bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation on the Sensitivity of Precipitation Simulation to Model Parameterization and Analysis Nudging over Hebei Province, China
Authors: Li Yuanhua , Tian Zhiguang , Chen Xia , Su Xiashu , Yu Entao
Published: April 2024

The physical parameterizations have important influence on model performance in precipitation simulation and prediction; however, previous investigations are seldom conducted at very high resolution over Hebei Province, which is often influenced by extreme events such as droughts and floods. In this paper, the influence of parameterization schemes and analysis nudging on precipitation simulation is investigated using the WRF (weather research and forecasting) model with many sensitivity experiments at the cumulus “gray-zone” resolution (5 km). The model performance of different sensitivity simulations is determined by a comparison with the local high-quality observational data. The results indicate that the WRF model generally reproduces the distribution of precipitation well, and the model tends to underestimate precipitation compared with the station observations. The sensitivity simulation with the Tiedtke cumulus parameterization scheme combined with the Thompson microphysics scheme shows the best model performance, with the highest temporal correlation coefficient (0.45) and lowest root mean square error (0.34 mm/day). At the same time, analysis nudging, which incorporates observational information into simulation, can improve the model performance in precipitation simulation. Further analysis indicates that the negative bias in precipitation may be associated with the negative bias in relative humidity, which in turn is associated with the positive bias in temperature and wind speed. This study highlights the role of parameterization schemes and analysis nudging in precipitation simulation and provides a valuable reference for further investigations on precipitation forecasting applications.
Impacts of Low-Carbon Pilot Policies on the Land Green Use Efficiency in Adjacent Non-Pilot Cities: An Empirical Study Based on 257 Prefecture-Level and above Cities in China
Authors: Li Xinle , Shi Yangyang , Li Xin , Luo Xiang
Published: April 2024

In the context of global climate change, the low-carbon city pilot policy has become an important strategy to promote green development. Based on the panel data from 257 prefecture-level and above cities in China, this study utilized the Super-Efficiency SBM (Slacks-Based Measure) to measure the land green use efficiency and analyzes the impact of the policy on adjacent non-pilot cities using a difference-in-differences model. The findings indicate that the implementation of low-carbon pilot policies can significantly improve the land green use efficiency in adjacent non-pilot cities, which can be primarily ascribed to the spillover effect and catfish effect. A heterogeneity analysis further revealed the positive effects of the policies in the eastern region and non-resource-based cities. This study provides valuable references for relevant legal provisions on environmental regulation and for continuously monitoring and evaluating the policy effects to achieve sustainable development goals.
Systematic Mapping of Circular Economy in Structural Engineering
Authors: Seeberg Hanne Rangnes , Haakonsen Sverre Magnus , Luczkowski Marcin
Published: April 2024

Facing increasing sustainability demands, the construction industry is at a turning point where the implementation of circular economy (CE) strategies plays an essential role in driving the necessary transformation aimed at reducing the environmental impact. To facilitate this shift, structural engineering must effectively integrate circular principles into building design. With the exponential growth of research articles within this field, it is crucial to map the evolution of the research area. The objective of this study is to detail the trends with, challenges to, and research contributions, integration, and material applications of CE principles within structural engineering. Consequently, a systematic mapping of the CE within the field of structural engineering has been conducted in this study. Initially, the mapping process began with the identification of relevant keywords, followed by searches across four databases. Each resulting article was carefully screened against content criteria, culminating in 91 publications that were thoroughly evaluated. The publications were then categorized and analyzed based on attributes such as research type, circular design, materials, and applications. The results are presented through informative figures and tables. The analysis of the research indicates a predominant focus on technical solutions for structural systems, with demountable connections designed to facilitate the future reuse of materials representing more than half of the literature reviewed. A significant portion of the literature also addresses designing from reclaimed elements; these articles reflect a transformation in engineering approaches, incorporating computational design and innovative methodologies. The focus on steel as a structural material is prominent in the reviewed literature. However, there is an increasing focus on timber, which signals a definitive shift toward sustainable structural systems. Recurring challenges identified in the literature regarding the transition to a circular economy (CE) in the construction industry include the need for industry-wide adoption, precise standardization, the integration of digital tools, and the overcoming of related obstacles in policy and market acceptances. Furthermore, the literature demonstrates a significant research gap: the absence of a comprehensive digital framework enabling an effective digital circular structural design workflow.
Mechanical Properties of Fire-Damaged RC Beams Reinforced with Carbon Fiber Mesh
Authors: Cheng Jinsheng , Wang Hao , Xu Zhisong , Yuan Guanglin , Li Qingtao
Published: April 2024

