bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum cold-inducible RNA-binding protein (CIRP) levels as a prognostic indicator in patients with acute ischemic stroke
Authors: Li Mingming , Yao Min , Shao Kangmei , Shen Xueyang , Li Yongnan , Ge Zhaoming
Published: July 2023

Background

Acute ischemic stroke (AIS) is the leading cause of morbidity and mortality among cerebrovascular diseases. While animal studies have suggested a correlation between cold-inducible RNA-binding protein (CIRP) serum levels and the severity and prognosis of cerebral infarction, there has been a lack of research exploring this association in humans with cerebral infarction.

Materials and methods

A total of 148 patients diagnosed with AIS within 7 days from symptom onset were included in this study. Comprehensive information regarding the patients' basic demographics, medical history, clinical parameters, the severity of cerebral infarction, and serum CIRP levels was collected. Follow-up data were obtained through telephonic interviews or by reviewing clinical notes for 3 months after the patients were discharged to assess the functional outcomes of treatment.

Results

The findings of this study demonstrated a significant increase in serum CIRP levels during the early stages of AIS, followed by a gradual decline after 3 days. Significant differences were observed in the serum CIRP levels between the 1-day group and the 4–7 day group (P < 0.0047), as well as between the 2–3 day group and the 4–7 day group (P < 0.0006). Moreover, a significant positive correlation was observed between the serum CIRP levels and the severity of cerebral infarction. Higher serum CIRP levels were associated with more severe National Institutes of Health Stroke Scale scores (P < 0.05) and larger cerebral infarction volumes (P < 0.05). Furthermore, patients with higher serum CIRP levels exhibited poorer modified Rankin scale scores (P < 0.05). These findings indicate that serum CIRP serves as an essential pro-inflammatory mediator and a valuable biomarker for assessing brain injury in patients with AIS.

Conclusion

The findings of this study suggest an elevation in serum CIRP levels among patients with AIS. These levels are positively correlated with the severity of AIS and serve as indicators of a poor prognosis. Therefore, CIRP could serve as a target for early clinical intervention while managing AIS, and further research should explore serum CIRP levels as prognostic indicators in AIS.
Localized proteomic differences in the choroid plexus of Alzheimer's disease and epilepsy patients
Authors: Leitner Dominique F. , Kanshin Evgeny , Faustin Arline , Thierry Manon , Friedman Daniel , Devore Sasha , Ueberheide Beatrix , Devinsky Orrin , Wisniewski Thomas
Published: July 2023

Introduction

Alzheimer's disease (AD) and epilepsy are reciprocally related. Among sporadic AD patients, clinical seizures occur in 10–22% and subclinical epileptiform abnormalities occur in 22–54%. Cognitive deficits, especially short-term memory impairments, occur in most epilepsy patients. Common neurophysiological and molecular mechanisms occur in AD and epilepsy. The choroid plexus undergoes pathological changes in aging, AD, and epilepsy, including decreased CSF turnover, amyloid beta (Aβ), and tau accumulation due to impaired clearance and disrupted CSF amino acid homeostasis. This pathology may contribute to synaptic dysfunction in AD and epilepsy.

Methods

We evaluated control (n = 8), severe AD (n = 8; A3, B3, C3 neuropathology), and epilepsy autopsy cases (n = 12) using laser capture microdissection (LCM) followed by label-free quantitative mass spectrometry on the choroid plexus adjacent to the hippocampus at the lateral geniculate nucleus level.

Results

Proteomics identified 2,459 proteins in the choroid plexus. At a 5% false discovery rate (FDR), 616 proteins were differentially expressed in AD vs. control, 1 protein in epilepsy vs. control, and 438 proteins in AD vs. epilepsy. There was more variability in the epilepsy group across syndromes. The top 20 signaling pathways associated with differentially expressed proteins in AD vs. control included cell metabolism pathways; activated fatty acid beta-oxidation (p = 2.00 x 10−7, z = 3.00), and inhibited glycolysis (p = 1.00 x 10−12, z = −3.46). For AD vs. epilepsy, the altered pathways included cell metabolism pathways, activated complement system (p = 5.62 x 10−5, z = 2.00), and pathogen-induced cytokine storm (p = 2.19 x 10−2, z = 3.61). Of the 617 altered proteins in AD and epilepsy vs. controls, 497 (81%) were positively correlated (p < 0.0001, R2 = 0.27).

