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19 pages, 6833 KB  
Article
Comparative RNA-Seq and Phytochemical Profiling Reveal Year-Dependent Bioactive Variations and Delineate Key Metabolic Pathways in Polygonatum sibiricum Red. Rhizome Nodes
by Chunming Li, Xiaoyu Su, Yaling Yang, Yiwen Cao, Lei Li, Dandan Lu, Yao Sun, Lina Wang, Mengfan Su, Yongliang Yu, Haitao Lu, Zhengwei Tan and Huizhen Liang
Int. J. Mol. Sci. 2026, 27(18), 8282; https://doi.org/10.3390/ijms27188282 - 17 Sep 2026
Abstract
Polygonatum sibiricum Red. is a medicinal and edible homologous plant whose rhizome quality determines its clinical efficacy and commercial value. However, conventional evaluations typically treat the entire rhizome as homogeneous, overlooking the intrinsic heterogeneity along age nodes, and the regulatory mechanisms governing such [...] Read more.
Polygonatum sibiricum Red. is a medicinal and edible homologous plant whose rhizome quality determines its clinical efficacy and commercial value. However, conventional evaluations typically treat the entire rhizome as homogeneous, overlooking the intrinsic heterogeneity along age nodes, and the regulatory mechanisms governing such age-dependent quality variation remain largely unclear. In this study, four-year-old rhizomes were precisely segmented into four age nodes (HJ1–HJ4), and the contents of polysaccharides, flavonoids, and saponins were systematically determined alongside comparative transcriptome sequencing to dissect the age-dependent bioactive variation and underlying molecular mechanisms. The three bioactive components exhibited markedly asynchronous accumulation patterns, with polysaccharides peaking at HJ3, flavonoids at HJ4, and saponins at HJ1. Transcriptomic analysis identified 19,638 differentially expressed genes (DEGs), with KEGG enrichment pointing to starch and sucrose metabolism, flavonoid biosynthesis, and steroid biosynthesis as the pivotal pathways. A coordinated transcriptional reprogramming emerged across development, characterized by early upregulation of backbone-construction genes and progressive activation of modification-and-decoration genes—yet it manifested through pathway-specific regulatory logics, with Mantel tests further confirming that key genes, including β-amylase3, CYP75B11, and squalene epoxidase (SQLE), were significantly correlated with the accumulation of polysaccharides, flavonoids, and saponins, respectively. These findings challenge the conventional assumption that older nodes are universally superior and establish that age-node differentiation reflects fundamental metabolic reprogramming, supporting a node-targeted utilization strategy encompassing HJ3 for polysaccharide-based products, HJ4 for antioxidant applications, HJ1 for saponin extraction, and HJ2 for bulk materials, while providing both mechanistic insights and practical guidance for precision harvesting and quality-oriented management of P. sibiricum. Full article
(This article belongs to the Special Issue Molecular and Adaptive Mechanisms in Plant Genetics)
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13 pages, 4113 KB  
Article
Volume 2: Retrospective Analysis of Clinicopathological Characteristics of Surgically Treated Squamous Cell Carcinoma of the Face—A Single-Centre Maxillofacial Surgery Experience
by Abdullah Saeidi, Shadia Elsayed, Jörg Wiltfang and Christian Flörke
J. Clin. Med. 2026, 15(18), 7218; https://doi.org/10.3390/jcm15187218 - 17 Sep 2026
Abstract
Background: Squamous cell carcinoma (SCC) is a common malignancy in Western countries and can lead to extensive tissue destruction, metastasis, and death. The study aimed to highlight the epidemiology, diagnostic patterns, histological variations, and prognostic significance of SCC of the facial skin region [...] Read more.
Background: Squamous cell carcinoma (SCC) is a common malignancy in Western countries and can lead to extensive tissue destruction, metastasis, and death. The study aimed to highlight the epidemiology, diagnostic patterns, histological variations, and prognostic significance of SCC of the facial skin region based on a single-center analysis. Methods: This retrospective study analyzed records of patients admitted to the Department of Maxillofacial Surgery, UKSH-Kiel, for treatment of SCC of the head and face from January 2019 to February 2021. Data were collected via the ORBIS/management-diagnostic codes system (ORBIS-AG, Saarbrücken, Germany). It included information on TNM classification, tumor depth, growth type, tumor localization, and surgical techniques, which were extracted from histopathology and surgical reports. Results: A total of 560 patients were admitted for treatment of malignancies of the facial skin region. Sixty patients (10.7%) had SCCs, and their mean age was 80.64 years. A total of 68.3% of the patients were male. The most common histopathological growth type was verrucous: 36.7% (n = 22). No significant correlation was found between growth type and recurrence (p = 0.266) or metastasis (p = 0.091). However, the correlation between growth type and CT morphology was significant (p = 0.032), with radiologically suspicious lymph nodes most frequently associated with a verrucous growth type (36.4%, n = 8/22). The most common locations for SCC were the temporal region (25%, n = 15) and the cheek (15%, n = 9). The majority of SCC cases (32%) were classified as T1, with T4 being the least common (5%). The mean tumor depth for SCC was 4.67 mm (SD: 3.05). Tumor depth showed a significant correlation with TNM classification (p = 0.0001). Conclusions: This study emphasizes the significance of early detection, accurate advanced T-classifications, tumor depth, and high-risk growth types in predicting recurrence and metastasis in SCC. In this cohort, CT findings were associated with lymph node status and may provide useful information for the preoperative assessment of selected patients. Full article
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16 pages, 1851 KB  
Article
Gastric Carcinoma with Exocrine and Neuroendocrine Components: A 16-Year Cohort Analysis and International Comparison
by Hu Ren, Zelin Wen, He Fei, Penghui Niu, Zefeng Li, Diliyaer Adili and Dongbing Zhao
Curr. Oncol. 2026, 33(9), 558; https://doi.org/10.3390/curroncol33090558 - 15 Sep 2026
Viewed by 81
Abstract
Background: Gastric carcinoma with coexisting exocrine and neuroendocrine components (GC-EN) is rare and clinically aggressive, but its temporal pattern and prognostic impact remain poorly characterized. Materials and Methods: We retrospectively analyzed 1043 patients who underwent curative gastrectomy at our center between 2008 and [...] Read more.
