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26 pages, 10001 KB  
Article
Dolomite Reservoir Genesis Controlled by Sedimentary Cycles: Geochemical Evidence from the Middle Permian Qixia Formation, SE Sichuan Basin
by Rui Xu, Guangwei Wang, Fang Hao, Li Quan, Ling Zhou, Lingao Kong, Dinglin Peng and Modong Duan
Minerals 2025, 15(11), 1114; https://doi.org/10.3390/min15111114 (registering DOI) - 27 Oct 2025
Abstract
Dolostone is an important reservoir for hydrocarbons, and significant hydrocarbons have been produced in the Middle Permian Qixia Formation dolostone reservoirs in the southeastern Sichuan Basin. The origin and formation process of the dolomite reservoir in the research area are studied through thin-section, [...] Read more.
Dolostone is an important reservoir for hydrocarbons, and significant hydrocarbons have been produced in the Middle Permian Qixia Formation dolostone reservoirs in the southeastern Sichuan Basin. The origin and formation process of the dolomite reservoir in the research area are studied through thin-section, geochemical, and sedimentary cycle analyses and U-Pb geochronology. Three types of dolomites were identified, including stratiform fine-crystalline dolomite (D1), patchy fine-crystalline dolomite (D2), and saddle dolomite cement (SD). D1 and D2 exhibit a range of δ13C values from 3.39‰ to 4.21‰ and a range of δ18O values from −6.06‰ to −5.75‰, indicating a mild depletion of δ18O relative to coeval seawater while maintaining seawater-equivalent δ13C signatures. Their 87Sr/86Sr ratios and REE patterns indicate seawater-derived fluids for D1 and D2 (both test results showed a U-Pb age of ≈274 Ma) and hydrothermal origin for SD. Sedimentary cycle analysis found that the regression process in the fourth-order sequence is conducive to the formation of dolomite under the background of regression in the third-order sequence. Exposure of bioclastic shoals enabled evaporated seawater reflux, forming penecontemporaneous D1 in fluid-saturated settings. Selective dolomitization occurred in the bioturbation structure with good porosity and permeability, forming D2. In the burial stage, the hydrothermal fluid had a slight transformation on the dolomite and formed SD. This model highlights transgressive–regressive cycle controls on reservoir development, providing exploration criteria for analogous carbonate systems. Full article
(This article belongs to the Special Issue Formation of Dolomite Reservoirs: Diagenetic and Tectonic Controls)
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18 pages, 6397 KB  
Article
Pyrite Trace-Element Signatures of Porphyry-Epithermal Systems in Xizang: Implications for Metallogenic Discrimination and Hydrothermal Evolution
by Hongzhong Guan, Jiancuo Luosang, Lutong Gao and Fuwei Xie
Minerals 2025, 15(11), 1113; https://doi.org/10.3390/min15111113 (registering DOI) - 26 Oct 2025
Abstract
The Zhunuo porphyry Cu deposit (2.9 Mt Cu @ 0.48%) in the Gangdese belt, southern Xizang, represents a key Miocene post-collisional system. This study integrates textural, major-, and trace-element analyses of pyrite from distinct alteration zones to unravel its hydrothermal evolution and metal [...] Read more.
The Zhunuo porphyry Cu deposit (2.9 Mt Cu @ 0.48%) in the Gangdese belt, southern Xizang, represents a key Miocene post-collisional system. This study integrates textural, major-, and trace-element analyses of pyrite from distinct alteration zones to unravel its hydrothermal evolution and metal precipitation mechanisms. Our study identifies four distinct pyrite types (Py1-Py4) that record sequential hydrothermal stages: main-stage Py2-Py3 formed at 354 ± 48 to 372 ± 43 °C (based on Se thermometry), corresponding to A and B vein formation, respectively, and late-stage Py4 crystallized at 231 ± 30 °C, coinciding with D-vein development. LA-ICP-MS data revealed pyrite contains diverse trace elements with concentrations mostly below 1000 ppm, showing distinct distribution patterns among different pyrite types (Py1-Py4). Elemental correlations revealed coupled behaviors (e.g., Au-As, Zn-Cd positive correlations; Mo-Sc negative correlation). Tellurium variability (7–82 ppm) records dynamic fO2 fluctuations during system cooling. A comparative analysis of pyrite from the regional deposits (Xiongcun, Tiegelongnan, Bada, and Xiquheqiao) highlighted discriminative geochemical signatures: Zhunuo pyrite was enriched in Co-Bi-Ag-Pb (galena inclusions); Tiegelongnan exhibited the highest Cu but low Au-As; Xiquheqiao had the highest Au-As coupling; and Bada showed epithermal-type As enrichment. Partial Least Squares Discriminant Analysis (PLS-DA) identified Cu, As, and Bi as key discriminators for deposit types (VIP > 0.8), with post-collisional systems (Zhunuo and Xiquheqiao) showing intermediate Cu-Bi and elevated As versus arc-related deposits. This study establishes pyrite trace-element proxies (e.g., Se/Te, Co/Ni, and As-Bi-Pb) for reconstructing hydrothermal fluid evolution and proposes mineral-chemical indicators (Cu-As-Bi) to distinguish porphyry-epithermal systems in the Qinghai-Tibet Plateau. The results underscore pyrite’s utility in decoding metallogenic processes and exploration targeting in collisional settings. Full article
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22 pages, 4279 KB  
Article
Development and Mechanism of the Graded Polymer Profile-Control Agent for Heterogeneous Heavy Oil Reservoirs Under Water Flooding
by Tiantian Yu, Wangang Zheng, Xueqian Guan, Aifen Li, Dechun Chen, Wei Chu and Xin Xia
Gels 2025, 11(11), 856; https://doi.org/10.3390/gels11110856 (registering DOI) - 26 Oct 2025
Abstract
During water flooding processes, the high viscosity of heavy oil and significant reservoir heterogeneity often lead to severe water channeling and low sweep efficiency. Addressing the limitations of traditional hydrophobically associating polymer-based profile-control agents—such as significant adsorption loss, mechanical degradation during reservoir migration, [...] Read more.
