Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.

OBJECTIVE: To determine the number of homologous blood transfusions received by canine surgical patients after introducing a cell salvage device (CSD), trends in surgeries requiring blood transfusion, and the incidence of transfusion reactions.
METHODS: Retrospective study.
METHODS: Single referral hospital.
METHODS: All dogs having surgery at a single center (November 2015 to February 2021).
METHODS: Medical records of dogs having surgical treatment, including those that received either an autologous or homologous blood transfusion, were reviewed. The surgical patients were the baseline population, and the 2 transfusion groups were compared within this population to analyze the trends.
RESULTS: A total of 37 and 86 dogs received autologous and homologous blood transfusions, respectively. There was an upward trend in the number of total monthly blood transfusions. No significant increase in the monthly number of homologous transfusions was observed before or after acquisition of the CSD. There was also an upward trend in total monthly surgeries, including those with higher risks of hemorrhage. Dogs receiving homologous blood transfusions had a higher incidence of clinical signs consistent with transfusion reactions (6.98%).
CONCLUSIONS: An upward trend in autologous blood transfusions was seen with the introduction of a CSD. Hospitals with large surgical caseloads at high risk of hemorrhage may see a decreased need for outsourced blood products with the use of the CSD. The device can lead to a more responsible use of an increasingly scarce resource and decrease the risk of a blood transfusion reaction in dogs.

A 34-year-old woman received umbilical cord blood transplantation for refractory T-cell prolymphocytic leukemia after salvage therapy with alemtuzumab. She developed right angular cheilitis on the 46th day after transplantation, which worsened after receiving systemic steroid therapy for extensive chronic graft versus host disease. The treatment dosage of acyclovir (ACV), ganciclovir, and vidarabine ointment was not effective due to ACV-resistant mutations of the herpes simplex virus type 1 (HSV-1) in the thymidine kinase domain. Foscarnet is expected to be effective against ACV-resistant HSV-1 infection. However, it could not be used because the patient developed renal dysfunction. Several viral thymidine kinase mutations related to ACV resistance were found in the patient\'s sample. Nevertheless, amenamevir, a helicase-primase complex inhibitor, was effective in our patient who was significantly immunocompromised after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ACV-resistant HSV infection after allo-HSCT is an rare but important complication in the era of low-dose long-term ACV prophylaxis. To date, there is no established treatment against ACV-resistant HSV infection. This case report showed that amenamevir could be a promising treatment option for ACV-resistant HSV infection in patients with renal failure after allo-HSCT.

BACKGROUND: Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored.
OBJECTIVE: To evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens.
METHODS: The study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals. Assessments included neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA levels.
RESULTS: The study found mRNA vaccines to exhibit superior immunogenicity in primary series vaccination compared to ChAd, with mRNA-1273 significantly enhancing NTAbs, TAbs, anti-S-RBD IgG, and anti-S1 IgA levels (p < 0.001). Both booster types improved antibody levels beyond primary outcomes, with no significant difference in TAbs and anti-S-RBD IgG levels between regimens. However, homologous mRNA boosters significantly outperformed heterologous boosters in enhancing NTAbs and anti-S1 IgA levels, with the BNT/BNT/BNT regimen yielding particularly higher enhancements (p < 0.05).
CONCLUSIONS: The study concludes that although TAbs and anti-S-RBD IgG antibody levels are similar for both regimens, homologous mRNA boosting outperform heterologous regimen by enhancing anti-S1 IgA and neutralizing antibody levels.

