bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcranial near-infrared laser improves postoperative neurocognitive disorder in aged mice via SIRT3/AMPK/Nrf2 pathway
Authors: Zhong Junying , Zhao Le , Wu Wensi , Chen Jiawei , Yuan Shangyan , Zhang Xiaojun , Wang Zhi 
Published: January 2023

BackgroundPostoperative neurocognitive disorder (PND) is a common central nervous system (CNS) complication that might increase the morbidity and mortality of elderly patients after anesthesia/surgery. Neuroinflammation, oxidative stress, and synaptic dysfunction are closely related to cognitive dysfunction, an important clinical feature of PND. Transcranial near-infrared laser (TNIL) is regarded as an effective treatment for cognitive-related diseases by improving mitochondrial function and alleviating neuroinflammation and oxidative stress damage.Materials and methodsAged male C57BL/6 mice underwent a carotid artery exposure procedure under isoflurane anesthesia. We treated PND-aged mice for three consecutive days (4 h post-operation, 1-laser) with 810 nm continuous wave (CW) laser 18 J/cm2 at 120 mW/cm2. The post-treatment evaluation included behavioral tests, RTq-PCR, immunofluorescence, and Western blot.ResultsThe results demonstrated that TNIL improved PND and the levels of synaptic function-associated proteins such as post-synaptic density protein 95 (PSD95), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Besides, neuroinflammatory cytokine levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β as well as microglia activation and oxidative stress damage were attenuated after TNIL treatment in aged mice with PND. Further investigation suggested that TNIL relieved oxidative stress response by activating the SIRT3/AMPK/Nrf2 pathway.ConclusionTranscranial near-infrared laser improved cognitive impairment in aged mice with PND, which may be a promising therapeutic for PND.
A genome-wide association study of a rage-related misophonia symptom and the genetic link with audiological traits, psychiatric disorders, and personality
Authors: Smit Dirk J. A. , Bakker Melissa , Abdellaoui Abdel , Hoetink Alexander E. , Vulink Nienke , Denys Damiaan 
Published: January 2023

IntroductionPeople with misophonia experience strong negative emotional responses to sounds and associated stimuli—mostly human produced—to an extent that it may cause impairment in social functioning. The exact nature of the disorder remains a matter of ongoing research and debate. Here, we investigated the genetic etiology of misophonia to understand contributing genetic factors and shed light on individual differences in characteristics that are related to the disorder.MethodsFor misophonia, we used an unpublished genome-wide association study (GWAS) from genetic service provider 23andMe, Inc., on a self-report item probing a single common misophonic symptom: the occurrence of rage when others produce eating sounds. First, we used gene-based and functional annotation analyses to explore neurobiological determinants of the rage-related misophonia symptom. Next, we calculated genetic correlations (rG) of this rage-related misophonia symptom GWAS with a wide range of traits and disorders from audiology (tinnitus, hearing performance, and hearing trauma), psychiatry, neurology, and personality traits.ResultsThe rage-related misophonia symptom was significantly correlated with tinnitus, major depression disorder (MDD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD; 0.12 &lt;rG&lt; 0.22). Stronger genetic correlations (0.21 &lt;rG&lt; 0.42) were observed for two clusters of personality traits: a guilt/neuroticism and an irritability/sensitivity cluster. Our results showed no genetic correlation with attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and psychotic disorders. A negative correlation with autism spectrum disorder (ASD) was found, which may be surprising given the previously reported comorbidities and the sensory sensitivity reported in ASD. Clustering algorithms showed that rage-related misophonia consistently clustered with MDD, generalized anxiety, PTSD, and related personality traits.DiscussionWe conclude that—based on the genetics of a common misophonia symptom—misophonia most strongly clusters with psychiatric disorders and a personality profile consistent with anxiety and PTSD.
m7G-related gene NUDT4 as a novel biomarker promoting cancer cell proliferation in lung adenocarcinoma
Authors: Liu Yafei , Jiang Bin , Lin Chunjie , Zhu Wanyinhui , Chen Dingrui , Sheng Yinuo , Lou Zhiling , Ji Zhiheng , Wu Chuanqiang , Wu Ming 
Published: January 2023

