bluuebunny/crossref_metadata_2025 huggingface dataset:
Benchmarking Low-Cost Particulate Matter Sensors: Evaluating Performance Under Controlled Environmental Conditions Using Low-Cost Experimental Setups
Authors: Alvarez Cruz Arianna , Schalm Olivier , Morera Hernández Luis Ernesto , Martínez Laguardia Alain , Alejo Sánchez Daniellys , Morales Pérez Mayra C. , González Rivero Rosa Amalia , Morera Gómez Yasser
Published: February 2025

Particulate matter (PM) is widely recognized as a major air pollutant with significant impacts on human health, highlighting the need for accurate monitoring. In developing countries, low-cost sensors are crucial for accessible PM monitoring, but their accuracy and reliability must first be assessed. This study benchmarked the Alphasense OPC-N3 and Next PM sensors through laboratory and field evaluations. Laboratory tests were performed in controlled conditions with HEPA-filtered air at low humidity and varying concentrations of water droplets from nebulized deionized water. A 27-day field study in Cienfuegos, Cuba, provided additional insights into real-world performance. The OPC-N3 showed susceptibility to perturbations and was more affected by outliers (especially PM10), relative humidity, and interference from aqueous aerosols. In contrast, the Next PM sensor demonstrated superior stability, lower noise levels, and consistent performance across different environmental conditions. Despite a substantial price difference, both sensors provided valid measurements. Additionally, both sensors produced lognormal PM concentration distributions during field campaigns. This feature could aid in addressing the calibration stability challenges commonly associated with low-cost sensors through in situ calibration methods. While the PM measurements by affordable sensors are not perfect, they are sufficiently reliable for supporting air quality assessments in resource-limited settings.
The Existence and Stability of a Periodic Solution of a Nonautonomous Delayed Reaction–Diffusion Predator–Prey Model
Authors: Jia Lili , Wang Changyou
Published: February 2025

In this study, we research a nonautonomous, three-species, delayed reaction–diffusion predator–prey model (RDPPM). Firstly, we derive sufficient conditions to guarantee the existence of a strictly positive, spatially homogeneous periodic solution (SHPS) for the delayed, nonautonomous RDPPM. These conditions are obtained using the comparison theorem for delayed differential equations and the fixed point theorem. Secondly, we present sufficient conditions to ensure the global asymptotic stability of the SHPS for the delayed, nonautonomous RDPPM. These conditions are established through the application of the upper and lower solution method (UALSM) for delayed parabolic partial differential equations (PDEs), along with Lyapunov stability theory. Finally, to demonstrate the practical application of our results, we numerically validate the proposed conditions using a 2-periodic, delayed, nonautonomous RDPPM.
Cathodes for Zinc-Ion Micro-Batteries: Challenges, Strategies, and Perspectives
Authors: Deng Ling , Lin Qunfang , Li Zeyang , Cao Juexian , Sun Kailing , Wei Tongye
Published: February 2025

The sustainable development of high-performance micro-batteries, characterized by miniaturized size, portability, enhanced safety, and cost-effectiveness, is crucial for the advancement of wearable and smart electronics. Zinc-ion micro-batteries (ZIMBs) have attracted widespread attention for their high energy density, environmental friendliness, excellent safety, and low cost. The key to designing high-performance ZIMBs lies in improving their volumetric capacity and cycle stability. This review focuses on material design, electrode fabrication, and the structural configuration of micro-batteries, providing a comprehensive analysis of the challenges and strategies associated with cathodes in ZIMBs. Additionally, the application of ZIMBs, which provide energy for electronics such as wearable devices, tiny robots, and sensors, is introduced. Finally, future perspectives on cathodes for ZIMBs are discussed, offering key insights into their design and fabrication in order to facilitate the successful integration of ZIMBs into practical applications.
Identification of DNA Methylation Differences in Pituitary Tissues of Sichuan White Geese Using Whole-Genome Bisulfite Sequencing (WGBS)
Authors: Ma Lin , Zhao Xianzhi , A Guoda , Song Tongtong , Wu Meng , Yan Zhihao , Xiao Min , Jiang Wenbo , Gao Yixiao , Wang Haiwei , Chen Zhuping , Zhang Keshan , Xue Jiajia , Luo Yi , Wang Chao , Xie Youhui , Chen Ying , Gao Guangliang , Wang Qigui
Published: February 2025

To explore the impact of epigenetic modifications on egg-laying traits in geese, we employed genome-wide bisulfite sequencing (WGBS) to analyze DNA methylation patterns in pituitary tissues of high-(HYP) and low-yield (LYP) Sichuan White geese. We achieved high-quality sequencing data (mean 19.09 Gb raw reads, 15.49 Gb clean reads, 79.1% unique mapping rate) with a bisulfite conversion efficiency of 99.88%. Comparative analysis revealed 2394 differentially methylated regions (DMRs) and 422 differentially methylated genes (DMGs) between HYP and LYP groups. We identified five key differentially methylated candidate genes (BMPER, INHA, NMBR, NK3R, and DSG2) linked to egg-laying traits in Sichuan White geese. Integrated GO and KEGG enrichment analysis conducted to explore the role of regulatory networks of epigenetic modification on egg-laying traits in Sichuan White geese identified multiple metabolic pathways associated with egg-laying traits (promoting egg transport, ovulation, and yolk protein synthesis and secretion), thus providing a basis for subsequent functional verification.
Screening of Bacteria Promoting Carbon Fixation in Chlorella vulgaris Under High Concentration CO2 Stress
Authors: Chen Chuntan , Wang Yu , Dai Qunwei , Du Weiqi , Zhao Yulian , Song Qianxi
Published: February 2025

