Search Results (320)

Redevelopment precincts are often assessed through price uplift, although price appreciation alone does not show whether a local housing market becomes more active or liquid. This study examines whether residential turnover and property valuation diverged around the Etihad Campus redevelopment precinct in East Manchester after the 2014Q4 consolidation of the wider campus setting. Using Office for National Statistics House Price Statistics for Small Areas, the analysis applies a neighborhood-scale synthetic control design to a compact Core-4 treatment precinct, using a filtered within-Manchester donor pool to construct the synthetic benchmark. Residential turnover is measured as the mean residential sales count per Lower Layer Super Output Area (LSOA), and valuation is measured as the average of LSOA-level median house-price trajectories. Robustness is assessed using alternative treatment definitions and pre-intervention calibration windows. The results show a persistent post-2014 turnover shortfall relative to the synthetic benchmark, supported by rank-based placebo diagnostics and retained across all valid turnover specifications. By contrast, valuation evidence is weaker, mixed, and more sensitive to design choice. These findings indicate selective housing-market reconfiguration rather than generalized uplift. Redevelopment evaluation should therefore distinguish transaction circulation from price-based valuation, particularly in cumulative precinct-scale redevelopment settings. Full article

Background: Follicular unit extraction (FUE) has become the dominant donor site harvesting technique in modern hair transplantation due to its ability to avoid linear scar formation and its procedural flexibility. However, the donor site is a limited non-regenerative source. Excessive or poorly planned extraction can lead to visible thinning, hypopigmented scarring, and reduced reserve for future procedures. Objective: This study aimed to synthesize current evidence on donor biology, preoperative assessment, extraction strategy, and complication prevention in FUE, and to propose a reproducible clinical framework for donor preservation. Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and Google Scholar to identify English-language publications related to donor site biology, donor evaluation, extraction density thresholds, complication prevention, repeat session planning, and emerging FUE technologies. Priority was given to recent reviews, clinical trials, consensus statements, and practice-oriented surgical literature. Articles were selected not for formal meta-analytic pooling, but because of their relevance to donor conservation and long-term donor management. Results: The literature reviewed consistently identifies excessive local extraction density, harvesting beyond conservative limits, donor miniaturization, and inadequate reassessment before repeated procedures as the primary drivers of donor morbidity. Evidence from reviews, clinical trials, and expert guidelines supports conservative extraction thresholds, widespread spatial distribution, individualized donor mapping, and phased long-term planning as key strategies for preserving donor aesthetics and reserve. Conclusions: Donor preservation is central to ethical and sustainable FUE surgery. Integration of biologically informed assessment, disciplined extraction control, and mandatory reassessment protocols can reduce morbidity while preserving long-term graft flexibility in patients with progressive androgenetic alopecia. Full article

Background/Objectives: Tuberculosis, caused by Mycobacterium tuberculosis, remains a major global health challenge requiring novel prevention strategies. This study aims to developed an immunoinformatics-guided framework coupled with experimental screening to prioritize for multi-epitope mRNA vaccine design. Methods: Eight immunologically relevant antigens were computationally analyzed to predict cytotoxic (CTL) epitopes and helper T lymphocyte (HTL) epitopes. Population coverage, immune simulation, molecular docking, and normal mode analysis (NMA) were performed in silico. To evaluate peptide immunoreactivity, human IFN-γELISPOT assays were conducted using the candidate peptides, though HLA restriction was not experimentally validated. Results: The workflow identified 14 candidate CTL and 8 HTL epitopes, yielding an estimated global population coverage of 82.6% (60.7% in China; 51.2% in Indonesia). Immune simulations predicted robust humoral and Th1-associated cellular responses, though sustained CD8⁺ memory responses appeared limited. Docking and NMA suggested favorable structural interactions with TLR3 and TLR4. Crucially, the IFN-γ ELISPOT assay validated eight reactive epitopes that partially coincided with computational predictions within the tested donor group. Conclusions: This study establishes an integrated computational–experimental workflow for T cell epitope prioritization. The identified reactive epitopes provide a preliminary immunological basis and candidate pool for the future design and evaluation of multi-epitope mRNA vaccine strategies against tuberculosis. Full article

