bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in Endoscopic Ultrasound in Pancreatic Cancer Screening, Diagnosis, and Palliative Care
Authors: Zhang Wenyu , Chen Jingzheng , Zhang Wei , Xu Min
Published: January 2025

Pancreatic cancer is a highly aggressive malignancy with a profoundly poor prognosis. Clinically, the condition most frequently manifests with symptoms including painless jaundice, abdominal discomfort, and back pain. Early diagnosis and the implementation of effective therapeutic strategies are critical for improving patient survival outcomes. However, merely 10–20% of patients are diagnosed at an early stage, with the majority presenting at advanced stages, often with metastasis. Consequently, early detection and intervention are crucial for enhancing prognosis. The widespread adoption of endoscopic ultrasonography (EUS) technology in recent years has significantly enhanced the diagnostic accuracy for pancreatic space-occupying lesions. EUS is increasingly recognized for its pivotal role in alleviating malignant biliary obstruction (MBO), gastric outlet obstruction (GOO), and refractory pain in advanced pancreatic cancer. This article aims to provide an overall review of the current applications of EUS in the diagnosis and treatment of pancreatic cancer, exploring its advantages and limitations in early screening, diagnosis, and palliative care. Furthermore, this review explores potential future directions in the field, aiming to provide valuable insights to inform and enhance the clinical management of pancreatic cancer.
Quantifying Stress and Relaxation: A New Measure of Heart Rate Variability as a Reliable Biomarker
Authors: Rudics Emese , Buzás András , Pálfi Antónia , Szabó Zoltán , Nagy Ádám , Hompoth Emőke Adrienn , Dombi József , Bilicki Vilmos , Szendi István , Dér András
Published: January 2025

Background/Objectives: For the rapid, objective characterization of the physiological stress response, there is currently no generally recognized standard. The stress measurement methods used in practice (e.g., for psychological measures of stress) are often subjective, or in the case of biological markers (e.g., cortisol, amylase), they usually require a blood test. For this reason, the use of heart rate variability (HRV) to characterize stress has recently come to the fore. HRV is the variability in the length of heartbeat intervals, which indicates the ability of the heart to respond to various physiological and environmental stimuli. However, the conventional HRV metrics are not corrected for heart rate dependence; hence, they fail to fully account for the complex physiology of stress and relaxation. In order to remedy this problem, here we introduce a novel HRV parameter, the normalized variability derived from an RMSSD “Master Curve”, and we compare it with the conventional metrics. Methods: In Study 1, the relaxation state was induced either by heart rate variability biofeedback training (N = 21) or by habitual relaxation (N = 21), while in Study 2 (N = 9), the Socially Evaluated Cold Pressor Test and the Socially Evaluated Stroop Test were used to induce stress in the subject. For a statistical evaluation of the data, the Kolmogorov–Smirnov test was used to compare the distributions of mean HR, log(RMSSD), log(SDNN), and normalized variability before, during, and after relaxation and stress. Results: The results of this study indicate that while log(RMSSD) and log(SDNN) did not change significantly, the normalized variability did undergo a significant change both in relaxation states and in stress states induced by the Socially Evaluated Cold Pressor Test. Conclusions: Overall, we suggest this novel type of normalized variability ought to be used as a sensitive stress indicator, and in general, for the characterization of the complex processes of the vegetative nervous system.
Rescue of Mutant CFTR Channel Activity by Investigational Co-Potentiator Therapy
Authors: Bacalhau Mafalda , Ferreira Filipa C. , Azevedo Marcelo Folhadella M. F. , Rosa Talita P. , Buarque Camilla D. , Lopes-Pacheco Miquéias
Published: January 2025

Background: The potentiator VX-770 (ivacaftor) has been approved as a monotherapy for over 95 cystic fibrosis (CF)-causing variants associated with gating/conductance defects of the CF transmembrane conductance regulator (CFTR) channel. However, despite its therapeutic success, VX-770 only partially restores CFTR activity for many of these variants, indicating they may benefit from the combination of potentiators exhibiting distinct mechanisms of action (i.e., co-potentiators). We previously identified LSO-24, a hydroxy-1,2,3-triazole-based compound, as a modest potentiator of p.Arg334Trp-CFTR, a variant with a conductance defect for which no modulator therapy is currently approved. Objective/Methods: We synthesized a new set of LSO-24 structure-based compounds, screened their effects on p.Arg334Trp-CFTR activity, and assessed the additivity of hit compounds to VX-770, ABBV-974, ABBV-3067, and apigenin. After validation by electrophysiological assays, the most promising hits were also assessed in cells expressing other variants with defective gating/conductance, namely p.Pro205Ser, p.Ser549Arg, p.Gly551Asp, p.Ser945Leu, and p.Gly1349Asp. Results: We found that five compounds were able to increase p.Arg334Trp-CFTR activity with similar efficacy, but slightly greater potency promoted by LSO-150 and LSO-153 (EC50: 1.01 and 1.26 μM, respectively). These two compounds also displayed a higher rescue of p.Arg334Trp-CFTR activity in combination with VX-770, ABBV-974, and ABBV-3067, but not with apigenin. When tested in cells expressing other CFTR variants, LSO-24 and its derivative LSO-150 increased CFTR activity for the variants p.Ser549Arg, p.Gly551Asp, and p.Ser945Leu with a further effect in combination with VX-770 or ABBV-3067. No potentiator was able to rescue CFTR activity in p.Pro205Ser-expressing cells, while p.Gly1349Asp-CFTR responded to VX-770 and ABBV-3067 but not to LSO-24 or LSO-150. Conclusions: Our data suggest that these new potentiators might share a common mechanism with apigenin, which is conceivably distinct from that of VX-770 and ABBV-3067. The additive rescue of p.Arg334Trp-, p.Ser549Arg-, p.Gly551Asp-, and p.Ser945Leu-CFTR also indicates that these variants could benefit from the development of a co-potentiator therapy.
Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development
Authors: Kwon Whi-An , Seo Ho Kyung , Song Geehyun , Lee Min-Kyung , Park Weon Seo
Published: January 2025