The cooperation between microalgae and bacteria can enhance the carbon fixation efficiency of microalgae. In this study, a microalgae-bacteria coexistence system under high-concentration CO2 stress was constructed, and the bacterial community structure of the entire system was analyzed using the 16S rDNA technique. Microbacterium sp., Bacillus sp., and Aeromonas sp. were screened and demonstrated to promote carbon fixation in Chlorella vulgaris HL 01 (C. vulgaris HL 01). Among them, the Aeromonas sp. + C. vulgaris HL 01 experimental group exhibited the most significant effect, with an increase of about 24% in the final biomass yield and a daily carbon fixation efficiency increase of about 245% (day 7) compared to the control group. Continuous cultivation of microalgae and bacterial symbiosis showed that bacteria could utilize the compounds secreted by microalgae for growth and could produce nutrients to maintain the vitality of microalgae. Detection of extracellular organic compounds of microorganisms in the culture broth by excitation-emission matrix spectral analysis revealed that bacteria utilized the aromatic proteinaceous compounds and others secreted by C. vulgaris HL 01 and produced new extracellular organic compounds required by C. vulgaris HL 01. The metabolic organic substances in the liquids of the experimental groups and the control group were analyzed by liquid chromatography-mass spectrometry, and it was found that 31 unique organic substances of C. vulgaris HL 01 were utilized by bacteria, and 136 new organic substances were produced. These differential compounds were mainly organic acids and their derivatives, benzene compounds, and organic heterocyclic compounds, etc. These results fully demonstrate that the carbon fixation ability and persistence of C. vulgaris HL 01 are improved through material exchange between microalgae and bacteria. This study establishes a method to screen carbon-fixing symbiotic bacteria and verifies that microalgae and bacteria can significantly improve the carbon fixation efficiency of microalgae for high-concentration CO2 through material exchange, providing a foundation for further research of microalgae-bacterial carbon fixation.
From Cardiovascular-Kidney-Metabolic Syndrome to Cardiovascular-Renal-Hepatic-Metabolic Syndrome: Proposing an Expanded Framework
Authors: Theodorakis Nikolaos , Nikolaou Maria
Published: February 2025

Cardiometabolic diseases represent an escalating global health crisis, slowing or even reversing earlier declines in cardiovascular disease (CVD) mortality. Traditionally, conditions such as obesity, type 2 diabetes mellitus (T2DM), atherosclerotic CVD, heart failure (HF), chronic kidney disease (CKD), and metabolic dysfunction-associated steatotic liver disease (MASLD) were managed in isolation. However, emerging evidence reveals that these disorders share overlapping pathophysiological mechanisms and treatment strategies. In 2023, the American Heart Association proposed the Cardiovascular-Kidney-Metabolic (CKM) syndrome, recognizing the interconnected roles of the heart, kidneys, and metabolic system. Yet, this model omits the liver—a critical organ impacted by metabolic dysfunction. MASLD, which can progress to metabolic dysfunction-associated steatohepatitis (MASH), is closely tied to insulin resistance and obesity, contributing directly to cardiovascular and renal impairment. Notably, MASLD is bidirectionally associated with the development and progression of CKM syndrome. As a result, we introduce an expanded framework—the Cardiovascular-Renal-Hepatic-Metabolic (CRHM) syndrome—to more comprehensively capture the broader inter-organ dynamics. We provide guidance for an integrated diagnostic approach aimed at halting progression to advanced stages and preventing further organ damage. In addition, we highlight advances in medical management that target shared pathophysiological pathways, offering benefits across multiple organ systems. Viewing these conditions as an integrated whole, rather than as discrete entities, and incorporating the liver into this framework fosters a more holistic management strategy and offers a promising path to addressing the cardiometabolic pandemic.
The Inhibitory Effect of Peptide Hydrolysate of Type I Collagen Derived from Pig Skin on Melanogenesis in B16F10 Melanoma Cells
Authors: Zheng Jialin , Xu Dandan , Li Tianduo
Published: February 2025

Collagen peptides, as a natural source of peptides, possess multiple advantages such as anti-aging, anti-inflammatory properties, tissue repair, and the ability to inhibit melanin production. In this study, type I collagen extracted from pig skin was hydrolyzed with 1% and 3% hydrochloric acid, yielding collagen peptides CPH1 and CPH3. The melanin content and tyrosinase activity in B16F10 cells were compared via direct and paracrine action when CPH1 and CPH3 were used to interfere with melanogenesis. It was found that CPH3 significantly inhibited melanogenesis in B16F10 through the paracrine action involving HaCaT keratinocytes. The intracellular melanin content was measured at 65.23 ± 1.30%, and the mRNA levels of tyrosinase and microphthalmia transcription factor in cells were 55.77 ± 6.09% and 50.70 ± 8.18% of the negative control, respectively. Furthermore, pigment deposition assays in zebrafish showed that, at a concentration of 1.0 mg/mL, CPH3 significantly inhibited melanogenesis compared to the negative control. Finally, tyrosinase inhibitory peptides were identified from CPH3 through peptide segment sequence identification and molecular dynamics simulation. The peptides of Nona-AGPPGFPGA, Octa-APGPVGPA, and Octa-GLPGPPGP have a double effect on the inhibition of tyrosinase and melanin content in B16F10 cells.
Impact of Routine and Selective Preoperative Endoscopic Retrograde Cholangiopancreatography with Stent Placement on Postoperative and Oncologic Outcomes Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma
Authors: Aeschbacher Pauline , Wenning Anna Silvia , Katou Shadi , Morgul Haluk , Juratli Mazen , Becker Felix , Büdeyri Ibrahim , Gloor Beat , Pascher Andreas , Struecker Benjamin , Andreou Andreas
Published: February 2025

