bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal neglect alters reward-anticipatory behavior, social status stability, and reward circuit activation in adult male rats
Authors: Ryakiotakis Ermis , Fousfouka Dimitra , Stamatakis Antonios 
Published: July 2023

IntroductionAdverse early life experiences affect neuronal growth and maturation of reward circuits that modify behavior under reward predicting conditions. Previous studies demonstrate that rats undergoing denial of expected reward in the form of maternal contact (DER-animal model of maternal neglect) during early post-natal life developed anhedonia, aggressive play-fight behaviors and aberrant prefrontal cortex structure and neurochemistry. Although many studies revealed social deficiency following early-life stress most reports focus on individual animal tasks. Thus, attention needs to be given on the social effects during group tasks in animals afflicted by early life adversity.MethodsTo investigate the potential impact of the DER experience on the manifestation of behavioral responses induced by natural rewards, we evaluated: 1) naïve adult male sexual preference and performance, and 2) anticipatory behavior during a group 2-phase food anticipation learning task composed of a context-dependent and a cue-dependent learning period.ResultsDER rats efficiently spent time in the vicinity of and initiated sexual intercourse with receptive females suggesting an intact sexual reward motivation and consummation. Interestingly, during the context-dependent phase of food anticipation training DER rats displayed a modified exploratory activity and lower overall reward-context association. Moreover, during the cue-dependent phase DER rats displayed a mild deficit in context-reward association while increased cue-dependent locomotion. Additionally, DER rats displayed unstable food access priority following food presentation. These abnormal behaviours were accompanied by overactivation of the ventral prefrontal cortex and nucleus accumbens, as assessed by pCREB levels.Conclusions/discussionCollectively, these data show that the neonatal DER experience resulted in adulthood in altered activation of the reward circuitry, interfered with the normal formation of context-reward associations, and disrupted normal reward access hierarchy formation. These findings provide additional evidence to the deleterious effects of early life adversity on reward system, social hierarchy formation, and brain function.
The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature
Authors: McGuigan Steven , Marie Daniel J. , O'Bryan Liam J. , Flores Francisco J. , Evered Lisbeth , Silbert Brendan , Scott David A. 
Published: July 2023

IntroductionXenon exhibits significant neuroprotection against a wide range of neurological insults in animal models. However, clinical evidence that xenon improves outcomes in human studies of neurological injury remains elusive. Previous reviews of xenon's method of action have not been performed in a systematic manner. The aim of this review is to provide a comprehensive summary of the evidence underlying the cellular interactions responsible for two phenomena associated with xenon administration: anesthesia and neuroprotection.MethodsA systematic review of the preclinical literature was carried out according to the PRISMA guidelines and a review protocol was registered with PROSPERO. The review included bothin vitromodels of the central nervous system and mammalianin vivostudies. The search was performed on 27th May 2022 in the following databases: Ovid Medline, Ovid Embase, Ovid Emcare, APA PsycInfo, and Web of Science. A risk of bias assessment was performed utilizing the Office of Health Assessment and Translation tool. Given the heterogeneity of the outcome data, a narrative synthesis was performed.ResultsThe review identified 69 articles describing 638 individual experiments in which a hypothesis was tested regarding the interaction of xenon with cellular targets including: membrane bound proteins, intracellular signaling cascades and transcription factors. Xenon has both common and subtype specific interactions with ionotropic glutamate receptors. Xenon also influences the release of inhibitory neurotransmitters and influences multiple other ligand gated and non-ligand gated membrane bound proteins. The review identified several intracellular signaling pathways and gene transcription factors that are influenced by xenon administration and might contribute to anesthesia and neuroprotection.DiscussionThe nature of xenon NMDA receptor antagonism, and its range of additional cellular targets, distinguishes it from other NMDA antagonists such as ketamine and nitrous oxide. This is reflected in the distinct behavioral and electrophysiological characteristics of xenon. Xenon influences multiple overlapping cellular processes, both at the cell membrane and within the cell, that promote cell survival. It is hoped that identification of the underlying cellular targets of xenon might aid the development of potential therapeutics for neurological injury and improve the clinical utilization of xenon.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: 336871.
Evaluation of the safety and potential lipid-lowering effects of oral hydrogen-rich coral calcium (HRCC) capsules in patients with metabolic syndrome: a prospective case series study
Authors: Chiu Szu-Han , Douglas Frank L. , Chung Jia-Ru , Wang Kuang-Yih , Chu Chao-Fang , Chou Hsia-Yun , Huang Wei-Chih , Wang Tian-Yu , Chen Wen-Wen , Shen Min-Chung , Liu Feng-Cheng , Hsiao Po-Jen 
Published: July 2023

