bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermittent Exposure to Aflatoxin B1 Did Not Affect Neurobehavioral Parameters and Biochemical Markers of Oxidative Stress
Authors: Braga Ana Claudia Monteiro , Souto Naieli Schiefelbein , Cabral Fernanda Licker , Dassi Micheli , Rosa Érica Vanessa Furlan , Guarda Naiara dos Santos , Royes Luiz Fernando Freire , Fighera Michele Rechia , Moresco Rafael Noal , Oliveira Mauro Schneider , Sari Marcel Henrique Marcondes , Furian Ana Flávia
Published: February 2023

Aflatoxin B1 (AFB1) is the most common toxic mycotoxin that contaminates food. The treatment of its intoxication and the management of contaminations are a constant subject of health agendas worldwide. However, such efforts are not always enough to avoid population intoxication. Our objective was to investigate whether intermittent exposure to AFB1 would cause any impairment in biochemical and behavioral parameters, intending to simulate an irregular consumption. Male Wistar rats received four AFB1 administrations (250 μg/kg) by intragastric route separated by a 96-h interval. Toxicity was evaluated using behavioral tests (open field, object recognition, nest construction, marble burying, and splash test), biochemical markers of oxidative stress (cerebral cortex, hippocampus, liver, and kidneys), and plasma parameters of hepatic and renal functions. The intermittent exposure caused no modification in body weight gain as well as in organ weight. Both control and AFB1 groups presented similar profiles of behavior to all tests performed. Furthermore, AFB1 administrations alter neither antioxidant defenses nor markers of oxidation in all assayed tissues and in the plasma markers of hepatic and renal functions. Therefore, AFB1 intermittent administration did not cause its common damage from exposure to this toxicant, which must be avoided, and additional studies are required.
Discourse Context Immediately Overrides Gender Stereotypes during Discourse Reading: Evidence from ERPs
Authors: Du Yanan , Zhang Yaxu
Published: February 2023

This study investigated how local gender stereotype information interacts with discourse context during Chinese discourse reading. Event-related potentials were recorded while participants read two-sentence discourses, in which the first sentence provided the discourse context that either introduced a gender stereotype-countering attitude towards roles, such as “One should strive for the target job, and getting a job should not be restricted by gender”., or was neutral. The second sentence contained the critical clause in which the stereotypical gender of the object noun (a role name) was either consistent or inconsistent with the gender specified by the head noun (a kinship term) of the subject noun phrase, as in “Li’s [daughter/son] became a nurse…”. The object nouns elicited a larger N400 and a larger late negativity (LN) for the inconsistent compared to the consistent conditions in the neutral contexts. Crucially, when the discourse context offered information countering gender stereotypes, both the N400 and LN effects were reversed, with the negativities being smaller for the inconsistent compared to the consistent conditions. The reversal of the N400 effects suggests that discourse contexts can immediately override the processing of gender stereotypes, and thus readers compute discourse context and local pragmatic information simultaneously during discourse reading.
Sensitivity, Specificity, and Predictive Values of Tru-Cut® Biopsy in Grading Primary Localized Myxoid Liposarcomas of the Extremities
Authors: Bianchi Giuseppe , Laranga Roberta , Spinnato Paolo , Ostetto Federico , Bubbico Elisa , Righi Alberto , Donati Davide Maria
Published: February 2023

(1) Background: Histological diagnosis and tumor grading are major prognostic and predictive factors in soft tissue sarcomas (STS), as they dictate the treatment strategies with a direct impact on patient survival. This study aims to investigate the grading accuracy, sensitivity, and specificity of Tru-Cut® biopsy (TCB) in primary localized myxoid liposarcomas (MLs) of the extremities and its impact on patient prognosis. (2) Methods: Patients with ML undergoing TCB and a subsequent tumor resection between 2007 and 2021 were evaluated. Concordance between the preoperative assessment and definitive histology was calculated with a weighted Cohen’s kappa coefficient. Sensitivity, specificity, and diagnostic accuracy were calculated. (3) Results: Of 144 biopsies, the histological grade concordance rate was 63% (Kappa 0.2819). Neoadjuvant chemotherapy and/or radiotherapy impacted concordance with a downgrading effect in high-grade tumors. Among forty patients not treated in neoadjuvant settings, the sensitivity of TCB was 57%, the specificity was 100%, and the overall predictive values of positive and negative TCB were 100% and 50%, respectively. Misdiagnosis did not impact overall survival. (4) Conclusions: TCB may underestimate ML grading due to tumor heterogeneity. Neoadjuvant ChT and/or radiotherapy are associated with pathological downgrading; however, discordance in diagnosis does not modify patient prognosis because systemic treatment decision-making also includes other variables.
PCSK9 Inhibitors in Cancer Patients Treated with Immune-Checkpoint Inhibitors to Reduce Cardiovascular Events: New Frontiers in Cardioncology
Authors: Quagliariello Vincenzo , Bisceglia Irma , Berretta Massimiliano , Iovine Martina , Canale Maria Laura , Maurea Carlo , Giordano Vienna , Paccone Andrea , Inno Alessandro , Maurea Nicola
Published: February 2023

Cancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due to systemic inflammatory conditions and immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein involved in metabolism of low-density lipoprotein (LDL) cholesterol. PCSK9 blocking agents are clinically available and involve monoclonal antibodies, and SiRNA reduces LDL levels in high-risk patients and atherosclerotic cardiovascular disease events in multiple patient cohorts. Moreover, PCSK9 induces peripheral immune tolerance (inhibition of cancer cell- immune recognition), reduces cardiac mitochondrial metabolism, and enhances cancer cell survival. The present review summarizes the potential benefits of PCSK9 inhibition through selective blocking antibodies and siRNA in patients with cancer, especially in those treated with ICIs therapies, in order to reduce atherosclerotic cardiovascular events and potentially improve ICIs-related anticancer functions.
Advances in Intralesional Therapy for Locoregionally Advanced and Metastatic Melanoma: Five Years of Progress
Authors: DePalo Danielle K. , Zager Jonathan S.
Published: February 2023

Locoregionally advanced and metastatic melanoma are complex diagnoses with a variety of available treatment options. Intralesional therapy for melanoma has been under investigation for decades; however, it has advanced precipitously in recent years. In 2015, the Food and Drug Administration (FDA) approved talimogene laherparepvec (T-VEC), the only FDA-approved intralesional therapy for advanced melanoma. There has been significant progress since that time with other oncolytic viruses, toll-like receptor agonists, cytokines, xanthene dyes, and immune checkpoint inhibitors all under investigation as intralesional agents. Further to this, there has been exploration of numerous combinations of intralesional therapies and systemic therapies as various lines of therapy. Several of these combinations have been abandoned due to their lack of efficacy or safety concerns. This manuscript presents the various types of intralesional therapies that have reached phase 2 or later clinical trials in the past 5 years, including their mechanism of action, therapeutic combinations under investigation, and published results. The intention is to provide an overview of the progress that has been made, discuss ongoing trials worth following, and share our opinions on opportunities for further advancement.
Comparing Oncological and Perioperative Outcomes of Open versus Laparoscopic versus Robotic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Multicenter, Multinational, Propensity Score-Matched Analysis
Authors: Grossmann Nico C. , Soria Francesco , Juvet Tristan , Potretzke Aaron M. , Djaladat Hooman , Ghoreifi Alireza , Kikuchi Eiji , Mari Andrea , Khene Zine-Eddine , Fujita Kazutoshi , Raman Jay D. , Breda Alberto , Fontana Matteo , Sfakianos John P. , Pfail John L. , Laukhtina Ekaterina , Rajwa Pawel , Pallauf Maximillian , Poyet Cédric , Cacciamani Giovanni E. , van Doeveren Thomas , Boormans Joost L. , Antonelli Alessandro , Jamil Marcus , Abdollah Firas , Ploussard Guillaume , Heidenreich Axel , Storz Enno , Daneshmand Siamak , Boorjian Stephen A. , Rouprêt Morgan , Rink Michael , Shariat Shahrokh F. , Pradere Benjamin
Published: February 2023

Objectives: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). Methods: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990–2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien–Dindo > 3) were assessed between groups. Results: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan–Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22–2.28, p = 0.001 and HR 1.73, 95%CI 1.22–2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta −1.1, 95% CI −2.2–0.02, p = 0.047 and beta −6.1, 95% CI −7.2–5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31–0.79, p = 0.003 and OR 0.27, 95% CI 0.16–0.46, p < 0.001, respectively). Conclusions: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.
How Warburg-Associated Lactic Acidosis Rewires Cancer Cell Energy Metabolism to Resist Glucose Deprivation
Authors: Daverio Zoé , Balcerczyk Aneta , Rautureau Gilles J. P. , Panthu Baptiste
Published: February 2023

Lactic acidosis, a hallmark of solid tumour microenvironment, originates from lactate hyperproduction and its co-secretion with protons by cancer cells displaying the Warburg effect. Long considered a side effect of cancer metabolism, lactic acidosis is now known to play a major role in tumour physiology, aggressiveness and treatment efficiency. Growing evidence shows that it promotes cancer cell resistance to glucose deprivation, a common feature of tumours. Here we review the current understanding of how extracellular lactate and acidosis, acting as a combination of enzymatic inhibitors, signal, and nutrient, switch cancer cell metabolism from the Warburg effect to an oxidative metabolic phenotype, which allows cancer cells to withstand glucose deprivation, and makes lactic acidosis a promising anticancer target. We also discuss how the evidence about lactic acidosis’ effect could be integrated in the understanding of the whole-tumour metabolism and what perspectives it opens up for future research.
Genomics-Driven Precision Medicine in Pediatric Solid Tumors
Authors: Suthapot Praewa , Chiangjong Wararat , Chaiyawat Parunya , Choochuen Pongsakorn , Pruksakorn Dumnoensun , Sangkhathat Surasak , Hongeng Suradej , Anurathapan Usanarat , Chutipongtanate Somchai
Published: February 2023