The bearing capacity of reinforced concrete (RC) beam will be weakened by fire. It is necessary to strengthen RC beams after fire. The carbon fiber mesh (CFM) can be used to reinforce RC beams. In this paper, RC beams were exposed to varying temperatures, followed by reinforcement with varying layers of CFM. The influence of the heating temperature and the number of CFM layers on the flexural performance of RC beams was investigated. The results indicated that the cracking loads of RC beams were 18.2, 16.4, 16.3, and 15.5 kN when the RC beams were subjected to room temperatures, 150, 350, and 550 °C. Compared to the unreinforced beams at room temperature, the cracking loads of the RC beams were reduced by 9.89%, 10.44%, and 14.84%. As the quantity of CFM reinforcement layers rises, so does the ultimate bearing capacity. For example, when the temperature was 150 °C, the ultimate loads of the beams with one and three layers of CFM were increased by 20% and 31.76% compared to the reference beam. When the temperature was 350 °C, the ultimate loads of the beams with one and three layers of CFM were increased by 19.51% and 28.04% compared to the RC beam without CFM. When the temperature was 550 °C, the ultimate loads of the beams with one and three layers of CFM were increased by 20% and 26.67% compared to the RC beam without CFM. Fire-damaged RC beams can be strengthened by one layer of CFM and mortar if the temperature was below 350 °C. Fire-damaged RC beams can be strengthened by three layers of CFM and mortar if the temperature was below 550 °C. The mechanical properties can be obviously enhanced.
Spatial Silhouette: A Study on the Creation Strategy of Strong Bamboo Architecture with “Negative Space” as the Main Feature—A Case Study of Phu Quoc Island Visitor Centre, Vietnam
Authors: Li Chaoxian , Ma Jiaojiao , Gao Xiaoming
Published: April 2024

The Gestalt theory of mental completeness in architecture gave rise to the ideas of “positive space” and “negative space”. This research digs into the sturdy structural building process of bamboo architecture, which is essentially distinguished by “negative space”. It examines how bamboo is articulated in architectural space, while attempting to establish a balance between form and structure, with the goal of discovering the current value and spiritual position that bamboo in architecture represents. Using the Phu Quoc Island Visitor Center in Vietnam as an example, we introduce the strong structure concept and examine its design process in terms of spatial operation technique and strong structural expression logic. The fundamental strategy for creating bamboo architecture under this concept is to take the lead in negative space design and use the material capabilities of bamboo to build structural space prototypes. This further encourages the use of green building materials and offers architects working with bamboo a reference.
Understanding Penetration Attenuation of Permeable Concrete: A Hybrid Artificial Intelligence Technique Based on Particle Swarm Optimization
Authors: Zhu Fei , Wu Xiangping , Lu Yijun , Huang Jiandong
Published: April 2024

Permeable concrete is a type of porous concrete with the special function of water permeability, but the permeability of permeable concrete will decrease gradually due to the clogging behavior arising from the surrounding environment. To reliably characterize the clogging behavior of permeable concrete, particle swarm optimization (PSO) and random forest (RF) hybrid artificial intelligence techniques were developed in this study to predict the permeability coefficient of permeable concrete and optimize the aggregate mix ratio of permeable concrete. Firstly, a reliable database was collected and established to characterize the input and output variables for the machine learning. Then, PSO and 10-fold cross-validation were used to optimize the hyperparameters of the RF model using the training and testing datasets. Finally, the accuracy of the developed model was verified by comparing the predicted value with the actual value of the permeability coefficients (R = 0.978 and RMSE = 1.3638 for the training dataset; R = 0.9734 and RMSE = 2.3246 for the testing dataset). The proposed model can provide reliable predictions of the clogging behavior that permeable concrete may face and the trend of its development.
The Impact of Building Information Modeling Technology on Cost Management of Civil Engineering Projects: A Case Study of the Mombasa Port Area Development Project
Authors: Nsimbe Allan , Di Junzhen
Published: April 2024

Introduction: This study examines the impact of building information modeling on the cost management of engineering projects, focusing specifically on the Mombasa Port Area Development Project. The objective of this research is to determine the mechanisms through which building information modeling facilitates stakeholder collaboration, reduces construction-related expenses, and enhances the precision of cost estimation. Furthermore, this study investigates barriers to execution, assesses the impact on the project’s transparency, and suggests approaches to maximize resource utilization. Methodology: This study employed a mixed-method research design comprising document reviews and surveys. During the document review, credible databases including ScienceDirect and Institute of Electrical and Electronics Engineers Xplore were explored. The survey included 69 professionals, among which were project managers, cost estimators, and building information modeling administrators. The mixed-methods approach prioritized ethical considerations and the statistical Package for the Social Sciences and Microsoft Excel were used in the analysis. Results: The results show that building information modeling is a valuable system for organizations looking to reduce project costs. The results note that the technology improves cost estimation accuracy, facilitates the identification of cost-related risks, and promotes collaborative decision-making. Conclusions: Building information modeling is an effective cost-estimating technology that positively impacts additional project aspects such as decision-making, collaboration, performance, and delivery time. Therefore, the Mombasa Port Area Development Project should inspire other stakeholders in engineering and construction to embrace building information modeling.
The Extraction of Roof Feature Lines of Traditional Chinese Village Buildings Based on UAV Dense Matching Point Clouds
Authors: Zhou Wenlong , Fu Xiangxiang , Deng Yunyuan , Yan Jinbiao , Zhou Jialu , Liu Peilin
Published: April 2024