During water flooding processes, the high viscosity of heavy oil and significant reservoir heterogeneity often lead to severe water channeling and low sweep efficiency. Addressing the limitations of traditional hydrophobically associating polymer-based profile-control agents—such as significant adsorption loss, mechanical degradation during reservoir migration, resulting in a limited effective radius and short functional duration—this study developed a polymeric graded profile-control agent suitable for highly heterogeneous conditions. The physicochemical properties of the system were comprehensively evaluated through systematic testing of its apparent viscosity, salt tolerance, and anti-aging performance. The microscopic oil displacement mechanisms in porous media were elucidated by combining CT scanning and microfluidic visual displacement experiments. Experimental results indicate that the agent exhibits significant hydrophobic association behavior, with a critical association concentration of 1370 mg·L−1, and demonstrates a “low viscosity at low temperature, high viscosity at high temperature” rheological characteristic. At a concentration of 3000 mg·L−1, the apparent viscosity of the solution is 348 mPa·s at 30 °C, rising significantly to 1221 mPa·s at 70 °C. It possesses a salinity tolerance of up to 50,000 mg·L−1, and a viscosity retention rate of 95.4% after 90 days of high-temperature aging, indicating good injectivity, reservoir compatibility, and thermal stability. Furthermore, within a concentration range of 500–3000 mg·L−1, the agent can effectively emulsify Gudao heavy oil, forming O/W emulsion droplets with sizes ranging from 40 to 80 μm, enabling effective plugging of pore throats of corresponding sizes. CT scanning and microfluidic displacement experiments further reveal that the agent possesses a graded control function: in the near-wellbore high-concentration zone, it primarily relies on its aqueous phase viscosity-increasing capability to control the mobility ratio; upon entering the deep reservoir low-concentration zone, it utilizes “emulsion plugging” to achieve fluid diversion, thereby expanding the sweep volume and extending the effective treatment period. This research outcome provides a new technical pathway for the efficient development of highly heterogeneous heavy oil reservoirs. Full article
(This article belongs to the Topic Polymer Gels for Oil Drilling and Enhanced Recovery)
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32 pages, 415 KB  
Review
Ferroptosis in the Ovarian Follicular Microenvironment: A Redox-Dependent Cell Death Pathway with Emerging Roles in PCOS, Oocyte Quality, and IVF Outcomes
by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Spyridon Polykalas, Despoina Mavrogianni, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Vasiliki Kanaka, Maria Kanaka, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis K. Papapanagiotou, Dimitrios Vaitsis, Charalampos Tsimpoukelis, Maria Anastasia Daskalaki, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakisadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(21), 10381; https://doi.org/10.3390/ijms262110381 (registering DOI) - 25 Oct 2025
Viewed by 70
Abstract
Ferroptosis is a novel kind of regulated cell death that occurs when redox equilibrium is disrupted, leading to iron-dependent lipid peroxidation. Ferroptosis is defined by the buildup of deleterious lipid hydroperoxides, the inactivation of glutathione peroxidase 4 (GPX4), and mitochondrial shrinkage, setting it [...] Read more.
