Search Results (952)

T-cell non-Hodgkin lymphomas, which arise from post-thymic mature T cells, constitute approximately 10–15% of all non-Hodgkin lymphomas. Their leukemic presentations, referred to here as mature T-cell leukemias, are relatively uncommon and present significant diagnostic and therapeutic challenges requiring an informed approach to diagnosis and management. The initial presentation is often persistent T-cell lymphocytosis that must be distinguished from reactive (non-malignant) causes. Unlike B-cell lymphocytosis, where clonality usually indicates malignancy, T-cell clonality can be detected in benign conditions such as autoimmune disorders and viral infections. Thus, establishing clonality is helpful but not sufficient, and a systematic diagnostic approach integrating clinical features, morphology, immunophenotype, and molecular findings is critical. This review outlines our approach to the diagnosis and treatment of four major subtypes of mature T-cell leukemias: T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), T-large granular lymphocytic leukemia (T-LGL), and Sézary syndrome (SS). Each section includes a discussion of clinical features, workup, and treatment options. Full article

Brucella is a neglected foodborne pathogen, which contaminates milk, dairy products, meat, and meat products of infected animals. However, the role of the Brucella putative effector (BPE) protein family, which relies on the type IV secretion system (T4SS) in Brucella abortus, remains unclear. We demonstrated that BPE159 mediates the regulation of host nuclei in autophagy. The host-interacting protein Eci1 was screened using yeast two-hybridization, molecular docking, and immunoprecipitation, and BPE159-deleted (ΔBPE159) and complementary (ΔBPE159-C) strains were constructed by homologous recombination. We evaluated their growth, survival, and replication and measured the expression of autophagy-related cytokine mRNAs in macrophages. BPE159 was localized in the nucleus of host cells and interacted with Eci1 to downregulate the expression of macrophage autophagy factors, thereby inhibiting host autophagy and enabling the persistence of Brucella. These findings highlight the critical role of BPE159 in mediating autophagy through Eci1 in host cells to promote Brucella survival in host cells. Full article

Background/Objectives: Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic cutaneous T-cell lymphomas frequently associated with pruritus, psychological distress, and impaired quality of life (QoL). While the impact of MF/SS on patients’ quality of life is well recognized, data on the burden experienced by cohabitants remain limited. The aim of this study was to assess dermatology-specific quality of life in patients with MF/SS and their cohabitants and to explore its associations with pruritus severity, depressive symptoms, and disease stage. Methods: This cross-sectional study included 25 patient–cohabitant pairs (25 patients with MF/SS and their cohabitants living in the same household) recruited at a tertiary dermatology center. Patients completed the Dermatology Life Quality Index (DLQI), Beck Depression Inventory I (BDI-I), and pruritus intensity scales (Numeric Rating Scale and Visual Analogue Scale), whereas cohabitants completed the Family Dermatology Life Quality Index (FDLQI) to assess the family burden of the disease. Associations between quality-of-life measures, clinical characteristics, pruritus, and depressive symptoms were analyzed. Results: Patients reported moderate impairment in dermatology-specific quality of life (mean DLQI score of 9.3 ± 6.1), which was significantly greater in patients with advanced-stage disease (p = 0.022). Cohabitants also experienced moderate impairment in quality of life (mean FDLQI score of 8.0 ± 4.8), independent of disease stage. DLQI scores showed significant positive correlations with pruritus severity, depressive symptoms, and cohabitants’ FDLQI scores. Pruritus severity was a key determinant of impaired quality of life but did not differ significantly between disease stages. Conclusions: MF/SS are associated with a substantial multidimensional burden affecting both patients and their cohabitants. Quality-of-life impairment in family members correlates closely with patient-reported symptoms and well-being, supporting the concept of MF/SS as conditions affecting the patient–family unit. Incorporating caregiver perspectives and systematic symptom assessment may improve holistic management of MF/SS. Full article