Traditional Chinese buildings serve as a carrier for the inheritance of traditional culture and national characteristics. In the context of rural revitalization, achieving the 3D reconstruction of traditional village buildings is a crucial technical approach to promoting rural planning, improving living environments, and establishing digital villages. However, traditional algorithms primarily target urban buildings, exhibiting limited adaptability and less ideal feature extraction performance for traditional residential buildings. As a result, guaranteeing the accuracy and reliability of 3D models for different types of traditional buildings remains challenging. In this paper, taking Jingping Village in Western Hunan as an example, we propose a method that combines multiple algorithms based on the slope segmentation of the roof to extract feature lines. Firstly, the VDVI and CSF algorithms are used to extract the building and roof point clouds based on the MVS point cloud. Secondly, according to roof features, village buildings are classified, and a 3D roof point cloud is projected into 2D regular grid data. Finally, the roof slope is segmented via slope direction, and internal and external feature lines are obtained after refinement through Canny edge detection and Hough straight line detection. The results indicate that the CSF algorithm can effectively extract the roofs of I-shaped, L-shaped, and U-shaped traditional buildings. The accuracy of roof surface segmentation based on slope exceeds 99.6%, which is significantly better than the RANSAC algorithm and the region segmentation algorithm. This method is capable of efficiently extracting the characteristic lines of roofs in low-rise buildings within traditional villages. It provides a reference method for achieving the high-precision modeling of traditional village architecture at a low cost and with high efficiency.
Genetic Diagnosis of Retinoblastoma Using Aqueous Humour—Findings from an Extended Cohort
Authors: Gerrish Amy , Mashayamombe-Wolfgarten Chipo , Stone Edward , Román-Montañana Claudia , Abbott Joseph , Jenkinson Helen , Millen Gerard , Gurney Sam , McCalla Maureen , Staveley Sarah-Jane , Kainth Anu , Kirk Maria , Bowen Claire , Cavanagh Susan , Bunstone Sancha , Carney Megan , Mohite Ajay , Clokie Samuel , Reddy M. Ashwin , Foster Alison , Allen Stephanie , Parulekar Manoj , Cole Trevor
Published: April 2024

The identification of somatic RB1 variation is crucial to confirm the heritability of retinoblastoma. We and others have previously shown that, when tumour DNA is unavailable, cell-free DNA (cfDNA) derived from aqueous humour (AH) can be used to identify somatic RB1 pathogenic variation. Here we report RB1 pathogenic variant detection, as well as cfDNA concentration in an extended cohort of 75 AH samples from 68 patients. We show cfDNA concentration is highly variable and significantly correlated with the collection point of the AH. Cell-free DNA concentrations above 5 pg/µL enabled the detection of 93% of known or expected RB1 pathogenic variants. In AH samples collected during intravitreal chemotherapy treatment (Tx), the yield of cfDNA above 5 pg/µL and subsequent variant detection was low (≤46%). However, AH collected by an anterior chamber tap after one to three cycles of primary chemotherapy (Dx1+) enabled the detection of 75% of expected pathogenic variants. Further limiting our analysis to Dx1+ samples taken after ≤2 cycles (Dx ≤ 2) provided measurable levels of cfDNA in all cases, and a subsequent variant detection rate of 95%. Early AH sampling is therefore likely to be important in maximising cfDNA concentration and the subsequent detection of somatic RB1 pathogenic variants in retinoblastoma patients undergoing conservative treatment.
Focused Ultrasound-Enhanced Liquid Biopsy: A Promising Diagnostic Tool for Brain Tumor Patients
Authors: Bakker Akke , Ixkes Anna E. , Venugopal Hema , Ries Mario G. , Lak Nathalie S. M. , de Vos Filip Y. F. L. , van Vuurden Dannis G. , Snijders Tom J.
Published: April 2024

The performance of minimally invasive molecular diagnostic tools in brain tumors, such as liquid biopsy, has so far been limited by the blood–brain barrier (BBB). The BBB hinders the release of brain tumor biomarkers into the bloodstream. The use of focused ultrasound in conjunction with microbubbles has been shown to temporarily open the BBB (FUS-BBBO). This may enhance blood-based tumor biomarker levels. This systematic review provides an overview of the data regarding FUS-BBBO-enhanced liquid biopsy for primary brain tumors. A systematic search was conducted in PubMed and Embase databases with key terms “brain tumors”, “liquid biopsy”, “FUS” and their synonyms, in accordance with PRISMA statement guidelines. Five preclinical and two clinical studies were included. Preclinical studies utilized mouse, rat and porcine glioma models. Biomarker levels were found to be higher in sonicated groups compared to control groups. Both stable and inertial microbubble cavitation increased biomarker levels, whereas only inertial cavitation induced microhemorrhages. In clinical studies involving 14 patients with high-grade brain tumors, biomarker levels were increased after FUS-BBBO with stable cavitation. In conclusion, FUS-BBBO-enhanced liquid biopsy using stable cavitation shows diagnostic potential for primary brain tumors. Further research is imperative before integrating FUS-BBBO for liquid biopsy enhancement into clinical practice.
National Experiences from 30 Years of Provider-Mediated Cascade Testing in Lynch Syndrome Families—The Danish Model
Authors: Lindberg Lars Joachim , Wadt Karin A. W. , Therkildsen Christina , Petersen Helle Vendel
Published: April 2024

