Search Results (44,121)

Necrotizing enterocolitis (NEC) and sepsis/late-onset sepsis (LOS) are significant contributors to preterm infant morbidity and mortality, with prematurity and low birth weight representing major risk factors for these interconnected conditions. Although the pathogenesis of NEC and LOS is not fully understood, there is a clear association with an immature intestinal mucosal barrier, which may enable bacterial invasion and translocation, resulting in an inflammatory cascade. Increasing recognition of the gut microbiome as a marker for health and disease has driven interest in probiotics, particularly Bifidobacterium spp. and Lactobacillus spp., as potential adjunctive agents for the prevention and management of NEC and LOS in preterm infants, which is the area of focus of this review. The focus of this paper was to analyze clinical studies using different probiotic strains, and compare single-strain versus multi-strain probiotic formulations. Several studies support that probiotic supplementation in preterm infants has the potential to decrease NEC incidence and, to a lesser extent, sepsis/LOS. Nonetheless, inconsistent results due to strain differences and clinical heterogeneity limit the widespread adoption of this mode of therapy, as do safety concerns in this vulnerable population. Further high-quality standardized studies are necessary to establish consistent guidelines for probiotic use in preterm infants. Full article

Background: Robot-assisted surgery has become increasingly used across multiple specialties; however, its integration into aesthetic plastic surgery remains limited. Individualized patient requirements, such as concealed scar placement, superficial soft tissue dissection, and patient-specific docking angles, are major challenges to its adoption, unlike in other specialties. This review aimed to evaluate the current use of robotic systems in plastic surgery, with a particular focus on aesthetic procedures, operative outcomes, and existing technological limitations. Methods: Multiple databases, including PubMed, Scopus, and Google Scholar, were extensively searched to identify studies published between 2011 and 2026. Data on robotic platforms, operative duration, rehabilitation outcomes, and aesthetic indications were extracted and analyzed. Robotic systems such as da Vinci, Symani, MUSA, and ARTAS demonstrated feasibility across reconstructive subspecialties. However, their clinical application remains limited, as purely aesthetic procedures are rare, highlighting a significant lack of standardized docking methods and dedicated instruments. Results: The data show that robotic platforms offer great advantages, such as precision and minimally invasive access; however, their high costs, bulky instrumentation, and limited docking methods represent barriers to their adoption in aesthetic surgery. Conclusions: Robot-assisted aesthetic plastic surgery remains in the early stage of development. Further research is required to establish reproducible docking standards and expand its clinical indications. Advancements in single-port systems, artificial intelligence integration, and surgeon training will facilitate broader clinical implementation. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, and although immunotherapy has transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC), durable benefit is limited to a subset of patients. PD-L1 immunohistochemistry and tumor mutational burden, while clinically utilized, demonstrate imperfect predictive capacity, underscoring the need for more robust biomarkers. This review highlights emerging multimodal biomarkers—including circulating tumor DNA (ctDNA), the gut microbiome, and artificial intelligence (AI)-driven radiomics—as promising tools to enhance the prediction of immunotherapy response. Longitudinal ctDNA monitoring offers a minimally invasive method to assess tumor burden dynamics, detect early molecular response, distinguish pseudo-progression from true progression, and stratify risk, with ctDNA clearance correlating with improved survival outcomes. The gut microbiome has also been associated with ICI efficacy, as specific bacterial taxa and composite scoring systems correlate with treatment response, though methodological heterogeneity limits clinical translation. Radiomic analyses leveraging CT and PET imaging extract quantitative tumor features that, when integrated with clinical and molecular data, demonstrate improved predictive performance compared to single-modality approaches. Despite promising advances, challenges including assay standardization, external validation, data harmonization, interpretability of AI models, and infrastructure requirements remain barriers to widespread adoption. Multimodal integration of genomic, microbiome, and imaging biomarkers represents a critical step toward precision immuno-oncology, with prospective validation needed to translate these approaches into improved outcomes for patients with advanced NSCLC. Full article

