bluuebunny/crossref_metadata_2025 huggingface dataset:
Inverse Analysis of Strata in Seepage Field Based on Regularization Method and Geostatistics Theory
Authors: Zhang Fansheng , Dong Lianglin , Wang Hongbo , Zhong Ke , Zhang Peiyuan , Jiang Jinyan
Published: March 2024

During the construction of underground engineering, the prediction of groundwater distribution and rock body permeability is essential for evaluating the safety of the project and guiding subsequent design and construction. This article proposes an objective function that solves an underdetermined inverse analysis problem based on the least-squares theory and regularization method and uses geostatistics theory and the variogram function to describe the spatial characteristics of the actual engineering system. It also establishes an optimization model of the analysis stratum seepage field and puts forward the method of using on-site test observation data to solve the stratum penetration coefficient. Relying on the foundation pit project of the Lingshanwei Station of Qingdao Metro, the on-site pumping and packer permeability test was conducted for different strata venues in the foundation pit, and the on-site water-head observation value was obtained. Physical detection of the influence area of foundation pit excavation confirms the correctness of the model from the region and verifies the accuracy of the model on the value through the on-site pumping test. Results show that the accuracy of the use of this objective function to solve the underdetermined inverse problem is above 85%, which proves the effectiveness of the method. The stratigraphic geological information obtained by the inverse analysis model provides an important basis for engineering design and security construction.
Experimental Study on Grout–Soil Interaction Effects in Sandy Soil under Different Water-to-Cement Ratios
Authors: Hu Huanxiao , Lu Yufan , Deng Chao , Gan Benqing , Xie Zhongliang , Cai Yuehui , Chu Aikun
Published: March 2024

Due to the unique characteristics of sandy soil layers, there is often a coupling effect of multiple grout diffusion patterns in the grouting process, and different slurry diffusion modes may lead to different responses of soil structures. In this study, laboratory grouting model tests were conducted with homogeneous sand under different water-to-cement (w/c) ratios to reveal the temporal variations in grouting pressure, soil stress fields, and displacement fields during the grout diffusion process. The results show that, during the grouting process in the fine sand layer, the grout mainly exhibited a compaction–splitting diffusion mode. The farther away from the grouting center, the more pronounced the hysteresis effect of soil pressure caused by grout diffusion. Meanwhile, as the w/c ratio increased, the diffusion mode between the slurry and the soil was in a transitional state. At w/c > 1.2, the primary pattern changed from the fracture–compaction pattern to the permeation–fracture–compaction pattern and fracture–permeation pattern. And the overall trend of the grouting pressure curve was similar under all of the w/c ratio conditions, showing a trend of increasing to the maximum value of the pressure first and then decreasing. With the increase in the water–cement ratio, the overall value of the grouting pressure curve showed a decreasing trend, the pressure value increased more slowly with time before reaching the maximum value, and the more obvious the influence of water–cement ratio was when w/c > 1.2. Additionally, the surface displacement also exhibited an overall decreasing trend, and it had no obvious lifting value under the condition of w/c = 1.6.
Supercapacitor Performance of MXene-Coated Carbon Nanofiber Electrodes
Authors: Kim Seon Kyung , Kim Seung Ah , Han Yoon Soo , Jung Kyung-Hye
Published: March 2024

MXenes consisting of thin layers of transition metal carbides or nitrides are good candidates for electrode materials due to their excellent electrical conductivity and fast ion transfer. Electrospun carbon nanofibers are highly porous and electrically conductive, making them attractive for electrode materials. In this study, free-standing electrodes were prepared by the dip-coating of carbon nanofibers (CNFs) in the MXene (Ti3C2) colloidal solution, which was synthesized via the wet-etching of MAX (Ti3AlC2) phase, and their chemical structures were investigated by X-ray diffraction and Fourier transform infrared spectroscopy. In addition, scanning and transmission electron microscopy were used to investigate the morphological and crystallographic features of MXene-coated CNFs. Surface area and pore volumes were investigated by nitrogen adsorption/desorption measurements. Supercapacitor performance was studied by assembling a 3-electrode system with 1M aqueous sodium sulfate solution as an electrolyte. MXene-coated CNFs exhibited a maximum specific capacitance of 514 F/g at 0.5 A/g, with energy and power densities of 71.4 Wh/kg at 0.5 A/g and 2.3 kW/kg at 5 A/g, respectively, which are relevantly higher compared to the pristine CNFs due to the pseudocapacitive behavior of MXenes. They also showed comparable cyclic stability during 5000 cycles with the CNFs. This result indicates that MXene-coated carbon nanofibers can be effective electrode materials for electrochemical energy storage.
Evaluating the Cytotoxicity of Functionalized MWCNT and Microbial Biofilm Formation on PHBV Composites
Authors: Montanheiro Thaís Larissa do Amaral , Schatkoski Vanessa Modelski , Camarena Denisse Esther Mallaupoma , de Oliveira Thais Cardoso , da Silva Diego Morais , Vegian Mariana Raquel da Cruz , Catalani Luiz Henrique , Koga-Ito Cristiane Yumi , Thim Gilmar Patrocínio
Published: March 2024

