Search Results (538)

Background/Objectives: Neoadjuvant therapy (NAT) is now central to the management of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic ductal adenocarcinoma (PDAC). This narrative review summarizes contemporary evidence and guidelines from a surgical perspective, with emphasis on pretreatment classification, post-NAT selection for exploration, intraoperative vascular strategy, and postoperative management. Methods: We conducted a structured narrative review of randomized and prospective studies, high-quality observational cohorts, and major international guidelines published through 31 July 2025. Results: BRPC and LAPC remain primarily defined by vascular anatomy, but biologic and conditional factors are increasingly integrated into decision-making. NAT is the preferred initial strategy for BRPC and the standard induction approach for LAPC, with resection considered only in carefully selected responders. After NAT, contrast-enhanced CT combined with CA19-9 kinetics remains the core restaging platform, while FDG-PET, diffusion-weighted MRI, radiomics, and circulating biomarkers may serve as adjuncts in equivocal cases. Surgical exploration should be guided by physiologic recovery, the absence of metastatic progression, and multidisciplinary reassessment. Staging laparoscopy remains useful for detecting occult metastatic disease. Intraoperatively, vascular resection should be margin-driven rather than routine, with portal–mesenteric venous resection established in expert centers, whereas arterial resection remains highly selective. Periarterial divestment represents an artery-sparing alternative in selected cases. NAT does not appear to worsen short-term postoperative outcomes, but anticoagulation after venous reconstruction remains non-standardized. Conclusions: NAT has transformed BRPC/LAPC PDAC into a biology-gated, time-sequenced surgical pathway. Standardized reassessment, careful candidate selection, and the centralization of complex vascular procedures are essential to optimize outcomes. Full article

Tuberculosis (TB) remains a major public health challenge in Peru, where interindividual variability in treatment response and drug-induced hepatotoxicity may be influenced by host genetic background. This study aimed to characterize clinically relevant polymorphisms in NAT2, CYP2E1, and SLCO1B1 in a cohort of TB patients from Southern Peru, a genetically underrepresented Andean population. Thirty-five adults receiving first-line therapy (isoniazid and rifampicin) underwent targeted Sanger sequencing of key functional variants among these three genes. NAT2 acetylator phenotypes were predominantly intermediate (68.6%), followed by rapid (20%) and slow (11.4%) profiles, with high minor allele frequencies for rs1041983 and rs1801280. CYP2E1 functional promoter variants were infrequent, whereas SLCO1B1 exhibited notable allelic heterogeneity, suggesting potential variability in rifampicin transport. Comparative analysis with previously reported Peruvian data revealed regional differences in acetylator distribution, supporting population-specific pharmacogenomic stratification. Although clinical toxicity outcomes were not evaluated, the high prevalence of reduced acetylation genotypes suggests a substantial proportion of patients may benefit from genotype-informed isoniazid dosing strategies. These findings provide foundational data for implementing precision medicine approaches using affordable and targeted technologies in TB management within Andean populations and support the integration of pharmacogenomics into national TB control programs. Full article

Gliomas are the most common type of primary brain tumors in adults, with a high level of recurrence and mortality. Their complex biology and adaptive resistance mechanisms pose major obstacles to existing treatment strategies. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), are crucial in tumor development and progression. Small RNA sequencing technology was performed in 25 patients with high-grade gliomas (HGGs) to analyze ncRNA expression in gliomas compared to normal adjacent tissues (NATs) aiming to elucidate their possible roles in these malignancies. Samples from patients with gliomas were examined, revealing an overall upregulation of ncRNAs. Specific ncRNA classes, including miRNAs, transfer RNAs (tRNAs), Piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs) showed notable shifts in abundance between tumor and normal samples. Among the upregulated miRNAs, a set of top five, such as miR-21, miR-221, miR-1321, miR-1306-5p, and miR-374a-5p, were validated by real-time quantitative PCR (RT-qPCR) in a cohort of 17 low-grade gliomas (LGGs) and 52 HGGs. These miRNAs are associated with critical oncogenic pathways and correlated with a worse prognosis. This study expanded the understanding of glioma biology and further confirmed the role of ncRNAs in the pathogenesis, supporting their potential use as novel possible biomarkers or therapeutic targets. Moreover, it provided an integrated analysis of multiple ncRNA classes, offering validation across both LGG and HGG, and uniquely incorporating a Kurdish cohort. Full article

