bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Biomechanical Effects of Cardiac Contractility Modulation in Living Myocardial Slices from End-Stage Heart Failure Patients
Authors: Bierhuizen Mark F. A. , Amesz Jorik H. , Langmuur Sanne J. J. , Lam Bobby , Knops Paul , Veen Kevin M. , Manintveld Olivier C. , Kluin Jolanda , de Groot Natasja M. S. , Taverne Yannick J. H. J.
Published: February 2025

Proof-of-concept to determine the direct biomechanical effects of cardiac contractility modulation (CCM) on living myocardial slices (LMS) from patients with end-stage heart failure (HF). Left ventricular LMS from patients with end-stage HF were produced and cultured in a biomimetic system with mechanical loading and electrical stimulation. CCM stimulation (80 mA, 40 ms delay, 21 ms duration) enhanced maximum contractile force (CCM: 1229 µN (587–2658) vs. baseline: 1066 µN (529–2128), p = 0.05) and area under the contractile curve (CCM: 297 (151–562) vs. baseline: 243 (129–464), p = 0.05) but did not significantly impact contractile duration, time to peak, or time to relaxation. Increasing CCM stimulation delay, duration, and amplitude resulted in a higher fraction of LMS with a positive inotropic response. Furthermore, CCM attenuated the negative force-frequency relationship in HF-LMS. CCM stimulation enhanced contractile force in HF-LMS. The fraction of LMS exerting a positive inotropic response to CCM increased with increasing delay, duration, and amplitude settings, suggesting that personalizing stimulation parameters could optimize the beneficial effects of CCM. CCM is a novel device-based therapy that may improve contractile function, ejection fraction, functional outcomes, and quality of life in patients with heart failure. However, continuous efforts are needed to identify true responders to CCM therapy, understand the exact mechanisms, and optimize the contractile response to CCM stimulation. The present study revealed that CCM enhanced the contractile force of HF-LMS in a stimulation setting-dependent manner, reaching a larger fraction of the myocardium while increasing delay, duration, and amplitude. This understanding may contribute to the individualization of CCM stimulation settings.
Quantifying and Predicting the Spread of Established Non-Native Fishes in Peninsular Florida, USA
Authors: Lawson Katelyn M. , Talbert Hannah G. , Hill Jeffrey E.
Published: February 2025

The spread of non-native species plays a substantial role in the designation of a species as invasive, yet the determination and measurement of non-native-species spread is challenging, particularly for fishes, which are limited by aquatic connectivity. Spread has been quantified for fishes in a variety of ways and exact methods vary by region and taxonomic group. In this study, we quantified fish spread in peninsular Florida and used life history traits to understand what factors contribute to the rate at which fish species spread. Using a variety of statistical analyses, we found that fast spreaders in peninsular Florida tend to have a larger body size, narrow diet, shorter time to hatch, greater salinity tolerance, and higher fecundity. However, some variables like parental care, egg diameter, and reproductive guild were the same or very similar across all established species that were included in the analyses. Predicting whether an established species will spread quickly or slowly in Florida may be more challenging than predicting whether an introduced fish species will establish, yet there is support across regions for the use of life history traits in the risk assessment process.
Three-Dimensional Printed Biomimetic Elastomeric Scaffolds: Experimental Study of Surface Roughness and Pore Generation
Authors: Marazzi Daniele , Trovalusci Federica , Nardo Paolo Di , Carotenuto Felicia
Published: February 2025

Tissue engineering is an emerging field within biomedicine, related to developing functional substitutes for damaged tissues or organs. Despite significant advancements, the development of effective engineering tissue constructs remains challenging, particularly when replicating elastic stretchability, which plays a critical role in many tissues. Therefore, the development of tough, elastomeric scaffolds that mimic the complex elasticity of native tissues, such as the myocardium, heart valves, and blood vessels, is of particular interest. This study aims to evaluate a flexible printable material (Formlabs’ Elastic 50A Resin V2) to develop porous 3D scaffolds using additive manufacturing stereolithography (SLA). The elastomeric samples were tested in relation to their swelling behaviour, mechanical properties, and exposure to low temperatures. Additionally, the effects of print orientation, water immersion, and exposure to low temperatures on surface roughness and porosity were investigated to determine the best conditions to enhance scaffold performance in biomedical applications. The results demonstrated that samples printed at 0°, immersed in water, and exposed to low temperature (−80 °C) showed a more uniform microporosity, which could improve the adhesion and growth of cells on the scaffold. This research highlights a practical and economical approach to enhancing elastomeric scaffolds, paving the way for improved outcomes in tissue engineering applications.
A Novel Neural Network Model Based on Real Mountain Road Data for Driver Fatigue Detection
Authors: Peng Dabing , Cai Junfeng , Zheng Lu , Li Minghong , Nie Ling , Li Zuojin
Published: February 2025

Mountainous roads are severely affected by environmental factors such as insufficient lighting and shadows from tree branches, which complicates the detection of drivers’ facial features and the determination of fatigue states. An improved method for recognizing driver fatigue states on mountainous roads using the YOLOv5 neural network is proposed. Initially, modules from Deformable Convolutional Networks (DCNs) are integrated into the feature extraction stage of the YOLOv5 framework to improve the model’s flexibility in recognizing facial characteristics and handling postural changes. Subsequently, a Triplet Attention (TA) mechanism is embedded within the YOLOv5 network to bolster image noise suppression and improve the network’s robustness in recognition. Finally, the Wing loss function is introduced into the YOLOv5 model to heighten the sensitivity to micro-features and enhance the network’s capability to capture details. Experimental results demonstrate that the modified YOLOv5 neural network achieves an average accuracy rate of 85% in recognizing driver fatigue states.
Probing Solid-Binding Peptide Self-Assembly Kinetics Using a Frequency Response Cooperativity Model
Authors: Bader Taylor , Boone Kyle , Johnson Chris , Berrie Cindy L. , Tamerler Candan
Published: February 2025

