Fusarium, an omnipresent fungus is known for its pathogenic potential. Pathogenic fungi like all other organisms need iron and are known to produce siderophores for iron acquisition. Siderophore producers possess transporters for their own siderophore as well as for siderophores secreted by other organisms known as xenosiderophore. Although iron is an essential nutrient it can also cause oxidative stress and cell-death at high concentrations. While siderophore utilization is employed by the fungi for efficient iron acquisition, it can be exploited against them by supplying xenosiderophore exogenously in turn increasing iron uptake that might prove lethal. A xenosiderophore-iron transporter MirA has been identified earlier in Aspergillus nidulans for the transport of bacterial siderophore enterobactin. MirA has not yet been identified in Fusarium spp. Present study is a computational analysis that focuses on searching possible orthologs of MirA in Fusarium and predicting its structure using deep-learning-based structural prediction and validation approaches. Docking confirmed binding of predicted Fusarium MiRA transporters with the enterobactin-Fe complex, and the most stable complex was further analyzed by molecular dynamics simulations. RMSD, RMSF, Rg, and SASA analyses demonstrated that interaction with the enterobactin-Fe complex stabilizes the MirA structure, supporting its functional adaptation for siderophore-chelated iron binding. In silico findings are further supported by experimental validation that shows growth inhibitory effect of catecholate siderophore produced by Escherichia coli on Fusarium sp. through anti-fungal plate assay, dry weight estimation and morphological changes through microscopy using LPCB staining. The results suggest possible involvement of MirA in xenosiderophore-mediated biocontrol via siderophore-iron uptake.
Background: Prostate cancer (PCa) is the most diagnosed cancer among men globally and a leading cause of cancer-related mortality. However, current conventional prostate diagnostic methods fail to meet the growing demands of clinical practice in terms of speed, simplicity, sensitivity, and specificity. To address these limitations, we established a molecular detection system based on MIRA-CRISPR/Cas12a technology. Using reverse transcription-multienzyme isothermal rapid amplification (RT-MIRA) to amplify minute PCA3-specific fragments in samples, we employ CRISPR/Cas12a to detect the fluorescence signal released by these fragments, enabling the detection of trace PCA3 molecules in urine. Methods: PCA3 standard strain cultivation and total RNA extraction; establishment and optimization of the MIRA amplification system using primers designed for the PCA3 molecular marker; design of crRNA targeting optimal sites within the detection sequence, combined with CRISPR/Cas12a technology to establish the detection system; preliminary validation of the technology's sensitivity and specificity. Results: the MIRA-CRISPR/Cas12a technology was successfully established for visual detection of PCA3 molecules in prostate cancer. Primer and crRNA sequences within the reaction system were determined. The detection sensitivity for PCA3 molecules in urine reached 1 × 100 copies per µL with excellent specificity. Conclusion: the MIRA-CRISPR/Cas12a technology enables specific detection of PCA3 molecules in urine. This technique features high sensitivity, high specificity, visual results, and simple operation. It does not require specialized laboratory UV imaging equipment; results are visible to the naked eye under LED blue light. Following further optimization, it offers a feasible technical solution for rapid molecular screening of prostate cancer.
Hepatopancreatic necrosis disease (HPND), which was linked to infections by the microsporidian Hepatospora eriocheir, was a disease of high mortality and prevalence that had caused significant losses in Chinese mitten crab (Eriocheir sinensis) aquaculture. In this study, two molecular detection methods, TaqMan quantitative PCR and multienzyme isothermal rapid amplification (MIRA) , were successfully established after designing specific primers and probes targeting the H. eriocheir CHI4 gene. The developed standard curve for TaqMan qPCR was y = -3.1654x + 43.925 (R2 = 0.9977), with an amplification efficiency of 107%. After optimization of the reaction conditions, MIRA was able to detect H. eriocheir in 25 min. Specificity tests confirmed that TaqMan qPCR and MIRA targeting H. eriocheir had no cross-reactivity with Enterocytozoon hepatopenaei, Vibrio parahaemolyticus, Spiroplasma eriocheiris, white spot syndrome virus, and decapod iridescent virus I. The sensitivity detection result revealed that the minimum detection limit of TaqMan qPCR and MIRA was 4.6 × 101 copies/μL and 4.6 × 100 copies/μL, respectively, while the minimum detection limit of PCR was 4.6 × 103 copies/μL. TaqMan qPCR and MIRA detection methods of H. eriocheir were established in this study and could be used for early diagnosis of HPND.