Background: According to current guidelines, preoperative endoscopic retrograde cholangiopancreatography (ERCP) with biliary stenting (ERCP/stenting) is often necessary in patients with obstructive jaundice due to pancreatic ductal adenocarcinoma (PDAC), including severe jaundice (bilirubin > 250 umol/l), pruritus, cholangitis, cholestatic liver dysfunction, renal failure, severe malnutrition, or delayed surgery for tumors requiring neoadjuvant chemotherapy. We aimed to investigate the impact of preoperative ERCP/stenting on postoperative and long-term outcomes following pancreaticoduodenectomy (PD) for PDAC. Methods: Clinicopathological data of patients who underwent partial/total PD for PDAC between 2012 and 2019 in two hepato-pancreato-biliary centers in Germany and Switzerland were assessed. We compared patients treated with preoperative ERCP/stenting with those directly undergoing surgery according to postoperative morbidity, postoperative mortality, overall survival (OS) and disease-free survival (DFS). Results: During the study period, 192 patients underwent partial/total PD for PDAC. ERCP/stenting was performed in 105 patients, and 87 patients underwent resection without prior intervention. Postoperative 90-day overall morbidity rate (71% vs. 56%, p = 0.029) and superficial surgical site infection (SSI) rate (39% vs. 17%, p < 0.001) were significantly worse following preoperative ERCP/stenting. Major postoperative morbidity rate (18% vs. 21%, p = 0.650), organ/space SSI rate (7% vs. 14%, p = 0.100), and 90-day postoperative mortality rate (4% vs. 2%, p = 0.549) did not significantly differ between the two groups. After excluding 44 patients for whom the indication for ERCP/stenting was not consistent with current guidelines, ERCP/stenting was associated with a higher superficial SSI rate (36% vs. 17%, p = 0.009) and shorter length of stay (12 vs. 16 days, p = 0.004). Median OS (ERCP/stenting: 18 months vs. no ERCP/stenting: 23 months, p = 0.490) and median DFS (ERCP/stenting: 14 months vs. no ERCP/stenting: 18 months, p = 0.645) were independent from the utilization of ERCP/stenting. Conclusions: Preoperative ERCP/stenting in patients with PDAC can be performed without increasing organ/space SSI, major perioperative morbidity, and mortality rates and without worsening oncologic outcomes. However, it is associated with higher superficial SSI rates. If ERCP/stenting is not performed routinely but according to current guidelines, it is also associated with a shorter length of hospital stay. Further refinement of the indications for preoperative ERCP/stenting may reduce superficial SSI rates.
Phenolic Content, Antioxidant Activity and In Vitro Anti-Inflammatory and Antitumor Potential of Selected Bulgarian Propolis Samples
Authors: Tumbarski Yulian , Ivanov Ivan , Todorova Mina , Apostolova Sonia , Tzoneva Rumiana , Nikolova Krastena
Published: February 2025

Background/objectives: Propolis (bee glue) is a valuable bee product widely used as a natural remedy, a cosmetic ingredient, a nutritional value enhancer and a food biopreservative. The present research aims to investigate the phenolic content, antioxidant activity and in vitro anti-inflammatory and antitumor potential of six propolis samples from three regions of Bulgaria (Vidin, Gabrovo and Lovech). Methods: the analysis of propolis phenolic compounds was determined by high-performance liquid chromatography (HPLC); the antioxidant activity of ethanolic propolis extracts was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and ferric-reducing antioxidant power (FRAP) assay; the in vitro anti-inflammatory activity was assessed by the inhibition of albumin denaturation method; the in vitro antitumor activity was determined in human metastatic breast cancer cell line MDA-MB-231 using 3-(4,5-Dimethyl -2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results: The ethanolic propolis extracts exhibited the total phenolic content from 190.4 to 317.0 mg GAE/g, total flavonoid content from 53.4 to 79.3 mg QE/g and total caffeic acid derivatives content from 5.9 to 12.1 mg CAE/g. The studied propolis extracts showed significant antioxidant capacity (between 1000.3 and 1606.0 mM TE/g determined by the DPPH assay, and between 634.1 and 1134.5 mM TE/g determined by the FRAP assay). The chemical composition analysis indicated high concentrations of caffeic acid benzyl ester, chrysin, pinocembrin and pinobanksin-3-O-propionate, predominantly in three of the propolis samples originating from Gabrovo and Lovech regions. All propolis samples demonstrated promising in vitro anti-inflammatory activity, expressed as the inhibition of thermally induced albumin denaturation by 73.59% to 78.44%, which was higher than that of the conventional anti-inflammatory drugs Aspirin (58.44%) and Prednisolone Cortico (57.34%). The propolis samples exhibited high in vitro cytotoxicity against cancer cells MDA-MB-231 with IC50 values ranging between 9.24 and 13.62 µg/mL as determined by MTT assay. Conclusions: Overall, we can suggest that the high phenolic content of Bulgarian propolis from respective areas contributes to its enhanced antioxidant, anti-inflammatory and antitumor activity. Taken together, our results support the beneficial properties of Bulgarian propolis, with potential application as a promising therapeutic agent.
Probiotic-Derived Metabolites from Lactiplantibacillus plantarum OC01 Reprogram Tumor-Associated Macrophages to an Inflammatory Anti-Tumoral Phenotype: Impact on Colorectal Cancer Cell Proliferation and Migration
Authors: Garavaglia Beatrice , Vallino Letizia , Ferraresi Alessandra , Amoruso Angela , Pane Marco , Isidoro Ciro
Published: February 2025

