INC Research (United Kingdom)

In this study, the genetic structure of honey bee populations in Türkiye was analyzed using eleven restriction endonuclease enzymes targeting the COI-COII, COI, 16S rDNA, ND5, and CYT B genes. A total of 553 worker honey bee samples were collected from 43 different districts across Türkiye, as well as from Greece, Bulgaria, and Georgia, neighboring countries of Türkiye. Analysis of the COI region using the HinfI restriction enzyme revealed the presence of two mitotypes. Type 1 was the predominant type in Türkiye, while Type 2 was detected exclusively in Hatay, a province in the southern part of the country. Notably, the absence of the HincII site in the COI region and the EcoRI site in the 16S rDNA gene in the Hatay samples suggests that these samples belong to the A lineage. However, several samples from Hatay were classified as belonging to mitochondrial lineage O due to the presence of BglII and HinfI restriction sites in the CYT B gene. With the exception of Hatay, which displayed an EcoRI site in the 16S rDNA fragment and lacked an HinfI site in the CYT B fragment, all samples were identified as belonging to the C lineage. Furthermore, the COI-COII restriction patterns with DraI for lineages C and Z were consistent with the findings. The restriction analysis revealed that several samples from Hatay exhibited the most divergent mitotype in comparison with other honey bee populations studied, resembling African or Arabian honey bees. The results of this study indicate that Anatolia serves as a genetic center for Middle Eastern honey bees, with Hatay acting as a transitional zone. However, the findings also suggest that the introduction of foreign commercial queen bees into Türkiye has led to some degree of hybridization between native and non-native honey bee subspecies.

This study focuses on Machi-Libraries, where local residents bring books and build bookshelves for common use, and aims to find out the characteristics of the location tendency in four prefectures. The results show that, while Machi-Libraries in Tokyo and Kanagawa tend to be located close to train stations, some in Osaka and Hyogo are far from stations. This might be related to differences in urban structure, population density and the location of the facility to which they are attached. The results also suggest that the proximity of the Machi-Libraries to others is one of the location factors in Hyogo.

Abstract Puropse We evaluated the efficacy and safety of Nuvastatic™ in improving cancer-related fatigue (CRF) among cancer patients. Methods This multicenter randomized double-blind placebo-controlled phase-2 trial included 110 solid malignant tumor patients (stage I–IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory [BFI]) and Visual Analog Scale for Fatigue [VAS-F]) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration, Eastern Cooperative Oncology Group scores, and biochemical and hematologic parameters. Clinical outcomes were assessed using two-way repeated-measures analysis of variance on intention-to-treat population. Results The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. The BFI estimated mean difference (eMD) was 15.29 (95% CI: 12.77–17.82) and VAS-F eMD was 11.19 (95% CI: 8.06–14.32) were significantly different between two groups at week 9 (p < 0.001). The overall treatment effect was significant for BFI (p < 0.001) and VAS-F (p < 0.001). Within group assessment showed significant fatigue improvement in both the groups (p < 0.001). Quality of life was significantly improved in the Nuvastatic™ group with eMD of 70.81, (95% CI: 58.34–83.28; p < 0.001) SF-36 scores. Additionally, F2-isoprostane concentrations significantly decreased in the Nuvastatic™ group (p = 0.006). Reported adverse events were vomiting (0.9%), fever (5.4%), and headache (2.7%). Conclusion Nuvastatic™ is an effective adjuvant for CRF in solid tumor patients.

CRISPR/Cas9, base editors and prime editors comprise the contemporary genome editing toolbox. Many studies have optimized the use of CRISPR/Cas9, as the original CRISPR genome editing system, in substituting single nucleotides by homology directed repair (HDR), although this remains challenging. Studies describing modifications that improve editing efficiency fall short of isolating clonal cell lines or have not been validated for challenging loci or cell models. We present data from 95 transfections using a colony forming and an immortalized cell line comparing the effect on editing efficiency of donor template modifications, concentration of components, HDR enhancing agents and cold shock. We found that in silico predictions of guide RNA efficiency correlated poorly withactivity in cells. Using NGS and ddPCR we detected editing efficiencies of 5–12% in the transfected populations which fell to 1% on clonal cell line isolation. Our data demonstrate the variability of CRISPR efficiency by cell model, target locus and other factors. Successful genome editing requires a comparison of systems and modifications to develop the optimal protocol for the cell model and locus. We describe the steps in this process in a flowchart for those embarking on genome editing using any system and incorporate validated HDR-boosting modifications for those using CRISPR/Cas9.

