Search Results (5,706)

Background: Drug–drug interactions (DDIs) may occur when two or more drugs are taken together, leading to undesired side effects or potential synergistic effects. Most clinical effects of drug combinations have not been assessed in clinical trials. Therefore, predicting DDIs can provide better patient management, avoid drug combinations that can negatively affect patient care, and exploit potential synergistic combinations to improve current therapies in women’s healthcare. Methods: A DDI prediction model was built to describe relevant drug combinations affecting reproductive treatments. Approved drug features (chemical structure of drugs, side effects, targets, enzymes, carriers and transporters, pathways, protein–protein interactions, and interaction profile fingerprints) were obtained. A unified predictive score revealed unknown DDIs between reproductive and commonly used drugs and their associated clinical effects on reproductive health. The performance of the prediction model was validated using known DDIs. Results: This prediction model accurately predicted known interactions (AUROC = 0.9876) and identified 2991 new DDIs between 192 drugs used in different female reproductive conditions and other drugs used to treat unrelated conditions. These DDIs included 836 between drugs used for in vitro fertilization. Most new DDIs involved estradiol, acetaminophen, bupivacaine, risperidone, and follitropin. Follitropin, bupivacaine, and gonadorelin had the highest discovery rate (42%, 32%, and 25%, respectively). Some were expected to improve current therapies (n = 23), while others would cause harmful effects (n = 11). We also predicted twelve DDIs between oral contraceptives and HIV drugs that could compromise their efficacy. Conclusions: These results show the importance of DDI studies aimed at identifying those that might compromise or improve their efficacy, which could lead to personalizing female reproductive therapies. Full article

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have modestly improved patient survival, their overall efficacy remains limited, and the prognosis is generally poor. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. Nevertheless, the immunosuppressive tumor microenvironment, tumor heterogeneity, and immune escape mechanisms significantly restrict the clinical benefit, which falls short of expectations. Within this context, cancer vaccines have emerged as a promising immunotherapeutic strategy. By activating the host immune system to eliminate tumor cells, cancer vaccines offer high specificity, low toxicity, and the potential to induce long-lasting immune memory. These advantages have positioned them as a focal point in cancer immunotherapy research. This paper provides a comprehensive overview of recent clinical advances in lung cancer vaccines, discusses the major challenges impeding their clinical application, and explores potential strategies to overcome these barriers. Full article

Background/Objectives: This single-cohort follow-up study describes the median overall survival (OS) in patients with unresectable head and neck squamous cell carcinoma (HNSCC) due to invasion of vital structures, which is under-represented in the current literature. Secondarily, subgroups were evaluated according to the type of presentation, in order to identify clinical characteristics and contribute to developing an appropriate treatment plan and managing patient’s expectations. Methods: This single-cohort observational study analysed the OS of 39 patients from the Otolaryngology Department with advanced-stage head and neck cancer with invasion of vital anatomical structures considered ineligible for surgical treatment. Secondarily, subgroups were evaluated according to type of presentation and various clinical characteristics. Results: A total of 39 patients radiologically classified as having unresectable HNSCC (i.e., unsuitable for surgical resection), with a mean age of 66.87 years, were included during a 24-month follow-up. By the end of the study, 56.4% of the patients had died. The median OS was 16.09 months. Statistically significant differences were observed when comparing human papilloma virus (HPV)-positive and -negative status and when comparing initial and recurrent tumours. Conclusions: The invasion of anatomical structures such as the skull base, internal carotid artery, and prevertebral space was associated with a marked decrease in survival, with an OS time of 16 months. This study provides valuable evidence in patients with unresectable HNSCC, highlighting tumour recurrence and HPV-negative status as important indicators of poor prognosis. Full article