Background: Tumor-associated macrophages (TAMs) are key players in the colorectal cancer (CRC) tumor microenvironment (TME), representing the most abundant immune cells within it. The interplay between the intestinal microbiota, macrophages, and cancer cells significantly impacts tumor progression by driving macrophage polarization. Particularly, the polarization into the pro-tumoral M2-like TAM phenotype promotes the extracellular matrix remodeling, cancer cell proliferation, metastasis, immune suppression, and therapy resistance. Probiotic metabolites can disrupt this crosstalk, possibly reverting the TAM polarization toward a pro-inflammatory anti-tumoral phenotype, thus potentially benefiting the intestinal mucosa and opposing CRC progression. Previously, we showed that Lactiplantibacillus plantarum OC01 metabolites counter interleukin (IL)-6-induced CRC proliferation and migration. Methods: Here, we explore how probiotics affect CRC secretome and how this influences TAM polarization, which then impacts CRC malignancy. Results: The conditioning medium (CM) from CRC cells indeed promoted the polarization of macrophage toward the M2-like phenotype, whereas the CM from CRC pre-treated with L. plantarum OC01 metabolites induced a pro-inflammatory macrophage phenotype, characterized by NLRP3 inflammasome activation and reactive oxygen species (ROS) production, and by decreased expression of the M2 phenotype markers CD206 and CD163. Consistently, the expression of tumor growth factor (TGF)-β, a promoter of M2 macrophage polarization, was reduced in CRC cells treated with L. plantarum OC01. The pro-inflammatory macrophages inhibited CRC proliferation and migration. Conclusions: Overall, our study highlights the potential of metabolites from L. plantarum OC01 to reprogram the metabolism in cancer cells and thus reshape the TME by shifting TAMs toward a more inflammatory and anti-tumoral phenotype, emphasizing the promise of probiotics in advancing novel therapeutic approaches for CRC.
Lower Levels of TAZ Expression Associated with Post-Surgical Wound Healing Complications in Soft Tissue Sarcoma Patients Treated with Preoperative Radiation
Authors: Gylten Jacob D. , Persons Jane E. , Miller Benjamin J. , An Qiang , Tanas Munir R. , Chen Stephanie J. T.
Published: February 2025

Background/Objectives: Pre-operative radiation (Pre-RT) decreases local recurrence following soft tissue sarcoma (STS) resection but carries the risk of wound healing complications (WHCs). This study evaluated skin specimens and clinical characteristics of STS patients to (1) compare patients with and without Pre-RT, (2) compare Pre-RT patients with and without WHCs, and (3) explore associations between clinical characteristics and WHCs. Methods: This retrospective study included 54 adults who underwent STS resection with primary closure (Pre-RT n = 30). A pathologist who was blinded to the clinical outcomes evaluated the skin specimens microscopically. Results: Irradiated skin had lower vessel density and was more likely to lack hair follicles and sebaceous glands, consistent with the effects of radiation. Irradiated skin was also more likely to include plasma cells. Irradiated skin demonstrated higher mean TAZ H-scores; however, within the Pre-RT subset, those patients who developed WHCs demonstrated comparatively lower TAZ. Conclusions: This novel finding may suggest that higher TAZ in irradiated skin reflects a response to injury but that comparatively lower TAZ in irradiated skin might contribute to WHCs. Future studies should consider more focused evaluation of TAZ in STS resections with Pre-RT as they may help to predict WHCs when used in combination with other histologic factors and could suggest a therapeutic target.
Artificial Intelligence in Higher Education: The Impact of Need Satisfaction on Artificial Intelligence Literacy Mediated by Self-Regulated Learning Strategies
Authors: Wang Kai , Cui Wencheng , Yuan Xue
Published: February 2025

Artificial intelligence (AI) technologies have profoundly influenced both professional environments and personal lives. In the rapidly developing sector of AI education, fostering essential AI literacy among university students has become vital. Nevertheless, the factors that determine AI literacy remain insufficiently defined. This research, grounded in self-determination theory (SDT), seeks to investigate the relationships among three components: the fulfillment of university students’ three psychological needs, self-regulated learning strategies (SRLSs), and AI literacy. The aim is to enhance human capital efficiency and prepare students to tackle future workplace challenges effectively. To examine these connections, a cross-sectional survey was administered to 1056 university students. The findings reveal that satisfying the three psychological needs—perceived autonomy, competence, and relatedness—plays a pivotal role in advancing AI literacy among university students. Additionally, four SRLSs—cognitive engagement, metacognitive knowledge, resource management, and motivational beliefs—acted as mediators between these psychological needs and AI literacy. Consequently, this study not only enhances our understanding of the psychological and behavioral development of university students during their engagement with AI education but also provides theoretical support and practical guidance for fostering their AI literacy.
The Relationship Between Basic Psychological Needs Satisfaction and Career Adaptability Among University Students: The Roles of Grit and Career Decision-Making Self-Efficacy
Authors: Xu Min , Lu Haidong , Fu Jinlan , Zhu Hairong , Zhao Yingfang
Published: February 2025

Enhancing the career adaptability of university students is a practical necessity for addressing the challenge of student employment. This study explores the relationship between basic psychological needs satisfaction and career adaptability among university students based on Basic Psychological Need Theory and Social Cognitive Career Theory and constructs a corresponding chain mediation model. A survey was conducted among 635 university students from six provinces across China. The results indicate the following findings: (1) grit partially mediates the relationship between basic psychological needs satisfaction and career adaptability among university students; (2) career decision-making self-efficacy also partially mediates this relationship; and (3) grit and career decision-making self-efficacy serve as chain mediators in the relationship between basic psychological needs satisfaction and career adaptability. This study provides empirical support and significant guidance for enhancing the career adaptability development of university students.
Radiomic Fingerprinting of the Peritumoral Edema in Brain Tumors
Authors: Azemi Ghasem , Di Ieva Antonio
Published: February 2025