Biomolecular adsorption has great significance in medical, environmental, and technological processes. Understanding adsorption equilibrium and binding kinetics is essential for advanced process implementation. This requires identifying intrinsic determinants that predict optimal adsorption properties at bio–hybrid interfaces. Solid-binding peptides (SBPs) have targetable intrinsic properties involving peptide–peptide and peptide–solid interactions, which result in high-affinity material-selective binding. Atomic force microscopy investigations confirmed this complex interplay of multi-step peptide assemblies in a cooperative modus. Yet, most studies report adsorption properties of SBPs using non-cooperative or single-step adsorption models. Using non-cooperative kinetic models for predicting cooperative self-assembly behavior creates an oversimplified view of peptide adsorption, restricting implementing SBPs beyond their current use. To address these limitations and provide insight into surface-level events during self-assembly, a novel method, the Frequency Response Cooperativity model, was developed. This model iteratively fits adsorption data through spectral analysis of several time-dependent kinetic parameters. The model, applied to a widely used gold-binding peptide data obtained using a quartz crystal microbalance with dissipation, verified multi-step assembly. Peak deconvolution of spectral plots revealed distinct differences in the size and distribution of the kinetic rates present during adsorption across the concentrations. This approach provides new fundamental insights into the intricate dynamics of self-assembly of biomolecules on surfaces.
Rapid Microfluidic Ion-Exchange Optode System for Point-of-Care Determination of Sodium Concentration in Serum
Authors: Huang Kuan-Hsun , Yu Cheng-Xue , Lee Chia-Chun , Tseng Chin-Chung , Fu Lung-Ming
Published: February 2025

A microfluidic system for detecting sodium ions (Na+) has been developed, incorporating a micro finger-pump chip and a micro-spectrometer platform to measure Na+ concentration in human serum. A small volume (10 μL) of serum sample is introduced into the microchip and reacted with a preloaded reagent mixture through a two-step finger-pump actuation process. The resulting purple complex is directed into the detection area of the chip and analyzed using the micro-spectrometer at wavelengths of 555 and 666 nm. The Na+ concentration is then inversely derived from the measured A555/A666 absorbance ratio using self-written software installed on a Raspberry Pi. The entire detection process is completed in just 3 min, offering a significant advantage in meeting clinical needs compared to the traditional reporting turnaround time of several hours in medical institutions. The experimental results indicate a linear relationship between the measured absorbance ratio and Na+ concentration within the range of 1–200 mM, with a correlation coefficient of R2 = 0.9989. Additionally, the detection results from 60 serum samples collected from chronic kidney disease (CKD) patients showed a strong agreement with those obtained using the conventional indirect ion-selective electrode (ISE) method, achieving a correlation coefficient of R2 = 0.9885 and an average recovery rate of 99.4%. In summary, the proposed system provides a practical, affordable, and rapid alternative to conventional Na+ detection methods, making it highly promising for point-of-care (POC) testing applications.
Biomass-Derived Carbon Dots as Fluorescent Probes for Label-Free Sensing of Hemin and as Radical Scavengers
Authors: Sharma Neha , Lee Hae-Jeung
Published: February 2025

Carbon dots (CDs) derived from biomass are promising fluorescent probes for specific analyte detection due to their specificity, biocompatibility, selectivity, and sensitivity. In this work, carbon dots were prepared hydrothermally from natural material, Myrica esculenta fruits (hereafter referred to as MPCDs), without adding any chemicals. The prepared MPCDs were characterized using optical, microscopic, and spectroscopic methods that revealed the presence of numerous functional groups and fluorescent properties. MPCDs exhibited exceptional characteristics such as water solubility, photostability, excitation-dependent fluorescence emission, and ionic stability. Transmission electron microscopy found that the average size of the MPCDs was 8 nm. MPCDs exhibited remarkable sensing ability for hemin, with a good linearity (R2 = 0.999) and a lower limit of detection of 14.1 nM. MPCDs demonstrated fluorescence quenching-based detection of hemin, primarily owing to ground state complex formation and the inner filter effect. Furthermore, the prepared material exhibited excellent antioxidant potential against 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl radicals with EC50 values of 25.4 and 205.4 µg/mL, respectively. The study suggests that CDs from Myrica esculenta fruits could be used as optical sensors for hemin detection as well as to scavenge selected radicals.
Unveiling the Truth in Pain: Neural and Behavioral Distinctions Between Genuine and Deceptive Pain
Authors: Zanelli Vanessa , Lui Fausta , Casadio Claudia , Ricci Francesco , Carpentiero Omar , Ballotta Daniela , Ambrosecchia Marianna , Ardizzi Martina , Gallese Vittorio , Porro Carlo Adolfo , Benuzzi Francesca
Published: February 2025