Largemouth bass (Micropterus salmoides) is an important freshwater-cultured species in China. M. salmoides rhabdovirus (MSRV) is a devastating pathogen that causes high mortality (exceeding 90% in acute outbreaks) in largemouth bass fry, posing a severe threat to the global largemouth bass aquaculture industry. To address the urgent demand for rapid, on-site MSRV detection, two multienzyme isothermal rapid amplification (MIRA)-derived methods-multienzyme isothermal rapid amplification with fluorescence detection (MIRA-FLU) and multienzyme isothermal rapid amplification with lateral flow dipstick (MIRA-LFD)-were established and optimized targeting the conserved nucleoprotein (N) gene of MSRV. The performance of both methods was systematically evaluated, and their practical applicability was verified using clinical samples collected from diseased fish farms. The results demonstrated that both methods exhibited high sensitivity, with a detection limit of 9 copies/μL for the standard plasmid. Both detection methods demonstrated high specificity and showed no cross-reactivity with other common aquatic viruses, indicating their high specificity for MSRV detection. MIRA-FLU completed amplification within 25 min at 42°C, while MIRA-LFD achieved amplification within 12 min at 37°C. MIRA-FLU is used for real-time fluorescent quantitative detection, whereas MIRA-LFD enables visual, instrument-free reading via lateral flow test strips. In comparative analyses of clinical samples, the diagnostic results of MIRA-FLU and MIRA-LFD were compared with those of the standard conventional PCR test and showed nearly 100% consistency. Therefore, our MIRA-FLU and MIRA-LFD detection methods demonstrate excellent specificity and sensitivity, providing two simple, rapid and reliable approaches for large-scale field surveys of MSRV in resource-limited settings.
The expeditious and precise diagnosis of dengue virus (DENV) and chikungunya virus (CHIKV) is paramount for effective patient management and the control of outbreaks. In this study, a duplex reverse transcription multi-enzyme isothermal amplification (RT-MIRA) assay was established for the simultaneous detection of DENV and CHIKV, followed by a nested RT-MIRA assay for DENV serotyping (DENV-1 to -4). Specific primers and probes targeting the DENV 3'-UTR, CHIKV E1 gene, and four DENV serotypes were designed. The duplex RT-MIRA and nested DENV RT-MIRA serotyping reaction systems were optimized at 39 °C with portable fluorescence or lateral flow dipstick readouts. For methodological validation, specificity was evaluated against 35 related pathogens, and the 95% limit of detection (LOD95) was determined via probit regression. For clinical validation, serum samples from 236 suspected patients were tested, benchmarking against RT-qPCR and serology. Statistical analyses included the Wilson score method for calculating 95% confidence intervals (CIs) and Cohen's kappa (κ). For external verification, 12 CHIKV-positive clinical samples and 5 artificially simulated co-infection samples were retrospectively analyzed to validate assay accuracy. The duplex RT-MIRA assay exhibited no cross-reactivity with other pathogens. The LOD95 values were 13.47 copies/μl for DENV and 10.49 copies/μl for CHIKV. Clinical validation demonstrated sensitivities of 96.15% (95% CI: 89.28%-98.67%) for DENV and 88.89% (95% CI: 67.20%-96.90%) for CHIKV. Specificity was 100% (95% CI: 92.87%-100%) for both. Agreement with RT-qPCR was strong for DENV (κ = 0.96) and CHIKV (κ = 0.92). The nested RT-MIRA serotyping assay showed high sensitivity (LOD95: 1.6-18.7 copies/μl) without cross-reactivity, accurately differentiating 75 DENV-positive samples into 71 DENV-1 and 4 DENV-2. In the external verification, the assay accurately detected 10 CHIKV mono-infections and 2 CHIKV/DENV co-infections, and distinguished four DENV serotypes in simulated matrices. A rapid and sensitive integrated method has been developed that combines duplex RT-MIRA for detecting DENV and CHIKV, and nested RT-MIRA for serotyping DENV. The simplicity and speed of the amplification and detection steps demonstrate this platform's potential for use in point-of-care testing and surveillance in areas with limited resources, particularly when used alongside portable extraction methods.