Over the past decades, several study programs have conducted genetic testing in cancer patients to identify potential genetic targets for the development of precision therapeutic strategies. These biomarker-driven trials have demonstrated improved clinical outcomes and progression-free survival rates in various types of cancers, especially for adult malignancies. However, similar progress in pediatric cancers has been slow due to their distinguished mutation profiles compared to adults and the low frequency of recurrent genomic alterations. Recently, increased efforts to develop precision medicine for childhood malignancies have led to the identification of genomic alterations and transcriptomic profiles of pediatric patients which presents promising opportunities to study rare and difficult-to-access neoplasms. This review summarizes the current state of known and potential genetic markers for pediatric solid tumors and provides perspectives on precise therapeutic strategies that warrant further investigations.
Prognostic Value and Immune Infiltration of HPV-Related Genes in the Immune Microenvironment of Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma
Authors: Gan Qiyu , Mao Luning , Shi Rui , Chang Linlin , Wang Guozeng , Cheng Jingxin , Chen Rui
Published: February 2023

Mounting evidence has highlighted the immune environment as a critical feature in the development of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the relationship between the clinical characteristics of the immune environment and CESC remain unclear. Therefore, the aim of this study was to further characterize the relationship between the tumor and immune microenvironment and the clinical features of CESC using a variety of bioinformatic methods. Expression profiles (303 CESCs and three control samples) and relevant clinical data were obtained from The Cancer Genome Atlas. We divided CESC cases into different subtypes and performed a differential gene expression analysis. In addition, gene ontology (GO) and gene set enrichment analysis (GSEA) were performed to identify potential molecular mechanisms. Furthermore, data from 115 CESC patients from East Hospital were used to help identify the relationship between the protein expressions of key genes and disease-free survival using tissue microarray technology. Cases of CESC (n = 303) were divided into five subtypes (C1–C5) based on their expression profiles. A total of 69 cross-validated differentially expressed immune-related genes were identified. Subtype C4 demonstrated a downregulation of the immune profile, lower tumor immune/stroma scores, and worse prognosis. In contrast, the C1 subtype showed an upregulation of the immune profile, higher tumor immune/stroma scores, and better prognosis. A GO analysis suggested that changes in CESC were primarily enriched nuclear division, chromatin binding, and condensed chromosomes. In addition, GSEA demonstrated that cellular senescence, the p53 signaling pathway, and viral carcinogenesis are critical features of CESC. Moreover, high FOXO3 and low IGF-1 protein expression were closely correlated with decreased clinical prognosis. In summary, our findings provide novel insight into the relationship between the immune microenvironment and CESC. As such, our results may provide guidance for developing potential immunotherapeutic targets and biomarkers for CESC.
Interpretable and Reliable Oral Cancer Classifier with Attention Mechanism and Expert Knowledge Embedding via Attention Map
Authors: Song Bofan , Zhang Chicheng , Sunny Sumsum , KC Dharma Raj , Li Shaobai , Gurushanth Keerthi , Mendonca Pramila , Mukhia Nirza , Patrick Sanjana , Gurudath Shubha , Raghavan Subhashini , Tsusennaro Imchen , Leivon Shirley T. , Kolur Trupti , Shetty Vivek , Bushan Vidya , Ramesh Rohan , Pillai Vijay , Wilder-Smith Petra , Suresh Amritha , Kuriakose Moni Abraham , Birur Praveen , Liang Rongguang
Published: February 2023

Convolutional neural networks have demonstrated excellent performance in oral cancer detection and classification. However, the end-to-end learning strategy makes CNNs hard to interpret, and it can be challenging to fully understand the decision-making procedure. Additionally, reliability is also a significant challenge for CNN based approaches. In this study, we proposed a neural network called the attention branch network (ABN), which combines the visual explanation and attention mechanisms to improve the recognition performance and interpret the decision-making simultaneously. We also embedded expert knowledge into the network by having human experts manually edit the attention maps for the attention mechanism. Our experiments have shown that ABN performs better than the original baseline network. By introducing the Squeeze-and-Excitation (SE) blocks to the network, the cross-validation accuracy increased further. Furthermore, we observed that some previously misclassified cases were correctly recognized after updating by manually editing the attention maps. The cross-validation accuracy increased from 0.846 to 0.875 with the ABN (Resnet18 as baseline), 0.877 with SE-ABN, and 0.903 after embedding expert knowledge. The proposed method provides an accurate, interpretable, and reliable oral cancer computer-aided diagnosis system through visual explanation, attention mechanisms, and expert knowledge embedding.
Personalized Medicine in Infant Population with Cancer: Pharmacogenetic Pilot Study of Polymorphisms Related to Toxicity and Response to Chemotherapy
Authors: Urtasun Andrea , Olivera Gladys G. , Sendra Luis , Aliño Salvador F. , Berlanga Pablo , Gargallo Pablo , Hervás David , Balaguer Julia , Juan-Ribelles Antonio , Andrés María del Mar , Cañete Adela , Herrero María José
Published: February 2023