Urothelial carcinoma (UC) is the most common histological subtype of bladder tumors; however, bladder cancer represents a heterogeneous group of diseases with at least 40 distinct histological subtypes. Among these, the 2022 World Health Organization classification of urinary tract tumors identifies a range of less common subtypes of invasive UC, formerly known as variants, which are considered high-grade tumors, including squamous cell, small-cell, sarcomatoid urothelial, micropapillary, plasmacytoid, and urachal carcinomas, and adenocarcinoma. Their accurate histological diagnosis is critical for risk stratification and therapeutic decision-making, as most subtype histologies are associated with poorer outcomes than conventional UC. Despite the importance of a precise diagnosis, high-quality evidence on optimal treatments for subtype histologies remains limited owing to their rarity. In particular, neoadjuvant and adjuvant chemotherapy have not been well characterized, and prospective data are scarce. For advanced-stage diseases, clinical trial participation is strongly recommended to address the lack of robust evidence. Advances in molecular pathology and the development of targeted therapies and immunotherapies have reshaped our understanding and classification of bladder cancer subtypes, spurring efforts to identify predictive biomarkers to guide personalized treatment strategies. Nevertheless, the management of rare bladder cancer subgroups remains challenging because they are frequently excluded from clinical trials. For localized disease, curative options such as surgical resection or radiotherapy are available; however, treatment options become more limited in recurrence or metastasis, where systemic therapy is primarily used to control disease progression and palliate symptoms. Herein, we present recent advances in the management of urothelial and non-urothelial bladder cancer subtypes and also explore the current evidence guiding their treatment and emphasize the challenges and perspectives of future therapeutic strategies.
An Intelligent Modeling Method for Protecting and Inheriting the Construction Techniques of Wooden Stilt Buildings
Authors: Wu Jie , Chi Feng , Wei Yujiao , Zhao Ye , Huang Shuoyuan , Xu Hongtao
Published: January 2025

This study examines the digital translation of traditional wooden architectural construction techniques through the application of Building Information Modeling (BIM) methods. The development of a Heritage Building Information Modeling (HBIM) model for these techniques necessitates interdisciplinary integration. Critical steps involve the intelligent incorporation of wooden architectural knowledge into parametric models and the creation of advanced modeling methods capable of translating such models. These aspects are essential for bridging existing gaps and enhancing HBIM applications. By using the Dong drum tower as a case study, this paper presents a parametric model for stilt-style wooden structures, emphasizing the generation rules of construction techniques and the extraction and translation of parameters. A smart automated modeling method was developed and programmed collaboratively using Grasshopper (version 1.0.0007) and Python (version 2.7.12.0). This method facilitates the generation of diverse, customizable drum tower models within 60 s and has successfully created the tallest drum tower model in Guangxi based on actual measurements, validating the method’s reliability and effectiveness. The findings of this study offer digital, automated, and intelligent support for the preservation and transmission of traditional architectural techniques.
Exploring the Driving Factors for Low-Carbon Development of the Construction Industry in China
Authors: Geng Yiyu , Xu Youquan , Ma Ke , Li Yuanyuan , Zhang Zhigang
Published: January 2025

The construction sector in China exhibits elevated levels of energy consumption and carbon emissions, which presents considerable obstacles to the attainment of carbon reduction objectives. Contemporary research predominantly focuses on the advancement of low-carbon building technologies and the measurement of carbon emissions. This study seeks to study the driving factors of low-carbon development in China’s construction industry and the complex relationships between different entities from the perspective of industrial systems. Initially, through a comprehensive literature review and expert interviews, six distinct stakeholders and twenty-one relevant driving factors were identified. Following this, Social Network Analysis was employed to evaluate the data collected from the surveys. The findings suggest that ten critical factors, such as the market demand for emerging market entities, the market demand and competition for construction entities, and business needs for non-governmental entities, significantly influence the low-carbon construction industry. Within the network of participants, the government, the public, and construction entities are positioned centrally, exerting substantial influence and emerging as focal points for industrial development. The insights derived from this study will provide critical guidance on the engagement of various stakeholders in low-carbon initiatives and will serve as a reference for policymakers in the transformation of the construction industry.
Considering the Effect of Various Silica Types on Chemical, Physical and Mechanical Properties in Cement Mortar Production via Substitution with Cement Content
Authors: Hansu Osman
Published: January 2025

