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22 pages, 2554 KiB  
Article
Modeling the Higher Heating Value of Spanish Biomass via Neural Networks and Analytical Equations
by Anbarasan Jayapal, Fernando Ordonez Morales, Muhammad Ishtiaq, Se Yun Kim and Nagireddy Gari Subba Reddy
Energies 2025, 18(15), 4067; https://doi.org/10.3390/en18154067 (registering DOI) - 31 Jul 2025
Abstract
Accurate estimation of biomass higher heating value (HHV) is crucial for designing efficient bioenergy systems. In this study, we developed a Backpropagation artificial neural network (ANN) that predicts HHV from routine proximate/ultimate composition data. The network (9-6-6-1 architecture, trained for 15,000 epochs with [...] Read more.
Accurate estimation of biomass higher heating value (HHV) is crucial for designing efficient bioenergy systems. In this study, we developed a Backpropagation artificial neural network (ANN) that predicts HHV from routine proximate/ultimate composition data. The network (9-6-6-1 architecture, trained for 15,000 epochs with learning rate 0.3 and momentum 0.4) was calibrated on 99 diverse Spanish biomass samples (inputs: moisture, ash, volatile matter, fixed carbon, C, H, O, N, S). The optimized ANN achieved strong predictive accuracy (validation R2 ≈ 0.81; mean squared error ≈ 1.33 MJ/kg; MAE ≈ 0.77 MJ/kg), representing a substantial improvement over 54 analytical models despite the known complexity and variability of biomass composition. Importantly, in direct comparisons it significantly outperformed 54 published analytical HHV correlations—the ANN achieved substantially higher R2 and lower prediction error than any fixed-form formula in the literature. A sensitivity analysis confirmed chemically intuitive trends (higher C/H/FC increase HHV; higher moisture/ash/O reduce it), indicating the model learned meaningful fuel-property relationships. The ANN thus provided a computationally efficient and robust tool for rapid, accurate HHV estimation from compositional data. Future work will expand the dataset, incorporate thermal pretreatment effects, and integrate the model into a user-friendly decision-support platform for bioenergy applications. Full article
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15 pages, 1800 KiB  
Article
Digital Orthodontic Setups in Orthognathic Surgery: Evaluating Predictability and Precision of the Workflow in Surgical Planning
by Olivier de Waard, Frank Baan, Robin Bruggink, Ewald M. Bronkhorst, Anne Marie Kuijpers-Jagtman and Edwin M. Ongkosuwito
J. Clin. Med. 2025, 14(15), 5270; https://doi.org/10.3390/jcm14155270 - 25 Jul 2025
Viewed by 302
Abstract
Background: Inadequate presurgical planning is a key contributor to suboptimal outcomes in orthognathic surgery. This study aims to assess the accuracy of a digital surgical planning workflow conducted prior to any orthodontic intervention. Methods: Digital planning was performed for 26 patients before orthodontic [...] Read more.
Background: Inadequate presurgical planning is a key contributor to suboptimal outcomes in orthognathic surgery. This study aims to assess the accuracy of a digital surgical planning workflow conducted prior to any orthodontic intervention. Methods: Digital planning was performed for 26 patients before orthodontic treatment (T0) and compared to the actual preoperative planning (T1). Digitized plaster casts were merged with CBCT data and converted to orthodontic setups to create a 3D virtual head model. After voxel-based registration of T0 and T1, dental arches were virtually osteotomized and repositioned according to planned outcomes. These T0 segments were then aligned with T1 planning using bony landmarks of the maxilla. Anatomical landmarks were used to construct virtual triangles on maxillary and mandibular segments, enabling assessment of positional and orientational differences. Transformations between T0 and T1 were translated into clinically meaningful metrics. Results: Significant differences were found between T0 and T1 at the dental level. T1 exhibited a greater clockwise rotation of the dental maxilla (mean: 2.85°) and a leftward translation of the mandibular dental arch (mean: 1.19 mm). In SARME cases, the bony mandible showed larger anti-clockwise roll differences. Pitch variations were also more pronounced in maxillary extraction cases, with both the dental maxilla and bony mandible demonstrating increased clockwise rotations. Conclusions: The proposed orthognathic surgical planning workflow shows potential for simulating mandibular outcomes but lacks dental-level accuracy, especially in maxillary anterior torque. While mandibular bony outcome predictions align reasonably with pretreatment planning, notable discrepancies exceed clinically acceptable thresholds. Current accuracy limits routine use; further refinement and validation in larger, homogeneous patient groups are needed to enhance clinical reliability and applicability. Full article
(This article belongs to the Special Issue Orthodontics: Current Advances and Future Options)
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19 pages, 2931 KiB  
Article
Prediction of Breast Cancer Response to Neoadjuvant Therapy with Machine Learning: A Clinical, MRI-Qualitative, and Radiomics Approach
by Rami Hajri, Charles Aboudaram, Nathalie Lassau, Tarek Assi, Leony Antoun, Joana Mourato Ribeiro, Magali Lacroix-Triki, Samy Ammari and Corinne Balleyguier
Life 2025, 15(8), 1165; https://doi.org/10.3390/life15081165 - 23 Jul 2025
Viewed by 323
Abstract
Background: Pathological complete response (pCR) serves as a prognostic surrogate endpoint for long-term clinical outcomes in breast cancer patients receiving neoadjuvant systemic therapy (NAST). This study aims to develop and evaluate machine learning-based biomarkers for predicting pCR and recurrence-free survival (RFS). Methods: This [...] Read more.
