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The transplantation of CD34 + hematopoietic stem-progenitor cells (HSPCs) derived from cord blood serves as the standard treatment for selected hematological, oncological, metabolic, and immunodeficiency disorders, of which the dose is pivotal to the clinical outcome. Based on numerous maternal and neonatal parameters, we evaluated the predictive power of mathematical pipelines to the proportion of CD34 + cells in the final cryopreserved cord blood product adopting both parametric and non-parametric algorithms. Twenty-four predictor variables associated with the cord blood processing of 802 processed cord blood units randomly sampled in 2020–2022 were retrieved and analyzed. Prediction models were developed by adopting the parametric (multivariate linear regression) and non-parametric (random forest and back propagation neural network) statistical models to investigate the data patterns for determining the single outcome (i.e., the proportion of CD34 + cells). The multivariate linear regression model produced the lowest root-mean-square deviation (0.0982). However, the model created by the back propagation neural network produced the highest median absolute deviation (0.0689) and predictive power (56.99%) in comparison to the random forest and multivariate linear regression. The predictive model depending on a combination of continuous and discrete maternal with neonatal parameters associated with cord blood processing can predict the CD34 + dose in the final product for clinical utilization. The back propagation neural network algorithm produces a model with the highest predictive power which can be widely applied to assisting cell banks for optimal cord blood unit selection to ensure the highest chance of transplantation success.

A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo , including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.

In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus. Emerging Microbes & Infections (2015) 4, e22; doi:10.1038/emi.2015.22

Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus.

IntroductionNeutropenic fever (NF) has a crude mortality rate of 3–18%. International guidelines recommend that all patients with NF receive ultrabroad-spectrum antibiotics (UBSAs) within 1 hour of emergency department (ED) registration. However, over 70% patients presenting to hospital with suspected NF (sNF) cannot access absolute neutrophil count (ANC) result within 1 hour, do not have NF and do not require UBSAs. In ED and hospitalised patients with sNF, we hypothesise that the ASTERIC protocol effectively and safely reduces the use of UBSAs compared with standard care alone.Methods and analysisThis pragmatic, parallel, multicentre, type 1, hybrid effectiveness-implementation, stepped-wedge, before-and-after, cluster randomised controlled trial aims to evaluate whether antibiotic prescribing can be safely reduced through implementing a multifaceted antibiotic stewardship intervention (ASTERIC) in adult patients with sNF presenting to EDs. The sNF was defined as a fever with a single oral temperature of ≥38.3°C (101°F) within 24 hours before ED registration or a temperature of ≥38.0°C (100.4°F) sustained over a 1-hour period, following last chemotherapy or targeted therapy within 6 weeks for any solid tumour, or in any period following therapies against leucaemia, lymphoma, myelodysplastic syndrome, aplastic anaemia, multiple myeloma or recipient of HSCT. The study will involve eight hospitals in Hong Kong with variable baseline practice. We will include 704 adult patients (352 patients in pre-implementation and post-implementation periods, respectively) with sNF (tympanic temperature ≥38.3°C) and 48 staff participants (6 staff participants in each hospital). Healthcare professionals will receive a multifaceted stewardship intervention consisting of risk assessment tools, fast-track ANCs, a decision tool for patient management and antibiotic use, supported by an educational package and staff interaction programmes (ASTERIC protocol). Patients’ blood ANC, and cancer therapy and chronic illness therapy scores will be measured. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) and Proctor conceptual frameworks will be followed for evaluation of implementation. The main outcome measures are the mean total dose of UBSAs prescribed in 7 days and serious adverse events at 30 days. Data analysis will incorporate intention-to-treat, per-protocol and as-treated analyses for service outcomes (effectiveness, safety, quality of life assessments and cost-effectiveness) and mixed methods for implementation outcomes, informed by the Theoretical Domains Framework. We expect that the study results will inform health policy with improvement in hospital services in treating stable sNF, evidenced by improved safe antibiotic stewardship, early antibiotic de-escalation and reduced costs and length of stay.Ethics and disseminationThe institutional review boards of all study sites approved this study. This study will establish the ASTERIC protocol safely improves antibiotic stewardship and clinical management in adult patients with sNF. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. All patients with sNF will be influenced by the new protocol which is agreed at hospital level. Randomisation is at hospital level, not patient level. Patient consent is sought for follow-up and data access, not for treatment. Staff consent is sought for interviewing.Trial registration numberNCT06794320.

