bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontier Revitalisation of Industrial Heritage with Urban–Rural Fringe in China
Authors: Gan Tingjiang , Chen Juan , Yao Muxia , Cenci Jeremy , Zhang Jiazhen , He Yunxiao
Published: April 2024

The urban–rural fringe is at the forefront of the confrontation between the agricultural and industrial civilisations. How to handle the relationship between the two civilisations in this region and ensure its sustainable development is an eternal topic in the science of the human-living environment. Thanks to the special historical background of the Third Line construction, China’s industrial heritage connects with the urban–rural fringe that surpasses other countries. For the first time, this study connects China’s Third Line construction, industrial heritage, and urban–rural integration within the same context, combining big data bibliometric methods to obtain the development characteristics and context of China’s industrial heritage research starting from 2004. It has strong policy characteristics, is influenced by administrative orders, and is aligned with urbanisation efforts. Theoretical exploration is the first step in research, followed by value connotations and cultural qualities. It addresses various topics, including industrial heritage conservation, regeneration approaches, and cultural heritage tourism. The research focuses primarily on the value appraisal of industrial heritage, exploring revitalisation tactics and routes, as well as regional development models in urban–rural periphery areas. This study also examines how scholars generally consider the impact of industrial heritage on the economic, social, and cultural development of urban–rural fringe areas in order to integrate and propose various protection and utilisation strategies, such as industrial heritage preservation, cultural and creative industry development, and tourism resource development.
Updates in Cancer Cachexia: Clinical Management and Pharmacologic Interventions
Authors: Pandey Sudeep , Bradley Lauren , Del Fabbro Egidio
Published: April 2024

Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition.
A Review of the Paradigmatic Role of Adipose Tissue in Renal Cancer: Fat Measurement and Tumor Behavior Features
Authors: Faiella Eliodoro , Vergantino Elva , Vaccarino Federica , Bruno Amalia , Perillo Gloria , Grasso Rosario Francesco , Zobel Bruno Beomonte , Santucci Domiziana
Published: April 2024

(1) Background: Renal-cell carcinoma (RCC) incidence has been steadily rising, with obesity identified as a potential risk factor. However, the relationship between obesity and RCC prognosis remains unclear. This systematic review aims to investigate the impact of different adipose tissue measurements on RCC behavior and prognosis. (2) Methods: A search of MEDLINE databases identified 20 eligible studies focusing on various fat measurements, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PRAT), and the Mayo adhesive probability (MAP) score. (3) Results: The review revealed conflicting findings regarding the association between adipose tissue measurements and RCC outcomes. While some studies suggested a protective role of certain fat deposits, particularly VAT, against disease progression and mortality, others reported contradictory results across different adipose metrics and RCC subtypes. (4) Conclusions: Methodological variations and limitations, such as retrospective designs and sample size constraints, pose challenges to standardization and generalizability. Further research is needed to understand these associations better and establish standardized approaches for adiposity assessment in RCC patients, which could inform clinical practice and therapeutic decision-making.
Application of Deep Learning for Real-Time Ablation Zone Measurement in Ultrasound Imaging
Authors: Zimmermann Corinna , Michelmann Adrian , Daniel Yannick , Enderle Markus D. , Salkic Nermin , Linzenbold Walter
Published: April 2024

Background: The accurate delineation of ablation zones (AZs) is crucial for assessing radiofrequency ablation (RFA) therapy’s efficacy. Manual measurement, the current standard, is subject to variability and potential inaccuracies. Aim: This study aims to assess the effectiveness of Artificial Intelligence (AI) in automating AZ measurements in ultrasound images and compare its accuracy with manual measurements in ultrasound images. Methods: An in vitro study was conducted using chicken breast and liver samples subjected to bipolar RFA. Ultrasound images were captured every 15 s, with the AI model Mask2Former trained for AZ segmentation. The measurements were compared across all methods, focusing on short-axis (SA) metrics. Results: We performed 308 RFA procedures, generating 7275 ultrasound images across liver and chicken breast tissues. Manual and AI measurement comparisons for ablation zone diameters revealed no significant differences, with correlation coefficients exceeding 0.96 in both tissues (p < 0.001). Bland–Altman plots and a Deming regression analysis demonstrated a very close alignment between AI predictions and manual measurements, with the average difference between the two methods being −0.259 and −0.243 mm, for bovine liver and chicken breast tissue, respectively. Conclusion: The study validates the Mask2Former model as a promising tool for automating AZ measurement in RFA research, offering a significant step towards reducing manual measurement variability.
Socioeconomic Deprivation and Invasive Breast Cancer Incidence by Stage at Diagnosis: A Possible Explanation to the Breast Cancer Social Paradox
Authors: Borghi Giulio , Delacôte Claire , Delacour-Billon Solenne , Ayrault-Piault Stéphanie , Dabakuyo-Yonli Tienhan Sandrine , Delafosse Patricia , Woronoff Anne-Sophie , Trétarre Brigitte , Molinié Florence , Cowppli-Bony Anne
Published: April 2024