Background/Objectives: Fake pain expressions are more intense, prolonged, and include non-pain-related actions compared to genuine ones. Despite these differences, individuals struggle to detect deception in direct tasks (i.e., when asked to detect liars). Regarding neural correlates, while pain observation has been extensively studied, little is known about the neural distinctions between processing genuine, fake, and suppressed pain facial expressions. This study seeks to address this gap using authentic pain stimuli and an implicit emotional processing task. Methods: Twenty-four healthy women underwent an fMRI study, during which they were instructed to complete an implicit gender discrimination task. Stimuli were video clips showing genuine, fake, suppressed pain, and neutral facial expressions. After the scanning session, participants reviewed the stimuli and rated them indirectly according to the intensity of the facial expression (IE) and the intensity of the pain (IP). Results: Mean scores of IE and IP were significantly different for each category. A greater BOLD response for the observation of genuine pain compared to fake pain was observed in the pregenual anterior cingulate cortex (pACC). A parametric analysis showed a correlation between brain activity in the mid-cingulate cortex (aMCC) and the IP ratings. Conclusions: Higher IP ratings for genuine pain expressions and higher IE ratings for fake ones suggest that participants were indirectly able to recognize authenticity in facial expressions. At the neural level, pACC and aMCC appear to be involved in unveiling the genuine vs. fake pain and in coding the intensity of the perceived pain, respectively.
Multiple Linear Regression Inversion of the Ground Stress Field in Rock Masses for Tunnel Engineering: A Novel Approach to Stress Field Reconstruction
Authors: Meng Wei , Zhou Hongyang , Luo Chun , Qin Shuai , Zhang Xuefu , Chen Binke
Published: February 2025

The inversion of the ground stress field in rock masses is critical for accurate tunnel and underground engineering design. This study addresses the challenge of accurately capturing both the primary and secondary stress field components in rock masses. The ground stress field consists of the primary stress field, generated by applied tectonic loads, and a secondary stress field, which cannot be fully explained by these loads and is attributed to long-term tectonic processes. This unexplained secondary stress field is often non-random in nature. To improve the accuracy of the ground stress field inversion, we propose prioritizing the use of a regression model with a constant term. This model better accounts for the secondary stress field by capturing long-term tectonic influences. The constant term in the regression model is shown to represent the non-random secondary stress field, which cannot be explained by applied tectonic loads. Furthermore, we define two key conditions for applying this regression model: (1) the constant term should not exceed the maximum measured stress and preferably should not surpass the minimum measured stress, and (2) the residual sum of squares of the regression model with a constant term should be smaller than that of the model without a constant term. By incorporating the constant term, the model improves the representation of both primary and secondary stress fields, offering a more accurate inversion of the ground stress field, especially when the stress field contribution from independent variables is incomplete.
Chemical Stabilisation of Clayey Soil—Comparison of a Variety of Additives with Respect to Their Effects on the Soil Compressive Strength and Shear Strength
Authors: Bonić Zoran , Zlatanović Elefterija , Marinković Nemanja , Romić Nikola , Davidović Nebojša , Djorić-Veljković Snežana , Djordjević Dragan M.
Published: February 2025

The unconfined compressive strength and shear strength represent the basic mechanical properties of clayey soil. If the soil in its natural state does not have sufficiently good mechanical properties, in engineering practice, it can be improved by chemical stabilisation of the soil. The stabilisation procedure involves adding reagent(s) to the soil with the aim of permanent improvement in the mechanical properties of the soil. In this study, the individual effects of seven different chemical stabilisers (traditional and alternative) on the mechanical properties of clayey soil were analysed. In the first stage of the research, comprehensive analyses were conducted on the effect of each of the selected stabilisers on the compressive strength of the soil. Each of the selected stabilisers was considered with three different content percentages in the soil mixture, with the aim of determining the optimal stabiliser content. Unconfined compressive tests were conducted to determine the unconfined compressive strength (UCS) of the soil. In the second stage of the research, extensive analyses of the effects of each of the selected stabilisers alone on the improvement in soil shear strength parameters (cohesion and internal friction angle), were carried out with the optimal content of each of the stabilisers. The shear strength parameters were determined by direct shear tests. Both stages of the research were conducted at three different time intervals after the chemical stabilisation (3, 14, and 28 days) in order to determine the long-term efficiency of the chemical treatment of clayey soil. Based on detailed comparative analyses, it was determined that all the selected stabilisers contributed to a lesser or greater extent to a significant improvement in the analysed mechanical properties of clayey soil. A statistical analysis of the obtained results was also conducted using the method of analysis of variance (ANOVA), on the basis of which the individual effect of each selected stabiliser on improving the mechanical properties of clayey soil was validated and quantified.
An Empirical Study of Contractors’ Bidding Trends in Recurrent Bidding: A Case of Singapore Public Sector Construction Projects
Authors: Zhang Yixi , Oo Bee Lan , Runeson Goran , Lim Benson Teck Heng
Published: February 2025

There have been limited empirical studies that aimed to establish the tenability of the stationarity assumption in recurrent construction bidding, and thus the need for and importance of allowing for continuity in bidding models remain unexplored. This study examined the bidding trends of individual contractors according to their level of experience in recurrent bidding, to test the tenability of the stationarity assumption. The data sample was a past bidding dataset of Singapore public sector construction projects over a five-year period between 2017 and 2021, with over 8000 bidding records from more than 900 contractors. The results show that there were statistically significant changes in the contractors’ bidding trends, irrespective of their level of experience in recurrent bidding and different time periodicities, ranging between 10 and 20 months. Thus, the stationarity assumption that contractors behave in a probabilistically consistent way over time, regardless of changing conditions, was untenable for the data sample involved. The observed changes in the contractors’ bidding trends cannot be regarded as random, but represent a continuous strategic process in response to changes in market forces. It is postulated that the possible causes of changes vary among individual contractors, in which there are a set of varying internal and external factors they consider at the time of bidding. The findings have implications for future bidding modelling attempts, in allowing for continuity in recurrent bidding. Contractors should systematically review and re-optimize their bidding strategy by leveraging their historical bidding data and bidding feedback information from clients, since their potential competitors will do the same thing for recurrent bidding.
Experimental Study of Energy Recovery Ventilator for Enhancing Indoor Air Quality in Daycare Centers: A Case Study in South Korea
Authors: Kim Daeung Danny , Kang Kyungmo
Published: February 2025