Background/Objectives: Free riding in healthcare occurs when actors benefit from health-related public goods, risk-pooling arrangements, common resources, or cooperative institutions while contributing less than is socially optimal. This review clarifies how free-rider dynamics differ across vaccination, health insurance and universal health coverage, antimicrobial resistance, organ donation and transplant allocation, and global health cooperation. Methods: A narrative review with conceptual synthesis was conducted. Searches of PubMed and Scopus were complemented by citation tracking and targeted inclusion of foundational economics, game theory, public-health ethics, and market-design sources. Sources were mapped by domain, actors, strategies, payoff structure, information conditions, time horizon, enforcement mechanism and policy relevance. Results: Across domains, free riding arises when private payoffs diverge from collective welfare, but the underlying game differs: threshold public-good and coordination games in vaccination, adverse-selection and participation games in insurance, common-pool-resource dilemmas in antimicrobial use, donor-registration and matching-market problems in transplantation, and repeated public-goods games in global health. The review identifies three policy functions: altering payoffs, altering information and beliefs, and changing the structure, repetition, or enforceability of the game. Conclusions: Game theory is most useful as a mechanism-based framework rather than a stand-alone policy prescription. Its policy value depends on empirical calibration, institutional context, ethical legitimacy, and attention to equity, incomplete information, behavioral responses, and enforcement capacity. The synthesis also emphasizes boundary conditions: game-theoretic prescriptions can fail when political economy, asymmetric power, implementation capacity, access barriers, or trust-related drivers are ignored. Full article

Folate is a central nutrient in one-carbon metabolism, contributing to nucleotide biosynthesis, methionine cycling, methyl-donor supply, and epigenetic regulation. In animals, the intestine is both a principal site of folate absorption and a key target organ for folate action. This narrative review focuses primarily on livestock, poultry, aquaculture species, ruminants, and animal-source food enrichment, while also using rodent, human, and in vitro studies as mechanistic or translational evidence. We synthesize evidence on folate absorption, transport, and metabolism and evaluate the mechanisms through which folate influences intestinal health. Available evidence suggests that adequate folate supply may support epithelial renewal, tight-junction integrity, mucosal immune balance, antioxidant capacity, gut microbiota stability, short-chain fatty acid production, and epigenetic regulation of intestinal development. These effects have been reported in poultry, pigs, fish, ruminants, rodents, and maternal–offspring models. However, the evidence is uneven across species, and dose–response relationships, folate forms, bioavailability, and species-specific requirements remain major limitations for translating current knowledge into animal production. Future studies should compare folic acid, 5-methyltetrahydrofolate, natural reduced folates, microbiota-derived folate, and folate-producing probiotics; quantify the contribution of microbiota-derived folate to host methyl-donor pools; and develop precision strategies that integrate folate with other one-carbon nutrients, probiotics, and product-enrichment technologies. Full article

Background: Lateral epicondylopathy is commonly approached as a tendinopathic disorder of the common extensor origin; however, persistent lateral elbow pain may also involve a superficial sensory nerve component related to the posterior antebrachial cutaneous nerve (PABCN). This proof-of-concept cadaveric anatomical feasibility study evaluated whether a single-window, humerus-parallel ultrasound-guided injectate pathway could simultaneously reach the superficial PABCN-related fascial plane and the common extensor origin. Methods: One fresh-frozen male cadaveric donor was used, and both elbows were injected under real-time ultrasound guidance. With the elbow flexed and the forearm pronated, the transducer was aligned parallel to the long axis of the humerus over the lateral epicondylar region. A 23-gauge, 6 cm needle was advanced in plane from distal to proximal over the common extensor aponeurosis, and 10 mL of 1% methylene blue was injected into each elbow. Layer-by-layer anatomical dissection was then performed by an anatomist who was not involved in the injection procedure. Gross linear dye spread was measured directly during dissection using the distal needle entry point as the reference point, and ruler-containing photographs were additionally reviewed using ImageJ software for supportive image-assisted assessment. Results: In both elbows, methylene blue stained the superficial PABCN-related fascial plane, including the anterior and posterior branches of the PABCN, and concomitantly covered the common extensor aponeurosis and lateral epicondylar enthesis. Dye spread measured approximately 10 cm proximally, 5 cm distally, and 4 cm anteriorly. No gross intra-articular dye deposition or focal intramuscular pooling was observed. Conclusions: This proof-of-concept cadaveric study demonstrates the anatomical plausibility of a single-window, enthesis-centered ultrasound-guided injectate pathway that includes both the superficial PABCN-related plane and the common extensor origin. These findings should be interpreted as descriptive anatomical feasibility observations and do not establish reproducibility across anatomical variants, clinical efficacy, safety, or procedural superiority. Full article

