Search Results (736)

Background: In some countries, community pharmacists provide advanced services to people with diabetes that improve glycaemic control and cardiovascular risk. This study aims to describe the cardiovascular risk profile of people with diabetes attending community pharmacy in Ireland. Methods: Data collection for this descriptive, observational, cross-sectional study took place in 10 pharmacies, in four Irish counties between July 2018 and October 2019. Participants were aged ≥18 years, with type 1 or type 2 diabetes, attending a participating pharmacy and were dispensed oral diabetes medicines, insulin, or devices for monitoring glycaemic control. Participants were asked about their demographics, medical history, and cardiovascular risk factors. Current medications were identified from dispensing software. Results: Data were available for 106 participants; 70 (66.0%) were male and 36 (34.0%) were female. The median age was 66.0 [56.5: 72.0] years. Of these, 90 (84.9%) had type 2 diabetes. Hypertension and dyslipidaemia were reported by 60 (56.6%) and 59 (55.7%) participants, respectively. Twenty-one participants (19.8%) were current smokers, 31 (29.2%) followed no specific diet, and 44 (41.5%) did not undertake exercise. Oral diabetes medication was prescribed to 85 (80.2%) and insulin was prescribed to 29 (27.4%) participants. Where an antihypertensive was prescribed, 21 participants (19.8%) achieved the systolic blood pressure on-treatment goal of ≤130 mmHg and 34 (32.1%) achieved the diastolic blood pressure on-treatment goal of <80 mmHg. Conclusions: Study participants demonstrated a high rate of characteristics associated with increased cardiovascular risk, including non-achievement of target blood pressure, smoking, and lack of exercise. A community pharmacist-led intervention aimed at potentially improving cardiovascular risk factors in people with diabetes warrants further study in an Irish setting. Full article

Background and Objectives: Cardiovascular disease remains a leading cause of mortality in Diabetes mellitus (DM), where chronic hyperglycemia induces oxidative stress, mitochondrial dysfunction, and hypoxia in cardiomyocytes. Liraglutide (Lir), a glucagon-like peptide-1 receptor agonist, is widely used for type 2 DM management and has been shown to exert cardioprotective and antioxidant effects. This study aimed to evaluate whether Lir mitigates hyperglycemia-induced oxidative and hypoxic stress in H9c2 cardiomyoblasts while preserving cellular ultrastructure. Materials and Methods: H9c2 cells were cultured under normoglycemic (5.5 mM) or hyperglycemic (30 mM) conditions, with or without Lir. Cell viability was assessed using MTT assay. Ultrastructural changes were examined by transmission electron microscopy (TEM). Hypoxia-inducible factor-1α (HIF-1α), lipid peroxidation markers (LOOH, MDA), advanced oxidation protein products (AOPP), and total antioxidant capacity (TAC) were quantified by spectrophotometric assays. Results: MTT assays revealed that Lir significantly improved cell viability under hyperglycemic conditions and the EC₅₀ was 1.05 ± 0.06 μM after 48 h of treatment. Under HG, HIF-1α, lipid hydroperoxides (LOOH), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) increased and total antioxidant capacity (TAC) decreased (p < 0.001, for all); Lir significantly reversed these changes, restoring values to near-NG levels. Ultrastructural analysis of HG + Lir-treated cells revealed reduced granules, increased vacuolization, and slight rough endoplasmic reticulum dilatation, though mitochondria appeared normal. Conclusions: Lir significantly attenuated oxidative stress and cellular injury in cardiomyocytes under hyperglycemic conditions, improving viability, modulating HIF-1α expression, and restoring antioxidant balance. These findings support a dual role for Lir in diabetic cardiomyopathy: glucose-independent cytoprotection and regulation of mitochondrial and hypoxia pathways, highlighting its therapeutic potential beyond glycemic control. Full article

