bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) versus Conventional Surgery on Patient-Reported Outcomes: A Comparative Cohort Study between the CAIRO6 Trial and the PROCORE Study
Authors: Bakkers Checca , van de Vlasakker Vincent C. J. , Rovers Koen P. B. , Lurvink Robin J. , Nienhuijs Simon W. , Burger Jacobus W. A. , Creemers Geert-Jan M. , Bonhof Cynthia S. , Mols Floortje , de Hingh Ignace H. J. T.
Published: January 2023

Purpose—To compare patient-reported outcomes (PROs) of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for colorectal peritoneal metastases to PROs of colorectal cancer (CRC) patients undergoing conventional surgery. Methods—Data were extracted from the CAIRO6 trial (CRS-HIPEC group) and the PROCORE study (conventional surgery group). Nine predefined PROs (derived from the EORTC QLQ-C30 questionnaire) were compared at baseline, in the early postoperative period and one year postoperatively, with correction for treatment with systemic therapy using linear mixed modeling. Results—In total, 331 patients were included: 71 in the CRS-HIPEC group and 260 in the conventional surgery group. All predefined PROs (fatigue, diarrhea, C30 summary score, Global Health Status, physical, role, emotional, cognitive, and social functioning) did not differ significantly between the groups at all three timepoints, and differential effects over time for all PROs did not differ significantly between the groups. Significant worsening of fatigue, C30 summary score, physical and role functioning (both groups), and cognitive and social functioning (conventional surgery group only) was present in the early postoperative period. All scores returned to baseline at one year postoperatively, except for physical and cognitive functioning in the conventional surgery group. Emotional functioning improved postoperatively in both groups compared to baseline. Conclusion—Despite a more extensive procedure with greater risk of morbidity, CRS-HIPEC in patients with colorectal peritoneal metastases did not have a greater negative impact on PROs than conventional surgery in patients with CRC. Further, systemic therapy did not affect these PROs. These findings may facilitate future patient counseling and shared decision making in clinical practice.
Gene-Transcript Expression in Urine Supernatant and Urine Cell-Sediment Are Different but Equally Useful for Detecting Prostate Cancer
Authors: Yazbek Hanna Marcelino , Winterbone Mark , O’Connell Shea P. , Olivan Mireia , Hurst Rachel , Mills Rob , Cooper Colin S. , Brewer Daniel S. , Clark Jeremy
Published: January 2023

There is considerable interest in urine as a non-invasive liquid biopsy to detect prostate cancer (PCa). PCa-specific transcripts such as the TMPRSS2:ERG fusion gene can be found in both urine extracellular vesicles (EVs) and urine cell-sediment (Cell) but the relative usefulness of these and other genes in each fraction in PCa detection has not been fully elucidated. Urine samples from 76 men (PCa n = 40, non-cancer n = 36) were analysed by NanoString for 154 PCa-associated genes-probes, 11 tissue-specific, and six housekeeping. Comparison to qRT-PCR data for four genes (PCA3, OR51E2, FOLH1, and RPLP2) was strong (r = 0.51–0.95, Spearman p < 0.00001). Comparing EV to Cells, differential gene expression analysis found 57 gene-probes significantly more highly expressed in 100 ng of amplified cDNA products from the EV fraction, and 26 in Cells (p < 0.05; edgeR). Expression levels of prostate-specific genes (KLK2, KLK3) measured were ~20× higher in EVs, while PTPRC (white-blood Cells) was ~1000× higher in Cells. Boruta analysis identified 11 gene-probes as useful in detecting PCa: two were useful in both fractions (PCA3, HOXC6), five in EVs alone (GJB1, RPS10, TMPRSS2:ERG, ERG_Exons_4-5, HPN) and four from Cell (ERG_Exons_6-7, OR51E2, SPINK1, IMPDH2), suggesting that it is beneficial to fractionate whole urine prior to analysis. The five housekeeping genes were not significantly differentially expressed between PCa and non-cancer samples. Expression signatures from Cell, EV and combined data did not show evidence for one fraction providing superior information over the other.
Complete Response in Metastatic Clear Cell Renal Cell Carcinoma Patients Treated with Immune-Checkpoint Inhibitors: Remission or Healing? How to Improve Patients’ Outcomes?
Authors: Thouvenin Jonathan , Masson Claire , Boudier Philippe , Maillet Denis , Kuchler-Bopp Sabine , Barthélémy Philippe , Massfelder Thierry
Published: January 2023

Renal-cell carcinoma (RCC) accounts for 2% of cancer diagnoses and deaths worldwide. Clear-cell RCCs represent the vast majority (85%) of kidney cancers and are considered morphologically and genetically as immunogenic tumors. Indeed, the RCC tumoral microenvironment comprises T cells and myeloid cells in an immunosuppressive state, providing an opportunity to restore their activity through immunotherapy. Standard first-line systemic treatment for metastatic patients includes immune-checkpoint inhibitors (ICIs) targeting PD1, in combination with either another ICI or with antiangiogenic targeted therapy. During the past few years, several combinations have been approved with an overall survival benefit and overall response rate that depend on the combination. Interestingly, some patients achieve prolonged complete responses, raising the question of whether these metastatic RCC patients can be cured. This review will focus on recent therapeutic advances in RCC and the clinical and biological aspects underpinning the potential for healing.
Prostate Cancer—PET Imaging Update
Authors: Jetty Sankarsh , Loftus James Ryan , Patel Abhinav , Gupta Akshya , Puri Savita , Dogra Vikram
Published: January 2023