Background: Pathological complete response (pCR) serves as a prognostic surrogate endpoint for long-term clinical outcomes in breast cancer patients receiving neoadjuvant systemic therapy (NAST). This study aims to develop and evaluate machine learning-based biomarkers for predicting pCR and recurrence-free survival (RFS). Methods: This retrospective monocentric study included 235 women (mean age 46 ± 11 years) with non-metastatic breast cancer treated with NAST. We developed various machine learning models using clinical features (age, genetic mutations, TNM stage, hormonal receptor expression, HER2 status, and histological grade), along with morphological features (size, T2 signal, and surrounding edema) and radiomics data extracted from pre-treatment MRI. Patients were divided into training and test groups with different MRI models. A customized machine learning pipeline was implemented to handle these diverse data types, consisting of feature selection and classification components. Results: The models demonstrated superior prediction ability using radiomics features, with the best model achieving an AUC of 0.72. Subgroup analysis revealed optimal performance in triple-negative breast cancer (AUC of 0.80) and HER2-positive subgroups (AUC of 0.65). Conclusion: Machine learning models incorporating clinical, qualitative, and radiomics data from pre-treatment MRI can effectively predict pCR in breast cancer patients receiving NAST, particularly among triple-negative and HER2-positive breast cancer subgroups. Full article
(This article belongs to the Special Issue New Insights Into Artificial Intelligence in Medical Imaging)
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18 pages, 10000 KiB  
Article
Predicting Neoadjuvant Chemotherapy Response in Triple-Negative Breast Cancer Using Pre-Treatment Histopathologic Images
by Hikmat Khan, Ziyu Su, Huina Zhang, Yihong Wang, Bohan Ning, Shi Wei, Hua Guo, Zaibo Li and Muhammad Khalid Khan Niazi
Cancers 2025, 17(15), 2423; https://doi.org/10.3390/cancers17152423 - 22 Jul 2025
Viewed by 274
Abstract
Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive behavior and lack of targeted therapies. Accurate early prediction of response to neoadjuvant chemotherapy (NACT) is essential for guiding personalized treatment strategies and improving patient outcomes. In this study, we [...] Read more.
Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive behavior and lack of targeted therapies. Accurate early prediction of response to neoadjuvant chemotherapy (NACT) is essential for guiding personalized treatment strategies and improving patient outcomes. In this study, we present an attention-based multiple instance learning (MIL) framework designed to predict pathologic complete response (pCR) directly from pre-treatment hematoxylin and eosin (H&E)-stained biopsy slides. The model was trained on a retrospective in-house cohort of 174 TNBC patients and externally validated on an independent cohort (n = 30). It achieved a mean area under the curve (AUC) of 0.85 during five-fold cross-validation and 0.78 on external testing, demonstrating robust predictive performance and generalizability. To enhance model interpretability, attention maps were spatially co-registered with multiplex immunohistochemistry (mIHC) data stained for PD-L1, CD8+ T cells, and CD163+ macrophages. The attention regions exhibited moderate spatial overlap with immune-enriched areas, with mean Intersection over Union (IoU) scores of 0.47 for PD-L1, 0.45 for CD8+ T cells, and 0.46 for CD163+ macrophages. The presence of these biomarkers in high-attention regions supports their biological relevance to NACT response in TNBC. This not only improves model interpretability but may also inform future efforts to identify clinically actionable histological biomarkers directly from H&E-stained biopsy slides, further supporting the utility of this approach for accurate NACT response prediction and advancing precision oncology in TNBC. Full article
(This article belongs to the Section Cancer Informatics and Big Data)
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14 pages, 1899 KiB  
Article
The Impact of Yes-Associated Protein 1 (YAP1) Expression Patterns in Locally Advanced Breast Cancer: Associations with Pathological Response and Tumor Features
by Osman Erinc, Sabin Goktas Aydin, Taskin Erkinuresin, Ozgur Yilmaz, Ahmet Aydin, Sevinc Dagistanli and Murat Akarsu
Medicina 2025, 61(7), 1297; https://doi.org/10.3390/medicina61071297 - 18 Jul 2025
Viewed by 244
Abstract
Background and Objectives: The Hippo pathway, via Yes-associated protein 1 (YAP1), regulates cell proliferation, apoptosis, and tissue regeneration. Aberrant YAP1 activation is linked to tumor progression and immune evasion in various cancers, including breast carcinoma, despite conflicting evidence on its prognostic value. [...] Read more.