Ferroptosis is a novel kind of regulated cell death that occurs when redox equilibrium is disrupted, leading to iron-dependent lipid peroxidation. Ferroptosis is defined by the buildup of deleterious lipid hydroperoxides, the inactivation of glutathione peroxidase 4 (GPX4), and mitochondrial shrinkage, setting it apart from apoptosis and necrosis. The relevance of this route to human reproduction remains unknown, despite its thorough investigation in neurodegeneration and cancer. Recent studies demonstrate that the ovarian follicular milieu is especially susceptible to ferroptosis owing to its high content of polyunsaturated fatty acids, iron-dependent metabolism, and the generation of reactive oxygen species. Dysregulation of ferroptosis may result in infertility by affecting granulosa cell survival, oocyte maturation, and embryonic competence. Ferroptotic activity correlates with oxidative stress indicators identified in clinical diseases including polycystic ovary syndrome, reduced ovarian reserve, and insufficient responsiveness to ovarian stimulation. Potential indicators include GPX4 expression, decreased glutathione levels, and the accumulation of lipid reactive oxygen species in granulosa cells and follicular fluid. Melatonin, which boosts antioxidant defences, and ferrostatin-1, a prototype inhibitor of ferroptosis that lowers lipid peroxidation, are two early candidates for treatment. For future evaluations, these agents should be used with standardised FF biomarker panels. Significantly, vitamin E, coenzyme Q10, and small-molecule ferroptosis inhibitors have shown efficacy in halting ferroptosis in experimental settings. These approaches have shown protective benefits in alternative systems and may signify viable treatment options for assisted reproduction. This narrative review encapsulates ferroptosis inside the ovarian follicle, its influence on oocyte quality, and the implications for in vitro fertilization results. Full article
11 pages, 722 KB  
Article
Unraveling the Burden of Viral and Bacterial Central Nervous System Infections: A Two-Year Retrospective Study
by Nabeel Alzahrani, Ahmed Alshehri, Ali Alshehri and Sameera Al Johani
Diagnostics 2025, 15(21), 2699; https://doi.org/10.3390/diagnostics15212699 (registering DOI) - 24 Oct 2025
Viewed by 119
Abstract
Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim [...] Read more.
Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim of this study was to assess the epidemiological trends, age distribution, and seasonality of CNS infections using multiplex PCR. Methods: A retrospective analysis was conducted on cerebrospinal fluid (CSF) samples collected between January 2021 and December 2022 from patients with CNS infections at King Abdulaziz Medical City. A BioFire FilmArray Meningitis/Encephalitis (ME) panel was used to detect pathogens. Patient demographics, pathogen distribution, and seasonal trends were analyzed. Results: A total of 2,460 CSF samples were tested, of which 130 (5%) were positive for at least one pathogen. Viral pathogens accounted for 82.3% of the infections, with human herpesvirus-6 (HHV-6) (31%) and enterovirus (EV) (20%) being the most common. Bacterial pathogens represented 17.7% of the cases, with Streptococcus pneumoniae (6%) and Escherichia coli K1 (5%) being the predominant bacterial agents. The highest infection burden was observed in infants aged 0–6 months, with a marked male predominance. Seasonal analysis revealed multiple peaks in viral infections, particularly of HHV-6 and EVs, whereas bacterial infections were sporadic, with Streptococcus agalactiae and Streptococcus pneumoniae peaking in October and November. Conclusions: Viral infections, particularly HHV-6 and EVs, dominated CNS infections, with distinct seasonal and age-related variations. These findings underscore the value of multiplex PCR in improving the rapid diagnosis of CNS infections and aiding in timely treatment and antimicrobial stewardship. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
27 pages, 5817 KB  
Article
Design Optimisation of Legacy Francis Turbine Using Inverse Design and CFD: A Case Study of Bérchules Hydropower Plant
by Israel Enema Ohiemi and Aonghus McNabola
Energies 2025, 18(21), 5602; https://doi.org/10.3390/en18215602 (registering DOI) - 24 Oct 2025
Viewed by 127
Abstract
The lack of detailed design information in legacy hydropower plants creates challenges for modernising their ageing turbine components. This research advances a digitalisation approach which combines inverse design methodology (IDM) with multi-objective genetic algorithms (MOGA) and computational fluid dynamics (CFD) to digitally reconstruct [...] Read more.
The lack of detailed design information in legacy hydropower plants creates challenges for modernising their ageing turbine components. This research advances a digitalisation approach which combines inverse design methodology (IDM) with multi-objective genetic algorithms (MOGA) and computational fluid dynamics (CFD) to digitally reconstruct and optimise the Bérchules Francis turbine runner and guide vane geometries using limited available legacy data, avoiding invasive techniques. A two-stage optimisation process was conducted. The first stage of runner blade optimisation achieved a 22.7% reduction in profile loss and a 16.8% decrease in secondary flow factor while raising minimum pressure from −877,325.5 Pa to −132,703.4 Pa. Guide vane optimisation during Stage 2 produced additional performance gains through a 9.3% reduction in profile loss and a 20% decrease in secondary flow factor and a minimum pressure increase to +247,452.1 Pa which represented an 183% improvement. The CFD validation results showed that the final turbine efficiency reached 93.7% while producing more power than the plant’s rated 942 kW. The sensitivity analysis revealed that leading edge loading at mid-span and normal chord proved to be the most significant design parameters affecting pressure loss and flow behaviour metrics. The research proves that legacy turbines can be digitally restored through hybrid optimisation and CFD workflows, which enables data-driven refurbishment design without needing complete component replacement. Full article
(This article belongs to the Special Issue Energy Security, Transition, and Sustainable Development)
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11 pages, 568 KB  
Systematic Review
Furosemide-Induced Nephrocalcinosis in Premature Neonates: A Critical Review of Observational Data
by John Dotis, Alexandra Skarlatou, Maria Fourikou, Athina Papadopoulou and Elpis Chochliourou
Children 2025, 12(11), 1442; https://doi.org/10.3390/children12111442 (registering DOI) - 24 Oct 2025
Viewed by 64
Abstract
Background/Objectives: Furosemide is frequently used in preterm neonates for respiratory and fluid management but has been linked to nephrocalcinosis (NC), a renal complication with unclear long-term impact. Clarifying this association is crucial for safe diuretic use. Methods: A focused literature review included observational [...] Read more.