Background/Objectives: Tumor interactions with their surrounding environment, particularly in the case of peritumoral edema, play a significant role in tumor behavior and progression. While most studies focus on the radiomic features of the tumor core, this work investigates whether peritumoral edema exhibits distinct radiomic fingerprints specific to glioma (GLI), meningioma (MEN), and metastasis (MET). By analyzing these patterns, we aim to deepen our understanding of the tumor microenvironment’s role in tumor development and progression. Methods: Radiomic features were extracted from peritumoral edema regions in T1-weighted (T1), post-gadolinium T1-weighted (T1-c), T2-weighted (T2), and T2 Fluid-Attenuated Inversion Recovery (T2-FLAIR) sequences. Three classification tasks using those features were then conducted: differentiating between Low-Grade Glioma (LGG) and High-Grade Glioma (HGG), distinguishing GLI from MET and MEN, and examining all four tumor types, i.e., LGG, HGG, MET, and MEN, to observe how tumor-specific signatures manifest in peritumoral edema. Model performance was assessed using balanced accuracy derived from 10-fold cross-validation. Results: The radiomic fingerprints specific to tumor types were more distinct in the peritumoral regions of T1-c images compared to other modalities. The best models, utilizing all features extracted from the peritumoral regions of T1-c images, achieved balanced accuracies of 0.86, 0.81, and 0.76 for the LGG-HGG, GLI-MET-MEN, and LGG-HGG-MET-MEN tasks, respectively. Conclusions: This study demonstrates that peritumoral edema, as characterized by radiomic features extracted from MRIs, contains fingerprints specific to tumor type, providing a non-invasive approach to understanding tumor-brain interactions. The results of this study hold the potential for predicting recurrence, distinguishing progression from pseudo-progression, and assessing treatment-induced changes, particularly in gliomas.
Evaluating Tumour Mutational Burden as a Key Biomarker in Personalized Cancer Immunotherapy: A Pan-Cancer Systematic Review
Authors: Zgura Anca , Chipuc Stefania , Bacalbasa Nicolae , Haineala Bogdan , Rodica Anghel , Sebastian Vâlcea
Published: February 2025

Background: Tumour mutational burden (TMB) is an emerging biomarker for predicting the efficacy of immune checkpoint inhibitors (ICIs) in cancer therapy. While its role is well established in lung cancer and melanoma, its predictive value for breast and prostate cancers remains unclear. Objective: This systematic review aimed to assess the predictive value of TMB for ICI therapy across four major cancer types—lung, melanoma, breast, and prostate—and to explore factors contributing to the variability in its effectiveness as a biomarker. Methods: A systematic search and a review of the literature were conducted in accordance with PRISMA guidelines. Studies examining the relationship between TMB levels and clinical outcomes following ICI therapy in the specified cancers were analyzed. The data were synthesized to evaluate TMB’s predictive value and identify gaps in the current research. Results: High TMB consistently correlated with improved outcomes in lung cancer and melanoma, confirming its predictive utility in these cancers. Conversely, the findings for breast and prostate cancers were inconclusive. The variability in TMB’s predictive value for these cancers suggests the need for complementary biomarkers or refined criteria to enhance its reliability. Methodological inconsistencies in TMB evaluation were also noted as a significant limitation. Conclusions: TMB serves as a robust biomarker for predicting ICI response in lung cancer and melanoma, but demonstrates limited predictive utility in breast and prostate cancers. Future research should prioritize standardizing TMB assessment protocols and investigating additional biomarkers to improve treatment personalization for these cancer types.
Robotic Surgery in Severely Obese Frail Patients for the Treatment of Atypical Endometrial Hyperplasia and Endometrial Cancer: A Propensity-Match Analysis at an ESGO-Accredited Center
Authors: Arcieri Martina , Paparcura Federico , Giorgiutti Cristina , Taliento Cristina , Bogani Giorgio , Driul Lorenza , Greco Pantaleo , Ercoli Alfredo , Chiantera Vito , Fanfani Francesco , Fagotti Anna , Scambia Giovanni , Mariani Andrea , Restaino Stefano , Vizzielli Giuseppe
Published: February 2025

Background and Objectives: Robotic-assisted laparoscopy (RS) has been widely adopted for the management of endometrial cancer (EC) due to favorable perioperative outcomes, especially in the context of obesity, which is an established risk factor for EC. This study retrospectively evaluated the perioperative outcomes of RS versus conventional laparoscopy (LS) in treating EC and atypical endometrial hyperplasia (AH). Methods: Between November 2021 and October 2023, 138 patients with AH or EC underwent surgery at the Clinic of Obstetric and Gynecological—Azienda Sanitaria Universitaria Friuli Centrale, Udine. All patients had total hysterectomy with bilateral salpingo-oophorectomy, with or without lymphadenectomy or sentinel lymph node biopsy. The study included 62 patients treated with LS and 62 with RS. Results: The median BMI was higher in the RS group (35.5 vs. 24 kg/m2, p = 0.001). There was no significant difference in operative time between the laparoscopic group and the robotic console time (median 130 vs. 130 min, p = 0.131). No significant differences were found in terms of blood loss, conversion to laparotomy, intraoperative complications, hospital stay, or early postoperative complications between the two groups. Conclusions: Our data confirm the feasibility of robotic surgery in obese patients, allowing surgical results comparable to those of laparoscopy in normal-weight patients.
Machine Learning Methods in Clinical Flow Cytometry
Authors: Spies Nicholas C. , Rangel Alexandra , English Paul , Morrison Muir , O’Fallon Brendan , Ng David P.
Published: February 2025