Background: Gastric carcinoma with coexisting exocrine and neuroendocrine components (GC-EN) is rare and clinically aggressive, but its temporal pattern and prognostic impact remain poorly characterized. Materials and Methods: We retrospectively analyzed 1043 patients who underwent curative gastrectomy at our center between 2008 and 2024. Following tumor–node–metastasis staging and 1:2 pTNM stage matching, 882 patients were included; 294 had GC-EN, of which 175 had GNEC, and 588 had GC. Clinicopathological characteristics were compared, survival outcomes were assessed using Kaplan–Meier estimates and multivariate Cox regression, and the proportion of GNEC cases in our center and the U.S. surveillance, epidemiology, and end results (SEER) database were evaluated. Survival patterns of GNEC were further compared with published international cohorts using Engauge Digitizer software. Results: Among the patients with gastric cancer admitted for treatment, the proportion of NEC fluctuated between 4.01% and 4.38% (2008–2013) and finally dropped to 1.6% (2020–2021), whereas the SEER database showed a modest rise with a late dip (1.67% → 2.72% → 2.44%). The overall survival (OS) of patients with NEC appeared to improve at our center (1-/2-/3-year OS: 85.1%/59.6%/34% in 2008–2012 to 94.1%/87.5%/76.2% in 2021–2024), whereas that in the SEER database declined over the same periods. The 5-year OS of the two databases remained similar (42.7% vs. 41.0%). The 1, 2 and 5-year survival rates of NEC in the external cohorts were higher than those in the SEER and Berlin series; however, the 3-year survival rates were similar, with the Italian multicenter cohort performing the worst. The Kaplan–Meier analysis demonstrated significantly worse OS for GC-EN versus GC (p < 0.001); within GC-EN, the NEC subgroup (NEC ≥ 70%) had the poorest outcomes (p < 0.001), whereas mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) and adenocarcinoma-dominant (AC-dominant) cases had similar outcomes as GC (p = 0.52, p = 0.81). In the multivariable Cox model, GC-EN histology remained independently associated with worse OS (HR = 1.49, 95% CI 1.15–1.92; p < 0.01). Metastatic lymph node burden and higher pTNM stage were associated with worse survival, whereas greater lymph node retrieval and age 40–65 years were protective. After adjustment, vascular invasion, tumor size, and location were not independently significant. Conclusions: Over the past 16 years at the National Cancer Center of China, the proportion of NEC cases decreased, and survival appeared to improve. NEC-dominant disease appeared to be the main driver of poor prognosis within GC-EN, whereas MiNEN and AC-dominant tumors showed survival patterns similar to GC in this cohort. These findings emphasize the need for GC-EN-specific risk stratification and tailored treatment strategies. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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16 pages, 1081 KB  
Article
Ocular Surface Recovery Following Corrective Eyelid Surgery: Course, Predictors, and Perioperative Management Implications
by Maria Angela Romeo, Alberto Cuccu, Valerio Calabresi, Filippo Lixi, Giulia Coco, Vanessa Ferraro, Alessandro Gaeta, Silvia Ferraro, Giuseppe Giannaccare and Alessandra Di Maria
Diagnostics 2026, 16(18), 2977; https://doi.org/10.3390/diagnostics16182977 - 15 Sep 2026
Viewed by 149
Abstract
Background/Objectives: The aim of this study was to evaluate ocular surface recovery following reconstructive eyelid surgery, to identify preoperative predictors of incomplete symptomatic recovery, and to propose a risk stratification framework to enable targeted perioperative management. Methods: This retrospective multicenter study included [...] Read more.