This study focuses on the cytotoxic evaluation of functionalized multi-walled carbon nanotubes (MWCNT) and microbial biofilm formation on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanocomposites incorporating MWCNTs functionalized with gamma-aminobutyric acid (GABA) and carboxyl groups. The materials were characterized for cytotoxicity to fibroblasts and antimicrobial effects against Escherichia coli, Staphylococcus aureus and Candida albicans. The functionalization of MWCNTs was performed through oxidation (CNT-Ox) and GABA attachment (CNT-GB). The PHBV/CNT nanocomposites were produced via melt mixing. All MWCNT suspensions showed non-toxic behaviors after 24 h of incubation (viability higher than 70%); however, prolonged incubation and higher concentrations led to increased cytotoxicity. The antibacterial potential of PHBV/CNT nanocomposites against S. aureus showed a reduction in biofilm formation of 64% for PHBV/CNT-GB and 20% for PHBV/CNT-Ox, compared to neat PHBV. Against C. albicans, no reduction was observed. The results indicate promising applications for PHBV/CNT nanocomposites in managing bacterial infections, with GABA-functionalized CNTs showing enhanced performance.
Editorial for C—Journal of Carbon Research in 2023
Authors: Banks Craig E.
Published: April 2024

Our journal, C—Journal of Carbon Research (https://www.mdpi.com/journal/carbon), is an international, scientific, peer-reviewed, open access journal on carbon research, published quarterly online by MDPI [...]
Sunglasses for Sunlight: Considerations on New Treatment Opportunities for Refractory Colorectal Cancer
Authors: Zaniboni Alberto
Published: March 2024

In 2023, two seminal studies were disseminated that significantly augmented the pharmacological armamentarium for the treatment of refractory metastatic colorectal carcinoma (MCRC) [...]
Identification of Interpretable Clusters and Associated Signatures in Breast Cancer Single-Cell Data: A Topic Modeling Approach
Authors: Malagoli Gabriele , Valle Filippo , Barillot Emmanuel , Caselle Michele , Martignetti Loredana
Published: March 2024

Topic modeling is a popular technique in machine learning and natural language processing, where a corpus of text documents is classified into themes or topics using word frequency analysis. This approach has proven successful in various biological data analysis applications, such as predicting cancer subtypes with high accuracy and identifying genes, enhancers, and stable cell types simultaneously from sparse single-cell epigenomics data. The advantage of using a topic model is that it not only serves as a clustering algorithm, but it can also explain clustering results by providing word probability distributions over topics. Our study proposes a novel topic modeling approach for clustering single cells and detecting topics (gene signatures) in single-cell datasets that measure multiple omics simultaneously. We applied this approach to examine the transcriptional heterogeneity of luminal and triple-negative breast cancer cells using patient-derived xenograft models with acquired resistance to chemotherapy and targeted therapy. Through this approach, we identified protein-coding genes and long non-coding RNAs (lncRNAs) that group thousands of cells into biologically similar clusters, accurately distinguishing drug-sensitive and -resistant breast cancer types. In comparison to standard state-of-the-art clustering analyses, our approach offers an optimal partitioning of genes into topics and cells into clusters simultaneously, producing easily interpretable clustering outcomes. Additionally, we demonstrate that an integrative clustering approach, which combines the information from mRNAs and lncRNAs treated as disjoint omics layers, enhances the accuracy of cell classification.
Association between Head and Neck Cancer and Increased Risk of Ischemic Heart Disease: A Retrospective Cohort Study Using National Population Data
Authors: Kim Chulho , Yu Hyunjae , Kim Dong-Kyu
Published: March 2024

Although cancer and ischemic heart disease (IHD) frequently manifest in the same individual, the risk of IHD events in cancer, especially head and neck cancer (HNC), remains unclear. We aimed to examine the incidence and risk of IHD events in patients with HNC using a population-based cohort dataset in South Korea (2002–2013). Through rigorous propensity score matching, we compared data from 2816 individuals without HNC and 704 individuals with HNC. Key independent variables were matched between groups, and the Charlson Comorbidity Index was used to match comorbidities. The Kaplan–Meier method depicted the cumulative probability of IHD throughout the follow-up period for both the study and control groups. The overall IHD incidence was significantly higher (19.93) in patients with HNC than in those without HNC (14.81), signifying an augmented IHD risk in the HNC cohort. Subsequent temporal analysis revealed a significant surge in IHD risk commencing 4 years after HNC diagnosis and persisting throughout the follow-up period. Subgroup analysis revealed an increased IHD risk in men with HNC and patients with cancers affecting the oral and sinonasal regions. This retrospective cohort study provides valuable scientific insights into the nuanced relationship between HNC and IHD, underscoring the need for tailored monitoring protocols and specialized care for susceptible individuals.
PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy
Authors: Maas Moritz , Hilsendecker Andreas , Pertoll Alexandra , Stühler Viktoria , Walz Simon , Rausch Steffen , Stenzl Arnulf , Tsaur Igor , Hennenlotter Jörg , Aufderklamm Stefan
Published: March 2024