Despite their reduced viability, kidneys from donors-after-circulatory-death (DCD) increase the pool of transplantable kidneys. Molecular hydrogen (H₂) is emerging as a gas with therapeutic potential against graft injury. We investigated the effect of H₂ in an ex vivo porcine model of DCD kidney transplantation. Renal arteries of male Yorkshire pigs (n = 6) were clamped in situ for 60 min to induce ischemia, and ureters and arteries were cannulated to mimic DCD kidney injury. Upon nephrectomy, kidneys were flushed with UW solution or H₂-saturated UW solution and then preserved by machine perfusion at 4 °C for 4 h followed by a 4-h reperfusion period with warm autologous blood. Urine and arterial blood samples were collected hourly. H₂ preserved renal architecture, evidenced by significantly reduced tubular necrosis and renal expression of damage markers, which corresponded with the downregulated renal expression of pro-inflammatory genes compared to the UW-only group (p < 0.05). H₂ also markedly reduced levels of serum creatinine, BUN and intrarenal resistance, while flow rate, creatinine clearance and urine output were significantly higher, which positively correlated with Trx-1 and HO-1 expression in comparison with UW only group (p < 0.05). Improvement in renal graft quality and function is associated with Trx-1/HO-1 activation, suggesting preliminary clinical trials in kidney transplantation. Full article

Background: ABO-incompatible living-donor liver transplantation (ABOi LDLT) can expand the donor pool for patients with hepatocellular carcinoma (HCC), but concerns remain regarding tumor recurrence and long-term survival. Methods: A systematic review and meta-analysis was performed according to PRISMA 2020. PubMed, Embase, and Web of Science were searched. Comparative studies evaluating oncologic outcomes after ABOi versus ABO-compatible (ABOc) LDLT for HCC were included in the quantitative synthesis; non-comparative studies were included in the qualitative synthesis. Hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival (OS) were pooled using a random-effects model. When HRs were not directly reported, they were estimated from Kaplan–Meier curves using established methods. Results: Sixteen reports were screened, 12 full-text articles were assessed, and 8 studies were included in the systematic review. Three comparative single-center cohort studies were eligible for meta-analysis. Pooled analysis showed no significant difference between ABOi and ABOc LDLT for RFS (HR 1.07, 95% confidence interval [CI] 0.77–1.49; I² = 0%) or OS (HR 1.08, 95% CI 0.74–1.57; I² = 0%). Five additional studies were synthesized qualitatively, suggesting that recurrence risk may be influenced more by tumor biology and peri-transplant management, including desensitization intensity and immunosuppression exposure, than by ABO incompatibility itself. Conclusions: Current limited comparative evidence does not demonstrate inferior RFS or OS after ABOi LDLT in carefully selected patients with HCC. Larger multicenter comparative studies with standardized reporting of tumor biology, desensitization protocols, and immunosuppression exposure are warranted to confirm these findings and clarify protocol-related effects on post-transplant recurrence. Full article

Autologous tooth-derived grafts are increasingly being investigated for bone regeneration, as dentin shares with bone a mineral phase and an organic matrix rich in type I collagen and non-collagenous proteins. Deciduous teeth are particularly attractive as biomaterials because they are easily obtained after physiological exfoliation, without additional surgical harvesting or donor-site morbidity and may expose a protein-rich matrix after processing. Whether deciduous teeth retain a biologic advantage after prolonged dry storage remains poorly documented. This proof-of-concept ex vivo and in vitro study compared pooled deciduous teeth from six different donors (exfoliated at least 10 years before the experiment and stored dry at room temperature conditions) with six freshly extracted third molars. The teeth were ground using a dedicated device, and conditioned supernatants were collected at 72 h (T1) and 28 days (T2). Osteocalcin, osteonectin, and BMP-2 were quantified by ELISA, and T1 supernatants were applied to human primary osteoblasts to assess the osteogenic response using qRT-PCR and immunofluorescence. Deciduous teeth-conditioned supernatants showed higher osteocalcin and osteonectin release than permanent teeth at both time points, whereas BMP-2 levels were comparable, though with higher values in deciduous samples. In osteoblasts, deciduous teeth-conditioned supernatants induced enhanced osteogenic responses, including greater activation of Collagen I, Osterix, RUNX-2, Osteocalcin, BMP-2 genes, and higher expression of bone-related proteins. Within the limits of this exploratory study, dry-stored deciduous teeth preserved a biologically active dentin matrix and showed a more favorable osteogenic profile than freshly extracted permanent teeth, supporting further investigation into standardized storage protocols and their potential use in regenerative applications. Full article