The main objective of this study is to reduce CO2 emissions resulting from rapidly increasing cement production and utilization rates worldwide. For this purpose, the effects of NS (nano-silica) and SF (silica fume) materials, which are the post-production wastes of industrial products, the substitute material obtained by grinding SG (silica gel) wastes used for packaging purposes in the preservation of industrial electronic products and many other areas, and MLS (micritic limestone) obtained by grinding limestone, a natural resource, on mortars after cement substitutions were evaluated. MLS and SG contents were sieved through a 0.063 mm sieve and substituted into the mixtures, while specific surface area values for SF and NS were obtained as 23 m2/g and 150 m2/g. Each of these materials was used in mortars by substituting between 0% and 10% cement by weight. The samples were subjected to consistency determination and then evaluated for setting time. Subsequently, flexural tests were carried out on 40 mm × 40 mm × 160 mm specimens placed in molds, and compressive tests were carried out on prism fragments broken after flexural tests. The experimental results showed that substitution of SG substitutes with cement at 3–10 wt% was highly effective against SF, NS and MLS in terms of strength and workability properties.
Agreement Between High-Risk Human Papillomavirus Testing in Paired Self-Collected and Clinician-Collected Samples from Cervical Cancer Screening in Spain
Authors: Ibáñez Raquel , Roura Esther , Morey Francisca , Andújar Miguel , Pavón Miquel Ángel , Acera Amelia , Bruni Laia , de Sanjosé Silvia
Published: January 2025

Background: Implementing self-sampling (SS) in cervical cancer screening requires comparable results to clinician-collected samples (CCS). Agreement measures are essential for evaluating HPV test performance. Previous studies on non-paired samples have reported higher viral cycle threshold (Ct) values in SS compared to CCS, affecting sensitivity for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Objectives: We aimed to evaluate the agreement of high-risk (hr)HPV testing results between SS and CCS using paired samples and to explore differences in Ct values. Methods: Women aged 30 to 65 years attending cervical cancer screening in two regions of Spain were invited to participated in this study. For each woman there was: CCS collected during the screening visit using liquid-based cytology and cytobrush, and a SS using a brush at home one month later. A PCR-based assay was used for hrHPV detection. Agreement in hrHPV results among both samples, Ct value differences, and their association with screening outcomes were analyzed. Results: This study included 981 women with paired samples. SS had a higher hrHPV prevalence than CCS (overall ratio of 1.3). Positive agreement for all hrHPV genotypes, HPV16, HPV18, and other hrHPV types were 85%, 91.3%, 66.7%, and 83.3%, respectively. Negative agreement was >95% for all results. Median Ct values was slightly higher in SS than in CSS (32.9 vs. 30.6, p = 0.02). Seven CIN2+ cases HPV positive were detected by both methods. One CIN3 case was missed by SS. Conclusions: This study showed a good agreement between SS and CCS for hrHPV testing in a routine screening in Spain. Despite the slightly higher Ct values for SS, no significant impact on sensitivity could be determined due to the low incidence of CIN2+ cases. Further research on larger paired samples is needed to assess the implications of Ct values on test sensitivity.
Modulation of Tumor-Associated Macrophages to Overcome Immune Suppression in the Hepatocellular Carcinoma Microenvironment
Authors: Singer Mahmoud , Zhang Zhuoli , Dayyani Farshid , Zhang Zigeng , Yaghmai Vahid , Choi April , Valerin Jennifer , Imagawa David , Abi-Jaoudeh Nadine
Published: January 2025

Hepatocellular carcinoma (HCC) is a major global health issue characterized by poor prognosis and complex tumor biology. One of the critical components of the HCC tumor microenvironment (TME) is tumor-associated macrophages (TAMs), which play a pivotal role in modulating tumor growth, immune evasion, and metastasis. Macrophages are divided into two major subtypes: pro-inflammatory M1 and anti-inflammatory M2, both of which may exist in TME with altered function and proportion. The anti-inflammatory M2 macrophages are further subdivided into four distinct immune suppressive subsets. TAMs are generally counted as M2-like macrophages with altered immune suppressive functions that exert a significant influence on both cancer progression and the ability of tumors to escape immune surveillance. Their involvement in modulating immune responses via different mechanisms at the local and systemic levels has made them a key target for therapeutic interventions seeking to enhance treatment outcomes. How TAMs’ depletion influences immune responses in cancer is the primary interest in cancer immunotherapies. The purpose of this review is to delve into the recent progress made in TAM-targeting therapies. We will explore the current theories, benefits, and challenges associated with TAMs’ depletion or inhibition. The manuscript concludes with future directions and potential implications for clinical practice.
Topical and Intralesional Treatments for Skin Metastases and Locoregionally Advanced Melanoma
Authors: Criado-Otero María , Navedo-de las Heras María , Samaniego-González Elia
Published: January 2025

Cutaneous melanoma is a malignant neoplasm with local and distant metastatic potential. When feasible, surgery is the first line of treatment in locoregionally advanced disease. Topical and intralesional treatments can be an alternative second-line treatment. The aim of this article was to perform a narrative review of the most widely used topical and intralesional treatments for locoregionally advanced melanoma. Diphenciprone, imiquimod and 5-florouracil were included as topical treatments and bacillus Calmette-Guerin, interleukin 2, rose bengal, talimogene laherparepvec and electrochemotherapy were included as intralesional treatments. Brief comments on other alternatives in development such as interferon-alpha, interleukin-12, ipilimumab and intralesional daromun are presented. Topical treatments generally have higher response rates in epidermal metastases than in deeper metastases. In addition, the larger the lesions, the worse they tend to respond to local treatments. Some reports show that combining certain systemic treatments and topical or intralesional therapies can improve response rates. It has also been described in a few papers that non-injected lesions may respond after the application of a local therapy in distant skin-metastases. Many of these intralesional treatments are being combined in different investigations with systemic immunotherapies, with the aim of obtaining synergic responses in those patients with refractory disease.
Differential Effects of GLP-1 Receptor Agonists on Cancer Risk in Obesity: A Nationwide Analysis of 1.1 Million Patients
Authors: Levy Shauna , Attia Abdallah , Elshazli Rami M. , Abdelmaksoud Ahmed , Tatum Danielle , Aiash Hani , Toraih Eman A.
Published: January 2025

