Search Results (348,110)

Background: Long-acting monoclonal antibodies have become an important strategy for preventing respiratory syncytial virus (RSV) disease in infants. Nirsevimab is the first product for which substantial post-licensure implementation data are available, whereas real-world evidence on clesrovimab remains limited. Although nirsevimab has demonstrated high efficacy, its uptake varies considerably across countries, healthcare systems, delivery settings, and population subgroups. This World Association for Infectious Diseases and Immunological Disorders (WAidid) consensus document examines the policy, organizational, economic, and equity-related determinants that shape real-world implementation of long-acting monoclonal antibodies for infant RSV prevention. Methods: This study was conducted as a structured narrative review and WAidid expert consensus document. A structured literature search was performed in PubMed and Embase for English-language publications relevant to nirsevimab uptake and implementation, complemented by targeted review of surveillance reports, policy documents, and public health guidance from the ECDC, UKHSA, and CDC, as well as reference lists of selected publications. Eligible sources included observational and real-world implementation studies, systematic reviews and meta-analyses, economic evaluations, guidelines, policy statements, surveillance reports, and relevant narrative reviews. Evidence was synthesized qualitatively according to policy frameworks, financing and reimbursement, delivery pathways, demographic and socioeconomic determinants, and healthcare-system factors influencing uptake. No statistical software was used because no quantitative re-analysis or meta-analysis was performed. Results: Nirsevimab uptake was strongly influenced by national RSV prevention policies, particularly whether countries adopted universal infant monoclonal antibody programs, maternal RSV vaccination strategies, dual maternal–infant approaches, or targeted risk-based models. Universal, publicly funded programs integrated into neonatal care achieved the highest and most homogeneous coverage, especially when administration occurred before hospital discharge and was supported by registry-based recall systems for infants born outside the RSV season. In contrast, fragmented, outpatient-only, insurance-dependent, or partially reimbursed models were associated with lower, delayed, or more variable uptake. Additional determinants included product cost, reimbursement pathways, provider practices, caregiver awareness and health literacy, insurance status, income, race and ethnicity, geographic deprivation, and access to primary pediatric care. Most available evidence comes from high-income countries, limiting generalizability to low- and middle-income settings, where RSV burden is greatest and implementation constraints may differ. Conclusions: Successful implementation of long-acting monoclonal antibodies for infant RSV prevention requires more than regulatory approval and demonstrated efficacy. Equitable uptake depends on clear national recommendations, sustainable public financing, reliable product supply, integration into neonatal and primary pediatric care, proactive identification and recall of eligible infants, and targeted strategies to reduce socioeconomic and geographic disparities. Although many determinants identified in high-income settings are likely relevant globally, their feasibility, relative importance, and impact require dedicated evaluation in low- and middle-income countries. Full article

This study aimed to investigate the production of color-enriched oleogels using sunflower oil enriched with natural pigments, and to evaluate their potential as fat replacers in cookie formulations. Tomato, carrot, and spinach were used as natural color sources to obtain red, orange, and green colored oils, which were subsequently structured with candelilla wax to produce colored oleogels. The physicochemical, structural, oxidative, textural, and color properties of both oils and oleogels were evaluated. Oleogel’s performance was further assessed in cookie systems compared with margarine-based control formulations. The results showed that all oleogels exhibited high oil-binding capacity (99.44–99.84%) and stable gelation behavior. Oxidative stability analysis indicated a tendency for peroxide, free fatty acid, and p-anisinide values to increase during storage. FTIR analysis confirmed that no chemical modification occurred in the lipid structure, indicating that oleogel formation was governed by physical interactions. Color analysis demonstrated that pigment incorporation significantly affected L*, a*, and b* values, while spinach oleogel showed superior color stability over 90 days. Oleogel-based cookies generally exhibited lower hardness and higher spread ratios (4.71–5.38) than the margarine control (3.04), while their expansion ratios (137.50–162.50%) were lower than that of the control (212.50%); however, baking weight loss remained unaffected. This study demonstrates that naturally pigment-enriched oleogels can serve as healthy fat replacers within clean-label bakery product development. Full article