In the expanding landscape of immune checkpoint inhibitors (CPI) in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC), the role of programmed death ligand 1 (PD-L1) as prognostic and predictive is increasingly significant. However, data evaluating its variability and susceptibility to Bacillus Calmette–Guérin (BCG) therapy in HR NMIBC patients is scarce. This retrospective study analyzed 126 HR NMIBC tissue samples from 63 patients (38× BCG-treated, 25× BCG-naïve) at two time points to assess PD-L1 expression using the ‘combined positivity score’ (CPS) with the 22C3 DAKO antibody method and correlated it with clinicopathological parameters. A CPS > 10 defined PD-L1 positivity. The impact of initial PD-L1 status and its change over time on time-to-recurrence, progression-free survival, and overall survival (TTR, PFS, OS) was analyzed using Kaplan–Meier and Cox proportional hazard models. BCG treatment significantly increased PD-L1 expression (5.31 vs. 0.22, p = 0.0423), with PD-L1 positive cases rising post-treatment in the BCG group and remaining unchanged in BCG-naïve patients. Multivariate analysis including T-stage, CIS, grading, tumor size, multifocality, age, and sex revealed a significant correlation between PD-L1 status change to positivity and improved TTR (p = 0.03). Our findings demonstrate a potential modulation of the PD-L1 status by an intravesical BCG therapy. However, its prognostic value appears limited.
Using Targeted Transcriptome and Machine Learning of Pre- and Post-Transplant Bone Marrow Samples to Predict Acute Graft-versus-Host Disease and Overall Survival after Allogeneic Stem Cell Transplantation
Authors: Rowley Scott D. , Gunning Thomas S. , Pelliccia Michael , Della Pia Alexandra , Lee Albert , Behrmann James , Bangolo Ayrton , Jandir Parul , Zhang Hong , Kaur Sukhdeep , Suh Hyung C. , Donato Michele , Albitar Maher , Ip Andrew
Published: March 2024

Acute graft-versus-host disease (aGvHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We performed RNA analysis of 1408 candidate genes in bone marrow samples obtained from 167 patients undergoing HSCT. RNA expression data were used in a machine learning algorithm to predict the presence or absence of aGvHD using either random forest or extreme gradient boosting algorithms. Patients were randomly divided into training (2/3 of patients) and validation (1/3 of patients) sets. Using post-HSCT RNA data, the machine learning algorithm selected 92 genes for predicting aGvHD that appear to play a role in PI3/AKT, MAPK, and FOXO signaling, as well as microRNA. The algorithm selected 20 genes for predicting survival included genes involved in MAPK and chemokine signaling. Using pre-HSCT RNA data, the machine learning algorithm selected 400 genes and 700 genes predicting aGvHD and overall survival, but candidate signaling pathways could not be specified in this analysis. These data show that NGS analyses of RNA expression using machine learning algorithms may be useful biomarkers of aGvHD and overall survival for patients undergoing HSCT, allowing for the identification of major signaling pathways associated with HSCT outcomes and helping to dissect the complex steps involved in the development of aGvHD. The analysis of pre-HSCT bone marrow samples may lead to pre-HSCT interventions including choice of remission induction regimens and modifications in patient health before HSCT.
Enhanced Therapeutic Efficacy of the Nanoscale Fluoropyrimidine Polymer CF10 in a Rat Colorectal Cancer Liver Metastasis Model
Authors: Okechukwu Charles Chidi , Ma Xue , Sah Naresh , Mani Chinnadurai , Palle Komaraiah , Gmeiner William H.
Published: March 2024

Combination chemotherapy regimens that include fluoropyrimidine (FP) drugs, e.g., 5-fluorouracil (5-FU), are central to the treatment of colorectal cancer liver metastases (CRLMs), a major cause of cancer mortality. We tested a second-generation FP polymer, CF10, in a CC531/WAGRij syngeneic orthotopic rat model of liver metastasis to determine if CF10 improved response relative to 5-FU. CF10 displayed increased potency relative to 5-FU in CC531 rat colorectal cancer cells based on clonogenic assay results and caused increased apoptosis, as shown using a live/dead assay. The increased potency of CF10 to CC531 cells was associated with increased replication stress, as assessed by Western blot for biomarkers of ATR/Chk1 and ATM/Chk2 pathway activation. CF10 dosed to deliver equivalent FP content as an established dose of 5-FU in rats (50 mg/kg) did not cause weight loss in WAGRij rats even when combined with ethynyl uracil (EU), an inhibitor of dihydropyrimidine dehydrogenase, the enzyme primarily responsible for 5-FU degradation in the liver. In contrast, 5-FU caused significant weight loss that was exacerbated in combination with EU. Importantly, CF10 was significantly more effective than 5-FU at inhibiting tumor progression (~90% reduction) in the CC531/WAG/Rij CRLM model. Our results reveal strong potential for CF10 to be used for CRLM treatment.
Zebrafish—A Suitable Model for Rapid Translation of Effective Therapies for Pediatric Cancers
Authors: Roy Debasish , Subramaniam Bavani , Chong Wai Chin , Bornhorst Miriam , Packer Roger J. , Nazarian Javad
Published: March 2024

Pediatric cancers are the leading cause of disease-related deaths in children and adolescents. Most of these tumors are difficult to treat and have poor overall survival. Concerns have also been raised about drug toxicity and long-term detrimental side effects of therapies. In this review, we discuss the advantages and unique attributes of zebrafish as pediatric cancer models and their importance in targeted drug discovery and toxicity assays. We have also placed a special focus on zebrafish models of pediatric brain cancers—the most common and difficult solid tumor to treat.
The Effect of Exercise on Reducing Lymphedema Severity in Breast Cancer Survivors
Authors: Lian Yanxue , Sandhu Simran , Asefa Yamikani , Gupta Ananya
Published: March 2024