Background/Objectives: Furosemide is frequently used in preterm neonates for respiratory and fluid management but has been linked to nephrocalcinosis (NC), a renal complication with unclear long-term impact. Clarifying this association is crucial for safe diuretic use. Methods: A focused literature review included observational studies published between 1982 and 2025 reporting NC incidence by renal ultrasound in preterm infants receiving furosemide. Data on sample size, gestational age, birth weight, NC prevalence, and furosemide dosing/duration were extracted. Results were synthesized descriptively. Results: Twenty-two studies with 1489 infants were included. NC prevalence ranged 6–83%, higher in infants <32 weeks’ gestation or <1500 g. Across studies, incidence clustered at 17–41% between 4 weeks and term-equivalent age. Cumulative furosemide doses were generally three- to fourfold higher in NC groups (10–19 mg/kg cumulative vs. ≤5 mg/kg cumulative, p < 0.001). A dose-dependent risk was noted, with odds ratios increasing above a cumulative dose of 10 mg/kg. Some studies found no significant dose–response, indicating variability and confounding factors. NC was detected during NICU stay or around term-equivalent age; ~60% resolved after discontinuation, while persistent cases were associated with prolonged exposure and renal dysfunction. A recent multicenter, dose-escalation randomized trial showed that carefully dosed furosemide (≤2 mg/kg/day for 28 days) did not increase NC risk, though electrolyte disturbances were more frequent. Conclusions: Evidence supports a dose-related association between furosemide and NC in preterm infants. When administered cautiously within defined limits, risk may be mitigated. Careful dosing, monitoring, and further studies are essential for safe use. Full article
(This article belongs to the Section Pediatric Neonatology)
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31 pages, 20520 KB  
Article
Genesis of the Baijianshan Skarn-Type Zn-Cu Polymetallic Deposit, Chinese Eastern Tianshan: Constraints from Geology, Geochronology and Geochemistry
by Fenwei Cheng, Shuai Zhang, Jianxin Wu, Baofeng Huang and Di Zhang
Minerals 2025, 15(11), 1107; https://doi.org/10.3390/min15111107 - 24 Oct 2025
Viewed by 141
Abstract
The Baijianshan deposit is the sole skarn Zn-Cu polymetallic deposit in the Xiaoshitouquan ore field, Xinjiang, China. Its ore genesis remains controversial, which hinders understanding of the relationship between skarn-type Zn-Cu and adjacent epithermal Ag-Cu-Pb-Zn mineralization and consequently impedes further regional exploration. LA-ICP-MS [...] Read more.
The Baijianshan deposit is the sole skarn Zn-Cu polymetallic deposit in the Xiaoshitouquan ore field, Xinjiang, China. Its ore genesis remains controversial, which hinders understanding of the relationship between skarn-type Zn-Cu and adjacent epithermal Ag-Cu-Pb-Zn mineralization and consequently impedes further regional exploration. LA-ICP-MS U-Pb dating on zircons from the granite and granite porphyry from the mining area yielded ages of 311 ± 1.7 Ma and 312 ± 1.6 Ma, respectively. The corresponding zircon εHf(t) values and TDM ages are 8.7–9.9 and 624–555 Ma for the granite, and 7.2–9.9 and 673–552 Ma for the granite porphyry. These granites are metaluminous, high-K calc-alkaline I-type granites, with high LREE/HREE ratios (4.92–9.03) and pronounced negative Eu anomalies. They are enriched in K, Th, U, Zr, and Hf, with significant depletions in Sr, P, and Ti. Combined geological and geochemical evidence indicate that these Late Carboniferous granites were derived from the juvenile crustal and formed in subduction-related back basin. Two-phase aqueous inclusions in the ore-bearing quartz and calcite have homogenization temperatures ranging from 117 to 207 °C and 112 to 160 °C, respectively, with the salinities in the ranges of 0.18~7.17 and 0.53~5.26 wt% NaCl eq. The S and Pb isotopic compositions of sulfides in the ores indicate that the ore-forming metals were sourced from the medium-acidic magmatite. The δ18OH2O and δDH2O values of hydrothermal fluids range from −6.97% to −5.84% and −106.8% to −99.6%, respectively, suggesting that the ore-forming fluids originated from the mixing of magmatic and meteoric water. Fluid mixing and corresponding conductive cooling were identified as the principal mechanism triggering the metallic mineral precipitation. The Baijianshan skarn Zn-Cu polymetallic deposit shares contemporaneous magmatic-mineralization ages and analogous material sources with the epithermal polymetallic deposits in the Xiaoshitouquan ore field, collectively constituting a unified skarn-epithermal metallogenic system. This hypothesis indicates that the deep parts of the epithermal deposits within the Yamansu volcanic rocks possess potential for exploring the porphyry-skarn-type deposits. Full article
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11 pages, 935 KB  
Systematic Review
Anterior Cervical Meningocele: Systematic Review of the Literature and Illustrative Case
by Edoardo Ricci, Antonio Meola, Ilario Scali, Paolo Manganotti and Leonello Tacconi
J. Clin. Med. 2025, 14(21), 7530; https://doi.org/10.3390/jcm14217530 - 24 Oct 2025
Viewed by 165
Abstract
Background/Objectives: Anterior cervical meningocele (ACM) is a rare congenital condition characterized by the herniation of the meninges through a defect in the anterior vertebral column. ACM clinical management is not standardized because this condition is rare, and guidelines are missing. Hereby, a [...] Read more.