Nateglinide (Nat) is an oral antidiabetic agent of the meglitinide class that has been reported to exert protective effects beyond glycemic control, particularly against oxidative stress and inflammation. Since oxidative stress and inflammation play a key role in the pathogenesis of acute kidney injury (AKI), especially following ischemia/reperfusion (I/R), this study aimed to evaluate the potential renoprotective effects of Nat in a rat model of I/R-induced AKI. Forty male Sprague Dawley rats were randomly divided into four groups (n = 10): Control, I/R, I/R + Nat (50 mg/kg), and I/R + Nat (100 mg/kg). Bilateral renal ischemia was induced by clamping renal arteries for 45 min, followed by 24 h of reperfusion. Nat was administered orally 1 h before ischemia. Renal levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and thiobarbituric acid reactive substances (TBARSs) were assessed. Serum blood urea nitrogen (BUN), creatinine, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were also measured, and histopathological analyses were performed. Nat significantly increased renal antioxidant parameters and reduced TBARS levels. Moreover, Nat markedly decreased serum BUN, creatinine, TNF-α, and IL-1β levels compared with the I/R group (p < 0.05). Histopathology confirmed attenuated renal damage in Nat-treated groups (p < 0.0001). These results indicate that Nat confers significant renoprotection against renal I/R injury via suppression of oxidative stress and inflammation. Full article

Objective: To develop and evaluate a nomogram integrating radiomic features from contrast-enhanced CT with clinical variables for pre-treatment predictions of the response to neoadjuvant therapy (NAT) in locally advanced gastric cancer (LAGC). Methods: In this retrospective multicenter study, 183 LAGC patients from the First Affiliated Hospital of Nanjing Medical University (2014–2023) were included. Radiomic features were extracted from manually delineated pre-treatment CT regions of interest. A machine learning-based predictive model combining radiomic scores and clinical data was constructed. Model performance was assessed using receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). Results: Multivariate analysis identified the radiomic score, preoperative N stage, and neoadjuvant regimen as independent predictors of NAT responses (all p < 0.05). The integrated nomogram achieved an area under the ROC curve of 0.807 and showed a moderate net benefit in DCA compared with the radiomics-only model. Conclusions: The radiomics–clinical nomogram demonstrates moderate predictive performance for pre-treatment stratification of NAT responses in LAGC. These findings are exploratory and hypothesis-generating, and further validation in independent cohorts is required before clinical application. Full article

Background/Objectives: Gastric cancer remains one of the most frequent abdominal malignancies, being the 5th in incidence, and it is often diagnosed at advanced stages. Perioperative chemotherapy has been introduced to improve oncological outcomes, although concerns persist regarding increased postoperative complications after radical gastrectomy following neoadjuvant treatment (NAT). Methods: We performed a retrospective study on a continuous series of gastric cancer patients who underwent radical gastrectomy between January 2016 and December 2025. Patients were divided into two groups: those receiving NAT and those undergoing upfront surgery (US). Demographic data, clinical characteristics, operative variables, postoperative complications, 30-day mortality, and pathological findings were compared. Results: There were 383 patients included in the study; NAT was performed in 105 (27.4%) cases and US in 278 (72.6%) cases, with a mean age of 64.99 (63.09–66.88) vs. 67.83 (66.44–68.91) years. Baseline characteristics (Charlson score 3.8 vs. 4.26, p = 0.131), hemoglobin, and albumin levels, were similar between groups. Tumors in the NAT group were more frequently located in the upper stomach 19 (18.1%) vs. 33 (11.9%) or at the gastro-esophageal junction (only Siewert III tumors were included) 17 (16.2%) vs. 23 (8.3%) p = 0.04. Tumor stage was most frequently stage IIIB for radical surgery 111 (28.9%) and for the NAT group 20 (19.1%) and surgery first group 91 (32.7%). The overall grade III and above complication rates were 26 (6.8%) esojejunal fistula, 19 (4.9%) duodenal stump fistula, seven (1.8%) hemorrhagic complications, 31 (8.1%) cases of sepsis, and 33 (8.6%) medical complications. Anastomotic fistulas were more frequent in the surgery-first group, with 23 cases (8.3%), compared with the neoadjuvant group, with 3 patients (2.9%)—the result were not statistically significant. The number of resected lymph nodes was similar (35.4 vs. 35.2; p = 0.96), while NAT group had significantly fewer positive lymph nodes (5.7 vs. 8.0; p < 0.001). Complete pathological response was achieved in 10 (9.5%) of NAT patients. Conclusions: Neoadjuvant treatment does not appear to increase the complications rate following radical gastrectomy. This study supports the surgical safety of the perioperative adjuvant treatment for advanced gastric cancer patients. Further studies are necessary to assess long-term outcomes. Full article