In this study, we assessed the influence of area-based socioeconomic deprivation on the incidence of invasive breast cancer (BC) in France, according to stage at diagnosis. All women from six mainland French departments, aged 15+ years, and diagnosed with a primary invasive breast carcinoma between 2008 and 2015 were included (n = 33,298). Area-based socioeconomic deprivation was determined using the French version of the European Deprivation Index. Age-standardized incidence rates (ASIR) by socioeconomic deprivation and stage at diagnosis were compared estimating incidence rate ratios (IRRs) adjusted for age at diagnosis and rurality of residence. Compared to the most affluent areas, significantly lower IRRs were found in the most deprived areas for all-stages (0.85, 95% CI 0.81–0.89), stage I (0.77, 95% CI 0.72–0.82), and stage II (0.84, 95% CI 0.78–0.90). On the contrary, for stages III–IV, significantly higher IRRs (1.18, 95% CI 1.08–1.29) were found in the most deprived areas. These findings provide a possible explanation to similar or higher mortality rates, despite overall lower incidence rates, observed in women living in more deprived areas when compared to their affluent counterparts. Socioeconomic inequalities in access to healthcare services, including screening, could be plausible explanations for this phenomenon, underlying the need for further research.
Targeting TRPV4 Channels for Cancer Pain Relief
Authors: Antoniazzi Caren Tatiane de David , Ruviaro Náthaly Andrighetto , Peres Diulle Spat , Rodrigues Patrícia , Viero Fernanda Tibolla , Trevisan Gabriela
Published: April 2024

Despite the unique and complex nature of cancer pain, the activation of different ion channels can be related to the initiation and maintenance of pain. The transient receptor potential vanilloid 4 (TRPV4) is a cation channel broadly expressed in sensory afferent neurons. This channel is activated by multiple stimuli to mediate pain perception associated with inflammatory and neuropathic pain. Here, we focused on summarizing the role of TRPV4 in cancer etiology and cancer-induced pain mechanisms. Many studies revealed that the administration of a TRPV4 antagonist and TRPV4 knockdown diminishes nociception in chemotherapy-induced peripheral neuropathy (CIPN). Although the evidence on TRPV4 channels’ involvement in cancer pain is scarce, the expression of these receptors was reportedly enhanced in cancer-induced bone pain (CIBP), perineural, and orofacial cancer models following the inoculation of tumor cells to the bone marrow cavity, sciatic nerve, and tongue, respectively. Effective pain management is a continuous problem for patients diagnosed with cancer, and current guidelines fail to address a mechanism-based treatment. Therefore, examining new molecules with potential antinociceptive properties targeting TRPV4 modulation would be interesting. Identifying such agents could lead to the development of treatment strategies with improved pain-relieving effects and fewer adverse effects than the currently available analgesics.
Survivin as a Therapeutic Target for the Treatment of Human Cancer
Authors: Wang Qiang , Greene Mark I.
Published: April 2024

Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in the regulation of apoptosis. More recent studies showed that survivin is a component of the chromosome passenger complex and acts as an essential mediator of mitotic progression. Other potential functions of survivin, such as mitochondrial function and autophagy, have also been proposed. Survivin has emerged as an attractive target for cancer therapy because its overexpression has been found in most human cancers and is frequently associated with chemotherapy resistance, recurrence, and poor survival rates in cancer patients. In this review, we discuss our current understanding of how survivin mediates various aspects of malignant transformation and drug resistance, as well as the efforts that have been made to develop therapeutics targeting survivin for the treatment of cancer.
Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors
Authors: Denu Ryan A. , Joseph Cissimol P. , Urquiola Elizabeth S. , Byrd Precious S. , Yang Richard K. , Ratan Ravin , Zarzour Maria Alejandra , Conley Anthony P. , Araujo Dejka M. , Ravi Vinod , Nassif Haddad Elise F. , Nakazawa Michael S. , Patel Shreyaskumar , Wang Wei-Lien , Lazar Alexander J. , Somaiah Neeta
Published: April 2024

