Search Results (118)

Background and Objectives: Long-acting cabotegravir and rilpivirine (LA-CAB/RPV) offers an alternative to daily oral antiretroviral therapy (ART) for people living with HIV (PLWH). Although LA-CAB/RPV has been approved in Turkey, the country remains in the pre-rollout period, and national data on patient perspectives are lacking. This is the first nationwide study from Turkey, a setting of increasing HIV incidence, assessing PLWH perspectives on switching to LA-CAB/RPV and the influence of motivational factors on treatment preferences. Materials and Methods: A prospective, multicenter, cross-sectional study was conducted across 11 HIV treatment centers representing all regions of Turkey. Virologically suppressed PLWH meeting current eligibility criteria for LA-CAB/RPV were included. Treatment preferences (switch to LA-CAB/RPV or remain on oral ART) and five anticipated motivational domains, namely perceived efficacy, safety, convenience, privacy, and cost, were systematically assessed through structured, face-to-face interviews. Results: Among 200 eligible participants, 86% (n = 172) preferred switching to LA-CAB/RPV. In all subgroups, LA-CAB/RPV was preferred over oral ART, except for those with no formal literacy. Prior awareness of LA-CAB/RPV was significantly associated with the switching preference (p < 0.001), with healthcare providers being the most common source of information, at 45.5% (n = 172) (p < 0.001). Residential proximity to the healthcare center (p = 0.018) and all motivational factors significantly influenced the preference (p < 0.05). Notably, when participants who initially chose to remain on oral ART were asked whether they would reconsider switching if injections were administered every six months, overall preference for long-acting therapy increased from 86% to 98%. Conclusions: High clinical eligibility and strong acceptability for LA-CAB/RPV were observed among Turkish PLWH. Our findings demonstrate that structured motivational factors significantly influence the treatment preference. Addressing these patient-centered factors and logistical barriers may support the successful integration of long-acting therapies into routine HIV care. Future longer-interval agents may improve patient-centered acceptability. Full article

Background/Objectives: Tegoprazan (TPZ) is a potassium-competitive acid blocker (P-CAB) used to treat conditions such as gastroesophageal reflux disease, peptic ulcer, and Helicobacter pylori infection. It exists in three solid forms: amorphous, Polymorph A, and Polymorph B. This study investigates the molecular basis of polymorph selection, focusing on conformational bias and solvent-mediated phase transformations (SMPTs). Methods: The conformational energy landscapes of two TPZ tautomers were constructed using relaxed torsion scans with the OPLS4 force field and validated by nuclear Overhauser effect (NOE)-based nuclear magnetic resonance (NMR). Hydrogen-bonded dimers were analyzed using DFT-D. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), solubility, and slurry tests were conducted using methanol, acetone, and water. Kinetic profiles were modeled with the Kolmogorov–Johnson–Mehl–Avrami (KJMA) equation. Results: Polymorph A was thermodynamically stable across all analyses. Both amorphous TPZ and Polymorph B converted to A in a solvent-dependent manner. Methanol induced direct A formation, while acetone showed a B → A transition. Crystallization was guided by solution conformers and hydrogen bonding. Conclusions: TPZ polymorph selection is governed by solution-phase conformational preferences, tautomerism, and solvent-mediated hydrogen bonding. DFT-D and NMR analyses showed that protic solvents favor the direct crystallization of stable Polymorph A, while aprotic solvents promote the transient formation of metastable Polymorph B. Elevated temperatures and humidity accelerate polymorphic transitions. This crystal structure prediction (CSP)-independent strategy offers a practical framework for rational polymorph control and the mitigation of disappearing polymorph risks in tautomeric drugs. Full article

Polymer blending techniques enable the tailoring of desired properties for diverse applications. This study investigates the effect of PMMA content on the thermomechanical, chemical, mechanical, and fatigue life properties of PC/ABS/PMMA (polycarbonate/acrylonitrile–butadiene–styrene/polymethylmethacrylate) ternary blends. To this end, various characterization analyses, as well as tensile, impact, and fatigue tests, were conducted. The results indicate that the viscoelastic modulus improves with increasing PMMA content in ternary blends. Furthermore, PC/ABS/PMMA blends exhibit an immiscible phase morphology. The elastic modulus, yield strength, and tensile strength increase with higher PMMA content, while the elongation at break and impact strength decrease. Fatigue strength and the fatigue strength exponent were found to vary nonlinearly with PMMA content. Compared to PC/ABS blends, PC/ABS/PMMA blends demonstrated improvements of approximately 12% to 58% and 26% to 117% in hysteresis energy and the dynamic elastic modulus, respectively. Additionally, fatigue life cycles improved by 5% to 11% at low stress amplitudes. This experimental study provides comprehensive insight into the complex interplay among the chemical, thermomechanical, mechanical, and fatigue properties of ternary PC/ABS/PMMA blends, highlighting their potential for applications requiring balanced or tailored structural and material characteristics. Full article