Because of concentrated connection damage, the impact of sequential hazards on CLT shear wall systems is much more severe than that on traditional concrete and steel structures considering ductile component behaviors. The present paper evaluated the dynamic response of CLT wall structures in wind-only and sequential seismic–wind scenarios and compared the structural dynamic responses and damage levels of different CLT wall systems. The structural models were established separately based on an SOM benchmark structure, a SOFIE project three-story CLT shear wall structure, and a PT CLT wall platform structure from the NHERI Tall Wood project. The equivalent fluctuating wind load was calculated with the ASCE 7 average wind speed, the reference ESDU wind profile, calibrated wind pressure distribution, and simulated fluctuation from the NatHaz Online Wind Simulator. The sequential load was applied to the structural models in the order of seismic excitation, resting time, and then dynamic wind load. The dynamic responses of different CLT wall structures were compared among loading scenarios with increasing seismic and wind intensities. The wind-excited peak story displacement and acceleration for both CLT structures were significantly magnified in the sequential seismic–wind scenarios compared with the wind-only scenarios. The simulation results indicated that the sequential seismic–wind scenarios caused significant acceleration in damaged connections for the conventional CLT shear wall structure. The PT CLT wall structure had minor displacement and acceleration, which were linear to the wind loading factors. For the conventional CLT shear wall structure, the magnification of the acceleration was found to have a strong correlation with the natural frequencies of the damaged structure. This study demonstrated that the wind responses of the PT wall structures were in a safe range after the seismic event, and conventional CLT wall structures need to be re-evaluated under sequential scenarios for structural resilience assessment. Full article

Purpose: HER2-targeted therapy has been incorporated into the standard neoadjuvant treatment (NAT) regimen for HER2-positive early-stage breast cancer, yet a subset of patients have shown a limited pathological response. This study aimed to evaluate clinicopathological factors associated with NAT sensitivity and to develop a predictive model. Methods: This retrospective study included 13,004 HER2-positive breast cancer patients from the National Cancer Database (2010–2022) who received neoadjuvant chemotherapy plus HER2-targeted therapy. Pathological complete response (pCR) was defined as no residual invasive carcinoma in the breast and axillary lymph nodes (ypT0/is, ypN0). NAT sensitivity was additionally defined using clinical-to-pathologic stage migration according to the AJCC 8th edition criteria. Baseline characteristics and overall survival (OS) were compared between NAT-sensitive and NAT-insensitive groups. A multivariable logistic regression model was developed based on age, clinical T stage, clinical N stage, histologic subtype, tumor grade, and hormone receptor (HR) status. Model performance was assessed using the area under the receiver operating characteristic curve and calibration curves. Results: Among the patients included, 3660 (28.1%) achieved pCR. Based on the predefined stage-based criteria, 10,451 (80.4%) were classified as NAT-sensitive and 2553 (19.6%) as NAT-insensitive. NAT-insensitive patients were older and more likely to present with clinical T1c and node-negative disease, whereas NAT-sensitive patients more frequently had higher clinical T and N stages. HR-positive and lower tumor grades were significantly associated with treatment insensitivity. NAT-insensitive patients demonstrated significantly worse OS compared with NAT-sensitive patients (p < 0.001). The predictive model showed acceptable discrimination with AUCs of 0.762 in the training cohort and 0.776 in the validation cohort, demonstrating good calibration. Conclusions: NAT sensitivity in HER2-positive early-stage breast cancer exhibited substantial biological and clinical heterogeneity in real-world practice. A younger age, higher clinical stage, invasive ductal histology, higher tumor grade, and HR-negative status were associated with improved responses. A predictive model based on routinely available baseline variables demonstrated reasonable performance for estimating treatment sensitivity, supporting its potential utility for baseline risk stratification pending external validation. Full article