BackgroundMetabolic syndrome is characterized by a cluster-like occurrence of conditions such as hypertension, hyperglycaemia, elevated low-density lipoprotein (LDL) cholesterol or triglycerides (TG) and high visceral fat. Metabolic syndrome is linked to the build-up of plaque within the artery, which leads to disorders of the circulatory, nervous and immune systems. A variety of treatments target the regulation of these conditions; nevertheless, they remain dominant risk factors for the development of type 2 diabetes (T2DM) and cardiovascular disease (CVD), which affect 26.9% of the US population. Management and intervention strategies for improving cholesterol and/or TG are worthwhile, and recent studies on hydrogen treatment are promising, particularly as molecular hydrogen is easily ingested. This study aimed to investigate the lipid-lowering effects and quality of life (QOL) improvement of hydrogen-rich coral calcium (HRCC) in patients with metabolic syndrome.MethodsThe patients, all Taiwanese, were randomly assigned to 3 different doses (low, medium, and high) of HRCC capsules. The primary outcome was the adverse effects/symptoms during this 4-week use of HRCC capsules. The secondary outcome was lipid profile changes. Complete blood count, inflammatory biomarkers, and QOL were also measured before and after the course of HRCC.ResultsSixteen patients with metabolic syndrome completed this study (7 males, 9 females; mean age: 62 years; range: 32–80). No obvious adverse effects were recorded. Only changes in blood TG reached significance. The baseline TG value was 193.19 μL (SD = 107.44), which decreased to 151.75 μL (SD = 45.27) after 4 weeks of HRCC (p = 0.04). QOL showed no significant changes.ConclusionThis study is the first human clinical trial evaluating HRCC capsules in patients with metabolic syndrome. Based on the safety and potential TG-lowering effects of short-term HRCC, further long-term investigations of HRCC are warranted.Clinical trial registration[ClinicalTrials.gov], identifier [NCT05196295].
Assessment of intrafraction motion and its dosimetric impact on prostate radiotherapy using an in-house developed position monitoring system
Authors: Arumugam Sankar , Young Tony , Do Viet , Chlap Phillip , Tawfik Christine , Udovitch Mark , Wong Karen , Sidhom Mark 
Published: July 2023

PurposeTo implement an in-house developed position monitoring software, SeedTracker, for conventional fractionation prostate radiotherapy, and study the effect on dosimetric impact and intrafraction motion.MethodsThirty definitive prostate radiotherapy patients with implanted fiducial markers were included in the study. All patients were treated with VMAT technique and plans were generated using the Pinnacle planning system using the 6MV beam model for Elekta linear accelerator. The target dose of 60 Gy in 20 fractions was prescribed for 29 of 30 patients, and one patient was treated with the target dose of 78 Gy in 39 fractions. The SeedTracker position monitoring system, which uses the x-ray images acquired during treatment delivery in the Elekta linear accelerator and associated XVI system, was used for online prostate position monitoring. The position tolerance for online verification was progressively reduced from 5 mm, 4 mm, and to 3 mm in 10 patient cohorts to effectively manage the treatment interruptions resulting from intrafraction motion in routine clinical practice. The delivered dose to target volumes and organs at risk in each of the treatment fractions was assessed by incorporating the observed target positions into the original treatment plan.ResultsIn 27 of 30 patients, at least one gating event was observed, with a total of 177 occurrences of position deviation detected in 146 of 619 treatment fractions. In 5 mm, 4 mm, and 3 mm position tolerance cohorts, the position deviations were observed in 13%, 24%, and 33% of treatment fractions, respectively. Overall, the mean (range) deviation of -0.4 (-7.2 to 5.3) mm, -0.9 (-6.1 to 15.6) mm, and -1.7 (-7.0 to 6.1) mm was observed in Left-Right, Anterior-Posterior, and Superior-Inferior directions, respectively. The prostate CTV D99 would have been reduced by a maximum value of 1.3 Gy compared to the planned dose if position deviations were uncorrected, but with corrections, it was 0.3 Gy. Similarly, PTV D98 would have been reduced by a maximum value of 7.6 Gy uncorrected, with this difference reduced to 2.2 Gy with correction. The V60 to the rectum increased by a maximum of 1.0% uncorrected, which was reduced to 0.5%.ConclusionOnline target position monitoring for conventional fractionation prostate radiotherapy was successfully implemented on a standard Linear accelerator using an in-house developed position monitoring software, with an improvement in resultant dose to prostate target volume.
Neoadjuvant nivolumab and cabozantinib in advanced renal cell carcinoma in a horseshoe kidney – how to achieve a safe and radical resection? a case report and review of the literature
Authors: Zemankova Anezka , Studentova Hana , Kopova Andrea , Tichy Tomas , Student Vladimir , Melichar Bohuslav 
Published: July 2023