This review will explore the integration of machine learning (ML) techniques to enhance the analysis of increasingly complex and voluminous flow cytometry data, as traditional manual methods are insufficient for handling this data. We attempt to provide a comprehensive introduction to ML in flow cytometry, detailing the transition from manual gating to computational methods and emphasizing the importance of data quality. Key ML techniques are discussed, including supervised learning methods like logistic regression, support vector machines, and neural networks, which rely on labeled data to classify disease states. Unsupervised methods, such as k-means clustering, FlowSOM, UMAP, and t-SNE, are highlighted for their ability to identify novel cell populations without predefined labels. We also delve into newer semi-supervised and weakly supervised methods, which leverage partial labeling to improve model performance. Practical aspects of implementing ML in clinical settings are addressed, including regulatory considerations, data preprocessing, model training, validation, and the importance of generalizability, and we underscore the collaborative effort required among pathologists, data scientists, and laboratory professionals to ensure robust model development and deployment. Finally, we show the transformative potential of ML in flow cytometry in uncovering new biological insights through advanced computational techniques.
Long-Term Reassurance with Negative High-Risk Human Papillomavirus (HR-HPV) and Clear Margins After Large Loop Excision of the Transformation Zone (LLETZ)
Authors: Heydari Fatima , de Sanjosé Silvia , Peñafiel Muñoz Judith , Fernández-Montolí Maria-Eulalia
Published: February 2025

Background/Objective: Women treated with large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia grade 2-3 (CIN2-3) remain at risk of CIN2-3 and cervical cancer for many years. We assessed the roles of high-risk human papillomavirus (HR-HPV) post-LLETZ, surgical margins, and LLETZ characteristics on the long-term risk of CIN2-3. Methods: A retrospective observational study was performed using data for 432 women with a histological diagnosis of CIN2-3 treated by LLETZ between 1996 and 2020 and followed-up until October 2021 at Hospital Bellvitge in Barcelona, Spain. Age, surgical margins, 6-month HR-HPV status, excision type, and cone volume/dimensions were analyzed in association with the risk of persistent/recurrent CIN2-3. The cumulative probability of persistent/recurrent CIN2-3 was calculated using the Kaplan–Meier and Cox models. Results: Persistent/recurrent CIN2-3 was detected in 7.4%, with over 90% found within 5 years post-LLETZ. Predictors of persistent/recurrent CIN2-3 were HR-HPV (HR = 7.36, 95% CI = 3.55–15.26), involved margins (HR = 3.94, 95% CI = 1.68–9.25), uncertain margins (HR = 4.42, 95% CI = 1.55–12.55), and age ≥ 35 years (HR = 2.92, 95% CI = 1.19–7.13). Type 3 excision (p = 0.035) and cone length (p = 0.010) correlated with clear margins. The negative predictive value (NPV) of both negative HR-HPV and clear margins post-LLETZ was 98.7%. Conclusions: The combination of negative HR-HPV and clear margins post-LLETZ provides stronger reassurance against the risk of persistent/recurrent CIN2-3 than do LLETZ characteristics. However, larger excisions in older women likely reduce the risk of involved margins. Close surveillance, including repeat HR-HPV testing in the first 5 years post-LLETZ, is crucial.
Defining the Role of Adjuvant Radiotherapy for Biliary Tract Cancers: A Site-Specific Propensity-Matched Analysis
Authors: Seo Yongwoo David , Acidi Belkacem , Newton Andrew , Haddad Antony , Chiang Yi-Ju , Coelho Rainna , Newhook Timothy E. , Tzeng Ching-Wei D. , Chun Yun Shin , Ludmir Ethan B. , Koay Eugene J. , Javle Milind , Vauthey Jean Nicolas , Cao Hop S. Tran
Published: February 2025

Background: Biliary tract cancers (BTCs) have distinct tumor biology but share a poor prognosis, with a 5-year-survival-rate of 5–19%. Surgical resection is the only potential cure, but recurrences are common. The role of adjuvant radiotherapy (XRT) remains unclear. Methods: Using the National Cancer Database (2006–2018), we analyzed resected non-metastatic BTCs. Patients who survived beyond 90 days post-surgery were included, while those with R2 resections or neoadjuvant therapy were excluded. Propensity matching was performed based on predictors of adjuvant radiation, age, and sex. Survival outcomes were compared between no adjuvant therapy, chemotherapy alone, and XRT ± chemotherapy. Results: Among 21,275 patients, including 5308 intrahepatic cholangiocarcinoma (IHC), 2689 perihilar cholangiocarcinoma (PHC), 3092 distal cholangiocarcinoma (DCC), and 10,186 gallbladder cancer (GBC) cases, adjuvant XRT did not improve survival for IHC. For PHC and DCC, XRT improved survival over no adjuvant therapy (PHC: 31.2 vs. 26.3 months, p = 0.004; DCC: 33.7 vs. 27.0 months, p = 0.015) but not over chemotherapy alone. For GBC, XRT significantly improved survival compared to both no adjuvant therapy and chemotherapy (30.2 vs. 26.6 and 24.6 months; p = 0.05 and p = 0.001). Conclusions: XRT provides a survival benefit for GBC, especially in node-positive and R1-resected patients. For PHC and DCC, XRT improves outcomes compared to no therapy, but its benefit over chemotherapy is uncertain. No benefit was observed for IHC.
Metabolic Singularities in Microsatellite-Stable Colorectal Cancer: Identifying Key Players in Immunosuppression to Improve the Immunotherapy Response
Authors: Gorría Teresa , Sierra-Boada Marina , Rojas Mariam , Figueras Carolina , Marin Silvia , Madurga Sergio , Cascante Marta , Maurel Joan
Published: February 2025