Prostate cancer is the most common non-dermatologic cancer in men, and one of the leading causes of cancer-related mortality. The incidence of prostate cancer increases precipitously after the age of 65 and demonstrates variable aggressiveness, depending on its grade and stage at diagnosis. Despite recent advancements in prostate cancer treatment, recurrence is seen in 25% of patients. Advancements in prostate cancer Positron Emission Tomography (PET) molecular imaging and recent United States Food and Drug Administration (FDA) approvals have led to several new options for evaluating prostate cancer. This manuscript will review the commonly used molecular imaging agents, with an emphasis on Fluorine-18 fluciclovine (Axumin) and PSMA-ligand agents, including their protocols, imaging interpretation, and pitfalls.
The Quality of Life in Surgically Treated Head and Neck Basal Cell Carcinoma Patients: A Comprehensive Review
Authors: Stundys Domantas , Ulianskaite Gintare , Stundiene Ieva , Grigaitiene Jurate , Jancoriene Ligita
Published: January 2023

In this review, we examine current literature analyzing the impact of surgical treatment on the QoL in patients with head and neck BCC. A comprehensive literature review was performed using the main databases. As many as six out of 322 articles were selected for the final analysis. The selected articles were published in the period between 2004 and 2021, most published within the last two years. All analyzed studies were prospective. Five out of six studies evaluated NMSC consisting of both BCC and SCC, and only one study selectively evaluated the impact of surgical treatment on QoL in patients with craniofacial BCC. Authors of the selected studies reported that QoL improves following the surgery; however, the effect on QoL varies. Patients’ age, gender, marital status, education level, and employment status had a stronger correlation with QoL postoperatively, especially during the late follow-up period. Younger patients were more bothered by appearance-related issues. One study concluded that elderly patients did not experience a statistically significant improvement in QoL. This literature review demonstrated that there is no clear consensus on the use of a single disease-specific QoL measurement tool. Furthermore, there is a lack of studies assessing the impact of surgical treatment on QoL exclusively in patients with head and neck BCC and studies analyzing the multivariate correlation between QoL and tumor type, size, anatomic site, and treatment outcomes.
Central Compartment Neck Dissection in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma: Clinical Considerations
Authors: Deganello Alberto , Ruaro Alessandra , Gualtieri Tommaso , Berretti Giulia , Rampinelli Vittorio , Borsetto Daniele , Russo Sabino , Boscolo-Rizzo Paolo , Ferrari Marco , Bussu Francesco
Published: January 2023

Metastatic lymph node involvement represents the most relevant prognostic factor in head and neck squamous cell carcinomas (HNSCCs), invariably affecting overall survival, disease-specific survival, and relapse-free survival. Among HNSCCs, laryngeal and hypopharyngeal cancers are known to be at highest risk to metastasize to the central neck compartment (CNC). However, prevalence and prognostic implications related to the CNC involvement are not well defined yet, and controversies still exist regarding the occult metastasis rate. Guidelines for the management of CNC in laryngeal and hypopharyngeal cancers are vague, resulting in highly variable selection criteria for the central neck dissection among different surgeons and institutions. With this review, the authors intend to reappraise the existing data related to the involvement of CNC in laryngeal and hypopharyngeal malignancies, in the attempt to define the principles of management while highlighting the debated aspects that are lacking in evidence and consensus. Furthermore, as definition and boundaries of the CNC have changed over the years, an up-to-date anatomical–surgical description of the CNC is provided.
CA125 for the Diagnosis of Advanced Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis
Authors: Lin Hsuan-Jen , Hu Rouh-Mei , Chen Hung-Chih , Lin Chung-Chih , Lee Chi-Yu , Chou Che-Yi
Published: January 2023

Background: Urothelial carcinoma of the bladder (UCB) is the second most common genitourinary cancer. This study aims to assess the diagnostic accuracy of CA125 in advanced UCB. Methods: We searched prevalent studies in PubMed, the Cochrane Library, Scopus, Embase, the Web of Science China National Knowledge Infrastructure database, and Wanfang data before October 2022. Pooled sensitivity, specificity, and summary receiver operating characteristics were used to assess the diagnostic value of CA125. Results: One thousand six hundred forty-one patients from 14 studies were analyzed. UCB stage T3–4N1 was defined as advanced UCB in ten studies; T2–4 was used in three studies; and N1M1 in one study. Patients’ age was between 21 to 92, and 21% to 48.6% of patients were female. The pooled sensitivity was 0.695 (95% confidence interval (CI): 0.426–0.875). The pooled specificity was 0.846 (95% CI: 0.713–0.924). The diagnostic odds ratio was 8.138 (95% CI: 4.559–14.526). The AUC was 0.797. Conclusion: CA125 may provide significant diagnostic accuracy in identifying muscle-invasive, lymph node-involved, and distant metastatic tumors in patients with urothelial carcinoma of the bladder. Limited studies have been conducted on the prognostic role of CA125. More studies are needed for a meta-analysis on the prognostic role of CA125 in UCB.
A Comprehensive Analysis of Cutaneous Melanoma Patients in Greece Based on Multi-Omic Data
Authors: Kontogianni Georgia , Voutetakis Konstantinos , Piroti Georgia , Kypreou Katerina , Stefanaki Irene , Vlachavas Efstathios Iason , Pilalis Eleftherios , Stratigos Alexander , Chatziioannou Aristotelis , Papadodima Olga
Published: January 2023