Purpose Catheter cryoablation (CRYO) may eliminate inadvertent atrioventricular block (AVB) in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT). However, higher recurrence was observed with CRYO delivered by 4 mm or 6 mm-tip catheter. This study was performed to investigate whether a comparably low treatment failure and recurrence rate as in radiofrequency (RF) ablation is achievable by CRYO with an 8-mm-tip catheter. Methods This is a retrospective case–control study including 40 patients with AVNRT treated with CRYO ( n  = 20) using an 8 mm-tip catheter or RF ablation ( n  = 20) from March 2009 to March 2011. Treatment failure was defined as the composite of acute procedural failure including inadvertent permanent AVB and documented recurrence. Results Acute procedural success of 90% (18/20) and 95% (19/20) were achieved in CRYO and RF ablation group, respectively ( p  = 0.998), with no permanent AVB in either group. With Kaplan–Meier analysis, there was no significant difference between the treatment groups in terms of recurrence rate (5.6% [1/18] vs. 0%; log-rank test p  = 0.304) and treatment failure (15% [3/20] vs. 5% [1/20]; log-rank test p  = 0.301). Shorter fluoroscopy time (15 ± 8.6 vs. 25.2 ± 12.1 min; p  = 0.005) and more energy applications (median 4 [2–15] vs. 2 [1–8]; p  = 0.005) were observed in the CRYO group compared with RF ablation group. Conclusions Compared to RF ablation, CRYO with an 8-mm-tip catheter for treating AVNRT achieves a comparable acute procedural success, comparably low recurrence rate and composite endpoint of treatment failure. Shorter fluoroscopy time and more energy applications were observed in the CRYO group.

Purpose This study aims to investigate whether the use of a novel inner lumen circular mapping catheter (IMC) can shorten the procedural duration and fluoroscopic exposure of the single transseptal big cryoballoon (CB) pulmonary vein isolation (PVI) procedures in patients with atrial fibrillation (AF). Methods This is a prospective non-randomized case–control study. Forty-two patients (28 men, mean age 55.7 ± 12.1) with drug-refractory paroxysmal or persistent AF and underwent CB PVI procedures were divided into Group A (conventional single transseptal big CB approach, n  = 21) and Group B (IMC-facilitated approach, n  = 21). They were compared in the co-primary endpoints: (1) procedural duration and (2) fluoroscopic exposure and secondary endpoints: (1) 6-month AF-free survival and (2) number of cryo-applications. Results Both the procedural duration (162 ± 26 vs. 215 ± 25 min; p  < 0.001) and fluoroscopic exposure (44.1 ± 10.4 vs. 56.8 ± 11.7 min; p  = 0.001) were significantly shorter in Group B than Group A patients. With multivariate stepwise regression, only the use of IMC was an independent predictor for procedural duration ( β  = −59; 95 % CI, −84.1 to −33.8; p  < 0.001) and fluoroscopic exposure ( β  = −16.9; 95 % CI, −28.4 to −5.4; p  = 0.006). The number of cryo-applications was significantly fewer in Group B than Group A patients (median 8 vs. 11; p  = 0.001). There was no significant difference in the 6-month AF-free survival between the two approaches (57 % vs. 71 %; p  = 0.351). Conclusions Compared to conventional single transseptal big CB PVI procedures, the use of IMC may reduce procedural duration, fluoroscopic exposure and the number of cryo-applications with comparable mid-term efficacy.

Purpose This study aimed to evaluate the utility of a novel pacing guidewire in pre-implantation testing of different left ventricular (LV) sites during cardiac resynchronization therapy (CRT) procedures. Methods Ten consecutive patients (8 male, mean age 65.8 ± 4.9) undergoing CRT procedures were studied. Pacing threshold and R-wave sensing measured by the guidewire and LV lead at different LV sites were compared. Results Thirty sites (6 apical, 13 middle, and 11 basal; 15 lateral and 15 anterior) were tested. There was significant correlation between pacing threshold ( r  = 0.878, p  < 0.0001), and R-wave sensing ( r  = 0.896, p  < 0.0001) obtained by guidewire and those obtained by LV lead. Separating into lateral and anterior sites, significant correlation was also found in pacing threshold (lateral r  = 0.658, p  = 0.008; anterior r  = 0.886, p  < 0.0001) and R-wave sensing (lateral r  = 0.887, p  < 0.0001; anterior 0.865, p  < 0.0001). For basal and middle sites, significant correlation was found in pacing threshold (basal r  = 0.890, p  < 0.0001; middle r  = 0.878, p  < 0.0001), and R-wave sensing (basal r  = 0.930, p  < 0.0001; middle r  = 0.823, p  < 0.001). No and borderline correlation was found in pacing threshold ( r  = 0.548, p  = 0.26) and R-wave sensing ( r  = 0.835, p  = 0.039), respectively, for apical sites. Concordance rate for the presence of phrenic nerve stimulation at high pacing output was 87%. Conclusion The accuracy of the novel pacing guidewire in pre-implantation testing in CRT procedures is site-dependent. There was good correlation with LV lead in the measurement of pacing threshold and R-wave sensing at basal and middle sites, but not apical sites. Presence of phrenic nerve stimulation can be predicted by guidewire testing with high accuracy.

A unique feature of Learning Diversity in the Chinese Classroom is its Chinese context for meeting the educational requirements of children with special needs. At a time when many of the currently available texts in the area have a general perspective, As