Glucose and lipid metabolism disorders are closely associated with type 2 diabetes mellitus (T2DM), obesity, hyperlipidemia, and metabolic dysfunction-associated steatotic liver disease (MASLD). Gynura divaricata (L.) DC., traditionally consumed as both a food and folk medicine, has attracted increasing attention for its potential regulatory effects on glucose and lipid metabolism. Existing in vitro and in vivo studies suggest that G. divaricata extracts and candidate bioactive constituents, including flavonoids, polysaccharides, phenolic acids, and peptides, may improve metabolic phenotypes such as hyperglycemia, dyslipidemia, and insulin resistance. These effects may involve the regulation of intestinal carbohydrate hydrolysis, insulin signaling, gut microbial homeostasis, pancreatic β-cell function, lipid metabolism, oxidative stress, and chronic inflammation. However, human evidence remains limited, and most studies have investigated compound formulations or combined interventions, which are insufficient to establish the clinical efficacy of G. divaricata as a standalone preparation. This review summarizes the major bioactive constituents of G. divaricata, reviews the current evidence for its glucose-lowering and lipid-regulating effects and related antioxidant and anti-inflammatory mechanisms, and discusses the limitations of existing research. This study aimed to provide a reference for elucidating the mechanisms by which G. divaricata regulates glucose and lipid metabolism and for its future clinical translation. Full article

The maneuverability standards established by the International Maritime Organization (IMO) primarily address merchant ships, while large fishing vessels generally fall outside their scope. This study investigated the relationships between selected design characteristics and maneuvering performance using full-scale trial data from four large fishing vessels. Their principal design characteristics and maneuvering indices were compared with the distributions of a 226-ship merchant-ship database and with four reference merchant ships for which complete design and trial data were available. The fishing-vessel cases were positioned toward the lower ranges of the available merchant-ship distributions for L/B and C_b/(L/B), whereas their B/d values substantially overlapped the principal merchant-ship range. Their P/Δ values were higher than those of the four reference merchant ships. Within the four fishing-vessel cases, B/d and P/Δ showed the most apparent tendencies with the Turning indices, L/B and C_b with the Zig-zag Overshoot angles, and C_b and P/Δ with Track reach/L. These observations indicate that the design variables associated with the most apparent tendencies differed among turning, course-checking, and stopping responses. Although the limited dataset does not permit statistical generalization or the establishment of causal relationships, the results suggest that the maneuvering characteristics of large fishing vessels are better characterized by considering combined hull-form and propulsion characteristics together with the balance among multiple maneuvering responses, rather than by interpreting individual design variables in isolation. These full-scale observations provide a basis for further systematic investigation and maneuverability assessment of large fishing vessels. Full article

Background: Lactiplantibacillus plantarum is a widely studied probiotic species; however, probiotic characteristics and safety profiles are strain-specific, requiring independent evaluation. This study characterized Lactiplantibacillus plantarum ATA-LPC98052 as a candidate probiotic raw material. Methods: ATA-LPC98052 was evaluated for hemolysis, acid/bile tolerance, Caco-2 adhesion, cytotoxicity, and storage stability. Subacute oral safety was assessed in Wistar rats by gavage for 28 days at 1.2 × 10¹¹ CFU/kg/day; the study design incorporated selected principles of OECD Test Guideline 407. Clinical, hematological, biochemical, organ-weight, and macroscopic endpoints were evaluated. Fecal microbiota was analyzed by 16S rRNA sequencing; WGS was used for taxonomic confirmation and genomic safety screening. Results: ATA-LPC98052 was γ-hemolytic and maintained 60% viability at pH 1.5 and 96% at pH 5.0, while viability ranged from 74% to 82% across 0.1–0.5% bile salt concentrations. Caco-2 cell viability was 99%, adhesion exceeded 90%, and the lyophilized preparation remained stable for 15 months, maintaining 9.6 log₁₀ CFU/g. Repeated oral administration caused no mortality or consistent treatment-related toxicological pattern. Longitudinal microbiota analysis showed no significant treatment × time effects on alpha diversity or Bray–Curtis community structure, and no genus-level MaAsLin2 association was FDR-significant. WGS confirmed L. plantarum identity and no contamination; ResFinder detected no acquired antimicrobial resistance determinants meeting specified thresholds, whereas CARD/RGI identified low-identity qacJ and vanY homologs requiring cautious interpretation. Conclusion: ATA-LPC98052 demonstrated favorable in vitro probiotic characteristics, technological stability, gut microbiota-modulating potential, and a favorable subacute safety profile under the tested conditions; however, microbiota findings were exploratory, and phenotypic MIC testing remains warranted. Full article