Exercise has been repeatedly shown to be safe and beneficial for cancer survivors. However, there is no normative guideline for exercise prescription, and it is still under exploration. Therefore, this literature review aims to provide some advice for the formulation of exercise prescriptions for patients with breast cancer-related lymphedema (BCRL) from the perspective of reducing lymphedema severity. A review of relevant studies published before November 2023 was conducted using three scientific databases: PubMed, Embase, and Scopus. A total of 2696 articles were found. Eventually, 13 studies fulfilled the inclusion criteria and were included in this literature review. We concluded that daily, or nearly daily, exercise at home can be recommended. Moreover, reduced lymphedema severity may not be maintained after ceasing the exercise program, so exercise should be a lifelong practice.
Occurrence and Management of Immunotherapy-Associated Adverse Events in Patients with Gynecological Cancers
Authors: Shehaj Ina , Schröder Maria , Linz Valerie Catherine , Krajnak Slavomir , Almstedt Katrin , Stewen Kathrin , Schwab Roxana , Hasenburg Annette , Schmidt Marcus , Heimes Anne-Sophie
Published: March 2024

Background: Immune checkpoint inhibitors (ICIs) have emerged as an essential therapeutic approach in treating many solid tumors. ICIs enhance the body’s anti-tumor T-cell activity, resulting in a novel spectrum of immunotherapy-related side effects. This novel spectrum of adverse events differs significantly from the side effects of conventional chemotherapy. It, therefore, requires special attention in the diagnosis and management of immunotherapy-related adverse events (irAEs). The present study aimed to retrospectively analyze the incidence, diagnosis, and management of irAEs in patients with gynecologic malignancies who received ICIs and to discuss these findings in the context of the recent literature. Methods: In the present retrospective overview, we evaluated patients with gynecologic malignancies (breast, endometrial, cervical, ovarian) who received ICIs with regard to the incidence, type, and time to onset of irAEs. A total of 61 patients treated at the Department of Gynecology and Obstetrics, University Medical Center Mainz, Germany, between 2018 and 2023 were included in the analysis. Results: A total of 32.8% of patients developed an irAE of any grade or type. The median time to irAE was 24 weeks. The most frequently observed irAEs were grade 1 (20%) or 2 (35%). Immunotherapy-related grade 3 or 4 adverse events occurred in 45% of patients (40% grade 3, 5% grade 4). The most common type of irAE in our cohort was hypothyroidism, followed by hepatitis and colitis. Cox regression analysis identified the duration of ICI therapy as the only significant factor influencing the incidence of irAEs (p = 0.004). Conclusion: The broad spectrum of irAEs and the onset time of irAEs are important challenges of therapy with ICIs, requiring proactive monitoring and tailored management strategies to optimize the safety and efficacy of immunotherapy.
The Impact of Radiofrequency Ablation on Survival Outcomes and Stent Patency in Patients with Unresectable Cholangiocarcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Balducci Daniele , Montori Michele , Martini Francesco , Valvano Marco , De Blasio Federico , Argenziano Maria Eva , Tarantino Giuseppe , Benedetti Antonio , Bendia Emanuele , Marzioni Marco , Maroni Luca
Published: March 2024

Endoluminal biliary radiofrequency ablation (RFA) has been proposed as a palliative treatment for patients with malignant biliary obstruction (MBO) in order to improve stent patency and survival. However, the existing data on patients with inoperable extrahepatic cholangiocarcinoma (eCCA) are conflicting. We performed a meta-analysis of randomized trials comparing RFA plus stenting versus stenting alone in patients with inoperable eCCA. We searched for trials published in the PubMed/MEDLINE, Scopus, and Cochrane databases up to November 2023. Data extraction was conducted from published studies, and a quality assessment was carried out in accordance with the guidelines recommended by the Cochrane Collaboration. Hazard ratios (HRs) with 95% CI were estimated from the trials. The primary endpoints of interest were overall survival and stent patency. Out of 275 results, 5 randomized trials and 370 patients were included. While overall survival was not different between the groups (HR 0.62; 95% CI 0.36–1.07; p = 0.09; I2 = 80%;), the subgroup analysis of studies employing plastic stents showed a trend toward better survival in the RFA-treated group (HR 0.42; 95% CI 0.22–0.80; p = 0.009; I2 = 72%). Stent patency was improved in patients receiving RFA (HR 0.64; 95% CI 0.45–0.90; p = 0.01; I2 = 23%). Adverse events were not different between the groups (OR 1.21; 95% CI 0.69–2.12; p = 0.50; I2 = 0%). Despite the promising results, high heterogeneity and potential biases in the included studies suggest the need for further high-quality randomized trials to explore the potential cumulative effects of RFA on CCA treatment outcomes.
Long-Term Oral Tamoxifen Administration Decreases Brain-Derived Neurotrophic Factor in the Hippocampus of Female Long-Evans Rats
Authors: Been Laura E. , Halliday Amanda R. , Blossom Sarah M. , Bien Elena M. , Bernhard Anya G. , Roth Grayson E. , Domenech Rosario Karina I. , Pollock Karlie B. , Abramenko Petra E. , Behbehani Leily M. , Pascal Gabriel J. , Kelly Mary Ellen
Published: March 2024