Improving indoor air quality (IAQ) in daycare centers is essential due to children’s vulnerability to pollutants and prolonged indoor exposure. To address these challenges, energy recovery ventilators (ERVs) with varying filtration efficiencies were evaluated through field measurements and CONTAM simulations. Baseline assessments of CO2 and PM2.5 levels revealed significant impacts from outdoor pollutant infiltration. ERVs successfully reduced CO2 concentrations, maintaining levels below 1000 ppm during most occupancy periods. However, low-efficiency filters (MERV 8 or lower) permitted outdoor particulate matter infiltration, increasing indoor PM2.5 levels. High-performance filters (MERV 13 or higher) reduced indoor PM2.5 concentrations by up to 50%, significantly improving air quality. Findings emphasize the necessity of combining high-efficiency filtration with ERVs to mitigate pollutant infiltration and ensure healthy indoor environments. Policymakers and practitioners are urged to implement ventilation systems equipped with MERV 13 or higher filters, particularly in regions with high outdoor pollution. These strategies are critical for safeguarding children’s health and meeting IAQ standards in daycare facilities.
Robotic Surgery in the Management of Renal Tumors During Pregnancy: A Narrative Review
Authors: Dell’Atti Lucio , Slyusar Viktoria
Published: February 2025

Renal masses are uncommon during pregnancy; they represent the most frequently encountered urological cancer in pregnant patients and require careful surgical planning. The introduction of robotic surgical systems aims to address these challenges by simplifying intra-corporeal suturing and reducing technical complexity. Robot-assisted laparoscopic renal surgery offers potential benefits over both open surgery and conventional laparoscopy, providing greater precision and reduced invasiveness, particularly in tumor excision and suturing. Although urological tumors during pregnancy are rare, early detection significantly improves outcomes by enabling intervention before the tumor advances and while the uterus remains relatively small. The decision regarding the timing and necessity of surgery in pregnant patients requires a careful assessment of maternal health, fetal development, and the progression of the disease. Risks for adverse pregnancy outcomes should be explained, and the patient’s decision about pregnancy termination should be considered. Radical nephrectomy or nephron-sparing surgery are essential treatments for the management of renal tumors. Effective management demands close collaboration between a multidisciplinary team and the patient to ensure individualized care. The aim of this review was to evaluate the renal tumors during pregnancy in terms of epidemiology, risk factors, diagnosis and the safety of a robot-assisted laparoscopic approach in the management of these tumors.
Relationship of Desmoplastic Reaction and Tumour Budding in Primary and Lung Metastatic Lesions of Colorectal Cancer and Their Prognostic Significance
Authors: Kobayashi Toshinori , Ishida Mitsuaki , Matsui Hiroshi , Uehara Hiroki , I Shoichiro , Yamada Norikazu , Igarashi Yuto , Hagiwara Chie , Mori Yoshihiro , Taniguchi Yohei , Saito Tomohito , Hino Haruaki , Hirose Yoshinobu , Murakawa Tomohiro , Watanabe Jun
Published: February 2025

Background/Objectives: Histopathological indicators, including desmoplastic reaction (DR) and tumour budding (TB), are significant prognostic indicators for metastatic liver lesions in patients with colorectal cancer (CRC). However, the relationship of DR and TB in primary CRC and metastatic lung lesions and their prognostic significance has not yet been examined. This study aimed to elucidate the association of DR and TB in primary CRC and metastatic lung lesions. Methods: Patients with pT3 or pT4 CRC with lung metastasis who underwent surgical resection of the primary CRC and synchronous or metachronous metastatic lung lesions were enrolled. DR was classified into immature (IM) and non-IM types, and TB was classified into TB1 (<4 buds), TB2 (5–9 buds) and TB3 (≥10 buds) in both the primary CRC and metastatic lung lesions. Results: Overall, 40 patients with CRC (males, 21; females, 19; median age, 70 years; right-side colon, 6; left-side colon, 9; rectum, 25; pT3, 31; pT4, 9) were evaluated. Six and thirty-four patients were classified as having IM and non-IM DR in the metastatic lung lesions, respectively. Thirty-one, seven, and two patients were classified as having TB1, TB2, and TB3, respectively. There was no significant correlation between primary and lung metastatic lesions for DR (κ = 0.08, p = 0.086), whereas TB demonstrated a moderate correlation (κ = 0.47, p = 0.015). The presence of IM DR and TB2/3 in metastatic lung lesions significantly correlated with poor overall survival (p = 0.0020 and 0.044, respectively). Conclusions: histological indicators of metastatic lung lesions in CRC may provide important prognostic information for better patient care.
Epidemiology and Outcome of Primary Central Nervous System Tumors Treated at King Hussein Cancer Center
Authors: Al-Hussaini Maysa , Al-Ani Abdallah , Amarin Justin Z. , Al Sharie Sarah , Obeidat Mouness , Musharbash Awni , Al Shurbaji Amer A. , Ibrahimi Ahmad Kh. , Al-Mousa Abdellatif , Sarhan Nasim , Amayiri Nisreen , Amarin Rula , Alawabdeh Tala , Alzoubi Qasem , Abu Laban Dima , Maraqa Bayan , Jamal Khaled , Mansour Asem
Published: February 2025