Objective: The vast majority of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in KIT, PDGFRA, or components of the succinate dehydrogenase (SDH) complex (SDHA, SDHB, SDHC, and SDHD genes). A small fraction of GISTs lack alterations in KIT, PDGFRA, and SDH. We aimed to further characterize the clinical and genomic characteristics of these so-called “triple-negative” GISTs. Methods: We extracted clinical and genomic data from patients seen at MD Anderson Cancer Center with a diagnosis of GIST and available clinical next generation sequencing data to identify “triple-negative” patients. Results: Of the 20 patients identified, 11 (55.0%) had gastric, 8 (40.0%) had small intestinal, and 1 (5.0%) had rectal primary sites. In total, 18 patients (90.0%) eventually developed recurrent or metastatic disease, and 8 of these presented with de novo metastatic disease. For the 13 patients with evaluable response to imatinib (e.g., neoadjuvant treatment or for recurrent/metastatic disease), the median PFS with imatinib was 4.4 months (range 0.5–191.8 months). Outcomes varied widely, as some patients rapidly developed progressive disease while others had more indolent disease. Regarding potential genomic drivers, four patients were found to have alterations in the RAS/RAF/MAPK pathway: two with a BRAF V600E mutation and two with NF1 loss-of-function (LOF) mutations (one deletion and one splice site mutation). In addition, we identified two with TP53 LOF mutations, one with NTRK3 fusion (ETV6-NTRK3), one with PTEN deletion, one with FGFR1 gain-of-function (GOF) mutation (K654E), one with CHEK2 LOF mutation (T367fs*), one with Aurora kinase A fusion (AURKA-CSTF1), and one with FANCA deletion. Patients had better responses with molecularly targeted therapies than with imatinib. Conclusions: Triple-negative GISTs comprise a diverse cohort with different driver mutations. Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.
Deep Learning Reconstruction for DWIs by EPI and FASE Sequences for Head and Neck Tumors
Authors: Ikeda Hirotaka , Ohno Yoshiharu , Yamamoto Kaori , Murayama Kazuhiro , Ikedo Masato , Yui Masao , Kumazawa Yunosuke , Shimamura Yurika , Takagi Yui , Nakagaki Yuhei , Hanamatsu Satomu , Obama Yuki , Ueda Takahiro , Nagata Hiroyuki , Ozawa Yoshiyuki , Iwase Akiyoshi , Toyama Hiroshi
Published: April 2024

Background: Diffusion-weighted images (DWI) obtained by echo-planar imaging (EPI) are frequently degraded by susceptibility artifacts. It has been suggested that DWI obtained by fast advanced spin-echo (FASE) or reconstructed with deep learning reconstruction (DLR) could be useful for image quality improvements. The purpose of this investigation using in vitro and in vivo studies was to determine the influence of sequence difference and of DLR for DWI on image quality, apparent diffusion coefficient (ADC) evaluation, and differentiation of malignant from benign head and neck tumors. Methods: For the in vitro study, a DWI phantom was scanned by FASE and EPI sequences and reconstructed with and without DLR. Each ADC within the phantom for each DWI was then assessed and correlated for each measured ADC and standard value by Spearman’s rank correlation analysis. For the in vivo study, DWIs obtained by EPI and FASE sequences were also obtained for head and neck tumor patients. Signal-to-noise ratio (SNR) and ADC were then determined based on ROI measurements, while SNR of tumors and ADC were compared between all DWI data sets by means of Tukey’s Honest Significant Difference test. Results: For the in vitro study, all correlations between measured ADC and standard reference were significant and excellent (0.92 ≤ ρ ≤ 0.99, p < 0.0001). For the in vivo study, the SNR of FASE with DLR was significantly higher than that of FASE without DLR (p = 0.02), while ADC values for benign and malignant tumors showed significant differences between each sequence with and without DLR (p < 0.05). Conclusion: In comparison with EPI sequence, FASE sequence and DLR can improve image quality and distortion of DWIs without significantly influencing ADC measurements or differentiation capability of malignant from benign head and neck tumors.
Clinical Theranostics in Recurrent Gliomas: A Review
Authors: Hoggarth Austin R. , Muthukumar Sankar , Thomas Steven M. , Crowley James , Kiser Jackson , Witcher Mark R.
Published: April 2024

Gliomas represent the most commonly occurring tumors in the central nervous system and account for approximately 80% of all malignant primary brain tumors. With a high malignancy and recurrence risk, the prognosis of high-grade gliomas is poor, with a mean survival time of 12–18 months. While contrast-enhanced MRI serves as the standard diagnostic imaging modality for gliomas, it faces limitations in the evaluation of recurrent gliomas, failing to distinguish between treatment-related changes and tumor progression, and offers no direct therapeutic options. Recent advances in imaging modalities have attempted to address some of these limitations, including positron emission tomography (PET), which has demonstrated success in delineating tumor margins and guiding the treatment of recurrent gliomas. Additionally, with the advent of theranostics in nuclear medicine, PET tracers, when combined with therapeutic agents, have also evolved beyond a purely diagnostic modality, serving both diagnostic and therapeutic roles. This review will discuss the growing involvement of theranostics in diagnosing and treating recurrent gliomas and address the associated impact on quality of life and functional recovery.
Direct Implantation of Patient Brain Tumor Cells into Matching Locations in Mouse Brains for Patient-Derived Orthotopic Xenograft Model Development
Authors: Qi Lin , Baxter Patricia , Kogiso Mari , Zhang Huiyuan , Braun Frank K. , Lindsay Holly , Zhao Sibo , Xiao Sophie , Abdallah Aalaa Sanad , Suarez Milagros , Huang Zilu , Teo Wan Yee , Yu Litian , Zhao Xiumei , Liu Zhigang , Huang Yulun , Su Jack M. , Man Tsz-Kwong , Lau Ching C. , Perlaky Laszlo , Du Yuchen , Li Xiao-Nan
Published: April 2024

Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice. Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors. Conclusions: The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing.
Applications of Urinary Extracellular Vesicles in the Diagnosis and Active Surveillance of Prostate Cancer
Authors: Smith Stephanie F. , Brewer Daniel S. , Hurst Rachel , Cooper Colin S.
Published: April 2024

Prostate cancer is the most common non-cutaneous cancer among men in the UK, causing significant health and economic burdens. Diagnosis and risk prognostication can be challenging due to the genetic and clinical heterogeneity of prostate cancer as well as uncertainties in our knowledge of the underlying biology and natural history of disease development. Urinary extracellular vesicles (EVs) are microscopic, lipid bilayer defined particles released by cells that carry a variety of molecular cargoes including nucleic acids, proteins and other molecules. Urine is a plentiful source of prostate-derived EVs. In this narrative review, we summarise the evidence on the function of urinary EVs and their applications in the evolving field of prostate cancer diagnostics and active surveillance. EVs are implicated in the development of all hallmarks of prostate cancer, and this knowledge has been applied to the development of multiple diagnostic tests, which are largely based on RNA and miRNA. Common gene probes included in multi-probe tests include PCA3 and ERG, and the miRNAs miR-21 and miR-141. The next decade will likely bring further improvements in the diagnostic accuracy of biomarkers as well as insights into molecular biological mechanisms of action that can be translated into opportunities in precision uro-oncology.
Safety and Effectiveness of Perioperative Hyperthermic Intraperitoneal Chemotherapy with Gemcitabine in Patients with Resected Pancreatic Ductal Adenocarcinoma: Clinical Trial EudraCT 2016-004298-41
Authors: Padilla-Valverde David , Bodoque-Villar Raquel , García-Santos Esther , Sanchez Susana , Manzanares-Campillo Carmen , Rodriguez Marta , González Lucia , Ambrós Alfonso , Cano Juana M. , Padilla-Marcote Maria , Redondo-Calvo Javier , Martin Jesus , Serrano-Oviedo Leticia
Published: April 2024

Background: Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer stem cells. Materials and methods: A randomized trial involving 42 patients. All patients were diagnosed with pancreatic ductal adenocarcinoma. Group I: R0 resection. Group II. R0 resection and HIPEC with gemcitabine (120 mg/m2 for 30 min). Effectiveness was measured with analysis of overall survival, disease-free survival, distant recurrence, locoregional recurrence, and measuring of pancreatic cancer stem cells (EpCAM+CXCR4+CD133+). Results: From 2017 to 2023, 63 patients were recruited for our clinical trial; 21 patients were included in each group, and 21 were excluded. Locoregional recurrence, p-value: 0.022, was lower in the experimental group. There were no significant differences between the two groups in hospital mortality, perioperative complications, or hospital costs. We found a significant decrease in pancreatic cancer stem cells in patients in the experimental group after treatment, p -value of 0.018. Conclusions: The use of HIPEC with gemcitabine after surgery in patients with resectable pancreatic ductal adenocarcinoma reduces locoregional recurrence and may be associated with a significant decrease in pancreatic cancer stem cells.
Do Oncologists Recommend the “Pill” of Physical Activity in Their Practice? Answers from the Oncologist and Patients’ Perspectives
Authors: Martínez Aguirre-Betolaza Aitor , Dobaran Amezua Ander , Yagin Fatma Hilal , Cacicedo Jon , Olasagasti-Ibargoien Jurgi , Castañeda-Babarro Arkaitz
Published: April 2024