Background/Objectives: Anterior cervical meningocele (ACM) is a rare congenital condition characterized by the herniation of the meninges through a defect in the anterior vertebral column. ACM clinical management is not standardized because this condition is rare, and guidelines are missing. Hereby, a systematic literature review is performed to determine management options and outcomes. Methods: The case of a 62-year-old patient with incidental diagnosis of C3-C5 ACM is presented. A systematic review was conducted using standard PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines for all cases of anterior cervical meningocele from 1837 to 2025. Results: The review provided nine clinical cases and our illustrative case. The median age was 47 years, with a predominance of female patients (70%). The most common presenting symptom was neck pain (60%), followed by paresthesia and hypoesthesia in the upper limbs. Four patients underwent conservative management with clinical and radiological follow-up, while four patients underwent neurosurgical intervention. Surgical treatment was complicated by cerebrospinal fluid (CSF) leak in two patients, and one of them developed meningitis. Conclusions: ACM is typically associated with mesodermal dysplasia and dural ectasia. ACM usually has a benign clinical course, requiring neurological follow-up and conservative management alone. However, a surgical approach should be considered in cases of vertebral instability or symptoms related to upper airway compression or upper gastrointestinal tract compression despite the high risk of CSF leak when surgical repair is attempted. Full article
(This article belongs to the Special Issue Treatment and Prognosis of Spinal Surgery)
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9 pages, 525 KB  
Article
High-Dose 8 mg Aflibercept for Neovascular Age-Related Macular Degeneration: Who Is Being Treated with This New Agent?
by Caspar Liesenhoff, Carolin Meyrl, Daniel Krause, Franziska Eckardt, Anna Lorger, Viktoria Deiters, Johannes Schiefelbein, Julian Elias Klaas, Benedikt Schworm, Siegfried G. Priglinger and Jakob Siedlecki
Life 2025, 15(11), 1657; https://doi.org/10.3390/life15111657 - 23 Oct 2025
Viewed by 223
Abstract
Purpose: To describe the indication spectrum for high-dose 8 mg aflibercept for neovascular age-related macular degeneration (nAMD) in a real-world cohort in a tertiary referral center. Methods: The database of the University Eye Hospital Munich, Ludwig Maximilians-University was screened for eyes with nAMD [...] Read more.