BackgroundLung cancer is the leading cause of mortality in cancer patients. N7-methylguanosine (m7G) modification as a translational regulation pattern has been reported to participate in multiple types of cancer progression, but little is known in lung cancer. This study attempts to explore the role of m7G-related proteins in genetic and epigenetic variations in lung adenocarcinoma, and its relationship with clinical prognosis, immune infiltration, and immunotherapy.MethodsSequencing data were obtained from the Genomic Data Commons (GDC) Data Portal and Gene Expression Omnibus (GEO) databases. Consensus clustering was utilized to distinguish m7G clusters, and responses to immunotherapy were also evaluated. Moreover, univariate and multivariate Cox and Least absolute shrinkage and selection operator LASSO Cox regression analyses were used to screen independent prognostic factors and generated risk scores for constructing a survival prediction model. Multiple cell types such as epithelial cells and immune cells were identified to verify the bulk RNA results. Short hairpin RNA (shRNA) Tet-on plasmids, Clustered Regularly Interspaced Short Palindromic Repeats CRISPR/Cas9 for knockout plasmids, and nucleoside diphosphate linked to moiety X-type motif 4 (NUDT4) overexpression plasmids were constructed to inhibit or promote tumor cell NUDT4 expression, then RT-qPCR, Cell Counting Kit-8 CCK8 proliferation assay, and Transwell assay were used to observe tumor cell biological functions.ResultsFifteen m7G-related genes were highly expressed in tumor samples, and 12 genes were associated with poor prognosis. m7G cluster-B had lower immune infiltration level, worse survival, and samples that predicted poor responses to immunotherapy. The multivariate Cox model showed that NUDT4 and WDR4 (WD repeat domain 4) were independent risk factors. Single-cell m7G gene set variation analysis (GSVA) scores also had a negative correlation tendency with immune infiltration level and T-cell Programmed Death-1 PD-1 expression, but the statistics were not significant. Knocking down and knocking out the NUDT4 expression significantly inhibited cell proliferation capability in A549 and H1299 cells. In contrast, overexpressing NUDT4 promoted tumor cell proliferation. However, there was no difference in migration capability in the knockdown, knockout, or overexpression groups.ConclusionsOur study revealed that m7G modification-related proteins are closely related to the tumor microenvironment, immune cell infiltration, responses to immunotherapy, and patients’ prognosis in lung adenocarcinoma and could be useful biomarkers for the identification of patients who could benefit from immunotherapy. The m7G modification protein NUDT4 may be a novel biomarker in promoting the progression of lung cancer.
Efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis of randomized controlled trials
Authors: Liang Zhanpeng , Lin Sihong , Lai Huiqin , Li Luzhen , Wu Jiaming , Zhang Huatang , Fang Cantu 
Published: January 2023

BackgroundThe addition of endocrine therapy to salvage radiotherapy (SRT) is expected to further improve the prognosis of patients with biochemical recurrence of prostate cancer after radical prostatectomy (RP). The quantitative synthesis of clinical outcomes of SRT combined with endocrine therapy is limited. Whether salvage radiotherapy plus endocrine therapy remains inconclusive. We performed a systematic review and meta-analysis of existing randomized controlled trials to evaluate the efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy.MethodsA systematic search of PubMed, EMBASE, and the Cochrane library was performed for articles published between January 1, 2012 and October 10, 2022. Data were analyzed using Review Manager 5.4.1 (Cochrane Collaboration Software). Main outcome and measures included biochemical progression-free survival (bPFS), metastasis free survival (MFS), overall survival (OS), and Grade 3 or higher adverse events (3+AEs), including acute and late adverse events.ResultsIn this systematic review and meta-analysis, 4 randomized controlled studies enrolling 2731 male (1374 of whom received SRT combined with endocrine therapy and 1357 controls) met the inclusion criteria. SRT combined with endocrine therapy were related to significantly improve bPFS (HR=0.52; 95% CI: 0.46 0.59; p&lt;0.00001) and MFS (HR=0.75; 95% CI: 0.64 0.88; p&lt;0.001). Compared with SRT alone, the combination therapy tended to be associated with prolong OS (HR=0.83; 95% CI: 0.69-1.01; p=0.06), but not statistically significant. At early follow-up, the risk of acute AEs was comparable in the two groups (RR=1.04; 95% CI: 0.22-4.85). However, the risk of late AEs was higher in the combination group at later follow-up (RR=1.33; 95% CI: 1.09-1.62).ConclusionsThis systematic review and meta-analysis found superior efficacy associated with adding endocrine therapy to SRT compared with SRT alone in patients with biochemical recurrence after RP. Additional endocrine therapy is safe and feasible for patients with biochemical recurrence after RP.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42022365432).
Occult hepatitis B in patients with cancer during immunotherapy with or without chemotherapy: A real-life retrospective single-center cohort study
Authors: Lasagna Angioletta , Albi Giuseppe , Maserati Renato , Zuccarini Andrea , Quaccini Mattia , Baldanti Fausto , Sacchi Paolo , Bruno Raffaele , Pedrazzoli Paolo 
Published: January 2023