Aims: International diabetes guidelines recommend inpatient glycaemic management protocols for bolus enteral feeding in people with diabetes to improve clinical outcomes. This study aims to evaluate before and after hospital-wide implementation of an inpatient bolus enteral feeding protocol: (1) the incidence of hyperglycaemia (>13.9 mmol/L) and hypoglycaemia (<4.0 mmol/L), (2) medication prescribing practices and capillary blood glucose monitoring and (3) health care professionals’ knowledge and confidence levels. Methods: We implemented an inpatient glycaemic management protocol for bolus enteral feeding developed by a multidisciplinary team of diabetes nurse educators and endocrinologists and approved by the institutional medical board in July 2024. This before-and-after quality improvement study was conducted over 3 months across eight inpatient wards. Adult inpatients were consecutively enrolled if they met the inclusion criteria: (1) a documented diagnosis of diabetes mellitus, (2) receiving bolus enteral feeding and (3) treatment with glucose-lowering medication. Patients listed as critically ill were excluded. Nurses working in the pilot wards were also recruited. Before implementing the protocol, diabetes nurse educators trained inpatient nurses on understanding and executing the protocol for administering capillary blood glucose monitoring and medications for patients with diabetes on enteral feeding. Nurses’ pre- and post-knowledge levels and perceived confidence were assessed using a structured questionnaire. Electronic medical records were reviewed to evaluate the incidence rates of hypoglycaemia and hyperglycaemia before and during the 3 months following protocol implementation. We also assessed adherence to protocol-recommended capillary blood glucose monitoring frequencies based on the diabetes medication regimen. Results: A total of 31 patients were observed during the 6-week baseline period and 28 patients following protocol implementation. A total of 192 clinical care episodes were audited, comprising 78 in the pre-intervention phase and 114 in the post-intervention phase. The incidence of hyperglycaemia decreased from 43.6% to 10.5%, while hypoglycaemia decreased from 3.8% to 2.6%. After adjusting for protocol adoption rates, protocol implementation was associated with significantly lower odds of hyperglycaemia (odds ratio [OR] 0.22, 95% CI [0.07, 0.65], p = 0.006). A significant increase in appropriate nursing practices was observed post-intervention (p < 0.001). Adoption of the protocol by nurses decreased the odds of hyperglycaemia by 70% (p = 0.014). Nurses’ knowledge scores improved significantly from baseline to 3 months post-implementation (p < 0.001). Conclusions: Implementation of a standardised inpatient glycaemic management protocol for PWD receiving bolus enteral feeding was associated with reduced rates of hyperglycaemia and hypoglycaemia. Larger-scale studies are warranted to evaluate the effectiveness and sustainability of wider implementation in improving clinical outcomes. Full article