Background/Objectives: Neutrophils express the receptor for advanced glycation end products (RAGE), yet its role in antibacterial responses remains incompletely defined. This study aims to elucidate the dual functionality of RAGE as a membrane-bound signaling sensor and a source of soluble RAGE (sRAGE) in human neutrophils challenged with Salmonella typhimurium, a clinically relevant Gram-negative pathogen. Methods: Human peripheral neutrophils from healthy donors were isolated and stimulated with S. typhimurium, LPS, or fMLP. Calcium flux, ROS/RNS production, and phagocytosis were assessed using fluorescent probes and spectroscopy. RAGE expression and localization were analyzed by immunofluorescence microscopy and flow cytometry. Soluble RAGE in supernatants was quantified by ELISA, and its molecular forms were characterized by Western blotting. Results: Resting neutrophils exhibited minimal surface RAGE but a substantial intracellular pool. RAGE inhibition with FPS-ZM1 attenuated bacteria-induced Ca²⁺ mobilization, oxidative burst, nitrosative output, and phagocytosis, with the most pronounced defect at the pathogen-attachment stage—consistent with impaired cytoskeletal remodeling. Upon activation, neutrophils rapidly released sRAGE (peak at ~10 min) via combined metalloprotease-dependent shedding and regulated secretion of pre-formed intracellular stores. Paradoxically, FPS-ZM1 amplified sRAGE release while suppressing membrane-proximal signaling. Conclusions: Neutrophil RAGE functions as a dynamic, multi-compartmental regulator: membrane-associated RAGE licenses effector responses to Gram-negative bacteria, while concomitant sRAGE release provides a fast negative-feedback loop to limit excessive inflammation. This self-limiting circuit balances antimicrobial defense with tissue protection, and its dysregulation may contribute to pathological outcomes in acute and chronic infections. Full article

Demineralized bone matrices (DBMs) are widely used in bone replacement therapy. Bone tissue of either cancellous or cortical origin is decellularized, demineralized, and sterilized during processing, while retaining portions of native organic extracellular matrix (ECM) proteins that regulate cell–matrix interactions during bone repair. The ECM largely accounts for the distinct functions of cortical and cancellous bone. Differences in three-dimensional architecture and matrix density between cancellous and cortical bone may therefore affect ECM proteome signatures and the resulting cellular microenvironment. In this study, ECM proteins were extracted from processed cancellous and cortical allografts at multiple processing steps and analyzed by quantitative mass spectrometry. We identified distinct extractable proteome signatures associated with bone metabolic functions. Cancellous grafts were relatively enriched in proteins associated with inflammatory, coagulative, and immune-related processes, whereas cortical grafts showed higher abundance of structural and matrix-organization-associated proteins. More extensively processed product formats showed fewer significant protein differences between the cortical and cancellous bone type. Within the limitations of pooled donor material and absent functional validation, these findings provide a proteomic framework for future characterization and evaluation of DBM-based allograft products. Full article

Liver transplantation is the definitive therapy for end-stage liver disease, yet persistent organ shortages result in approximately 10% of recovered livers being discarded, with markedly higher discard rates among marginal grafts from elderly donors, donation after circulatory death (DCD), and those with macrovesicular steatosis. Machine perfusion (MP) has emerged as a paradigm-shifting preservation strategy with the potential to safely expand the usable donor pool. This narrative review examines the current evidence for three MP modalities—hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), and normothermic regional perfusion (NRP)—across various marginal donor populations, including elderly donors, steatotic grafts, donors with infectious diseases, and split liver transplantation. Current evidence demonstrates that MP significantly increases utilization of steatotic grafts with up to an eightfold rise in usage of severely steatotic organs. HMP consistently reduces non-anastomotic biliary strictures and early allograft dysfunction across donor types, while NMP enables real-time viability assessment and reduces post-reperfusion syndrome in steatotic grafts. NRP shows particular benefit in DCD organs, reducing biliary complications and improving one-year survival. Additionally, MP extends preservation times enabling next-day split liver transplantation and shows promise as a platform for ex situ antiviral therapy. Despite compelling evidence supporting MP in marginal grafts, widespread adoption remains constrained by high costs, logistical complexity, and the absence of standardized protocols. Future progress will require multicenter studies evaluating long-term outcomes alongside consensus-driven implementation frameworks. Full article