Cascade genetic testing and surveillance reduce morbidity and mortality in Lynch syndrome. However, barriers to conveying information about genetic disorders within families result in low uptake of genetic testing. Provider-mediated interventions may increase uptake but raise legal and ethical concerns. We describe 30 years of national experience with cascade genetic testing combining family- and provider-mediated contact in Lynch syndrome families in the Danish Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Register. We aimed to estimate the added value of information letters to family members in Lynch syndrome families (provider-mediated contact) compared to family members not receiving such letters and thus relying on family-mediated contact. National clinical practice for cascade genetic testing, encompassing infrastructure, legislation, acceptance, and management of the information letters, is also discussed. Cascade genetic testing resulted in 7.3 additional tests per family. Uptake of genetic testing was 54.4% after family-mediated and 64.9% after provider-mediated contact, corresponding to an odds ratio of 1.8 (p < 0.001). The uptake of genetic testing was highest in the first year after diagnosis of Lynch syndrome in the family, with 72.5% tested after provider-mediated contact. In conclusion, the Danish model combining family- and provider-mediated contact can increase the effect of cascade genetic testing.
Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges
Authors: Zheng Shunzhen , Chan Siew Wee , Liu Fei , Liu Jun , Chow Pierce Kah Hoe , Toh Han Chong , Hong Wanjin
Published: April 2024

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for ~90% of liver neoplasms. It is the second leading cause of cancer-related deaths and the seventh most common cancer worldwide. Although there have been rapid developments in the treatment of HCC over the past decade, the incidence and mortality rates of HCC remain a challenge. With the widespread use of the hepatitis B vaccine and antiviral therapy, the etiology of HCC is shifting more toward metabolic-associated steatohepatitis (MASH). Early-stage HCC can be treated with potentially curative strategies such as surgical resection, liver transplantation, and radiofrequency ablation, improving long-term survival. However, most HCC patients, when diagnosed, are already in the intermediate or advanced stages. Molecular targeted therapy, followed by immune checkpoint inhibitor immunotherapy, has been a revolution in HCC systemic treatment. Systemic treatment of HCC especially for patients with compromised liver function is still a challenge due to a significant resistance to immune checkpoint blockade, tumor heterogeneity, lack of oncogenic addiction, and lack of effective predictive and therapeutic biomarkers.
HPV DNA Integration at Actionable Cancer-Related Genes Loci in HPV-Associated Carcinomas
Authors: Sastre-Garau Xavier , Estrada-Virrueta Lilia , Radvanyi François
Published: April 2024

In HPV-associated carcinomas, some examples of cancer-related genes altered by viral insertion and corresponding to potential therapeutic targets have been described, but no quantitative assessment of these events, including poorly recurrent targets, has been reported to date. To document these occurrences, we built and analyzed a database comprised of 1455 cases, including HPV genotypes and tumor localizations. Host DNA sequences targeted by viral integration were classified as “non-recurrent” (one single reported case; 838 loci), “weakly recurrent” (two reported cases; 82 loci), and highly recurrent (≥3 cases; 43 loci). Whereas the overall rate of cancer-related target genes was 3.3% in the Gencode database, this rate increased to 6.5% in “non-recurrent”, 11.4% in “weakly recurrent”, and 40.1% in “highly recurrent” genes targeted by integration (p = 4.9 × 10−4). This rate was also significantly higher in tumors associated with high-risk HPV16/18/45 than other genotypes. Among the genes targeted by HPV insertion, 30.2% corresponded to direct or indirect druggable targets, a rate rising to 50% in “highly recurrent” targets. Using data from the literature and the DepMap 23Q4 release database, we found that genes targeted by viral insertion could be new candidates potentially involved in HPV-associated oncogenesis. A more systematic characterization of HPV/host fusion DNA sequences in HPV-associated cancers should provide a better knowledge of HPV-driven carcinogenesis and favor the development of personalize patient treatments.
Theranostic Risk Stratification for Thyroid Cancer in the Genomic Paradigm
Authors: Gulec Seza A. , Meneses Evander
Published: April 2024