Platelet-rich fibrin, the coagulated plasma fraction of blood, is commonly used to support natural healing in clinical applications. The rat calvaria defect is a standardized model to study bone regeneration. It remains, however, unclear if the rat calvaria defect is appropriate to investigate the impact of human PRF (Platelet-Rich Fibrin) on bone regeneration. To this end, we soaked Bio-Gide® collagen membranes in human or rat liquid concentrated PRF before placing them onto 5 mm calvarial defects in Sprague Dawley rats. Three weeks later, histology and micro-computed tomography (μCT) were performed. We observed that the collagen membranes soaked with rat PRF show the characteristic features of new bone and areas of mineralized collagen matrix, indicated by a median mineralized volume of 1.5 mm3 (range: 0.9; 5.3 mm3). Histology revealed new bone growing underneath the membrane and hybrid bone where collagen fibers are embedded in the new bone. Moreover, areas of passive mineralization were observed. The collagen membranes soaked with human PRF, however, were devoid of histological features of new bone formation in the center of the defect; only occasionally, new bone formed at the defect margins. Human PRF (h-PRF) caused a median bone volume of 0.9 mm3 (range: 0.3-3.3 mm3), which was significantly lower than what was observed with rat PRF (r-PRF), with a BV median of 1.2 mm3 (range: 0.3-5.9 mm3). Our findings indicate that the rat calvaria defect model is suitable for assessing the effects of rat PRF on bone formation, but caution is warranted when extrapolating conclusions regarding the efficacy of human PRF.

microRNAs (miRNAs) are short non-coding RNAs that have been increasingly recognized for their significant roles in the progression of cancer. Distinct miRNAs exhibit diverse functions attributed to variations in their sequences. As a result of possessing highly homologous seed sequences, these miRNAs target overlapping or similar gene sets, thus performing analogous roles. However, different from this sight, our study discovered that miR-135a-5p and miR-135b-5p, despite differing by only one nucleotide, exhibit distinct functional roles. Using non-small cell lung cancer (NSCLC) as a paradigm, our findings unveiled the downregulation of miR-135a-5p and upregulation of miR-135b-5p within NSCLC through TCGA database. Consequently, we further investigated their functional differences in A549 cells. Overexpression of miR-135b-5p enhanced the proliferation and migration capabilities of A549 cells, whereas miR-135a-5p transfection exhibited the opposite effect. We demonstrated that the activation of specific enhancers serves as a crucial mechanism underlying the disparate functions exerted by miR-135a-5p and miR-135b-5p in the context of NSCLC, consequently instigating a shift from inhibition to activation in NSCLC progression. Finally, we validated through animal experiments that miR-135b-5p promoted tumor progression, while miR-135a-5p exerted inhibitory effects on NSCLC development. This study offers a novel perspective for researchers to elucidate functional disparities exhibited by highly homologous miRNAs (miR-135a-5p and miR-135b-5p) in the context of NSCLC, along with the transition from inhibitory to progressive states in NSCLC. This study provides a solid foundation for future investigations into the functional roles of highly homologous miRNAs in pathological situation.

Background: The level of adherence to drug therapy after allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) can affect the patient\'s outcome, and poor adherence is one of the factors in first-year mortality after HSCT. Material and Methods: This study assessed adherence to cyclosporine and prednisolone as the immunosuppressant regimen in 110 post-HSCT patients (> 18 years). Demographic characteristics, clinical information, and cyclosporine levels were obtained. A validated Persian medication adherence scale was used to assess adherence to cyclosporine and prednisolone. Results: For 110 patients, the calculated mean of the total score of cyclosporine and prednisolone was 7.73 ± 0.62 and 7.63 ± 0.73, respectively. Poor adherence to medication in this population was 27.7% and 22.7% to prednisolone and cyclosporine, respectively. A significant correlation was observed between adherence total score and cyclosporine levels at the third- and fourth-month post-transplant (r = 0.52, P < 0.001 and r = 0.60, P = 0.001). In the first, second, and third months, the mean of cyclosporine levels in the high adherence level was higher than the moderate and poor adherence levels. Additionally, there was an association between adherence score and the level of cyclosporine. One score increase in adherence scale on average increased cyclosporine level by 34.48 ng/ml. Conclusion: In this study, medication non-adherence was high, which indicates the need for more careful monitoring of post-HSCT patients\' medication use. This is even more crucial currently since it has been confirmed that adherence can affect cyclosporine levels as the most effective immunosuppressant agent in preventing graft-versus-host disease (GVHD).