Urban industrialization is a major driver of water pollution, particularly through emerging contaminants that pose significant health risks for humans and ecosystems. This critical review focuses on Bangladesh’s Buriganga and Dhaleshwari rivers, which pass through highly industrialized and urban areas, analyzing contaminant types, sources, pathways, and impacts. By synthesizing data from studies published between 2005 and 2024, the paper examines pollutants such as heavy metals (e.g., Cr, Cd, Pb, Ni, Zn, Hg, As, Mn, Cu, Fe) and microplastics in water, sediments, and biota. The Buriganga River shows extreme heavy metal contamination, with surface water Cr concentrations reaching up to 167,160 μg/L, Pb up to 3830 μg/L, and Fe up to 30,000 μg/L, and sediment Cr up to 4249 μg/g, Pb up to 3312 μg/g, and Fe up to 15,435 μg/g. In contrast, the Dhaleshwari River exhibits elevated but comparatively lower heavy metal concentrations in surface water (e.g., Cr up to 3350 μg/L; Cd up to 1890 μg/L; Pb up to 1320 μg/L; Ni up to 1732 μg/L; Fe up to 6040 μg/L) and sediments (Cr up to 282 μg/g; Fe up to 14,375 μg/g). Microplastic contamination in Buriganga is widespread across water, sediments, and biota and dominated by polymers such as polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET). Industrial discharges, particularly from the textile, leather, and metal processing industries, are identified as primary sources for heavy metals and microplastics. Additional inputs from domestic waste, agricultural runoff, and municipal sewage intensify pollution, with Cr, Cd, and Pb notably frequently exceeding safety thresholds. Microplastics, originating from municipal waste and atmospheric deposition, persist in these rivers, posing ecological and public health risks. The persistence and bioaccumulation of heavy metals and microplastics threaten aquatic biodiversity by disrupting food chains and pose significant risks to local communities that depend on these rivers for agriculture, fishing, and daily water use. This review highlights the urgent need for comprehensive bioaccumulation studies, long-term monitoring, and enhanced detection techniques to better assess contamination levels. Strengthening environmental regulations, improving waste management, and adopting sustainable industrial practices are critical to mitigating emerging contaminant impacts and safeguarding these vital river ecosystems and public health. Full article

Background: Coverage uniformity is pivotal in whole genome sequencing (WGS), as uneven read distributions can obscure clinically relevant variants and compromise downstream analyses. While enzyme-based fragmentation methods for WGS library preparation are widely used, they can introduce sequence-specific biases that disproportionately affect high-GC or low-GC regions. Here, we compare four PCR-free WGS library preparation workflows—one employing mechanical fragmentation and three based on enzymatic fragmentation—to assess their impact on coverage uniformity and variant detection. Results: Libraries were generated with Coriell NA12878 and DNA isolated from DNA blood, saliva, and formalin-fixed paraffin-embedded (FFPE) samples. Sequencing was performed on an Illumina NovaSeq 6000, followed by alignment to the human reference genome (GRCh38/hg38) and local realignment. We assessed coverage at both chromosomal and gene levels, including 504 clinically relevant genes detected in the TruSight™ Oncology 500 (TSO500) panel. Additionally, we examined the relationship between GC content and normalized coverage, as well as variant detection across high- and low-GC regions. Conclusions: Our findings show that mechanical fragmentation yields a more uniform coverage profile across different sample types and across the GC spectrum. Enzymatic workflows, on the other hand, demonstrated more pronounced coverage imbalances, particularly in high-GC regions, potentially affecting the sensitivity of variant detection. This effect was evident in analyses focusing on the TSO500 gene set, where uniform coverage is critical for accurate identification of disease-associated variants and for minimizing false negatives. Downsampling experiments further revealed that mechanical fragmentation maintained lower Single Nucleotide Polymorphism (SNPs) false-negative and false-positive rates at reduced sequencing depths, thereby highlighting the advantages of consistent coverage for resource-efficient WGS. This study introduces a novel framework for evaluating WGS coverage uniformity, providing guidance for optimizing library preparation protocols in clinical and translational research. By quantifying how fragmentation strategies influence coverage depth and variant calling accuracy, laboratories can refine their sequencing workflows to ensure more reliable detection of clinically actionable variants—especially in high-GC regions often implicated in hereditary disease and oncology. Full article