IntroductionNeoadjuvant nivolumab and cabozantinib in locally advanced renal cell carcinoma in a horseshoe kidney is a novel therapeutic approach in the preoperative setting.MethodsWe report a case of a 52-year old male who presented with a large inoperable tumor of the horseshoe kidney and achieved major partial radiologic response after neoadjuvant therapy with nivolumab and cabozantinib leading to radical resection of the tumor. The patient remains tumor free on the subsequent follow-up and his renal function is only mildly decreased. The systemic treatment was complicated by hepatotoxicity leading to early nivolumab withdrawal.ResultsCurrently, the combination therapy based on immune checkpoint inhibitors and tyrosine kinase inhibitors represents the treatment of choice in treatment-naïve patients with metastatic renal cell carcinoma in any prognostic group. The neoadjuvant treatment approach is being tested in prospective clinical trials and results are eagerly awaited. Renal cell carcinoma in a horseshoe kidney is an uncommon finding that is always challenging. Additionally, management guidance in this patient population is lacking. In some patients neoadjuvant therapy could be the only way to preserve kidney function. The initial treatment strategy should be individualized to patient needs aiming at the radical resection of the primary tumor as the only chance of getting the tumor under control in the long term.ConclusionHerein, we highlight the feasibility of neoadjuvant systemic therapy with nivolumab and cabozantinib allowing the subsequent performance of radical tumor resection with negative margins in a patient with advanced renal cell carcinoma in a horseshoe kidney, removing the primary tumor while sparing the patient from lifelong dialysis.
Contrast enhanced ultrasound combined with serology predicts hepatocellular carcinoma recurrence: a retrospective observation cohort study
Authors: Tu Haibin , Feng Siyi , Chen Lihong , Huang Yujie , Zhang Juzhen , Wu Xiaoxiong 
Published: July 2023

ObjectivesTo construct a novel model based on contrast-enhanced ultrasound (CEUS) and serological biomarkers to predict the early recurrence (ER) of primary hepatocellular carcinoma within 2 years after hepatectomy.MethodsA total of 466 patients who underwent CEUS and curative resection between 2016.1.1 and 2019.1.1 were retrospectively recruited from one institution. The training and testing cohorts comprised 326 and 140 patients, respectively. Data on general characteristics, CEUS Liver Imaging Reporting and Data System (LI-RADS) parameters, and serological were collected. Univariate analysis and multivariate Cox proportional hazards regression model were used to evaluate the independent prognostic factors for tumor recurrence, and the Contrast-enhanced Ultrasound Serological (CEUSS) model was constructed. Different models were compared using prediction error and time-dependent area under the receiver operating characteristic curve (AUC). The CEUSS model's performances in ER prediction were assessed.ResultsThe baseline data of the training and testing cohorts were equal. LI-RADS category, α-fetoprotein level, tumor maximum diameter, total bilirubin level, starting time, iso-time, and enhancement pattern were independent hazards, and their hazards ratios were 1.417, 1.309, 1.133, 1.036, 0.883, 0.985, and 0.70, respectively. The AUCs of CEUSS, BCLC,TNM, and CNLC were 0.706, 0.641, 0.647, and 0.636, respectively, in the training cohort and 0.680, 0.583, 0.607, and 0.597, respectively, in the testing cohort. The prediction errors of CEUSS, BCLC, TNM, and CNLC were 0.202, 0.205, 0.205, and 0.200, respectively, in the training cohort and 0.204, 0.221, 0.219, and 0.211, respectively, in the testing cohort.ConclusionsThe CEUSS model can accurately and individually predict ER before surgery and may represent a new tool for individualized treatment.
Long-term outcomes of symptomatic optic pathway glioma: 32-year experience at a single Western Australian tertiary pediatric oncology center
Authors: Rajagopal Revathi , Khan Mumtaz , Lethbridge Robert , Lee Gabriel , Lee Sharon , Dyke Jason , Fabian Vicki , McGrath Alycea , Taylor Mandy , Jacoby Peter , Endersby Raelene , Nagabushan Sumanth , Gottardo Nicholas G. 
Published: July 2023