Background/Objectives: Citrus limon leaf essential oil (EO) is traditionally used for its calming and cognitive-enhancing properties. Although the chemical composition of C. limon leaf essential oils (EOs) obtained by means of hydrodistillation (HD) and solvent-free microwave extraction (SFME) has been previously characterized, the influence of the extraction method on their neuroprotective efficacy and dose–response effects remains insufficiently explored. In the present study, EOs obtained by means of HD (CEH) and SFME (CEM) were compared for their behavioral, biochemical, and in silico neuroprotective effects against scopolamine (SCOP)-induced cognitive and anxiety-like impairments in adult zebrafish. Methods: Adult Tübingen zebrafish were exposed to CEH or CEM via immersion at 10, 100, and 150 µL/L for 19 days prior to SCOP challenge (100 µM). Cognitive performance was evaluated using the Y-maze and novel object recognition (NOR) tests, while anxiety-like behavior was assessed using the novel tank test (NTT) and novel approach test (NAT). Brain acetylcholinesterase (AChE) activity and oxidative stress markers were quantified. Molecular docking analyses were conducted to investigate interactions between major EO constituents and AChE and monoamine oxidase A (MAO A). Results: Both CEH and CEM significantly attenuated SCOP-induced memory deficits, improved spontaneous alternation and NOR discrimination, and reduced anxiety-like behaviors. These effects were associated with AChE inhibition and restoration of redox balance. Notably, CEM generally exhibited stronger neurobehavioral and biochemical effects at comparable doses. In silico analyses supported these findings, revealing favorable binding affinities of key EO constituents toward cholinergic and monoaminergic targets. Conclusions: This study demonstrates that the extraction method influences the neuroprotective efficacy of C. limon leaf EOs. While both CEH and CEM exert antioxidant and cholinergic modulatory effects, CEM shows enhanced neuroprotective potential in a zebrafish model of SCOP-induced cognitive impairment, supporting the relevance of extraction-dependent biological profiling in EO-based neurotherapeutic research. Full article

Soil erosion assessments for policy are often derived from continental-scale datasets, but their suitability for regional planning remains unclear. This study compares two Revised Universal Soil Loss Equation (RUSLE) applications for Tuscany, Italy: one using high-resolution regional data (TuscReg) and another using European-scale data from the European Soil Data Centre (TuscNat). We found the mean estimated actual soil erosion rate was 58% higher in the regional assessment (10.7 vs. 6.8 Mg ha⁻¹ yr⁻¹). Remarkably, the spatial patterns diverged significantly in the complex landscapes characterizing some Tuscan soil regions. In mountainous areas like the Apuan Alps, TuscReg estimated soil erosion control (potential minus actual erosion) to be over 500 Mg ha⁻¹ yr⁻¹ greater than TuscNat for 30% of the area. Correlation analysis revealed these major differences were primarily driven by disparities in the rainfall erosivity (R) and soil erodibility (K) factors. Our results demonstrate that while EU-scale models provide a consistent, broad-scale overview, they can substantially underestimate erosion and the ecosystem service of erosion control in specific, high-risk environments. To implement policies like the EU Soil Monitoring Law (Directive (EU) 2025/2360), regional-scale data are essential to accurately identify priority areas for soil conservation and set meaningful local thresholds. Full article

A theorem of Sheshadri (Proc. Nat. Acad. Sci. USA 44 (1958) 456–458) shows that, when $\Lambda$ is a commutative principal ideal domain, finitely generated projective modules over the polynomial ring $\Lambda \left[t\right]$ are all free. The ring $\Gamma$ of Hurwitz quaternions, that is, the unique maximal order in the ring of rational quaternions, is the simplest example of a non-commutative principal ideal domain which is not a division ring. In contrast to the commutative case, we show that $\Gamma \left[t\right]$ has infinitely many isomorphically distinct projective modules; these are stably free of rank 1. Full article

Erbium-165 (¹⁶⁵Er) is an Auger electron emitter with 7.2 electrons per decay and very few other emissions, making it an interesting candidate for Auger electron therapy. We present here a procedure for producing ¹⁶⁵Er by the ^natHo(p,n)¹⁶⁵Er nuclear reaction on a 16.5 MeV medical cyclotron. The target was prepared by pressing a Ho₂O₃:Al 1:1 (w/w) powder mixture on a Ag disc with a cylindrical depression in the center. With a 0.1 mm Nb foil in front, degrading the energy to 15 MeV, and water cooling at the back of the Ag disc, the target could withstand irradiation at currents up to 45 µA without showing any signs of damage. The beam tolerance of the target was also estimated by calculating the temperature and heat dissipation in the target via the numerical solution of the heat transport equations. For a 180 mg target, the production yield was 12.3 ± 1.9 MBq/µAh. The separation of two neighboring lanthanides is challenging, which led us to study the distribution coefficients for Er and Ho on commercially available LN2 resin for both HNO₃ and HCl eluents. Based on these values, we propose a purification procedure involving two successive LN2 columns for separating the ¹⁶⁵Er from Ho and Al, followed by a small TK221 column to concentrate the final eluate. No radionuclidic impurities were detected, and the chemical impurities found in the final formulation were traces of Ho, Er, Ca, Pb, and Fe. For three different chelators (DOTA, DTPA, and CHX-A″-DTPA), the effective molar activity of the final formulation was measured. The stability of the three complexes formed was also assessed upon incubation in mouse serum for 28 h. Full article