IntroductionFew data about the safety of immune checkpoint inhibitors (ICIs) in the patients with solid tumor with Occult Hepatitis B Virus (OBI) are available. According to the Taormina Workshop on Occult HBV Infection Faculty Members we defined as potential-OBI (pOBI) the HBV DNA negativity with anti-hepatitis B core antibody (anti-HBc) positivity (pOBI seropositive), and the patients with HBsAg–negative and anti-HBc–negative and Hepatitis B surface antibody (anti-HBs)–negative are defined pOBI seronegative. The aim of this study is to investigate the prevalence of OBI in patients with solid tumors undergoing ICIs with or without chemotherapy and the incidence of reactivation (HBVr).MethodsWe retrospectively enrolled all HBsAg negative subjects who had received ICIs for at least three months. HBsAg and HBV DNA levels were repeated every 3 months until the end of the study and/or in case of ALT alterations. A univariate analysis was conducted in order to study for each variable available its ability to distinguish a potential OBI seropositive patient from a seronegative one.Results150 patients in our Oncology Unit were eligible. One hundred and seventeen patients (78%) received ICI as monotherapy, whereas 33 patients (22%) were treated with chemo-immunotherapy. The mainly used drugs for the ICI monotherapy were Pembrolizumab (47%), Nivolumab (33%) and Atezolizumab (11%). The prevalence of pOBI seropositive patients was 25.3%. We did not observe alterations of liver biochemistry nor HBVr.DiscussionThis study highlights that about a quarter of our population had a potential occult hepatitis B. Immunotherapy might be considered as low risk of reactivation, regardless of the potential presence of episomal covalently closed circular DNA (cccDNA) in the liver, but the correct management still represents a challenge for oncologists and hepatologists.
Relationship between polymorphisms in homologous recombination repair genes RAD51 G172T、XRCC2 & XRCC3 and risk of breast cancer: A meta-analysis
Authors: Yu Jiayang , Wang Chun-Guang 
Published: January 2023