Discussion

We found altered signaling pathways in the choroid plexus of severe AD cases and many correlated changes in the protein expression of cell metabolism pathways in AD and epilepsy cases. The shared molecular mechanisms should be investigated further to distinguish primary pathogenic changes from the secondary ones. These mechanisms could inform novel therapeutic strategies to prevent disease progression or restore normal function. A focus on dual-diagnosed AD/epilepsy cases, specific epilepsy syndromes, such as temporal lobe epilepsy, and changes across different severity levels in AD and epilepsy would add to our understanding.
Cinematographic continuity edits across shot scales and camera angles: an ERP analysis
Authors: Sanz-Aznar Javier , Bruni Luis Emilio , Soto-Faraco Salvador
Published: July 2023

Film editing has attracted great theoretical and practical interest since the beginnings of cinematography. In recent times, the neural correlates of visual transitions at edit cuts have been at the focus of attention in neurocinematics. Many Event Related Potential (ERP) studies studies have reported the consequences of cuts involving narrative discontinuities, and violations of standard montage rules. However, less is known about edits that are meant to induce continuity. Here, we addressed the neural correlates of continuity editing involving scale, and angle variations across the cut within the same scene, two of the most popular devices used for continuity editing. We recorded the electroencephalographic signal obtained from 20 viewers as they watched four different cinematographic excerpts to extract ERPs at edit points. First, we were able to reproduce the general time and scalp distribution of the typical ERPs to filmic cuts in prior studies. Second, we found significant ERP modulations triggered by scale changes (scale out, scale in, or maintaining the same scale). Edits involving an increase in scale (scale out) led to amplification of the ERP deflection, and scale reduction (scale in) led to decreases, compared to edits that kept scale across the cut. These modulations coincide with the time window of the N300 and N400 components and, according to previous findings, their amplitude has been associated with the likelihood of consciously detecting the edit. Third, we did not detect similar modulations as a function of angle variations across the cut. Based on these findings, we suggest that cuts involving reduction of scale are more likely to go unnoticed, than ones that scale out. This relationship between scale in/out and visibility is documented in film edition manuals. Specifically, in order to achieve fluidity in a scene, the edition is designed from the most opened shots to the most closed ones.
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

Introduction

Adverse 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.

Methods

To 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.

Results

DER 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/discussion

Collectively, 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

Introduction

Xenon 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.

Methods

A 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.

Results

The 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.

Discussion

The 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 registration

https://www.crd.york.ac.uk/prospero/, identifier: 336871.
An intellectual-disability-associated mutation of the transcriptional regulator NACC1 impairs glutamatergic neurotransmission
Authors: Daniel James A. , Elizarova Sofia , Shaib Ali H. , Chouaib Abed A. , Magnussen Helge M. , Wang Jianlong , Brose Nils , Rhee JeongSeop , Tirard Marilyn
Published: July 2023

Advances in genome sequencing technologies have favored the identification of rare de novo mutations linked to neurological disorders in humans. Recently, a de novo autosomal dominant mutation in NACC1 was identified (NM_052876.3: c.892C > T, NP_443108.1; p.Arg298Trp), associated with severe neurological symptoms including intellectual disability, microcephaly, and epilepsy. As NACC1 had never before been associated with neurological diseases, we investigated how this mutation might lead to altered brain function. We examined neurotransmission in autaptic glutamatergic mouse neurons expressing the murine homolog of the human mutant NACC1, i.e., Nacc1-R284W. We observed that expression of Nacc1-R284W impaired glutamatergic neurotransmission in a cell-autonomous manner, likely through a dominant negative mechanism. Furthermore, by screening for Nacc1 interaction targets in the brain, we identified SynGAP1, GluK2A, and several SUMO E3 ligases as novel Nacc1 interaction partners. At a biochemical level, Nacc1-R284W exhibited reduced binding to SynGAP1 and GluK2A, and also showed greatly increased SUMOylation. Ablating the SUMOylation of Nacc1-R284W partially restored its interaction with SynGAP1 but did not restore binding to GluK2A. Overall, these data indicate a role for Nacc1 in regulating glutamatergic neurotransmission, which is substantially impaired by the expression of a disease-associated Nacc1 mutant. This study provides the first functional insights into potential deficits in neuronal function in patients expressing the de novo mutant NACC1 protein.
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

Background

Metabolic 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.

Methods

The 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.

Results

Sixteen 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.

Conclusion

This 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

Purpose

To implement an in-house developed position monitoring software, SeedTracker, for conventional fractionation prostate radiotherapy, and study the effect on dosimetric impact and intrafraction motion.