Theranostics define diagnostic evaluations directing patient-specific therapeutic decisions. Molecular theranostics involves genomic, transcriptomic, proteomic, metabolomic and finally phenonic definitions thyroid cancer differentiation. It is the functional differentiation that determines the sensitivity and accuracy of RAI imaging as well as the effectiveness of RAI treatment. Total thyroidectomy is performed to empower an anticipated RAI treatment. A preoperative determination of the genomic and transcriptomic profile of the tumor is a strong predictor of response to therapeutic interventions. This article discusses the oncopathophysiologic basis of the theranostic risk stratification approach.
Th2 Cells Are Associated with Tumor Recurrence Following Radiation
Authors: Abdelhakiem Mohamed K. , Bao Riyue , Pifer Phillip M. , Molkentine David , Molkentine Jessica , Hefner Andrew , Beadle Beth , Heymach John V. , Luke Jason J. , Ferris Robert L. , Pickering Curtis R. , Wang Jing H. , Patel Ravi B. , Skinner Heath D.
Published: April 2024

The curative treatment of multiple solid tumors, including head and neck squamous cell carcinoma (HNSCC), utilizes radiation. The outcomes for HPV/p16-negative HNSCC are significantly worse than HPV/p16-positive tumors, with increased radiation resistance leading to worse locoregional recurrence (LRR) and ultimately death. This study analyzed the relationship between immune function and outcomes following radiation in HPV/p16-negative tumors to identify mechanisms of radiation resistance and prognostic immune biomarkers. A discovery cohort of 94 patients with HNSCC treated uniformly with surgery and adjuvant radiation and a validation cohort of 97 similarly treated patients were utilized. Tumor immune infiltrates were derived from RNAseq gene expression. The immune cell types significantly associated with outcomes in the discovery cohort were examined in the independent validation cohort. A positive association between high Th2 infiltration and LRR was identified in the discovery cohort and validated in the validation cohort. Tumor mutations in CREBBP/EP300 and CASP8 were significantly associated with Th2 infiltration. A pathway analysis of genes correlated with Th2 cells revealed the potential repression of the antitumor immune response and the activation of BRCA1-associated DNA damage repair in multiple cohorts. The Th2 infiltrates were enriched in the HPV/p16-negative HNSCC tumors and associated with LRR and mutations in CASP8, CREBBP/EP300, and pathways previously shown to impact the response to radiation.
tRNA-Derived Fragments as Biomarkers in Bladder Cancer
Authors: Strømme Olaf , Heck Kathleen A. , Brede Gaute , Lindholm Håvard T. , Otterlei Marit , Arum Carl-Jørgen
Published: April 2024

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying noninvasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small noncoding RNA such as transfer RNA-derived fragments (tRF) and microRNA. Here, we performed small-RNA next-generation sequencing from EVs from urine and serum, as well as from serum supernatant. RNA was extracted from 15 non-cancer patients (NCPs) with benign findings in cystoscopy and 41 patients with non-muscle invasive BC. Urine and serum were collected before transurethral resection of bladder tumors (TUR-b) and at routine post-surgery check-ups. We compared levels of tRFs in pre-surgery samples to samples from NCPs and post-surgery check-ups. To further verify our findings, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between T1 stage BC patients and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing pre-surgery to post-surgery samples and four DEtRFs were found when comparing pre-surgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.
Targeted Nanoparticle-Based Diagnostic and Treatment Options for Pancreatic Cancer
Authors: Gu Xin , Minko Tamara
Published: April 2024

Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest cancers, presents significant challenges in diagnosis and treatment due to its aggressive, metastatic nature and lack of early detection methods. A key obstacle in PDAC treatment is the highly complex tumor environment characterized by dense stroma surrounding the tumor, which hinders effective drug delivery. Nanotechnology can offer innovative solutions to these challenges, particularly in creating novel drug delivery systems for existing anticancer drugs for PDAC, such as gemcitabine and paclitaxel. By using customization methods such as incorporating conjugated targeting ligands, tumor-penetrating peptides, and therapeutic nucleic acids, these nanoparticle-based systems enhance drug solubility, extend circulation time, improve tumor targeting, and control drug release, thereby minimizing side effects and toxicity in healthy tissues. Moreover, nanoparticles have also shown potential in precise diagnostic methods for PDAC. This literature review will delve into targeted mechanisms, pathways, and approaches in treating pancreatic cancer. Additional emphasis is placed on the study of nanoparticle-based delivery systems, with a brief mention of those in clinical trials. Overall, the overview illustrates the significant advances in nanomedicine, underscoring its role in transcending the constraints of conventional PDAC therapies and diagnostics.
Outcomes of Modified Mayo Stage IIIa and IIIb Cardiac Light-Chain Amyloidosis: Real-World Experience in Clinical Characteristics and Treatment—67 Patients Multicenter Analysis
Authors: Charliński Grzegorz , Steinhardt Maximilian , Rasche Leo , Gonzalez-Calle Veronica , Peña Camila , Parmar Harsh , Wiśniewska-Piąty Katarzyna , Dávila Valls Julio , Olszewska-Szopa Magdalena , Usnarska-Zubkiewicz Lidia , Gozzetti Alessandro , Ciofini Sara , Gentile Massimo , Zamagni Elena , Kurlapski Michał , Legieć Wojciech , Vesole David H. , Jurczyszyn Artur
Published: April 2024