Purpose To develop a fine-tuned large language model (Medical Imaging Report Assistant [MIRA]) and evaluate its performance in generating radiology impressions from multicenter data with respect to accuracy, reporting efficiency, and clinical applicability. Materials and Methods A retrospective multicenter dataset comprising 1.87 million radiology reports (including CT, MRI, and digital radiography data) from 42 hospitals across 22 provinces in China (January 2019-August 2024) was compiled. The dataset was used to fine-tune a large language model via a prompt-based strategy. The evaluation framework incorporated both automated and human evaluation metrics. Radiologists evaluated internal and external datasets and three open-source datasets to compare impressions generated by the fine-tuned large language model and GPT-4o (Open AI). Twenty-four radiologists from six centers performed blinded comparisons of MIRA-generated and reference impressions to assess interrater consistency and drafting efficiency. Data were analyzed using appropriate parametric and nonparametric tests and χ2 tests, with Holm-Bonferroni correction for multiple comparisons. Results The internal test set included data for 78 544 reports (median age, 52 years; IQR, 35-65 years; 39 351 male), and the external test set included data for 27 471 reports (median age, 53 years; IQR, 37-66 years; 13 955 male). Site- and modality-aware prompting improved similarity (internal BERTScore F1 and sentence similarity, 0.92 and 0.92, respectively; external BERTScore F1 and sentence similarity, 0.82 and 0.80, respectively, under optimal settings; P < .001). Human evaluation (n = 2327) showed MIRA beat GPT-4o on both similarity and F1 score (P < .001). MIRA-generated impressions were rated as at least as good as the reference impressions in 69.0% (1657 of 2400) of blinded comparisons, reduced draft time by 0.46 minutes per report, and increased interradiologist agreement (P < .001). Conclusion MIRA, a fine-tuned large language model using a prompt-based strategy, generated clinically aligned radiology impressions in multicenter settings, improving accuracy, efficiency, and reporting consistency. Keywords: Computer-aided Diagnosis, CAD, Supervised Learning, Transfer Learning, Conventional Radiography, MRI, Computer Applications-General Informatics, Statistics Supplemental material is available for this article. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license.
Nepal has significantly improved maternal health service coverage, including antenatal care (ANC), with a growing focus on quality care. The mobile health Integrated Rural Antenatal care (mIRA) project evaluated an electronic decision support system (EDSS) to improve ANC quality in primary healthcare facilities. This sub-study was undertaken within the context of a mixed-method evaluation. It aimed to explore how auxiliary nurse midwives (ANMs) implemented the EDSS and to provide insight into the real-world challenges and processes of the mIRA implementation project. We conducted a focused ethnography in four primary health facilities, where ANMs implemented the EDSS. Data were collected between December 2021 and January 2023 and involved repeat ethnographic observations, informal conversations, formal interviews (n = 16), and validation workshops for participants to respond to and reflect on findings. The data were analyzed thematically, drawing on street-level bureaucracy theory. ANMs verbalized they valued the EDSS, but this was not reflected in their use of it. ANMs adopted the EDSS primarily for recordkeeping and did not comply with care recommendations that conflicted with their usual way of working. ANMs viewed themselves as providing care for normal pregnancies and believed that quality was not an issue, as they felt they were already delivering good care at their level. This perception, coupled with a risk-averse attitude, led them to refer cases to doctors or higher centers rather than implement the EDSS recommendations. The EDSS recommendations to improve the quality of ANC did not align well with ANMs' usual practices, which were influenced by contextual factors and the complexities of organizing ANC in primary health facilities. By triangulating longitudinal data collected through multiple methods, the study provided a comprehensive insight into ANC provision in Nepal, revealing the challenges associated with improving quality, unpacking the realities of intervention implementation, and highlighting the disconnects between rhetoric and practice.