Background and Objectives: The Hippo pathway, via Yes-associated protein 1 (YAP1), regulates cell proliferation, apoptosis, and tissue regeneration. Aberrant YAP1 activation is linked to tumor progression and immune evasion in various cancers, including breast carcinoma, despite conflicting evidence on its prognostic value. Preclinical studies have explored drugs targeting YAP1–TEAD interactions, but therapeutic application is limited. Materials and Methods: This study included 50 patients with locally advanced breast cancer, who were assessed by a multidisciplinary tumor board and underwent neoadjuvant treatment per tumor subtype and clinical guidelines. Eligibility required both pre-treatment core biopsy and post-treatment surgical resection samples. Due to the absence of residual tumor in some patients achieving complete pathological response, post-treatment tissue was available and analyzable in 30 patients. YAP1 expression was evaluated immunohistochemically for nuclear and cytoplasmic staining patterns. ROC analysis identified a cutoff for YAP1 expression, defining tumors with ≥70% nuclear and ≥80% cytoplasmic staining. Results: YAP1 expression had a significant relationship with tumor subtype (p = 0.001), being most frequent in HER-2-positive tumors (55.6%) and least frequent in luminal tumors (11.1%). YAP1 positivity significantly predicted axillary pathological complete response (pCR) (p = 0.01). In YAP1-positive patients, 77.8% achieved axillary pCR compared to 31.7% in YAP1-negative patients, though the YAP1 status and breast pCR association were insignificant (p = 0.07). The Mann–Whitney U test indicated that higher Ki-67 values were significantly associated with positive YAP1 expression (p = 0.028). In contrast, there was no association between ER, PR status, age, and tumor size. Following treatment, there was a statistically significant change in YAP1 expression, with nuclear staining decreasing (p = 0.004) while cytoplasmic staining increased (p = 0.002). YAP1 was significantly linked to axillary pCR, HER-2 status, and Ki-67. Conclusions: Post treatment, nuclear YAP1 decreased, whereas cytoplasmic expression increased, showing a localization shift. These results suggest that YAP1 may predict treatment response and become a future therapeutic target. Full article
(This article belongs to the Section Oncology)
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15 pages, 2610 KiB  
Article
CT-Based Radiomics for a priori Predicting Response to Chemoradiation in Locally Advanced Lung Adenocarcinoma
by Erika Z. Chung, Laurentius O. Osapoetra, Patrick Cheung, Ian Poon, Alexander V. Louie, May Tsao, Yee Ung, Mateus T. Cunha, Ines B. Menjak and Gregory J. Czarnota
Cancers 2025, 17(14), 2386; https://doi.org/10.3390/cancers17142386 - 18 Jul 2025
Viewed by 266
Abstract
The standard treatment for patients with locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiation. However, clinical responses are heterogeneous and generally not known until after the completion of therapy. Multiple studies have investigated imaging predictors (radiomics) for different cancer histologies, but [...] Read more.