Cutaneous melanoma (CM) is the most aggressive type of skin cancer, and it is characterised by high mutational load and heterogeneity. In this study, we aimed to analyse the genomic and transcriptomic profile of primary melanomas from forty-six Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from Greek patients. Molecular analysis for both germline and somatic variations was performed in genomic DNA from peripheral blood and melanoma samples, respectively, exploiting whole exome and targeted sequencing, and transcriptomic analysis. Detailed clinicopathological data were also included in our analyses and previously reported associations with specific mutations were recognised. Most analysed samples (43/46) were found to harbour at least one clinically actionable somatic variant. A subset of samples was profiled at the transcriptomic level, and it was shown that specific melanoma phenotypic states could be inferred from bulk RNA isolated from FFPE primary melanoma tissue. Integrative bioinformatics analyses, including variant prioritisation, differential gene expression analysis, and functional and gene set enrichment analysis by group and per sample, were conducted and molecular circuits that are implicated in melanoma cell programmes were highlighted. Integration of mutational and transcriptomic data in CM characterisation could shed light on genes and pathways that support the maintenance of phenotypic states encrypted into heterogeneous primary tumours.
Genetics of Hepatocellular Carcinoma: From Tumor to Circulating DNA
Authors: Campani Claudia , Zucman-Rossi Jessica , Nault Jean-Charles
Published: January 2023

Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies and is one of the major causes of cancer-related death. Over the last 15 years, the molecular landscape of HCC has been deciphered, with the identification of the main driver genes of liver carcinogenesis that belong to six major biological pathways, such as telomere maintenance, Wnt/b-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase. The combination of genetic and transcriptomic data composed various HCC subclasses strongly related to risk factors, pathological features and prognosis. However, translation into clinical practice is not achieved, mainly because the most frequently mutated genes are undruggable. Moreover, the results derived from the analysis of a single tissue sample may not adequately catch the intra- and intertumor heterogeneity. The analysis of circulating tumor DNA (ctDNA) is broadly developed in other types of cancer for early diagnosis, prognosis and monitoring under systemic treatment in order to identify primary and secondary mechanisms of resistance. The aim of this review is to describe recent data about the HCC molecular landscape and to discuss how ctDNA could be used in the future for HCC detection and management.
Systematic Review of Nutrition Interventions to Improve Short Term Outcomes in Head and Neck Cancer Patients
Authors: Leis Claire , Arthur Anna E. , Chen Xin , Greene Michael W. , Frugé Andrew D.
Published: January 2023

Head and neck cancer (HNC) is associated with high rates of malnutrition. We conducted a systematic review and descriptive analysis to determine the effects of nutrition interventions on the nutrition status, quality of life (QOL), and treatment tolerance of HNC patients. PubMed, Web of Science, and Embase were searched to include all potentially relevant studies published between 2006–2022. Meta-analysis was not conducted due to heterogeneity of study designs and outcomes reported. Studies were categorized as nutrition interventions: (1) with oral nutrition supplements (ONS) and medical nutrition therapy (MNT) delivered by an RD; (2) with enteral nutrition (EN) support and MNT delivered by an RD; (3) with motivational interviewing and no ONS or EN; and (4) with ONS and no RD. Seven articles met inclusion criteria. Studies measured outcomes from immediately following treatment to 12 months post-treatment. Interventions resulted in benefits to lean mass/weight maintenance (three studies), QOL (two studies), nutrient intake adequacy (one study) and treatment tolerance (two studies). Nutrition counseling by a registered dietitian leads to improved nutrition status and QOL. Further research is needed to determine best practices related to timing of initiation, duration of nutrition intervention, as well as frequency of dietitian follow-up.
Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue
Authors: Beaulieu Marie-Eve , Martínez-Martín Sandra , Kaur Jastrinjan , Castillo Cano Virginia , Massó-Vallés Daniel , Foradada Felip Laia , López-Estévez Sergio , Serrano del Pozo Erika , Thabussot Hugo , Soucek Laura
Published: January 2023

MYC is an oncoprotein causally involved in the majority of human cancers and a most wanted target for cancer treatment. Omomyc is the best-characterized MYC dominant negative to date. In the last years, it has been developed into a therapeutic miniprotein for solid tumor treatment and recently reached clinical stage. However, since the in vivo stability of therapeutic proteins, especially within the tumor vicinity, can be affected by proteolytic degradation, the perception of Omomyc as a valid therapeutic agent has been often questioned. In this study, we used a mass spectrometry approach to evaluate the stability of Omomyc in tumor biopsies from murine xenografts following its intravenous administration. Our data strongly support that the integrity of the functional domains of Omomyc (DNA binding and dimerization region) remains preserved in the tumor tissue for at least 72 hours following administration and that the protein shows superior pharmacokinetics in the tumor compartment compared with blood serum.
Deep Learning with Transformer or Convolutional Neural Network in the Assessment of Tumor-Infiltrating Lymphocytes (TILs) in Breast Cancer Based on US Images: A Dual-Center Retrospective Study
Authors: Jia Yingying , Wu Ruichao , Lu Xiangyu , Duan Ying , Zhu Yangyang , Ma Yide , Nie Fang
Published: January 2023