Purpose: To describe the indication spectrum for high-dose 8 mg aflibercept for neovascular age-related macular degeneration (nAMD) in a real-world cohort in a tertiary referral center. Methods: The database of the University Eye Hospital Munich, Ludwig Maximilians-University was screened for eyes with nAMD treated with 8 mg aflibercept. Demographic data, multimodal imaging and treatment parameters were recorded. Reasons for treatment with 8 mg aflibercept were analyzed. Results: Thirty-four consecutive eyes of 31 patients (mean age 78.6 ± 8.9 years) were identified. There were 22 women (70.1%) and 9 men (29.9%). In all eyes (100%), 8 mg Aflibercept was applied as switching therapy. Prior to switching, the mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 3.9 ± 2.9 years, pretreatment amounted to a mean of 34.5 ± 26.3 injections, equaling 9.2 ± 2.4 injections/year, and the mean visual acuity (VA) was 0.4 ± 0.4 logMAR. The last treatment before switching was 2 mg aflibercept in 76%, faricimab in 18%, ranibizumab in 3% and bevacizumab in 3% of cases. Reasons for switching included (A) recalcitrant nAMD with persistent fluid despite q4w dosing (17 eyes, 50%), (B) the wish for interval extension (15 eyes, 44%) and (C) macular hemorrhage (2 eyes, 6%). In group B, two-thirds of eyes (10/15, 66.7%) were maintained at ≤q6w prior to switching. Conclusions: In this study, high-dose 8 mg aflibercept was exclusively used as a switch therapy. Most eyes (76%) switched were from pretreatment with 2 mg aflibercept. The main reasons for switching were recalcitrant nAMD with persistent fluid despite q4w dosing (50%) or the wish for treatment extension beyond 6 weeks (32%). In the future, these data will aid in the design of prospective real-world studies comparing the efficacy of high-dose 8 mg aflibercept with older generation treatment options, especially 2 mg aflibercept. Full article
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19 pages, 2328 KB  
Article
Comparative Analysis of Bacterial Diversity and Composition in Oral Fluid from Pigs of Different Ages and Water Pipe Wall Biofilms
by Qinghai Ren, Wenlong Lu, Tingting Zhang, Shengkai Hao, Jiawen Wang, Xinrui Xu, Fei Wang, Zetong Huang, Xiaojing Lei, Shengliang Cao, Duanduan Chen and Yubao Li
Vet. Sci. 2025, 12(11), 1022; https://doi.org/10.3390/vetsci12111022 - 22 Oct 2025
Viewed by 108
Abstract
Drinking water pipe biofilms, comprising viable microorganisms, microbial residues, and organic/inorganic particulates, pose significant risks to water safety by promoting the proliferation of opportunistic pathogens, pipe corrosion, and degradation of water quality. Their formation is strongly influenced by environmental conditions within the piping [...] Read more.
Drinking water pipe biofilms, comprising viable microorganisms, microbial residues, and organic/inorganic particulates, pose significant risks to water safety by promoting the proliferation of opportunistic pathogens, pipe corrosion, and degradation of water quality. Their formation is strongly influenced by environmental conditions within the piping system. However, there is a lack of systematic research investigating the potential correlations between biofilm microbiota and the oral microbiomes of intensively farmed swine, as well as the age-dependent regulatory mechanisms shaping aquatic microbial communities. This pioneering study conducted a comparative analysis of biofilm microbiota from swine house water pipes and oral microbiomes across three growth stages (30-day BBF, 70-day NBF, and 110-day FBF groups), yielding three key findings. First, the biofilm biomass and dominant bacterial genera (e.g., Brevibacterium in BBF vs. Brevundimonas in FBF) exhibited stage-specific variations associated with swine age. Second, while the oral microbiomes showed no significant taxonomic divergence at the phylum or genus level, they shared characteristic phyla, including Actinobacteria and Bacteroidetes, with pipe biofilms, indicating potential cross-habitat microbial interactions. Third, the antibiotic resistance gene (ARG) adeF was consistently detected at high prevalence across all biofilm groups. These findings offer new insights into microbial transmission dynamics and inform risk mitigation strategies for livestock water supply systems. Full article
(This article belongs to the Special Issue Exploring Innovative Approaches in Veterinary Health)
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23 pages, 1451 KB  
Article
CCNA2 and CCNB3 as Early Potential Molecular Candidates of Oocyte Maturation in Cumulus-Oophorous Complex Cells from Follicular Fluid
by Nergis Özlem Kılıç, Çağrı Öner, Duygu Kütük, Belgin Selam, İbrahim Orçun Olcay and Ertuğrul Çolak
Diagnostics 2025, 15(20), 2658; https://doi.org/10.3390/diagnostics15202658 - 21 Oct 2025
Viewed by 384
Abstract
Background/Objectives: Oocyte maturation is a process involving both nuclear and cytoplasmic development regulated by epigenetic changes in gene expression. Cyclin-B3 (CCNB3) and cyclin-A2 (CCNA2) genes are thought to be involved in oocyte maturation; however, the expression profiles and key function in Metaphase-I [...] Read more.