Background/Objectives: The aim of this study was to evaluate ocular surface recovery following reconstructive eyelid surgery, to identify preoperative predictors of incomplete symptomatic recovery, and to propose a risk stratification framework to enable targeted perioperative management. Methods: This retrospective multicenter study included 50 eyes of 32 patients (mean age 73.0 ± 13.9 years; 44% female) affected by ptosis (eyes = 23) or ectropion (eyes = 27) who underwent standardized corrective surgery at two Italian centers. Ocular surface evaluation was performed preoperatively (T0) and 1 week (T1), 1 month (T2), and 3 months (T3) postoperatively. Outcomes included the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test, non-invasive tear breakup time (NI-BUT), and corneal fluorescein staining (Oxford staining score). Pre-existing dry eye disease (preDED) was defined as OSDI ≥ 23 combined with at least one objective sign using conservative thresholds (NI-BUT < 5 s, Schirmer I ≤ 7 mm, or Oxford staining score ≥ 2). Results: At 3 months, patient-level OSDI decreased by a median of 11.0 points (p < 0.001) and eye-level Oxford staining score by 0.96 grades (p < 0.001, r = 0.870). Ectropion patients achieved greater OSDI improvement than ptosis patients (median 21 vs. 2 points, p = 0.002) yet converged to comparable final values (median 16 vs. 18, p = 0.715). PreDED was identified in 10 patients (32%), all with severe baseline disease (OSDI ≥ 33 plus objective signs). All preDED patients (100%) achieved the minimal clinically important difference (≥7.3 points) versus 33% of no-DED patients (p < 0.001). However, 50% of preDED patients maintained moderate symptoms (OSDI ≥ 23) at 3 months versus 19% of no-DED patients (p = 0.105). Overall, the assessed parameters suggested a biphasic postoperative course, with transient worsening at 1 week, followed by progressive recovery by 3 months. Conclusions: Reconstructive eyelid surgery produces sustained ocular surface improvement within 3 months, yet preDED was associated with incomplete symptomatic recovery despite universal achievement of clinically meaningful improvement. These exploratory findings suggest that patients with severe baseline preDED may benefit from preoperative identification and individualized counseling regarding realistic expectations; whether intensified perioperative management improves outcomes should be tested prospectively. Randomized trials are needed to determine whether preoperative optimization with anti-inflammatory therapy and meibomian gland treatment improves outcomes in this higher-risk subgroup. Full article
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14 pages, 840 KB  
Article
Lower Severity, Denser Network: Profile-Specific Symptom Architecture in Adolescent Internalizing and Externalizing Problems
by Huina Teng, Cui Zhou, Yue Li, Boyu Qiu and Wei Zhang
Behav. Sci. 2026, 16(9), 1643; https://doi.org/10.3390/bs16091643 - 14 Sep 2026
Viewed by 158
Abstract
Introduction: This study examined whether severity-defined profiles of internalizing and externalizing problems among Chinese adolescents differed in their symptom connectivity. Method: Participants were 1200 Chinese adolescents aged 9 to 15 years who were assessed in 2018 and 2022. Fourteen internalizing and externalizing problem [...] Read more.
Introduction: This study examined whether severity-defined profiles of internalizing and externalizing problems among Chinese adolescents differed in their symptom connectivity. Method: Participants were 1200 Chinese adolescents aged 9 to 15 years who were assessed in 2018 and 2022. Fourteen internalizing and externalizing problem items were analyzed. Latent profile analysis was used to obtain a coarse severity-based grouping at each wave, after which Gaussian graphical models were estimated within profiles. Profile networks were formally compared using permutation-based Network Comparison Tests, and robustness to the EBIC hyperparameter was examined across γ = 0, 0.25, and 0.50. Results: A two-profile solution was retained at each wave as an interpretable lower- versus higher-symptom partition with adequate group sizes. Formal comparisons showed greater global strength in the lower-symptom profile at both waves. Overall network structure differed significantly between profiles at Time 1 but not at Time 2. Several node strength differences were detected, although the exact ordering of central nodes was not uniformly robust across regularization settings. Conclusions: Severity-defined profiles differed reliably in overall symptom connectivity, whereas evidence for broader profile-specific network configurations was wave-specific. These cross-sectional network findings describe conditional association patterns and should be treated as hypothesis-generating rather than as evidence of causal mechanisms or optimal intervention targets. Full article
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14 pages, 6080 KB  
Article
Dual-Layer Spectral CT for Locoregional Assessment of Rectal Cancer: A Comparison with MRI in a Pilot Study
by Silvio Mazziotti, Giorgio Ascenti, Tommaso D’Angelo, Ludovica R. M. Lanzafame, Pasquale Arena, Alfredo Blandino, Sarah Doria, Simone Barbera, Robert Runinski, Velio Ascenti, Laura Pipino, Giuseppe Costantino, Anna Viola and Giuseppe Cicero
Diagnostics 2026, 16(18), 2948; https://doi.org/10.3390/diagnostics16182948 - 12 Sep 2026
Viewed by 191
Abstract
Background/Objectives: To evaluate the concordance of dual-layer spectral CT (DLSCT) with MRI in locoregional staging of rectal cancer, focusing on 40 keV virtual monoenergetic reconstructions. Methods: This retrospective single-center study included 31 patients (mean age, 69 ± 13.3 years) with rectal cancer who [...] Read more.
