Search Results (25,312)

Objectives: Head and neck squamous cell carcinoma (HNSCC) ranks sixth globally, with a 50% five-year survival rate. SAR1A exhibits high expression levels in various tumor types, yet its specific role in HNSCC remains to be clarified. Methods: In vitro assays, such as CCK8, EdU, colony formation, wound-healing, transwell, and Western blotting analyses, as well as in vivo assays, such as tumor xenografts and lung metastasis models, were conducted to evaluate the impacts of SAR1A on HNSCC proliferation, migration, and invasion. Transcriptome sequencing and KEGG enrichment pathway analysis revealed evident alterations in the PI3K/AKT/mTOR(PAM) pathways. LY294002 (a PI3K/AKT inhibitor) was used to investigate the role of the PAM pathway in proliferation, migration, and invasion in HNSCC. Results: Univariate and multivariate Cox regression were conducted to screen SAR1A as a gene prognostic biomarker in HNSCC, and it was validated in the Cancer Genome Atlas (TCGA) database. Functional assays demonstrated that the depletion of SAR1A leads to suppressed proliferation, migration, and invasion of HNSCC cells. This is accompanied by a decrease in the expression of epithelial–mesenchymal transition (EMT)-related markers in HNSCC cell lines. In addition, the diminished capacities of proliferation, migration, and invasion observed in SAR1A knockdown cells were reversed upon the overexpression of SAR1A. Furthermore, RNA-seq and KEGG enrichment analysis demonstrated a significant alteration in the PAM pathway following SAR1A knockdown. LY294002 effectively mitigated the increased proliferation, migration, and invasion induced by SAR1A overexpression. Conclusions: SAR1A facilitates HNSCC proliferation and EMT via the PI3K/AKT/mTOR pathway. Full article

Background: Timely detection and aggressive management of interstitial lung disease (ILD) in systemic sclerosis (SSc) are essential to improving outcomes and reducing risks of irreversible lung injury. Objective: to explore the usefulness of an ultraportable ultrasound device for the management of SSc-related ILD and to compare it with clinical and instrumental data. Methods: A total of 19 consecutive SSc patients underwent a comprehensive pulmonary evaluation: clinical, pulmonary function tests (PFTs) (spirometry, DLCO), lung CT (1.5 mm slice thickness reconstruction; HRCT), and lung ultrasound (LUS). A total score was calculated based on the number of color-coded B-lines recorded for each lung sliding. B-lines were analyzed against dyspnea, cough, Velcro, CT imaging (Warrick’s score), and PFTs. Global and subgroup analysis were performed (diffuse versus limited cutaneous SSc, Warrick’s < 7 versus >7). Results: Symptomatic lung involvement with varying degrees of dyspnea was reported in about 74% of cases (functional NYHA > 2 in more than half), chronic dry cough in one-third, Velcro rales in 42%. A total of 84.24% were classified as SSc with ILD on CT imaging. Statistically significant mild-to-moderate correlations between B-lines and clinical manifestations were demonstrated, as well as PFTs and Warrick’s scores (more B-lines, lower pulmonary function, but higher extent and severity on CT) (p < 0.05); there were differences between SSc patients without and with ILD in terms of the number and distribution of B-lines (p < 0.05), as well as different B-lines patterns and numbers in diffuse versus limited SSc (p < 0.05). Conclusions: Ultraportable handheld LUS is a promising method suitable for the management (screening, early detection, and evaluation) of SSc patients. Full article