Background/Objectives: Advanced glycation end products (AGEs) accumulate in long-lived extracellular matrix proteins and have been implicated in skin aging and tissue remodeling, particularly in photo-exposed skin. High-frequency ultrasound (HFU) offers a non-invasive assessment of structural skin parameters that may reflect these changes. This study aimed to explore the associations between serum AGEs and HFU-derived structural parameters of cervico-facial skin, with a focus on UV-exposed dermal tissue. Methods: This cross-sectional study included 113 adults recruited in Cluj-Napoca, Romania. Fasting serum samples were analyzed for fructosyl-lysine (FruLys), pyrraline (Pyr), methylglyoxal-derived hydroimidazolone-1 (MG-H1), carboxyethyl-lysine (CEL), carboxymethyl-lysine (CML), arginine (Arg), and lysine (Lys). HFU, using a 22 MHz probe, was performed on the left zygomatic area to assess epidermal depth and density, UV-exposed dermal damage depth and density, dermis depth and density, and subcutaneous tissue depth and density. Associations between serum AGEs and HFU parameters were evaluated using Spearman correlation, with Benjamini–Hochberg false discovery rate (FDR) correction for multiple testing. Results: After FDR correction, epidermal depth was inversely correlated with serum CML (r = −0.402, adjusted p = 0.018). UV-exposed dermal density was inversely correlated with serum Pyr (r = −0.547, adjusted p < 0.019), Arg (r = −0.369, adjusted p < 0.019), and Lys (r = −0.270, adjusted p < 0.019). Subcutaneous tissue depth was also inversely correlated with serum CML (r = −0.290, adjusted p = 0.020). Conclusions: The study showed that higher levels of specific serum AGEs were associated with selected HFU-derived structural alterations in cervico-facial skin, particularly in UV-exposed dermal tissue. These exploratory findings support the biological plausibility that systemic glycation may be reflected by non-invasive skin ultrasound parameters. Full article

Background/Objectives: Glioblastoma remains the most lethal primary brain tumor in adults, and progress in oncolytic virotherapy is limited by the lack of immunocompetent models permissive to human-tropic viruses. Methods: Here, murine CT-2A and GL261 glioma and B16 melanoma cell lines were engineered to express human Coxsackievirus and Adenovirus Receptor (CXADR) fused to tagBFP, generating “humanized” tumors that preserve parental growth characteristics while acquiring high susceptibility to group B Coxsackieviruses (CVBs) and adenovirus serotype 5. Results: CXADR expression in CT-2A, GL261, and B16 cells markedly enhanced binding, internalization, and replication of CVBs in vitro, with the strongest effect observed for LEV14 (attenuated CVB5), which reached up to 10⁵-fold higher viral titers in humanized cells compared with parental cells. Unchanged sensitivity to vesicular stomatitis virus indicated receptor-specific effects. Humanized CT-2A-CXADR-BFP and GL261-CXADR-BFP cells initiated aggressive subcutaneous and intracranial tumors in syngeneic C57BL/6 mice without signs of immune rejection, and histology and MRI confirmed invasive high-grade glioma phenotypes. In intracranial CT-2A-CXADR-BFP tumors, repeated intratumoral LEV14 administration induced extensive tumor necrosis and prolonged survival despite the rapid development of neutralizing antibodies. Systemic intravenous LEV14 dosing produced strong oncolytic activity against subcutaneous CT-2A-CXADR-BFP tumors, as demonstrated by pronounced tumor growth inhibition, long-lasting regression in a subset of animals with gliomas, and improved overall survival. Conclusions: Collectively, these data establish CXADR-humanized models as versatile, immunocompetent platforms for evaluation of CXADR-dependent oncolytic enteroviruses. Full article

Non-muscle-invasive bladder cancer (NMIBC) is characterized by high recurrence rates and necessitates lifelong cystoscopic surveillance, underscoring the need for minimally invasive biomarkers to improve early detection and risk stratification. Therefore, this study aimed to investigate the role of trimethylamine-N-oxide (TMAO) and its precursors as diagnostic biomarkers for NMIBC. A total of 50 male patients with NMIBC (25 pTa and 25 pT1) were included in this study. Additionally, 52 age-matched healthy individuals were included as controls. Serum TMAO and its dietary precursors were quantified using liquid chromatography–tandem mass spectrometry. Group differences were analyzed using nonparametric tests, associations were assessed using Spearman’s correlation, and diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Multivariate logistic regression was performed to identify independent predictors, and a composite risk score was generated. Serum TMAO, carnitine, and choline levels were significantly higher in patients with NMIBC than in controls (p ≤ 0.0001), whereas betaine showed a nonsignificant trend toward higher levels (p ≥ 0.05). The pathological stage (pTa vs. pT1) showed the strongest correlation with TMAO levels. The ROC analysis revealed that TMAO had the highest individual diagnostic accuracy (area under the curve [AUC] = 0.875, 95% confidence interval [CI] 0.812–0.939), whereas carnitine and choline provided complementary diagnostic performance. In multivariate models, TMAO, carnitine, and choline remained independent predictors of NMIBC (p ≤ 0.0001). A composite risk score integrating all four metabolites demonstrated excellent discriminatory capacity (AUC = 0.958, 95% CI 0.926–0.991). The TMAO metabolic axis can be used as a minimally invasive biomarker panel for NMIBC. Further large, prospective, multicenter studies integrating metabolomic and microbiome profiling are needed to validate the findings. Full article