Objectives: The purposes of this current questionnaire-based study were to analyse whether oncologists prescribed PA to their patients in Spain, as well as the type of exercise recommended, the variables that influence whether or not to recommend it and to compare these recommendations with the values reported by their patients. Methods: Two online questionnaires were designed for this study. The first one, filled in by the oncologists (n = 93), contained aspects such as the attitude or barriers to promoting PA. The second was designed for patients with cancer (n = 149), which assessed PA levels and counselling received from oncologists, among other facets. Results: The majority of oncologists (97%) recommend PA during their consultations. Instead, only 62% of patients reported participating in exercise within the last 7 days. Walking was the most common form of exercise, reported by 50% of participants. Patients who received exercise recommendations from their oncologist walked for more days (p = 0.004; ES = 0.442) and more minutes per day (p = 0.022; ES = 0.410). The barriers most highlighted by patients were lack of time and not knowing how to perform PA. Conclusion: Oncologists and patients seem to be interested and able to participate in PA counselling and programmes. However, there was a discrepancy between what was reported by oncologists and expressed by patients in terms of recommendations for PA and the modality itself.
Textbook Neoadjuvant Outcome—Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment
Authors: Pelc Zuzanna , Sędłak Katarzyna , Leśniewska Magdalena , Mielniczek Katarzyna , Chawrylak Katarzyna , Skórzewska Magdalena , Ciszewski Tomasz , Czechowska Joanna , Kiszczyńska Agata , Wijnhoven Bas P. L. , Van Sandick Johanna W. , Gockel Ines , Gisbertz Suzanne S. , Piessen Guillaume , Eveno Clarisse , Bencivenga Maria , De Manzoni Giovanni , Baiocchi Gian Luca , Morgagni Paolo , Rosati Riccardo , Fumagalli Romario Uberto , Davies Andrew , Endo Yutaka , Pawlik Timothy M. , Roviello Franco , Bruns Christiane , Polkowski Wojciech P. , Rawicz-Pruszyński Karol
Published: April 2024

The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the “All or None” method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the “ideal” and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.
Integration of Computational Pipeline to Streamline Efficacious Drug Nomination and Biomarker Discovery in Glioblastoma
Authors: Maeser Danielle , Gruener Robert F. , Galvin Robert , Lee Adam , Koga Tomoyuki , Grigore Florina-Nicoleta , Suzuki Yuta , Furnari Frank B. , Chen Clark , Huang R. Stephanie
Published: April 2024

Glioblastoma multiforme (GBM) is the deadliest, most heterogeneous, and most common brain cancer in adults. Not only is there an urgent need to identify efficacious therapeutics, but there is also a great need to pair these therapeutics with biomarkers that can help tailor treatment to the right patient populations. We built patient drug response models by integrating patient tumor transcriptome data with high-throughput cell line drug screening data as well as Bayesian networks to infer relationships between patient gene expression and drug response. Through these discovery pipelines, we identified agents of interest for GBM to be effective across five independent patient cohorts and in a mouse avatar model: among them are a number of MEK inhibitors (MEKis). We also predicted phosphoglycerate dehydrogenase enzyme (PHGDH) gene expression levels to be causally associated with MEKi efficacy, where knockdown of this gene increased tumor sensitivity to MEKi and overexpression led to MEKi resistance. Overall, our work demonstrated the power of integrating computational approaches. In doing so, we quickly nominated several drugs with varying known mechanisms of action that can efficaciously target GBM. By simultaneously identifying biomarkers with these drugs, we also provide tools to select the right patient populations for subsequent evaluation.
Taking a BiTE out of Lymphoma: Bispecific Antibodies in B-Cell Non-Hodgkin Lymphoma
Authors: Weiss Jonathan M. , Phillips Tycel J.
Published: April 2024

B-cell non-Hodgkin’s lymphoma (NHL) refers to a heterogenous group of diseases, all of which have a wide range of treatment strategies and patient outcomes. There have been multiple novel, immune-based therapies approved in NHL in the last decade, including bispecific antibodies (BsAbs) and chimeric antigen receptor therapy (CAR-T). With a host of new therapies, an important next step will be determining how these therapies should be sequenced in contemporary management strategies. This review seeks to offer a framework for the ways in which BsABs can be incorporated into the current management paradigm for NHL, with special attention paid to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL).
Racial and Ethnic Disparities in European Breast Cancer Clinical Trials
Authors: Bania Angelina , Adamou Antonis , Saloustros Emmanouil
Published: April 2024

Breast cancer is the most prevalent female cancer worldwide with known correlations between the race and tumor characteristics of the patients and prognosis. International and US-based studies, however, have reported a disproportionate representation of Black and Hispanic patients in clinical trials. This is the first study assessing race and ethnicity reporting trends and inclusion in European breast cancer trials. The PubMed and ClinicalTrials.gov databases were systematically searched for trials on breast cancer treatment conducted exclusively in Europe between 2010 and 2022. Of the 97 identified trials, race was reported in 10.31%. Multinational participation, but not the study size or trial phase, was significantly associated with higher race reporting trends. These 10 trials featured a White-predominant population, with 1.08% Asian and 0.88% Black patients included. The acquisition of the race and ethnicity data of patients in European trials is lower compared to the U.S. or worldwide studies and does not permit extensive analysis of minority participation. In a limited analysis, the low rates of minority participation are concerning, based on population-based data on minorities in select European countries. These observations should encourage race reporting practices in European breast cancer trials and adequate minority participation to support the generalizability of the results of the studies and promote healthcare equity.
The Tumor Stroma of Squamous Cell Carcinoma: A Complex Environment That Fuels Cancer Progression
Authors: Buruiană Alexandra , Gheban Bogdan-Alexandru , Gheban-Roșca Ioana-Andreea , Georgiu Carmen , Crișan Doința , Crișan Maria
Published: April 2024