Background/Objectives: To evaluate the efficacy and safety of finerenone compared to placebo in improving renal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Methods: A systematic review and meta-analysis were conducted, compiling RCTs evaluated the effect of finerenone compared to placebo in patients with CKD and T2D. Inclusion criteria included adults with CKD and T2D. Outcomes included kidney failure, end-stage renal disease (ESKD), and persistently decreased glomerular filtration rate (eGFR). Secondary outcomes included cardiovascular events, hospitalization due to hyperkalemia, and serious adverse events. Pooled relative risks (RRs) and mean differences (MDs) were calculated using a random-effects model. Results: Three RCTs with a total of 19,027 patients were included. Finerenone demonstrated a potential reduction in kidney failure risk (RR 0.86, 95% CI: 0.35–2.13) and ESKD (RR 0.82, 95% CI: 0.54–1.23); however, confidence intervals included the null effect. There were no statistically significant differences, as seen in the decrease in eGFR (RR 1.03; 95% CI: 0.27–3.85), but also in mortality due to renal causes (RR 0.62; 95% CI: 0.00–7168.81). Finerenone increased hyperkalemia-related hospitalizations (RR 4.57, 95% CI: 1.07–19.48) but had no significant effect on serious adverse events (RR 0.94, 95% CI: 0.92–0.97) or systolic BP (MD 0.08 mmHg, 95% CI: −0.36 to 0.52). Conclusions: Finerenone may provide renal protection in CKD and T2D, though benefits remain uncertain due to wide confidence intervals and study heterogeneity. The increased risk of hyperkalemia warrants careful patient selection and monitoring. Further research is needed to refine its clinical applicability. Review registration: PROSPERO CRD420250642593. Full article

Introduction: Myotonic dystrophies (DM) are progressive genetic disorders with multisystemic involvement, particularly affecting the muscular, respiratory, and neuropsychological systems. Myotonic dystrophy type 1 (DM1), or Steinert’s disease, may lead to severe respiratory complications, including sleep-disordered breathing and hypercapnia, often requiring noninvasive ventilation to manage respiratory failure. However, adherence to NIV remains a major challenge, often influenced by cognitive and psychological factors such as apathy and depression. This study aims to investigate the presence of depression and SDB in patients with DM1 initiating NIV, and to evaluate factors influencing adherence to ventilatory support. Materials and Methods: We selected 13 adult patients (≥18 years) with diagnosis of Steinert’s disease with respiratory impairment who needed to start respiratory support. Dysphagia was assessed in all patients at baseline by a videofluoroscopic swallow study. Beck’s Depression Inventory II was administered for measuring the severity of depression. The Montreal Cognitive Assessment was used as a screening tool to detect signs of neurocognitive disorders. We evaluated adherence to NIV. Results: The study population presented with sleep-disordered breathing, as indicated by a median apnea–hypopnea index (AHI) of 24 events per hour (IQR: 14.2–34.5) and an oxygen desaturation index (ODI) of 25 events per hour (IQR: 18–33). Adherence to NIV was obtained in seven patients. No difference in baseline lung function was observed. Adherent subjects had moderate hypercapnia at baseline; pCO2 was 52 vs. 49 mmHg. Non-adherent patients showed a higher prevalence of depression with a median BDI-II score of 18 vs. 6 in adherent patients. The findings highlight that psychological factors, especially depression, play a crucial role in adherence to NIV. Interestingly, depression was not linked to initial respiratory measurements but showed a significant association with nocturnal oxygen desaturation. This suggests that relying solely on clinical and respiratory assessments may not be adequate to predict or improve treatment adherence. Conclusions: Incorporating psychological evaluations and addressing mental health issues, such as depression, are essential steps to enhance NIV compliance and overall DM1 patient outcomes. A multidisciplinary approach combining respiratory and psycho-emotional interventions is crucial for effective disease management. Full article

