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Cancer vaccines induce cancer-specific T-cells capable of eradicating cancer cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal cancer. This exploratory study investigated the immunologic mechanism of action of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 doses) by analyzing the expression of immune-related molecules, cytotoxic T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants with HLA-A*24:02-positive esophageal cancer. Densities of CD8+, CD8+ Granzyme B+, CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL response was induced in all patients for at least one of five peptides. The same sequences of peptide-specific TCRs were identified in post-vaccination T-lymphocytes derived from both tumor tissue and blood, suggesting that functional peptide-specific CTLs infiltrate tumor tissue after vaccination. Twelve (80%) participants had treatment-related adverse events (AEs). Injection site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, n = 11). In conclusion, S-588410 induces a tumor immune response in esophageal cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 antibodies may offer a clinically useful therapy.Trial registration UMIN-CTR registration identifier: UMIN000023324.

 To compare postoperative outcomes of haptic fixation sites, single versus dual haptics, in capsule-preserving intraocular lens (IOL) intrascleral fixation for zonular weakness.  This retrospective study analyzed 88 eyes (65 patients) with zonular weakness and at least two additional risk factors for IOL dislocation. Conducted at a single center from May 2019 to July 2023, the study followed patients for 6-56 months (mean: 26.5±16.0 months). Fixation methods included single or dual haptics, selected based on the operator's subjective assessment of zonular weakness and patient age. Initially, scleral tunnel-style was used, transitioning to flange-style in October 2021. Outcomes assessed included IOL tilt, decentration, refractive error, and complications.  Final assessments showed an average IOL tilt of 6.54±3.14° and decentration of 0.60±0.36mm. Refractive error at six months post-surgery averaged -0.33±0.99D. Dual fixation resulted in greater myopic shifts than single fixation (-0.79±0.93D vs -0.16±0.96D, p<0.01), especially tunnel-dual fixation compared to tunnel-single fixation (-1.31±0.61D vs -0.25±0.89D, p<0.001) and tunnel-dual fixation compared to flange-dual fixation (-1.31±0.61D vs -0.17±0.88D, p=0.001). Large IOL tilts (>10°) occurred in six eyes (6.8%), all with tunnel style, with a refractive error of -0.59±0.78D; not statistically significant, but a correlation was observed between tilt and refractive error (R²=0.851, p=0.0176). Large IOL decentration (>1mm) occurred in 12 eyes (13.6%), with a significant myopic shift of -1.01±0.93D. Capsule damage was noted in 15.9% of cases, vitreous prolapse was infrequent (4.5%), and no cases had iris capture or severe retinal complications.  Despite the risk of capsule damage, this method, which preserves the capsule and avoids posterior segment surgery, appears viable for cases with significant zonular weakness and anticipated progression, without iris capture or retinal complications. Improving the T-style or adopting F-style, particularly FD-fixation, may help prevent tilt and decentration, reduce refractive errors, and improve postoperative visual function.

This paper describes the Linguistic Annotation Framework under development within ISO TC37 SC4 WG1. The Linguistic Annotation Framework is intended to serve as a basis for harmonizing existing language resources as well as developing new ones. [PUBLICATION ABSTRACT]

The top-seeded and interior seeded methods, together with infiltration growth (IG) technique were used to produce YBa2Cu3Oy (Y-123) samples with Y2BaCuO5 (Y-211) secondary phase particles. Tc (onset) was around 91.5. K. When interior seeding process was used, a complete growth of Y-123 single grain starting at the lower part of the bulk was observed by optical microscopy. The Y-211 particles dispersion was quite uniform in lower and upper parts of the samples, both in the a- and c-axis growth sectors, both at the beginning and end of the grain growth. In the sample produced by infiltration growth and interior seeding the critical current density at 77 K with H//c-axis was 44,000 A/cm2 and 7,750 A/cm2 in self-field and 2 T, respectively. It is a good basis for optimization of processing conditions, which can further improve the superconductor's performance and enable to grow large-size Y-123 bulks.

YBa2Cu3Oy (YBCO) foam samples show an open, porous foam structure, which may have benefits for many applications of high-Tc superconductors. As the basic material of these foams is a pseudo-single crystalline material with the directional growth initiated by a seed crystal similar to standard melt-textured samples, the achieved texture of the YBCO is a very important parameter. We analyzed the local texture and grain orientation of the individual struts forming the foam by means of atomic force microscopy and electron backscatter diffraction (EBSD). Furthermore, the magnetic properties of a foam strut are evaluated by means of SQUID measurements, from which the flux pinning forces were determined. A scaling of the pinning forces in the temperature range between 60 K and 85 K was performed. These data and the details of the microstructure are compared to IG-processed, bulk material.