The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays a crucial role in driving tumor progression, shaping treatment responses, and influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) tumor stroma, highlighting its key constituents and their dynamic contributions. We examine how significant changes within the cSCC ECM—specifically, alterations in fibronectin, hyaluronic acid, laminins, proteoglycans, and collagens—promote cancer progression, metastasis, and drug resistance. The cellular composition of the cSCC TME is also explored, detailing the intricate interplay of cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, and various immune cell populations. These diverse players modulate tumor development, angiogenesis, and immune responses. Finally, we emphasize the TME’s potential as a therapeutic target. Emerging strategies discussed in this review include harnessing the immune system (adoptive cell transfer, checkpoint blockade), hindering tumor angiogenesis, disrupting CAF activity, and manipulating ECM components. These approaches underscore the vital role that deciphering TME interactions plays in advancing cSCC therapy. Further research illuminating these complex relationships will uncover new avenues for developing more effective treatments for cSCC.
Efficacy and Safety of Cemiplimab for the Management of Non-Melanoma Skin Cancer: A Drug Safety Evaluation
Authors: Potestio Luca , Scalvenzi Massimiliano , Lallas Aimilios , Martora Fabrizio , Guerriero Luigi , Fornaro Luigi , Marano Laura , Villani Alessia
Published: April 2024

Non-melanoma skin cancer includes several types of cutaneous tumors, with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) as the commonest. Among the available therapeutic options, surgical excision is the mainstay of treatment for both tumors. However, tumor features and patients’ comorbidities may limit the use of these techniques, making the treatment challenging. As regards BCC, even if hedgehog inhibitors revolutionized the therapeutic scenario, there are still patients unresponsive or intolerant to these drugs. In this context, cemiplimab has been approved as second-line treatment. As regards SCC, cemiplimab was the first systemic therapy approved. The objective of this manuscript was to investigate the efficacy and safety of cemiplimab for the management of BCC and cSCC. Cemiplimab has a durable and significant effect for the management of BCC and CSCC, with a favorable safety profile. Different specialists including oncologists, radiologists, dermatologists, and surgeons are required to guarantee an integrated approach, leading to the best management of patients. Moreover, the collaboration among specialists will allow them to best manage the TEAEs, reducing the risk of treatment suspension or discontinuation. Certainly, ongoing studies and more and more emerging real-world evidence, will allow us to better characterize the role of cemiplimab for the management of advanced non-melanoma skin cancer.
A Role for iNOS in Erastin Mediated Reduction of P-Glycoprotein Transport Activity
Authors: Brown Shalyn M. , Sinha Birandra K. , Cannon Ronald E.
Published: April 2024

The blood–brain barrier is composed of both a physical barrier and an enzymatic barrier. Tight junction (TJ) proteins expressed between endothelial cells of brain capillaries provide the physical barrier to paracellular movement of ions and molecules to the brain, while luminal-facing efflux transporters enzymatically restrict the entry of blood-borne molecules from entering the brain. The expression and activity of ATP Binding Cassette transporters or “ABC” transporters in endothelial cells of the BBB and in human tumor cells are dynamically regulated by numerous signaling pathways. P-glycoprotein (P-gp), (ABCB1), is arguably the most studied transporter of the BBB, and in human cell lines. P-glycoprotein transport activity is rapidly inhibited by signaling pathways that call for the rapid production of nitric oxide (NO) from the inducible nitric oxide synthase enzyme, iNOS. This study investigated how nano-molar levels of the selective chemotherapeutic erastin affect the activity or expression of P-glycoprotein transporter in brain capillaries and in human tumor cell lines. We chose erastin because it signals to iNOS for NO production at low concentrations. Furthermore, erastin inhibits the cellular uptake of cystine through the XC− cystine/glutamate antiporter. Since previous reports indicate that NO production from iNOS can rapidly inhibit P-gp activity in tumor cells, we wondered if induction of iNOS by erastin could also rapidly reduce P-glycoprotein transport activity in brain endothelial cells and in human tumor cell lines. We show here that low concentrations of erastin (1 nM) can induce iNOS, inhibit the activity of P-glycoprotein, and reduce the intracellular uptake of cystine via the Xc- cystine/glutamate antiporter. Consistent with reduced P-glycoprotein activity in rat brain capillary endothelial cells, we show that human tumor cell lines exposed to erastin become more sensitive to cytotoxic substrates of P-glycoprotein.
Improving Breast Cancer Outcomes for Indigenous Women in Australia
Authors: Christie Vita , Riley Lynette , Green Deb , Amin Janaki , Skinner John , Pyke Chris , Gwynne Kylie
Published: April 2024