Seijas Naya, F. Bernabeu Mira, J., C. Pérez Jardón, et al. "Influence of Abutment Shape on Implant Marginal Bone Remodeling: A Double-Blind, Randomized 24-Month Clinical Study." Clinical Oral Implants Research 1-11; https://doi.org/10.1111/clr.70085 DESIGN: A 24-month follow-up of a split-mouth randomised clinical trial with two parallel experimental groups: straight aesthetic antirotational abutments (Nueva Galimplant, Sarria, Spain) and concave antirotational abutments (Nueva Galimplant, Sarria, Spain). This continuation study, with 24-month post-loading data, re-analysed the 8 week post-placement and 6 month post-loading data, from the original study1. The primary outcome defined in the protocol was stability, measured as Implant Stability Quotient (ISQ), and secondary outcomes were Marginal Bone Loss (MBL), and Probing Depth (PD). 30 partially dentate patients (n = 80 implants) who required at least two posterior implants to be restored with single-unit crowns, were recruited at a secondary care academic department. Adults over 20 years old, who smoked less than 5 cigarettes per day, were at least 6 months post-extraction with healed bone able to accommodate 4 mm diameter and 10 mm length implants, without hard or soft tissue augmentation, were considered. Implants were placed transmucosally 4 mm from the future gingival margin, 1 mm below the alveolar crest, utilising 2 mm or 3 mm height abutments. Healing caps were removed at 8 weeks and outcomes measured, the implants were then loaded with crowns and outcomes measured again at 6- and 24-months post-loading. A per-protocol analysis was done using independent-sample t-tests for dichotomous variables and paired-sample t-tests for intra-group bone level changes. Mixed linear regression models were used to assess the impact of abutment type and height on MBL, with individual variations weighted based on implant count per patient. Generalised Additive Models were also constructed. There was no statistical difference in stability, measured through ISQ, between groups at 24 months. There was no statistical difference in PD, bleeding and plaque scores either. At 8 weeks post placement, prior to loading, there was a statistically significant (p = 0.002) difference in MBL: straight abutments had an average of 0.54 mm (95% confidence interval 0.35 to 0.73) and concave abutments of 0.18 mm (95% confidence interval 0.05 to 0.31). A linear mixed-effects regression model was used to evaluate changes in marginal bone levels. Overall, implants restored with concave abutments showed significantly less MBL than those with straight abutments. The model also indicated that this difference appeared early after loading and remained consistent over the follow-up period. In addition, greater abutment height was associated with reduced MBL, suggesting a protective effect of increased abutment height independent of abutment type. Two implants 'failed' and one abutment fractured. Of the 12 implants excluded from the analysis, two had abutment fractures and four crown fractures, the rest were lost to follow-up. Concave abutments in this cohort had the same MBL at 24 months compared to straight abutments and had no effect on implant stability (ISQ) or periodontal indices such as, bleeding on probing, and PD. At 8 weeks there was a small disparity, less than 0.5 mm difference in MBL, but this appears to be clinically insignificant regarding the final 24-month MBL value.
The Par complex regulates cell polarity in diverse animal cells, but how it is restricted to a specific membrane domain remains unclear. The tumor suppressor Lethal giant larvae (Lgl) is thought to inhibit Par complex membrane binding, yet in metaphase Drosophila neural stem cells (NSCs), Lgl is cytoplasmic while the Par complex is apically polarized, raising the question of how Lgl controls Par localization when it is not on the membrane. Using live imaging, we found that Lgl and atypical Protein Kinase C (aPKC) exhibit tightly coordinated, opposing membrane dynamics: aPKC displaces Lgl at mitotic entry, while Lgl displaces aPKC at mitotic exit. In Lgl-depleted NSCs, aPKC is not fully cleared from the membrane after mitosis, and this residual aPKC persists into the subsequent division, disrupting Miranda polarization. Apical aPKC recruitment still occurs, indicating that Lgl is not required for Par polarization per se, but rather for ensuring aPKC absence from the basal membrane before mitosis. These findings reveal a temporal mode of mutual antagonism between Lgl and the Par complex that may license proper asymmetric division.