Background: Pharmacogenetics is a personalized medicine tool that aims to optimize treatments by adapting them to each individual’s genetics, maximizing their efficacy while minimizing their toxicity. Infants with cancer are especially vulnerable, and their co-morbidities have vital repercussions. The study of their pharmacogenetics is new in this clinical field. Methods: A unicentric, ambispective study of a cohort of infants receiving chemotherapy (from January 2007 to August 2019). The genotypes of 64 patients under 18 months of age were correlated with severe drug toxicities and survival. A pharmacogenetics panel was configured based on PharmGKB, drug labels, and international experts’ consortiums. Results: Associations between SNPs and hematological toxicity were found. Most meaningful were: MTHFR rs1801131 GT increasing the anemia risk (OR 1.73); rs1517114 GC, XPC rs2228001 GT, increasing neutropenia risk (OR 1.50 and 4.63); ABCB1 rs1045642 AG, TNFRSF11B rs2073618 GG, CYP2B6 rs4802101 TC and SOD2 rs4880 GG increasing thrombocytopenia risk (OR 1.70, 1.77, 1.70, 1.73, respectively). Regarding survival, MTHFR rs1801133 GG, TNFRSF11B rs2073618 GG, XPC rs2228001 GT, CYP3A4 rs2740574 CT, CDA rs3215400 del.del, and SLC01B1 rs4149015 GA were associated with lower overall survival probabilities (HR 3.12, 1.84, 1.68, 2.92, 1.90, and 3.96, respectively). Lastly, for event-free survival, SLC19A1 rs1051266 TT and CDA rs3215400 del.del increased the relapse probability (HR 1.61 and 2.19, respectively). Conclusions: This pharmacogenetic study is a pioneer in dealing with infants under 18 months of age. Further studies are needed to confirm the utility of the findings in this work to be used as predictive genetic biomarkers of toxicity and therapeutic efficacy in the infant population. If confirmed, their use in therapeutic decisions could improve the quality of life and prognosis of these patients.
ATF4 Transcriptionally Activates SHH to Promote Proliferation, Invasion, and Migration of Gastric Cancer Cells
Authors: Wang Yang , Ali Muhammad , Zhang Qi , Sun Qiannan , Ren Jun , Wang Wei , Tang Dong , Wang Daorong
Published: February 2023

Activating transcription factor 4 (ATF4) is a DNA-binding protein widely generated in mammals, which has two biological characteristics that bind the cAMP response element (CRE). The mechanism of ATF4 as a transcription factor in gastric cancer affecting the Hedgehog pathway remains unclear. Here, we observed that ATF4 was markedly upregulated in gastric cancer (GC) using immunohistochemistry and Western blotting assays in 80 paraffin-embedded GC samples and 4 fresh samples and para-cancerous tissues. ATF4 knockdown using lentiviral vectors strongly inhibited the proliferation and invasion of GC cells. ATF4 upregulation using lentiviral vectors promoted the proliferation and invasion of GC cells. We predicted that the transcription factor ATF4 is bound to the SHH promoter via the JASPA database. Transcription factor ATF4 is bound to the promoter region of SHH to activate the Sonic Hedgehog pathway. Mechanistically, rescue assays showed that ATF4 regulated gastric cancer cells’ proliferation and invasive ability through SHH. Similarly, ATF4 enhanced the tumor formation of GC cells in a xenograft model.
Liquid Biopsies in Lung Cancer
Authors: Kemper Marcel , Krekeler Carolin , Menck Kerstin , Lenz Georg , Evers Georg , Schulze Arik Bernard , Bleckmann Annalen
Published: February 2023

As lung cancer has the highest cancer-specific mortality rates worldwide, there is an urgent need for new therapeutic and diagnostic approaches to detect early-stage tumors and to monitor their response to the therapy. In addition to the well-established tissue biopsy analysis, liquid-biopsy-based assays may evolve as an important diagnostic tool. The analysis of circulating tumor DNA (ctDNA) is the most established method, followed by other methods such as the analysis of circulating tumor cells (CTCs), microRNAs (miRNAs), and extracellular vesicles (EVs). Both PCR- and NGS-based assays are used for the mutational assessment of lung cancer, including the most frequent driver mutations. However, ctDNA analysis might also play a role in monitoring the efficacy of immunotherapy and its recent accomplishments in the landscape of state-of-the-art lung cancer therapy. Despite the promising aspects of liquid-biopsy-based assays, there are some limitations regarding their sensitivity (risk of false-negative results) and specificity (interpretation of false-positive results). Hence, further studies are needed to evaluate the usefulness of liquid biopsies for lung cancer. Liquid-biopsy-based assays might be integrated into the diagnostic guidelines for lung cancer as a tool to complement conventional tissue sampling.
Conversion of Minimally Invasive Liver Resection for HCC in Advanced Cirrhosis: Clinical Impact and Role of Difficulty Scoring Systems
Authors: Cipriani Federica , Ratti Francesca , Fornoni Gianluca , Marino Rebecca , Tudisco Antonella , Catena Marco , Aldrighetti Luca
Published: February 2023