Background: Metabolic memory refers to the long-term adverse effects of short-term disturbances in glucose metabolism. Recent evidence indicates that hyperglycemia-induced metabolic memory contributes to sustained cellular damage even after glycemic control, driven by increased production of reactive oxygen species (ROS), activation of inflammatory pathways, and accumulation of advanced glycation end products (AGEs). Although well characterized in endothelial and smooth muscle cells, this phenomenon may also occur in other cell types, including glial cells. Objective: This study aimed to evaluate the persistence of high-glucose (HG)-induced alterations after returning to normal glucose (NG) conditions in primary mixed glial cell (MGC) cultures. Methods: Primary MGCs were obtained from neonatal Wistar rat pups and cultured under three conditions for 21 days: NG (5.5 mM glucose), HG (25 mM glucose), and HG-NG (14 days in HG followed by 7 days in NG). Cell proliferation, apoptosis, ROS production, lipid peroxidation, mitochondrial activity, TNF-α, IL-6, and AGE formation were assessed. Results: MGCs cultured under HG and HG-NG conditions exhibited reduced proliferation without increased apoptosis. Both HG and HG-NG conditions promoted ROS overproduction accompanied by reduced mitochondrial activity, whereas only HG increased lipid peroxidation. Notably, TNF-α and AGE levels were elevated in both HG and HG-NG conditions, while IL-6 production decreased exclusively in HG-NG. Conclusions: These findings demonstrate the persistence of deleterious effects induced by HG in MGCs, even after restoration to NG conditions. Full article

Carlin-type gold deposits in southwestern Guizhou, China require systematic exploration methods to identify deep and peripheral prospecting potential beyond known deposits. We conducted a 1:50,000-scale soil geochemical survey across 928 km² in the Nibao gold deposit and its surrounding areas, with a total of 8842 samples collected. Fifteen elements were systematically analyzed, with particular focus on pathfinder elements associated with Carlin-type gold mineralization. Building on previous comparative analyses of soil geochemical and tectono-geochemical characteristics, this research systematically examines the enrichment patterns of soil geochemistry and their significance for ore prospecting. The results demonstrate that (1) elements such as Au, As, Sb, Hg, W, and Mo show significant positive correlation and strong enrichment patterns, indicating excellent metallogenic potential; (2) 176 and 12 single- and composite-element anomalies were delineated, respectively, with HS-2, HS-3, and HS-7 anomalies exhibiting high intensity and distinct concentration zonation, similar to those of the high factor score distribution of Au-As-Sb-Hg-W-Mo; (3) three prospecting targets were identified based on anomaly characteristics and geological conditions, including Nibao, Baogudi, and Sandaogou; (4) multiple mineralized bodies were revealed through engineering verification, indicating good prospecting potential in the deep and surrounding areas of the targets. These findings provide a scientific basis for further exploration of Carlin-type gold deposits in the study area and southwestern Guizhou. Full article

Hemorrhagic shock (HS) is a type of hypovolemic shock and is a leading cause of mortality worldwide. Enolase 1 (ENO1), a key enzyme in glycolysis, has been implicated in the pathogenesis of inflammatory disorders. We hypothesize that Kupffer cell (KC) ENO1 contributes to liver inflammation and that inhibiting ENO1 with ENOblock protects the liver from HS-induced injury. HS was induced in mice by lowering mean arterial pressure to 25 mmHg for 90 min, followed by fluid resuscitation. Twenty-four hours later, KCs were isolated. To mimic HS in vitro, KCs were isolated from healthy mice and exposed to hypoxia/reoxygenation (H/R). Hypoxic KCs were treated with ENOblock during reoxygenation, and cytokines (IL-1β, TNF-α, IL-6) were measured. In mice subjected to HS and treated with ENOblock, the liver was harvested. In KCs isolated from HS mice as well as in H/R exposed KCs, ENO1 mRNA and protein expression were significantly increased. In KCs exposed to H/R as well as in liver tissues from HS mice, cytokine mRNA and protein levels (IL-1β, TNF-α, IL-6) were increased; however, ENOblock treatment significantly decreased these parameters. HS also markedly increased ENO1 activity and cleaved caspase-1 in KCs, while these parameters were significantly attenuated by ENOblock treatment. These findings suggest that targeting ENO1 in KCs could be a promising therapeutic strategy for mitigating HS-induced liver injury. Full article