The primary objective of this study was to evaluate the effects of injectable platelet-rich fibrin (I-PRF), titanium-prepared platelet-rich fibrin (T-PRF), and 0.8% hyaluronic acid (HA) gel compared with a naturally healing control group on gingival wound healing and epithelialization following gingivectomy and gingivoplasty in plaque-induced gingival enlargement. Secondary objectives were to assess clinical periodontal parameters and patient-reported outcomes during a 28-day follow-up period. The study included four groups: a control group and three test groups treated with I-PRF, T-PRF, and 0.8% HA gel. All patients underwent gingivectomy and gingivoplasty after the first step of periodontal therapy. Pain and burning were recorded using VAS during the first postoperative week, and analgesic consumption and bleeding were also recorded. Oral health–related quality of life was assessed using OHIP-14. Wound healing was evaluated using Mira-2 Tone staining with digital image analysis, the Landry, Turnbull, and Howley (LTH) wound-healing index, and the H₂O₂ foaming test at days 7, 14, 21, and 28, while clinical periodontal parameters were reassessed at day 28. A total of 60 systemically healthy patients were included in the study: I-PRF (n = 15), T-PRF (n = 15), 0.8% HA (n = 15), and control (n = 15). Significant intergroup differences were observed in several clinical and wound-healing parameters. At day 28, the HA group showed significantly lower gingival inflammation and bleeding compared with the I-PRF, T-PRF, and control groups (p < 0.05). All intervention groups demonstrated improved wound healing compared with the control group. On day 7, the control group exhibited a significantly larger non-epithelialized area (169,440 ± 23,583) than the HA group (122,262 ± 18,363), representing a mean reduction difference of 47,178. LTH wound-healing scores were significantly higher in the intervention groups than in the control group across all time points (all p ≤ 0.005). Pain, burning, and oral health–related quality of life improved significantly over time in all groups (p < 0.001), with the HA and I-PRF groups reporting lower discomfort scores. I-PRF, T-PRF, and HA enhanced epithelial wound healing and patient comfort compared with control, with HA providing superior reductions in gingival inflammation and bleeding. However, due to the subjective nature of some measures and the lack of histological/molecular analyses, further long-term studies are necessary to confirm these clinical outcomes and understand the underlying biological mechanisms. Adjunctive use of HA, I-PRF, and T-PRF may improve soft-tissue healing and patient comfort after gingivectomy. HA may be particularly practical in routine clinical settings because it does not require blood collection or centrifugation. Therefore, the choice of adjunctive treatment may depend on clinical logistics and cost considerations. The online version contains supplementary material available at 10.1007/s00784-026-06860-5.
Methylphenidate (MPH) is a psychostimulant widely used to enhance attention and executive functions through increased dopaminergic and noradrenergic transmission. Although its effects on cognitive performance are well documented, its acute influence on cortical oscillatory activity, particularly α power, during tasks requiring simultaneous motor and cognitive processing remains poorly understood in healthy adults.To investigate the acute effects of 10 mg MPH on absolute α power (8-12 Hz) in frontal regions during a visuomotor task in healthy subjects.A total of 13 right-handed healthy adults (7 men; age 25.6 ± 4.5 years) participated in a randomized, double-blind, placebo-controlled, crossover study. A 20-channel electroencephalography (EEG) was recorded before and after execution of the MIRA visuomotor task (joystick response when a moving target crosses a previously memorized position) under placebo and MPH (10 mg) conditions, with sessions 1 week apart. Absolute α power was compared using two-way ANOVA (condition vs. moment: pre- vs. post-joystick press), followed by paired t-tests when appropriate.Significant condition versus moment interactions were observed at F3 (p = 0.006), F4 (p = 0.003), and F8 (p = 0.023). The main effects of condition and/or moment occurred at Fp1, Fp2, and Fz (all p < 0.05). The use of MPH attenuated or reversed the typical task-related α desynchronization seen under placebo, especially in right frontal regions.A single 10 mg dose of MPH homogeneously modulates frontal α power during a visuomotor task, promoting sustained cortical activation. This paradigm emerges as a sensitive tool for studying motor-cognitive coupling and may contribute to understanding MPH mechanisms in both healthy and clinical populations.