Methods

Thirty 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.

Results

In 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%.

Conclusion

Online 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

Introduction

Neoadjuvant nivolumab and cabozantinib in locally advanced renal cell carcinoma in a horseshoe kidney is a novel therapeutic approach in the preoperative setting.

Methods

We 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.

Results

Currently, 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.

Conclusion

Herein, 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

Objectives

To 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.

Methods

A 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.

Results

The 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.

Conclusions

The CEUSS model can accurately and individually predict ER before surgery and may represent a new tool for individualized treatment.
Characterization of 3D heterocellular spheroids of pancreatic ductal adenocarcinoma for the study of cell interactions in the tumor immune microenvironment
Authors: Giustarini Giulio , Teng Germaine , Pavesi Andrea , Adriani Giulia
Published: July 2023

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies nowadays. The available chemo- and immunotherapies are often ineffective in treating PDAC due to its immunosuppressive and highly desmoplastic tumor immune microenvironment (TIME), which is hardly reproduced in the existing preclinical models. The PDAC TIME results from a peculiar spatial organization between different cell types. For this reason, developing new human models recapitulating the tissue organization and cell heterogeneity of PDAC is highly desirable. We developed human 3D heterocellular tumor spheroids of PDAC formed by cancer cells, endothelial cells, pancreatic stellate cells (PSC), and monocytes. As a control, we formed spheroids using immortalized epithelial pancreatic ductal cells (non-cancerous spheroids) with cellular heterogeneity similar to the tumor spheroids. Normal spheroids containing endothelial cells formed a complex 3D endothelial network significantly compromised in tumor spheroids. Monocyte/macrophages within the 4-culture tumor spheroids were characterized by a higher expression of CD163, CD206, PD-L1, and CD40 than those in the non-cancerous spheroids suggesting their differentiation towards an immunosuppressive phenotype. The heterocellular tumor spheroids presented a hypoxic core populated with PSC and monocytes/macrophages. The 4-culture tumor spheroids were characterized by spatial proximity of PSC and monocytes to the endothelial cells and a cytokine signature with increased concentrations of CXCL10, CCL2, and IL-6, which have been observed in PDAC patients and associated with poor survival. Further, 4-culture tumor spheroids decreased the concentrations of T-cell chemoattracting cytokines, i.e., CCL4, CCL5, and CXCL9, when compared with the non-cancerous spheroids, revealing a critical immunosuppressive feature of the different types of cells forming the tumor spheroids. Our results showed that the 4-culture tumor spheroids better resembled some critical features of patients’ PDAC TIME than monoculture tumor spheroids. Using the proposed human 3D spheroid model for therapy testing at the preclinical stage may reveal pitfalls of chemo- and immuno-therapies to help the development of better anti-tumor therapies.
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

Introduction

Optic 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.

Methods

Retrospective review of patients with symptomatic OPG treated in a single tertiary pediatric oncology center from 1984 to 2016.

Results

A 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.

Conclusion

25-year OS in this cohort was 77.5% but survivorship carried significant long-term morbidities including radiation-induced second malignant brain tumors.
Refractory and progressively worsening nasal obstruction: case report of nasal osteoblastoma and literature review
Authors: Fang Caishan , Wang Ruizhi , Zhou Min , Chen Tengyu , Zhang Qinxiu , Ruan Yan , Li Chunqiao
Published: July 2023

Nasal osteoblastoma (OB) is a rare and locally aggressive osteogenic tumor that has rarely been reported, and there is a lack of effective evidence data for its diagnosis and treatment. In this study, we report a 31-year-old female patient who presented with nasal congestion and associated progressive painless swelling of the left maxillofacial region. A preoperative computed tomography (CT) examination of the paranasal sinuses was performed, and based on the imaging presentation, the surgeon was unable to differentiate between OB, osteoid osteoma (OO), fibrous dysplasia of bone (FDB) and osteoblastic fibroma (OF). After excluding contraindications to surgery, the patient underwent nasal endoscopic excision of the left nasal mass, which was found to be gravel-like and difficult to remove cleanly during the operation. The mass was brittle and bled easily, resulting in inadequate exposure of the operative field, prolonged operation time, and substantial intraoperative blood loss. This indicates that definite preoperative diagnosis (biopsy of deeper parts of the mass is recommended) and appropriate preoperative preparations (e.g., preoperative angiography and embolization, adequate blood preparation) are very important. The intraoperative frozen and postoperative pathological results clearly identified the tumor as OB. No local recurrence of the tumor was observed at the 11-month postoperative follow-up.
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

Background

Most 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.