Hepatocellular carcinoma (HCC) progression is shaped by crosstalk between the tumor immune microenvironment (TME) and metabolic reprogramming. This study aims to characterize a macrophage–lactylation molecular axis in HCC and to develop a quantitative prognostic stratification model. Using the TCGA-LIHC cohort, differentially expressed genes were intersected with Paeoniflorin (PF)-related targets, HCC disease targets, and macrophage-/lactylation-related genes to identify candidate genes. Prognostic genes were selected through Cox and LASSO-Cox analyses to construct a risk score model, followed by survival analysis and ROC curve evaluation. Immune infiltration was assessed using ESTIMATE and ssGSEA algorithms, and PF–protein binding interactions were explored via molecular docking and molecular dynamics simulations. Intersection analysis identified eight key genes, and prognostic model genes (HNRNPU, LDHA, and NPM1) were used to construct the prognostic model. High-risk patients exhibited significantly poorer overall survival (p < 0.001), with 1- and 3-year AUC values ranging from 0.70 to 0.90. HNRNPU was positively correlated with activated CD4 T cells (r = 0.385) and negatively correlated with eosinophils (r = −0.498). Molecular docking indicated favorable binding of PF to the model proteins, with the highest predicted affinity observed for LDHA (Vina score = −8.9 kcal/mol), and molecular dynamics simulations suggested the formation of a stable LDHA–PF complex during the later stage of the simulation. We propose a prognostic risk model for HCC constructed using three prognostic model genes and provide computational evidence linking PF to key molecular nodes such as LDHA. External cohort validation and experimental studies are warranted. Full article

Background: The emergence of carbapenem-resistant enterobacteriaceae (CRE) co-harboring the mcr-1.1 gene and carbapenemase-encoding genes poses a severe threat to public health. Urban wastewater treatment plants (WWTPs) act as natural reservoirs and hotspots for the dissemination of antimicrobial resistance genes (ARGs). This study aimed to elucidate the molecular characteristics of CRE carrying mcr-1.1 in urban WWTPs. Methods: Samples were collected from the influent of urban WWTPs in Fengxian, Shanghai, from April 2024 to March 2025. mcr-1.1-positive Escherichia coli (E. coli) isolates were screened using real-time PCR, and their antimicrobial susceptibility was determined via the broth microdilution method. Plasmid conjugation assays were performed with E. coli C600 as the recipient strain. Whole-genome sequencing (WGS) was carried out to analyze the molecular characteristics of mcr-1.1-positive E. coli isolates. Results: A total of 312 samples were collected, and 5 (1.6%) mcr-1.1-positive E. coli isolates were identified. All isolates were multidrug-resistant (MDR) but susceptible to tigecycline (TIG). WGS of strain EC0176 (sequence type 156 [ST156], enteroaggregative E. coli [EAEC]) detected the presence of bla_NDM-5, bla_TEM-1, bla_CTX-M-55, and mcr-1.1 as well as related virulence genes. Further analysis revealed that pEC0176 was an IncHI2-type plasmid co-harboring mcr-1.1, bla_NDM-5, arr-3, aph(4)-Ia, aph(3′)-Ia, aac(3)-IVa, and mph(A). The plasmid pEC0176 harbored similar backbones as p20014-MCR, p2017.03.02CC_1, pSC2017167-mcr-256k, pEC17CM13_MCR and pGDE043-mcr1, including the type IV secretion system (T4SS) and IncHI-type conjugal transfer genes. Conjugation experiments confirmed that pEC0176 could be horizontally transferred into E. coli C600, with an average transfer efficiency of 3.3 × 10⁻². Phylogenetic analysis showed that the MCR-1 protein of EC0176 is closely related to that of two human-derived E. coli strains from China (GenBank accession: AVR64822.1 and WP_076611062.1). Conclusions: To our knowledge, this is the first report of E. coli ST156 carrying an IncHI2-type plasmid co-harboring mcr-1.1 and bla_NDM-5 from urban WWTPs in Fengxian, Shanghai. Our findings underscore the severe status of bacterial antimicrobial resistance and emphasize the necessity of enhancing antimicrobial resistance surveillance in urban WWTPs. Full article