This study aimed to explore the feasibility of using a deep-learning (DL) approach to predict TIL levels in breast cancer (BC) from ultrasound (US) images. A total of 494 breast cancer patients with pathologically confirmed invasive BC from two hospitals were retrospectively enrolled. Of these, 396 patients from hospital 1 were divided into the training cohort (n = 298) and internal validation (IV) cohort (n = 98). Patients from hospital 2 (n = 98) were in the external validation (EV) cohort. TIL levels were confirmed by pathological results. Five different DL models were trained for predicting TIL levels in BC using US images from the training cohort and validated on the IV and EV cohorts. The overall best-performing DL model, the attention-based DenseNet121, achieved an AUC of 0.873, an accuracy of 79.5%, a sensitivity of 90.7%, a specificity of 65.9%, and an F1 score of 0.830 in the EV cohort. In addition, the stratified analysis showed that the DL models had good discrimination performance of TIL levels in each of the molecular subgroups. The DL models based on US images of BC patients hold promise for non-invasively predicting TIL levels and helping with individualized treatment decision-making.
Tumour Cell Seeding to Lymph Nodes from In Situ Colorectal Cancer
Authors: Rodrigo-Calvo Maria Teresa , Saez de Gordoa Karmele , Lopez-Prades Sandra , Archilla Ivan , Diaz Alba , Berrios Mario , Camps Jordi , Musulen Eva , Cuatrecasas Miriam
Published: January 2023

Lymph node (LN) metastasis is an important prognostic factor in colorectal cancer (CRC). We aimed to demonstrate the presence of lymphatic vessels (LV) in the mucosa of in-situ (pTis) CRC, and of detectable tumour burden in regional LNs. This is an observational retrospective study of 39 surgically resected in situ CRCs. The number of LVs was evaluated in both pTis and normal mucosa using D2-40 immunostains. All LNs were assessed with both H&E and the One Step Nucleic Acid Amplification (OSNA) assay, and the results were correlated with clinicopathological features. D2-40 immunohistochemisty revealed LVs in the lamina propria of all pTis CRC (100%), being absent in normal mucosa. A median of 16 LNs were freshly dissected per patient, and all cases were pN0 with H&E. Molecular LN analysis with OSNA revealed the presence of low amounts of tumour burden in 11/39 (28%) cases (range 400 to 4270 CK19 mRNA copies/µL), which had no clinical consequences. This study demonstrates the presence of LVs in the lamina propria in 100% of pTis CRC, as well as the presence of low amounts of tumour burden in regional LNs, only detected by molecular methods. Given the prognostic value of LN tumour burden, its molecular quantification may help a patient’s clinical management.
A Series-Based Deep Learning Approach to Lung Nodule Image Classification
Authors: Balcı Mehmet Ali , Batrancea Larissa M. , Akgüller Ömer , Nichita Anca
Published: January 2023

Although many studies have shown that deep learning approaches yield better results than traditional methods based on manual features, CADs methods still have several limitations. These are due to the diversity in imaging modalities and clinical pathologies. This diversity creates difficulties because of variation and similarities between classes. In this context, the new approach from our study is a hybrid method that performs classifications using both medical image analysis and radial scanning series features. Hence, the areas of interest obtained from images are subjected to a radial scan, with their centers as poles, in order to obtain series. A U-shape convolutional neural network model is then used for the 4D data classification problem. We therefore present a novel approach to the classification of 4D data obtained from lung nodule images. With radial scanning, the eigenvalue of nodule images is captured, and a powerful classification is performed. According to our results, an accuracy of 92.84% was obtained and much more efficient classification scores resulted as compared to recent classifiers.
Effectiveness of Repeated Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma—Consideration of the Locations of Target Lesions
Authors: Yano Shigeki , Kimura Tomoki , Kawaoka Tomokazu , Kinami Takahiro , Yamasaki Shintaro , Johira Yusuke , Kosaka Masanari , Amioka Kei , Naruto Kensuke , Ando Yuwa , Yamaoka Kenji , Fujii Yasutoshi , Uchikawa Shinsuke , Fujino Hatsue , Ono Atsushi , Nakahara Takashi , Murakami Eisuke , Okamoto Wataru , Yamauchi Masami , Imamura Michio , Hirokawa Junichi , Nagata Yasushi , Aikata Hiroshi , Oka Shiro
Published: January 2023

The present study retrospectively evaluated the efficacy of stereotactic body radiation therapy (SBRT), including repeated SBRT, for hepatocellular carcinoma. Participants comprised 220 HCC patients treated with SBRT in Hiroshima University Hospital between December 2008 and December 2021. Median overall survival (OS) and disease-free survival were 52 months (range, 45–64 months) and 17 months (range, 14–23 months), respectively. The 5-year local tumor recurrence rate was 3.4% (95% confidence interval (CI), 1.3–6.9%). Fifty-three patients underwent repeated SBRT (twice, 53 cases; three times, 10 cases; four times, 4 cases; five times, 1 case). Median interval between first and second SBRT was 20 months. Median OS from first SBRT was 76 months (95% CI, 50–102 months). Among patients with repeated SBRT, only one case showed local recurrence after second SBRT. Albumin–bilirubin score increased significantly from 6 to 12 months after repeated SBRT, both in the same segment and in remote segments, but the increase was not significant in the same segment. Only one case of grade 3 bile duct stricture was observed in patients who were treated with repeated SBRT. In conclusion, repeated SBRT provides good local control and a low risk of side effects.
Blastoid B-Cell Neoplasms: Diagnostic Challenges and Solutions
Authors: Qiu Lianqun , Wang Sa A. , Tang Guilin , Wang Wei , Lin Pei , Xu Jie , Yin C. Cameron , Khanlari Mahsa , Medeiros L. Jeffrey , Li Shaoying
Published: January 2023