A quantitative understanding of the intracellular trafficking of plasmids delivered by nonviral vectors is essential for optimizing vector functions to increase their transfection efficiency. In this study, quantitative methods were developed to measure plasmids delivered to the nucleus, and the relationship between transfection activity and the number of plasmids in the nucleus were analyzed. AH130 cells were transfected with plasmids in cationic liposomes at various doses. The nuclear fraction was isolated after NP-40 lysis. and the unincorporated plasmids were enzvmatically degraded and washed away. Intranuclear plasmids were amplified by quantitative PCR. and the number of plasmids was determined. Plasmid amounts in the nucleus were also measured by Southern analysis to confirm the quantification. Both methods led to similar results in measuring the nuclear plasmids within the same order of magnitude. A remarkable saturation was found for transfection activity vs. number of plasmids in the nucleus, whereas no saturation was observed in nuclear-delivered plasmids vs. dose. These results clearly demonstrate the importance of the quantitative measurement of intracellular trafficking of plasmids after transfection. The findings herein described suggest that efficient transgene expression as well as enhanced nuclear delivery is required in order to achieve the maximal transfection activity of nonviral vectors.

Background Interprofessional collaborative practice competency (ICPC) is key to providing safe, high-quality, accessible, patient-centred care. Effective delirium management, particularly, requires a multi-component intervention, including the use of interprofessional teams at care point. This research aims to investigate the effectiveness of the flipped classroom approach for improving ICPC in simulation-based delirium case management. Method An embedded mixed-methods study was designed to investigate the effects of the flipped classroom approach on health professionals’ performance in delirium management. The study population comprised nine health professionals (three physicians, nurses, and pharmacists each). They used pre-class study materials about delirium management via a digital learning platform before a simulation case training session. A readiness assurance process test was conducted on key concepts, covered in the pre-class study material. Participants were randomly assigned to three teams, each of which included health professionals. Each team participated in a simulation case scenario. For the quantitative outcome measures, the Chiba Interprofessional Competency Scale (CICS29), a validated scale for measuring competencies of interprofessional practice, was used before, after, and three months after the educational intervention. The qualitative component consisted of a post-training questionnaire and semi-structured focused group interviews about the impact of the flipped classroom approach. Result The CICS29 measured after the intervention and three months after was noted to be significantly higher than before the intervention. Three semi-structured focused group interviews were conducted (n=9), which, upon analysis revealed that the flipped classroom approach effected on four stages of Bloom's taxonomy level. A total of nine categories and 17 subcategories were identified corresponding to four levels of the revised Bloom’s taxonomy: remember (1), understand (12), apply (23), and analyse (3). Conclusion The simulation-based skill training using flipped classroom approach can be an effective method for improving ICPC for health professionals. In this approach, an elevated level of cognitive activity is practiced in the Bloom’s taxonomy, and the participants worked on an application-based case simulation that promoted higher level learning and engagement in interprofessional collaborative practice. This approach also established a basic common language of delirium assessment and management, thus facilitating communication among health professionals and improving ICPC.

Trained individuals may require variations in training stimuli and advanced resistance training paradigms (ADV) to increase skeletal muscle hypertrophy. However, no meta-analysis has examined how ADV versus traditional (TRAD) approaches may differentially affect hypertrophic outcomes in trained populations. The aim of this review was to determine whether the skeletal muscle hypertrophy responses induced by TRAD differed from ADV in resistance-trained individuals. Furthermore, we sought to examine potential effects of dietary factors, participants’ training status, and training loads. We searched for peer-reviewed, randomized controlled trials (published in English) conducted in healthy resistance-trained adults performing a period of TRAD and ADV with pre-to-post measurement(s) of muscle hypertrophy in PubMed, Web of Science, SPORTDiscus, and MEDLINE databases up to October 2022. A formal meta-analysis was conducted in Revman5, and risk of bias was assessed by ROB2. Ten studies met the inclusion criteria. Results indicated no difference between ADV and TRAD for muscle thickness (SMD = 0.05, 95% CI: −0.20 0.29, p = 0.70), lean mass (SMD = −0.01, 95% CI: −0.26 0.23, p = 0.92), muscle cross-sectional area (SMD = −0.07, 95% CI: −0.36 0.22, p = 0.64), or all measurements analyzed together (SMD = −0.00, 95% CI: −0.15 0.14, p = 0.95). No heterogeneity or inconsistencies were observed; however, unclear risk of bias was present in most of the studies. Short-term ADV does not induce superior skeletal muscle hypertrophy responses when compared with TRAD in trained individuals. This review was not previously registered.

This article reviews the history and current status of clinical trial registrations and results data posted on the National Library of Medicine's Web site ClinicalTrials.gov. The ClinicalTrials.gov trial registry was launched more than a decade ago. Since that time, it has been evolving in response to various policy initiatives. The registry now contains information on more than 100,000 clinical studies and has emerged as a key element of many public health policy initiatives aimed at improving the clinical research enterprise. In 2008, a database for reporting summary results was added to the registry. In this article, we present an update on relevant policies, summarize the structure and contents of the results database, and show how ClinicalTrials.gov data can be used to gain insight into the . . .