Although immune checkpoint inhibitor (ICI) therapy is currently the standard of care in microsatellite-unstable (MSI) metastatic colorectal cancer (CRC), ICI therapy, alone or in combination with other therapies, is not a treatment approach in microsatellite-stable (MSS) CRC, which is present in 95% of patients. In this review, we focus on metabolic singularities—at the transcriptomic (either bulk or single cell), proteomic, and post-translational modification levels—that induce immunosuppression in cancer and specifically in MSS CRC. First, we evaluate the current efficacy of ICIs in limited and metastatic disease in MSS CRC. Second, we discuss the latest findings on the potential biomarkers for evaluating ICI efficacy in MSS CRC using strict REMARK criteria. Third, we review the current evidence on metabolic patterns in CRC tumors and immune cell metabolism to advance our understanding of metabolic crosstalk and to pave the way for the development of combination strategies to enhance ICI efficacy.
Low Phosphatidylserine+ Cells Within the CD34+/CD45dim/CD117(c-kit)+ Subpopulation Are Associated with Poor Outcomes in Metastatic Colorectal Cancer
Authors: Brocco Davide , Simeone Pasquale , Marino Pietro Di , De Bellis Domenico , D’Ascanio Francesca , Colasante Giulia , Grassadonia Antonino , De Tursi Michele , Florio Rosalba , Di Ianni Mauro , Cama Alessandro , Tinari Nicola , Lanuti Paola
Published: February 2025

Background: Colorectal cancer is among the most prevalent causes of tumor-related deaths worldwide. Antiangiogenic therapy represents a cornerstone of metastatic CRC treatment, and biomarkers are advocated for the optimization of this therapeutic strategy. Methods: In this observational prospective study, we employed an optimized flow cytometry protocol to investigate the prognostic and predictive potential of blood circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), and related subsets in a cohort of patients with metastatic colorectal cancer (n = 40). Results: Computational FC analysis revealed a differential enrichment of blood cell clusters with a CD34+/CD45dim/CD117(c-kit)+ phenotype between responders and non-responders both to antiangiogenic and non-antiangiogenic treatments. Intriguingly, our results show that a high percentage of annexin V-negative cells in a putative circulating progenitor population with a CD34+/CD45dim/CD117+ phenotype was correlated with a reduced response to systemic anticancer treatments (p = 0.015) and worse overall survival (log-rank p = 0.03). In addition, we observed increased blood concentrations of CD34+/CD45dim/CD117+/annexin V- cells in patients with a higher number of metastatic sites (p = 0.03). Conclusions: Overall, these findings hold promise for the identification of novel circulating biomarkers to develop more personalized treatment approaches in patients with metastatic colorectal cancer.
Lesion Conspicuity in Contrast-Enhanced Mammography: A Retrospective Analysis of Tumor Characteristics
Authors: Bellini Chiara , Susini Tommaso , Toncelli Kassandra , Pandolfi Martina , Migliaro Giuliano , Pugliese Francesca , Vanzi Bianca , Incardona Ludovica , Bicchierai Giulia , di Naro Federica , de Benedetto Diego , Vidali Sofia , Pancani Silvia , Miele Vittorio , Nori Cucchiari Jacopo
Published: February 2025

Background/Objectives: The aim of this study is to evaluate the impact of tumor characteristics on lesion conspicuity in contrast-enhanced mammography (CEM) and identify factors associated with different levels of conspicuity. Methods: In this retrospective study, we analyzed 552 patients with breast cancer who underwent CEM. Lesion conspicuity was categorized into three levels: 1 (low), 2 (moderate), and 3 (high). Tumor characteristics included age, histological subtype, hormone receptor status, HER2 status, Ki67 index, tumor grade, and molecular subtype. Univariate and multivariate analyses were conducted to assess associations between lesion conspicuity and these factors. Results: Of the 552 cases, the majority showed mass enhancement (78.1%), followed by non-mass enhancement (NME) (16.8%), and a combination of mass and NME (4.0%). Lesion conspicuity was significantly associated with enhancement type on CEM (p < 0.001). High conspicuity (score 3) was predominantly observed in masses (84.8%) compared to NME (7.6%). Larger tumor dimensions (median 20 mm) were also associated with higher conspicuity (p < 0.001). Molecular subtypes differed significantly in conspicuity, with Luminal A tumors showing lower conspicuity compared to HER2-positive and triple-negative breast cancers (p = 0.025). In multivariate analysis, lesion conspicuity was strongly associated with enhancement type (p < 0.001) and tumor dimensions (p < 0.001), while histological subtype and molecular characteristics had no significant independent impact. Conclusions: Lesion conspicuity in CEM is primarily influenced by the type of enhancement and tumor size. Mass-forming lesions, particularly larger ones, are more conspicuous, while NME tends to result in lower conspicuity. These findings suggest that enhancement patterns and tumor dimensions are key factors to consider when interpreting CEM in breast cancer diagnosis.
Serosal Patching with Glubran®2 on the Pancreatic Stump for Reducing Postoperative Pancreatic Fistulae After Robot-Assisted Distal Pancreatectomy: A Single-Center Retrospective Study
Authors: Mahamid Ahmad , Gerszman Eden , Kazlow Esther , Abu Shtaya Aasem , Goldberg Natalia , Froylich Dvir , Haddad Riad
Published: February 2025