In 2022, 20 million women globally were living with HIV, yet they remain underrepresented in clinical trials, including those for antiretroviral treatments (ART). This study assesses the safety and efficacy of the long-acting cabotegravir-rilpivirine (CAB-RPV) regimen in a cohort of 54 women living with HIV (WLWH) over 24 weeks. A retrospective cohort study from the Sardinian HIV Network and Sicilian HIV Cohort (SHiNe-SHiC) included WLWH who switched to CAB-RPV. Primary objectives were achieving and maintaining HIV RNA levels <50 copies/mL at 24 weeks. Secondary objectives included treatment safety, durability, and reasons for discontinuation. Data on demographics, viro-immunological markers, lipid profiles, and treatment interruptions were analyzed. Of 54 WLWH, 46 reached 24 weeks. The median age was 50 years. A total of 71.8% transitioned from dolutegravir (DTG) regimens. Virological suppression was 97.8% at baseline and 95.5% at 24 weeks. Significant increases in the CD4/CD8 ratio (p = 0.0076) and decreases in serum creatinine levels (p = 0.0109) were observed. Cholesterol, triglycerides, ALT, and AST levels remained unchanged. The CAB-RPV regimen demonstrated significant virological and immunological efficacy and safety in women living with HIV over 24 weeks. Notably, the improvement in the CD4/CD8 ratio and the increase in the percentage of women achieving target not detected (TND) status highlight the regimen’s effectiveness. These findings emphasize the importance of gender-focused research in HIV treatment and the need for equitable access to effective treatment options for women, which is crucial for global efforts to eliminate HIV. Full article

Mineral nutrition management in sweet cherry orchards remains a critical challenge due to the lack of site-specific fertilization guidelines, particularly in Greece, a significant cherry-producing country. This study aimed to develop a predictive framework for total nutrient losses in sweet cherry orchards by proposing simplified estimations using fresh fruit yield as the sole input variable. Field experiments were conducted in two orchards with distinct rootstocks (MxM 14 and CAB-6P), analyzing soil properties, leaf nutrient status, and uptake patterns on different plant components. Results indicated that despite differences in soil texture and pH, nutrient availability was generally sufficient, with only Fe and Zn marginally below optimal levels in leaf tissue. Principal Component Analysis (PCA) revealed distinct nutrient distribution patterns, with N evenly distributed across fruits, peduncles, and prunings, while K was concentrated in fruits and peduncles, and Ca and Mg predominantly in fallen leaves. Notably, K was redistributed from leaves to fruits under high yields, evidenced by negative correlations between leaf biomass and K uptake. Strong relationships (r² > 0.8) were found between fresh fruit yield and uptake of N, P, K, Mg, B, and Cu, enabling reliable predictions of total nutrient losses. Estimated annual nutrient removals were 85.6 kg ha⁻¹ N, 8.94 kg ha⁻¹ P, 42.7 kg ha⁻¹ K, and 12.0 kg ha⁻¹ Mg, with significant fractions retained in prunings and fallen leaves (e.g., 51.8 kg ha⁻¹ N, 6.2 kg ha⁻¹ P). The developed yield-based models provide a practical tool for optimizing fertilization strategies, while our findings highlight the potential for nutrient recycling through sustainable residue management. Full article