Objective: This study aimed to improve the understanding of the lives of patients with chronic neuropathic pain planned for invasive motor cortex stimulation (iMCS) and assess their expectations towards this intervention and its impact. Methods: Semi-structured face-to-face interviews were conducted until saturation of data was reached. Patients were recruited from one university medical center in the Netherlands. All interviews were audio-recorded, transcribed verbatim, and subjected to thematic analysis using iterative and inductive coding by two researchers independently. Results: Fifteen patients were included (11 females; mean age 63 ± 9.4 yrs). Analysis of the coded interviews revealed seven themes: (1) the consequences of living with chronic neuropathic pain; (2) loss of autonomy and performing usual activities; (3) balancing energy and mood; (4) intimacy; (5) feeling understood and accepted; (6) meaning of life; and (7) the expectations of iMCS treatment. Conclusions: This is the first qualitative study that describes the suffering of patients with chronic neuropathic pain, and their expectations prior to invasive brain stimulation. Significant themes in the lives of patients with chronic pain have been brought to light. The findings strengthen communication between physicians, caregivers, and patients. Practice Implications: The insights gathered from the interviews create a structured framework for comprehending the values and expectations of patients living with central pain and reveal the impact of symptoms due to the central pain. This knowledge improves the communication between physicians and caregivers on one side and the patient on the other side. Furthermore, the framework enhances the capacity for shared decision-making, particularly in managing expectations related to iMCS. Full article

Cardiovascular disease (CVD) is the leading cause of death worldwide, with pathophysiological mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about drug interactions with the platelet-activating factor (PAF) pathway, a key mediator of inflammation. This study aimed to evaluate the effects of several commonly used cardiovascular and anti-inflammatory drug classes—including clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin II receptor blockers (ARBs), β-blockers, and analgesics—on platelet function via both the ADP and PAF pathways. Using human platelet-rich plasma (hPRP) from healthy donors, we assessed platelet aggregation in response to these two agonists in the absence and presence of graded concentrations of each of these drugs or of their usually prescribed combinations. The study identified differential drug effects on platelet aggregation, with some agents showing pathway-specific activity. Clopidogrel and NSAIDs demonstrated expected antiplatelet effects, while some (not all) antihypertensives exhibited additional anti-inflammatory potential. These findings highlight the relevance of evaluating pharmacological activity beyond traditional targets, particularly in relation to PAF-mediated inflammation and thrombosis. This dual-pathway analysis may contribute to a broader understanding of drug mechanisms and inform the development of more comprehensive therapeutic strategies for the prevention and treatment of cardiovascular, hypertension, and inflammation-driven diseases. Full article

Malignant gastric outlet obstruction (MGOO) is a serious complication arising from advanced gastric or pancreatic head cancer, significantly impairing patients’ quality of life by disrupting oral intake and inducing severe gastrointestinal symptoms. With benign causes such as peptic ulcer disease on the decline, malignancies now account for 50–80% of gastric outlet obstruction (GOO) cases globally. This review outlines the pathophysiology, evolving epidemiology, and treatment modalities for MGOO. Therapeutic approaches include conservative management, endoscopic stenting, surgical gastrojejunostomy (GJ), stomach partitioning gastrojejunostomy (SPGJ), and endoscopic ultrasound-guided gastroenterostomy (EUS-GE). While endoscopic stenting offers rapid symptom relief with minimal invasiveness, it has higher rates of re-obstruction. Surgical options like GJ and SPGJ provide more durable palliation, especially for patients with longer expected survival. SPGJ, a modified surgical technique, demonstrates reduced incidence of delayed gastric emptying and may improve postoperative oral intake and survival compared to conventional GJ. EUS-GE represents a promising, minimally invasive alternative that combines surgical durability with endoscopic efficiency, although long-term data remain limited. Treatment selection should consider patient performance status, tumor characteristics, prognosis, and institutional resources. This comprehensive review underscores the need for individualized, multidisciplinary decision-making to optimize symptom relief, nutritional status, and overall outcomes in patients with MGOO. Full article

Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, in turn, has had an impact on the overall statistics regarding the prognosis and outcome of the condition. Given the increase in life expectancy, it is critical to better predict outcomes and prognosticate in CF. Thus, each person’s choice to aggressively treat specific disease components can be more appropriate and tailored, further increasing survival. The objective of our narrative review is to summarize the most recent information concerning the value and significance of clinical parameters in predicting outcomes, such as gender, diabetes, liver and pancreatic status, lung function, radiography, bacteriology, and blood and sputum biomarkers of inflammation and disease, and how variations in these parameters affect prognosis from the prenatal stage to maturity. Materials and methods: A methodological search of the available data was performed with regard to prognostic factors in the evolution of CF in children and young adults. We evaluated articles from the PubMed academic search engine using the following search terms: prognostic factors AND children AND cystic fibrosis OR mucoviscidosis. Results: We found that it is crucial to customize CF patients’ care based on their unique clinical and biological parameters, genetics, and related comorbidities. Conclusions: The predictive significance of more dynamic clinical condition markers provides more realistic future objectives to center treatment and targets for each patient. Over the past ten years, improvements in care, diagnostics, and treatment have impacted the prognosis for CF. Although genotyping offers a way to categorize CF to direct research and treatment, it is crucial to understand that a variety of other factors, such as epigenetics, genetic modifiers, environmental factors, and socioeconomic status, can affect CF outcomes. The long-term management of this complicated multisystem condition has been made easier for patients, their families, and physicians by earlier and more accurate identification techniques, evidence-based research, and centralized expert multidisciplinary care. Full article

Background/Objectives: Anterior dental trauma in adolescents presents complex restorative challenges due to ongoing craniofacial development and high aesthetic expectations. This study evaluated the long-term clinical performance of feldspathic ceramic veneers and lithium disilicate crowns used in the anterior region following dental trauma in adolescents. Methods: A total of 209 restorations were placed in 85 adolescents (50 females, 35 males), aged 11.1–17.9 years (mean age: 15.1 years). Of these, 144 were lithium disilicate crowns, and 65 were feldspathic ceramic veneers. All restorations were fabricated using minimally invasive protocols and followed up for periods ranging from 3 to 60 months. Outcomes were assessed based on standardized clinical criteria for success and failure. Results: Lithium disilicate crowns exhibited superior long-term performance, with the majority of failures occurring in feldspathic veneers (p < 0.001), primarily due to chipping or structural fracture. Age and gender had no statistically significant influence on failure rates. Conclusions: Both feldspathic and lithium disilicate ceramic restorations represent viable treatment options for anterior dental trauma in adolescents. However, lithium disilicate demonstrates greater mechanical reliability, particularly in teeth with significant hard tissue loss. These results support the use of durable ceramic materials in adolescent restorative protocols involving dental trauma. Full article

Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models offer unparalleled insights into tumor biology, therapeutic vulnerabilities, and resistance mechanisms. These models maintain essential tumor characteristics such as cellular diversity, spatial structure, and interactions with the microenvironment, making them extremely valuable for disease modeling and drug testing. This review emphasizes recent progress in the development and use of thyroid cancer organoids and spheroids, focusing on their role in replicating disease features, evaluating targeted therapies, and investigating epithelial–mesenchymal transition (EMT), cancer stem cell behavior, and treatment resistance. Patient-derived organoids have shown potential in capturing individualized drug responses, supporting precision oncology strategies for both differentiated and aggressive subtypes. Additionally, new platforms, such as thyroid organoid-on-a-chip systems, provide dynamic, high-fidelity models for functional studies and assessments of endocrine disruption. Despite ongoing challenges, such as standardization, limited inclusion of immune and stromal components, and culture reproducibility, advancements in microfluidics, biomaterials, and machine learning have enhanced the clinical and translational potential of these systems. Organoids and spheroids are expected to become essential in the future of thyroid cancer research, particularly in bridging the gap between laboratory discoveries and patient-focused therapies. Full article