Background: Gastric cancer (GC) is characterized by aggressive invasion and early peritoneal dissemination, which are strongly driven by chronic inflammation and epithelial–mesenchymal transition (EMT). c-Jun N-terminal kinase (JNK), a stress-responsive serine/threonine kinase within the mitogen-activated protein kinase (MAPK) family, integrates inflammatory cues to promote EMT and metastasis. Huangjin Shuangshen granules (HJSS) is a multi-component traditional Chinese medicine (TCM) formula derived from Simiao Yong’an Decoction and clinically used as an adjuvant therapy for GC. However, whether HJSS restrains inflammation-driven metastasis through modulation of JNK-associated EMT signaling remains unclear. Methods: The anti-metastatic efficacy of HJSS was evaluated using integrated in vivo and in vitro models, combined with transcriptomics, network pharmacology and molecular validation. Results: HJSS markedly attenuated LPS-induced metastatic behavior and inflammatory activation. Multilevel analyses converged on MAPK8/JNK as a central regulatory node. HJSS reversed EMT progression and inhibited nuclear phosphorylation of JNK without affecting its upstream kinases. Thermal-shift assays and molecular docking supported potential target engagement of HJSS-derived constituents, including possible interactions with JNK-related signaling targets. Pharmacologic reactivation of JNK partially abrogated the inhibitory effects of HJSS, confirming JNK-dependent action. Conclusions: HJSS suppresses inflammation-driven GC metastasis primarily by attenuating JNK-associated EMT, potentially through modulation of JNK activation by its bioactive constituents. These findings provide mechanistic insight into HJSS as a low-toxicity anti-metastatic strategy and support further exploration of its active constituents. Full article

Assessing individual animal health is essential for detecting early ecological stress that may scale to population-level impacts. Yet, conventional capture-based methods are invasive and logistically challenging, particularly for large mammals. This study evaluates the accuracy of drone-based morphometric measurements as a non-invasive approach for estimating elephants’ Body Condition Index (BCI). Research was conducted in Way Kambas National Park, Sumatra, using a DJI Matrice 300 RTK equipped with a multisensor camera to acquire aerial imagery, primarily from a top-down perspective. Morphometric parameters were extracted through image preprocessing, segmentation, and edge detection using an OpenCV-based Canny algorithm, followed by coordinate and Euclidean distance analyses. Drone-derived measurements were validated against field-based morphometry in captive Sumatran elephants. Linear regression revealed strong agreement between methods, with R² values ranging from 0.91 to 0.97. Mid-body width showed the highest accuracy (R² = 0.97, MAPE = 2.66%, RMSE = 2.36), while other body dimensions also performed consistently well. BCI-related morphometric ratios exhibited minimal differences between drone and field measurements, confirming methodological reliability. As an exploratory extension, a preliminary allometric scaling framework was applied to estimate body condition proxies in free-ranging wild elephants except for mid-body width; however, these estimates are model-derived from total body length and should be interpreted as indicative rather than as direct morphometric assessments of body condition. These findings demonstrate that drone-based photogrammetry provides a validated, practical, and non-invasive method for morphometric measurement in captive elephants, with promising but as yet incompletely validated potential for application to wild populations. Full article