Light-chain amyloidosis (AL) is a rare multisystem disorder characterized by the deposition of misfolded amyloid fibrils derived from monoclonal immunoglobulin light chains in various organs. One of the most common organs involved in AL is the heart, with 50–70% of patients clinically symptomatic at diagnosis. We conducted a multi-center, retrospective analysis of 67 patients diagnosed between July 2012 and August 2022 with the European 2012 modification of Mayo 2004 stage III cardiac AL. The most important factors identified in the univariate Cox analysis contributing to a longer OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1, New York Heart Association functional classification (NYHA FC) ≤ 2, the use of autologous stem cell transplantation (ASCT) after induction treatment, achieving a hematological response (≥very good partial response) and cardiac (≥partial response) response after first-line treatment. The most important prognostic factors with the most significant impact on OS improvement in patients with modified Mayo stage III cardiac AL identified by multivariate Cox analysis are ECOG PS ≤ 1, NYHA FC ≤ 2, and achieving hematological response ≥ VGPR and cardiac response ≥ PR after first-line treatment.
Endovascular Applications for the Management of High-Grade Gliomas in the Modern Era
Authors: Kappel Ari D. , Jha Rohan , Guggilapu Saibaba , Smith William J. , Feroze Abdullah H. , Dmytriw Adam A. , Vicenty-Padilla Juan , Alcedo Guardia Rodolfo E. , Gessler Florian A. , Patel Nirav J. , Du Rose , See Alfred P. , Peruzzi Pier Paolo , Aziz-Sultan Mohammad A. , Bernstock Joshua D.
Published: April 2024

High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood–brain barrier (BBB) penetration, hemodynamic complexities, and drug–tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care.
Robotic versus Laparoscopic Liver Resections for Colorectal Metastases: A Systematic Review and Meta-Analysis
Authors: Safiejko Kamil , Pedziwiatr Michal , Pruc Michal , Tarkowski Radoslaw , Juchimiuk Marcin , Domurat Marian , Smereka Jacek , Anvarov Khikmat , Sielicki Przemyslaw , Kurek Krzysztof , Szarpak Lukasz
Published: April 2024

Colorectal cancer is the third most common cancer worldwide, and the liver is the most common localization of metastatic disease. The incidence of minimally invasive liver surgery is increasing, and robotic surgery (RLR) is believed to overcome some limitations of a laparoscopic approach (LRL). We performed a systematic review and meta-analysis of operative and short-term oncologic outcomes of the laparoscopic versus robotic-assisted liver resection for colorectal liver metastases. An online search of PubMed, Embase, Scopus, and the Cochrane databases was performed. Eight studies involving 3210 patients were considered eligible for the meta-analysis. In the LRL group, a higher conversion to open rate (12.4%) was observed compared to the RLR (6.7%; p = <0.001). 30-day mortality was 0.7% for the LRL group compared to 0.5% for the RLR group (p = 0.76). Mortality in longer periods among LLR and RLR amounted to 18.2% vs. 8.0% for 1-year mortality (p = 0.07), 34.1% vs. 26.7% for 2-year mortality (p = 0.13), and 52.3% vs. 48.3% for 3-year mortality (p = 0.46). The length of hospital stay was 5.6 ± 2.5 vs. 5.8 ± 2.1 days, respectively (p = 0.47). There were no significant differences between the incidence of individual complications in the LRL and RLR groups (p = 0.78). Laparoscopic or robotic approaches for colorectal liver metastases are comparable in terms of safety and effectiveness. There are significant advantages to robotic surgery, although there is still no long-term evidence concerning overall survival, and the number of patients operated on using RLR remains small.
Chimeric Antigen Receptor (CAR) T-Cell Therapy in Hematologic Malignancies: Clinical Implications and Limitations
Authors: Blüm Philipp , Kayser Sabine
Published: April 2024

Chimeric antigen receptor (CAR) T-cell therapy has become a powerful treatment option in B-cell and plasma cell malignancies, and many patients have benefited from its use. To date, six CAR T-cell products have been approved by the FDA and EMA, and many more are being developed and investigated in clinical trials. The whole field of adoptive cell transfer has experienced an unbelievable development process, and we are now at the edge of a new era of immune therapies that will have its impact beyond hematologic malignancies. Areas of interest are, e.g., solid oncology, autoimmune diseases, infectious diseases, and others. Although much has been achieved so far, there is still a huge effort needed to overcome significant challenges and difficulties. We are witnessing a rapid expansion of knowledge, induced by new biomedical technologies and CAR designs. The era of CAR T-cell therapy has just begun, and new products will widen the therapeutic landscape in the future. This review provides a comprehensive overview of the clinical applications of CAR T-cells, focusing on the approved products and emphasizing their benefits but also indicating limitations and challenges.
Treatment of Gastric Cancer Means Surgery, but Not Surgery Alone
Authors: Fabbi Manrica , Bali Christina D. , Lianos Georgios D. , Rausei Stefano
Published: April 2024