Background and Objectives: Primary central nervous system (CNS) tumors are often associated with relatively poor outcomes. Data on the epidemiology and outcome of CNS tumors in Jordan are scarce. We aim to report the epidemiology and outcome of primary CNS tumors of patients managed at a comprehensive cancer care center in Jordan. Methods: We performed a retrospective chart review of all Jordanian patients with a primary CNS tumor diagnosis who were managed at the center between July 2003 and June 2019. We included all entities described in the 2021 CNS WHO classification system, in addition to pituitary neuroendocrine tumors (PitNETs). We used the Kaplan–Meier method to estimate the 1-year, 2-year, and 5-year overall survival (OS) rates for each entity. Results and Findings: We included 2094 cases. The numbers of pediatrics and adults were 652 (31.1%) and 1442 (68.9%), respectively. The three most common groups of tumors were “gliomas, glioneuronal tumors, and neuronal tumors” (n = 1200 [57.30%]), followed by meningiomas (n = 261 [12.5%]), embryonal tumors (n = 234 [11.2%]). The three most common tumor families were adult-type diffuse gliomas (n = 709 [33.8%]), medulloblastoma (n = 199 [9.5%]), and circumscribed astrocytic gliomas (n = 183 [8.7%]). The median survival for the entire cohort was 97 months (95CI; 81–112). Survival was significantly worse for males and adults compared to their respective counterparts. Among the most common tumor group, “gliomas, glioneuronal tumors, and neuronal tumors”, OS rates for adult-type diffuse gliomas were significantly lower than all other types. Overall, adult gliomas with IDH-mutations had a survival advantage over wildtype cases (IDH-mutant 1-year OS, 89% [82–97%] vs. IDH-wildtype 1-year OS, 60% [52–70%]; p < 0.001). Conclusions: We present a detailed analysis of the primary CNS tumors diagnosed in the largest cancer center in Jordan between 2003 and 2019. We compared the epidemiology and overall survival of these patients to worldwide estimates and found the epidemiology and outcome of these tumors comparable to worldwide trends.
Cell Models of Castration Resistant and High Dose Testosterone-Resistant Prostate Cancer Recapitulate the Heterogeneity of Response Observed in Clinical Practice
Authors: Graham Laura S. , Su Lih-Jen , Nicklawsky Andrew , Feng Frances Xiuyan , Orlicky David , Petraccione Joseph , Salzmann-Sullivan Maren , Nordeen Steven K. , Flaig Thomas W.
Published: February 2025

The use of supraphysiologic testosterone, particularly when alternated with an anti-androgen agent in men with metastatic castration-resistant prostate cancer (CRPC), has demonstrated promising results in clinical trials. As the use of this therapy in clinical practice is more widely adopted, there will be a growing need to understand the mechanisms of resistance. To that end, we independently derived three separate cell models of testosterone-sensitive CRPC. From each CRPC line, high dose testosterone-resistance (HTR) lines were selected. We demonstrated the differential response of the three CRPC lines to a high dose of testosterone in vitro and in vivo. We subsequently demonstrated the resistance of the HTR lines to testosterone and varying responses to testosterone withdrawal in vivo. The heterogeneity in responses to hormonal manipulation is correlated with varying levels of androgen receptor expression within the population. Overall, we show that we have developed three models of HTR that can be used to study the mechanisms of high dose testosterone resistance and identify potential therapeutic targets.
Risk Assessment Models for Predicting Venous Thromboembolism in Patients with Pancreatic Cancer
Authors: Frere Corinne , Gourgou Sophie , Winter Audrey , Gauthier Ludovic , Canivet Cindy , Crichi Benjamin , Marjanovic Zora , Yannoutsos Alexandra , Bensaoula Okba , Buscail Louis , Bournet Barbara , Farge Dominique
Published: February 2025

Background: Data on the performance of the Khorana, PROTECHT, and ONKOTEV risk assessment models (RAMs) to predict venous thromboembolism (VTE) in patients with pancreatic cancer (PC) receiving outpatient chemotherapy remain limited. We performed a head-to-head comparison of these RAMs in patients with newly diagnosed PC enrolled in the nationwide, multicenter, and prospective BACAP cohort. Methods: The Khorana, PROTECHT, and ONKOTEV scores were calculated at enrollment prior to chemotherapy. Patients were stratified into intermediate- and high-VTE-risk groups according to each RAM. The primary study outcome was VTE at a 6-month follow-up. The accuracy and discriminatory performance of the scores were assessed by calculating time-dependent Brier scores and c-indexes. Sub-distribution hazard ratios (SHRs) between high- and intermediate-risk patients were estimated. Results: Of 762 PC patients, 73 developed VTE within 6 months. In the competing risk analysis, the cumulative incidence of VTE at 6 months was 16.4% (95% CI, 13.8–19.1). The time-dependent Brier score was 0.14 (95% CI, 0.12–0.15) for all scores, indicating well-calibrated predictions. The respective time-dependent c-index of the Khorana, the PROTECHT, and the ONKOTEV scores was 0.50 (95% CI, 0.46–0.55), 0.50 (95% CI, 0.49–0.51), and 0.53 (95% CI, 0.48–0.58), indicating poor discrimination. The SHRs between high- and intermediate-risk patients ranged from 1.05 (95% CI, 0.76–1.44) for the ONKOTEV score to 1.06 (95% CI, 0.77–1.45) for the Khorana score. Conclusion: In newly diagnosed PC patients receiving outpatient chemotherapy, the Khorana, PROTECHT, and ONKOTEV scores demonstrated a poor performance in predicting VTE at 6 months, highlighting the need for new tools to guide thromboprophylaxis decisions.
Endoscopic and Surgical Treatment in Early Gastric Cancer: The Gray Zone in Treatment Decision-Making from the Perspectives of Endoscopists
Authors: Bae Jun Yong , Ryu Chang Beom , Lee Moon Sung , Dimitriadis Stavros
Published: February 2025