Ticks of the genus Ixodes are recognized as important vectors of a wide range of viral pathogens with potential implications for public and veterinary health. Recent advances in metagenomic sequencing have uncovered an unprecedented diversity within tick-associated viromes, yet much of the global tick metavirome remains unexplored, particularly in vast and ecologically diverse regions such as Northwestern Russia. In this study, we present a comprehensive metaviromic and phylogenetic characterization of viruses detected in Ixodes persulcatus and Ixodes ricinus ticks collected from five regions in Northwestern Russia between 2021 and 2023. Using high-throughput RNA sequencing, we identified viral sequences representing families Nairoviridae, Partitiviridae, Phenuiviridae, Flaviviridae, Chuviridae, and Narnaviridae, Orthototiviridae. Putative novel viral lineages were identified. Phylogenetic analyses revealed strong geographic structuring of some viral lineages. This suggests either the presence of local genotypes, or underrepresentation of Eurasian tick-associated viromes, in current databases. In addition to TBEV, other viruses previously associated with human illness were detected in ticks in Northwestern Russia (Beiji nairovirus, Mukawa virus). Our findings provide the first high-resolution snapshot of the tick virome in Northwestern Russia. They emphasize the importance of continued viral surveillance in underrepresented biogeographic zones. These data contribute to the growing global virome map and may inform the development of region-specific vector-borne disease countermeasures.
Despite recent advances in technology to map RNA chemical modifications transcriptome-wide, the distribution of N1-methyladenosine (m1A) in messenger RNA (mRNA) remains contested, hindering a clear understanding of its function. Additionally, the enzyme(s) that installs the majority of reported mRNA m1A sites has yet to be identified. In this study, we characterized TRMT61B, an m1A methyltransferase known to methylate mitochondrial RNAs, but whose sequence preferences have been underexplored. By integrating cellular overexpression of TRMT61B and in vitro methylation of a synthetic pool of diverse human mRNA sequences, we identified a preference for a YMRA consensus motif in single-stranded RNA regions. In these experiments, TRMT61B methylated thousands of novel human mRNA sites, revealing activity on cytosolic mRNAs. We used these novel m1A-modifiable sequences to test the effects of m1A on translation of luciferase reporters and on ribosome recruitment to modified transcripts in the pool. We found that m1A addition can significantly affect translation and ribosome recruitment, but that these effects vary by transcript. Taken together, our results inform future studies of TRMT61B and mRNA modifications, and emphasize that studies of m1A regulation of mRNA must be carried out and interpreted in a highly context-aware manner.
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The optimal intake of artificial nutrition in critically ill patients remains unclear. While calorie and protein intakes affect glomerular function in patients with chronic kidney disease, their relation to renal function at the acute phase of intensive care is insufficiently documented. We aimed to study associations of a low-calorie and low-protein diet with renal outcomes in critically ill patients. This post hoc analysis of the NUTRIREA-3 randomized-controlled trial included 3036 mechanically ventilated patients with shock. Calorie and protein intakes during the first 7 days were either low (6 kcal/kg and 0.2-0.4 g protein/kg/d) or standard (25 kcal/kg and 1.0-1.3 g protein/kg/d). The primary outcome was the incidence of acute kidney disease (AKD) during the ICU stay (up to ICU discharge or day 90 after inclusion, whichever occurred first). AKD during the ICU stay occurred in 669 (44.6%) low-group patients and 691 (46.1%) standard-group patients (hazard ratio, 0.97; 95% CI 0.88-1.07; P = 0.53). The highest urea level and the urea level at ICU discharge were significantly lower in the low group (P = 0.002). No differences were found for renal replacement therapy requirements or other renal outcomes. The results were similar in patients with early kidney dysfunction, severe organ failures, or end-stage chronic kidney disease. In critically ill patients with shock, early low-calorie and low-protein nutrition for 7 days was not associated with worse renal outcomes or mortality compared to standard feeding, even in patients with preexisting renal dysfunction.
We demonstrate an exceptional radiation hardness of thin films of pristine fullerene C60 and its organic derivative phenyl-C61-butyric acid methyl ester (PC61BM) in lateral resistor and field-effect transistor device geometries under exposure to ultra-high doses of 60Co gamma rays approaching 5-8 MGy (5-8 MRad). The obtained results exhibit the great promise of organic semiconductors for the development of radiation-hard electronics for outer space exploration and other extreme environments.