Background/Objectives: To evaluate the concordance of dual-layer spectral CT (DLSCT) with MRI in locoregional staging of rectal cancer, focusing on 40 keV virtual monoenergetic reconstructions. Methods: This retrospective single-center study included 31 patients (mean age, 69 ± 13.3 years) with rectal cancer who underwent both MRI and DLSCT within 30 days before treatment. Venous-phase CT images were reconstructed at 40 keV. Assessed parameters included tumor location, longitudinal extent, distance from the anorectal junction and anal verge, mesorectal infiltration, circumferential resection margin (CRM) involvement, suspicious lymph nodes, extramural vascular invasion (EMVI), desmoplastic reaction, peritoneal involvement, and anal canal invasion. Two radiologists performed consensus readings. Paired continuous measurements were compared with the Wilcoxon signed-rank test. Agreement for categorical variables was evaluated using Cohen’s kappa; sensitivity, specificity, and accuracy were calculated using MRI as the imaging reference standard. Results: No significant differences were found between MRI and DLSCT for the continuous measurements evaluated. Complete agreement was observed for CRM involvement, anal canal invasion, peritoneal involvement, desmoplastic reaction, and suspicious lymph-node classification (accuracy, 100%; κ = 1.00). Agreement was almost perfect for mesorectal infiltration (κ = 0.84). For EMVI, DLSCT reproduced all MRI-positive classifications but generated two additional positive findings, resulting in 100% sensitivity, 71.4% specificity, 93.5% accuracy, and substantial agreement (κ = 0.79). Conclusions: DLSCT showed high concordance with MRI for several locoregional imaging features of rectal cancer. It may provide complementary information, particularly when MRI is contraindicated or inconclusive. In addition, when DLSCT is performed for systemic staging, it has the potential to provide both locoregional and distant disease assessment within a single examination. However, these findings do not establish equivalence to MRI or diagnostic accuracy against histopathology, and further prospective studies with pathological correlation are warranted. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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19 pages, 18193 KB  
Article
Oncoplastic Breast Surgery Taking “Center” Stage—Managing Centrally Located Breast Tumors in Indian Cohort
by Chaitanyanand B. Koppiker, Aijaz Ul Noor, Rupa Mishra, Vaibhav Jain, Priya Sivadasan, Sneha Bhandari, Namrata Athavale, Vishesha Lulla, Sanika Limaye, Mugdha Pai, Chetan Deshmukh, Mansi Munshi, Beenu Varghese, Upendra Dhar and Sneha Joshi
J. Clin. Med. 2026, 15(18), 7076; https://doi.org/10.3390/jcm15187076 - 12 Sep 2026
Viewed by 219
Abstract
Background: Centrally located breast tumors (CLBTs) present unique challenges in surgical management, requiring a delicate balance between oncological outcomes and cosmetic preservation. Oncoplastic techniques have emerged as a promising solution, allowing larger excisions while maintaining cosmetic appearance and function. This study aims to [...] Read more.
Background: Centrally located breast tumors (CLBTs) present unique challenges in surgical management, requiring a delicate balance between oncological outcomes and cosmetic preservation. Oncoplastic techniques have emerged as a promising solution, allowing larger excisions while maintaining cosmetic appearance and function. This study aims to evaluate the surgical management of CLBT using oncoplastic breast surgery (OBS) treated at a single surgeon center in India. Methods: Among 138 patients with CLBT who underwent OBS, diagnosis and staging adhered to NCCN guidelines, with treatment decisions made via a multidisciplinary tumor board and patient counseling. Intraoperative ultrasound, specimen mammography, and frozen-section evaluation guided resection margins and axillary staging. Results: The median patient age was 52.7 years. Seventy-three percent of patients had unifocal disease, with 67% presenting at the cT2–cT3 stage, and 50% being clinically node-positive. Level 1 OBS was used in 21.73% of cases, Level 2 in 42.75%, and Level 3 in 35%, with 28% qualifying as extreme oncoplasty. Post-surgical complications were observed in 13% cases. Cosmetic outcomes were good to excellent in 94% of cases. At a median follow-up of 57 months, overall survival (OS) was 91.93%, and disease-free survival (DFS) was 88.17%. The BREAST-Q PROM response rate was 94%, with high satisfaction across all domains. Conclusions: This study highlights the safety and efficacy of OBS in CLBT. Key factors such as multidisciplinary management, meticulous surgical planning, and rigorous intraoperative rad-path assessment contributed to its success. These findings highlight the potential of OBS to optimize outcomes and enhance quality of life, even in difficult cases and resource-limited settings. Full article
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20 pages, 2515 KB  
Article
Factors Associated with Prolonged Hospitalisation in Women with Breast Cancer: Evidence from a Large German Multicentre Study
by Lisa Cordes, Karel Kostev and Matthias Kalder
Clin. Pract. 2026, 16(9), 169; https://doi.org/10.3390/clinpract16090169 - 11 Sep 2026
Viewed by 106
Abstract
Background/Objectives: Breast cancer is the most common malignancy among women worldwide and poses a significant burden on healthcare systems. Despite evidence that treatment type is associated with hospital length of stay (LOS), current Germany-wide data on this topic are lacking. The present [...] Read more.