Background: The perfusion of viscera, kidney, and spinal cord represents one of the main concerns during open repair (OR) of Thoraco-Abdominal Aortic Aneurisms (TAAAs). Passive shunting (PS) has been historically used for intraoperative distal aortic perfusion but has been progressively replaced almost entirely by partial left-sided heart or total cardiopulmonary bypass with extra-corporeal circulation (ECC). Despite several advantages of these methods, PS still has potential in mitigating some drawbacks of long extracorporeal circuits connected with centrifugal or roller pumps, such as the need for cardiac and great vessels cannulation, priming and large intravascular fluid volume shifts, high heparin dose, immunosuppressive effects, and systemic inflammatory response syndrome. Methods: This study prospectively analyzed data of a cohort of patients who underwent TAAA OR using a PS in a single institution. Outcomes of interest were mortality, rate of mesenteric, renal and spinal cord ischemia, cardiac complications, and intraoperative hemodynamic stability achieved in this setting. Our institutional bundle and a comprehensive literature review about the different configurations and applicability of PS for TAAA OR is also reported. The search was performed based on three databases (PubMed, EMBASE, and Cochrane Library) by two independent reviewers (LS and AA) from inception to 31 December 2023, and the reported clinical results (visceral, renal, and spinal cord complications and mortality) using PS during TAAAs OR were analyzed. Results: Between March 2021 and December 2023, 51 TAAA repairs were performed and eleven patients (n = 8, 73% male; mean age 67 years, range 63–79) were operated using a PS for a total of one (9%) type I, one (9%) type II, two (18%) type III, five (45%) type IV, and two (18%) type V TAAA. In our early experience, PS was indicated for limited staff resources during the COVID-19 pandemic to treat five non-deferable cases. The sixth and seventh patients were selected for PS as they already had a functioning axillo-bifemoral bypass that was used for this purpose. For the most recent cases, PS was chosen as the primary perfusion method according to a score based on clinical and anatomical factors with ECC as a bailout strategy. Selective renal perfusion with cold (4 °C) Custodiol solution was the method of choice for renal protection in all cases while antegrade perfusion of the coeliac trunk and the superior mesenteric artery was assured by PS through a loop graft (8–10mm) proximally anastomosed to the axillary artery (10 patients, 90.9%) or the descending thoracic aorta (one patient, 9%) and distally anastomosed to the infrarenal aorta (3), common iliac (3), or femoral vessels (5). In-hospital mortality was 9% as one patient died on the 10th postoperative day from mesenteric ischemia following hemodynamic instability; permanent spinal cord ischemia rate was 0% and the rate of AKI stage 3 was 9% (one patient). Bailout shifting to ECC was never required. No cardiac complications, nor a significant increase in serum CK-MB were reported in any patient. No prolonged severe intraoperative hypotension episodes (Mean Arterial Pressure < 50 mmHg) were assessed using the Software Acumen Analytics (Edwards LifeSciences, Irvine CA, USA). No peri-operative coagulopathy nor major bleeding was reported. Conclusions: Our experience showed satisfactory outcomes with the use of PS in specifically selected cases. Current data indicate that PS may represent an alternative to ECC techniques during TAAAs OR in high volume centers where assisted extracorporeal circulation could eventually be applied as a bailout strategy. However, due to the small sample size of this and previously published series, more data are needed to clearly define the potential role of such approach during TAAA OR. Full article