Bronchopulmonary dysplasia (BPD) is a condition of poor alveolar formation that causes chronic breathing impairment in infants born prematurely. Preterm lungs lack surfactant and are vulnerable to oxidative injuries driving the development of BPD. Our recent studies reported that surfactant protein A (SP-A) genetic variants influence susceptibility to neonatal lung disease. SP-A modulates activation of alveolar macrophages and parturition onset in late gestation. We asked whether a lack of SP-A alters alveolarization in a mouse model of hyperoxia-induced BPD. SP-A-deficient and control newborn mice were exposed to either clinically relevant 60% O₂ hyperoxia or normoxia for 5–7 days. Alveolar formation was then assessed by mean linear intercept (MLI) and radial alveolar count (RAC) measurements in lung tissue sections. We report that the combination of SP-A deficiency and hyperoxia reduces alveolar growth compared to WT mice. The morphometric analysis of normoxic SP-A-deficient lungs showed lower RAC compared to controls, indicating reduced alveolar number. In the presence of hyperoxia, MLI was higher in SP-A-deficient lungs compared to controls. Differences were statistically significant for female pups. Spatial proteomic profiling of lung tissue sections showed that hyperoxia caused a 4-fold increase in the DNA damage marker γH2Ax in macrophages of SP-A-deficient lungs compared to normoxia. Our short report suggests an important role for SP-A in perinatal lung development and the protection of lung macrophages from oxidant injury. These studies warrant future investigation to discern the temporal interaction of SP-A, gender, oxidant injury, and lung macrophages in perinatal alveolar formation and development of BPD. Full article

Objectives: The choice of the best Video-Assisted Thoracic Surgery (VATS) surgical approach is still debated. Surgeons are often faced with the choice between innovation and self-confidence. The present study reports the experience of a high-volume single institute, comparing data of uni-portal, bi-portal and tri-portal VATS, to find out the safest and most effective mini-invasive approach, leading surgeon’s choice. Methods: Between 2015 and 2022, a total of 210 matched patients underwent VATS lobectomy for early-stage cancer, using uni-portal (fifth intercostal space), bi-portal (seventh space for optic and the fifth), and tri-portal (seventh and the fifth/four) access. Patients were matched for age, BPCO, smoke, comorbidities, lesions (size and staging) to obtain three homogenous groups (A: uni-portal; B: bi-portal; C: tri-portal). The surgeons had comparable expertise. Data were retrospectively collected from institutional database and analyzed. Results: No differences were detected considering time of surgery, length of hospital stay, complications, conversion rate, specific survival, and days of chest tube length of stay. Better results on chest tube removal were described in group A (mean 1.1 days) compared to B (mean 2.6 days) and C (mean 4.7 days); nevertheless, they not statistically significant (p = 0.106). Conclusions: No significant differences among the groups were described, except for the reduction in chest tube permanence in group A. This allows to hypothesize an enhanced recovery after surgery in this group but the different approaches in this series seem to guarantee comparable safety and effectiveness. Considering no superiority of one method above the others, the best suggested approach should be the one for which the surgeon feels more confident. Full article

Background: Although BRAF V600E mutations are common in solid tumors and select hematologic neoplasms, they are reported less frequently in myeloid malignancies. Of the cases of BRAF V600E-mutant acute myeloid leukemia (AML) that have been described, most display monocytic morphology and concurrent KMT2A rearrangement. Strikingly, all cases have been associated with poor survival. Case Presentation: Here, we report two cases of AML, one diagnosed in an elderly male with metastatic lung adenocarcinoma and hepatocellular carcinoma and the other diagnosed in a young boy previously treated for B-cell acute lymphoblastic leukemia. Peripheral blood NGS revealed oncogenic mutations in BRAF p.V600E (VAF = 33%), TET2 p.M508Cfs*25 (VAF = 48%), TET2 p.C211* (VAF = 49%), ZRSR2 p.R295* (VAF = 71%), BRAF p.N581S (VAF = 6%), and EZH2 c.118-2A>G, p.? (VAF = 4%) in case 1 and BRAF p.V600E (VAF = 1%) and KRAS p.G12A (VAF = 28%) in case 2. Cytogenetic workup revealed a complex karyotype in case 1 and an abnormal karyotype with non-clonal aberrations and KMT2A (MLL) rearrangement in case 2. Morphologically, both patients were found to have AML with monocytic features. The post-mortem examination of case 2 also revealed extensive solid organ infiltration, consistent with a monocytic leukemia. Both patients died within days of diagnosis, demonstrating the lethality of this molecular subgroup of AML. Conclusions: Our cases add to the literature, highlighting the poor prognosis of patients diagnosed with BRAF-mutant AML. Although it is uncertain whether the complex karyotype and somatic mutations observed in case 1 and KMT2A rearrangement and variants identified in case 2 may have either independently or cooperatively conferred a poor prognosis, we contend that additional comprehensive studies are needed to further understand the pathophysiology and prognosis of BRAF mutations in AML. We further posit whether patients with BRAF V600E-mutant AML may benefit from the combined use of BRAF inhibitors and/or RAS-pathway-targeting regimens, which are currently FDA-approved for the treatment of BRAF V600-mutant solid tumors and BRAF-mutant histiocytic neoplasms. Full article