To treat early gastric cancer, one must choose between endoscopic treatment and surgical treatment. Endoscopic treatment has been developing significantly since the late 1990s and has made great progress up to the present. However, many patients with early gastric cancer still undergo unnecessary surgery or endoscopic procedures. This is due to the existence of a “gray zone” of ambiguities between endoscopic and surgical treatment. These ambiguities arise because the important factors in determining the treatment for early gastric cancer can only be fully understood after endoscopic or surgical resection or because of discrepancies between the factors identifiable before treatment and those identifiable after treatment. This article aims to explore these ambiguous factors and discuss methods and efforts to reduce them.
Challenges and Opportunities for the Clinical Application of the Combination of Immune-Checkpoint Inhibitors and Radiation Therapy in the Treatment of Advanced Pancreatic Cancer
Authors: Kanai Masashi
Published: February 2025

The treatment landscape of pancreatic ductal adenocarcinoma (PDAC) has seen slow progress, with immune-checkpoint inhibitors (ICIs) failing to replicate the success observed in other malignancies. The immune-suppressive tumor microenvironment (TME) in PDAC represents a significant barrier, limiting the activation of an effective antitumor immune response following ICI administration. Radiation therapy (RT), with its immunomodulatory effects, has emerged as a promising partner for ICIs. This review discusses the recent efforts evaluating the combination of ICIs and RT in advanced PDAC. While the combination therapy has demonstrated an acceptable safety profile, the reported clinical efficacy remains modest, particularly for patients with refractory metastatic PDAC. The ongoing phase III trial (JCOG1908E) will clarify whether the combination of ICI and RT improves overall survival in chemo-naïve patients with locally advanced PDAC.
BRCA1 and BRCA2 Mutations in Polish Women with Ductal Carcinoma In Situ
Authors: Feszak Sylwia , Feszak Igor Jarosław , Kluźniak Wojciech , Wokołorczyk Dominika , Stempa Klaudia , Gliniewicz Katarzyna , Uciński Jan , Huzarski Tomasz , Dębniak Tadeusz , Gronwald Jacek , Lubiński Jan , Narod Steven A. , Cybulski Cezary
Published: February 2025

Background/Objectives: Ductal carcinoma in situ (DCIS) is the most common non-invasive form of breast cancer. It is not clear to what extent DCIS is a part of the hereditary breast/ovarian cancer syndrome caused by BRCA1/2 mutations. Therefore, we investigated the association of BRCA1/2 mutations in patients with DCIS and assessed their impact on survival. Methods: We studied 564 Polish women with DCIS for six alleles in BRCA1 (c.181T>G, c.5266dupC, c.4035delA, c.3700_3704del5, c.68_69del and c.5251C>T) and four in BRCA2 (c.658_659del, c.3847_3848del, c.5946del and c.7913_7917del). To investigate the association of BRCA1/2 founder mutations with DCIS risk, we tested 4702 controls as a reference. To analyze survival, mutation carriers were followed for an average of 110 months. Results: A BRCA1 mutation was present in seven (1.24%) cases and in twenty-two (0.47%) controls (OR = 3.27, 95%CI 1.36 to 7.87, p = 0.01). A BRCA2 mutation was present in eight (1.42%) cases versus six (0.13%) controls (OR = 11.3, 95%CI 3.9 to 32.6, p < 0.0001). Three of the fifteen cases with BRCA1/2 mutations developed invasive ipsilateral or contralateral breast cancer, on average 6 years from the diagnosis of DCIS. There were no deaths reported among the 15 mutation carriers with DCIS. Conclusions: DCIS is a part of the hereditary breast/ovarian cancer syndrome caused by BRCA1/2 mutations. Women with DCIS should receive genetic counseling and testing for BRCA1/2 mutations. BRCA1/2 mutations may predispose women to a better DCIS prognosis, but further studies are needed.
Optimizing Pharmacotherapy During Implementation of Enhanced Recovery After Surgery (ERAS) in Ambulatory Urologic Oncology Surgery: Narrative Review
Authors: Shook Jaret K. , Hutson Thomas E. , Singer Eric A. , Ghodoussipour Saum B.
Published: February 2025