The standard treatment for patients with locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiation. However, clinical responses are heterogeneous and generally not known until after the completion of therapy. Multiple studies have investigated imaging predictors (radiomics) for different cancer histologies, but little exists for NSCLC. The objective of this study was to develop a multivariate CT-based radiomics model to a priori predict responses to definitive chemoradiation in patients with lung adenocarcinoma. Methods: Patients diagnosed with locally advanced unresectable lung adenocarcinoma who had undergone chemoradiotherapy followed by at least one dose of maintenance durvalumab were included. The PyRadiomics Python library was used to determine statistical, morphological, and textural features from normalized patient pre-treatment CT images and their wavelet-filtered versions. A nested leave-one-out cross-validation was used for model building and evaluation. Results: Fifty-seven patients formed the study cohort. The clinical stage was IIIA-C in 98% of patients. All but one received 6000–6600 cGy of radiation in 30–33 fractions. All received concurrent platinum-based chemotherapy. Based on RECIST 1.1, 20 (35%) patients were classified as responders (R) to chemoradiation and 37 (65%) patients as non-responders (NR). A three-feature model based on a KNN k = 1 machine learning classifier was found to have the best performance, achieving a recall, specificity, accuracy, balanced accuracy, precision, negative predictive value, F1-score, and area under the curve of 84%, 70%, 80%, 77%, 84%, 70%, 84%, and 0.77, respectively. Conclusions: Our results suggest that a CT-based radiomics model may be able to predict chemoradiation response for lung adenocarcinoma patients with estimated accuracies of 77–84%. Full article
(This article belongs to the Section Cancer Therapy)
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14 pages, 1509 KiB  
Article
A Multi-Modal Deep Learning Approach for Predicting Eligibility for Adaptive Radiation Therapy in Nasopharyngeal Carcinoma Patients
by Zhichun Li, Zihan Li, Sai Kit Lam, Xiang Wang, Peilin Wang, Liming Song, Francis Kar-Ho Lee, Celia Wai-Yi Yip, Jing Cai and Tian Li
Cancers 2025, 17(14), 2350; https://doi.org/10.3390/cancers17142350 - 15 Jul 2025
Viewed by 314
Abstract
Background: Adaptive radiation therapy (ART) can improve prognosis for nasopharyngeal carcinoma (NPC) patients. However, the inter-individual variability in anatomical changes, along with the resulting extension of treatment duration and increased workload for the radiologists, makes the selection of eligible patients a persistent challenge [...] Read more.
Background: Adaptive radiation therapy (ART) can improve prognosis for nasopharyngeal carcinoma (NPC) patients. However, the inter-individual variability in anatomical changes, along with the resulting extension of treatment duration and increased workload for the radiologists, makes the selection of eligible patients a persistent challenge in clinical practice. The purpose of this study was to predict eligible ART candidates prior to radiation therapy (RT) for NPC patients using a classification neural network. By leveraging the fusion of medical imaging and clinical data, this method aimed to save time and resources in clinical workflows and improve treatment efficiency. Methods: We collected retrospective data from 305 NPC patients who received RT at Hong Kong Queen Elizabeth Hospital. Each patient sample included pre-treatment computed tomographic (CT) images, T1-weighted magnetic resonance imaging (MRI) data, and T2-weighted MRI images, along with clinical data. We developed and trained a novel multi-modal classification neural network that combines ResNet-50, cross-attention, multi-scale features, and clinical data for multi-modal fusion. The patients were categorized into two labels based on their re-plan status: patients who received ART during RT treatment, as determined by the radiation oncologist, and those who did not. Results: The experimental results demonstrated that the proposed multi-modal deep prediction model outperformed other commonly used deep learning networks, achieving an area under the curve (AUC) of 0.9070. These results indicated the ability of the model to accurately classify and predict ART eligibility for NPC patients. Conclusions: The proposed method showed good performance in predicting ART eligibility among NPC patients, highlighting its potential to enhance clinical decision-making, optimize treatment efficiency, and support more personalized cancer care. Full article
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12 pages, 803 KiB  
Article
Evaluation of Recurrence Risk in Irreversible Electroporation-Treated Pancreatic Adenocarcinoma Patients Using Radiomics Signatures
by Jacob W. H. Gordon, Akshay Goel and Robert C. G. Martin
Cancers 2025, 17(14), 2338; https://doi.org/10.3390/cancers17142338 - 15 Jul 2025
Viewed by 276
Abstract
Purpose: To investigate if radiomics signatures generated from longitudinal CT scans could predict IRE treatment effectiveness and outcomes in patients with locally advanced pancreatic cancer (LAPC). Methods: A cohort of 50 (60% male, mean [SD] age 60.7 [8.7] years) LAPC patients treated with [...] Read more.