Background: This study aimed to evaluate the relationship between thoracolumbar kyphosis (TLK) and lumbar degenerative spondylolisthesis (LDS) and to determine whether TLK can serve as an independent radiological predictor for both the presence and the specific affected level of LDS. Methods: Initially, 211 patients were screened for this study. After applying exclusion criteria, a final cohort of 129 patients (76 women and 53 men; mean age 62.1 ± 9.1 years) who underwent surgical intervention for degenerative lumbar spinal stenosis and had preoperative full-spine standing radiographs were retrospectively analyzed. Patients were divided into two groups: an LDS group (n = 54) comprising patients with concurrent degenerative spondylolisthesis, and a control group (n = 75) consisting of surgical patients without spondylolisthesis. Sagittal parameters, including TLK (T10–L2 angle), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), and thoracic kyphosis (TK), were measured. LDS was classified by the affected level (L3–L4, L4–L5, L5–S1). Group differences were compared, ROC analysis was performed to identify a threshold value, and multivariate logistic regression was used to determine independent predictors. Results: Multivariate analysis revealed that the T10–L2 angle (TLK) (OR: 1.15, p = 0.001), sacral slope (OR: 1.40, p = 0.017), pelvic tilt (OR: 1.50, p = 0.003), pelvic incidence (OR: 0.68, p = 0.004), and lumbar lordosis (OR: 1.09, p = 0.005) were significant independent predictors of LDS. Conversely, global thoracic kyphosis (TK) demonstrated an inverse relationship (OR: 0.88, p = 0.001), indicative of a secondary compensatory adaptation. ROC analysis established a TLK cut-off of ≥19.5° (AUC = 0.68, p = 0.001) for predicting LDS. Furthermore, Roussouly Type 3 alignment was significantly more prevalent in the L5–S1 LDS cohort (48.1%) Conclusions: Increased TLK is independently associated with LDS, particularly at lower lumbar levels. A TLK value ≥ 19.5° may serve as a practical radiographic marker, and TLK assessment should be incorporated into sagittal alignment evaluation and surgical planning. Full article

Neutrophils and their extracellular traps (NETs) are pivotal elements of the immune response. This study investigates the dynamics of neutrophil-related markers during the perioperative period of branched endovascular aortic repair (BEVAR) in patients with thoracoabdominal aortic aneurysms (TAAAs) and evaluates their association with one-year clinical outcomes. A prospective, single-center study was conducted on 20 TAAA patients treated with T-branch devices. The analysis focused on surrogate markers associated with NETosis, including double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and citrullinated histone H3 (citH3). Peripheral venous blood was collected 24 h before BEVAR, and on the third and fifth postoperative days. Patients were monitored for one year to evaluate mortality and hospitalization risks, with predictors identified using Cox regression analysis. Increased postoperative levels of inflammatory markers were significantly associated with higher risks of mortality and hospital readmission. On the third postoperative day, key parameters emerged as predictors of adverse outcomes: dsDNA (HR = 1.000; 95% CI 1.000–1.000; p = 0.027), ssDNA (HR = 1.000; 95% CI 1.000–1.000; p = 0.022), and NLR (HR = 1.226; 95% CI 1.043–1.440; p = 0.013). Markers assessed in the early postoperative period (the third postopearive day) demonstrated superior predictive utility compared to those measured on the fifth postoperative day. CitH3 levels did not show statistical significance as a prognostic factor. Early postoperative evaluation of NET-associated markers, particularly dsDNA and ssDNA, offers prognostic value for predicting mortality and hospitalization risks in TAAA patients undergoing BEVAR. These markers may provide superior predictive accuracy compared to conventional post-implantation syndrome criteria. Enhanced postoperative monitoring of these markers could help identify high-risk patients who may benefit from intensified follow-up. Full article

V. parahaemolyticus has several virulence factors, including thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH), and two separate type III secretion systems (T3SSs), T3SS1 and T3SS2. T3SS1 is responsible for cytotoxicity, primarily through the activity of its effector VP1680. To gain a detailed understanding of the relationship between the amount of effector, its expression timing, and cytotoxicity, a system is required to regulate protein expression levels and timing. In the present study, we developed an effector protein expression system controlled by an arabinose-dependent transcription factor and found that cytotoxicity toward mammalian cells increased in a VP1680-dependent manner. To ensure specific protein degradation, we also established a targeted protein degradation system, including VP0917 (ClpP) and VP0918 (ClpX)-, or VP0917 and VP1014 (ClpA)-mediated degradation of ssrA-tagged proteins (proteins bearing the C-terminal degradation tag encoded by tmRNA). By combining these systems, more than 50% of the targeted protein could be degraded within 20 min. As a byproduct of creating the systems, we obtained an enhanced green fluorescent protein variant that emits strong fluorescence in V. parahaemolyticus. The protein degradation system developed in this study has demonstrated the potential to control intracellular protein levels to a certain extent. Moreover, experimentally controlling intracellular protein levels will allow for a more detailed examination of the relationship between protein quantity and cellular phenotype, potentially overcoming the limitations of the “all-or-nothing” model. Full article