Contemporary mural paintings contribute a significant part of urban cultural heritage, yet their conservation remains challenging due to the complex materials used and the aggressive conditions of the urban environment. Among the main deterioration factors, vandalic graffiti is particularly problematic, as its removal must be carried out without damaging the original paint layer, which often has a similar chemical composition. In this context, laser cleaning is a promising alternative to conventional mechanical and chemical methods. This study evaluates the effectiveness and selectivity of a nanosecond Nd:YAG laser (1064 nm) for the removal of a blue alkyd graffiti spray paint applied over mock-ups prepared with alkyd and polyvinyl acetate (PVA) paints on concrete substrates. The cleaning results were evaluated by stereomicroscopy, colour spectrophotometry, measurement of static contact angle, profilometry, near-infrared (NIR) hyperspectral imaging, Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS) to assess physical and chemical changes after laser treatment. The results show that the effectiveness and selectivity of the process depend strongly on the chemical composition of both the vandalism layer and the original paint system, highlighting the importance of preliminary material characterisation prior to laser cleaning interventions. Although laser cleaning enabled the partial or substantial removal of the blue alkyd graffiti in all cases, alkyd-based paints exhibited greater resistance to laser irradiation and allowed more effective graffiti removal with fewer surface alterations than PVA-based paints. Among them, the green alkyd paint achieved the highest cleaning efficiency. These results indicate that the interaction between laser radiation and the materials was governed not only by the binder type, but also by the pigment composition and the optical properties of the paint layers. Full article

Background: Prostate cancer is one of the most commonly diagnosed cancers in men. Robot-assisted radical prostatectomy (RARP) is one of the recommended surgical treatment options; however, knowledge regarding changes in illness acceptance, psychological adjustment, and quality of life after surgery remains limited. Objective: To evaluate changes in illness acceptance, psychological adjustment, and quality of life in patients undergoing RARP. Materials and Methods: A total of 150 patients diagnosed with prostate cancer and scheduled for RARP were enrolled. Longitudinal analysis was performed in 93 patients who completed both study assessments. Evaluations were conducted before surgery and 3–4 months postoperatively using a self-developed questionnaire, the Acceptance of Illness Scale (AIS), the Mini-Mental Adjustment to Cancer (Mini-MAC), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and the prostate cancer-specific module (EORTC QLQ-PR25). Results: Following RARP, illness acceptance did not change significantly after Holm adjustment (p_Holm = 0.465). Psychological adjustment showed an adverse postoperative pattern, characterised by increased anxious preoccupation, helplessness–hopelessness, and destructive style, together with reduced fighting spirit and constructive style. After adjustment across 25 paired outcome comparisons, significant increases remained in emotional and cognitive functioning scores, while constipation and diarrhoea decreased significantly. Sexual activity also decreased significantly after surgery. Among participants who completed both assessments, incontinence-aid use increased from 15/93 (16.1%) before surgery to 38/93 (40.9%) at follow-up (exact two-sided McNemar test, p < 0.001). Conclusions: During the early postoperative period following RARP, favourable changes were observed in selected quality-of-life scores, whereas illness acceptance did not change significantly after adjustment for multiple comparisons. At the same time, psychological adjustment showed an adverse pattern, characterised by reduced fighting spirit and constructive style together with increased anxious preoccupation, helplessness–hopelessness, and destructive style. Decreased sexual activity and increased incontinence-aid use further illustrate the multidimensional nature of early postoperative recovery. These exploratory findings indicate that favourable changes in selected quality-of-life outcomes do not necessarily coincide with improved psychological adaptation and support the inclusion of psycho-oncological assessment and support in postoperative care. Full article

Background: Classical reverse transcriptase (RT) drug resistance mutations (DRMs) are primary determinants of antiretroviral treatment failure, but polymorphisms within the RT connection and RNase H domains may also influence RT inhibitor susceptibility. These regions remain poorly characterised in HIV-1 subtype C (HIV-1C), the predominant subtype in sub-Saharan Africa. This study investigated RT connection and RNase H polymorphisms in treatment-experienced people with HIV (PWH) experiencing virologic failure (VF) in Botswana. Methods: Seventeen plasma samples from the Botswana National HIV Drug Resistance Programme with documented VF (viral load >200 copies/mL) and prior Sanger resistance results were selected. One sample was excluded because of insufficient Oxford Nanopore Technologies (ONT) sequencing coverage, leaving 16 samples for analysis. Samples were amplified using the DeepChek^® HIV-1 Full PR/RT/INT assay and analysed using the HIVgenomeR™ v2.0 ONT pol DRM pipeline. ONT-derived RT resistance profiles were compared with historical Sanger results, and RT connection and RNase H polymorphisms were characterised. Results: ONT identified additional RT DRMs in five sequences previously classified as lacking classical RT DRMs. Of the remaining six sequences without classical DRMs, four harboured minority RT variants. RT connection polymorphisms were common, including G335D (13/16) and T377M (9/16). Recurrent mutation combinations included T377M–T470A, A371V–E399D, T377M–E399D, and T377M–A360T. Conclusions: The extended HIV-1 pol genotyping assay enabled characterisation of the RT connection and RNase H domains while improving detection of classical RT DRMs and minority variants. These findings support further investigation of extended RT sequencing for HIV-1C molecular surveillance. Full article