Despite numerous studies, gastric cancer (GC) still presents a high mortality rate in Eastern and Western countries, increasing attention for new therapeutic strategies [...]
Robot-Assisted Radical Prostatectomy Performed with the Novel Surgical Robotic Platform Hugo™ RAS: Monocentric First Series of 132 Cases Reporting Surgical, and Early Functional and Oncological Outcomes at a Tertiary Referral Robotic Center
Authors: Totaro Angelo , Scarciglia Eros , Marino Filippo , Campetella Marco , Gandi Carlo , Ragonese Mauro , Bientinesi Riccardo , Palermo Giuseppe , Bizzarri Francesco Pio , Cretì Antonio , Presutti Simona , Russo Andrea , Aceto Paola , Bassi Pierfrancesco , Pierconti Francesco , Racioppi Marco , Sacco Emilio
Published: April 2024

Background: Robotic-assisted surgery is the gold standard for performing radical prostatectomy (RARP), with new robotic devices such as HugoTM RAS gaining prominence worldwide. Objective: We report the surgical, perioperative, and early postoperative outcomes of RARP using HugoTM RAS. Design, setting, and participants: Between April 2022 and October 2023, we performed 132 procedures using the Montsouris technique with a four-robotic-arm configuration in patients with biopsy-proven prostate cancer (PCa). Outcome measures: We collected intraoperative and perioperative data during hospitalization, along with follow-up data at predefined postoperative intervals of 3 and 6 months. Results and limitations: Lymphadenectomy was performed in 25 procedures, with a bilateral nerve-sparing technique in 33 and a monolateral nerve-sparing technique in 33 cases. The mean total surgery time was 242 (±57) min, the mean console time was 124 (±48) min, and the mean docking time was 10 (±2) min. We identified 17 system errors related to robotic arm failures, 9 robotic instrument breakdowns, and 8 significant conflicts between robotic arms. One post-operative complication was classified as Clavien–Dindo 3b. None of the adverse events, whether singular or combined, increased the operative time. Positive margins (pR1) were found in 54 (40.9%) histological specimens, 37 (28.0%) of which were clinically significant. At 3 and 6 months post-surgery, the PSA levels were undetectable in 94.6% and 92.1% of patients, respectively. Social urinary continence was regained in 86% after 6 months. Limitations of our study include its observational monocentric case-series design and the short follow-up data for functional and oncological outcomes. Conclusions: Our initial experience highlights the reliability of the HugoTM RAS system in performing RARP. Additionally, we also list problems and solutions found in our daily work.
Treatment of Pelvic and Spinal Bone Metastases: Radiotherapy and Hyperthermia Alone vs. in Combination
Authors: Kim Jong-Hun , Shin Jin-Yong , Lee Sun-Young
Published: April 2024

Painful pelvic and spinal bone metastases are a considerable challenge for doctors and patients. Conventional therapies include morphine-equivalent medication (MeM) and local radiotherapy (RT), but these interventions are not always successful. More recently, hyperthermia (HT) has been applied to complement RT and MeM, and this complex approach has shown promising synergistic results. The objective of our study was to present the results of RT combined with a special kind of HT (modulated electrohyperthermia, mEHT), in which some of the thermal effect is contributed by equivalent nonthermal components, drastically reducing the necessary power and energy. This retrospective study included 61 patients divided into three groups with pelvic and spinal bone metastases to compare the effects of RT and mEHT alone and in combination (RT + mEHT). A detailed evaluation of pain intensity, measured by the brief pain inventory score, MeM use, and breakthrough pain episodes, revealed no significant differences between RT and mEHT alone; thus, these individual methods were considered equivalent. However, RT + mEHT yielded significantly better results in terms of the above parameters. Clinically, mEHT has a lower risk of adverse thermal effects, and due to its efficacy, mEHT can be used to treat RT-resistant lesions.
Deferral of Treatment for Small Choroidal Melanoma and the Risk of Metastasis: An Investigation Using the Liverpool Uveal Melanoma Prognosticator Online (LUMPO)
Authors: Damato Bertil , Eleuteri Antonio , Taktak Azzam , Hussain Rumana , Fili Maria , Stålhammar Gustav , Heimann Heinrich , Coupland Sarah E.
Published: April 2024