Background: Heterocycle compounds with acridine, quinoline, indole, and pyridine nuclei are potentially active for anticancer activity since they can promote inhibition of vital enzymes, decreasing cell survival after binding to biomolecules. However, unspecific biological interactions can result in unwanted effects, which should be defined during the synthesis and proposition of new molecules. Thus, the objective of this study was to investigate the biological and teratogenic effects of four nitrogen heterocycles proposed for anticancer therapy. Methods: Four 2-cyano-N-phenylacrylamine type derivatives containing acridine (3a), quinoline (3b), indole (3c), and pyridine (3d) nuclei were synthesized and characterized. They were evaluated for their ability to interact with DNA, physicochemical and pharmacokinetic predictions, in vitro and in silico methodologies, besides in vitro inhibition of the Topoisomerase IIα enzyme, antiproliferative activity in tumor and non-tumor cells, hemolytic activity with human erythrocytes, and in vivo toxicological studies with zebrafish embryos. Results: UV–vis absorption studies with ssDNA revealed different spectroscopic effects, with binding constants (Kb) ranging from 1.41 × 10⁵ to 6.46 × 10⁴ M⁻¹. The fluorescence quenching constant (Ksv) with ethidium bromide (EB) varied between 0.53 and 0.67 × 10³ M⁻¹. The compounds intercalated into DNA base pairs, a mechanism confirmed by molecular docking, with 3b (quinoline) showing the most substantial interaction. All derivatives exhibited antitopoisomerase IIα activity at 100 μM and were cytotoxic against MCF-7 and T47-D breast tumor cells, particularly against the more aggressive T47-D lineage. No hemolytic activity was observed in human erythrocytes. In vivo assays in zebrafish embryos showed no toxicological or cardiotoxic effects. However, all compounds altered superoxide dismutase (SOD) and catalase (CAT) enzymatic activity, requiring further studies on reactive oxygen species (ROS) generation to assess potential adverse effects. Furthermore, significant results were observed in the physicochemical and pharmacokinetic parameters of the synthesized compounds. Conclusions: The findings highlight the quinoline derivative (3b) as the most promising nitrogen heterocycle due to its antiproliferative activity and biomolecular interactions without adverse effects in zebrafish embryos, distinguishing it from clinically available agents. Full article

In this paper, we present and describe a new type of fuzzy open sets, called fuzzy $(\mathfrak{n},\mathfrak{m})$-e-open sets in double fuzzy topological spaces (DFT Ss,) based on Šostak’s approach. This type belongs to the group of fuzzy $(\mathfrak{n},\mathfrak{m})$-$\delta$-$\beta$-open sets and includes all fuzzy $(\mathfrak{n},\mathfrak{m})$-$\delta$-$\alpha$-open sets, fuzzy $(\mathfrak{n},\mathfrak{m})$-$\delta$-pre-open sets, and fuzzy $(\mathfrak{n},\mathfrak{m})$-$\delta$-semi-open sets. We then explore the idea of $DF$-e-continuity between DFT Ss $(Q,\Gamma ,{\Gamma }^{*})$ and $(K,\mathcal{T},{\mathcal{T}}^{*})$. We also introduce and examine the concepts of $DF$-almost e-continuity and $DF$-weakly e-continuity, which are less strict than $DF$-e-continuity. Subsequently, we introduce and analyze new $DF$ mappings through Fuzzy $(\mathfrak{n},\mathfrak{m})$-e-open and Fuzzy $(\mathfrak{n},\mathfrak{m})$-e-closed sets. Finally, we present and introduce some novel new types of $DF$-separation axioms, named Fuzzy $(\mathfrak{n},\mathfrak{m})$-e-regular and Fuzzy $(\mathfrak{n},\mathfrak{m})$-e-normal spaces, and we examine some of their properties. Full article