Methods

Two 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).

Results

By 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.

Conclusions

The developed chemotherapy response prediction model can be used as a valuable clinical decision tool to guide chemotherapy in HGSOC patients.
Multidrug resistance in the standardized treatment of colon cancer harboring a rare fibrosarcoma B-type (BRAF) p.N581I mutation: a case report
Authors: Wang Xiaoyan , Zhao Chenyi , Gong Yang , Wang Ying , Guo Feng
Published: July 2023

BRAF non-V600 mutations are a distinct molecular subset of colorectal cancer (CRC) that has little to no clinical similarity to the BRAF V600 mutations. It is generally considered that the BRAF non-V600 mutations correlate with better survival of CRC patients. In this report, we present an unusual case of that a midlife female patient who was initially diagnosed with stage IIIC colon cancer, and multiple metastases were found 25 months after radical surgery. Next-generation sequencing (NGS) revealed the BRAF p.N581I (c.1742A>T) mutation. She received chemotherapy, targeted therapy, and immunotherapy. However, the disease progressed rapidly with rare metastasis of the bone and cerebellum. This case highlights that the BRAF non-V600 mutations, such as BRAF p.N581I mutant, may lead to resistance to epidermal growth factor receptor (EGFR) inhibitors and result in a rapid course in colorectal cancer. The role of BRAF p.N581I mutation in colorectal cancer demands more attention.
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

Background

Inflammation 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).

Methods

469 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.

Results

A 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<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<0.001) and AUC.

Conclusions

LMR 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

Purpose

Neuroblastoma 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.

Methods

Literature 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.

Results

There 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].

Conclusion

High 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 registration

https://www.crd.york.ac.uk/PROSPERO/, identifier 340729.
HPV infection and breast cancer risk: insights from a nationwide population study in Taiwan
Authors: Lin Chuck , Tsai Stella Chin-Shaw , Huang Jing-Yang , Lin Frank Cheau-Feng
Published: July 2023

Background

The prevalence of cancer, specifically breast cancer, has raised globally. The etiology of breast cancer has been attributed to age, genetic mutations, reproductive history, hormone therapy, lifestyle factors, and viral infections. The human papillomavirus (HPV) has been one of the most widespread sexually transmitted infection in the United States. The role of HPV in breast oncogenesis was hypothesized before, yet the association remained unclear.

Methods

In this study, we employed a nationwide population study using centralized patient data managed by the Ministry of Health and Welfare in Taiwan and the Taiwan Cancer Registry database. The breast cancer incidence rates of the 467,454 HPV patients were compared to twice as many non-HPV patients with matching sex and age. Cumulative breast cancer incidence rates were presented by a Kaplan-Meier curve, and the relative risk of breast cancer for HPV and non-HPV patients were calculated using Cox-regression model.

Results

Our results indicated a crude hazard ratio (HR) and an adjusted hazard ratio (aHR) of 2.336 and 2.271, respectively, when comparing the risk of breast cancer in the HPV and non-HPV group. The risk of breast cancer was comparable or higher than those of head and neck cancer (aHR=1.595) and cervical cancer (aHR=2.225), which both were found to have causal relationships with HPV. The Kaplan-Meier curve further illustrated a higher cumulative risk across 84 months for HPV patients (p<.0001). Besides HPV, age (p<.0001), insurance providers (p<.001), and comorbidities such as abnormal liver function (aHR=1.191, p=.0069) and hyperlipidemia (aHR=1.218, p=.0002) were found to be correlated with higher risks of breast cancer.

Conclusion

A correlation between HPV and breast cancer can be inferred using national health databases. More molecular studies are required to understand the mechanism of the virus-induced oncogenesis of the breast.
Global development of artificial intelligence in cancer field: a bibliometric analysis range from 1983 to 2022
Authors: Wang Sui-Han , Chen Guoqiao , Zhong Xin , Lin Tianyu , Shen Yan , Fan Xiaoxiao , Cao Liping
Published: July 2023

Background

Artificial intelligence (AI) is widely applied in cancer field nowadays. The aim of this study is to explore the hotspots and trends of AI in cancer research.

Methods

The retrieval term includes four topic words (“tumor,” “cancer,” “carcinoma,” and “artificial intelligence”), which were searched in the database of Web of Science from January 1983 to December 2022. Then, we documented and processed all data, including the country, continent, Journal Impact Factor, and so on using the bibliometric software.