Blastoid B-cell neoplasms mainly include B-lymphoblastic leukemia/lymphoma (B-ALL), blastoid mantle cell lymphoma, and high-grade B-cell lymphoma with blastoid morphologic features (blastoid HGBL). Distinguishing blastoid HGBL from B-ALL can be challenging and we previously developed six-point flow cytometry-focused and three-point immunohistochemistry-focused scoring systems to aid in differential diagnosis. However, the six-point scoring system was derived from bone marrow cases and occasional cases may have a misleading score using either system. In this study, we assessed 121 cases of blastoid-HGBL (37 BM and 84 extramedullary) to validate the six-point scoring system in all tissue types and to further compare the two scoring systems. Compared with 47 B-ALL cases enriched for CD34-negative neoplasm, the 121 blastoid-HGBL cases showed distinctive pathologic features. The six-point scoring system showed a sensitivity of 100%. A comparison of the two scoring systems in blastoid HGBL (n = 64) and B-ALL (n = 37) showed a concordance score rate of 88%. Thirteen cases showed misleading scores, including five HGBL and eight B-ALL, and the diagnosis was further validated by gene transcriptome profiling. Twelve of thirteen cases had discordant scores between the two scoring systems. Simultaneous employment of both scoring systems improved the accuracy of classification of blastoid B-cell neoplasms to 99%. In conclusion, the previously defined six-point scoring system showed an excellent performance regardless of the tissue origin. Using both scoring systems together improves the accuracy of classification of blastoid B-cell neoplasms. Cases with discordant scores between the two scoring systems were extremely challenging neoplasms and classification required correlation with all available clinical and genetic features.
HO-1089 and HO-1197, Novel Herbal Formulas, Have Antitumor Effects via Suppression of PLK1 (Polo-like Kinase 1) Expression in Hepatocellular Carcinoma
Authors: Song Yeonhwa , Lee Su-Yeon , Kim Sanghwa , Choi Inhee , Kim Namjeong , Park Jongmin , Seo Haeng Ran
Published: January 2023

The treatment for hepatocellular carcinoma (HCC), a severe cancer with a very high mortality rate, begins with the surgical resection of the primary tumor. For metastasis or for tumors that cannot be resected, sorafenib, a multi-tyrosine protein kinase inhibitor, is usually the drug of choice. However, typically, neither resection nor sorafenib provides a cure. The drug discovery strategy for HCC therapy is shifting from monotherapies to combination regimens that combine an immuno-oncology agent with an angiogenesis inhibitor. Herbal formulas can be included in the combinations used for this personalized medicine approach. In this study, we evaluated the HCC anticancer efficacy of the new herbal formula, HO-1089. Treatment with HO-1089 inhibited HCC tumor growth by inducing DNA damage-mediated apoptosis and by arresting HCC cell replication during the G2/M phase. HO-1089 also attenuated the migratory capacity of HCC cells via the inhibition of the expression of EMT-related proteins. Biological pathways involved in metabolism and the mitotic cell cycle were suppressed in HO-1089-treated HCC cells. HO-1089 attenuated expression of the G2/M phase regulatory protein, PLK1 (polo-like kinase 1), in HCC cells. HCC xenograft mouse models revealed that the daily oral administration of HO-1089 retarded tumor growth without systemic toxicity in vivo. The use of HO-1197, a novel herbal formula derived from HO-1089, resulted in statistically significant improved anticancer efficacy relative to HO-1089 in HCC. These results suggest that HO-1089 is a safe and potent integrated natural medicine for HCC therapy.
Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials
Authors: Rahman Ruman , Janowski Miroslaw , Killick-Cole Clare L. , Singleton William G. B. , Campbell Emma , Walczak Piotr , Khatua Soumen , Faltings Lukas , Symons Marc , Schneider Julia R. , Kwan Kevin , Boockvar John A. , Gill Steven S. , Oliveira J. Miguel , Beccaria Kevin , Carpentier Alexandre , Canney Michael , Pearl Monica , Veal Gareth J. , Meijer Lisethe , Walker David A.
Published: January 2023

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30–40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood–brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored.
Circulating Tumor DNA Methylation Biomarkers for Characterization and Determination of the Cancer Origin in Malignant Liver Tumors
Authors: Draškovič Tina , Zidar Nina , Hauptman Nina
Published: January 2023