Background and Objectives: Obstetric anal sphincter injuries (OASISs) are severe complications of vaginal delivery that can result in long-term pelvic floor dysfunction and reduced quality of life. Global data indicate a rising incidence of OASISs, including in Lithuania. This study aimed to identify risk factors for OASISs and evaluate their impact on urinary (UI) and fecal incontinence (FI), pelvic organ prolapse (POP), and quality of life in affected women. Materials and Methods: A retrospective case–control study was conducted at the Lithuanian University of Health Sciences Hospital (LUHS) Kauno Klinikos in 2024. Women who gave birth between 2004 and 2023 and experienced OASIS (n = 90) were compared with women matched for birth history but without perineal tears (n = 90). Data were collected from medical records and electronic questionnaires, including the International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF), Wexner score, Pelvic Organ Prolapse Symptom Score (POP-SS), and Pelvic Floor Impact Questionnaire (PFIQ-7). Participants were grouped by delivery year (2004–2013 or 2014–2023). Statistical analysis was performed using Mann–Whitney U, Chi-square, Fisher’s exact and Student’s t-tests, with p < 0.05 considered significant. Results: Newborn weight and vacuum-assisted delivery were significantly associated with OASIS (p < 0.05 and p = 0.029). In the 2014–2023 cohort, women with OASIS reported significantly higher rates and severity of UI, FI, and POP symptoms compared to controls. Quality of life scores related to UI and FI were significantly worse in the recent OASIS group, whereas no significant differences were observed in the 2004–2013 cohort. Conclusions: Between 2004 and 2023, 0.4% of women who gave birth at LUHS experienced third- or fourth-degree perineal tears, with newborn weight and vacuum extraction identified as risk factors. These women reported higher rates of UI and FI and POP, and those who delivered between 2014 and 2023 rated their related quality of life significantly worse than women without OASIS. Full article

Intensive porcine livestock production generates approximately 15 million cubic meters of slurry annually, exerting significant environmental pressure on groundwater and contributing to greenhouse gas emissions. The AEROFER project aims to mitigate this impact by demonstrating the conversion of nitrogen-rich waste into liquid fertilizers for soilless cultivation. Using an Internet of Things (IoT)-enabled aeroponic platform controlled by an ESP32 microcontroller, this study evaluated filtration (40 microns) and ozone-based stabilization (N-Amatic technology). Three lettuce varieties (Lactuca sativa L.)—Longifolia (Romaine lettuce), Capitata (Butterhead lettuce), and Capitata (Red leaf lettuce)—were grown to compare Filtered Slurry (FS) and Filtered–Ozonated Slurry (FOS) against a mineral control standard solution (SS). The results indicate that ozone treatment eliminated detectable E. coli and coliforms while increasing the phosphorus availability by 78% (from 30.9 to 55 mg/L), despite an 11% reduction in the potassium content (from 180 to 160 mg/L). Agronomic data reveal variety-specific responses, and mass balance analysis shows that the solutions are potassium-deficient, meeting only 32–64% of crop needs. In conclusion, while aeroponics is a viable tool for nutrient recovery and requires targeted mineral supplementation to achieve full parity with commercial fertilizers, it satisfies a substantial proportion of plant nutritional requirements. Consequently, it represents a sustainable approach to food production through waste recycling, contributing to a circular economy in the pig industry without apparent sanitary risks. Full article

Background: Hypoxia is a key driver of cancer progression. However, its specific prognostic significance in gastric cancer (GC) remains insufficiently characterized. Methods: Single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network analysis (WGCNA), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression were employed to identify a hypoxia-related prognostic signature. Subsequently, immune microenvironment profiling and single-cell RNA sequencing analyses were employed to further characterize the biological characteristics of the signature. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to validate the expression levels of key hypoxia-associated genes in human GC tissues. Results: Elevated hypoxia levels were linked to worse survival outcomes in GC patients. Through integrated WGCNA, Cox, and LASSO analyses, a hypoxia-related prognostic signature (HYS) consisting of four genes—SPARC, AXL, NRP1, and VCAN—was established. Patients in the HYS-high group exhibited markedly poorer overall survival than their HYS-low counterparts [p = 0.000126, hazard ratio (HR) = 1.936]. Moreover, the HYS-high group exhibited increased infiltration of resting CD4⁺ memory T cells, monocytes, M2 macrophages, and resting mast cells, as well as elevated expression of immunosuppressive molecules, including PDCD1LG2 and HAVCR2. Single-cell RNA sequencing analysis revealed that the signature genes were predominantly expressed in cancer-associated fibroblasts. Consistently, qPCR analysis in five paired GC and para-carcinoma tissues confirmed higher expression of these genes in tumor samples (p < 0.01). Conclusions: Our findings indicate that hypoxia is a critical determinant of prognosis in GC and is closely associated with an immunosuppressive tumor microenvironment, highlighting its potential value as a prognostic biomarker and therapeutic target. Full article