Background: Minimally invasive liver resections (MILRs) in cirrhosis are at risk of conversion since cirrhosis and complexity, which can be estimated by scoring systems, are both independent factors for. We aimed to investigate the consequence of conversion of MILR for hepatocellular carcinoma in advanced cirrhosis. Methods: After retrospective review, MILRs for HCC were divided into preserved liver function (Cohort-A) and advanced cirrhosis cohorts (Cohort-B). Completed and converted MILRs were compared (Compl-A vs. Conv-A and Compl-B vs. Conv-B); then, converted patients were compared (Conv-A vs. Conv-B) as whole cohorts and after stratification for MILR difficulty using Iwate criteria. Results: 637 MILRs were studied (474 Cohort-A, 163 Cohort-B). Conv-A MILRs had worse outcomes than Compl-A: more blood loss; higher incidence of transfusions, morbidity, grade 2 complications, ascites, liver failure and longer hospitalization. Conv-B MILRs exhibited the same worse perioperative outcomes than Compl-B and also higher incidence of grade 1 complications. Conv-A and Conv-B outcomes of low difficulty MILRs resulted in similar perioperative outcomes, whereas the comparison of more difficult converted MILRs (intermediate/advanced/expert) resulted in several worse perioperative outcomes for patients with advanced cirrhosis. However, Conv-A and Conv-B outcomes were not significantly different in the whole cohort where “advanced/expert” MILRs were 33.1% and 5.5% in Cohort A and B. Conclusions: Conversion in the setting of advanced cirrhosis can be associated with non-inferior outcomes compared to compensated cirrhosis, provided careful patient selection is applied (patients elected to low difficulty MILRs). Difficulty scoring systems may help in identifying the most appropriate candidates.
The Resection Rate of Synchronously Detected Liver and Lung Metastasis from Colorectal Cancer Is Low—A National Registry-Based Study
Authors: Engstrand Jennie , Taflin Helena , Rystedt Jenny Lundmark , Hemmingsson Oskar , Urdzik Jozef , Sandström Per , Björnsson Bergthor , Hasselgren Kristina
Published: February 2023

Population-based data on the incidence and surgical treatment of patients with colorectal cancer (CRC) and synchronous liver and lung metastases are lacking as are real-life data on the frequency of metastasectomy for both sites and outcomes in this setting. This is a nationwide population-based study of all patients having liver and lung metastases diagnosed within 6 months of CRC between 2008 and 2016 in Sweden identified through the merging of data from the National Quality Registries on CRC, liver and thoracic surgery and the National Patient Registry. Among 60,734 patients diagnosed with CRC, 1923 (3.2%) had synchronous liver and lung metastases, of which 44 patients had complete metastasectomy. Surgery of liver and lung metastases yielded a 5-year OS of 74% (95% CI 57–85%) compared to 29% (95% CI 19–40%) if liver metastases were resected but not the lung metastases and 2.6% (95% CI 1.5–4%) if non-resected, p < 0.001. Complete resection rates ranged from 0.7% to 3.8% between the six healthcare regions of Sweden, p = 0.007. Synchronous liver and lung CRC metastases are rare, and a minority undergo the resection of both metastatic sites but with excellent survival. The reasons for differences in regional treatment approaches and the potential of increased resection rates should be studied further.
Surgical Planning after Neoadjuvant Treatment in Breast Cancer: A Multimodality Imaging-Based Approach Focused on MRI
Authors: Conti Marco , Morciano Francesca , Bufi Enida , D’Angelo Anna , Panico Camilla , Di Paola Valerio , Gori Elisabetta , Russo Gianluca , Cimino Giovanni , Palma Simone , Belli Paolo , Manfredi Riccardo
Published: February 2023

Neoadjuvant chemotherapy (NACT) today represents a cornerstone in the treatment of locally advanced breast cancer and highly chemo-sensitive tumors at early stages, increasing the possibilities of performing more conservative treatments and improving long term outcomes. Imaging has a fundamental role in the staging and prediction of the response to NACT, thus aiding surgical planning and avoiding overtreatment. In this review, we first examine and compare the role of conventional and advanced imaging techniques in preoperative T Staging after NACT and in the evaluation of lymph node involvement. In the second part, we analyze the different surgical approaches, discussing the role of axillary surgery, as well as the possibility of non-operative management after-NACT, which has been the subject of recent trials. Finally, we focus on emerging techniques that will change the diagnostic assessment of breast cancer in the near future.
Prediction of the Molecular Subtype of IDH Mutation Combined with MGMT Promoter Methylation in Gliomas via Radiomics Based on Preoperative MRI
Authors: Sha Yongjian , Yan Qianqian , Tan Yan , Wang Xiaochun , Zhang Hui , Yang Guoqiang
Published: February 2023

Background: The molecular subtype of IDH mut combined with MGMT meth in gliomas suggests a good prognosis and potential benefit from TMZ chemotherapy. The aim of this study was to establish a radiomics model to predict this molecular subtype. Method: The preoperative MR images and genetic data of 498 patients with gliomas were retrospectively collected from our institution and the TCGA/TCIA dataset. A total of 1702 radiomics features were extracted from the tumour region of interest (ROI) of CE-T1 and T2-FLAIR MR images. Least absolute shrinkage and selection operator (LASSO) and logistic regression were used for feature selection and model building. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the predictive performance of the model. Results: Regarding clinical variables, age and tumour grade were significantly different between the two molecular subtypes in the training, test and independent validation cohorts (p < 0.05). The areas under the curve (AUCs) of the radiomics model based on 16 selected features in the SMOTE training cohort, un-SMOTE training cohort, test set and independent TCGA/TCIA validation cohort were 0.936, 0.932, 0.916 and 0.866, respectively, and the corresponding F1-scores were 0.860, 0.797, 0.880 and 0.802. The AUC of the independent validation cohort increased to 0.930 for the combined model when integrating the clinical risk factors and radiomics signature. Conclusions: radiomics based on preoperative MRI can effectively predict the molecular subtype of IDH mut combined with MGMT meth.
Rapamycin-Induced Feedback Activation of eIF4E-EIF4A Dependent mRNA Translation in Pancreatic Cancer
Authors: Nguyen Trang Uyen , Hector Harrison , Pederson Eric Nels , Lin Jianan , Ouyang Zhengqing , Wendel Hans-Guido , Singh Kamini
Published: February 2023