Background: The accurate prediction of response to neoadjuvant therapy (NAT) is crucial for optimizing breast cancer management. Conventional breast Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) radiomics typically relies on single post-contrast phases and may not fully capture temporal enhancement patterns related to tumor heterogeneity. This study evaluated a machine learning model based on time-dependent radiomic features extracted from pre-treatment DCE-MRI for predicting NAT response in breast cancer patients. Methods: Breast DCE-MRI examinations of women scheduled for NAT, acquired on 1.5 T scanners from three different vendors, were retrospectively collected from two centers. Tumors were automatically segmented on the third post-contrast DCE image using a 3D nnUNet model trained on 30 lesions. All DCE phases were registered to the reference image, and radiomic features were extracted from a consistent tumor region of interest across all phases. Time-dependent radiomic features were computed using linear regression modeling of feature evolution over time. A random forest classifier integrating static and time-dependent radiomic features was developed to predict pathological complete response (pCR), partial response (pPR), and non-response (pNR). Model performance was evaluated using internal validation (Center 1) and an independent external test cohort (Center 2). Results: A total of 212 patients were included (173 from Center 1 and 39 from Center 2), comprising 103 pCR, 103 pPR and 6 pNR cases. Among 759 extracted features, 30 showed significant differences across response groups. Several time-dependent texture features related to intratumoral heterogeneity were significantly associated with pNR. The model achieved AUC values of 0.80, 0.81, and 0.95 in the internal validation cohort and 0.75, 0.74, and 0.86 in the external test cohort for predicting pCR, pPR, and pNR, respectively. Conclusions: Time-dependent radiomic features derived from pre-treatment breast DCE-MRI enable the accurate prediction of response to NAT, with particularly strong performance in identifying non-responders. This approach may support imaging-based risk stratification and contribute to more personalized treatment. Full article

Active compensation for perturbed space telescopes is an effective means of improving the image quality. In common-aperture dual-channel telescopes, compensation can only be achieved by adjusting a shared secondary mirror (SM), making it difficult to balance the inconsistent misalignment aberrations between the channels. To address this issue, an analytic method for simultaneous compensation of dual-channel aberrations is proposed. Based on the improved Nodal Aberration Theory (NAT), the analytic solution for the common compensation position of the SM is derived by establishing a geometric balance between the aberration field nodes in the image planes of the two channels. On this basis, the theoretical conditions required for the consistency of the optimal compensation positions in the dual channels are also presented. The robustness of the method is validated through Monte Carlo simulations under conditions of random noise and surface figure errors. The results show that the average RMS wavefront error (WFE) of each channel is reduced to less than λ/16 (λ = 632.8 nm) after compensation under various misalignment conditions. Compared with the traditional Sensitivity Matrix Method (SMM), the proposed method exhibits superior compensation accuracy and decoupling capability in correcting dual-channel aberrations, thereby significantly improving the optical performance of the system. Full article

Background: Circulating tumor (ct)DNA is a prognostic biomarker in gastrointestinal malignancies. In rectal cancer, its utility to inform perioperative management and predict recurrence, particularly in patients undergoing non-operative management (NOM), remains unclear. Studies are needed to clarify how post-neoadjuvant therapy (NAT) and post-surgical ctDNA status correlate with clinical outcomes in localized rectal cancer. Methods: We retrospectively analyzed ctDNA data from 220 patients with rectal cancer using a personalized tumor-informed assay (Signatera™, Natera, Inc., Austin, TX, USA). Of these, 148 (67.3%) underwent NAT followed by surgery, and 72 (32.7%) underwent NAT followed by NOM. We assessed associations between post-NAT ctDNA status and survival outcomes. In the surgical cohort, we examined associations between post-operative ctDNA status and clinical response, pathological response, survival outcomes, and NAR scores. Results: In the surgical cohort, ctDNA positivity at the post-operative MRD timepoint was a strong predictor of recurrence, with an 88.3% relapse rate compared to 11.5% in ctDNA-negative patients (p < 0.001). Among the 64 NOM patients with post-NAT ctDNA, 21.9% (14/64) were ctDNA-positive, of whom 100% (14/14) relapsed (92.9% local-only), 13 relapsed by the time of data cut-off, and one relapsed 8 months after the cut-off. Only 10% (5/50) of the ctDNA-negative NOM patients experienced local recurrence (p < 0.0001). ctDNA positivity post-NAT was associated with inferior DFS (p = 0.003). Conclusion: ctDNA was a strong predictor of recurrence in rectal cancer, including in NOM settings. In NOM patients, ctDNA detected local recurrences, highlighting its potential to guide post-NAT surveillance and treatment. Full article