Fungal infections present a significant health risk, particularly in immunocompromised individuals. Berberine, a natural isoquinoline alkaloid, has demonstrated broad-spectrum antimicrobial activity, though its antifungal potential and underlying mechanisms against both yeast-like and filamentous fungi are not fully understood. This study investigates the antifungal efficacy of berberine against Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, and Trichophyton mentagrophytes in vitro, as well as its therapeutic potential in a murine model of cryptococcal infection. Berberine showed strong antifungal activity, with MIC values ranging from 64 to 128 µg/mL. SEM and TEM analyses revealed that berberine induced notable disruptions to the cell wall and membrane in C. neoformans. No signs of cell necrosis or apoptosis were observed in fungal cells treated with 2 × MIC berberine, and it did not increase intracellular ROS levels or affect mitochondrial membrane potential. Molecular docking and binding affinity assays demonstrated a strong interaction between berberine and the fungal enzyme CYP51, with a dissociation constant (KD) of less than 1 × 10⁻¹² M, suggesting potent inhibition of ergosterol biosynthesis. In vivo studies further showed that berberine promoted healing in guinea pigs infected with T. mentagrophytes, and in a murine cryptococcal infection model, it prolonged survival and reduced lung inflammation, showing comparable efficacy to fluconazole. These findings indicate that berberine exerts broad-spectrum antifungal effects through membrane disruption and CYP51 inhibition, highlighting its potential as a promising therapeutic option for fungal infections. Full article

Background/Objectives: Phyllanthus species are renowned in traditional medicine for their diverse therapeutic properties, including potential anticancer activities. This study explored the antiproliferative potential of six Phyllanthus species by integrating chemical composition with bioactivity assays to identify key antiproliferative compounds. Methods: The integration of liquid chromatography–mass spectrometry (LC-MS)-based chemical composition data with antiproliferative activity against three cancer cell lines—PC-3 (prostate adenocarcinoma), SiHa (cervical carcinoma), and A549 (lung carcinoma)—as well as a normal mouse fibroblast line (L929) was performed by covariate analysis. These compounds were subsequently isolated and structurally characterized using spectroscopic methods. Results: Through covariate statistics, seven m/z features were found to be plausible active compounds, and after isolation, they were related to butyrolactone and arylnaphthalide lignans. Among the active isolates, an unreported compound, (+)-phyllanlathyrin 6, was discovered in the aerial part of Phyllanthus lathyroides. The isolated compounds exhibited moderate to good antiproliferative activity (IC₅₀ < 20 µM) with selectivity to SiHa, validating the covariate-based identification approach. Conclusions: These findings highlight the potential of Phyllanthus species as sources of novel anticancer agents, with specific arylnaphthalide lignans showing promising cytotoxic effects that could be further developed into therapeutic leads. Additionally, this study underscores the value of combining advanced analytical techniques with bioactivity testing to uncover bioactive compounds from natural sources. The results contribute to the growing body of evidence supporting the therapeutic relevance of Phyllanthus species and provide a foundation for future drug development efforts targeting cancer treatment. Full article