Abstract In the absence of a framework designed to evaluate medicines for rare diseases in the UK, most orphan medicines are appraised by the National Institute for Health and Care Excellence (NICE) through the Single Technology Appraisal (STA) process. An analysis of STA appraisals of orphan and non-orphan medicines revealed that orphan medicines were subject to a significantly longer mean time in the NICE process than non-orphan medicines (370 days (n=44) vs 277 days (n=118), p=<0.0001). A higher proportion of orphan STAs required more than one Appraisal Committee Meeting (ACM) vs. non-orphan STAs, and orphan STAs were disadvantaged by worse outcomes with respect to positive recommendations than those orphan medicines assessed by Highly Specialised Technology evaluation (HST). The uncertainties inherent to developing orphan medicines may contribute to these disadvantages. Improved understanding of the challenges in drug development for orphan medicines and clearer guidance for decision makers on navigating uncertainty in the HTA process may promote greater equity in access to medicines across rare and common conditions.

ИССЛЕДОВАНИЕ ИНВЕСТИЦИОННОЙ АКТИВНОСТИ ЭКОНОМИКИ РЕГИОНААннотация: определяющим фактором устойчивого экономического роста является обеспечение своевременного и достаточного объема инвестиционных ресурсов.Для региона важно, чтобы такие источники могли быть использованы на долгосрочной основе.Также важно, чтобы они были направлены не просто на поддержание действующих технологий и производств, а способствовали формированию производств нового технологического уклада, сопряженного с активным продвижением цифровизации.Подтверждаемые данными официальной статистики диспропорции социально-экономического развития регионов России усугубляются как неоднородностью в природногеографических и демографических параметрах, так и неравномерностью регионального инвестиционного пространства.В этой связи теоретический и практический интерес представляет анализ текущей динамики и перспектив активизации инвестиционного обеспечения регионального развития.

This chapter discusses the system and developments in corporate governance in Korea and addresses important lessons Korea has derived from some studies on comparative corporate governance. The issue of corporate governance of banks is given particular attention in view of the few failures of some large Korean conglomerates and the consequential negative impact on major Korean banks. The chapter describes the traditional “Korean institution” and its problems, singling out the so-called Chaebol-question and representative issues of corporate governance in Korea. It analyzes various corporate governance mechanisms newly introduced in Korea. The chapter explores the relationship between market various corporate governance mechanisms various corporate governance mechanisms corporate governance with reference to the case of Korean firms. One of the most contentious issues in Korea is corporate governance of banks. It is widely believed that many failures in Korea have been caused by bank managers’ breach of their fiduciary duties.

In order to ensure end-to-end links between the users of communication systems, the underlying physical communication network is usually designed independently. We present two design methods for such networks that depend on a particular logical communication network among users. The designs are optimized by minimizing the average path length between logically linked users. One physical network maintains a homogeneous distribution of degrees between nodes, whereas the other network permits each node to have as many degrees as possible. The data traffic capacity of the homogeneous network is always greater than that of the heterogeneous network. Moreover, the average path length of the homogeneous network is not much larger than in the heterogeneous case. This result supports the assertion that the limitation of degree in physical communication networks to meet the physical constraints of network equipment does not act as a harmful factor in the design of communication infrastructure.

To correlate glucose (and lactate) results obtained from microdialysate to recent studies suggesting that glucose transporter activity may be significantly altered in seizures. We used a fluorometric technique to quantify glucose and lactate levels in microdialysates collected from two to four depth electrodes implanted per patient in the temporal and frontal lobes of a series of four patients. Hour-by-hour and day-to-day changes in brain glucose and lactate levels at the same site were recorded. Additionally we compared regional variations in lactate/glucose ratios around the predicted epileptogenic region. Lactate/glucose ratios in the range of 1-2:1 were the most commonly seen. When the lactate/glucose ratio was <1:1, we typically observed a relative increase in local glucose concentration (rather than decreased lactate), suggesting increased transport, perhaps without increased glycolysis. In some sites, lactate/glucose ratios of 3:1-15:1 were seen, suggesting that a circumscribed zone of inhibition of tricarboxylic acid cycle activity may have been locally induced. In these dialysates, collected from probes closer to the epileptogenic region, the large increase in lactate/glucose ratios was a result of both increased lactate and reduced glucose levels. We conclude that regional variations in brain extracellular glucose concentrations may be of greater magnitude than previously believed and become even more accentuated in partial seizure patients. Data from concomitant assays of microdialysate lactate and glucose may aid in understanding cerebral metabolism.