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated significant efficacy in obesity treatment beyond their original development for type-2 diabetes management. This comprehensive study investigated the relationship between GLP-1RA use and cancer incidence in individuals with obesity across a 5-year follow-up period. Methods: We conducted a large-scale cohort study using the TriNetX US Collaborative Network database (2013–2023) examining adult patients with obesity. The study utilized propensity score matching to pair GLP-1RA-treated patients with controls (1:1) using the nearest neighbor method. Cancer incidence served as the primary outcome measure over the 5-year follow-up, with subgroup analyses considering individual GLP-1RA agents, patient sex, and BMI categories. Results: Analysis revealed significant cancer-risk reductions associated with GLP-1RA use across multiple cancer types compared to matched controls. Notable risk reductions were observed in gastrointestinal (HR 0.67, 95% CI 0.59–0.75), skin (HR 0.62, 95% CI 0.55–0.70), breast (HR 0.72, 95% CI 0.64–0.82), female genital (HR 0.61, 95% CI 0.53–0.71), prostate (HR 0.68, 95% CI 0.58–0.80), and lymphoid/hematopoietic cancers (HR 0.69, 95% CI 0.60–0.80). Semaglutide demonstrated superior protective effects, particularly in gastrointestinal cancers (HR 0.45, 95% CI 0.37–0.53). Conversely, liraglutide showed increased risks for thyroid (HR 1.70, 95% CI 1.03–2.82) and respiratory cancers (HR 1.62, 95% CI 1.13–2.32). Conclusions: This research provides compelling evidence for GLP-1RA’s potential role in cancer-risk reduction, with semaglutide showing particularly promising results. The differential effects observed among GLP-1RA agents emphasize the importance of personalized medicine approaches. These findings suggest significant implications for clinical practice and future research in both obesity management and cancer prevention.
The Vimentin-Targeting Drug ALD-R491 Partially Reverts the Epithelial-to-Mesenchymal Transition and Vimentin Interactome of Lung Cancer Cells
Authors: Rosier Marieke , Krstulović Anja , Kim Hyejeong Rosemary , Kaur Nihardeep , Enakireru Erhumuoghene Mary , Symmes Deebie , Dobra Katalin , Chen Ruihuan , Evans Caroline A. , Gad Annica K. B.
Published: January 2025

Background: The epithelial-to-mesenchymal transition (EMT) is a common feature in early cancer invasion. Increased vimentin is a canonical marker of the EMT; however, the role of vimentin in EMT remains unknown. Methods: To clarify this, we induced EMT in lung cancer cells with TGF-β1, followed by treatment with the vimentin-targeting drug ALD-R491, live-cell imaging, and quantitative proteomics. Results: We identified 838 proteins in the intermediate filament fraction of cells. TGF-β1 treatment increased the proportion of vimentin in this fraction and the levels of 24 proteins. Variants of fibronectin showed the most pronounced increase (137-fold), followed by regulators of the cytoskeleton, cell motility, and division, such as the mRNA-splicing protein SON. TGF-β1 increased cell spreading and cell migration speed, and changed a positive correlation between cell migration speed and persistence to negative. ALD-R491 reversed these mesenchymal phenotypes to epithelial and the binding of RNA-binding proteins, including SON. Conclusions: These findings present many new interactors of intermediate filaments, describe how EMT and vimentin filament dynamics influence the intermediate filament interactome, and present ALD-R491 as a possible EMT-inhibitor. The observations support the hypothesis that the dynamic turnover of vimentin filaments and their interacting proteins govern mesenchymal cell migration, EMT, cell invasion, and cancer metastasis.
Factors Influencing the Duration of Maintenance Therapy in Metastatic Colorectal Cancer
Authors: Fourrier Théo , Truntzer Caroline , Peroz Morgane , Derangère Valentin , Vincent Julie , Bengrine-Lefèvre Leila , Hennequin Audrey , Palmier Rémi , Orry David , Rabel Thomas , Ghiringhelli François
Published: January 2025

Background/Objectives: Metastatic colorectal cancer (mCRC) is mainly treated with 5-Fluoro-Uracil (5-FU), Oxaliplatin and Irinotecan chemotherapies and anti-Epidermal Growth Factor Receptor (EGFR) or anti-Vascular Endothelial Growth Factor (VEGF) targeted therapies. Due to chemotherapy-related toxicity, patients receive induction treatment to achieve tumour response followed by maintenance therapy with less cytotoxic molecules or a chemotherapy-free interval to reduce chemotherapy-related toxicity. In this study, the aim was to determine the patient, cancer and treatment factors that influence the duration of maintenance therapy (DMT). Methods: We collected retrospective data on a cohort of 133 patients treated at the Centre Georges François Leclerc (CGFL) cancer centre in Dijon between March 2014 and June 2022. Patients had unresectable or potentially resectable diseases. They received first-line induction treatment with chemotherapy and/or targeted therapy and maintenance treatment, defined as the interruption of at least one chemotherapy agent. Results: In the multivariate analysis, age (HR: 1.02, 95% CI 1.00–1.04, p = 0.031), N2 nodal status (HR: 1.78, 95% CI 1.09–2.89, p = 0.021) and the presence of peritoneal metastases (HR: 2.05, 95% CI 1.25–3.36, p = 0.004), as well as baseline carcino-embryonic antigen (CEA) level (HR: 1.10, 95% CI 1.00–1.20, p = 0.052), were significantly associated to poor DMT. Local treatment of liver metastases also significantly reduced the DMT (HR: 0.49, 95% CI 0.28–0.86, p = 0.013). In our cohort, induction triplet chemotherapy significantly increased the CEA delta (70% vs. 44%, p = 0.047) compared to doublet chemotherapy and led to a higher rate of liver surgery (40% vs. 21%, p = 0.014) and a trend for a higher rate of local treatment of metastases (62% vs. 45%, p = 0.059). Conclusions: Duration of maintenance therapy is determined by the initial patient and colorectal cancer characteristics. However, it is significantly increased by local treatment of liver metastases. By reducing the tumour burden, a triplet induction chemotherapy regimen increases the rate of liver metastase resection.
Endoscopic Ultrasound-Guided Treatments for Pancreatic Cancer: Understanding How Endoscopic Ultrasound Has Revolutionized Management of Pancreatic Cancer
Authors: Singh Sahib , Facciorusso Antonio , Vinayek Rakesh , Dutta Sudhir , Dahiya Dushyant Singh , Aswath Ganesh , Sharma Neil , Inamdar Sumant
Published: January 2025

