBioPortal were used to explore the genes co-expressed with AGTRAP in HCC. To further understand the potential mechanism of AGTRAP in HCC, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathway analyses were performed using R software, the protein-protein interaction (PPI) network was established using the STRING database, and the immune infiltration and T-cell exhaustion related to AGTRAP were explored via Timer and GEPIA. In addition, immunohistochemistry was used to detect the expression of AGTRAP protein in HCC tissues and paired adjacent tissues from clinical specimens.ResultsThis study found that the mRNA and protein levels of AGTRAP in HCC tissues were higher than those in normal liver tissues and adjacent tissues, and higher mRNA levels of AGTRAP were associated with higher histological grade and a poor overall survival in HCC patients. The area under the receiver operating characteristic curve (AUC) of AGTRAP was 0.856, suggesting that it could be a diagnostic marker for HCC. Moreover, the alteration rate of AGTRAP in HCC was 8%, and AGTRAP was involved in HCC probably through the NF-κB and MAPK signaling pathways. Furthermore, AGTRAP was positively correlated with the infiltration of CD8+ T cells, CD4+ T cells, B cells, macrophages, dendritic cells, and neutrophils, and the levels of AGTRAP were significantly correlated with T-cell exhaustion biomarkers. The immunohistochemistry results confirmed that the protein levels of AGTRAP were consistently higher in HCC tissues than in paired adjacent tissues.ConclusionThe clinical value of AGTRAP and its correlation with immune infiltration in HCC was effectively identified in clinical data from multiple recognized databases. These findings indicate that AGTRAP could serve as a potential biomarker in the treatment of HCC, thereby informing its prognosis, diagnosis, and even immunotherapy.
Incidence, Clinical Characteristics, and Survival of Collecting Duct Carcinoma of the Kidney: A Population-Based Study
Authors: Tang Chaopeng , Zhou Yulin , Ge Silun , Yi Xiaoming , Lv Huichen , Zhou Wenquan 
Published: September 2021

ObjectiveTo investigate the exact age‐adjusted incidence (AAI), clinical characteristics, and survival data of collecting duct carcinoma of the kidney (CDCK) recorded in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute.MethodsPatients with CDCK confirmed by microscopic examination from 2004 to 2018 were selected from the SEER database. AAI rates were calculated using SEER*Stat software (version 8.3.9). The Kaplan‐Meier method was used to evaluate cancer-specific survival (CSS) rates according to tumor size, tumor stage, and treatment methods, and differences among these variables were assessed by the log‐rank test. Cox regression analysis was employed to identify variables independently related to CSS.ResultsA total of 286 patients with CDCK were identified from the database. The majority of the patients were white (69.2%), male (67.5%), and married (60.5%), and the median age was 59 years. Most patients with CDCK (74.4%) presented with stages III or IV disease. The diameter of most (59.4%) tumors was less than 7 cm, and the tumors were more commonly found on the left than on the right (55.2% vs. 44.8%). The incidence of CDCK decreased over time. The median CSS time was 17 months. In terms of the treatment modalities used, 83.9% of the patients underwent surgery; 32.9% underwent chemotherapy, and 13.6% underwent radiotherapy. The CSS rates at 1, 2, and 5 years were 57.3%, 43.2%, and 30.7%, respectively. In patients with stage IV CDCK treated with surgery alone, chemotherapy alone, and surgery plus chemotherapy, the median survival time was 5 months, 9 months, and 14 months, respectively (P =0.024). Multivariate Cox regression analysis showed surgery, chemotherapy, stage, regional lymph node metastasis, and distant metastasis were independent prognostic factors for patients with CDCK.ConclusionsCDCK is an uncommon malignant renal carcinoma, and its incidence is decreasing based on the analysis of current data. CDCK is a high stage, regional lymph-nodes positive, and metastatic disease. Compared with surgery alone or chemotherapy alone, patients with stage IV could gain survival benefit from surgery combined with chemotherapy.
Ginsenoside Rb1 Lessens Gastric Precancerous Lesions by Interfering With β-Catenin/TCF4 Interaction
Authors: Zeng Jinhao , Ma Xiao , Zhao Ziyi , Chen Yu , Wang Jundong , Hao Yanwei , Yu Junrong , Zeng Zhongzhen , Chen Nianzhi , Zhao Maoyuan , Tang Jianyuan , Gong Daoyin 
Published: September 2021