Therapeutics derived from donated blood or its constituents are classifiable into blood components and plasma derivatives. The latter are defined as medicines/drugs/pharmaceuticals produced from the industrial fractionation of thousands of pooled plasma donations and characterised with relative precision to a pre-defined specification through sampling of a homogenous pharmaceutical batch. The former are defined as components/biologicals produced using relatively simple (but increasingly complex) technologies in blood centres from single or small pools of isolated components from whole blood and are pre-specified through regulatory standards with relatively wide limits because of the inherent biologic variability of individual donors. This review discusses the evolution of technology to reduce the risk of pathogen transmission by blood-derived therapeutics, assess the state of the approved technologies for pathogen-reduced blood components, and examine the features of the blood-provider and regulatory framework globally that have shaped, and in some instances impeded, the implementation of component pathogen reduction to an extent equivalent to that achieved for plasma derivatives. The ensuing risks to the public’s confidence in the blood supply are discussed, and remedial actions are proposed. The features of a new paradigm for blood safety are outlined. Full article

Shoot tip cryopreservation is essential for the long-term conservation of plant genetic resources. It provides the only reliable method for establishing a long-term, readily available gene pool of clonally propagated crops and elite in vitro clones used in the pharmaceutical, food, and cosmetic industries. Still, its success is often limited by the inherent sensitivity of many species to the osmotic and chemical stresses imposed by concentrated cryoprotectant (vitrification) solutions and severe dehydration. The optimization of modern cryopreservation protocols primarily focuses on modifying shoot tip preculture, cryoprotectant treatments, or regrowth conditions, while frequently overlooking donor plant preconditioning or relegating it to a secondary role. However, the physiological state of in vitro plants from which apical or axillary shoot tips are extracted may hold the key to successful post-cryopreservation recovery, especially in cryo-sensitive taxa. This review revisits the critical role of donor plant vigor and induced stress tolerance in the cryopreservation of clonal crops by systematically evaluating preconditioning strategies, including cold acclimation, sucrose pretreatment, and the use of growth regulators and signaling molecules such as abscisic, jasmonic, and salicylic acids, involved in stress signaling and tolerance development. The beneficial physiological changes induced by donor plant pretreatment, such as reduced freezable water content and the accumulation of protective compounds, are discussed in the context of contemporary cryopreservation methods. The effects of culture conditions, including the roles of ammonium and nitrates, light quality, culture density and aeration, medium strength, culture age, and subculture duration, are also considered. We analyze how different treatments of in vitro donor plants improve shoot tip tolerance to osmotic and/or chemical toxicity imposed by specific cryopreservation methods to support a material-centered selection of a cryopreservation procedure. Future directions and potential approaches for integrating target donor plant preconditioning into modern cryopreservation protocols for shoot tips, particularly in stress-sensitive species, are discussed. Full article

Background/Objectives: Delayed graft function (DGF) remains a common early complication after deceased donor kidney transplantation and is challenging to anticipate using routine pre-implant clinical variables alone. We investigated whether high-throughput Fourier transform infrared (FTIR) spectroscopy of static cold storage preservation fluid (not machine perfusion perfusate) captures biochemical information associated with DGF and warrants further evaluation alongside routine pre-implant clinical predictors. Methods: In this single-center retrospective cohort, we analyzed preservation fluid samples from 56 kidney transplants originating from 49 deceased donors (7 donors contributed two kidneys); DGF occurred in 14/56 (25.0%). Dried-film FTIR spectra were acquired using a plate-based high-throughput accessory, and analyses focused on the fingerprint region (900–1800 cm⁻¹) with prespecified preprocessing and quality control. We developed and compared clinical-only, FTIR-only, and combined predictive models and estimated performance using donor-blinded 5-fold StratifiedGroupKFold cross-validation (grouped by donor code) to prevent leakage across paired kidneys. Results: Donor-blinded discrimination (pooled out-of-fold ROC-AUC) was 0.775 for the clinical-only model, 0.814 for the FTIR-only model, and 0.796 for the combined model; probabilistic accuracy (Brier score; lower is better) was 0.162, 0.194, and 0.177, respectively. Calibration intercepts were negative and slopes were <1, indicating overly extreme risk estimates under strict donor-blinded validation and supporting recalibration prior to deployment. Decision curve analysis suggested a positive net benefit for clinically plausible thresholds. Conclusions: These findings support the feasibility of rapid, low-cost FTIR profiling of routinely available preservation fluid as a proof-of-concept approach for exploratory DGF risk stratification, rather than as a clinically deployable prediction tool. Given the small sample size and the instability of subgroup estimates, the main next steps are external validation in larger multicenter cohorts, prospective workflow studies, and model updating/recalibration. Full article