Pancreatic cancer cells adapt molecular mechanisms to activate the protein synthesis to support tumor growth. This study reports the mTOR inhibitor rapamycin’s specific and genome-wide effect on mRNA translation. Using ribosome footprinting in pancreatic cancer cells that lack the expression of 4EBP1, we establish the effect of mTOR-S6-dependent mRNAs translation. Rapamycin inhibits the translation of a subset of mRNAs including p70-S6K and proteins involved in the cell cycle and cancer cell growth. In addition, we identify translation programs that are activated following mTOR inhibition. Interestingly, rapamycin treatment results in the translational activation of kinases that are involved in mTOR signaling such as p90-RSK1. We further show that phospho-AKT1 and phospho-eIF4E are upregulated following mTOR inhibition suggesting a feedback activation of translation by rapamycin. Next, targeting eIF4E and eIF4A-dependent translation by using specific eIF4A inhibitors in combination with rapamycin shows significant growth inhibition in pancreatic cancer cells. In short, we establish the specific effect of mTOR-S6 on translation in cells lacking 4EBP1 and show that mTOR inhibition leads to feedback activation of translation via AKT-RSK1-eIF4E signals. Therefore, targeting translation downstream of mTOR presents a more efficient therapeutic strategy in pancreatic cancer.
Cell Replacement Therapy for Type 1 Diabetes Patients: Potential Mechanisms Leading to Stem-Cell-Derived Pancreatic β-Cell Loss upon Transplant
Authors: Shilleh Ali H. , Russ Holger A.
Published: February 2023

Cell replacement therapy using stem-cell-derived insulin-producing β-like cells (sBCs) has been proposed as a practical cure for patients with type one diabetes (T1D). sBCs can correct diabetes in preclinical animal models, demonstrating the promise of this stem cell-based approach. However, in vivo studies have demonstrated that most sBCs, similarly to cadaveric human islets, are lost upon transplantation due to ischemia and other unknown mechanisms. Hence, there is a critical knowledge gap in the current field concerning the fate of sBCs upon engraftment. Here we review, discuss effects, and propose additional potential mechanisms that could contribute toward β-cell loss in vivo. We summarize and highlight some of the literature on phenotypic loss in β-cells under both steady, stressed, and diseased diabetic conditions. Specifically, we focus on β-cell death, dedifferentiation into progenitors, trans-differentiation into other hormone-expressing cells, and/or interconversion into less functional β-cell subtypes as potential mechanisms. While current cell replacement therapy efforts employing sBCs carry great promise as an abundant cell source, addressing the somewhat neglected aspect of β-cell loss in vivo will further accelerate sBC transplantation as a promising therapeutic modality that could significantly enhance the life quality of T1D patients.
Self-Immobilizing Quinone Methides for the Fluorescent Sensing of Enzyme Activity
Authors: Kern Dóra , Kormos Attila
Published: February 2023

Gaining insight into biological processes relies on sensitive analytical techniques. These often require labeling of biomolecules that help visualize them. Selective covalent labeling without preliminary modification of the biomolecules is an advantageous method. For example, this can be achieved by using probes that are capable of in situ quinone methide (QM) formation. The QM can be masked to give a stable precursor, and the highly reactive form is only generated upon activation by a specific trigger. The in situ formed QM then binds covalently to the nucleophilic side chains of either the target protein or a protein in close proximity. Using fluorogenic probes further improves this method by reducing non-specific background signals, thus improving signal-to-noise ratios. In this review we summarize the development of quinone methide-based probes from mechanism-based inactivation to red-emitting, fluorogenic activity probes, focusing on enzyme-triggered activation.
Autism and ADHD: A Literature Review Regarding Their Impacts on Parental Divorce
Authors: Anchesi Smeralda Diandra , Corallo Francesco , Di Cara Marcella , Quartarone Angelo , Catalioto Rino , Cucinotta Francesca , Cardile Davide
Published: February 2023