The prevalence of food allergy (FA) is increasing worldwide and becoming more widely recognized as a public health concern. Estimates of FA prevalence have relied on heterogenous methodologies across studies making it difficult to compare patients' groups or to generalize findings. This study aims to report the prevalence of FA in the general population across multiple countries using a standardized methodology. This was a cross-sectional, international, population-based study including children, adolescents, and adults from 9 countries (USA, Canada, UK, France, Germany, Italy, Spain, Japan, and China). Participants completed an online questionnaire developed to recognize FA based on different levels of evidence. The prevalence of FA was estimated based on data indicative of symptom-convincing FA to at least one allergen. A total of 46,711 children and 44,219 adults participated in the study. The prevalence of symptom-convincing FA in children was the highest in Canada and the lowest in Germany; 7.5% versus 2.4% respectively. Among adults, the highest prevalence was 6.6% in Italy, and the lowest was 2.1% in Japan. In both age groups, the majority had FA to only one allergen. Peanut, milk and/or dairy products, and tree nut were the most identified allergens in children, while peanut, shrimp, and shellfish were the most common among adults. This study is one of the few that have comprehensively assessed FA globally, offering consistent evidence that FA is prevalent internationally and across age groups, making itself a public health burden that affects a wide spectrum of demographics.
As home-based care expands globally, informal caregivers are responsible for medical and nursing responsibilities, raising serious concerns about safety and risk management. This study proposes expert-informed, safety recommendations tailored to informal caregiving in home settings. The study used a six-phase mixed methods design combining a Consensus Development Conference (CDC) process with elements of Failure Modes and Effects Analysis (FMEA). In the first five phases, 13 healthcare professionals, hereafter referred to as "the professionals" (10 nurses, one physician, one occupational therapist, and one social worker), engaged in deliberations and risk assessments. The professionals agreed on 15 caregiving domains such as medication administration, mobility, and caregiver well-being, mapped them to 53 home caregiving procedures, identified 160 potential failure modes (errors), and rated the effect severity of each failure mode. This process led to the development of an initial set of 450 safety recommendations. In the final phase, a multidisciplinary expert review conducted by the research team merged overlapping items, eliminating redundancies and ensuring accuracy, confirming 53 procedures, 147 distinct failure modes (errors), refining 213 procedure failure mode effect associations, and consolidating the corpus to 288 recommendations. The resulting recommendations are intended to guide the development of safety guidance for informal caregiving in home settings. These recommendations are considered expert-derived guidance, since end users did not participate in the study.
Study DesignNetwork Meta-Analysis.ObjectiveTo compare the efficacy and safety of osteobiologics used in posterior lumbar spinal fusion (LSF) for degenerative lumbar disorders, setting autologous iliac crest bone graft (AICBG) as the reference standard.MethodsA systematic search of randomized controlled trials (RCTs) evaluating osteobiologics in adult patients undergoing posterior LSF was performed. Primary outcomes were radiologic fusion and osteobiologic-related complications. Secondary outcomes included disability, low back pain, operative time, blood loss, and length of stay (LOS). A frequentist random-effects network meta-analysis (NMA) was performed. Meta-regression was employed to assess the influence of surgical technique on primary outcomes. Risk of bias was evaluated using the Cochrane RoB-2 tool, and certainty of evidence was assessed with the GRADE framework.ResultsThirty-five RCTs including 2298 patients were analyzed. Compared with AICBG, recombinant human bone morphogenetic protein-2 (rhBMP-2) showed significantly higher fusion rates (OR 3.86; 95% CI 2.60-5.74; P < 0.0001) and lower complication risk (OR 0.50; 95% CI 0.34-0.73; P = 0.0004). Disability and pain outcomes were comparable across treatments. rhBMP-2 (MD -21.8 minutes; 95% CI -28.0 to -15.7; P < 0.0001), autologous local bone (MD -12.0 minutes; 95% CI -21.5 to -2.5; P = 0.0133), and ABM/P-15 (MD -17.0 minutes; 95% CI -32.6 to -1.5; P = 0.0322) were associated with shorter operative time. Only rhBMP-2 significantly decreased blood loss (MD -72.6 mL; 95% CI -118.9 to -26.4; P = 0.002), while no treatment reduced LOS.ConclusionsAmong evaluated osteobiologics, rhBMP-2 demonstrated superior efficacy and safety compared to AICBG in posterior LSF. Other agents showed favourable trends without statistical significance, reflecting persistent uncertainty rather than confirmed equivalence.