IntroductionOptic pathway gliomas (OPGs) are associated with significant risk of visual and endocrine morbidity, but data on long-term outcomes in symptomatic patients is sparse. This study reviews the clinical course, disease progression, survival outcomes and long-term sequelae in pediatric patients with symptomatic OPGs in our institution over three decades.MethodsRetrospective review of patients with symptomatic OPG treated in a single tertiary pediatric oncology center from 1984 to 2016.ResultsA total of 37 patients were diagnosed with symptomatic OPG. Decreased visual acuity was the commonest presenting symptom (75.7%). Surgical intervention was performed in 62.2%; 56.5% underwent biopsy, 26.1% surgical debulking and 17.4% had orbital decompression with cystic fenestration and cosmetic optic nerve excision at different treatment intervals. CSF diversion was performed in 47.8% patients. Histopathologic examination confirmed 86% to be pilocytic astrocytoma and 1 ganglioglioma. 46% received chemotherapy and 48% had radiotherapy, at different intervals. Median follow-up was 13.74 years. In NF1 patients, overall survival (OS) was 100% at 5 years and 55.6 ± 24.8% at 25 years while progression-free-survival (PFS) was 50 ± 15.8% at 5 and 20 years. In non-NF1 patients, OS was 96.2 ± 3.8% at 5 years and 87.4 ± 9% at 25-years. 5-year PFS was 53.8 ± 9.8% and 25-year PFS was 49.0 ± 10%. Cumulative PFS was 53 ± 8.3% at 5 years and 49.7 ± 8.4% at 20 years while cumulative OS was 97.2 ± 2.7% at 5 years and 77.5 ± 10.8% at 25 years. 59.5% patients developed post-operative endocrinopathy. Long-term vision was normal in 8.1%, improved in 13.5%, stabilized in 40.5% but worsened in 37.8% patients. Three patients treated with radiotherapy developed second brain tumors.Conclusion25-year OS in this cohort was 77.5% but survivorship carried significant long-term morbidities including radiation-induced second malignant brain tumors.
A chemotherapy response prediction model derived from tumor-promoting B and Tregs and proinflammatory macrophages in HGSOC
Authors: Xi Yue , Zhang Yingchun , Zheng Kun , Zou Jiawei , Gui Lv , Zou Xin , Chen Liang , Hao Jie , Zhang Yiming 
Published: July 2023

BackgroundMost patients with high-grade serous ovarian cancer (HGSOC) experienced disease recurrence with cumulative chemoresistance, leading to treatment failure. However, few biomarkers are currently available in clinical practice that can accurately predict chemotherapy response. The tumor immune microenvironment is critical for cancer development, and its transcriptomic profile may be associated with treatment response and differential outcomes. The aim of this study was to develop a new predictive signature for chemotherapy in patients with HGSOC.MethodsTwo HGSOC single-cell RNA sequencing datasets from patients receiving chemotherapy were reinvestigated. The subtypes of endoplasmic reticulum stress-related XBP1+B cells, invasive metastasis-related ACTB+Tregs, and proinflammatory-related macrophage subtypes with good predictive power and associated with chemotherapy response were identified. These results were verified in an independent HGSOC bulk RNA-seq dataset for chemotherapy. Further validation in clinical cohorts used quantitative real-time PCR (qRT-PCR).ResultsBy combining cluster-specific genes for the aforementioned cell subtypes, we constructed a chemotherapy response prediction model containing 43 signature genes that achieved an area under the receiver operator curve (AUC) of 0.97 (p= 2.1e-07) for the GSE156699 cohort (88 samples). A huge improvement was achieved compared to existing prediction models with a maximum AUC of 0.74. In addition, its predictive capability was validated in multiple independent bulk RNA-seq datasets. The qRT-PCR results demonstrate that the expression of the six genes has the highest diagnostic value, consistent with the trend observed in the analysis of public data.ConclusionsThe developed chemotherapy response prediction model can be used as a valuable clinical decision tool to guide chemotherapy in HGSOC patients.
Nomogram incorporating potent inflammatory indicators for overall survival estimation of patients with primary oral squamous cell carcinoma
Authors: Wu Hai-xuan , Cheng Shi , Liu Fan , Lin Jun-jie , Huang Su-na , Wang Cheng-li , Zhou Bin , Liu Zhong-qi , Cao Ming-hui 
Published: July 2023