Background/Objectives: Potassium-competitive acid blockers (P-CABs) offer rapid gastric acid inhibition and lower toxicity compared to proton pump inhibitors (PPIs). This study investigates the drug–drug interaction between P-CABs and immunosuppressants tacrolimus and mycophenolate in kidney transplant recipients (KTRs). Methods: Sixty-two KTRs were randomized to receive either 50 mg of tegoprazan or 20 mg of pantoprazole. Patients were monitored using a smart clinical trial platform incorporating remote monitoring and safety management systems, which tracked drug adherence and vital signs. General and gastrointestinal (GI) symptoms were surveyed via a self-developed app on patients’ phones. Trough levels of tacrolimus and mycophenolate were measured every 4 weeks over 12 weeks. Results: Medication adherence was 100% in both groups. A total of 13,726 biometric data points and 5031 questionnaire responses were collected, with 5704 feedback messages and 56 video visits conducted. At 12 weeks, the mean trough levels of tacrolimus and mycophenolate were similar between the tegoprazan and pantoprazole groups (5.5 ± 1.6 vs. 5.8 ± 2.0 ng/mL, p = 0.50 and 2.7 ± 1.4 vs. 2.6 ± 1.4 µg/mL, p = 0.57, respectively). The intragroup difference in trough levels from baseline to week 12 was not significant in either group. GI symptoms scores, vital signs, and allograft function remained stable and comparable between groups. Conclusions: Tegoprazan does not alter the blood trough levels of tacrolimus and mycophenolate during the 12-week follow-up in KTRs and has a similar impact on GI symptoms as pantoprazole. This study confirms the feasibility and safety of using a smart clinical trial system with remote monitoring for randomized trials. Full article

Background/Objectives: The nephrotoxicity of immune checkpoint inhibitors (ICIs) combined with proton pump inhibitors (PPIs) has been recognized but lacks a comprehensive analysis. We conducted an in-depth investigation of renal adverse events (rAEs) associated with ICIs and different acid-suppressing agents (ASAs)—including PPIs, histamine-2 receptor antagonists (H₂RAs), and potassium-competitive acid blockers (P-CABs)—using real-world data from the FDA’s Adverse Event Reporting System (FAERS). Methods: We analyzed rAE reports from the FAERS database covering Q1 2004 to Q1 2023. Disproportionality analysis was conducted to identify rAEs associated with ICI or ASA monotherapy or combination therapy. Univariate logistic regression was employed to explore influencing factors. Results: No eligible rAE reports were retrieved for H₂RAs and P-CABs. However, 6,775 reports in the ICI group, 54,055 reports in the PPI group, and 210 reports in the ICI–PPI combination therapy group were included in the final analysis. In PPI–ICI combination settings, tubulointerstitial nephritis had the highest reporting frequency and signal intensity; the overall risk of rAEs was significantly elevated compared to ICI or PPI monotherapy, with reporting odds ratios of 14. 65 (95% confidence interval [CI] 12.93–16.58) and 3.24 (95% CI 2.87–3.66), respectively; the median onset time was shortest at 21 days (interquartile range 5.5–135); and PD-1 monotherapy, omeprazole, and rabeprazole were associated with higher rAE risks. Conclusions: Our findings confirm that the combination of PPIs (but not other ASAs) with ICIs further increases the risk of various acute and chronic rAEs. Healthcare providers should exercise caution when managing patients on these therapies. Full article

Gastroesophageal reflux disease (GERD) is a prevalent chronic gastrointestinal disorder that affects a substantial proportion of the global population. It is characterized by the extensive backward flow of stomach contents into the esophagus, leading to troublesome symptoms and potential complications. Proton pump inhibitors (PPIs) have long been the cornerstone of pharmacological treatment for GERD, effectively suppressing gastric acid secretion. However, a substantial subset of patients, referred to as PPI-refractory GERD, experience inadequate symptom control despite optimal PPI therapy. GERD significantly impacts patients’ quality of life, affecting domains, such as vitality, pain, and physical functioning. Consequently, there is an urgent need for alternative therapeutic strategies and novel pharmacologic agents to provide more effective, long-term relief. Emerging treatment options include potassium-competitive acid blockers (PCABs) like vonoprazan, which offer more potent and sustained inhibition of gastric acid secretion compared to traditional PPIs. Additionally, prokinetic agents such as itopride have gained attention due to their potential to improve GERD symptoms by enhancing gastrointestinal motility and accelerating gastric emptying. This article reviews the mechanisms of action, clinical efficacy, and potential of these novel therapeutic approaches in improving patient outcomes in GERD management. With the growing prevalence of PPI resistance and side effects, a personalized, multifaceted approach to treatment is becoming increasingly necessary to optimize care for patients with GERD. Full article