Non-invasive temperature estimation during online operation is a critical challenge in enclosed micro-reaction systems, particularly when the thermal mass of the working fluid varies dynamically or is uncertain. Conventional model-based approaches typically rely on fixed thermal parameters, leading to significant estimation errors when the actual reagent volume deviates from nominal conditions. To address this limitation, this study proposes a volume-adaptive temperature estimation framework applied to an ultrafast quantitative polymerase chain reaction (qPCR) system. By modeling the heat-transfer pathways via a simplified resistance–capacitance (RC) network, a nonlinear least squares (NLS) algorithm within an output-error (OE) framework is employed to identify key thermal parameters online. The framework separates the estimation into an offline calibration stage—where a thermocouple-equipped chip provides ground-truth data—and an online deployment stage that relies solely on non-invasive external measurements. This approach allows the system to explicitly compensate for volume-induced variations in thermal inertia. Validation experiments on an ultrafast qPCR platform with reagent volumes ranging from 100 to 250 $\mathsf{\mu }\mathrm{L}$ and heating rates exceeding 20 °C/s demonstrate that the method achieves robust performance, maintaining a mean absolute error (MAE) of reagent temperature at 0.24 ℃ and restricting the average volume estimation error to within 1.37 $\mathsf{\mu }\mathrm{L}$. DNA gel electrophoresis results further confirm the biological reliability of the temperature prediction strategy by verifying amplification specificity. This work provides a generalised solution for precise thermal management in micro-systems subject to variable thermal loads. Full article

Laser acupuncture (LA) integrates principles of traditional acupuncture with photobiomodulation (PBM) and has gained increasing attention as a non-invasive modality for pain management. PBM-based integrative LA in medicine refers to the application of low-level laser irradiation to acupuncture points, combining contemporary biomedical mechanisms with holistic, system-oriented therapeutic principles. This narrative review aimed to critically assess the scientific evidence on the efficacy of LA for pain management within the framework of the Principles of Clinical Integration of Photobiomodulation (PCIPBM) in LA, summarizing frequently used laser parameters and clinical indications. LA involves special protocols in standardized acupoints, using defined parameters of wavelength, irradiation, and energy density, consistent with PBM dosing principles. Therapeutic effects are mediated through point-specific neuromodulation and photobiological mechanisms, including modulation of peripheral and central nociceptive processing, reduction in pro-inflammatory mediators, improvement of microcirculation, and mitochondrial activation via cytochrome c oxidase-dependent adenosine triphosphate (ATP) synthesis. Clinical studies report statistically and clinically significant analgesic effects, particularly in chronic musculoskeletal pain, osteoarthritis, low back and neck pain, temporomandibular disorders, neuropathic pain, and selected postoperative pain conditions, when appropriate laser parameters are applied. Reported adverse effects are minimal, and tolerability is high. LA represents a safe, non-invasive therapeutic option and patient-friendly approach with clinically relevant efficacy in pain management. When applied according to PCIPBM, including evidence-based PBM parameters, it may serve as an effective adjunct or alternative to conventional pharmacologic and interventional approaches. Further standardization and high-quality randomized controlled trials are still required. Full article

The fractures of Weixinan oil shale simultaneously influence drilling fluid invasion and solid strength and makes the collapse pressure difficult to predict. The indentation–NMR combined experiments were conducted to analyze the collapse characteristics, and the relationship between water porosity and shale strength was established. The experiment results show that water infiltration still occurs in oil-based drilling fluids in the short term and leads to a significant strength decrease. 3D numerical modeling was used to analyze water migration and shale strength weakening under fluid–solid coupling. It was found that fractures act as seepage channels and this aggravates the clay hydration and the shale instability. This causes high collapse pressure under specific well inclination angles and azimuth angles. The research results provide important references for shale wellbore stability analysis and engineering practice with complex geostress conditions and hydration. Full article

Oral cancer remains a major global health problem with high morbidity and mortality rates, and despite advances in therapeutic approaches, challenges persist in early diagnosis and effective disease management. MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that regulate gene expression at the post-transcriptional level and play fundamental roles in maintaining cellular homeostasis, as well as in the initiation and progression of multiple malignancies, including oral cancer. Dysregulation of miRNAs contributes to oral carcinogenesis by modulating key cellular processes such as cell proliferation, apoptosis, invasion, metastasis, and angiogenesis. Altered miRNA expression profiles have been consistently identified in oral cancer tissues and body fluids, including saliva and blood, supporting their potential utility as reliable biomarkers for early detection, prognosis, and disease monitoring. Circulating miRNAs, in particular, represent a promising non-invasive diagnostic tool for assessing disease progression and therapeutic response. Moreover, miRNAs are actively involved in regulating sensitivity and resistance to chemotherapy and radiotherapy, with specific miRNAs either enhancing treatment efficacy or promoting therapeutic resistance. This review aims to highlight the critical role of miRNAs in oral cancer pathogenesis, diagnosis, prognosis, and treatment, exploring their potential as biomarkers and therapeutic targets to improve early detection, patient outcomes, and personalized treatment strategies. Full article