Background/Objectives: Breast cancer is the most common malignancy among women worldwide and poses a significant burden on healthcare systems. Despite evidence that treatment type is associated with hospital length of stay (LOS), current Germany-wide data on this topic are lacking. The present study aims to identify clinical and procedural factors associated with prolonged hospitalisation in women hospitalised for breast cancer in Germany. Methods: This multicentre cross-sectional study analysed anonymised inpatient data from 38 German hospitals (IQVIA database), including 16,062 female breast cancer hospitalisation episodes (inpatient cases; patient-level linkage was not possible due to anonymisation, so these may not represent 16,062 distinct women) treated between January 2019 and December 2024. The primary outcome was LOS; prolonged hospitalisation was defined as LOS > 7 days (75th percentile). Comorbidities were assessed using individual comorbidity categories defined according to the Elixhauser classification (retained at ≥1% prevalence). The primary multivariable analysis was restricted to characteristics documented independently of the in-hospital course (age, tumour site, metastatic status, chronic comorbidities). In-hospital complications, procedures, and diagnoses of ambiguous timing were analysed separately as secondary, descriptive associations. LOS was modelled using negative binomial regression (Poisson regression as a sensitivity analysis) and prolonged LOS using logistic regression, both with hospital-clustered robust (sandwich) standard errors. Results: The overall median LOS was 4 days (IQR 3–7); 19.3% of hospitalisation episodes were prolonged. In the primary analysis, longer LOS was associated with age > 70 years (RR 1.14; 95% CI 1.08–1.20), distant metastases (RR 1.76; 95% CI 1.51–2.04), lymph node metastases (RR 1.09; 95% CI 1.05–1.12), congestive heart failure (RR 1.44; 95% CI 1.31–1.59), anaemia (RR 1.41; 95% CI 1.14–1.75) and depression (RR 1.14; 95% CI 1.03–1.26). In the secondary descriptive analysis, in-hospital complications showed the strongest associations with longer LOS, particularly postoperative infection (RR 2.28), wound disruption (RR 1.92) and pneumonia (RR 1.45). Breast-conserving surgery and partial breast resection were associated with shorter LOS, while mastectomy, blood transfusions, and complex intensive care were associated with prolonged stays; the small inpatient radiotherapy subgroup (1.9%) most likely reflects a highly selected, predominantly palliative population rather than an association attributable to radiotherapy itself. Conclusions: Prolonged hospitalisation was associated with older age, documented lymph node and distant metastases, and chronic somatic comorbidities including congestive heart failure, anaemia, chronic kidney disease and depression, and, in secondary descriptive analyses, with perioperative complications and intensive procedures. The strongest correlates of prolonged stay—in-hospital complications and intensive procedures—are documented during rather than before the hospitalisation and therefore cannot themselves support early risk identification; however, the baseline characteristics documented independently of the in-hospital course (age, metastatic disease, chronic comorbidity burden) may usefully inform structured perioperative management and discharge planning in Germany. Full article
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15 pages, 723 KB  
Article
Prognostic Impact of Visceral Pleural Invasion in Node-Negative Non-Small Cell Lung Cancer with Tumors ≤ 3 cm
by Ezgi Gürel Akan, Pınar Akın Kabalak, Suna Kavurgacı, Tuba İnal Cengiz, Funda Demirağ, Hakan Nomenoğlu, Hasan İbiş and Ülkü Yılmaz
Cancers 2026, 18(18), 2944; https://doi.org/10.3390/cancers18182944 - 11 Sep 2026
Viewed by 273
Abstract
Background and Objectives: Visceral pleural invasion (VPI) up-classifies non-small cell lung cancer (NSCLC) tumors measuring ≤3 cm from T1 to T2; however, whether this stage migration translates into worse survival in pathologically node-negative disease remains uncertain. This study evaluated the prognostic impact [...] Read more.
Background and Objectives: Visceral pleural invasion (VPI) up-classifies non-small cell lung cancer (NSCLC) tumors measuring ≤3 cm from T1 to T2; however, whether this stage migration translates into worse survival in pathologically node-negative disease remains uncertain. This study evaluated the prognostic impact of VPI on overall survival (OS) and progression-free survival (PFS) in this selected population. Materials and Methods: This retrospective single-center cohort study included patients who underwent surgical resection for pathologically node-negative NSCLC with tumors ≤ 3 cm between 2015 and 2021. In the primary analysis, patients with PL0 were compared with those with PL1–PL2, whereas PL3 cases were excluded from the primary comparison and evaluated only in exploratory analyses. Survival outcomes were assessed using Kaplan–Meier analysis and univariable and multivariable Cox regression models. Results: A total of 241 patients were included in the overall cohort (PL0, n = 179; PL1, n = 48; PL2, n = 9; PL3, n = 5). After exclusion of PL3 from the primary analysis, 236 patients remained, including 179 with PL0 and 57 with PL1–PL2. During follow-up, 58 deaths and 81 PFS events occurred in the primary analytic cohort. Kaplan–Meier analysis showed no significant differences between PL0 and PL1–PL2 in OS (log-rank p = 0.655) or PFS (log-rank p = 0.904). In multivariable analysis, VPI was not independently associated with OS (HR 0.785, 95% CI 0.389–1.582; p = 0.498) or PFS (HR 0.908, 95% CI 0.507–1.624; p = 0.744). Increasing age was independently associated with worse OS and PFS, whereas male sex and pneumonectomy were independently associated with worse OS. Conclusions: In surgically treated patients with pathologically node-negative NSCLC and tumors ≤ 3 cm, VPI defined as PL1–PL2 was not independently associated with OS or PFS. These findings suggest that the prognostic implications of VPI-driven up-classification may be context-dependent and should be interpreted together with other clinicopathological factors. Full article
(This article belongs to the Special Issue Clinical Pathology of Lung Cancer (2nd Edition))
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15 pages, 1448 KB  
Article
Evolving Clinicopathological Characteristics of Women with Locally Advanced Cervical Cancer Treated with Definitive Chemoradiation Before and After Implementation of Organized Cervical Cancer Screening in Serbia
by Jelena Stanić, Marija Popović-Vuković, Predrag Nikić, Ivana Šović, Luka Jovanović, Predrag Petrašinović, Marko Jovanović, Tatjana Arsenijević and Aleksandar Tomašević
Cancers 2026, 18(17), 2891; https://doi.org/10.3390/cancers18172891 - 7 Sep 2026
Viewed by 271
Abstract
Background: Organized cervical cancer screening aims to reduce the burden of advanced disease through earlier detection. However, a substantial proportion of women continue to present with locally advanced cervical cancer (LACC) requiring definitive chemoradiation. This study evaluated temporal changes in the demographic and [...] Read more.