Malignant liver tumors include primary malignant liver tumors and liver metastases. They are among the most common malignancies worldwide. The disease has a poor prognosis and poor overall survival, especially with liver metastases. Therefore, early detection and differentiation between malignant liver tumors are critical for patient treatment selection. The detection of cancer and the prediction of its origin is possible with a DNA methylation profile of the tumor DNA compared to that of normal cells, which reflects tissue differentiation and malignant transformation. New technologies enable the characterization of the tumor methylome in circulating tumor DNA (ctDNA), providing a variety of new ctDNA methylation biomarkers, which can provide additional information to clinical decision-making. Our review of the literature provides insight into methylation changes in ctDNA from patients with common malignant liver tumors and can serve as a starting point for further research.
Investigation of Different Aqueous Electrolytes for Biomass-Derived Activated Carbon-Based Supercapacitors
Authors: Rajasekaran Sofia Jeniffer , Grace Andrews Nirmala , Jacob George , Alodhayb Abdullah , Pandiaraj Saravanan , Raghavan Vimala
Published: January 2023

The present work reports the synthesis of biomass derived activated carbon and its electrochemical behaviour in different electrolytes. Ricinus communis shell (RCS) was used as a raw material in this study for the synthesis of activated carbon (AC) following a high-temperature activation procedure using potassium hydroxide as the activating agent. The physical and structural characterization of the prepared Ricinus communis shell-derived activated carbon (RCS-AC) was carried by Brunauer-Emmett-Teller analysis, X-ray diffraction analysis, Fourier Transform Infrared Spectroscopy, Raman Spectroscopy and Scanning Electron Microscopy. The synthesized AC was electrochemically characterized using various techniques such as Cyclic voltammetry (CV), galvanostatic charge–discharge (GCD) tests, and Electrochemical impedance spectroscopy (EIS) measurements in different aqueous electrolytes (KOH, H2SO4, and Na2SO4). The results show that the double layer properties of the RCS-AC material in different electrolytes are distinct. In specific, the working electrode tested in 3 M KOH showed excellent electrochemical performance. It demonstrated a specific capacitance of 137 F g−1 (at 1 A g−1 in 3 M KOH) and exhibited high energy and power densities of 18.2 W hkg−1 and 663.4 W kg−1, respectively. The observed capacitance in 3 M KOH remains stable with 97.2% even after 5000 continuous charge and discharge cycles, indicating long-term stability. The study confirmed that the synthesized RCS-derived activated carbon (RCS-AC) exhibits good stability and physicochemical characteristics, making them commercially promising and appropriate for energy storage applications.
Recent Progress in the Mechanism and Engineering of α/β Hydrolases for Chiral Chemical Production
Authors: Qiu Mingzhe , Dong Sheng , Cui Qiu , Feng Yingang , Xuan Jinsong
Published: January 2023

Chiral compounds are valuable industrial products and intermediates, and the production of chemicals with high enantiopurity is one of the major objects in asymmetric catalysis. Compared with traditional chemical synthesis, enzymatic synthesis can produce chiral molecules under sustainable conditions which are much greener, more economical, and more environmentally friendly. The superfamily of α/β hydrolases includes a lot of diverse enzymes showing excellent chemo-, regio-, and enantio-selectivity in asymmetric synthesis and many of them are biocatalysts in industry. This review outlines the current knowledge of the structures and reaction mechanism of α/β hydrolases and summarizes the screening and protein engineering efforts to develop biocatalysts for chiral chemicals production in recent years. Other strategies such as whole-cell catalysis and protein immobilization to improve the performance of α/β hydrolases are also discussed. The progress in biocatalyst development based on α/β hydrolases will promote the biosynthesis of chiral compounds, thus contributing to the green and sustainable development of the chemical and pharmaceutical industry.
Catalytic Distillation of Atmospheric Residue of Petroleum over HY-MCM-41 Micro-Mesoporous Materials
Authors: Morais Camila G. D. P. , Silva Jilliano B. , Almeida Josue S. , Oliveira Rafaela R. , Araujo Marcio D. S. , Fernandes Glauber J. T. , Delgado Regina C. O. B. , Coriolano Ana C. F. , Fernandes Valter J. , Araujo Antonio S.
Published: January 2023

Catalytic distillation is a technology that combines a heterogeneous catalytic reaction and the separation of reactants and products via distillation in a single reactor/distillation system. This process combines catalysis, kinetics, and mass transfer to obtain more selective products. The heterogeneous catalyst provides the sites for catalytic reactions and the porous surface for liquid/vapor separation. The advantages of catalytic distillation are energy savings, low waste streams, catalyst longevity, higher conversion, and product selectivity; these properties are interesting for petrochemical and petroleum industries. For this study, 100 mL of atmospheric residue of petroleum (ATR) was distilled in the presence of 1.0 g of a micro/mesoporous catalyst composed of a HY-MCM-41, and the reactor used was an OptiDist automatic distillation device, operating according to ASTM D-86 methodology. The products were collected and analyzed by gas chromatography. The samples of ATR, HY/ATR, and HY-MCM-41/ATR were analyzed by thermogravimetry (TG) to determine the activation energies (Ea) relative to the thermal decomposition of the process, using the Ozawa–Flynn–Wall (OFW) kinetic model. The obtained results show a potential catalytic distillation system for use in the reaction of heavy petroleum fractions and product separation from the HY/MCM-41 micro/mesoporous catalyst. The TG data revealed two mass loss events for ATR in the ranges of 100–390 and 390–590 °C, corresponding to volatilization and thermal cracking, respectively. The Ea determined for the thermal degradation of the ATR without a catalyst was in the range of 83–194 kJ/mol, whereas in the presence of the HY-MCM-41 catalyst, it decreased to 61–105 kJ/mol, evidencing the catalytic effect of the micro-mesoporous material. The chromatography analysis allowed for the identification of gasoline and a major production of diesel and gasoil when the HY-MCM-41 mixture was used as the catalyst, evidencing the synergism of the combined effect of the acid sites, the crystalline phase, and the microporosity of the HY zeolite with the accessibility of the hexagonal mesoporous structure of the MCM-41 material.
Rapeseed Oil Transesterification Using 1-Butanol and Eggshell as a Catalyst
Authors: Gaide Ieva , Makareviciene Violeta , Sendzikiene Egle , Gumbytė Milda
Published: January 2023