Tamoxifen, a selective estrogen receptor modulator (SERM), is commonly used as an adjuvant drug therapy for estrogen-receptor-positive breast cancers. Though effective at reducing the rate of cancer recurrence, patients often report unwanted cognitive and affective side effects. Despite this, the impacts of chronic tamoxifen exposure on the brain are poorly understood, and rodent models of tamoxifen exposure do not replicate the chronic oral administration seen in patients. We, therefore, used long-term ad lib consumption of medicated food pellets to model chronic tamoxifen exposure in a clinically relevant way. Adult female Long-Evans Hooded rats consumed tamoxifen-medicated food pellets for approximately 12 weeks, while control animals received standard chow. At the conclusion of the experiment, blood and brain samples were collected for analyses. Blood tamoxifen levels were measured using a novel ultra-performance liquid chromatography–tandem mass spectrometry assay, which found that this administration paradigm produced serum levels of tamoxifen similar to those in human patients. In the brain, brain-derived neurotrophic factor (BDNF) was visualized in the hippocampus using immunohistochemistry. Chronic oral tamoxifen treatment resulted in a decrease in BDNF expression across several regions of the hippocampus. These findings provide a novel method of modeling and measuring chronic oral tamoxifen exposure and suggest a putative mechanism by which tamoxifen may cause cognitive and behavioral changes reported by patients.
Posterior and Para-Aortic (D2plus) Lymphadenectomy after Neoadjuvant/Conversion Therapy for Locally Advanced/Oligometastatic Gastric Cancer
Authors: Marrelli Daniele , Piccioni Stefania Angela , Carbone Ludovico , Petrioli Roberto , Costantini Maurizio , Malagnino Valeria , Bagnacci Giulio , Rizzoli Gabriele , Calomino Natale , Piagnerelli Riccardo , Mazzei Maria Antonietta , Roviello Franco
Published: March 2024

Super-extended (D2plus) lymphadenectomy after chemotherapy has been reported in only a few studies. This retrospective study evaluates survival outcomes in a Western cohort of locally advanced or oligometastatic gastric cancer patients who underwent D2plus lymphadenectomy after neoadjuvant chemotherapy. A total of 97 patients treated between 2010 and 2022 were included. Of these, 62 had clinical stage II/III disease, and 35 had stage IV disease. Most patients (65%) received preoperative DOC/FLOT chemotherapy. The mean number of lymph nodes harvested was 39. Pathological positive nodes in the posterior/para-aortic stations occurred in 17 (17.5%) patients. Lymphovascular invasion, ypN stage, clinical stage, and perineural invasion were predictive factors for positive posterior/para-aortic nodes. Postoperative complications occurred in 21 patients, whereas severe complications (grade III or more) occurred in 9 cases (9.3%). Mortality rate was 1%. Median overall survival (OS) was 59 months (95% CI: 13–106), with a five-year survival rate of 49 ± 6%; the five-year OS after R0 surgery was 60 ± 7%. In patients with positive posterior/para-aortic nodes, the median OS was 15 months (95% CI: 13–18). D2plus lymphadenectomy after chemotherapy for locally advanced or oligometastatic gastric cancer is feasible and associated with low morbidity/mortality rates. The incidence of pathological metastases in posterior/para-aortic nodes is not negligible even after systemic chemotherapy, with poor long-term survival.
Outpatient Palliative Care Program: Impact on Home Death Rate in Brazil
Authors: Gomes Sarah Ananda , Silva Danielle Nunes Moura , Sorice Flavia , Arantes Alexandra , Peixoto Rafaela , Ferrari Renata , Martins Matheus , Jácome Alexandre , Bergerot Cristiane , de Melo Andreia Cristina , Ferrari Bruno
Published: March 2024

While the positive impact of early palliative care on the quality of life of cancer patients is well established, there is a noticeable research gap in developing countries. This study sought to determine the impact of an outpatient palliative care (OPC) program on the location of death among patients in Brazil. This was a retrospective study including patients with cancer who died between January 2022 and December 2022 in 32 private cancer centers in Brazil. Data were collected from medical records, encompassing demographics, cancer characteristics, and participation in the OPC program. The study involved 1980 patients, of which 32.3% were in the OPC program. OPC patients were predominantly younger (average age at death of 66.8 vs. 68.0 years old, p = 0.039) and composed of women (59.4% vs. 51.3%, p = 0.019) compared to the no-OPC patients. OPC patients had more home/hospice deaths (19.6% vs. 10.4%, p < 0.001), and participation in the outpatient palliative care program strongly predicted home death (OR: 2.02, 95% CI: 1.54–2.64). Our findings suggest a significant impact of the OPC program on increasing home and hospice deaths among patients with cancer in our sample. These findings emphasize the potential of specialized OPC programs to enhance end-of-life care, particularly in low-resource countries facing challenges related to social and cultural dimensions of care and healthcare access.
A Comprehensive Overview of Intraoperative Complications during Retzius-Sparing Robot-Assisted Radical Prostatectomy: Single Series from High-Volume Center
Authors: Olivero Alberto , Tappero Stefano , Chierigo Francesco , Maltzman Ofir , Secco Silvia , Palagonia Erika , Piccione Antonio , Bocciardi Aldo Massimo , Galfano Antonio , Dell’Oglio Paolo
Published: March 2024