Objectives: Carotid geometry and cardiovascular risk factors play a significant role in the development of carotid atherosclerotic plaques. This study aimed to investigate the correlation between carotid plaque formation and carotid artery geometry characteristics. Methods: A retrospective cross-sectional analysis was performed on 1227 patients, categorized into a normal group (n = 685) and carotid plaque groups causing either mild stenosis (<50% stenosis based on NASCET criteria, n = 385) or moderate-to-severe stenosis (>50%, n = 232). The left and right carotid were evaluated individually for each group. Patient data, including cardiovascular risk factors and laboratory test results, were collected. Carotid geometric measurements were obtained from 3D models reconstructed from cranio-cervical computed tomography angiography (CTA) using semi-automated software (MIMICS). The geometric variables analyzed included the vascular diameter and sectional area of the common carotid artery (CCA), internal carotid artery (ICA), external carotid artery (ECA), and carotid artery bifurcation (CAB), as well as the carotid bifurcation angles and carotid tortuosity. Results: Compared to the normal group, in both the right and left carotid arteries, patients with carotid plaques exhibited a significantly higher age (p < 0.001) and a greater prevalence of hypertension (p < 0.001) and diabetes mellitus (p < 0.001). Additionally, they demonstrated a larger CCA and a smaller carotid bifurcation dimension (p < 0.05). In the analysis of the left carotid artery, patients with carotid plaques also had a significantly smaller ICA dimension (p < 0.05) than the normal group. Conclusions: This study found that patients with carotid plaques were older and had a higher prevalence of hypertension and diabetes, larger CCAs, and smaller carotid bifurcations. The plaque-positive left ICA was significantly smaller than that of the plaque-negative group, suggesting a side-specific vulnerability. These findings highlight the role of carotid geometry in plaque formation and its potential clinical implications for personalized risk assessment and targeted interventions. Full article

Cabozantinib (CAB) causes a high incidence of adverse events in unresectable hepatocellular carcinoma (u-HCC) and requires dose adjustments. We evaluated the efficacy and safety of the 7-on/7-off regimen composed of 7 consecutive days’ administration of CAB followed by a 7-day rest period. This was a retrospective analysis of 35 patients with u-HCC, who were treated with CAB in a multicenter cohort in Japan from 2020 to 2024. The clinical outcomes of 12 patients treated with the 7-on/7-off regimen and 23 patients treated with daily dosing were compared. There were significant differences in overall survival (12.4 months vs. 6.3 months, p = 0.03), median progression-free survival (4.8 months vs. 3.2 months, p < 0.01), objective response rate (16.7% vs. 0.0%, p = 0.04), and incidence of any adverse events (75.0% vs. 100.0%, p = 0.03) between the 7-on/7-off regimen group and daily dosing group. The median duration of drug exposure (122 days vs. 42 days, p < 0.01) and median duration of dose reduction (100 days vs. 23 days, p < 0.01) were prolonged significantly in the 7-on/7-off group than in the daily dosing group. CAB in a 7-on/7-off regimen may improve the tolerability and treatment response in patients with u-HCC. Full article

This study explores the mechanical performance of polycarbonate (PC) and acrylonitrile butadiene styrene (ABS) filaments fabricated using fused filament fabrication (FFF), Arburg plastic freeforming (APF), and injection moulding (IM). A series of controlled experiments, including differential scanning calorimetry (DSC), scanning electron microscopy (SEM), dynamic mechanical thermal analysis (DMA), and mechanical tests, were conducted to evaluate the material’s mechanical, thermal, and chemical properties. The results highlight the influence of process parameters and material choice on the mechanical properties of PC/ABS components. The FFF samples exhibited the highest impact strength (up to 28.82 kJ/m²), attributed to porosity acting as a stress absorber under impact load. However, this same porosity led to a 9.14% and 19.27% reduction in flexural and tensile strength, respectively, compared to the APF samples, where stress concentration effects were more pronounced under flexural loads. APF’s mechanical properties were comparable to those of IM, with the process achieving the highest tensile strength, highlighting its potential for producing robust PC/ABS samples. This study aims to provide valuable insight into the selection of additive manufacturing (AM) processes for PC/ABS components. Full article

Tegoprazan is a potassium ion-competitive acid blocker (P-CAB) and a novel inhibitor of gastric acid secretion. The compound exists in two crystalline polymorphs, A and B, whose structures had not previously been reported. In this study, both polymorphs were analyzed by liquid- and solid-state NMR, revealing identical tautomeric states. Using this information, the crystal structures were determined from laboratory powder X-ray diffraction data by simulated annealing and Rietveld refinement. Both forms were found to crystallize in the monoclinic space group P2₁, with Z = 4 and two independent molecules in the asymmetric unit (Z′ = 2). To assess the stability and reliability of the refined structures, we attempted geometry optimization and vibrational analysis using DFT-D methods. However, due to the high conformational complexity of Z′ = 2 systems, these calculations failed to converge or produced imaginary frequencies. Instead, single-point energy calculations were performed on the refined models. The resulting relative energy differences, together with solubility data, van’t Hoff enthalpies, and DSC profiles, consistently indicated that Polymorph A is more stable than Polymorph B. These results highlight the challenges of structure validation via DFT-D for complex molecular crystals and demonstrate the value of integrating experimental and computational approaches for polymorph characterization. Full article