Background/Objectives: Oocyte maturation is a process involving both nuclear and cytoplasmic development regulated by epigenetic changes in gene expression. Cyclin-B3 (CCNB3) and cyclin-A2 (CCNA2) genes are thought to be involved in oocyte maturation; however, the expression profiles and key function in Metaphase-I (MI) and Metaphase-II (MII) phases have yet to be fully elucidated. Small non-coding RNA sequences are involved in epigenetic regulation of specific transcriptional targets, whereas microRNAs (miRNAs) participate in the post-transcriptional and translational repression of target genes. This study examined the expression levels of CCNB3, CCNA2, and their associated miRNAs (miR-17, miR-106b, miR-190a, miR-1275) in cumulus oophorous complex (COC) cells derived from MI and MII oocytes of NOR and DOR IVF cases, with particular emphasis on elucidating their functions during the transition from MI to MII stage. Methods: Follicular fluid containing cumulus–oocyte complex (COC) cells obtained from oocytes of 120 cases in each group NOR MI (n = 30), NOR MII (n = 30), DOR MI (n = 30), and DOR MII (n = 30) who were admitted to the Istanbul Bahçeci Health Group Assisted Reproductive Treatment Center. Following total RNA isolation from COC cells, the gene and protein expression levels of CCNB3 and CCNA2, along with the expression of miR-17, miR-106b, miR-190a, and miR-1275, were assessed using (qPCR-based assay) and immunohistochemistry (IHC). To investigate the functional roles of COC cell populations, morphological analysis was performed using H&E staining. Additionally, metadata of the cases, including age, number of oocytes, fertilization, and embryonic development rates, were evaluated. Results: The expressions of miR-17 and miR-1275 were significantly elevated in both NOR MI and DOR MI groups compared to their respective NOR MII and DOR MII groups (p < 0.05). Additionally, miR-106b levels were higher in the NOR MII group relative to NOR MI (p < 0.05), while an increase was also observed in DOR MI compared to DOR MII (p < 0.05). No difference was observed in miR-190a expression between the NOR and DOR (p > 0.05). Based on the results of H and E staining, the NOR MI, NOR MII, DOR MI, and DOR MII groups exhibited distinct variations in cellular morphology, nuclear characteristics, cytoplasmic volume, and cell density. Conclusions: CCNB3 is predicted to be a potential candidate for determining MI between the NOR and DOR cases. On the other hand, only for the NOR MII cases could CCNA2 provide evidence of oocyte maturation. Moreover, we determined the relationship between related genes and miRNAs which target CCNA2 and CCNB3. Genetic and protein expression analysis across diverse molecular pathways and miRNAs yielded comprehensive preliminary data regarding the developmental stages of oocytes at the MI and MII phases, and their fertilization potential following maturation shows potential and warrants prospective validation with clinical performance evaluation. Full article
(This article belongs to the Special Issue Biomarker-Guided Advances in Diagnostic Medicine)
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22 pages, 2367 KB  
Article
From Microbleeds to Iron: AI Prediction of Cerebrospinal Fluid Erythrocyte Load in Alzheimer’s Disease
by Rafail C. Christodoulou, Georgios Vamvouras, Maria Daniela Sarquis, Vasileia Petrou, Platon S. Papageorgiou, Ludwing Rivera, Celimar Morales Gonzalez, Gipsany Rivera, Sokratis G. Papageorgiou and Evros Vassiliou
J. Clin. Med. 2025, 14(20), 7360; https://doi.org/10.3390/jcm14207360 - 17 Oct 2025
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Abstract
Background/Objectives: Cerebrospinal fluid erythrocyte load (CTRED) reflects occult red-blood-cell ingress into brain/CSF and consequent heme–iron exposure, a toxic pathway relevant to Alzheimer’s disease (AD). We aimed to develop explainable machine learning (ML) models that classify high vs. low CTRED from routine, largely [...] Read more.
Background/Objectives: Cerebrospinal fluid erythrocyte load (CTRED) reflects occult red-blood-cell ingress into brain/CSF and consequent heme–iron exposure, a toxic pathway relevant to Alzheimer’s disease (AD). We aimed to develop explainable machine learning (ML) models that classify high vs. low CTRED from routine, largely non-invasive inputs, and to position a blood-first workflow leveraging contemporary plasma amyloid–tau biomarkers. Methods: Twenty-six ADNI participants were analyzed. Inputs were age, sex, mean arterial pressure (MAPres), amyloid (Aβ42), total tau, phosphorylated tau, and hippocampal atrophy rate (APC) derived from longitudinal MRI. APC was computed from normalized hippocampal volumes. CTRED was binarized at the median (0 vs. >0). Data were split into train (n = 20) and held-out test (n = 6). Five classifiers (linear SVM, ridge, logistic regression, random forests, and MLP) were trained in leakage-safe pipelines with stratified five-fold cross-validation. To provide a comprehensive assessment, we presented the contribution AUC, thresholded performance metrics, summarized model performance, and the permutation feature importance (PFI). Results: On the test set, SVM, ridge, logistic regression, and random forests achieved AUC = 1.00, while the MLP achieved AUC = 0.833. Across models, PFI consistently prioritized p-tau/tau, Aβ42, and MAPres; age, sex, and APC contributed secondarily. The attribution profile aligns with mechanisms linking BBB dysfunction and amyloid-related microvascular fragility with tissue vulnerability to heme–iron. Conclusions: In this proof-of-concept study, explainable ML predicted CTRED from routine variables with biologically coherent drivers. Although ADNI measurements were CSF-based and the sample was small, the framework is non-invasive by adding plasma p-tau217/Aβ1–42 for amyloid, tau inputs, and integrating demographics, hemodynamic context, and MRI. External, plasma-based validation in larger cohorts is warranted, alongside extension to MCI and multimodal correlation (QSM, DCE-MRI) to establish clinically actionable CTRED thresholds. Full article
(This article belongs to the Special Issue Innovative Approaches to the Challenges of Neurodegenerative Disease)
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11 pages, 2587 KB  
Article
Switching from Aflibercept to Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration: Short-Term Results from Real-Life Study
by Jan Kucharczuk, Hubert Kasprzak and Maciej Gawęcki
J. Clin. Med. 2025, 14(20), 7345; https://doi.org/10.3390/jcm14207345 - 17 Oct 2025
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Abstract
Purpose: To evaluate anatomical and functional outcomes after switching from aflibercept to faricimab in patients with neovascular age-related macular degeneration (nAMD) with suboptimal response. Methods: This retrospective study included 72 eyes of 66 patients with nAMD previously treated with intravitreal aflibercept using a [...] Read more.