Purpose: To investigate if radiomics signatures generated from longitudinal CT scans could predict IRE treatment effectiveness and outcomes in patients with locally advanced pancreatic cancer (LAPC). Methods: A cohort of 50 (60% male, mean [SD] age 60.7 [8.7] years) LAPC patients treated with IRE were retrospectively selected. Preoperative and 12-week follow-up CT scans were reviewed by two radiologists for tumor segmentation. A total of 2078 features were extracted: shape (n = 16), texture (n = 68), filter (n = 1892), intensity (n = 18), and local texture (n = 84). Principal component analysis (PCA) was applied to develop composite radiomics features. Composite signatures and clinically relevant radiomics features were correlated with time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), recurrence-free survival (RFS) and overall survival (OS). Risk stratification performance was evaluated using hazard ratios (HRs), and significance was evaluated using the log-rank test. Results: Statistically significant separation between high and low patient TTR risk groups was observed in the following: gray-level co-occurrence matrix (HR = 2.65, p < 0.01, median survival difference = 6.6 mo); composite radiomics features derived from the following feature groups: all radiomics features (HR = 2.27, p = 0.01, median survival difference = 6.4 mo), intensity features (HR = 3.13, p < 0.01, median survival difference = 14.0 mo), and filter features (HR = 2.27, p = 0.01, median survival difference = 6.4 mo). Conclusions: Pre-treatment radiomics signatures were significantly associated with LAPC patient outcomes. The observed correlations used pre-treatment CT scans, implying that the features predict the individual risk of disease recurrence. Full article
(This article belongs to the Special Issue Current Clinical Studies of Pancreatic Ductal Adenocarcinoma)
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19 pages, 815 KiB  
Article
Oxygen-Enhanced R2* Weighted MRI and Diffusion Weighted MRI of Head and Neck Squamous Cell Cancer Lymph Nodes in Prediction of 2-Year Outcome Following Chemoradiotherapy
by Harbir Singh Sidhu, David Price, Tim Beale, Simon Morley, Sola Adeleke, Marianthi-Vasiliki Papoutsaki, Martin Forster, Dawn Carnell, Ruheena Mendes, Stuart Andrew Taylor and Shonit Punwani
Cancers 2025, 17(14), 2333; https://doi.org/10.3390/cancers17142333 - 14 Jul 2025
Viewed by 256
Abstract
Background: We evaluated the utility of HNSCC LN R2* relaxation times to infer the oxygenation status of LN non-invasively at baseline and when breathing air and 100% oxygen to predict chemoradiotherapeutic locoregional response at 2 years. Hypoxia within LNs has been associated with [...] Read more.
Background: We evaluated the utility of HNSCC LN R2* relaxation times to infer the oxygenation status of LN non-invasively at baseline and when breathing air and 100% oxygen to predict chemoradiotherapeutic locoregional response at 2 years. Hypoxia within LNs has been associated with poorer outcomes following CRT. Deoxyhaemoglobin decreases MRI transverse relaxation time (T2*) (lengthening inverse, R2*). Methods: A total of 54 patients underwent 1.5T-MRI before CRT. Conventional MR sequences were supplemented with T2* sequences breathing both air and 100% oxygen; pathological nodes identified in consensus were volumetrically contoured to T2* parametric maps. Results: Patients followed-up with for >2 years were categorised by multidisciplinary consensus into post-therapy complete local response (CR; n = 32/54) and local nodal disease relapse (RD; n = 22/54). Our data demonstrated, by R2*, that nodes that sustained post-therapy CR are significantly more hypoxic compared with relapsing nodes and paradoxically demonstrate a significant increase in hypoxia on 100% oxygen. Pre-treatment LN short axis diameter, various qualitative descriptors of malignancy, and quantitative DWI were not useful in discriminating successful response to CRT. Conclusions: This study demonstrates that a significant differential response to 100% oxygen and higher baseline R2* LN measurements could be exploited in risk stratification prior to CRT, and future work could be directed towards understanding the contrast mechanisms of R2* imaging, underpinning the observed differences in the context of hypoxia. Full article
(This article belongs to the Special Issue Clinical and Translational Research in Head and Neck Cancer)
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15 pages, 638 KiB  
Article
Efficacy, Toxicity and Effect of Pretreatment Cardiologic Consultation on Outcomes of Ibrutinib Therapy for Chronic Lymphocytic Leukemia—A KroHem Study
by Inga Mandac Smoljanović, Igor Aurer, Nikola Bulj, Barbara Dreta, Antonija Miljak, Fran Petričević, Marija Ivić, Sandra Bašić-Kinda, Viktor Zatezalo, Sanja Madunić, Dubravka Čaržavec, Jasminka Sinčić-Petričević, Dragana Grohovac, Ozren Jakšić, Ivan Krečak, Martina Morić-Perić, Božena Coha, Petra Berneš, Neno Živković and Vlatko Pejša
Cancers 2025, 17(14), 2302; https://doi.org/10.3390/cancers17142302 - 10 Jul 2025
Viewed by 300
Abstract
Background/Objectives: Ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia but has off-target side effects, most notably cardiac. In order to evaluate the efficacy and toxicity of ibrutinib treatment, risk factors for adverse outcomes and the influence of pretreatment cardiologic evaluation, KroHem collected [...] Read more.