UNASSIGNED: We previously demonstrated the efficacy of Japanese cedar (JC) pollen sublingual immunotherapy (SLIT) tablets for treating seasonal allergic rhinitis in a clinical trial (trial no. 206-2-1) that covered 5 pollen dispersal seasons from 2015 to 2019.
UNASSIGNED: Our aim was to perform post hoc analysis of the 206-2-1 trial data to evaluate the efficacy of JC pollen SLIT tablets for patients with rhinitis induced by pollen from Japanese cypress (JCY), a related Cupressaceae species that has a pollen dispersal season overlapping with that of JC.
UNASSIGNED: Data were analyzed for 240 patients who received placebo during the first pollen dispersal season in 2015, were then rerandomized to receive JC SLIT tablets (the PA group) or placebo (the PP group) for 18 months (the 2016 and 2017 dispersal seasons), and were observed untreated for 2 years (the 2018 and 2019 dispersal seasons). The PA and PP groups were assigned to \"high\" and \"low\" subgroups if their rhinitis symptoms were exacerbated/did not change or decreased, respectively, during the peak JCY pollen dispersal period in 2015. The mean total nasal symptom and medication scores and other outcomes were compared for the high-PP, high-PA, low-PP, and low-PA groups during the 2016 to 2019 peak JCY pollen dispersal periods.
UNASSIGNED: The mean total nasal symptom and medication scores were significantly lower for the high-PA and low-PA groups than for the corresponding PP groups over the 4 years of treatment and observation. JCY pollen-specific IgE levels increased in both PA groups.
UNASSIGNED: JC pollen SLIT tablets effectively suppressed JCY pollinosis symptoms, supporting the clinical relevance of immunologic cross-reactivity between JC and JCY allergens.

Patients exquisitely sensitive to cashew/pistachio are at risk for allergic reactions to citrus seeds and pectin.
In this study, we sought to evaluate whether pectin is contaminated with citrus seeds, to identify a culprit antigen in citrus seeds, and to assess for cross-reactivity among allergens in citrus seeds, citrus pectin, and cashew or pistachio.
Proteins from orange seed coats, orange seed endosperms, lemon seeds, grapefruit seeds, citrus pectin, apple pectin, and grapefruit pectin were extracted. Protein concentrations in all extracts were determined and visualized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis technique. Immunoglobulin E-binding capacity was determined with Western blot analyses and tandem mass spectrometry for the identification of the culprit allergen in citrus seeds and pectin.
In subjects with citrus seed, pectin, and cashew allergies, there was strong immunoglobulin E-reactivity to bands between 17 to 28 kDa and 28 to 38 kDa. The tandem mass spectrometry analysis of these bands indicated the presence of citrin as the culprit allergen. Citrin and Ana o 2 are both 11S globulins belonging to the cupin superfamily, and significant homology was found between these proteins.
Citrus pectin may be contaminated with citrus seeds. Citrin, a newly identified allergen in citrus seeds, seems to be the culprit antigen in citrus seeds and contaminated citrus pectin. Citrin is highly homologous with Ana o 2 in cashew and Pis v 2 in pistachio, suggesting potential for cross-reactivity and providing an explanation for co-allergenicity of cashew or pistachio, citrus seeds, and citrus pectin.

This study used multilocus sequence typing (MLST) to investigate the prevalence of Helicobacter pylori (H. pylori) mixed infections and H. pylori mixed infections involving unrelated strains; and determined the phylogeographic groups of H. pylori recovered from patients in Ningbo, China. A total of 156 H. pylori isolates were obtained from a convenience sample of 33 patients with culture-positive H. pylori infection. MLST was used to classify 150 H. pylori clinical isolates and 12 methodological control strains (6 clinical isolates and 6 strains of American Type Culture Collection H. pylori) into 43 and 12 sequence types (STs), respectively. In this study, 246 new alleles and 53 new STs were identified by MLST. The prevalence of mixed infections was 41% (11/27). The prevalence of H. pylori mixed infections involving unrelated strains was 46% (5/11) and the prevalence of H. pylori mixed infections involving completely unrelated strains (strains with all 7 housekeeping genes different) was 36% (4/11). A phylogenetic tree was created to determine the evolutionary relationships between different strains. The STs in this study were clustered within the hspEAsia subgroup (98%) and hpEurope group (2%). H. pylori mixed infections were common in Ningbo, China. The H. pylori isolates belonging to the hpEurope group were recovered from three different biopsy samples in a native Chinese patient. Most of H. pylori strains colonizing the antrum, corpus, and duodenum bulb were homologous.