In Australia, the incidence rate of breast cancer is lower in Indigenous* women than non-Indigenous women; however, the mortality rate is higher, with Indigenous women 1.2 times more likely to die from the disease. This paper provides practical and achievable solutions to improve health outcomes for Indigenous women with breast cancer in Australia. This research employed the Context–Mechanism–Outcome (CMO) framework to reveal potential mechanisms and contextual factors that influence breast cancer outcomes for Indigenous women, stratified into multiple levels, namely, micro (interpersonal), meso (systemic) and macro (policy) levels. The CMO framework allowed us to interpret evidence regarding Indigenous women and breast cancer and provides nine practical ways to improve health outcomes and survival rates.
Engineering Materials for Catalysis
Authors: Pintar Albin , Tušar Nataša Novak , Rupprechter Günther
Published: April 2024

The Special Issue “Engineering Materials for Catalysis” was inspired by the preceding 2020 Summer School of the European Federation of Catalysis Societies (EFCATS, https://skd2020 [...]
Palladium Complexes Derived from Waste as Catalysts for C-H Functionalisation and C-N Bond Formation
Authors: Jantan Khairil A. , Ekart Gregor , McCarthy Sean , White Andrew J. P. , Braddock D. Christopher , Serpe Angela , Wilton-Ely James D. E. T.
Published: April 2024

Three-way catalysts (TWCs) are widely used in vehicles to convert the exhaust emissions from internal combustion engines into less toxic pollutants. After around 8–10 years of use, the declining catalytic activity of TWCs causes them to need replacing, leading to the generation of substantial amounts of spent TWC material containing precious metals, including palladium. It has previously been reported that [NnBu4]2[Pd2I6] is obtained in high yield and purity from model TWC material using a simple, inexpensive and mild reaction based on tetrabutylammonium iodide in the presence of iodine. In this contribution, it is shown that, through a simple ligand exchange reaction, this dimeric recovery complex can be converted into PdI2(dppf) (dppf = 1,1′-bis(diphenylphosphino)ferrocene), which is a direct analogue of a commonly used catalyst, PdCl2(dppf). [NnBu4]2[Pd2I6] displayed high catalytic activity in the oxidative functionalisation of benzo[h]quinoline to 10-alkoxybenzo[h]quinoline and 8-methylquinoline to 8-(methoxymethyl)quinoline in the presence of an oxidant, PhI(OAc)2. Near-quantitative conversions to the desired product were obtained using a catalyst recovered from waste under milder conditions (50 °C, 1–2 mol% Pd loading) and shorter reaction times (2 h) than those typically used in the literature. The [NnBu4]2[Pd2I6] catalyst could also be recovered and re-used multiple times after the reaction, providing additional sustainability benefits. Both [NnBu4]2[Pd2I6] and PdI2(dppf) were also found to be active in Buchwald–Hartwig amination reactions, and their performance was optimised through a Design of Experiments (DoE) study. The optimised conditions for this waste-derived palladium catalyst (1–2 mol% Pd loading, 3–6 mol% of dppf) in a bioderived solvent, cyclopentyl methyl ether (CPME), offer a more sustainable approach to C-N bond formation than comparable amination protocols.
Species Composition and Distribution of Terrestrial Herbs in a High Montane Forest in Ecuador
Authors: Quintana Catalina , Balslev Henrik , Valencia Renato
Published: April 2024

In mountain tropical forests, understory herbs have received little attention compared to trees, and their commonness and rarity are virtually unknown. We studied ground herbs to explore how they are assembled in a full one-hectare plot and to test the influence of light intensity (LI) and topographic habitats in species composition. The plot is a humid montane forest located in the Pasochoa Volcano, at 3300 m. We found 43 genera and 50 perennial species (30 angiosperms in 17 families, and 20 ferns). Interestingly, herbs are 64% richer in species than trees in the same study plot (50 vs. 32). Herbs were mostly obligately terrestrial (70% of the species), while 30% were fallen climbers and epiphytes rooted in the ground. Across the forest, there were 31,119 individuals that covered 8.5% of the ground. We concluded that both LI and topography shaped the species distribution, the floristic composition, and the community structure of ground herbs. For instance, 12% of the species were exclusively found in places with high LI; the rest of species grew in medium- to low-LI environments. Concerning rarity, we found that 39% of the species are rare (judging by botanical collections; <100), which stresses the need of conservation strategies for this group of plants.
Monitoring Change and Recovery of an Embayed Beach in Response to Typhoon Storms Using UAV LiDAR
Authors: Lei Qiujia , Wang Xinkai , Liu Yifei , Guo Junli , Cai Tinglu , Xia Xiaoming
Published: April 2024