Anaerobic digestion is a critical method for producing bioenergy from organic waste; however, its efficiency is highly influenced by several factors. This study aimed to enhance the AD process using the removed solid phase generated by the canning plant Amor Benamor (CAB) during the production of harissa. This research sought to identify the optimum pH conditions and inoculum/substrate ratio (I/S) for achieving the maximum biogas production while ensuring a high methane yield, using response surface methodology (RSM) and numerical optimization. The batch anaerobic digestion of pepper waste as a substrate and sewage sludge as an inoculum was conducted. The 11 experimental runs generated by Design Expert Software were conducted in reactors with a capacity of 150 mL and a working volume of 90 mL, under thermophilic conditions. The effects of pH in the range of 7 to 8 and an I/S ratio in the range of 0.167 to 0.5, and their interaction in terms of biogas and methane yield (mL/g VS), were evaluated using a central composite design (CCD). The findings highlighted that a pH of around 7.5 and an I/S ratio of 0.48 could give the highest predicted yield of 884.35 mL/g VS for biogas and 422.828 mL/g VS for methane. These predicted values were confirmed with an experimental validation run which exhibited a deviation of less than 5%. These results offer new opportunities for enhanced biogas production from accumulated waste, contributing to the growth of sustainable energy alternatives. Full article

Three dimensional (3D) printing materials are widely used in dental applications, but their biocompatibility and interactions with human cells require evaluation. This study aimed to identify materials meeting biocompatibility, mechanical strength, and tissue-forming requirements for safe dental applications. We assessed the cytotoxicity of resins and thermoplastic filaments in human HaCaT keratinocytes, gingival fibroblasts (hGFs), and stem cells from human exfoliated deciduous teeth (SHED) using PrestoBlue assays. Three resins, including two types of surgical guide resins, exhibited strong cytotoxicity after 4–72 h, while 2 h exposure to an FDA-approved surgical guide resin did not affect SHED cell viability. In contrast, six thermoplastic filaments showed no significant cytotoxicity even after 72 h. Among these, polycarbonate–acrylonitrile butadiene styrene (PC-ABS) demonstrated excellent toughness, heat resistance, and surface quality at a low cost. SHED cells cultured on PC-ABS dishes and micro bone structures showed strong proliferation and osteogenic potential. Culture inserts made of PC-ABS also supported the growth of HaCaT keratinocytes and the hGFs formed gingival tissue, which was superior to that formed on commercially available PET inserts. In conclusion, PC-ABS is a promising 3D printing material for dental applications due to its biocompatibility, ability to promote osteogenesis, and support for gingival tissue formation, with no observed cytotoxicity. Full article

This study aims to investigate the influence of cadmium (Cd) speciation transformation on P-wave velocity under different soil moisture conditions, providing critical insights into the subsurface characteristics of contaminated soils. Taking Cd-contaminated soil as the research subject, P-wave velocity and the speciation distribution of Cd in soils with different moisture contents and Cd adsorption levels were measured. The results reveal that when the soil is contaminated by Cd, the porosity is altered and it eventually lead to change P-wave velocity. By increasing the moisture content of soils, the redox potential (Eh) rises and the pH decreases, which lead to the speciation transformation of Cd from carbonate-bound state (CAB), Fe-Mn oxide-bound state (FMO), and organic and sulfide-bound state (ORB) to the exchangeable state (EX). These transformations of Cd to EX result in the increase in soil porosity, which lead to the decrease in P-wave velocity. In addition, linear regression analysis was conducted the P-wave velocity (∆V) and the EX (∆EX) at various Cd adsorption levels. The analysis shows that there is a strong linear relationship between exchangeable Cd content and P-wave velocity, and the determination coefficient is about 0.9, which provides a reliable basis for monitoring soil Cd contamination by using P-wave velocity. This study provides valuable insights into the relationship between the speciation distribution of heavy metals in soil and the properties of acoustic wave. Full article