Adapting Enhanced Recovery After Surgery (ERAS) protocols to the ambulatory surgery setting is an ongoing need. While all surgical procedures necessitate the need for recovery protocols, urologists looking to perform outpatient surgical oncology procedures must be cognizant of the restrictive discharge criteria for an ambulatory procedure. Furthermore, a surgery being performed in the ambulatory setting should not imply that the procedure is without the risk of morbidity. With this in mind, ERAS protocols are paramount to ensuring optimal surgical outcomes. The individual components of such protocols encompass the perioperative period in its entirety. They include patient education, the stabilization of chronic medical conditions, perioperative nutrition, frailty mitigation, and the management of various postoperative sequalae. This review paper evaluates and summarizes the essential role of pharmacotherapy in ERAS protocols for ambulatory urologic oncology surgery.
Long-Term Outcomes After Multidisciplinary Treatment for Pediatric Orbital Rhabdomyosarcoma
Authors: Khatib Nur , Merks Johannes H. M. , Markenstein Jeroen E. , Balgobind Brian V. , Savci-Heijink Cemile. D. , Morfouace Michele , Pieters Bradley R. , Saeed Peerooz
Published: February 2025

(1) Background: Orbital rhabdomyosarcoma is a rare and aggressive soft tissue tumor that primarily occurs in the eye socket (orbit) of children. Treatment usually involves a combination of surgery, chemotherapy, and radiation therapy, aiming to remove the tumor and prevent metastasis. (2) Methods: An institutional retrospective study was conducted with data from 39 patients with primary orbital RMS treated between 1995 and 2016 at the Amsterdam University Medical Centers/Emma Children Hospital. (3) Results: The median age at presentation was 7 years (range, 9 months to 16 years). The median follow-up period was 9.4 years (range, 3 to 25 years). Ten underwent chemotherapy and excision without additional radiotherapy. A total of 29 patients received additional local treatment: Ablative surgery MOld technique with after loading brachytherapy and surgical REconstruction (AMORE) (N = 21), proton (N = 4) or external beam radiation treatment (EBRT; N = 4). We found 14 cases with recurrences, 9 of which underwent exenteration and two of which died. The 10-year overall survival rate was 95% and the EFS was 63%. (4) Conclusions: long-term follow-up with 10-year survival rate of orbital RMS in this series was 95% achieved by local tumor control and eye preservation in 77% of our study population.
Unravelling Vacuum Gas Oil Catalytic Cracking: The Influence of the Catalyst-to-Oil Ratio on FCC Catalyst Performance
Authors: Acosta-López Jansen Gabriel , Muñoz José Luis , de Lasa Hugo
Published: February 2025

This study evaluates the impact of the catalyst-to-oil (C/O) ratio in the 1 to 7 range on the catalytic cracking of vacuum gas oil (VGO). Experiments are conducted using fluid catalytic cracking (FCC)-type catalysts, in a mini-fluidized bench-scale Riser Simulator reactor invented at the Chemical Reactor Engineering Centre (CREC), University of Western Ontario. The CREC Riser Simulator replicates FCC industrial operating conditions such as temperature, species partial pressure, and reaction times. The results indicate that increasing the C/O ratio above 5 slightly impacts VGO conversion, increases light gases yield, decreases light cycle oil (LCO) yield, and stabilizes gasoline yield. These findings align with temperature-programmed desorption (TPD) data, showing how the retention of a larger number of acid sites at a C/O of 7 boosts light gas production and reduces LCO selectivity. These elevated C/O ratios also lead to higher coke formation. The results reported together with future studies conducted by our research team on the impact of higher catalyst flows, larger potential catalyst attrition, higher catalyst loading in the cyclones, and excess heat generated in the catalyst regenerator unit, are of critical value for establishing the impact of C/O ratios in the overall FCC refinery operation.
Glioblastoma Cell Migration, Invasion and Vasculogenic Mimicry Downmodulated by Novel uPAcyclin Derivatives
Authors: Santoro Federica , Merlino Francesco , Brancaccio Diego , Camerino Iolanda , Belli Stefania , Cimmino Amelia , Grieco Paolo , Colucci-D’Amato Luca , Stoppelli Maria Patrizia , Franco Paola , Carotenuto Alfonso
Published: February 2025

Despite extensive efforts to develop new treatments, the prognosis for glioblastoma multiforme (GBM) is extremely unfavorable, urging the identification of new chemotherapeutics. A previous work identified the cyclic decapeptide uPAcyclin as a potent inhibitor of GBM cell migration, matrix invasion and vascular-like structures’ formation, acting through binding to αV integrins and not interfering with cell proliferation or survival. These clearcut activities prompted us to design and test novel derivatives on cultured U87-MG and U251 GBM-MG human cells. With the exception of the residues involved in peptide cyclization, residues were Ala-substituted one by one and the single peptides tested for binding affinity for the αV target integrin, the inhibition of migration, invasion and vasculogenic mimicry. The first screening highlighted peptides with a low binding affinity and low inhibitory ability (Ala4,7,9 derivatives) and peptides with affinity and inhibitory capacity higher than uPAcyclin (Ala2,5,6,8 derivatives). The integration of these results with conformational studies led to the design of the di-substituted variant uPAcyclin. Intriguingly, at least ten-fold greater anti-migratory and anti-invasive effects of the [Ala2,Ala5]uPAcyclin variant compared to uPAcyclin were found. The latter variant also exhibited a greater inhibitory potential for vascular-like structures’ formation by matrix-seeded GBM cells. These studies shed light on the functional relevance of single amino acid residues in uPAcyclin and lead to the identification of therapeutically interesting new variants as promising candidates for anti-GBM therapies.
Mitogen-Activated Protein Kinase Phosphatase-2 Deletion Promotes Hyperglycemia and Susceptibility to Streptozotocin-Induced Diabetes in Female Mice In Vivo
Authors: Ghimire Nabin , Welch Morgan , Secunda Cassandra , Fink Alexis , Lawan Ahmed
Published: February 2025