Results

A total of 6,920 papers were collected and analyzed. We presented the annual publications and citations, most productive countries/regions, most influential scholars, the collaborations of journals and institutions, and research focus and hotspots in AI-based cancer research.

Conclusion

This study systematically summarizes the current research overview of AI in cancer research so as to lay the foundation for future research.
PANoptosis-related molecular subtype and prognostic model associated with the immune microenvironment and individualized therapy in pancreatic cancer
Authors: Zhang Biao , Huang Bingqian , Zhang Xiaonan , Li Shuang , Zhu Jingyi , Chen Xu , Song Huiyi , Shang Dong
Published: July 2023

Background

PANoptosis is an inflammatory type of programmed cell death regulated by PANopotosome. Mounting evidence has shown that PANoptosis could be involved in cancer pathogenesis and the tumor immune microenvironment. Nevertheless, there have been no studies on the mechanism of PANoptosis on pancreatic cancer (PC) pathogenesis.

Methods

We downloaded the data on transcriptomic and clinical features of PC patients from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Additionally, the data on copy number variation (CNV), methylation and somatic mutations of genes in 33 types of cancers were obtained from TCGA. Next, we identified the PANoptosis-related molecular subtype using the consensus clustering analysis, and constructed and validated the PANoptosis-related prognostic model using LASSO and Cox regression analyses. Moreover, RT-qPCR was performed to determine the expression of genes involved in the model.

Results

We obtained 66 PANoptosis-related genes (PANRGs) from published studies. Of these, 24 PC-specific prognosis-related genes were identified. Pan-cancer analysis revealed complex genetic changes, including CNV, methylation, and mutation in PANRGs were identified in various cancers. By consensus clustering analysis, PC patients were classified into two PANoptosis-related patterns: PANcluster A and B. In PANcluster A, the patient prognosis was significantly worse compared to PANcluster B. The CIBERSORT algorithm showed a significant increase in the infiltration of CD8+ T cells, monocytes, and naïve B cells, in patients in PANcluster B. Additionally, the infiltration of macrophages, activated mast cells, and dendritic cells were higher in patients in PANcluster A. Patients in PANcluster A were more sensitive to erlotinib, selumetinib and trametinib, whereas patients in PANcluster B were highly sensitive to irinotecan, oxaliplatin and sorafenib. Moreover, we constructed and validated the PANoptosis-related prognostic model to predict the patient’s survival. Finally, the GEPIA and Human Protein Atlas databases were analyzed, and RT-qPCR was performed. Compared to normal tissues, a significant increase in CXCL10 and ITGB6 (associated with the model) expression was observed in PC tissues.

Conclusion

We first identified the PANoptosis-related molecular subtypes and established a PANoptosis-related prognostic model for predicting the survival of patients with PC. These results would aid in exploring the mechanisms of PANoptosis in PC pathogenesis.
Peripherally inserted central catheters versus implantable port catheters for cancer patients: a meta-analysis
Authors: Lin Li , Li Wei , Chen Chen , Wei Anhua , Liu Yu
Published: July 2023

Background

The implanted vascular access ports (PORTs) were compared with peripherally inserted central catheters (PICCs) as the administration of chemotherapy regarding different clinical effects and adverse effects. Which is better is debatable. Hence, the current study was conducted to assess the safety and efficacy of these two optimal vascular access strategies.

Methods

The following electronic databases were searched: PubMed, Embase, and the Cochrane Library updated in May 2023. Studies on the differences in complication rates in patients with cancer using either PICC or PORT for chemotherapy were included. Meta-analysis Revman 5.3 software was used for statistical analysis.

Results

A total of 22 articles were retrieved. The results suggested that PORT has a superior safety profile, with lower incidences of overall adverse effects (OR=2.72, 95% CI=1.56–4.72 P=0.0004), catheter-related thrombosis (OR=2.84, 95% CI=1.97–4.11, P<0.00001), and allergic reactions (OR=6.26, 95% CI=1.86–21.09, P=0.003) than typically expected with PICC. Moreover, PICC was non-inferior to the PORT group with respect to DVT (OR=2.00, 95% CI=0.86–4.65, P=0.11) and infection (OR=1.55, 95% CI=0.75–3.22, P=0.24).

Conclusion

PORT achieved safety benefits compared with chemotherapy through PICC. Therefore, PORT is regarded as safe and effective vascular access for the administration of chemotherapy. When considering economic factors and some key elements, more high-quality research would help verify these clinical benefits.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identififier CRD42023421690.