Introduction: The change in family structure as a consequence of divorce can be a traumatic event for a child that can undermine his or her emotional security. For this reason, it becomes a major health concern. Many divorce-related risk factors have been identified, including attention deficits or autism spectrum disorder (ASD) in children. The aim of this review is to evaluate if and how a diagnosis of ASD or attention deficit hyperactivity disorder (ADHD) in children is associated with an increase in divorce within families. Method: Searches were performed in two databases evaluating studies focusing on articles pertaining to the topic. A total of 20 articles were found, but only 8 were included in the study according to the criteria. Results: The results showed that divorce does not appear to be specifically related to a diagnosed pathology of the child, but rather presents itself as a risk factor in certain situations. In particular, this occurs when the coping strategies required to deal with the diagnosis are dysfunctional. However, it would appear that families in which there are children with ADHD have a greater chance of divorce than families in which there is a child with a diagnosis of ASD. It may be hypothesised that in the latter case, parents receiving a diagnosis early in the child’s life have more time to develop adaptive strategies to cope with the condition than parents with children with ADHD who mostly find themselves having to deal with their child’s behavioural problems at a school age. Moreover, ASD is a disorder more likely genetic than environment-related, so parents receive more socio-medical support, and they are less likely to blame themselves or be blamed by others.
Title: Caring for Children with Cerebral Palsy: A Challenge to Caregivers in Rural Areas of South Africa
Authors: Manyuma Duppy , Maluleke Mary , Raliphaswa Ndidzulafhi Selina , Masutha Thingahangwi Cecilia , Rangwaneni Mphedziseni Esther , Thabathi Takalani Eldah , Lavhelani Ndivhaleni Robert
Published: February 2023

Background: In South Africa, children with cerebral palsy are nested within a family setting by immediate relatives, particularly in the rural areas. These immediate relatives are regarded as caregivers and are not trained with regard to providing care to children with special needs. Therefore, they have to find ways to adapt to their new roles of caregiving using the available resources. The aim of this paper is to present the challenges encountered by caregivers of children with cerebral palsy in rural areas of South Africa. Methods: This qualitative, explorative, descriptive, and contextual study included 10 caregivers for children with cerebral palsy who were purposively recruited from the three respective hospitals in Vhembe District within Limpopo Province. Data were collected through individual in-depth interviews and analysed using a thematic approach. Ethical considerations and measures to ensure trustworthiness were upheld throughout the study. Results: Four themes emerged from the study, namely economic problems facing caregivers; health problems encountered by caregivers; maltreatment of caregivers by community members, as well as access to transport for caregivers and children. Conclusion: Participants narrated that caring for a child with cerebral palsy is not an easy task for the caregiver, particularly in the rural areas of South Africa. They encounter various challenges as they strive to provide quality care to the children that they are caring for. An investigation is recommended concerning the kind of model which should be developed to support caregivers in caring for children with cerebral palsy in the rural areas.
Archaeometric Investigations of the Chalcolithic Pottery from Topolița—Neamț County, Romania
Authors: Ion Rodica-Mariana , Diaconu Vasile , Vasilievici Gabriel , Iancu Lorena , Grigorescu Ramona Marina , Mîrț Luiza-Andreea , Alexandrescu Elvira , Gheboianu Anca Irina , Slamnoiu-Teodorescu Sofia
Published: February 2023

The current work deals with specific investigations on the ceramic fragment samples from the archaeological site of Topolița (Eastern Romania), which is essentially unexplored to date. X-ray diffraction (XRD) has shown that the ceramics contain quartz, berlinite, mica (muscovite), calcite, and opaque minerals, such as hematite. All evidence indicates the use of raw materials with a low limestone content (poor Ca clays) for the manufacture of these ceramics (Ca < 3.6%). The wavelength dispersive X-ray fluorescence (WDXRF) measurements indicated the presence of Al, Si, Fe, Ca, Zn, P, and K. All these data are well correlated with energy dispersive spectroscopy (EDS), which is used as an additional technique of scanning electron microscopy (SEM). Through thermogravimetry and porosimetry, some information have been obtained, with the results being correlated with the chromatic parameters that characterize the samples after burning: Various shades of color (red color with sparkles and partially or totally black interior), differently colored engobes, white pigment encrusted with white color from calcite, gypsum, clays, and quartz, as well as carbon deposits in the pores of the pottery, all specific to the Chalcolithic ceramics from this region. The recorded FTIR spectra of these samples led to the identification of calcite, quartz, gypsum, and aluminum phosphate, present as berlinite in all the pottery specific to this area. In addition, the presence/absence and the amount of specific chemical elements in the white pigments (e.g., calcium, aluminum, phosphorus, silicon, sulfur) could be used as indicative for the identified mineral compounds (XRD and FTIR). Calcite and silica-rich sediments as the primary decoration pigments, have been identified in this case.
A Ru-Doped VTi2.6O7.2 Anode with High Conductivity for Enhanced Sodium Storage
Authors: Zhang Guangwan , Han Chunhua , Han Kang , Liu Jinshuai , Chen Jinghui , Wang Haokai , Zhang Lei , Wang Xuanpeng
Published: February 2023