Background: In our companion study, the gingival mesenchymal stem cell (GMSC) secretome suppresses oxidative stress and induces apoptosis in primary oral squamous cell carcinoma (OSCC) cells, where those wet-lab results are themselves reported as preliminary; here we ask whether it also engages a proliferation × migration programme in patient tissue. The two arms differ in read-out type (apoptosis and redox there, transcript abundance here), not in opposed function. Methods: Primary OSCC cells received GMSC-conditioned medium (GMSC-CM) or indirect Transwell co-culture, assayed by RT-qPCR (VEGFA, TGFB1, MMP9, CXCL12, CCND1, PCNA, MYC, EGFR), MTT, and scratch-wound migration. Thirteen computational layers plus a GeoMx spatial verify-and-decide layer were applied to public data: TCGA-HNSC, GEO, CPTAC, single-cell inference, prognostic modelling, DepMap and LINCS L1000. Results: All eight transcripts were raised in all three arms (16 of 24 comparisons significant), indicating a pro-tumour transcriptional shift; metabolic activity was unchanged and wound closure was reduced under conditioned medium (p < 0.01). Of 1358 genes significant in all three modalities, 1219 (89.8%, 95% CI 88.0–91.3%) share direction against 25.0% expected by chance (3.59-fold; exact binomial p below machine precision). The pre-registered oral-cavity signature did not validate externally (GSE41613; C = 0.562), and no ligand–receptor pair survived permutation calibration. Conclusions: GMSC paracrine exposure induces a pro-tumour transcriptional programme in primary OSCC cells that replicates at patient level, without demonstrated functional or therapeutic consequence; gefitinib is nominated only as a hypothesis-generating candidate. The evidence rests on three primary cultures (n = 3), one GMSC donor preparation, one 24 h time point, a single reference gene, no cell-line authentication and no test of gefitinib; the study programme has concluded, and these experiments cannot be performed now. Full article

Studying protein structure dynamics is key to understanding protein function modulation. Alternative protein conformations are well discriminated from each other by nanoESI mass spectrometry and ion mobility measurements. Experimentally determined collisional cross-sections were compared to calculated collisional cross-sections of fifteen peptides, single-domain proteins, and protein complexes. The multi-domain proteins investigated here, four immunoglobulin G (IgG) antibodies and protein G, are present as compacted/folded “native” conformations in neutral buffered solutions, and they are identified by molecular ions with narrow charge-state distributions, relatively few charges, and small collisional cross-sections. Simultaneously present extended/folded but nevertheless “native” conformations produced additional ions with higher charge states, different charge-state distributions, and larger collisional cross-sections. Computed collisional cross-sections from compacted “o-shape” and extended “l-shape” protein G three-dimensional (3D) structures match experimental data, indicating equilibrium, and suggest a dynamic “o2l” flip process. Likewise, “m-shape” (compacted) and “Y-shape” (extended) IgGs are regarded as two supposedly reversibly adopted antibody conformations which may interchange by an “m2Y” flip. Adopting an m-shape would prevent an antibody-based initiation of humoral and cellular immune system responses, such as opsonophagocytosis, prior to antigen contact, which stands in line with the rearrangement hypothesis. Full article