Eph receptor B2 (EphB2) overexpression is associated with poor clinical outcomes in various tumors. EphB2 is involved in malignant tumor progression through the promotion of invasiveness and metastasis. Genetic and transcriptome analyses implicated that EphB2 is a therapeutic target for specific tumor types. A monoclonal antibody (mAb) is one of the essential therapeutic strategies for EphB2-positive tumors. We previously developed an anti-EphB2 mAb, Eb₂Mab-12 (IgG₁, kappa), by immunizing mice with EphB2-overexpressed glioblastoma. Eb₂Mab-12 specifically reacted with the EphB2-overexpressed Chinese hamster ovary-K1 (CHO/EphB2) and some cancer cell lines in flow cytometry. In this study, we engineered Eb₂Mab-12 into a mouse IgG_2a type (Eb₂Mab-12-mG_2a) and a human IgG₁-type (Eb₂Mab-12-hG₁) mAb. Eb₂Mab-12-mG_2a and Eb₂Mab-12-hG₁ retained the reactivity to EphB2-positive cells and exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in the presence of effector cells and complements, respectively. In CHO/EphB2, triple-negative breast cancer, and lung mesothelioma xenograft models, both Eb₂Mab-12-mG_2a and Eb₂Mab-12-hG₁ exhibited potent antitumor efficacy. These results indicated that Eb₂Mab-12-derived mAbs could be applied to mAb-based therapy against EphB2-positive tumors. Full article

Background/objectives: Individuals with type 1 diabetes (T1DM) face an elevated risk of cardiovascular disease (CVD), yet the factors driving atherosclerosis remain unclear. This study aimed to assess factors associated with preclinical atherosclerosis development or progression in T1DM. Methods: We conducted a prospective study in T1DM individuals without established CVD, aged ≥40 years, with diabetic kidney disease and/or ≥10 years of T1DM plus another cardiovascular risk factor (CVRF). Baseline evaluation followed a standardized CV risk assessment protocol, including carotid ultrasound and cardiovascular risk estimation using the Steno Type 1 Risk Engine (ST1RE). Ultrasound was repeated after 3–5 years; progression was defined as an increase in plaque number. CVRF control was considered optimal when LDL-cholesterol was within target based on atherosclerotic burden, blood pressure <130/80 mmHg, HbA1c <7%, and non-smoking status. Logistic regression models identified predictors of progression. Results: We included 151 participants (55.6% women; mean age 49.8 ± 8.9 years; T1DM duration 27.3 ± 9.1 years); 42.4% had plaques at baseline. Over a follow-up of 5.22 ± 1.29 years, despite improved CVRF control (p < 0.05), 40.4% experienced progression. Older age (OR 1.38 [1.1–1.8]) and active smoking (OR 3.29 [1.4–7.5]) were significant predictors of progression. Baseline cardiovascular risk measured by the ST1RE independently predicted progression (OR 1.09 [1.03–1.15]) after adjusting for other CVRFs. Persistent smoking (OR 2.52 [1.06–5.99]) and baseline ST1RE (OR 1.06 [1.02–1.11]) remained significant after accounting for baseline and follow-up CVRFs. Conclusions: Despite improved CVRF control, atherosclerosis progression is common in T1D. ST1RE may help identify individuals at highest risk for targeted preventive strategies. Full article

Isocitrate dehydrogenase (IDH) catalyzes the conversion of NAD(P)⁺ and isocitrate to NAD(P)H and α-ketoglutarate (αKG). The cytoplasmic enzyme IDH1 is important for producing NADPH for biosynthesis and for protecting against oxidative stress. IDH1 mutants, such as R132H found in glioblastomas and other types of human cancers, have a neomorphic activity that uses NADPH to reduce αKG to 2-hydroxyglutarate (2HG). 2HG interferes with the activity of important enzymes such as histone demethylases and TET demethylases. We hypothesized that Caenorhabditis elegans could be a good model system for studying oncogenic properties of mutant IDH1. To test this, we purified C. elegans cytoplasmic IDH-1 and two mutants, G98N and R133H, which correspond to human IDH1 mutants G97N and R132H, respectively. We found that the wild-type IDH-1 had similar kinetic properties to human IDH1, and it could produce small amounts of 2HG. We also found that the R133H mutant had a lower K_M for αKG than human R132H in steady-state enzyme kinetic experiments, and it produced almost exclusively 2HG in the presence of NADPH and αKG. The G98N mutant had a higher k_cat in the forward direction than the comparable human G97N mutant, and the G98N mutant produced a smaller amount of 2HG compared to the R133H mutant. These results suggest that C. elegans strains with IDH-1 mutations could be a good model system for studying the effects of 2HG in eukaryotic organisms. Full article