Background/Objectives: Stroke is a sudden neurological event caused by disrupted cerebral blood flow and represents a leading cause of acquired disability worldwide. Motor impairments and spasticity are among the most prevalent sequelae, significantly limiting functional independence and quality of life. Non-invasive electrotherapy has emerged as a complementary strategy in neurorehabilitation aimed at enhancing neuroplasticity and improving motor recovery. To systematically review current evidence regarding the effectiveness of non-invasive electrotherapy modalities in the rehabilitation of motor sequelae and spasticity following stroke, and to examine their theoretical and clinical rationale. Methods: A systematic literature review was conducted in accordance with PRISMA 2020 guidelines. The protocol was prospectively registered in the Open Science Framework (OSF). A comprehensive search was performed in Pubmed, Web of Science (WoS), and Scopus for studies published up to 14 November 2023, using the terms “Electric Stimulation Therapy” and “Stroke”. The methodological quality was assessed using the PEDro scale. The levels of evidence were classified according to the Oxford Centre for Evidence-Based Medicine criteria, and the risk of bias was evaluated using the Cochrane Risk of Bias tool (RoB 2). Results: Sixteen studies were included in the review. The analyzed interventions comprised neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), functional electrical stimulation (FES), neuromuscular electrical stimulation combined with transcranial magnetic stimulation (NMES + rTMS), transcranial direct current stimulation (tDCS), and afferent electrical stimulation (AES). Overall, the methodological quality of the included studies ranged from moderate to high, with PEDro scores between 6 and 9 out of 10. According to the Oxford Centre for Evidence-Based Medicine classification, most studies corresponded to level 1b evidence, while a smaller proportion were classified as level 2b. A risk of bias assessment using the Cochrane RoB 2 tool showed that the majority of the included studies presented a low risk of bias across most domains, although some concerns were identified in the domains of randomization and measurement in a limited number of trials. Across modalities, consistency within group improvement in motor function and spasticity was reported. However, between group comparisons with conventional rehabilitation were often inconsistent and did not consistently demonstrate superiority. The variability in stimulation parameters, intervention duration, and outcome measures further limited direct comparisons across studies. Conclusions: Non-invasive electrotherapy appears to be a safe and promising adjunct to conventional stroke rehabilitation. Nevertheless, further high-quality studies are required to clarify the underlying neurophysiological mechanisms and to establish standardized treatment protocols. Full article

The starch and moisture content of saffron corms are critical indicators of their flowering potential and yield. This study investigated the use of rapid, minimally invasive VNIR reflectance spectroscopy measurement to assess these parameters. The measurements were used to develop predictive models through four machine learning algorithms (PLSR, RF, SVR, and GPR). Spectral data were obtained from 130 fresh corm samples. Wavelength analysis identified key starch-sensitive intervals (~930–1000 nm and ~1150–1220 nm) and a broad moisture-sensitive region (~900–1350 nm). Among the evaluated models, the combination of the multiplicative scatter correction pre-processing method and Gaussian process regression (MSC-GPR) demonstrated the optimal predictive performance for water content (R² = 0.92, RMSE = 0.71%, RPD = 4.56, RPIQ = 5.37), and the combination of the MSC method and partial least squares regression (PLSR-MSC) demonstrated moderate performance for starch content (R² = 0.73, RMSE = 28.7 mg g⁻¹, RPD = 2.14, RPIQ = 2.81, dry weight). These results demonstrate the viability of VNIR spectroscopy as a minimally invasive tool for the pre-planting assessment of saffron corm quality under laboratory conditions. The method provides a laboratory-based framework for corm screening and selection, with potential for future adaptation to field settings using portable spectrometers following expanded calibrations and advanced modeling techniques. Full article