Pancreatic cancer is associated with high rates of morbidity and mortality. Endoscopic ultrasound (EUS)-guided biopsy has become the standard diagnostic modality per the guidelines. The use of EUS has been growing for providing various treatments in patients with pancreatic cancers: biliary and gallbladder drainage for those with malignant biliary obstruction, gastroenterostomy for malignant gastric outlet obstruction, celiac plexus/ganglia neurolysis for pain control, radiofrequency ablation, placement of fiducial markers, and injection of local chemotherapeutic agents. In this review, we explore the recent clinical studies evaluating the EUS-guided treatments in pancreatic cancer.
Complication Rates After Mastectomy and Reconstruction in Breast Cancer Patients Treated with Hypofractionated Radiation Therapy Compared to Conventional Fractionation: A Single Institutional Analysis
Authors: Falick Michaeli Tal , Hatoom Feras , Skripai Antoni , Wajnryt Ella , Allweis Tanir M. , Paluch-Shimon Shani , Shachar Yair , Popovtzer Aron , Wygoda Marc , Blumenfeld Philip
Published: January 2025

Introduction: Radiation therapy plays an important role in the treatment of localized breast cancer. Hypofractionated (HF) radiation therapy has emerged as a promising alternative to conventional fractionation (CF) schedules, offering comparable efficacy with reduced treatment duration and costs. However, concerns remain regarding its safety and rate of toxicity, particularly in patients undergoing mastectomy with breast reconstruction. This study aimed to assess the implant-related complications in breast cancer patients receiving HF post-mastectomy radiation therapy (PMRT) and reconstruction compared to CF PMRT. Methods: A retrospective study was conducted on 59 breast cancer patients who underwent mastectomy and breast reconstruction between 2013 and 2021 and received adjuvant PMRT. Patient demographics, treatment characteristics, and implant-related complications were analyzed. Statistical tests including chi-square, Fischer’s exact test, and multivariable Cox regression were employed for analysis. Results: Of the 59 patients, 29 received HF PMRT and 30 received CF PMRT. At a median follow-up of 23.4 months, there was no significant difference in major implant-related complications between the two groups (24.1% in HF vs. 33.3% in CF, p = 0.436). Most complications in the HF group occurred within the first two years post-radiation. Age over 40 was identified as a significant predictor for higher implant-related complications (p = 0.029). Conclusions: Our findings indicate that HF PMRT and reconstruction does not increase the risk of major implant-related complications compared to CF PMRT. These results align with the existing literature, supporting the safety of HF radiation in breast cancer patients who underwent mastectomy with reconstruction.
The Impact of Radioactive Iodine on Outcomes Among Pediatric and Adolescent Thyroid Cancer Patients: A SEER Database Analysis
Authors: Persons Emily M. , Hussein Mohammad H. , Herrera Marcela , Pinion Dylan , Webster Alyssa , Pineda Eric , Fawzy Manal S. , Toraih Eman A. , Kandil Emad
Published: January 2025

Background/Objectives: Pediatric populations with well-differentiated thyroid cancer typically have favorable prognoses. However, the role of radioactive iodine (RAI) ablation in these patients remains uncertain. This investigation evaluates the national trends, therapeutic practices, and the impact of RAI on clinical outcomes. Methods: Patients aged 21 years or younger with differentiated thyroid cancer, identified from the SEER database between 2000 and 2019, were analyzed. We compared the treatment approaches and survival outcomes of patients who underwent RAI ablation with those who did not. Results: This retrospective cohort study encompassed 5318 pediatric patients, with 55.9% (n = 2973) who underwent RAI ablation. RAI utilization declined from 65% to 38.4% in 2019. Compared with those who did not undergo RAI, RAI patients presented with a larger tumor size (mean size: 27.7 vs. 20.4 mm), a higher T3/T4 stage (35.8% vs. 15.3%), nodal metastases (60.7% vs. 28.8%), and distant metastases (2.7% vs. 0.9%) (all p < 0.001). Despite this, RAI was not an independent predictor of recurrence, second malignancy, or mortality. The analysis showed no significant differences in long-term survival between the RAI and non-RAI groups (p > 0.05), with African American patients having an increased risk of mortality (HR = 3.81; p = 0.038). Cancer-directed surgery emerged as a protective factor (HR = 0.08; p = 0.018), while RAI treatment did not significantly affect mortality risk (p = 0.09). Conclusions: Excellent pediatric thyroid cancer outcomes were achieved regardless of RAI use. Further research should clarify appropriate RAI indications while addressing racial outcome inequities.
Fertility Sparing in Endometrial Cancer: Where Are We Now?
Authors: Centini Gabriele , Colombi Irene , Ianes Ilaria , Perelli Federica , Ginetti Alessandro , Cannoni Alberto , Habib Nassir , Negre Ramon Rovira , Martire Francesco Giuseppe , Raimondo Diego , Lazzeri Lucia , Zupi Errico
Published: January 2025