Background: Seeking novel and effective therapies for gastric precancerous lesions (GPL) is crucial to reducing the incidence of gastric cancer. Ginsenoside Rb1 (GRb1) is a major ginsenoside in ginseng and has been proved to possess multiple bioactivities. However, whether GRb1 could protect against GPL and the underlying mechanisms have not been explored.Methods: We evaluated the effects of GRb1 on gastric precancerous lesions in rats on macroscopic, microscopic and ultramicroscopic levels. Then, an antibody array was employed to screen differential expression proteins (DEPs). Validation for the targeting DEP and investigation for the possible mechanism was conducted using immunohistochemistry, qRT-PCR, TUNEL apoptosis assay, immunoprecipitation and immunoblotting.Results: GRb1 was found to reverse intestinal metaplasia and a portion of dysplasia in the MNNG-induced GPL rats. The antibody array assay revealed seven DEPs in GPL rats as compared to control rats (5 DEPs were up-regulated, while two DEPs were down-regulated). Among the DEPs, β-catenin, beta-NGF and FSTL1 were significantly down-regulated after GRb1 administration. Our validation results revealed that enhanced protein expression and nuclear translocation of β-catenin were present in animal GPL samples. In addition, analysis of human gastric specimens demonstrated that β-catenin up-regulation and nuclear translocation were significantly associated with advanced GPL pathology. GRb1 intervention not only decreased protein expression and nuclear translocation of β-catenin, but interfered with β-catenin/TCF4 interaction. Along with this, declined transcriptional and protein expression levels of downstream target genes including c-myc, cyclin D1 and Birc5 were observed in GRb1-treated GPL rats.Conclusion: GRb1 is capable of preventing the occurrence and progression of GPL, which might be contributed by diminishing protein expression and nuclear translocation of β-catenin and interfering with β-catenin/TCF4 interaction.
Arbutin Ameliorates Murine Colitis by Inhibiting JAK2 Signaling Pathway
Authors: Wang Liang , Feng Yuntao , Wang Jianwen , Luo Tenglong , Wang Xinyue , Wu Mengze , Wang Runxia , Chen Dapeng , Li Jiyan , Wang Jingyu 
Published: September 2021

Background and objective: Abnormal activation of Janus kinase 2 (JAK2) promotes the pathogenesis and progress of inflammatory bowel disease (IBD) by stimulating the cytokine traffic. Based on docking studies, arbutin, a natural product extracted from a traditional medicinal plant bearberry, was found to bind to JAK2. The study aimed to investigate the effects and mechanisms of regulating JAK2 by arbutin on colitis in mice.Methods: A mice colitis model was established to mimic human IBD. The mice freely drank water containing dextran sulfate sodium. Inflammation in epithelial (IEC6) and immune (RAW264.7) cells was analyzed following treatment with lipopolysaccharides (LPS).Results: Colitis symptoms, including body weight loss, increased disease activity index, and increased colon weight/length ratio, were significantly alleviated by arbutin. Mediators of colonic pro-inflammatory cytokines as well as apoptosis markers in colitis were suppressed by the glycoside. High expression of phosphorylated JAK2 in colitis was significantly reversed by arbutin. The effects of arbutin treatment on colitis were considerably inhibited by the JAK2 inhibitor AG490. LPS-induced inflammatory responses were also suppressed by arbutin, which was notably inhibited by the JAK2 inhibitor AG490.Conclusion: The findings obtained herein suggest the protective role of arbutin and provide novel insights into alternative colitis treatments, which involve inhibition of the JAK2 signaling pathway.
Opioids and Gabapentinoids Utilisation and Their Related-Mortality Trends in the United Kingdom Primary Care Setting, 2010–2019: A Cross-National, Population-Based Comparison Study
Authors: Kurdi Amanj 
Published: September 2021

Background: There is growing concern over the increasing utilisation trends of opioids and gabapentinoids across but there is lack of data assessing and comparing the utilisation trends across the four United Kingdom countries. We assessed/compared opioids and gabapentinoids utilisation trends across the four United Kingdom countries then evaluated the correlation between their utilisation with related mortality.Methods: This repeated cross-national study used Prescription Cost Analysis (PCA) datasets (2010–2019). Opioids and gabapentinoids utilisation were measured using number of items dispensed/1,000 inhabitants and defined daily doses (DDDs)/1,000 inhabitant/day. Number of Opioids and gabapentinoids-related mortality were extracted from the United Kingdom Office for National Statistics (2010–2018). Data were analysed using descriptive statistics including linear trend analysis; correlation between the Opioids and gabapentinoids utilisation and their related mortality using Pearson correlation coefficient.Results: The results illustrated an overall significant increasing trend in the utilisation of opioids (12.5–14%) and gabapentinoids (205–207%) with substantial variations among the four United Kingdom countries. For opioids, Scotland had the highest level of number of items dispensed/1,000 inhabitant (156.6% higher compared to the lowest level in England), whereas in terms of DDD/1,000 inhabitant/day, NI had the highest level. Utilisation trends increased significantly across the four countries ranging from 7.7% in Scotland to 20.5% in NI (p &lt; 0.001). Similarly, for gabapentinoids, there were significant increasing trends ranging from 126.5 to 114.9% in NI to 285.8–299.6% in Wales (p &lt; 0.001) for number of items/1,000 inhabitants and DDD/1,000 inhabitant/day, respectively. Although the utilisation trends levelled off after 2016, this was not translated into comparable reduction in opioids and gabapentinoids-related mortality as the latter continued to increase with the highest level in Scotland (3.5 times more deaths in 2018 compared to England- 280.1 vs. 79.3 deaths/million inhabitants). There were significant moderate-strong positive correlations between opioids and gabapentinoids utilisation trends and their related mortality.Conclusion: The utilisation trends of opioids and gabapentinoids have increased significantly with substantial variations among the four United Kingdom countries. This coincided with significant increase in their related mortality. Our findings support the call for immediate actions including radical changes in official United Kingdom policies on drug use and effective strategies to promote best clinical practice in opioids and gabapentinoids prescribing.