Introduction: Medication adherence is essential for treatment and recovery following hematopoietic stem cell transplantation (HSCT). However, limited data exist on the most effective methods to measure adherence and the factors influencing it in HSCT patients. Materials and Methods: A prospective longitudinal study assessed immunosuppressant medication adherence in 150 patients with hematologic malignancies undergoing allogeneic HSCT. Adherence was assessed using pill counts, immunosuppressant medication levels, patient-reported medication logs, and the Medication Adherence Response Scale-5 (MARS-5) at 30, 100, and 180 days post-HSCT. We evaluated adherence rates, agreement between methods, and sociodemographic and clinical predictors. From patient-reported logs, we calculated dose adherence (comparing reported doses to expected doses) and timing adherence (comparing medication intake within ±3 h of the prescribed time). Kappa analysis assessed agreement among methods. Results: Of 190 eligible patients, 150 (78.9%) enrolled. The mean age was 57.5 years (SD = 13.5); 41.3% (n = 62) were female, 85.3% (n = 128) were non-Hispanic White, and 73.3% (n = 110) were married or living with a partner. Medication adherence varied across the three timepoints and by measurement type: 52–64% (pill counts), 18–24% (medication levels), 96–98% (medication log dose adherence), 83–84% (medication log timing adherence), and 97–98% (MARS−5). There was minimal agreement between measures (Kappa range: 0.008–0.12). Conclusions: Despite the feasibility of leveraging objective and patient-reported measures to assess medication adherence in HSCT patients, there was little agreement between these measures. Patient-reported measures showed high adherence, while objective measures like pill counts and medication levels revealed more modest adherence. The complexity of medication regimens likely contributes to this discrepancy. A rigorous approach to understanding medication adherence in the HSCT population may entail both objective and subjective measures of medication adherence. Full article

Aortic valve diseases affect a significant percentage of the population, and with the extension of survival expectancy, they are expected to increase furthermore. Surgical treatment of aortic valve diseases mainly includes valve replacement and, rarely, its repair. The technology of both surgical and transcatheter valves is evolving, and new prosthetic valves with improved characteristics are available, e.g., longer lifespan, faster implantation, better hemodynamic performance with better effective orifice area, suitable for small aortic annuli, etc. Minimally invasive surgical techniques are constantly evolving and spreading. New access sites are used for transcatheter valve implantation. The Heart Team determines the most appropriate intervention for each patient based on their anatomical and clinical profiles, aiming to optimize long-term outcomes. Full article

Diabetic nephropathy affects approximately 30–40% of individuals with diabetes mellitus (DM) and is a major contributor to end-stage renal disease (ESRD). While angiotensin II receptor blockers (ARBs) have long served as a standard treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently gained attention for their renal and cardiovascular benefits. However, comparative real-world data on their long-term renal effectiveness remain limited. We conducted a retrospective, longitudinal study over a 2-year period to compare the impact of ARB monotherapy versus SGLT2i and angiotensin-converting enzyme inhibitor (ACEi) combination therapy on the progression of chronic kidney disease (CKD) in patients with DM. A total of 126 patients were included and grouped based on treatment regimen. Renal biomarkers were analyzed using t-tests and ANOVA (p < 0.01). Albuminuria was qualitatively classified via urinalysis as negative, level 1 (+1), level 2 (+2), or level 3 (+3). The ARB group demonstrated higher estimated glomerular filtration rate (eGFR) and lower serum creatinine (sCr) levels than the combination therapy group, with glycated hemoglobin (HbA1c), potassium (K⁺), and blood pressure remaining within normal limits in both cohorts. Albuminuria remained stable over time, with 60.8% of ARB users and 73.1% of combination therapy users exhibiting persistently or on-average negative results. Despite the expected additive benefits of SGLT2i/ACEi therapy, ARB monotherapy was associated with slightly more favorable renal function markers and a lower incidence of severe albuminuria. These findings suggest a need for further controlled studies to clarify the comparative long-term renal effects of these treatment regimens. Full article