Background: We estimated metastatic-death risk when the treatment of small choroidal melanomas is deferred until growth is observed. Methods: In 24 patients with choroidal melanoma (median diameter 5.85 mm), the exponential growth rate estimated by a mixed-effects model was 4.3% per year. Using the Liverpool Uveal Melanoma Prognosticator Online v.3 (LUMPO3), we measured changes in 15-year metastatic and non-metastatic death risks according to whether the tumor is treated immediately or after observing growth 4 or 12 months later, considering age, sex, and metastasis predictors. Results: In 40-year-old females with 10 mm, disomy 3 and monosomy 3 choroidal melanomas (prevalence 16%), the 15-year absolute risks of metastatic death are 4.2% and 76.6%, respectively, increasing after a 4-month delay by 0.0% and 0.2% and by 3.0% and 2.3% with tumor growth rates of 5.0% and 20.0%, respectively. With 12-month delays, these risks increase by 0.0% and 0.5% and by 1.0% and 7.1%, respectively. Increases in metastatic-death risk are less with smaller tumors and with a higher risk of non-metastatic death. Conclusions: Deferring treatment of choroidal melanomas until documentation of growth may delay iatrogenic visual loss by months or years and is associated with minimal increase in metastatic mortality, at least with small tumors with usual growth rates of up to 40% per year.
Imiquimod Is Effective in Reducing Cervical Intraepithelial Neoplasia: A Systematic Review and Meta-Analysis
Authors: Hamar Balázs , Teutsch Brigitta , Hoffmann Eszter , Hegyi Péter , Harnos Andrea , Nyirády Péter , Hunka Zsombor , Ács Nándor , Bánhidy Ferenc , Melczer Zsolt
Published: April 2024

Introduction: Topical Imiquimod is an immune response modifier approved for the off-label use of vulvar intraepithelial neoplasia. We conducted this systematic review and meta-analysis to investigate the efficacy and safety of Imiquimod in treating cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)-positive patients. Methods: The study was prospectively registered (CRD420222870) and involved a comprehensive systematic search of five medical databases on 10 October 2022. We included articles that assessed the use of Imiquimod in cervical dysplasia and HPV-positive patients. Pooled proportions, risk ratios (RRs), and corresponding 95% confidence intervals (CIs) were calculated using a random effects model to generate summary estimates. Statistical heterogeneity was assessed using I2 tested by the Cochran Q tests. Results: Eight articles reported on 398 patients who received Imiquimod out of 672 patients. Among CIN-2–3 patients, we observed a pooled regression rate of 61% (CI: 0.46–0.75; I2: 77%). When compared, Imiquimod was inferior to conization (RR: 0.62; CI: 0.42–0.92; I2: 64%). The HPV clearance rate in women who completed Imiquimod treatment was 60% (CI: 0.31–0.81; I2: 57%). The majority of side effects reported were mild to moderate in severity. Conclusions: Our findings indicate that topical Imiquimod is safe and effective in reducing cervical intraepithelial neoplasia and promoting HPV clearance. However, it was found to be inferior compared to conization. Imiquimod could be considered a potential medication for high-grade CIN patients and should be incorporated into guidelines for treating cervical dysplasia.
Considerations for Treatment in Clinical Care of Spinal Muscular Atrophy Patients
Authors: Voight Stephanie , Arya Kapil
Published: April 2024

Spinal Muscular Atrophy is a neurodegenerative disease which can lead to muscle weakness, paralysis, and in some cases death. There are many factors that contribute to the severity of symptoms and those factors can be used to determine the best course of treatment for the patients. We looked through published literature to create a set of considerations for treatment in patients with Spinal Muscular Atrophy including age, type, SMN2 copies, and any familial considerations. This can serve as a guide for what to consider in the treatment of SMA patients clinically.
Exploring the Influence of Soil Salinity on Microbiota Dynamics in Vitis vinifera cv. “Glera”: Insights into the Rhizosphere, Carposphere, and Yield Outcomes
Authors: Colautti Andrea , Mian Giovanni , Tomasi Diego , Bell Luke , Marcuzzo Patrick
Published: April 2024

In a world grappling with the severe effects induced by climate change, one of the most significant concerns affecting agriculture is the gradual decline in water quality for irrigation associated with reduced rainfalls and the consequent increase in soil salinity. This issue is particularly crucial for grapevine cultivation (Vitis vinifera L.) and the associated winemaking industry. The aroma of the resulting wines and the yield parameters can be influenced both directly by water quality and indirectly due to the effects exerted by salinity on the microbiota, which directly impacts plant health. To gain insights into this topic, our study aimed to analyse the changes induced in the microbiota of both the rhizosphere and the carposphere due to salt stress using a metabarcoding approach, focusing on Vitis vinifera cv. Glera. The control plants were irrigated with rainwater, while the treated plants were irrigated with water containing salt (NaCl). Our findings revealed significant differences in the microbiota (both fungi and bacteria) of the rhizosphere and carposphere between the two treatments. For instance, the Shannon diversity index (i.e., alpha diversity) was lower in the treated plants compared to the control not-treated ones, whilst the beta diversity did not show any differences. Several microbial phyla exhibited better resilience to this abiotic stress (e.g., Ascomycota, Saccharomycetes, Acidobacteria, Proteobacteria, Bacteroidetes), shedding light on their impact on crucial bacterial and fungal groups essential for the subsequent winemaking stages. Additionally, the salt stress negatively affected the yield parameters. This study contributes valuable insights to the viticultural community, providing a deeper understanding of the complex interplay between soil characteristics, microbial communities, and their influence on productivity.