Biodiesel can be produced both in homogeneous and heterogeneous ways. Heterogeneous synthesis allows to easily separate catalyst from esters. In this work, eggshells as a heterogeneous catalyst were used for triglyceride transesterification with 1-butanol. Response surface methodology was used for process optimization. It was obtained that eggshells are a suitable catalyst for transesterification processes. A longer process duration and higher catalyst amount have a high influence on ester yield. However, the amount of 1-butanol should not be maximized. Optimum transesterification reaction conditions were obtained when the process temperature was 110 °C, 1-butanol-to-oil molar ratio 11.3:1, eggshells amount 7.41 wt%, and process duration 11.81 h. Under these conditions, 98.78 wt% of ester yield was obtained.
Preformed Pd(II) Catalysts Based on Monoanionic [N,O] Ligands for Suzuki-Miyaura Cross-Coupling at Low Temperature
Authors: Andrews Matthew J. , Brunen Sebastian , McIntosh Ruaraidh D. , Mansell Stephen M.
Published: January 2023

This paper describes the synthesis and catalytic testing of a palladium complex with a 5-membered chelating [N,O] ligand, derived from the condensation of 2,6-diisopropylphenyl aniline and maple lactone. This catalyst was active towards the Suzuki-Miyaura cross-coupling reaction, and its activity was optimised through the selection of base, solvent, catalytic loading and temperature. The optimised conditions are mild, occurring at room temperature and over a short timescale (1 h) using solvents considered to be ‘green’. A substrate scope was then carried out in which the catalyst showed good activity towards aryl bromides with electron-withdrawing groups. The catalyst was active across a broad scope of electron-donating and high-withdrawing aryl bromides with the highest activity shown for weak electron-withdrawing groups. The catalyst also showed good activity across a range of boronic acids and pinacol esters with even boronic acids featuring strong electron-withdrawing groups showing some activity. The catalyst was also a capable catalyst for the cross-coupling of aryl chlorides and phenylboronic acid. This more challenging reaction requires slightly elevated temperatures over a longer timescale but is still considered mild compared to similar examples in the literature.
Carbon Dioxide Conversion on Supported Metal Nanoparticles: A Brief Review
Authors: Posada-Pérez Sergio , Solà Miquel , Poater Albert
Published: January 2023

The increasing concentration of anthropogenic CO2 in the air is one of the main causes of global warming. The Paris Agreement at COP 21 aims to reach the global peak of greenhouse gas emissions in the second half of this century, with CO2 conversion towards valuable added compounds being one of the main strategies, especially in the field of heterogeneous catalysis. In the current search for new catalysts, the deposition of metallic nanoparticles (NPs) supported on metal oxides and metal carbide surfaces paves the way to new catalytic solutions. This review provides a comprehensive description and analysis of the relevant literature on the utilization of metal-supported NPs as catalysts for CO2 conversion to useful chemicals and propose that the next catalysts generation can be led by single-metal-atom deposition, since in general, small metal particles enhance the catalytic activity. Among the range of potential indicators of catalytic activity and selectivity, the relevance of NPs’ size, the strong metal–support interactions, and the formation of vacancies on the support are exhaustively discussed from experimental and computational perspective.
UPF1—From mRNA Degradation to Human Disorders
Authors: Staszewski Jacek , Lazarewicz Natalia , Konczak Julia , Migdal Iwona , Maciaszczyk-Dziubinska Ewa
Published: January 2023

Up-frameshift protein 1 (UPF1) plays the role of a vital controller for transcripts, ready to react in the event of an incorrect translation mechanism. It is well known as one of the key elements involved in mRNA decay pathways and participates in transcript and protein quality control in several different aspects. Firstly, UPF1 specifically degrades premature termination codon (PTC)-containing products in a nonsense-mediated mRNA decay (NMD)-coupled manner. Additionally, UPF1 can potentially act as an E3 ligase and degrade target proteins independently from mRNA decay pathways. Thus, UPF1 protects cells against the accumulation of misfolded polypeptides. However, this multitasking protein may still hide many of its functions and abilities. In this article, we summarize important discoveries in the context of UPF1, its involvement in various cellular pathways, as well as its structural importance and mutational changes related to the emergence of various pathologies and disease states. Even though the state of knowledge about this protein has significantly increased over the years, there are still many intriguing aspects that remain unresolved.
Association of Autofluorescent Advanced Glycation End Products (AGEs) with Frailty Components in Chronic Kidney Disease (CKD): Data from a Single-Center Cohort Study
Authors: Molinari Paolo , Caldiroli Lara , Dozio Elena , Rigolini Roberta , Giubbilini Paola , Carminati Francesca Maria Ida , Castellano Giuseppe , Corsi Romanelli Massimiliano M. , Vettoretti Simone
Published: January 2023