Endometrial cancer is the most common gynecological neoplasm with an increased incidence in the premenopausal population in recent decades. This raises the problem of managing endometrial cancer in fertile women who have not yet achieved pregnancy. In these women, after careful selection, hysterectomy may be postponed in favor of conservative management if specific requirements are met. The latest evidence is focused on early endometrial carcinoma, endometrioid histotype, Grading 1, with no evidence of myometrial infiltration. Few clinical trials have opened this possibility also for women with an endometrial cancer Grading 2 diagnosis. There are still questions about the best medical therapy, dosage, route, and duration of treatment. Oral progestins or levonorgestrel-releasing intrauterine devices appear to be the options associated with the best outcome in terms of complete response and lower recurrence rates. Other options include the use of GnRH analogues, surgical hysteroscopy, or metformin, in a therapeutic approach that takes into account the characteristics of the patient. The pursuit of pregnancy should start as soon as two consecutive endometrial biopsies are obtained 3 months apart from each other; it is recommended to refer the patients to ART centers to maximize the success rate. After having reached the fulfillment of the reproductive desire, surgical radical treatment is still recommended.
Richness for Tumor-Infiltrating B-Cells in the Oral Cancer Tumor Microenvironment Is a Prognostic Factor in Early-Stage Disease and Improves Outcome in Advanced-Stage Disease
Authors: Nauta Irene H. , Nijenhuis Dennis N. L. M. , Ganzevles Sonja H. , Raaff Pamela I. , Kloosterman Jan , Bloemena Elisabeth , Brakenhoff Ruud H. , Leemans C. René , van de Ven Rieneke
Published: January 2025

Background/Objectives: Most studies on the interaction between the immune system and cancer focus on T-cells, whereas studies on tumor-infiltrating B-lymphocytes (TIL-Bs) are still underrepresented. The aim of this study was to assess the prognostic impact of TIL-Bs in early- and advanced-stage oral cavity squamous cell carcinoma (OCSCC). Methods: In total, 222 OCSCCs were studied. Consecutive sections were stained for CD45 and CD19. OCSCCs were categorized as either “TIL-B-rich” or “TIL-B-poor”, and the survival of both groups was analyzed. Similar analyses were performed for CD45+ TILs and the CD19/CD45 ratio. Matched subgroups of twelve TIL-B-rich and TIL-B-poor tumors were stained for CD3 and CD8 to determine differences in T-cell infiltration, and further spatial interaction between T- and B-cells was evaluated in six samples. Results: Five-year OS was 75.0% for TIL-B-rich and 54.2% for TIL-B-poor OCSCCs (p < 0.001). The survival benefit of TIL-B-rich OCSCCs remained significant after correction for the histopathological characteristics (p = 0.033). While for early-stage tumors, TIL-B richness benefited OS independent of demographic-, clinical, or histopathological features, for advanced-stage disease, this was not the case, although a clear benefit of a TIL-B-rich status was observed, specifically up until 36 months after diagnosis. TIL-B-rich tumors contained more CD3+ TILs (p = 0.007), but not CD8+ TILs. Spatial characterization suggested that TIL-Bs mostly co-localized with CD3+CD8− TILs and that this interaction was increased in TIL-B-rich OCSCC. Conclusions: The presence of TIL-Bs is associated with a more favorable prognosis in OCSCC, in particular for early-stage disease.
Common Genetic Variants in Rare Disorders: Hematology and Beyond
Authors: Evangelidis Paschalis , Gavriilaki Maria , Kotsiou Nikolaos , Gavriilaki Eleni
Published: January 2025

Emerging evidence suggests that common genetic variants play a significant role in various rare but life-threatening hematological and non-hematological conditions [...]
Identifying Flood Source Areas and Analyzing High-Flow Extremes Under Changing Land Use, Land Cover, and Climate in the Gumara Watershed, Upper Blue Nile Basin, Ethiopia
Authors: Belay Haile , Melesse Assefa M. , Tegegne Getachew , Tamiru Habtamu
Published: January 2025