Background: Organized cervical cancer screening aims to reduce the burden of advanced disease through earlier detection. However, a substantial proportion of women continue to present with locally advanced cervical cancer (LACC) requiring definitive chemoradiation. This study evaluated temporal changes in the demographic and clinicopathological characteristics of women with LACC treated with definitive chemoradiation before and after implementation of the organized cervical cancer screening program in Serbia. Methods: This retrospective single-center cohort study included 200 consecutive women with histologically confirmed LACC treated with definitive chemoradiation at the Institute of Oncology and Radiology of Serbia. Two cohorts were analyzed: a pre-screening cohort (2010–2011, n = 100) and a post-screening cohort (2022–2023, n = 100). Demographic and clinicopathological characteristics, including age, histopathology, FIGO stage, lymph node involvement, and geographic distribution, were compared. For study purposes, all patients were retrospectively restaged according to the FIGO 2018 classification using the best available clinical, radiological, and pathological data. Results: Women in the post-screening cohort were significantly older at diagnosis than those in the pre-screening cohort (mean age 54.9 vs. 49.7 years, p = 0.0046), with a substantially higher proportion of patients older than 64 years (28% vs. 2%, p < 0.0001). Although the overall distribution of FIGO stages II–IV did not differ significantly, a marked redistribution of FIGO 2018 substages was observed (p < 0.0001), characterized by an increased proportion of stage IIIC disease and significantly more frequent lymph node involvement (63% vs. 41%, p = 0.0018). Geographic distribution remained stable, with most patients referred from the Belgrade administrative district. Conclusions: This study demonstrated clinically relevant temporal changes in the demographic and clinicopathological characteristics of women requiring definitive chemoradiation for LACC in Serbia. More than a decade after implementation of organized cervical cancer screening, tertiary referral centers continue to manage a substantial burden of patients with locally advanced disease requiring complex, resource-intensive treatment. These findings should not be interpreted as a direct evaluation of the national screening program but may provide valuable insights for healthcare planning in Serbia and other countries with similarly resource-constrained healthcare systems. Strengthening participation in organized screening, ensuring timely diagnostic evaluation, and improving HPV vaccination uptake remain essential to reduce the burden of advanced cervical cancer. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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15 pages, 839 KB  
Article
Impact of Residual Mediastinal Nodal Disease After Neoadjuvant Chemoimmunotherapy for Non-Small Cell Lung Cancer
by Berta Mosleh, Anastasia Papaporfyriou, Thorsten Fuereder, Helmut Prosch, Joachim Widder, Felicitas Oberndorfer, Clemens Aigner, Marco Idzko, Daniela Gompelmann and Mir Alireza Hoda
Cancers 2026, 18(17), 2871; https://doi.org/10.3390/cancers18172871 - 5 Sep 2026
Viewed by 396
Abstract
Background/Objectives: In recent years, neoadjuvant chemoimmunotherapy followed by surgery has improved outcomes in patients with stage II/III non-small cell lung cancer (NSCLC). However, the prognostic impact of residual mediastinal nodal disease after chemoimmunotherapy remains insufficiently defined, particularly with the introduction of the Union [...] Read more.
Background/Objectives: In recent years, neoadjuvant chemoimmunotherapy followed by surgery has improved outcomes in patients with stage II/III non-small cell lung cancer (NSCLC). However, the prognostic impact of residual mediastinal nodal disease after chemoimmunotherapy remains insufficiently defined, particularly with the introduction of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) 9th edition nodal subclassification. Methods: In this retrospective study, 90 consecutive patients with clinically node-positive (cN1-2) resectable locally advanced NSCLC who underwent neoadjuvant chemoimmunotherapy followed by curative-intent resection were included. Disease-free survival (DFS) was analyzed according to postoperative pathologic nodal status. Nodal status was assessed using the UICC/AJCC 8th edition (ypN0, ypN1, ypN2) and reclassified according to the 9th edition (ypN0, ypN1, ypN2a, ypN2b). Residual postoperative nodal disease was defined as residual pathologic nodal involvement (ypN+) in patients with clinically node-positive (cN+) disease at baseline. Results: The cohort comprised 90 patients (60% male, median age 63 years [interquartile range (IQR) 58–69]). Following neoadjuvant therapy, surgery revealed pathologic nodal clearance in 53 (58.9%) and residual nodal disease in 37 (41.1%) patients (ypN1, n = 16 [17.8%]; ypN2a, n = 15 [16.7%]; and ypN2b, n = 6 [6.7%]). DFS differed significantly by postoperative nodal status (global log-rank p < 0.001), with progressively poorer outcomes with increasing residual nodal burden. Conclusions: Residual nodal disease after neoadjuvant chemoimmunotherapy and surgery is associated with progressively inferior DFS according to its anatomic extent. The UICC/AJCC 9th-edition staging system provides clinically relevant prognostic granularity, supporting further investigation of mediastinal restaging and postoperative treatment strategies. Full article
(This article belongs to the Collection Diagnosis and Treatment of Primary and Secondary Lung Cancers)
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19 pages, 4144 KB  
Article
Primary Tumor Epigenetic and Transcriptomic Alterations Associated with Nodal Burden and Metastatic Risk in ER+/HER2− Breast Cancer
by Sandra Iñiguez-Muñoz, Andrés F. Bedoya-López, Miquel Ensenyat-Mendez, Pere Llinàs-Arias, Sookyung Ahn, Rachel E. Factor, Diego M. Marzese and Maggie L. DiNome
Int. J. Mol. Sci. 2026, 27(17), 7901; https://doi.org/10.3390/ijms27177901 - 4 Sep 2026
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Abstract
De-escalation of axillary surgery has resulted in the loss of pathologic nodal information, yet the extent of lymph node involvement remains an important determinant of treatment decisions in estrogen receptor-positive (ER+)/HER2− disease. We examined whether primary tumors differed molecularly according to the extent [...] Read more.