Respiratory disorders are commonly regarded as complex disorders to diagnose due to their multi-factorial nature, encompassing the interplay between hereditary variables, comorbidities, environmental exposures, and therapies, among other contributing factors. This study presents a Clinical Decision Support System (CDSS) for the early detection of respiratory disorders using a one-dimensional convolutional neural network (1D-CNN) model. The ICBHI 2017 Breathing Sound Database, which contains samples of different breathing sounds, was used in this research. During pre-processing, audio clips were resampled to a uniform rate, and breathing cycles were segmented into individual instances of the lung sound. A One-Dimensional Convolutional Neural Network (1D-CNN) consisting of convolutional layers, max pooling layers, dropout layers, and fully connected layers, was designed to classify the processed clips into four categories: normal, crackles, wheezes, and combined crackles and wheezes. To address class imbalance, the Synthetic Minority Over-sampling Technique (SMOTE) was applied to the training data. Hyperparameters were optimized using grid search with k−fold cross-validation. The model achieved an overall accuracy of 0.95, outperforming state-of-the-art methods. Particularly, the normal and crackles categories attained the highest F1-scores of 0.97 and 0.95, respectively. The model’s robustness was further validated through 5−fold and 10−fold cross-validation experiments. This research highlighted an essential aspect of diagnosing lung sounds through artificial intelligence and utilized the 1D-CNN to classify lung sounds accurately. The proposed advancement of technology shall enable medical care practitioners to diagnose lung disorders in an improved manner, leading to better patient care. Full article

Background/Objectives: This study aimed to investigate the accuracy of Tumor, Node, Metastasis (TNM) classification based on radiology reports using GPT3.5-turbo (GPT3.5) and the utility of multilingual large language models (LLMs) in both Japanese and English. Methods: Utilizing GPT3.5, we developed a system to automatically generate TNM classifications from chest computed tomography reports for lung cancer and evaluate its performance. We statistically analyzed the impact of providing full or partial TNM definitions in both languages using a generalized linear mixed model. Results: The highest accuracy was attained with full TNM definitions and radiology reports in English (M = 94%, N = 80%, T = 47%, and TNM combined = 36%). Providing definitions for each of the T, N, and M factors statistically improved their respective accuracies (T: odds ratio [OR] = 2.35, p < 0.001; N: OR = 1.94, p < 0.01; M: OR = 2.50, p < 0.001). Japanese reports exhibited decreased N and M accuracies (N accuracy: OR = 0.74 and M accuracy: OR = 0.21). Conclusions: This study underscores the potential of multilingual LLMs for automatic TNM classification in radiology reports. Even without additional model training, performance improvements were evident with the provided TNM definitions, indicating LLMs’ relevance in radiology contexts. Full article

Background: Superparamagnetic properties and excitation independence have been incorporated into carbon-decorated manganese ferrite nanodots (MnFe@C) to introduce an economical and safer multimodal agent for use in both T1-T2 MRI and fluorescence-based imaging to replace the conventional highly toxic heavy metal contrast agents. Methods: The surface conjugation of 8-anilino-1-naphthalenesulfonate (ANS) to MnFe@C nanodots (ANS-MnFe@C) enhances both longitudinal and transverse MRI relaxation, improves fluorescence for optical imaging, and increases protein detection sensitivity, showing higher multimodal efficacy in terms of molar relaxivity, radiant efficiencies, and fluorescence sensitivity compared to MnFe@C. Results: The band gap energy was determined using Tauc’s equation to be 3.32 eV, while a 72% quantum yield demonstrated that ANS-MnFe@C was highly fluorescent, with the linear range and association constant calculated using the Stern–Volmer relation. The synthesized ANS-MnFe@C demonstrated excellent selectivity and sensitivity for bovine serum albumin (BSA), with a nanomolar detection limit of 367.09 nM and a broad linear range from 0.015 to 0.225 mM. Conclusions: In conclusion, ANS-MnFe@C holds ease of fabrication, good biocompatibility, as assessed in A375 cells, and an effective pH-sensitive doxorubicin release profile to establish anticancer activity in lung cancer cell line (A549), highlighting its potential as an affordable therapeutic agent for multimodal imaging, drug delivery, and protein sensing. Full article