Changes in land use and land cover (LULC) and climate increasingly influence flood occurrences in the Gumara watershed, located in the Upper Blue Nile (UBN) basin of Ethiopia. This study assesses how these factors impact return period-based peak floods, flood source areas, and future high-flow extremes. Merged rainfall data (1981–2019) and ensemble means of four CMIP5 and four CMIP6 models were used for historical (1981–2005), near-future (2031–2055), and far-future (2056–2080) periods under representative concentration pathways (RCP4.5 and RCP8.5) and shared socioeconomic pathways (SSP2-4.5 and SSP5-8.5). Historical LULC data for the years 1985, 2000, 2010, and 2019 and projected LULC data under business-as-usual (BAU) and governance (GOV) scenarios for the years 2035 and 2065 were used along with rainfall data to analyze flood peaks. Flood simulation was performed using a calibrated Hydrologic Engineering Center–Hydrologic Modeling System (HEC-HMS) model. The unit flood response (UFR) approach ranked eight subwatersheds (W1–W8) by their contribution to peak flood magnitude at the main outlet, while flow duration curves (FDCs) of annual maximum (AM) flow series were used to analyze changes in high-flow extremes. For the observation period, maximum peak flood values of 211.7, 278.5, 359.5, 416.7, and 452.7 m3/s were estimated for 5-, 10-, 25-, 50-, and 100-year return periods, respectively, under the 2019 LULC condition. During this period, subwatersheds W4 and W6 were identified as major flood contributors with high flood index values. These findings highlight the need to prioritize these subwatersheds for targeted interventions to mitigate downstream flooding. In the future period, the highest flow is expected under the SSP5-8.5 (2056–2080) climate scenario combined with the BAU-2065 land use scenario. These findings underscore the importance of strategic land management and climate adaptation measures to reduce future flood risks. The methodology developed in this study, particularly the application of RF-MERGE data in flood studies, offers valuable insights into the existing knowledge base on flood modeling.
Impedance Controller Analysis for a Two-Degrees-Of-Freedom Ankle Rehabilitation Machine with Serious Game Interactions
Authors: Cirilo-Piñon Oscar I. , Barrera-Sánchez Agustín , Guzmán-Valdivia Cesar H. , Adam-Medina Manuel , Campos-Amezcua Rafael , Blanco-Ortega Andrés , Martínez-Mata Arturo
Published: January 2025

An ankle sprain can be caused by daily activities such as running, walking, or playing sports. In many cases, the patient’s ankle suffers severe or permanent damage that requires rehabilitation to return to its initial state. Thanks to technological advances, robotics has allowed for the development of machines that generate precise, efficient, and safe movements. In addition, these machines are manipulated by a specific control depending on the rehabilitation objective. Impedance control is used in ankle rehabilitation machines for active–resistive-type rehabilitation, where the patient participates by exerting a force on the machine repeatedly. Serious games are an example of an activity where the patient can interact with a video game while rehabilitating. Currently, most machines involving impedance control and targeted at serious gaming applications are mechanically composed of one degree of freedom, so the addition of another degree is a novelty. This paper presents simulation results comparing different impedance controls reported in the literature to determine the best option for applying a 2-DOF ankle rehabilitation machine using serious games. The results obtained are presented by comparing them according to the force applied to the rehabilitation machine (emulating the behavior of a patient). From the impedance controllers analyzed for horizontal (abduction/adduction) and vertical (dorsiflexion/plantarflexion) movements in the rehabilitation machine, it was determined that the PD control, which considers some mechanical parameters, presents a better performance. With this controller, fast and smooth angular movements are generated, while the consumption of kinetic energy is kept in a low range, proportional to the applied forces, compared to the other impedance controls analyzed.
Advancements in Predictive Analytics: Machine Learning Approaches to Estimating Length of Stay and Mortality in Sepsis
Authors: Ben Khalfallah Houssem , Jelassi Mariem , Demongeot Jacques , Bellamine Ben Saoud Narjès
Published: January 2025

Sepsis remains a major global health concern, causing high mortality rates, prolonged hospital stays, and substantial economic burdens. The accurate prediction of clinical outcomes, such as mortality and length of stay (LOS), is critical for optimizing hospital resource allocation and improving patient management. The present study investigates the potential of machine learning (ML) models to predict these outcomes using a dataset of 1492 sepsis patients with clinical, physiological, and demographic features. After rigorous preprocessing to address missing data and ensure consistency, multiple classifiers, including Random Forest, Extra Trees, and Gradient Boosting, were trained and validated. The results demonstrate that Random Forest and Extra Trees achieve high accuracy for LOS prediction, while Gradient Boosting and Bernoulli Naïve Bayes effectively predict mortality. Feature importance analysis identified ICU stay duration (ICU_DAYS_OBS) as the most influential predictor for both outcomes, alongside vital signs, white blood cell counts, and lactic acid levels. These findings highlight the potential of ML-driven clinical decision support systems (CDSSs) to enhance early risk assessment, optimize ICU resource planning, and support timely interventions. Future research should refine predictive features, integrate advanced biomarkers, and validate models across larger and more diverse datasets to improve scalability and clinical impact.
Two-Dimensional Shear-Wave Elastography: Accuracy in Liver Fibrosis Staging Using Magnetic Resonance Elastography as the Reference Standard
Authors: Charoenchue Puwitch , Khorana Jiraporn , Chitapanarux Taned , Inmutto Nakarin , Na Chiangmai Wittanee , Amantakul Amonlaya , Pojchamarnwiputh Suwalee , Tantraworasin Apichat
Published: January 2025