De-escalation of axillary surgery has resulted in the loss of pathologic nodal information, yet the extent of lymph node involvement remains an important determinant of treatment decisions in estrogen receptor-positive (ER+)/HER2− disease. We examined whether primary tumors differed molecularly according to the extent of this regional dissemination. Genome-wide DNA methylation profiling of primary ER+/HER2− tumors from 47 patients with pN1 (n = 29) vs. >pN1 (n = 18) disease showed differences concentrated at promoters of developmental and cell-adhesion genes. By integrating methylomes with transcriptomes from the TCGA-BRCA cohort (n = 148) and clinical outcomes from KM Plotter (RFS, n = 1154; OS, n = 442; DMFS, n = 423), we identified four genes (ARL10, RIC3, CXCL14, KCNH2) showing concordant molecular and clinical associations, from which we derived the Lymph-node Involvement Outcome Numerator (LION) score. Lower LION scores were observed in metastatic lesions from the AURORA US cohort (n = 45). In SCAN-B (n = 3969), lower scores were associated with shorter distant recurrence-free intervals (HR = 0.38; 95% CI 0.23–0.62); this association persisted after adjustment for age, nodal and tumor category but was lost after adjustment for histological grade (HR = 0.83; 95% CI 0.48–1.44), indicating that the score and grade capture overlapping biology. These findings suggest that primary tumors already display coordinated epigenetic and transcriptional alterations associated with the extent of metastatic dissemination. Full article
(This article belongs to the Special Issue Molecular Research and Cellular Biology of Breast Cancer: 2nd Edition)
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21 pages, 4560 KB  
Article
Intermediate-Term Oncological, Anastomotic and Nutritional Outcomes of the Sutureless L-Shaped Esophagojejunostomy with Endoscopic Assistance (SLEJ) in Totally Laparoscopic Total Gastrectomy: A Follow-Up Analysis of This Technique
by Sevket Baris Morkavuk, Sumeyra Guler, Ibrahim Burak Bahcecioglu, Mujdat Turan, Gokhan Giray Akgul, Kubilay Kenan Ozluk, Erdi Aydin, Kahraman Dinler, Cagdas Karaman and Mehmet Ali Gulcelik
Medicina 2026, 62(9), 1685; https://doi.org/10.3390/medicina62091685 - 2 Sep 2026
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Abstract
Background and Objectives: Intra-corporeal esophagojejunostomy after totally laparoscopic total gastrectomy (TLTG) remains one of the most technically demanding steps of minimally invasive gastric surgery. The management of the common entry hole in linear stapler-based reconstructions still relies on advanced intra-corporeal suturing. The [...] Read more.
Background and Objectives: Intra-corporeal esophagojejunostomy after totally laparoscopic total gastrectomy (TLTG) remains one of the most technically demanding steps of minimally invasive gastric surgery. The management of the common entry hole in linear stapler-based reconstructions still relies on advanced intra-corporeal suturing. The sutureless L-shape esophagojejunostomy with endoscopic assistance (SLEJ) technique, previously described by our group, was developed to overcome this limitation by combining an L-shaped linear stapler configuration with intraoperative endoscopic quality control. Building upon our initial results on the perioperative feasibility of the technique, the present study aimed to evaluate its intermediate-term anastomotic, functional, and oncological outcomes. Materials and Methods: Patients who underwent TLTG with D2 lymph node dissection and SLEJ reconstruction for gastric cancer between July 2024 and January 2026 were evaluated. Eligibility criteria included a minimum postoperative follow-up of six months, clinical and endoscopic surveillance, and complete contrast-enhanced thoraco-abdominopelvic computed tomography records. Protocol-based upper gastrointestinal endoscopy was performed at six-month intervals irrespective of symptoms to objectively assess anastomotic lumen width, mucosal healing, reflux findings, and possible intraluminal recurrence. The primary endpoint was anastomosis complication-free survival (anastomotic stenosis, alkaline reflux/reflux esophagitis, marginal ulcer, bleeding due to ulceration, and intraluminal recurrence); secondary endpoints were disease-free survival (DFS), local recurrence and changes to nutritional status. Results: A total of 26 patients (18 men and 8 women; mean age 59.0 ± 7.8 years) were analyzed. Anastomotic stricture developed in two patients and was successfully managed with two sessions of endoscopic balloon dilation in both. Similarly, alkaline reflux was documented in two additional patients and resolved under medical treatment. None of the patients required surgical revision. The mean ACFS follow-up duration was 12.42 months with ACFS rates of 92.3% at six months and 81.1% from the twelfth month onward. No local anastomotic recurrence was detected during follow-up. Disease progression occurred in four patients (15.4%), presenting as distant organ metastasis (n = 2) or peritoneal carcinomatosis (n = 2). The mean DFS follow-up duration was 12.62 ± 6.18 months, and the twelve-month OS and DFS rates were 82.1% and 84.0%. Postoperative body weight decreased significantly compared with preoperative values (76.69 ± 15.59 kg vs. 63.23 ± 10.55 kg; p < 0.001). A significant decrease was observed in the mean SMI between the preoperative and follow-up assessments (p < 0.001). The mean preoperative SMI was 49.90 ± 9.04 cm2/m2, compared with 44.53 ± 7.98 cm2/m2 at follow-up. No statistically significant changes were observed between the preoperative and follow-up periods for serum albumin and PNI variables (p = 0.703 and p = 0.970). Conclusions: The present intermediate-term analysis suggests that the SLEJ technique is feasible and associated with acceptable intermediate-term anastomotic, functional, and oncological outcomes in this preliminary single-center cohort. By standardizing common entry-hole management without intra-corporeal suturing and incorporating intraoperative endoscopic quality control, the technique offers a feasible alternative to established linear stapler-based reconstructions. Full article
(This article belongs to the Section Surgery)
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23 pages, 5602 KB  
Article
Design and Field Evaluation of an IoT-Based Smart Tree Monitoring Network for Continuous Standing-Tree Diameter Monitoring
by Aiping Cao, Bicheng Zhou, Qiang Chen, Lei Song, Ming Gong, Zhen Chen, Weisheng Zeng, Bo Xu, Yiming Dai, Zimeng Li and Yuanyong Dian
Forests 2026, 17(9), 1034; https://doi.org/10.3390/f17091034 - 1 Sep 2026
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Abstract
Conventional forest inventories provide standardized but temporally discrete DBH observations, whereas some research and management applications require continuous observations of diameter dynamics between remeasurement campaigns. This study designed and implemented a Smart Tree Monitoring Network based on Internet of Things (IoT) and cloud [...] Read more.