Background/Objectives: Ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia but has off-target side effects, most notably cardiac. In order to evaluate the efficacy and toxicity of ibrutinib treatment, risk factors for adverse outcomes and the influence of pretreatment cardiologic evaluation, KroHem collected data on Croatian patients with chronic lymphocytic leukemia treated with this drug. Methods: This is a retrospective survey performed in order to analyze the efficacy and toxicity of ibrutinib in a real-life setting. Patients starting therapy with ibrutinib for chronic lymphocytic leukemia between the time the drug became reimbursable in 2015 and 31 December 2021 were included, irrespective of treatment line. Results: We identified 436 patients fulfilling entry criteria; 404 (92.7%) responded to treatment. Cardiovascular side effects occurred in 25.0% of patients and hemorrhagic in 15.6%. The dose of ibrutinib was permanently reduced in 22.2% of patients. Median follow-up of the cohort was 29 months (IQR 18–41 months), estimated median overall survival 75 months (IQR 36 months–not reached), progression-free survival 54 months (IQR 24–81 months) and time on ibrutinib treatment 44 months (IQR 14–78 months). Factors significantly related to overall survival in multivariate analysis were stage, treatment line and age. Factors significantly related to progression-free survival in multivariate analysis were treatment line, age and pretreatment history or ECG finding of cardiac arrhythmia. Factors significantly related to time on ibrutinib treatment in multivariate analysis were age, pretreatment history or ECG finding of cardiac arrhythmia, and permanent dose reduction for toxicity. Sex, FISH and the presence of arterial hypertension were not independently significantly related to any of these outcomes. Pretreatment cardiologic consultation did not improve time on ibrutinib therapy, progression-free survival, overall survival, risk of stopping treatment due to cardiovascular side effects or risk of cardiovascular or sudden death, neither in the whole cohort nor in the subgroup of patients with and without pretreatment cardiac arrhythmia. Conclusions: Our analysis confirms the efficacy and tolerability of ibrutinib for the treatment of chronic lymphocytic leukemia. Patients older than 75 do significantly less well. Routine pretreatment cardiologic consultation does not improve outcomes and should not be considered part of standard pretreatment assessment without additional proof of its usefulness. Future investigations should aim at identifying predictive factors, mechanisms, and preventive strategies for reducing cardiotoxicity in chronic lymphocytic leukemia patients taking Bruton tyrosine kinase inhibitors. Full article
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18 pages, 1231 KiB  
Review
Narrative Review: Predictive Biomarkers of Tumor Response to Neoadjuvant Radiotherapy or Total Neoadjuvant Therapy of Locally Advanced Rectal Cancer Patients
by Joao Victor Machado Carvalho, Jeremy Meyer, Frederic Ris, André Durham, Aurélie Bornand, Alexis Ricoeur, Claudia Corrò and Thibaud Koessler
Cancers 2025, 17(13), 2229; https://doi.org/10.3390/cancers17132229 - 3 Jul 2025
Viewed by 772
Abstract
Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely [...] Read more.
Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens. Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC. Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI. Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT. Full article
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30 pages, 13274 KiB  
Article
Modeling the Risks of Poisoning and Suffocation in Pre-Treatment Pools Workshop Based on Risk Quantification and Simulation
by Bingjie Fan, Kaili Xu, Jiye Cai and Zhenhui Yu
Appl. Sci. 2025, 15(13), 7373; https://doi.org/10.3390/app15137373 - 30 Jun 2025
Viewed by 188
Abstract
Poisoning and suffocation accidents occurred frequently in the pre-treatment pool workshops of biogas plants, so this paper provided a multi-dimensional risk analysis model: Bow-Tie-Qualitative Comparative Analysis (QCA)-Bayesian Neural Network-Consequence Simulation. First, the reasons for biogas poisoning and suffocation accidents were clarified through Bow-Tie. [...] Read more.