Background: The limited aqueous solubility of BCS Class II drugs, exemplified by itraconazole (ITR), continues to hinder their bioavailability and therapeutic performance following oral administration. The present study investigated the development of amorphous solid dispersions (ASDs) of ITR via continuous manufacturing technologies, such as hot melt extrusion (HME) and spray drying (SD), to improve drug release. Methods: Polymer selection was guided by Hansen solubility parameter (HSP) analysis, film casting, and molecular modeling, leading to the identification of aminoalkyl methacrylate copolymer type A (Eudragit^® EPO), polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus^®), and hypromellose acetate succinate HG (AQOAT^® AS-HG) as suitable carriers. ASDs were prepared at drug-to-polymer ratios of 1:1, 1:2, and 2:1. Comprehensive characterization was performed using ATR-FTIR, NMR, DSC, PXRD, SEM, PLM, and contact angle analysis. Results: HME demonstrated higher process efficiency, solvent-free operation, and superior dissolution enhancement compared to SD. Optimized HME-based ASDs were formulated into tablets. The ITR–Eudragit^® EPO formulation achieved 95.88% drug release within 2 h (Weibull model, R² > 0.99), while Soluplus^® and AQOAT^® AS-HG systems achieved complete release, best described by the Peppas–Sahlin model. Molecular modeling confirmed favorable drug–polymer interactions, correlating with the formation of stable complex and enhanced release performance. Conclusions: HME-based continuous manufacturing provides a scalable and robust strategy for improving the oral delivery of poorly water-soluble drugs. Integrating predictive modeling with experimental screening enables the rational design of ASD formulations with optimized dissolution behavior, offering potential for improved therapeutic outcomes in BCS Class II drug delivery. Full article

The Eastern Kazakhstan Gold Belt is a major black-shale-hosted gold province in Central Asia where the main types of deposits comprise mineralized zones with auriferous sulfides (micro- and nano-inclusions of gold and refractory gold) and quartz veins with visible gold. The quartz vein deposits are economically less important but may potentially represent the upper parts of bigger ore systems concealed at depth. In this work, the mineralogy of the quartz vein deposits and related wall rock alteration zones was studied using microscopy and SEM-EDS analysis, and the geochemical dispersion of the ore elements in primary alteration haloes was documented utilizing spatial distribution maps and statistical treatment methods. The studied auriferous quartz veins are classified as epizonal black-shale-hosted orogenic gold deposits. The veins generally have linear shapes with an average width of ca. 1 m and length up to 150 m and contain high-grade native gold with minor amounts of sulfides. In supergene oxidation zones, the native gold is closely associated with Fe-hydroxide minerals cementing brecciated zones within the veins. The auriferous quartz veins are usually enclosed by the wall rock alteration envelopes, where two types of alteration are distinguished. Proximal phyllic alteration (sericite-albite-pyrite ± chlorite, Fe-Mg-Ca carbonates, arsenopyrite, and pyrrhotite) develops as localized alteration envelopes, and pervasive carbonation accompanied by chlorite ± sericite and albite is the dominant process in the distal alteration zones. The rocks within the alteration zones are enriched in Au and chalcophile elements, and three groups of chemical elements showing significant positive mutual correlation have been identified: (1) an early geochemical assemblage includes V, P, and Co (±Ni), which are the chemical elements characteristic for black shale formations, (2) association of Au, As, and other chalcophile elements is distinctly overprinting, and manifests the main stage of sulfide-hosted Au mineralization, and (3) association of Bi and Hg (±Sb and U) includes the chemical elements that are mobile at low temperatures, and can be explained by activity of the late-stage hydrothermal or supergene fluids. The chalcophile elements show negative slopes from proximal to distal alteration zones and form overlapping positive anomalies on spatial distribution mono-elemental maps. Thus, the geochemical methods can provide useful tools to delineate the ore elemental associations and to outline reproducible anomalies for subsequent regional gold prospecting. Full article