Sodium-ion batteries (SIBs) are considered a potential replacement for lithium-ion batteries in the area of low-cost large-scale energy storage. Due to its low operating voltage, high capacity, non-toxicity and low production cost, titanium dioxide is now among the anode materials under investigation and shows the most promise. However, its poor electrical conductivity is one of the main reasons limiting its large-scale application. Herein, we designed a ruthenium-doped anatase-type VTi2.6O7.2 ultrafine nanocrystal (Ru-VTO). As the anode of SIBs, Ru-VTO delivers a high specific capacity of 297 mAh g−1 at 50 mA g−1, a long cycle life of 2000 cycles and a high rate capability (104 mAh g−1 at 1000 mA g−1). The excellent performance may be related to the solid-solution interatomic interactions and the enhanced conductivity after ruthenium doping. These studies demonstrate the potential of Ru-VTO as an anode material for advanced SIBs.
The Development of Cement-Based, Intumescent and Geopolymer Fire-Retardation Coatings for Metal Structures: A Review
Authors: Wang Kaibao , Le Huirong
Published: February 2023

Coating, as one of the significant applications in the building and construction sector, is crucial to prevent steel from reaching critical temperature and fire-induced structural collapse. This article reviews the current use of conventional coatings and assesses the potential use of novel geopolymer coatings on the metal substrate, particularly on the steel structure. The conventional passive fireproofing systems, including cement-based coatings and intumescent coatings, exhibit unavoidable limitations either due to the high thickness and weight or poor thermal and chemical resistance of the coating. Thus, innovations in conventional and novel coatings are constantly developing and growing rapidly. In recent years, geopolymer coatings have attracted much attention due to their higher mechanical strength and excellent resistance to chemicals and heat. Moreover, the green and environmentally friendly characteristics make geopolymer an admirable coating material for many applications. The main challenge that lies in the development of geopolymer coating is the interfacial bonding with the metal structure. Therefore, the influencing factors, including precursor materials, alkaline activator, and curing processes on the adhesion and thermal and chemical resistance of the geopolymer coating have been well explored. The performance comparison between these coatings indicates that geopolymer coating offers a superior mechanical and thermal performance, along with a substantially lower environmental impact compared with cement-based coating. This suggests that geopolymer coatings have great potential for fire protection on steel structures.
The Leakage Current Characteristics of High-Gradient MOA Plate and Its Heating Analysis with Coatings under High-Frequency Overvoltage
Authors: Sun Jixing , Fan Yongzhi , Zhang Kun , Liu Jiyong , Wang Xin , Yan Shengchun
Published: February 2023

High-frequency overvoltage generated in railways results in explosions of Electric Multiple Units’ (EMUs) arrestors. To solve this problem, the leakage current characteristics and heat transfer process of high-gradient MOA plates under high-frequency overvoltage has been studied. The leakage current characteristics of arrestor plates under high-frequency voltage was obtained and the element distribution has been analyzed. Heat transfer distribution and the thermal properties of the Metal Oxide Arrestor (MOA) have been modelled. According to the results, for a given voltage, the higher the harmonic frequency, the greater the leakage current of the arrestor valve plate, and the greater the resistive component of the leakage current. The Zn and O elements in high-gradient MOA plates are more uniform. Under the same leakage current as conventional ones, the undertake voltage of a high-gradient MOA plate will increase by 10%. Longtime high-order harmonic action will still significantly improve the core rod temperature when MOA plates are coated. The temperature rise in the power supply section of EMUs during operation is roughly 35 °C. This result will provide a foundation and supporting data for the applicability of high-gradient valve plates in railroads and coating improvements for traditional arrestor plates.
Hirshfeld and AIM Analysis of the Methylone Hydrochloride Crystal Structure and Its Impact on the IR Spectrum Combined with DFT Study
Authors: Minaeva Valentina , Karaush-Karmazin Nataliya , Panchenko Olexandr , Minaev Boris , Ågren Hans
Published: February 2023

Herein, the Hirshfeld surfaces analysis of the crystalline methylone hydrochloride was performed in order to analyze NH⋯Cl, CH⋯Cl, and CH⋯O intermolecular interactions and study the formation of the NН2+–Cl− salt fragment in methylone hydrochloride crystal. There are two isomeric dimers with parallel and side-by-side orientation extracted from the crystal packing to model the IR spectrum of the crystalline methylone hydrochloride within the framework of density functional theory (DFT) and B3LYP/6-31G(d,p) method. We have assigned and interpreted all observed IR bands in the experimental spectrum of the 3,4-methylenedioxymethcathinone hydrochloride standard crystal sample that is important for forensic-medical examination. It was shown that intermolecular interactions between the NН2+ and Cl− ionic moieties occur in crystalline samples that confirm the presence of the ionized form of the methylone hydrochloride compound with the NН2+Cl− fragment.
Supramolecular Association via Hg···S Secondary-Bonding Interactions in Crystals of Organomercury(II) Species: A Survey of the Cambridge Structure Database
Authors: Tiekink Edward R. T.
Published: February 2023

The Cambridge Structural Database has been surveyed for crystals featuring organo-Hg···S secondary-bonding interactions within supramolecular aggregates. Nearly 50% of crystals where Hg···S interactions could potentially form, featured Hg···S contacts within zero- or one-dimensional supramolecular assemblies with only a few examples of two-dimensional arrays featuring Hg···S interactions. This high propensity of Hg···S contact formation reflects the inherent thiophilic nature of mercury but also the relatively open access to mercury owing to the linear C–Hg–S coordination geometries, the prevalence of close intramolecular Hg···S, Hg···O and Hg···N interactions notwithstanding.