Background: Chronic kidney disease (CKD) is characterized by an overproduction and accumulation of advanced glycation end products (AGEs). Because AGEs may play a role in the development of malnutrition and sarcopenia, two essential components of frailty, we evaluated whether they may also contribute to the onset of frailty in CKD patients. Methods: We performed a cross-sectional analysis of 117 patients. AGEs were quantified using a fluorescence spectrophotometer and soluble receptor for AGE (sRAGE) isoforms by ELISA. We defined frailty according to the frailty phenotype (FP) proposed by Fried. Results: The average age of patients was 80 ± 11 years, 70% were male, and the mean eGFR was 25 + 11 mL/min/1.73m2. Frailty was diagnosed in 51 patients, and 40 patients were classified as pre-frail. AGEs and RAGE isoforms seem not to correlate with overall frailty. Instead, AGEs were associated with specific frailty domains, inversely associated with BMI (R = −0.22, p = 0.016) and directly associated with gait test time (R = 0.17, p = 0.049). AGEs were also associated with involuntary weight loss (OR 1.84 p = 0.027), independent of age and sex. Conclusions: AGEs are associated with some pivotal components of the frailty phenotype, although they are not associated with frailty overall.
Future Perspectives of Prime Editing for the Treatment of Inherited Retinal Diseases
Authors: Hansen Silja , McClements Michelle E. , Corydon Thomas J. , MacLaren Robert E.
Published: January 2023

Inherited retinal diseases (IRD) are a clinically and genetically heterogenous group of diseases and a leading cause of blindness in the working-age population. Even though gene augmentation therapies have shown promising results, they are only feasible to treat a small number of autosomal recessive IRDs, because the size of the gene is limited by the vector used. DNA editing however could potentially correct errors regardless of the overall size of the gene and might also be used to correct dominant mutations. Prime editing is a novel CRISPR/Cas9 based gene editing tool that enables precise correction of point mutations, insertions, and deletions without causing double strand DNA breaks. Due to its versatility and precision this technology may be a potential treatment option for virtually all genetic causes of IRD. Since its initial description, the prime editing technology has been further improved, resulting in higher efficacy and a larger target scope. Additionally, progress has been achieved concerning the size-related delivery issue of the prime editor components. This review aims to give an overview of these recent advancements and discusses prime editing as a potential treatment for IRDs.
Molecular Structure Underlying the Allosteric Mechanism of Caffeine Detection in Taste Sensor
Authors: Xu Hengwei , Zhao Zeyu , Kimura Shunsuke , Onodera Takeshi , Toko Kiyoshi
Published: January 2023

The use of taste sensors with lipid/polymer membranes is one of the methods to evaluate taste. As previously reported, taste sensors can detect non-charged substances such as caffeine by modifying the lipid/polymer membranes with hydroxybenzoic acids (HBAs). The mechanism of caffeine detection by taste sensors was identified to be an allosteric one. Generally, the allosteric mechanism, defined as “regulation at distant sites”, is used to describe the regulation process for proteins. In this study, to improve the sensitivity of taste sensors to caffeine and its analogs using the allosteric mechanism, we used various modifiers of lipid/polymer membranes, and we detected caffeine using taste sensors with the modified membranes. The detection of the caffeine analogs theophylline and theobromine was also analyzed. The results of caffeine detection clarified that the molecular structure underlying the allosteric mechanism capable of effective caffeine detection involves both the carboxyl and hydroxyl groups, where the hydroxyl group can form intermolecular H bonds with caffeine. Furthermore, the taste sensors with a modifier, which has the molecular structure underlying the allosteric mechanism, showed high sensitivity to caffeine and caffeine analogs. The use of an allosteric mechanism may help improve the sensitivity of taste sensors to other non-charged pharmaceutical substances, such as dexamethasone and prednisolone, in the future.
Assessing Effectiveness of Shape Memory Alloys on the Response of Bolted T-Stub Connections Subjected to Cyclic Loading
Authors: Torabipour Ahmadreza , Asghari Nima , Haghighi Homa , Yaghoubi Shaghayegh , Urgessa Girum
Published: January 2023

This study presents finite element analysis of double split tee (DST) connections with high-strength steel bolts and coupled split tee sections, to evaluate various cyclic response parameters and elements. The investigation included quantifying connection behavior and hysteretic response, damage indexes, and failure modes. Over 40 specimens were simulated in ABAQUS under cyclic loading, including shape memory alloy (SMA)-built specimens. In the post-analysis phase, the T-stub thickness, the T-stub yield strength, the bolt preload and bolt number, and the stiffener type and stiffener material for the most significant parts of the DST connection were calculated. Simulation results showed that a lower ultimate moment yielded fewer needed stem bolts. The energy dissipation (ED) capacity increased as the horizontal distance between the stem bolts decreased. Additionally, increasing the strength of the bolt and T-stub by 15% resulted in a 3.86% increase in residual displacement (RD) for the bolt and a 1.73% decrease in residual displacement for the T-stub. T-stub stiffeners enhanced ED capacity by 31.7%. SMA materials were vulnerable to mode 1 failure when used in T-stubs, bolts, or stiffeners. However, the use of SMA increased the rate of energy dissipation. Adding stiffeners to the T-stubs altered the failure indexes and improved the pattern of failure modes. In addition, stiffeners decreased the rupture and pressure indexes. As a result, the failure index of a T-stub shifted from brittle failure to ductile failure.