Poisoning and suffocation accidents occurred frequently in the pre-treatment pool workshops of biogas plants, so this paper provided a multi-dimensional risk analysis model: Bow-Tie-Qualitative Comparative Analysis (QCA)-Bayesian Neural Network-Consequence Simulation. First, the reasons for biogas poisoning and suffocation accidents were clarified through Bow-Tie. Then, the QCA method explored the accident cause combination paths in management. Next, the frequency distribution of biogas poisoning and suffocation accidents in the pre-treatment pool workshop was predicted to be 0.61–0.66 using the Bayesian neural network model, and the uncertainty of the forecast outcome was given. Finally, the ANSYS Fluent 16.0 simulation of biogas diffusion in three different ventilation types and a grid-independent solution of the simulation were conducted. The simulation results showed the distribution of methane, carbon dioxide and hydrogen sulfide gases and the hazards of the three gases to workers were analyzed. In addition, according to the results, this paper discussed the importance and necessity of ventilation in pre-treatment pool workshops and specified the hazard factors in biogas poisoning and suffocation accidents in the pre-treatment pool workshops. Some suggestions on gas alarms were also proposed. Full article
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17 pages, 4220 KiB  
Article
Disease-Resistance Functional Analysis and Screening of Interacting Proteins of ZmCpn60-3, a Chaperonin 60 Protein from Maize
by Bo Su, Lixue Mao, Huiping Wu, Xinru Yu, Chongyu Bian, Shanshan Xie, Temoor Ahmed, Hubiao Jiang and Ting Ding
Plants 2025, 14(13), 1993; https://doi.org/10.3390/plants14131993 - 30 Jun 2025
Viewed by 436
Abstract
Chaperonin 60 proteins plays an important role in plant growth and development as well as the response to abiotic stress. As part of the protein homeostasis system, molecular chaperones have attracted increasing attention in recent years due to their involvement in the folding [...] Read more.
Chaperonin 60 proteins plays an important role in plant growth and development as well as the response to abiotic stress. As part of the protein homeostasis system, molecular chaperones have attracted increasing attention in recent years due to their involvement in the folding and assembly of key proteins in photosynthesis. However, little is known about the function of maize chaperonin 60 protein. In the study, a gene encoding the chaperonin 60 proteins was cloned from the maize inbred line B73, and named ZmCpn60-3. The gene was 1, 818 bp in length and encoded a protein consisting of 605 amino acids. Phylogenetic analysis showed that ZmCpn60-3 had high similarity with OsCPN60-1, belonging to the β subunits of the chloroplast chaperonin 60 protein family, and it was predicted to be localized in chloroplasts. The ZmCpn60-3 was highly expressed in the stems and tassels of maize, and could be induced by exogenous plant hormones, mycotoxins, and pathogens; Overexpression of ZmCpn60-3 in Arabidopsis improved the resistance to Pst DC3000 by inducing the hypersensitive response and the expression of SA signaling-related genes, and the H2O2 and the SA contents of ZmCpn60-3-overexpressing Arabidopsis infected with Pst DC3000 accumulated significantly when compared to the wild-type controls. Experimental data demonstrate that flg22 treatment significantly upregulated transcriptional levels of the PR1 defense gene in ZmCpn60-3-transfected maize protoplasts. Notably, the enhanced resistance phenotype against Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) in ZmCpn60-3-overexpressing transgenic lines was specifically abolished by pretreatment with ABT, a salicylic acid (SA) biosynthetic inhibitor. Our integrated findings reveal that this chaperonin protein orchestrates plant immune responses through a dual mechanism: triggering a reactive oxygen species (ROS) burst while simultaneously activating SA-mediated signaling cascades, thereby synergistically enhancing host disease resistance. Additionally, yeast two-hybrid assay preliminary data indicated that ZmCpn60-3 might bind to ZmbHLH118 and ZmBURP7, indicating ZmCpn60-3 might be involved in plant abiotic responses. The results provided a reference for comprehensively understanding the resistance mechanism of ZmCpn60-3 in plant responses to abiotic or biotic stress. Full article
(This article belongs to the Special Issue Functional Genomics and Molecular Breeding of Crops—2nd Edition)
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21 pages, 4428 KiB  
Article
Civil Aircraft Landing Attitude Ultra-Limit Warning System Based on mRMR-LSTM
by Fei Lu, Tong Jing, Chunsheng Xie and Haonan Chen
Aerospace 2025, 12(7), 581; https://doi.org/10.3390/aerospace12070581 - 27 Jun 2025
Viewed by 365
Abstract
To achieve the forward movement of the aircraft landing attitude ultra-limit, this paper builds a deep learning-based aircraft landing attitude warning system. The early warning system includes four modules: data pretreatment, feature dimensionality reduction, prediction, and judgment. Subsequently, through data pretreatment methods such [...] Read more.