BackgroundInflammation has been recognized to be a factor that substantially influences tumorigenesis and tumor prognosis. Hence, this study was aimed to investigate an inflammatory marker with the most potent prognostic ability and to evaluate the survival estimation capability of dynamic change in this marker for patients suffered from oral squamous cell carcinoma (OSCC).Methods469 patients’ inflammatory indicators including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory response index (SIRI), were calculated. Their predictive abilities for overall survival (OS) were evaluated by Kaplan-Meier curves to screen for the one with the most potent prognostic value. The predictive ability of dynamic changes in this marker was verified and a predictive nomogram incorporating inflammatory indicators was developed.ResultsA high LMR was identified to be an indicator of a satisfactory survival rate. Compared with that of other inflammatory markers, area under the receiver operating characteristics (ROC) curve (AUC) of LMR for 1-year and 3-year OS was significantly larger (P&lt;0.001). Dynamic LMR change remained an significant parameter for predicting OS (OR: 2.492, 95% CI: 1.246–4.981, p = 0.010). The nomogram incorporating LMR exhibited a superior prognostic significance than the TNM system, as suggested by the C-index (0.776 vs 0.651 in primary cohort; 0.800 vs 0.707 in validation cohort, P&lt;0.001) and AUC.ConclusionsLMR was demonstrated to possess a more potent survival estimation capability than the other three inflammatory parameters. Dynamic changes in LMR serves as a significant parameter for overall survival estimation of primary OSCC patients. The established nomogram incorporating inflammatory markers showed more accuracy and sensitivity for survival estimation of primary OSCC patients.
Prognostic prediction by 18F-FDG-PET/CT parameters in patients with neuroblastoma: a systematic review and meta-analysis
Authors: Hu Ruimin , Zhang Yan , Liu Siying , Lee Pamela , Liu Chaohong , Liu Aiguo 
Published: July 2023

PurposeNeuroblastoma is a solid malignant tumor with high malignancy and high risk for metastasis. The prognosis of neuroblastoma ranges from spontaneous regression to insensitivity to therapies and widespread metastasis. There is a non-invasive, panoramic imaging technique called 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET/CT), which can provide both complete anatomical information via CT and extent of FDG uptake value in tumors via positron emission detection. PET/CT is a powerful approach to estimating tumoral metabolic activities, and PET/CT parameters have been demonstrated to be associated with the prognosis of various tumors. However, the predictive performance of PET/CT for the prognosis of neuroblastoma remains unclear. This meta-analysis aims to assess the predictive values of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) in neuroblastoma patients.MethodsLiterature in PubMed, Embase, Cochrane Library, and Web of Science from January 1985 to June 2023 was searched for studies evaluating predictive values of PET/CT parameters for the prognosis of neuroblastoma. Search items mainly included “Positron Emission Tomography Computed Tomography” and “Neuroblastoma”. Hazard ratio (HR) was used as a pooled statistic to assess the association of SUVmax, MTV, and TLG with PFS, EFS, and OS in neuroblastoma patients. Heterogeneity test and sensitivity analysis were performed.ResultsThere were eight studies included, with 325 participants. Meta-analysis showed that higher SUVmax was associated with shorter OS [HR = 1.27, 95% CI (1.11, 1.45), p = 0.001], while no association with PFS [HR = 1.03, 95% CI (0.99, 1.07), p = 0.222] and EFS [HR = 2.58, 95% CI (0.37, 18.24), p = 0.341] was presented. MTV showed no association with OS [HR = 2.46, 95% CI (0.34, 18.06), p = 0.376] and PFS [HR = 2.60, 95% CI (0.68, 9.88), p = 0.161]. There was a statistically significant association between TLG and OS [HR = 1.00, 95% CI (1.00, 1.00), p = 0.00], while the HR was 1, so the association could not be concluded, and TLG showed no association with PFS [HR = 1.00, 95% CI (0.99, 1.00), p = 0.974].ConclusionHigh SUVmax indicates poor OS in patients with neuroblastoma. The MTV and TLG are potential prognostic predictors that need to be further validated by more well-designed studies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier 340729.