During red wine production, managing the pomace cap is key for a successful fermentation, allowing the extraction of phenolics and other metabolites and providing the necessary oxygen for yeast activity. In recent years, automatic cap management systems based on the injection of gases have gained popularity, despite the limited scientific information regarding the outcomes of their use. This trial aimed to evaluate the composition of wine during industrial red wine fermentations using an automatic sequential air injection system (i.e., AirMixing MI^TM). Fourteen lots of Cabernet Sauvignon grapes were fermented using four air injection regimes, where the intensity and daily frequency of air injections were set to either low or high. As expected, the treatment combining high-intensity and high-frequency air injection produced the largest dissolved oxygen peaks reaching up to 1.9 mg L⁻¹ per cycle, compared to 0.1 mg L⁻¹ in the low-intensity and low-frequency treatment. Yet, in all cases, little to no accumulation of oxygen overtime was observed. Regarding phenolics, the highest intensity and frequency of air injections led to the fastest increase in total phenolics, anthocyanins, short polymeric pigments, and tannin concentration, although compositional differences among treatments equilibrate by the end of fermentation. The main differences in phenolic compounds observed during fermentation were mediated by temperature variation among wine tanks. Based on these findings, it is advisable to keep the characterizing kinetics of phenolic extraction and expand the study to the aroma evolution of wines fermented with this technology. Full article

This study systematically investigates the homogenization-induced Laves phase dissolution kinetics and recrystallization mechanisms in laser powder bed fusion (L-PBF) processed IN718 superalloy. The as-built material exhibits a characteristic fine dendritic microstructure with interdendritic Laves phase segregation and high dislocation density, featuring directional sub-grain boundaries aligned with the build direction. Laves phase dissolution demonstrates dual-stage kinetics: initial rapid dissolution (0–15 min) governed by bulk atomic diffusion, followed by interface reaction-controlled deceleration (15–60 min) after 1 h at 1150 °C. Complete dissolution of the Laves phase is achieved after 3.7 h at 1150 °C. Recrystallization initiates preferentially at serrated grain boundaries through boundary bulging mechanisms, driven by localized orientation gradients and stored energy differentials. Grain growth kinetics obey a fourth-power time dependence, confirming Ostwald ripening-controlled boundary migration via grain boundary diffusion. Such a study is expected to be helpful in understanding the microstructural development of L-PBF-built IN718 under heat treatments. Full article

Volcanic rock is a natural mineral material which has garnered interest for its potential application in water treatment due to its unique physicochemical properties. In this study, we prepared a polysilicate aluminum chloride (PSAC) coagulant using volcanic rock which exhibited good coagulation–flocculation performance. Further investigation into the influence of synthetic parameters, such as calcination temperature, reaction time, and alkali types, on the structure and performance of a volcanic rock-derived coagulant was conducted. Techniques including Scanning Electron Microscopy, Energy-Dispersive Spectroscopy, Fourier-Transform Infrared Spectroscopy, and X-Ray Diffraction were utilized to characterize it. Also, a ferron-complexation timed spectrophotometric method was used to study the distribution of aluminum species in the coagulant. Results indicated that the volcanic rock that was treated with acidic and alkaline solutions had the potential to form PSAC with Al-OH, Al-O-Si, Fe-OH, and Fe-O-Si bonds, which influenced the coagulation–flocculation efficiency. An acid leaching temperature of 90 °C, 8 mL of 2 mol/L NaOH, a reaction time of 0.5 h, and a reaction temperature of 60 °C were conducive to the preparation. A higher temperature could result in a higher proportion of Alb species, and, at 100 °C, the Ala, Alc, and Alb were 29%, 24%, and 47%, respectively, achieving a residual turbidity lower than 1 NTU at an appropriate dosage, as well as a reduction of over 0.1 to 0.018 in the level of UV₂₅₄. The findings of this study provide a feasible method to prepare a flocculant using volcanic rock. Further application is expected to yield good results in wastewater/water treatment. Full article