The development of type 2 diabetes (T2D) is largely dependent on the maintenance of pancreatic islet function and mass. Sexual dimorphism in T2D is evident in many areas, such as pathophysiology, treatment, and prevention. Mitogen-activated protein kinase phosphatase-2 (MKP-2) has a distinct role in the regulation of cell proliferation and the development of metabolic disorders. However, whether there is a causal relationship between MKP-2 and diabetes onset is unclear. The aim of this study was to determine the role of MKP-2 in the regulation of whole-body glucose homeostasis and the impact on pancreatic islet function using streptozotocin-induced pancreatic injury. Here, we show that female mice with whole-body deletion of MKP-2 exhibit hyperglycemia in mouse models treated with multiple low doses of streptozotocin (STZ). In comparison, both male MKP-2 wild-type and knockout mice were hyperglycemic. Consistent with the hyperglycemia, female MKP-2-deficient mice exhibited reduced islet size. Under T2D conditions, MKP-2-deficient mice display enhanced pancreatic JNK and ERK phosphorylation that is associated with the downregulation of genes important for pancreatic islet development and function, Pdx-1 and MafA. Furthermore, we found impaired metabolic flux in adipose tissue that is consistent with hyperglycemia and dysfunctional pancreas. MKP-2 deletion results in reduced Akt activation that is associated with increased adiposity and insulin resistance in female MKP-2 KO mice. These studies demonstrate the critical role of MKP-2 in the development of T2D diabetes in vivo. This suggests that MKP-2 may have a gender-specific role in diabetes development. This discovery raises the possibility that postmenopausal prevention of T2D may benefit from the activation of MKP-2 activity in islet cells.
Rapid Isolation of Circulating Tumor Cells from Glioblastoma Patients Using a Lateral Filter Array Microfluidic Device
Authors: Gavioli Victória D’Amario , Filho Marcos Vilas Boas , Castro Gustavo R. , Filho Pedro Tadao Hamamoto , Ferrasi Adriana Camargo , Pedrosa Valber A.
Published: February 2025

Glioblastoma is the most common form of brain cancer in adults, representing 35–40% of all malignant brain tumors. This highly aggressive malignancy originates in the central nervous system, and despite notable advancements in treatment strategies, it continues to be an incurable disease. The isolation of circulating tumor cells (CTC) at an early stage is challenging due to the low probability of their presence in peripheral blood. Detection and enumeration as early as possible can reportedly lead to more effective treatment. This study proposes a novel label-free, rapid, and continuous CTC separation device based on a lateral filter array microfluidic device for the highly efficient immunoaffinity isolation of CTCs. Our methodology successfully captured and isolated circulating tumor cells (CTCs) from the whole blood of glioblastoma (GBM) patients prior to surgery, achieving over 90% capture efficiency in under 40 min of analysis. These findings highlight the potential of this technology to enhance our understanding of the clinical significance of CTCs in the management of GBM in future research.
Sleep Apnea Syndrome in Children: A Retrospective Study of 419 Cases and Polysomnographic Findings with Implications for Rapid Treatment
Authors: Chmielik Lechosław Paweł , Kasprzyk Anna , Sala Zuzanna , Chmielik Tadeusz , Hatliński Grzegorz Jacek , Mielnik-Niedzielska Grażyna , Niedzielski Artur
Published: February 2025

Sleep-related disorders are responsible for many serious health conditions, one of these being sleep apnea syndrome, which arises through various mechanisms. Polysomnography is currently used as the gold standard method for diagnosing patients suffering from sleep breathing disorders, thus enabling accurate and swift clinical diagnosis. Background/Objectives: By using the parameters obtained from polysomnography, this retrospective study has aimed to determine the groups of children that are particularly vulnerable to severe forms of breathing disorders, divided according to diagnoses made of tonsillar hypertrophy forms and sleep apnea as well as by the severity grades and types of apnea, to facilitate rapid and appropriate treatment. Methods: The subjects were 419 children (from 2017 to 2024) who had been initially diagnosed with sleep apnea syndrome (36.99% girls and 63.01% boys), upon whom various parameters of polysomnography examinations were retrospectively evaluated. The subjects were broken down into groups according to three diagnoses and the types and severities of apnea. The following statistical analyses were used: Kruskal–Wallis tests, post-hoc testing and correlation. Results: Tonsillar hyperplasia was found in 334/419 subjects. The total apnea incidence was highest in the total mild severity grouping (53.33%), while the highest total apnea incidence in the apnea type grouping was found in the central apnea grouping at 31.74%, of which the highest sub-group incidence of apnea was found in those with the mild form (25.54%). The highest incidence of apnea was found in its mild form in subjects with pharyngeal and palatine tonsil hypertrophy (19.57%). The highest apnea incidence for those initially diagnosed with sleep apnea was 10.74% for the central apnea type. Children with hypertrophy of the pharyngeal tonsil and palatine tonsils had the more severe form of apnea than in the other cases in terms of AHI. Apnea severity, AHI, ODI and BS below 89% were highest/longest in the peripheral apnea type, whereas the REM sleep time %-age was lowest in this type. Strong positive correlations were found between AHI with ODI and sleep time below 89%, whereas strong negative correlations were found between AHI with average and minimum saturation variables. Conclusions: Polysomnography findings of especially mild or severe sleep apnea in children with tonsillar hyperplasia should indicate that surgical treatment is needed as soon as possible.