Purpose: To evaluate anatomical and functional outcomes after switching from aflibercept to faricimab in patients with neovascular age-related macular degeneration (nAMD) with suboptimal response. Methods: This retrospective study included 72 eyes of 66 patients with nAMD previously treated with intravitreal aflibercept using a treat-and-extend regimen. Indications for switching included persistent retinal fluid, pigment epithelial detachment (PED), lack of best-corrected visual acuity (BCVA) improvement, or inability to extend treatment intervals beyond four weeks. Patients received three monthly loading doses of faricimab followed by individualized 8- to 16-week dosing. Follow-up comprised six visits over a mean of 8.5 ± 1.4 months. Outcomes included BCVA (logMAR), retinal morphology (subretinal fluid—SRF; intraretinal fluid—IRF; pigment epithelial detachment—PED), central subfoveal thickness (CST), and treatment interval changes. Results: Switching to faricimab led to significant short-term anatomical improvement, primarily reduction in subretinal fluid (p < 0.0001), with maximal effect during the loading phase. Resolution of SRF was significant at the end of the follow up; however, IRF changes were transient and not sustained beyond three months. PED reduction reached borderline significance (p = 0.0455). CST decreased during the loading phase (p < 0.0001) but returned to baseline thereafter. BCVA improved only after loading (p = 0.0287) but not at final follow-up. Treatment intervals were extended by a mean of ~2 weeks (p < 0.0001), increasing in 80% of eyes. Eyes with fewer prior injections and better baseline BCVA achieved superior final visual outcomes. Conclusions: Switching to faricimab provides short-term anatomical benefits and treatment-interval extension without sustained visual gain. Functional improvements tended to be greater in patients with fewer injections and shorter treatment duration prior to switch. Full article
(This article belongs to the Special Issue New Advances in Age-Related Macular Degeneration)
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12 pages, 341 KB  
Article
Exploring Frailty Status and Blood Biomarkers: A Multidimensional Approach to Alzheimer’s Diagnosis
by Aurora Cermelli, Armando Crisafi, Alberto Mario Chiarandon, Giorgia Mirabelli, Chiara Lombardo, Virginia Batti, Silvia Boschi, Elisa Maria Piella, Fausto Roveta, Innocenzo Rainero and Elisa Rubino
Geriatrics 2025, 10(5), 133; https://doi.org/10.3390/geriatrics10050133 - 17 Oct 2025
Viewed by 256
Abstract
Background: Frailty is a multidimensional syndrome reflecting reduced physiological reserve, increasingly recognized as a relevant factor in the clinical assessment of older adults with cognitive disorders. Objective: To explore the association between frailty, as measured by the Multidimensional Prognostic Index (MPI), cognitive performance, [...] Read more.
Background: Frailty is a multidimensional syndrome reflecting reduced physiological reserve, increasingly recognized as a relevant factor in the clinical assessment of older adults with cognitive disorders. Objective: To explore the association between frailty, as measured by the Multidimensional Prognostic Index (MPI), cognitive performance, and plasma biomarkers of Alzheimer’s disease (AD), and to examine the correlation between plasma and cerebrospinal fluid (CSF) biomarkers. Methods: This cross-sectional observational study included 40 patients (mean age 68.0 ± 9.0 years; 42.5% female) undergoing a diagnostic workup for cognitive decline. Patients were classified into AD (n = 20) and non-AD (n = 20) groups based on CSF AT[N] profiles. Frailty was assessed using the MPI. Linear and logistic regression models adjusted for age, sex, and education examined associations between MPI, cognitive scores, and plasma biomarkers (Aβ42, Aβ42/40, p-tau181, NfL). Correlations between plasma and CSF biomarkers and ROC analyses were also performed. Results: The AD group showed significantly higher plasma p-tau181 levels and MPI scores. MPI was positively associated with plasma p-tau181 levels (β = 4.26, p = 0.009). Plasma p-tau181 correlated strongly with CSF p-tau181 (R = 0.523, p < 0.001) and with CSF Aβ42/40 ratio (R = −0.541, p < 0.001) and showed high diagnostic accuracy (AUC = 0.910). Combining MPI with plasma biomarkers improved classification between AD and non-AD cases (AUC = 0.941). Conclusions: These findings support the value of incorporating frailty assessment in the diagnostic process of AD. The integration of geriatric tools and blood-based biomarkers may improve early detection and promote a more comprehensive approach in dementia evaluation. Full article
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