Background: Intraoperative complications (ICs) are invariably underreported in urological surgery despite the recent endorsement of new classification systems. We aimed to provide a detailed overview of ICs during Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). Methods: We prospectively collected data from 1891 patients who underwent RS-RARP at a single high-volume European center from January 2010 to December 2022. ICs were collected based on surgery reports and categorized according to the Intraoperative Adverse Incident Classification (EAUiaiC). The quality criteria for accurate and comprehensive reporting of intraoperative adverse events proposed by the Intraoperative Complications Assessment and Reporting with Universal Standards (ICARUS) Global Surgical Collaboration Project were fulfilled. To better classify the role of the RS-RARP approach, ICs were classified into anesthesiologic and surgical ICs. Surgical ICs were further divided according to the timing of the complication in RARP-related ICs and ePNLD-related ICs. Results: Overall, 40 ICs were reported in 40 patients (2.1%). Ten out of thirteen ICARUS criteria were satisfied. According to EAUiaiC grading of ICs, 27 (67.5%), 7 (17.5%), 2 (5%), 2 (5%), and 2 (5%) patients experienced Grade 1, 2, 3, 4A, and 4B, respectively. When we classified the ICs, two cases (5%) were classified as anesthesiologic ICs. Among the 38 surgical ICs, 16 (42%) were ePNLD-related, and 22 (58%) were RARP-related. ICs led to seven (0.37%) post-operative sequelae (four non-permanent and three permanent). Patients who suffered ICs were significantly older (67 years vs. 65 years, p = 0.02) and had a higher median BMI (27.0 vs. 26.1, p = 0.01), but did not differ in terms of comorbidities or tumor characteristics (all p values ≥ 0.05). Conclusions: Intraoperative complications during RS-RARP are relatively infrequent, but should not be underestimated. Patients suffering from ICs are older, have a higher body mass index, a higher rate of intraoperative blood transfusion, and a longer length of stay.
Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation
Authors: Wang Weiyuan , Lopez McDonald Melanie Cristina , Hariprasad Rajashree , Hamilton Tiara , Frank David A.
Published: March 2024

Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.
Editorial Catalysts: Catalysis for the Removal of Water Pollutants
Authors: Palomares Antonio Eduardo
Published: March 2024

Water is an essential resource for society, and it is necessary to guarantee its supply and quality [...]
Flower-like Titanium Dioxide/Cellulose Acetate Nanofibers for Catalytic Decomposition of Organic Pollutants Including Particulate Matter Removal
Authors: Ko Yun-Tso , Ruiz Jao Jancen B. , Leron Rhoda B. , Chang Chang-Tang
Published: March 2024

Volatile organic compounds (VOCs) are common organic pollutants that can cause adverse effects on human health. Treatment techniques, including photocatalytic oxidation, have been studied to remediate VOCs. Acetone was used as a model pollutant to investigate the photocatalytic degradation performance of electrospun photocatalytic nanofibers with synthesized flower-like titanium dioxide (F-TiO2) and cellulose acetate (CA). The synthesized F-TiO2 and photocatalytic nanofibers were characterized using FE-SEM, XRD, FTIR, UVVis, XPS, and a pore size and porosity analyzer. The addition of F-TiO2 decreases the diameter of the nanofibers. The photocatalytic degradation performance test showed an enhanced acetone degradation efficiency on F-TiO2/CA photocatalytic nanofibers (FT-CFs), with an up to 95.0% acetone degradation efficiency under optimum conditions, over P25 TiO2/CA photocatalytic nanofibers (T-CFs). The filtration efficiency of 3.0%FT-CF reached 99.9% with a filter basis weight of 0.660 g m−2 and face velocity of 5.0 cm−1 s. The filtration and photocatalytic degradation cycle tests revealed excellent reusability, with 97% particle filtration and no sign of material deterioration. Moreover, the biodegradability tests showed that the material can biodegrade in water and in soil for 30 and 40 days, respectively. This study demonstrates that electrospun FT-CFs exhibit exceptional photocatalytic degradation of acetone, a high filtration efficiency, excellent reusability, and biodegradability, making them a promising solution for VOC remediation.
Genetic Signature of Human Pancreatic Cancer and Personalized Targeting
Authors: Reshkin Stephan J. , Cardone Rosa Angela , Koltai Tomas
Published: March 2024

Pancreatic cancer is a highly lethal disease with a 5-year survival rate of around 11–12%. Surgery, being the treatment of choice, is only possible in 20% of symptomatic patients. The main reason is that when it becomes symptomatic, IT IS the tumor is usually locally advanced and/or has metastasized to distant organs; thus, early diagnosis is infrequent. The lack of specific early symptoms is an important cause of late diagnosis. Unfortunately, diagnostic tumor markers become positive at a late stage, and there is a lack of early-stage markers. Surgical and non-surgical cases are treated with neoadjuvant and/or adjuvant chemotherapy, and the results are usually poor. However, personalized targeted therapy directed against tumor drivers may improve this situation. Until recently, many pancreatic tumor driver genes/proteins were considered untargetable. Chemical and physical characteristics of mutated KRAS are a formidable challenge to overcome. This situation is slowly changing. For the first time, there are candidate drugs that can target the main driver gene of pancreatic cancer: KRAS. Indeed, KRAS inhibition has been clinically achieved in lung cancer and, at the pre-clinical level, in pancreatic cancer as well. This will probably change the very poor outlook for this disease. This paper reviews the genetic characteristics of sporadic and hereditary predisposition to pancreatic cancer and the possibilities of a personalized treatment according to the genetic signature.
Unraveling Desmin’s Head Domain Structure and Function
Authors: Vlachakis Dimitrios , Tsilafakis Konstantinos , Kostavasili Ioanna , Kossida Sophia , Mavroidis Manolis
Published: March 2024