BackgroundGenetic variability in DNA double-strand break repair genes such as RAD51 gene and its paralogs XRCC2、XRCC3 may contribute to the occurrence and progression of breast cancer. To obtain a complete evaluation of the above association, we performed a meta-analysis of published studies.MethodsElectronic databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were comprehensively searched from inception to September 2022. The Newcastle-Ottawa Scale (NOS) checklist was used to assess all included non-randomized studies. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by STATA 16.0 to assess the strength of the association between single nucleotide polymorphisms (SNPs) in these genes and breast cancer risk. Subsequently, the heterogeneity between studies, sensitivity, and publication bias were performed. We downloaded data from The Cancer Genome Atlas (TCGA) and used univariate and multivariate Cox proportional hazard regression (CPH) models to validate the prognostic value of these related genes in the R software.ResultsThe combined results showed that there was a significant correlation between the G172T polymorphism and the susceptibility to breast cancer in the homozygote model (OR= 1.841, 95% CI=1.06–3.21, P=0.03). Furthermore, ethnic analysis showed that SNP was associated with the risk of breast cancer in Arab populations in homozygous models (OR=3.52, 95% CI=1.13-11.0, P= 0.003). For the XRCC2 R188H polymorphism, no significant association was observed. Regarding polymorphism in XRCC3 T241M, a significantly increased cancer risk was only observed in the allelic genetic model (OR=1.05, 95% CI= 1.00–1.11, P=0.04).ConclusionsIn conclusion, this meta-analysis suggests that Rad51 G172T polymorphism is likely associated with an increased risk of breast cancer, significantly in the Arab population. The relationship between the XRCC2 R188H polymorphism and breast cancer was not obvious. And T241M in XRCC3 may be associated with breast cancer risk, especially in the Asian population.
Geographic variation in malignant cardiac tumors and their outcomes: SEER database analysis
Authors: Rahouma Mohamed , Khairallah Sherif , Dabsha Anas , Baudo Massimo , El-Sayed Ahmed Magdy M. , Gambardella Ivancarmine , Lau Christopher , Esmail Yomna M. , Mohamed Abdelrahman , Girardi Leonard , Gaudino Mario , Lorusso Roberto , Mick Stephanie L. 
Published: January 2023

IntroductionPrimary malignant cardiac tumors (PMCTs) are rare. Geographical distribution has been demonstrated to affect cancer outcomes, making the reduction of geographical inequalities a major priority for cancer control agencies. Geographic survival disparities have not been reported previously for PMCT and the aim of this study is to compare the prevalence and the long-term survival rate with respect to the geographic location of PMCTs using the Surveillance, Epidemiology, and End Results (SEER) research plus data 17 registries between 2000 and 2019.MethodsThe SEER database was queried to identify geographic variation among PMCTs. We classified the included states into 4 geographical regions (Midwest, Northeast, South and West regions) based on the U.S. Census Bureau-designated regions and divisions. Different demographic and clinical variables were analyzed and compared between the four groups. Kaplan Meier curves and Cox regression were used for survival assessment.ResultsA total of 563 patients were included in our analysis. The median age was 53 years (inter-quartile range (IQR): 38 - 68 years) and included 26, 90, 101, and 346 patients from the Midwest, Northeast, South, and West regions respectively. Sarcoma represented 65.6% of the cases, followed by hematological tumors (26.2%), while mesothelioma accounted for 2.1%. Treatment analysis showed no significant differences between different regions. Median overall survival was 11, 21, 13, and 11 months for Midwest, Northeast, South and West regions respectively and 5-year overall survival was 22.2%, 25.4%, 14.9%, and 17.6% respectively. On multivariate Cox regression, significant independent predictors of late overall mortality among the entire cohort included age (Hazard Ratio [HR] 1.028), year of diagnosis (HR 0.967), sarcoma (HR 3.36), surgery (HR 0.63) and chemotherapy (HR 0.56).ConclusionPrimary malignant cardiac tumors are rare and associated with poor prognosis. Sarcoma is the most common pathological type. Younger age, recent era diagnosis, surgical resection, and chemotherapy were the independent predictors of better survival. While univariate analysis revealed that patients in the South areas had a worse survival trend compared to other areas, geographic disparity in survival was nullified in multivariate analysis.
Impact of MRI resolution for Linac-based stereotactic radiosurgery
Authors: Huang Yimei , Liang Evan , Schaff Eric M. , Zhao Bo , Snyder Karen C. , Chetty Indrin J. , Shah Mira M. , Siddiqui Salim M. 
Published: January 2023