Conventional forest inventories provide standardized but temporally discrete DBH observations, whereas some research and management applications require continuous observations of diameter dynamics between remeasurement campaigns. This study designed and implemented a Smart Tree Monitoring Network based on Internet of Things (IoT) and cloud storage technologies as a complementary intensive-monitoring approach for selected forest plots. The system enables automatic, continuous, networked observation of standing-tree diameter growth and consists of Tree Sensor Nodes (TSNs), Stand Gateways (SGs), and a cloud management platform. The independently designed tree diameter growth monitoring instrument senses micro-variations in DBH and conducts scheduled data acquisition. Low-power wireless transmission from TSNs to gateways is achieved through LoRa/LoRaWAN, while stand gateways aggregate multi-node data and environmental parameters and upload them to the cloud platform via a 4G network. Field deployment involved 426 devices in 10 sample plots with different terrain and climatic conditions in Hubei Province. The results showed that (1) with a 3.6 V, 19,000 mAh lithium battery and a 5 min sampling interval, daily power consumption was 5.37 mAh, corresponding to a theoretical battery-life estimate of 9.69 years under the tested duty-cycle assumptions; (2) at initial deployment, device-measured DBH showed strong agreement with manual measurements, with R2 = 0.9996, RMSE = 0.215 cm, MAE = 0.170 cm, and Bias = −0.089 cm, while subgroup analyses indicated larger underestimation for large-diameter trees; and (3) monthly mean RSSI and SNR remained above the adopted reference thresholds throughout 2025, while rainfall and temperature were associated with limited variation in signal quality. These results support the technical feasibility of the system for high-frequency DBH monitoring in selected plots, while long-term measurement drift, end-to-end data completeness, battery life under field aging, and physical durability require further validation. Full article
(This article belongs to the Special Issue Forest Resources Inventory, Monitoring, and Assessment)
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22 pages, 20612 KB  
Article
Foliar and Root Dynamic Analyses Reveal a Coordinated Defense Regulatory Network Against Aeolesthes induta Infestation in Tea Plants
by Chengcong Lu, Jialin Zhang, Ke Chen, Xuanyi Zhang, Xi Du, Fajie Feng, Pumo Cai and Yongcong Hong
Insects 2026, 17(9), 911; https://doi.org/10.3390/insects17090911 - 1 Sep 2026
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Abstract
The stem-boring herbivore Aeolesthes induta severely threatens tea (Camellia sinensis) production, yet the systemic defense mechanisms of tea plants remain largely elusive. The unique age-dependent infestation pattern of A. induta—with minimal damage to young tea plants but infestation rates reaching [...] Read more.
The stem-boring herbivore Aeolesthes induta severely threatens tea (Camellia sinensis) production, yet the systemic defense mechanisms of tea plants remain largely elusive. The unique age-dependent infestation pattern of A. induta—with minimal damage to young tea plants but infestation rates reaching 20% in 30-year-old trees and nearly 100% in ancient tea trees—necessitated field sampling from naturally infested old tea plantations rather than controlled laboratory conditions. By integrating rhizosphere microbiomics, transcriptomics, and multi-omics modeling, this study characterized the defensive regulatory networks of 30-year-old Shuixian tea cultivars under A. induta infestation. Rhizosphere microbiome analysis revealed that herbivore attack significantly reshaped the microbial community structure, reducing bacterial diversity and simplifying co-occurrence network complexity. Transcriptomic and metabolomic profiling demonstrated a precise source–sink defense allocation between host tissues. In leaves acting as the photosynthetic source, metabolic reprogramming was dominated by the systematic accumulation of soluble sugars and sugar acids for systemic energy reallocation. Concurrently, the roots acting as the metabolic sink vigorously activated the jasmonic acid (JA) signaling cascade and upregulated genes enriched in phenylpropanoid biosynthesis and alpha-linolenic acid metabolism. This molecular activation drove the substantial de novo synthesis of defensive phenolic acids, while downregulating growth-related flavonoids. Integrated network modeling further highlighted the phenylpropanoid pathway as the central regulatory node coupling transcript–metabolite fluctuations. This study constructs an integrated soil microbiome–root–leaf defense network, providing novel mechanistic insights into plant–borer interactions and a valuable foundation for future insect-resistant breeding programs in the tea industry. Full article
(This article belongs to the Special Issue Tea Pest Research and Control)
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