Understanding the structure and function of intermediate filaments (IFs) is necessary in order to explain why more than 70 related IF genes have evolved in vertebrates while maintaining such dramatically tissue-specific expression. Desmin is a member of the large multigene family of IF proteins and is specifically expressed in myocytes. In an effort to elucidate its muscle-specific behavior, we have used a yeast two-hybrid system in order to identify desmin’s head binding partners. We described a mitochondrial and a lysosomal protein, NADH ubiquinone oxidoreductase core subunit S2 (NDUFS2), and saposin D, respectively, as direct desmin binding partners. In silico analysis indicated that both interactions at the atomic level occur in a very similar way, by the formation of a three-helix bundle with hydrophobic interactions in the interdomain space and hydrogen bonds at R16 and S32 of the desmin head domain. The interactions, confirmed also by GST pull-down assays, indicating the necessity of the desmin head domain and, furthermore, point out its role in function of mitochondria and lysosomes, organelles which are disrupted in myopathies due to desmin head domain mutations.
Synthetic Lethality between Cohesin and WNT Signaling Pathways in Diverse Cancer Contexts
Authors: Pallotta Maria Michela , Di Nardo Maddalena , Musio Antonio
Published: March 2024

Cohesin is a highly conserved ring-shaped complex involved in topologically embracing chromatids, gene expression regulation, genome compartmentalization, and genome stability maintenance. Genomic analyses have detected mutations in the cohesin complex in a wide array of human tumors. These findings have led to increased interest in cohesin as a potential target in cancer therapy. Synthetic lethality has been suggested as an approach to exploit genetic differences in cancer cells to influence their selective killing. In this study, we show that mutations in ESCO1, NIPBL, PDS5B, RAD21, SMC1A, SMC3, STAG2, and WAPL genes are synthetically lethal with stimulation of WNT signaling obtained following LY2090314 treatment, a GSK3 inhibitor, in several cancer cell lines. Moreover, treatment led to the stabilization of β-catenin and affected the expression of c-MYC, probably due to the occupancy decrease in cohesin at the c-MYC promoter. Finally, LY2090314 caused gene expression dysregulation mainly involving pathways related to transcription regulation, cell proliferation, and chromatin remodeling. For the first time, our work provides the underlying molecular basis for synthetic lethality due to cohesin mutations and suggests that targeting the WNT may be a promising therapeutic approach for tumors carrying mutated cohesin.
The Role of Cardiolipin in Mitochondrial Function and Neurodegenerative Diseases
Authors: Fuentes José , Morcillo Patricia
Published: March 2024

Cardiolipin (CL) is a mitochondria-exclusive phospholipid synthesized in the inner mitochondrial membrane. CL plays a key role in mitochondrial membranes, impacting a plethora of functions this organelle performs. Consequently, it is conceivable that abnormalities in the CL content, composition, and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of diseases. This review concentrates on papers published in recent years, combined with basic and underexplored research in CL. We capture new findings on its biological functions in the mitochondria, as well as its association with neurodegenerative diseases such as Alzheimer’s disease or Parkinson’s disease. Lastly, we explore the potential applications of CL as a biomarker and pharmacological target to mitigate mitochondrial dysfunction.
Polycystin-2 Mediated Calcium Signalling in the Dictyostelium Model for Autosomal Dominant Polycystic Kidney Disease
Authors: Allan Claire Y. , Sanislav Oana , Fisher Paul R.
Published: March 2024

Autosomal dominant polycystic kidney disease (ADPKD) occurs when the proteins Polycystin-1 (PC1, PKD1) and Polycystin-2 (PC2, PKD2) contain mutations. PC1 is a large membrane receptor that can interact and form a complex with the calcium-permeable cation channel PC2. This complex localizes to the plasma membrane, primary cilia and ER. Dysregulated calcium signalling and consequential alterations in downstream signalling pathways in ADPKD are linked to cyst formation and expansion; however, it is not completely understood how PC1 and PC2 regulate calcium signalling. We have studied Polycystin-2 mediated calcium signalling in the model organism Dictyostelium discoideum by overexpressing and knocking down the expression of the endogenous Polycystin-2 homologue, Polycystin-2. Chemoattractant-stimulated cytosolic calcium response magnitudes increased and decreased in overexpression and knockdown strains, respectively, and analysis of the response kinetics indicates that Polycystin-2 is a significant contributor to the control of Ca2+ responses. Furthermore, basal cytosolic calcium levels were reduced in Polycystin-2 knockdown transformants. These alterations in Ca2+ signalling also impacted other downstream Ca2+-sensitive processes including growth rates, endocytosis, stalk cell differentiation and spore viability, indicating that Dictyostelium is a useful model to study Polycystin-2 mediated calcium signalling.
Spotlight on New Hallmarks of Drug-Resistance towards Personalized Care for Epithelial Ovarian Cancer
Authors: Frezzini Simona , Lonardi Sara
Published: March 2024