Background: The accurate staging of liver fibrosis is crucial for managing chronic liver disease (CLD). Although magnetic resonance elastography (MRE) is the reference standard for noninvasive fibrosis assessment, its cost, specialized hardware, and operational demands restrict accessibility. In contrast, two-dimensional shear-wave elastography (2D-SWE) is more affordable, accessible, and widely integrated into routine ultrasound systems. Objective: Our aim was to determine the optimal 2D-SWE cut-offs for detecting significant fibrosis (≥F2) and evaluate its diagnostic performance across fibrosis stages. Methods: In this prospective study, 71 patients with suspected CLD underwent same-day MRE and 2D-SWE. MRE-defined cut-offs categorized fibrosis stages (≥3.5 kPa for significant fibrosis). Sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and likelihood ratios were calculated for various 2D-SWE thresholds. Results: At a 2D-SWE cut-off of 7.0 kPa, sensitivity for detecting ≥F2 fibrosis was 100% with a specificity of 85.7% and a positive likelihood ratio (LR+) of 7.0. Increasing the threshold to 8.0 kPa improved specificity to 91.8% while maintaining a sensitivity of 86.4% and achieving an AUROC of 0.89. For cirrhosis, a cut-off of 11.0 kPa achieved 100% sensitivity and 96.9% specificity. A 5.0 kPa cut-off reliably excluded abnormal stiffness with 89.1% sensitivity. Conclusions: Two-dimensional SWE is a reliable method for staging liver fibrosis. Thresholds of 7.0 kPa for screening significant fibrosis, 8.0 kPa for confirmation, and 11.0 kPa for diagnosing cirrhosis demonstrate high diagnostic accuracy. A 5.0 kPa cut-off effectively excludes abnormal liver stiffness.
SmartSkin-XAI: An Interpretable Deep Learning Approach for Enhanced Skin Cancer Diagnosis in Smart Healthcare
Authors: Hamim Sultanul Arifeen , Tamim Mubasshar U. I. , Mridha M. F. , Safran Mejdl , Che Dunren
Published: January 2025

Background: Skin cancer, particularly melanoma, poses significant challenges due to the heterogeneity of skin images and the demand for accurate and interpretable diagnostic systems. Early detection and effective management are crucial for improving patient outcomes. Traditional AI models often struggle with balancing accuracy and interpretability, which are critical for clinical adoption. Methods: The SmartSkin-XAI methodology incorporates a fine-tuned DenseNet121 model combined with XAI techniques to interpret predictions. This approach improves early detection and patient management by offering a transparent decision-making process. The model was evaluated using two datasets: the ISIC dataset and the Kaggle dataset. Performance metrics such as classification accuracy, precision, recall, and F1 score were compared against benchmark models, including DenseNet121, InceptionV3, and esNet50. Results: SmartSkin-XAI achieved a classification accuracy of 97% on the ISIC dataset and 98% on the Kaggle dataset. The model demonstrated high stability in precision, recall, and F1 score measures, outperforming the benchmark models. These results underscore the robustness and applicability of SmartSkin-XAI for real-world healthcare scenarios. Conclusions: SmartSkin-XAI addresses critical challenges in melanoma diagnosis by integrating state-of-the-art architecture with XAI methods, providing both accuracy and interpretability. This approach enhances clinical decision-making, fosters trust among healthcare professionals, and represents a significant advancement in incorporating AI-driven diagnostics into medicine, particularly for bedside applications.
[18F]FDG PET/CT Radiomics in Cervical Cancer: A Systematic Review
Authors: Hotton Judicael , Beddok Arnaud , Moubtakir Abdenasser , Papathanassiou Dimitri , Morland David
Published: January 2025

Background/Objectives: Cervical cancer is a significant global health concern, with high incidence and mortality rates, especially in less-developed regions. [18F]FDG PET/CT is now indicated at various stages of management, but its analysis is essentially based on SUVmax, a measure of [18F]FDG uptake. Radiomics, by extracting a multitude of parameters, promises to improve the diagnostic and prognostic performance of the examination. However, studies remain heterogeneous, both in terms of patient numbers and methods, so a synthesis is needed. Methods: This systematic review was conducted following PRISMA-P guidelines and registered in PROSPERO (CRD42024584123). Eligible studies on PET/CT radiomics in cervical cancer were identified through PubMed and Scopus and assessed for quality using the Radiomics Quality Score (RQS v2.0), with data extraction focusing on study design, population characteristics, radiomic methods, and model performances. Results: The review identified 22 studies on radiomics in cervical cancer, 19 of which focused specifically on locally advanced cervical cancer (LACC) and assessed various clinical outcomes, such as survival, relapse, treatment response, and lymph node involvement prediction. They reported significant associations between prognostic indicators and radiomic features, indicating the potential of radiomics to improve the predictive accuracy for patient outcomes in LACC; however, the overall quality of the studies was relatively moderate, with a median RQS of 12/36. Conclusions: While radiomic analysis in cervical cancer presents promising opportunities for survival prediction and personalized care, further well-designed studies are essential to provide stronger evidence for its clinical utility.
Non-Optic Glioma-like Lesions in Adult Neurofibromatosis Type 1 Patients
Authors: Taal Walter , Zick Bart , Emmer Bart J. , van den Bent Martin J.
Published: January 2025

Background/Objectives: Physicians face clinical dilemmas in the diagnosis of non-optic intraparenchymal lesions on MRI brain scans of patients with neurofibromatosis type 1. As the incidence and evolution of these lesions into adulthood remain unclear, we conducted a retrospective study on this topic. Methods: All adult neurofibromatosis type 1 patients who had at least one MRI brain scan in our center were selected for this study. Brain lesions with contrast enhancement after gadolinium administration and/or mass effect were named “glioma-like lesions”. Results: In our cohort of 396 adult neurofibromatosis type 1 patients, 182 had at least one MRI scan of the brain. A total of 48 glioma-like lesions were found in 38/182 patients. The majority of glioma-like lesions remained stable, decreased in size or even disappeared during a median follow-up time of 8.5 years. Twelve glioma-like lesions in 11/182 patients were resected or biopsied, and histology showed gliomas of astrocytic origin (WHO grade 1–4). Conclusions: It was concluded from these data that asymptomatic glioma-like lesions on MRI brain scans in neurofibromatosis type 1 patients, either with contrast enhancement and/or mass effect, had an indolent nature. Mildly symptomatic or asymptomatic patients can therefore be followed without invasive diagnostic and therapeutic procedures.