Background: Postoperative pancreatic fistulae (POPFs) are a significant cause of morbidity following left pancreatectomy. We hypothesized that incorporating serosal patching with the application of a synthetic sealant, a modified cyanoacrylate (Glubran®2), to the pancreatic stump, would decrease the incidence rate of clinically significant POPFs. Methods: This is a retrospective study of consecutive patients who underwent robot-assisted left pancreatectomy. The primary outcome was clinically significant POPFs within 90 days of surgery. Secondary outcomes included the incidence rate of POPFs (all the grades), 90-day morbidity, and 90-day mortality. Results: We compared outcomes between Glubran®2 sealant with serosal patching (GSP, n = 6) and Glubran®2 sealant without serosal patching (GNSP, n = 12) groups. The GSP group had significantly lower incidence rates of clinically significant POPFs (grades B/C) (p = 0.034) and overall POPFs (all the grades) (p = 0.046). No significant differences in 90-day postoperative morbidity were observed between the two groups (p = 0.56), and no 90-day mortality occurred in either group. Conclusions: Incorporating serosal patching along with Glubran®2 sealant in the management of the pancreatic stump during left pancreatectomy demonstrates promising results in reducing the incidence rate of clinically significant POPFs. This finding highlights the need for further research with larger sample sizes in order to confirm the observed outcomes and explore the long-term implications for postoperative complications and recovery in patients undergoing this procedure during pancreatic surgery.
Interval Analysis-Based Optimization: A Robust Model for Intensity-Modulated Radiotherapy (IMRT)
Authors: Sevilla-Moreno Andrés Camilo , Puerta-Yepes María Eugenia , Wahl Niklas , Benito-Herce Rafael , Cabal-Arango Gonzalo
Published: February 2025

Background: Cancer remains one of the leading causes of mortality worldwide, with radiotherapy playing a crucial role in its treatment. Intensity-modulated radiotherapy (IMRT) enables precise dose delivery to tumors while sparing healthy tissues. However, geometric uncertainties such as patient positioning errors and anatomical deformations can compromise treatment accuracy. Traditional methods use safety margins, which may lead to excessive irradiation of healthy organs or insufficient tumor coverage. Robust optimization techniques, such as minimax approaches, attempt to address these uncertainties but can result in overly conservative treatment plans. This study introduces an interval analysis-based optimization model for IMRT, offering a more flexible approach to uncertainty management. Methods: The proposed model represents geometric uncertainties using interval dose influence matrices and incorporates Bertoluzza’s metric to balance tumor coverage and organ-at-risk (OAR) protection. The θ parameter allows controlled robustness modulation. The model was implemented in matRad, an open-source treatment planning system, and evaluated on five prostate cancer cases. Results were compared against traditional Planning Target Volume (PTV) and minimax robust optimization approaches. Results: The interval-based model improved tumor coverage by 5.8% while reducing bladder dose by 4.2% compared to PTV. In contrast, minimax robust optimization improved tumor coverage by 25.8% but increased bladder dose by 23.2%. The interval-based approach provided a better balance between tumor coverage and OAR protection, demonstrating its potential to enhance treatment effectiveness without excessive conservatism. Conclusions: This study presents a novel framework for IMRT planning that improves uncertainty management through interval analysis. By allowing adjustable robustness modulation, the proposed model enables more personalized and clinically adaptable treatment plans. These findings highlight the potential of interval analysis as a powerful tool for optimizing radiotherapy outcomes, balancing treatment efficacy and patient safety.
Pain Accelerates, Swelling and Sensory Disturbances Delay Diagnosis in Mesenchymal Tumors
Authors: Elyes Maria , Heesen Philip , Schelling Georg , Bode-Lesniewska Beata , Studer Gabriela , Fuchs Bruno ,   on behalf of the Swiss Sarcoma Network
Published: February 2025

Sarcomas are rare mesenchymal tumors with significant heterogeneity, encompassing both bone and soft tissue neoplasms that can range from benign to malignant and from superficial to deep-seated lesions [...]
Knockout of p21-Activated Kinase 4 Stimulates MHC I Expression of Pancreatic Cancer Cells via an Autophagy-Independent Pathway
Authors: Ma Yi , Dumesny Chelsea , Dong Li , Ang Ching-Seng , Nikfarjam Mehrdad , He Hong
Published: February 2025

Background/Objectives: Pancreatic ductal adenocarcinoma (PDA) is one of the most malignant solid cancers. KRAS mutation accounts for over 90% of cases. p21-activated kinases (PAKs) act downstream of KRAS and are involved in tumorigenesis. The inhibition of PAK4 suppresses PDA by stimulating the tumor infiltration of cytotoxic T cells. The major histocompatibility complex class I (MHC I) is a key in presenting antigens to cytotoxic T cells. MHC I degradation via autophagy promotes the immune evasion of pancreatic cancer. We investigated the effect of PAK4 inhibition on MHC I expression and autophagy. Methods: In this study, using proteomic analysis, fluorescence-activated cell sorting (FACS), and immunoblotting, we examined the effect of PAK4 knockout (KO) in human PDA cells on the expression of MHC I and autophagy to identify the mechanism involved in the stimulation of cytotoxic T cells by PAK4 inhibition. Results: We found that PAK4 KO increased MHC I expression in two human PDA cell lines: MiaPaCa-2 and PANC-1. PAK4 KO also increased cancer cell autophagy. However, the inhibition of autophagy by chloroquine (CQ) did not affect the effect of PAK4 KO on apoptosis and cell death. More importantly, the inhibition of autophagy by CQ did not alter the expression of MHC I stimulated by PAK4 KO, indicating that PAK4 KO stimulated MHC I expression via an autophagy-independent pathway. Conclusions: We identified a role of PAK4 in MHC I expression by PDA cells, which is independent of autophagy.