The monitoring of beach topographical changes and recovery processes under typhoon storm influence has primarily relied on traditional techniques that lack high spatial resolution. Therefore, we used an unmanned aerial vehicle light detection and ranging (UAV LiDAR) system to obtain the four time periods of topographic data from Tantou Beach, a sandy beach in Xiangshan County, Zhejiang Province, China, to explore beach topography and geomorphology in response to typhoon events. The UAV LiDAR data in four survey periods showed an overall vertical accuracy of approximately 5 cm. Based on the evaluated four time periods of the UAV LiDAR data, we created four corresponding DEMs for the beach. We calculated the DEM of difference (Dod), which showed that the erosion and siltation on Tantou Beach over different temporal scales had a significant alongshore zonal feature with a broad change range. The tidal level significantly impacted beach erosion and siltation changes. However, the storm surge did not affect the beach area above the spring high-tide level. After storms, siltation occurred above the spring high-tide zone. This study reveals the advantage of UAV LiDAR in monitoring beach changes and provides novel insights into the impacts of typhoon storms on coastal topographic and geomorphological change and recovery processes.
VizNav: A Modular Off-Policy Deep Reinforcement Learning Framework for Vision-Based Autonomous UAV Navigation in 3D Dynamic Environments
Authors: AlMahamid Fadi , Grolinger Katarina
Published: April 2024

Unmanned aerial vehicles (UAVs) provide benefits through eco-friendliness, cost-effectiveness, and reduction of human risk. Deep reinforcement learning (DRL) is widely used for autonomous UAV navigation; however, current techniques often oversimplify the environment or impose movement restrictions. Additionally, most vision-based systems lack precise depth perception, while range finders provide a limited environmental overview, and LiDAR is energy-intensive. To address these challenges, this paper proposes VizNav, a modular DRL-based framework for autonomous UAV navigation in dynamic 3D environments without imposing conventional mobility constraints. VizNav incorporates the Twin Delayed Deep Deterministic Policy Gradient (TD3) algorithm with Prioritized Experience Replay and Importance Sampling (PER) to improve performance in continuous action spaces and mitigate overestimations. Additionally, VizNav employs depth map images (DMIs) to enhance visual navigation by accurately estimating objects’ depth information, thereby improving obstacle avoidance. Empirical results show that VizNav, by leveraging TD3, improves navigation, and the inclusion of PER and DMI further boosts performance. Furthermore, the deployment of VizNav across various experimental settings confirms its flexibility and adaptability. The framework’s architecture separates the agent’s learning from the training process, facilitating integration with various DRL algorithms, simulation environments, and reward functions. This modularity creates a potential to influence RL simulation in various autonomous navigation systems, including robotics control and autonomous vehicles.
Comparison and Optimal Method of Detecting the Number of Maize Seedlings Based on Deep Learning
Authors: Jia Zhijie , Zhang Xinlong , Yang Hongye , Lu Yuan , Liu Jiale , Yu Xun , Feng Dayun , Gao Kexin , Xue Jianfu , Ming Bo , Nie Chenwei , Li Shaokun
Published: April 2024

Effective agricultural management in maize production operations starts with the early quantification of seedlings. Accurately determining plant presence allows growers to optimize planting density, allocate resources, and detect potential growth issues early on. This study provides a comprehensive analysis of the performance of various object detection models in maize production, with a focus on the effects of planting density, growth stages, and flight altitudes. The findings of this study demonstrate that one-stage models, particularly YOLOv8n and YOLOv5n, demonstrated superior performance with AP50 scores of 0.976 and 0.951, respectively, outperforming two-stage models in terms of resource efficiency and seedling quantification accuracy. YOLOv8n, along with Deformable DETR, Faster R-CNN, and YOLOv3-tiny, were identified for further examination based on their performance metrics and architectural features. The study also highlights the significant impact of plant density and growth stage on detection accuracy. Increased planting density and advanced growth stages (particularly V6) were associated with decreased model accuracy due to increased leaf overlap and image complexity. The V2–V3 growth stages were identified as the optimal periods for detection. Additionally, flight altitude negatively affected image resolution and detection accuracy, with higher altitudes leading to poorer performance. In field applications, YOLOv8n proved highly effective, maintaining robust performance across different agricultural settings and consistently achieving rRMSEs below 1.64% in high-yield fields. The model also demonstrated high reliability, with Recall, Precision, and F1 scores exceeding 99.00%, affirming its suitability for practical agricultural use. These findings suggest that UAV-based image collection systems employing models like YOLOv8n can significantly enhance the accuracy and efficiency of seedling detection in maize production. The research elucidates the critical factors that impact the accuracy of deep learning detection models in the context of corn seedling detection and selects a model suited for this specific task in practical agricultural production. These findings offer valuable insights into the application of object detection technology and lay a foundation for the future development of precision agriculture, particularly in optimizing deep learning models for varying environmental conditions that affect corn seedling detection.