Pseudomonas syringae pv. syringae (Pss) is an economically significant bacterial pathogen that causes canker in sweet cherry trees. In Chile, sweet cherry (Prunus avium L.) is a key crop whose exponential production growth has increased phytosanitary pressure. However, the genetic diversity and adaptive mechanisms of local Pss populations have remained poorly understood. This study characterized 41 Pss isolates from major Chilean production regions. Their genomes were sequenced and compared with 152 public genomes from the PG2 phylogenetic group. The analysis revealed a predominance of the PG2d subgroup among the Chilean isolates, with a population structure defined by at least 18 genomic clusters, some of which are exclusive to Chile. A characteristic feature of this entire PG2d subgroup is the presence of indole-3-acetic acid (IAA) synthesis genes (iaaM and iaaH). Furthermore, this subgroup displayed a marked increase in ancestral gene gain and loss events, indicating extensive remodeling of the shell genome and supporting a model of lineage-specific adaptive evolution. We also identified lineage-specific orthogroups, structural variants of the T-PAI pathogenicity island, and a differential distribution of Hop-type effector proteins. Furthermore, an extended copper resistance operon (cop and cus systems) was detected in a subset of strains, and a dominant lineage was found to have a dual i1-type of T6SS system. These findings highlight the local diversification of Pss in Chile, likely driven by agro-environmental pressures. This study provides crucial insights into the evolution, adaptation, and pathogenic potential of this important pathogen in a crop of high strategic value. Full article

Objective: The purpose of this study was to assess the outcome of sinus grafting with a beta-tricalcium phosphate/hydroxyapatite (ß-TCP/HA) alloplast particulate biofunctionalized with cross-linked hyaluronic acid (xHya), comparing two surgical access techniques. Clinical, histological, histochemical, immunohistochemical and histomorphometrical parameters were used to characterize the tissue samples, which were retrieved at the second surgery for implant placement five months after sinus floor elevation (SFE). Materials and Methods: Twenty patients with a residual bone height ≤ 4 mm, estimated by a Cone Beam Computed Tomography (CBCT), were randomly allocated either to an innovative transcrestal sinus floor elevation (tSFE = tests) approach or a conventional lateral window approach (lSFE = controls) using piezoelectric preparation. The tSFE was carried out using the hydraulic Jeder^®-System. Grafting in both groups was performed using a ß-TCP–HA combination, which was biofunctionalized with a cross-linked hyaluronic acid. For both access techniques, a cross-linked collagen membrane covered either the bone window or transcrestal osteotomy. For second-stage surgery, a second CBCT was used to assess the bone volume and possible implant positioning to compare it with the baseline CBCT. Bone cores were harvested at implant placement and evaluated histomorphometrically. Patients were followed for 1-year post-op for survival rate estimation. Non-superiority was hypothesized for both surgical methods; thus, the primary outcome measure assessed different discomfort levels using patient-reported outcome measures (PROMs) for each therapeutic approach. Secondary outcomes were the volume change in subantral bone after sinus floor elevation, the chance of placing a 10 mm long implant with no need for additional augmentation, histological evaluation of the newly gained tissue, and implant integration and one-year survival. Results: Eighteen patients (n = 18/20) qualified for implant placement at five months, and ten donated tissue biopsies for microscopic analysis. Primary outcome reporting using PROMs was discarded due to truncated patient enrollment. The secondary parameter, placement of a ≥10 mm long implant without additional augmentation, was achieved for nine sites/patients from the lSFE control group. All patients from the tSFE test group received an implant that was positioned alongside additional augmentation. In both groups, all implants integrated and were functionally loaded. A total of 10 core samples (3 from the tSFE group and 7 from the lSFE group) were obtained and analyzed. Microscopically, new bone formation appeared consistent in all obtained samples. Specimens revealed advanced and ongoing osteogenesis, with most histological markers reacting positively in the immunohistochemical (IHC) staining. The histomorphometric calculation revealed that a mean of 61.17 ± 16.55% of the total area was occupied by newly formed bone, 30.43 ± 10.09% by connective tissue and 8.92 ± 15.29% by residual graft substitute. One-year follow-up of the loaded implants showed a 100% implant survival rate. Conclusions: Biofunctionalizing ß-TCP + HA particulate with cross-linked hyaluronic acid in sinus floor elevation procedures appears to be a safe and beneficial approach, resulting in satisfactory clinical, radiographic and histological parameters. In our study population, which presented with very atrophic residual subantral bone conditions, the hydrodynamic transcrestal sinus floor elevation method required a back-up treatment by the conventional lateral approach. Full article