ObjectiveMagnetic resonance imaging (MRI) is a standard imaging modality in intracranial stereotactic radiosurgery (SRS) for defining target volumes. However, wide disparities in MRI resolution exist, which could directly impact accuracy of target delineation. Here, sequences with various MRI resolution were acquired on phantoms to evaluate the effect on volume definition and dosimetric consequence for cranial SRS.Materials/MethodsFour T1-weighted MR sequences with increasing 3D resolution were compared, including two Spin Echo (SE) 2D acquisitions with 5mm and 3mm slice thickness (SE5mm, SE3mm) and two gradient echo 3D acquisitions (TFE, BRAVO). The voxel sizes were 0.4×0.4×5.0, 0.5×0.5×3.0, 0.9×0.9×1.25, and 0.4×0.4×0.5 mm3, respectively. Four phantoms with simulated lesions of different shape and volume (range, 0.53–25.0 cm3) were imaged, resulting in 16 total sets of MRIs. Four radiation oncologists provided contours on individual MR image set. All observer contours were compared with ground truth, defined on CT image according to the absolute dimensions of the target structure, using Dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and the ratio between reconstructed and true volume (Ratiovol). For dosimetric consequence, SRS plans targeting observer volumes were created. The true Paddick conformity index (CIpaddicktrue), calculated with true target volume, was correlated with quality of observer volume.ResultsAll measures of observer contours improved as increasingly higher MRI resolution was provided from SE5mm to BRAVO. The improvement in DSC, HD and MDA was statistically significant (p&lt;0.01). Dosimetrically, CIpaddicktrue strongly correlated with DSC of the planning observer volume (Pearson’s r=0.94, p&lt;0.00001).ConclusionsSignificant improvement in target definition and reduced inter-observer variation was observed as the MRI resolution improved, which also improved the quality of SRS plans. Results imply that high resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequences should be avoided.
Spatial distribution of supratentorial diffuse gliomas: A retrospective study of 990 cases
Authors: Li Gen , Yin Chuandong , Zhang Chuanhao , Xue Bowen , Yang Zuocheng , Li Zhenye , Pan Yuesong , Hou Zonggang , Hao Shuyu , Yu Lanbing , Ji Nan , Gao Zhixian , Deng Zhenghai , Xie Jian 
Published: January 2023

BackgroundGliomas distribute unevenly in the supratentorial brain space. Many factors were linked to tumor locations. This study aims to describe a more detailed distributing pattern of these tumors with age and pathological factors concerned.MethodsA consecutive series of 990 adult patients with newly-diagnosed supratentorial diffuse gliomas who underwent resection in Beijing Tiantan Hospital between January 2013 and January 2017 were retrospectively reviewed. For each patient, the anatomic locations were identified by the preoperative MRI, and the pathological subtypes were reviewed for histological grade and molecular status (if any) from his medical record. The MNI template was manually segmented to measure each anatomic location’s volume, and its invaded ratio was then adjusted by the volume to calculate the frequency density. Factors of age and pathological subtypes were also compared among locations.ResultsThe insulae, hippocampi, and corpus callosum were locations of the densest frequencies. The frequency density decreased from the anterior to posterior (frontal - motor region - sensory region - parietal - occipital), while the grade (p &lt; 0.0001) and the proportion of IDH-wt (p &lt; 0.0001) increased. More tumors invading the right basal ganglion were MGMT-mt (p = 0.0007), and more of those invading the left frontal were TERT-wt (p = 0.0256). Age varied among locations and pathological subtypes.ConclusionsThis study demonstrated more detailed spatial disproportions of supratentorial gliomas. There are potential interactions among age, pathological subtypes, and tumor locations.
Human epidermal growth factor receptor 2 expression in women with uterine cervix adenocarcinoma from Appalachian Kentucky
Authors: Kunos Charles A. , Fabian Denise , Piecoro Dava W. , Napier Dana , Miller Rachel W. , Ueland Frederick R. 
Published: January 2023

IntroductionHigh-risk human epidermal growth factor receptor 2 (HER2)-positive adenocarcinomas associate with early recurrence and death, prompting consideration of novel radiotherapeutic options like a trastuzumab-linked thorium-227 alpha-particle emitting radionuclide.MethodsWe conducted a retrospective pilot biomarker study of uterine cervix cancers among patients in Appalachian Kentucky, to characterize an exploitable triage biomarker like HER2 expression before starting a prospective phase 0 trial.ResultsMost (60%) adenocarcinomas showed HER2 cell-surface overexpression, whereas squamous cell carcinomas (4%) did not do so.DiscussionFurther validation tests of HER2 expression as a triage biomarker for radiopharmaceutical selection are warranted.