Background: Over the last few decades, the efficacy of biological therapies for COPD has been evaluated by different randomized controlled trials (RCTs). Still, the evaluation of real-world data and patient-reported outcome measures (PROMs) have not been performed in this field before. In the current work, we present a systematic literature review of the real-world data and PROMs of biological treatments for COPD. Methods: Three large databases (MEDLINE/PubMed, Scopus, and ScienceDirect) were utilized for the systematic literature review. Clinical studies (RCT, cohorts, case series/reports) assessing patients with COPD treated by any biological therapy were included. Results: The review resulted in twelve eligible studies (nine randomized controlled trials and three “real-world” case series/reports). The evaluation of PROMs in the included studies was mainly limited to the severity and burden of respiratory symptoms. Most biological therapies were associated with improved PROMs compared to the baseline, although not for the placebo. Dupilumab was the only biologic therapy with proven efficacy in RCT for both objective and subjective measures. One prior study reported patients’ self-perceived drug effects, and none evaluated patients’ perceived disease status. Only 25 patients were assessed in a real-world setting for all biologic therapies combined. Real-world data were retrospective in the form of case reports or series. Conclusions: There are limited data on patients’ experience with biological therapies for COPD. While real-world data and PROMs are missing, biases such as a placebo effect must be considered, requiring their incorporation with objective outcomes from prospective controlled trials. Full article

Background: A remote dielectric sensing (ReDS) system quickly quantifies pulmonary congestion. Nonetheless, its efficacy in predicting an in-hospital increase in plasma B-type natriuretic peptide levels, the potential surrogate of worsening heart failure, remains undetermined. Methods: Patients who underwent ReDS measurement on admission during their hospitalization in the general wards for heart failure between 2021 and 2022 were eligible. The impact of the baseline ReDS value, completely blinded to the attending clinicians, on the in-hospital increase in plasma B-type natriuretic peptide levels of >100 pg/mL from index admission was evaluated. Results: A total of 147 patients admitted with acute-on-chronic heart failure (median age: 79 years; 76 men) were included. The median ReDS value on admission was 28% (25%, 34%). Eighteen patients experienced the primary outcome: plasma B-type natriuretic peptide levels increasing from 461 (207, 790) pg/mL (baseline) to 958 (584, 1290) pg/mL (maximum) (p < 0.001). The ReDS value on admission was an independent predictor of the primary outcome, with an adjusted odds ratio of 1.07 (95% confidence interval: 1.01–1.14; p = 0.028) with an optimal cutoff of 32%. Conclusions: The ReDS system could be a promising tool for predicting in-hospital worsening heart failure in patients hospitalized for heart failure when measured upon admission. The clinical implication of ReDS-guided management of heart failure during index hospitalization requires further studies. Full article

Background: Underweight is a prevalent condition among older adults in developing countries and poses a substantial burden on health, social, and aged-care systems. In this study, we examined the influence of tobacco use and food insecurity on the risk of being underweight among adults aged 60 or older in India. Methods: We used data from the 2017–2018 Longitudinal Aging Study in India. The sample size was 27,902 adults aged 60 years and above. We distinguished between smoking and smokeless tobacco use to examine how they may independently contribute to the outcome, while food insecurity was measured using the four-item version of the Food Insecurity Experience scale. Multivariable logistic regressions were conducted to assess the impact of tobacco use and food insecurity on the outcome. Additionally, we tested interactions between tobacco use and education, as well as between tobacco use and wealth. Results: The prevalence of underweight was 27% in the study population. Older adults who used smoking tobacco were twice more likely to be underweight than non-users (OR = 2.07, 95% CI = 1.79 to 2.40, p < 0.001), controlling for other confounders. The positive association between smokeless tobacco use and underweight was weaker but still significant (OR = 1.26, 95% CI = 1.11 to 1.42, p < 0.001). Food-insecure older adults were also more likely to be underweight (OR = 1.27, 95% CI = 1.10 to 1.48, p < 0.001). Other risk factors of underweight included males, rural residents, lower socioeconomic status (in terms of education, wealth, and caste), chewing disability, poor self-rated health, chronic lung disease, and tuberculosis. Interestingly, tobacco use moderated the relationship between wealth and underweight, such that smokers are more likely to be underweight as they become more affluent. Conclusions: Tobacco use and food insecurity have adverse implications on the nutritional status of the older persons in developing countries such as India. More targeted tobacco cessation measures and active food assistance programs for older adults are warranted to improve the overall health status of the older demographic. Full article