To achieve the forward movement of the aircraft landing attitude ultra-limit, this paper builds a deep learning-based aircraft landing attitude warning system. The early warning system includes four modules: data pretreatment, feature dimensionality reduction, prediction, and judgment. Subsequently, through data pretreatment methods such as data cleaning, frequency normalization, data standardization, and feature classification, the experimental dataset is transformed into a form recognizable by machine learning algorithms and neural network models. The necessary feature parameters are extracted to form a deep learning training dataset. Then, the Max-Relevance and Min-Redundancy algorithm was applied to screen the QAR (Quick Access Recorder) parameters with the highest correlation with the predictor variables, and the LSTM network model was established to predict the pitch and roll angles of the aircraft landing, respectively. Evaluation metrics are used to determine the optimal model parameters. Finally, the confusion matrix is introduced to test the prediction effect of the model, and through the secondary indicators of the confusion matrix, the prediction accuracy of the established landing attitude warning system is 94.83% for the pitch angle and 91.18% for the roll angle. It also provides pilots with a 5 s time margin to avoid risks. The system can effectively issue early warnings for ultra-limit landing attitude events and, based on the prediction results, identify the types of risks. Full article
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14 pages, 1362 KiB  
Article
Serum Complement Factor H: A Marker for Progression and Outcome Prediction Towards Immunotherapy in Cutaneous Squamous Cell Carcinoma
by Glenn Geidel, Laura Adam, Sabrina Bänsch, Nathan Fekade, Benjamin Deitert, Alessandra Rünger, Julian Kött, Tim Zell, Isabel Heidrich, Daniel J. Smit, Klaus Pantel, Stefan W. Schneider and Christoffer Gebhardt
Cancers 2025, 17(13), 2162; https://doi.org/10.3390/cancers17132162 - 26 Jun 2025
Viewed by 345
Abstract
Background/Objectives: Tumor-immune system interactions shape the progression of cutaneous squamous cell carcinoma (cSCC). Serum biomarkers for risk stratification remain limited. Complement factor H (CFH) regulates the alternative complement pathway. It has been linked to immunosuppression and cSCC development in tissue-based studies. We investigated [...] Read more.
Background/Objectives: Tumor-immune system interactions shape the progression of cutaneous squamous cell carcinoma (cSCC). Serum biomarkers for risk stratification remain limited. Complement factor H (CFH) regulates the alternative complement pathway. It has been linked to immunosuppression and cSCC development in tissue-based studies. We investigated whether serum CFH is associated with tumor aggressiveness and may help predict immunotherapy outcomes in advanced cSCC. Methods: In this retrospective, single-center study, pre-treatment serum CFH levels were measured in 104 cSCC patients (62 high-risk and 42 advanced) using ELISA. Associations with clinical characteristics, disease stage, and response to cemiplimab were analyzed. Subgroup comparisons considered immune status and inflammatory comorbidities. Results: Advanced cSCC patients had significantly higher CFH levels than high-risk patients (OR 0.13, p = 0.026), independent of tumor diameter or invasion depth. Among advanced cSCC cases, lower baseline CFH was associated with more prolonged progression-free survival (median 19.8 vs. 3.07 months, p = 0.029; HR 0.29, p = 0.014), independent of covariates including immunosuppression. CFH levels during therapy did not predict treatment response. ROC analysis showed moderate discriminatory ability with CFH alone (AUC 0.625), which improved when combined with clinical variables in a multivariable risk model (AUC 0.767). Conclusions: Serum CFH is an independent predictor of cemiplimab response and reflects biological aggressiveness in cSCC beyond conventional high-risk features. These findings support the use of CFH in clinical risk models and warrant external validation in multicenter cohorts. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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