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Despite the latest advances, a major clinical issue in EOC is the disappointing prognosis related to chemoresistance in almost one-third of cases. Drug resistance relies on heterogeneous cancer stem cells (CSCs), endowed with tumor-initiating potential, leading to relapse. No biomarkers of chemoresistance have been validated yet. Recently, major signaling pathways, micro ribonucleic acids (miRNAs), and circulating tumor cells (CTCs) have been advocated as putative biomarkers and potential therapeutic targets for drug resistance. However, further investigation is mandatory before their routine implementation. In accordance with the increasing rate of therapeutic efforts in EOC, the need for biomarker-driven personalized therapies is growing. This review aims to discuss the emerging hallmarks of drug resistance with an in-depth insight into the underlying molecular mechanisms lacking so far. Finally, a glimpse of novel therapeutic avenues and future challenges will be provided.
An Enzyme Immunoassay Developed for the Determination of Methylene Blue in Aquatic Products Based on a Novel Hapten
Authors: Huang Xuanyun , Yang Guangxin , Tang Yunyu , Wang Liqing
Published: March 2024

Methylene blue (MB) is a chemical dye which is used as an alternative drug for malachite green. In this study, based on computational chemistry, a novel hapten (TM) of MB was designed by comparing the conformational and electronic properties of MB. TM was synthesized and further conjugated with bovine serum albumin (BSA) and Ovalbumin (OVA). Then, the polyclonal antibodies were obtained by immunization with the immunogen of TM-BSA. Under optimal conditions, a sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed for the determination of MB, with an IC50 value of 41.5 μg L−1 and displaying a cross reaction of 78.2~88.9% with three different MB metabolins. The limit of detection (LOD) and the limit of quantitation (LOQ) for MB were validated to be 4.8 µg/kg and 6.0 µg/kg, respectively. Spiking experiments showed recoveries between 82.3% and 84.3%, with a relative standard deviation (RSD) of ≤6%. The results showed the generated polyclonal antibodies from the new hapten TM were reliable and could be used for detecting MB in fishery productions.
Trust-Based Relational Intervention® (TBRI®) Impact for Traumatized Children—Meaningful Change on Attachment Security and Mental Health after One Year
Authors: Misevičė Monika , Gervinskaitė-Paulaitienė Lina , Lesinskienė Sigita , Grauslienė Izabelė
Published: March 2024

Children from vulnerable backgrounds often have insecure attachment or disorganized attachment, which are related to psychological troubles, and such children need interventions to help them heal. The attachment system reorganizes in middle childhood, and other important adults play a considerable role in children’s lives. Thus, it is essential to weigh the impact of psychosocial interventions, while the main focus of the intervention is the staff member’s direct work with the child through a trusting relationship. The primary purpose of this study is to investigate whether children’s attachment security and mental health outcomes change after participating in a trauma-informed, attachment-based, Trust-Based Relational Intervention (TBRI) provided in a daycare center. It was a case-series study involving twelve children aged 8–11 years. The child attachment interview (CAI), CBCL/6-18, TRF/6-18, and clinical interviews for parents and children were used, measuring the change between the TBRI implementation in the daycare center and after one year. For ten participants, we noticed an improvement in mental health; for seven participants, security scales improved; for two participants, their disorganized attachment changed into insecure–dismissing. We have preliminary evidence that vulnerable children may benefit in terms of attachment security and mental health from the trusting relationship that staff build using the TBRI.
Novel Polyamide/Chitosan Nanofibers Containing Glucose Oxidase and Rosemary Extract: Fabrication and Antimicrobial Functionality
Authors: Fard Ghazaleh Chizari , Parvinzadeh Gashti Mazeyar , Dehdast Seyed Ahmad , Shabani Mohammad , Zarinabadi Ehsan , Seifi Negin , Berenjian Ali
Published: March 2024

In recent years, the synthesis of nanofibers using plant extracts and bioactive materials has been extensively studied and recognized as a suitable and efficient method applicable in the food packaging field. In this research, an antimicrobial material was introduced by the immobilization of glucose oxidase (GOx) in Nylon–Ag masterbatch/chitosan/Rosmarinus officinalis extract nanofiber via electrospinning technology. Nylon–Ag masterbatch/chitosan/Rosmarinus officinalis composite nanofibrous membranes with an average diameter of 207 ± 18 nm were successfully prepared using the electrospinning technique. The chemical properties of membranes were analyzed by Fourier transform infrared spectroscopy (FTIR) and the morphological characterization of nanofibers was evaluated with field emission scanning electron microscopy (FE-SEM). Moreover, enzymatic activity of GOx was determined by the Carmine method. FTIR results showed the successful incorporation of glucose oxidase and Rosmarinus officinalis into the nanofiber composite. Immobilized GOx showed high (79.5%) enzymatic activity in the optimum sample. The Rosmarinus officinalis, glucose oxidase-incorporated Nylon–Ag masterbatch/chitosan nanofibrous exhibited excellent antimicrobial activity on both gram-negative bacterium Escherichia coli (97.5%) and gram-positive bacterium Staphylococcus aureus (99.5%). The antibacterial and antioxidant Nylon–Ag masterbatch/chitosan/Rosmarinus officinalis/GOx nanofibrous membrane showed higher potential, compared to the control sample, to be used as food packaging by improving the shelf life and maintaining the quality of food stuffs. Therefore, this research recommends it as a promising candidate for food preservation applications.