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Background: Hepatitis B core antibody (anti‐HBc) screening has been implemented in many blood establishments to help prevent transmission of hepatitis B virus (HBV), including from donors with occult HBV infection (OBI). We review HBV screening algorithms across blood establishments globally and their potential effectiveness in reducing transmission risk. Materials and Methods: A questionnaire on HBV screening and follow‐up strategies was distributed to members of the International Society of Blood Transfusion working party on transfusion‐transmitted infectious diseases. Screening data from 2022 were assimilated and analyzed. Results: A total of 30 unique responses were received from 25 countries. Sixteen respondents screened all donations for anti‐HBc, with 14 also screening all donations for HBV DNA. Anti‐HBc prevalence was 0.42% in all blood donors and 1.19% in new donors in low‐endemic countries; however, only 44% of respondents performed additional anti‐HBc testing to exclude false reactivity. 0.68% of anti‐HBc positive, HBsAg‐negative donors had detectable HBV DNA. Ten respondents did universal HBV DNA screening without anti‐HBc, whereas four respondents did not screen for either. Deferral strategies for anti‐HBc positive donors were highly variable. One transfusion‐transmission from an anti‐HBc negative donor was reported. Discussion: Anti‐HBc screening identifies donors with OBI but also results in the unnecessary deferral of a significant number of donors with resolved HBV infection and donors with false‐reactive anti‐HBc results. Whilst confirmation of anti‐HBc results could be improved to reduce donor deferral, transmission risks associated with anti‐HBc negative OBI donors must be considered. In high‐endemic areas, highly sensitive HBV DNA testing is required to identify infectious donors. [ABSTRACT FROM AUTHOR]

Objective To evaluate the performance of a blood nucleic acid testing kit, construct a consistency assessment system, and analyze the influencing factors of the test results. Methods A total of 18 644 samples of voluntary blood donors in our center were collected, and 189 double positive samples of hepatitis B surface antigen (HBsAg) by ELISA were eliminated, and the remaining 18 455 samples were tested for HBV DNA in parallel with the test reagent and the control reagent (Roche Company). Samples with inconsistent results were confirmed with third-party reagents (Grifols Company, with the sensitivity of HBV DNA, HCV RNA and HIV RNA of 4.5 IU/mL, 2.4 IU/mL and 17.3 IU/mL by single reagent, which were significantly better than other reagents), and the consistency between the two methods was compared. Results No HCV RNA or HIV RNA positive samples were detected in this study. Among the 18 455 samples in initial test, 12 were positive with consistent results, 18 378 were negative with consistent results, and 65 were with inconsistent results between the test reagent and the control reagent, with positive concordance rate, negative concordance rate and concordance rate of the two reagents at 85.17%, 99.66% and 99.65%, respectively. In order to further clarify the infection of 65 inconsistent samples, five qualitative tests of hepatitis B and single NAT were conducted to comprehensively evaluate the infection. The results showed that there were 60 positive samples with consistent results, 18 371 negative samples with consistent results, and 24 samples with inconsistent results between the test reagent and the control reagent, with positive concordance rate, negative concordance rate and the concordance rate for the two reagents at 86.96%, 99.92% and 99.87%, respectively. The Kappa value was 0.83, and the Youden index was 0.40. The ROC curve was plotted with the false-positive rate (1-specificity) as the horizontal coordinate and the true-positive rate (sensitivity) as the vertical coordinate, and the area under the ROC curve was 0.705. 189 double-positive samples were selected for conformance testing, and the Ct values of the test reagent and the control reagent were analyzed and fitted linearly, with correlation coefficient r=0.972. A Bland-Altman model was constructed with the mean value of the logarithm of the quantitative values of the test reagent and the control reagent as the horizontal coordinate and the difference as the vertical coordinate, and 96.30% of the difference values of the test reagents were within the confidence interval. Conclusion The construction of the consistency evaluation system showed that the test reagent has similar detection efficiency with the control reagent, and is suitable for HBV DNA routine screening, which can effectively ensure the safety and effectiveness of blood screening.

Invisible social groups are systematically left out of the process of development and have to make choices that are predetermined. Research suggests that the tribal and nomadic communities have been majorly affected by such processes. Nat, a peripatetic nomadic tribe in India has undergone similar exclusionary process. However, they continue to survive as a social group and maintain their distinguishing character. This study, therefore, is an attempt to understand their survival within the mainstream society by systematically analysing the following sociocultural attributes: identity construction, education and mobility, and multi-religious belonging. The Nat of Paschim Champaran, in the state of Bihar in India, were the focus of the study. Data was collected from 30 respondents and analysed by applying narrative inquiry. The findings suggest that their professional identity as acrobats continues to define their distinctiveness even when a few have chosen to shift towards other forms of livelihood. This distinctiveness continues to negatively influence their access to education and as a result no major change is witnessed in terms of social mobility of the group. However, it is observed that they have intelligently assimilated themselves within the popular culture by adopting multiple identities with respect to religion and which are activated for diverse purposes and at different times. [ABSTRACT FROM AUTHOR]

Background: The large dengue (DENV) and chikungunya (CHIKV) outbreaks observed during the last decade across the world, as well as local transmissions in non‐endemic areas are a growing concern for blood safety. The aim of this study was to evaluate and compare the sensitivity of nucleic acid tests (NAT) detecting DENV and CHIKV RNA. Materials and Methods: Using DENV 1 to 4 International Standards, the limits of detection (LODs) calculated by probit analysis of two NAT assays; the cobas CHIKV/DENV assay (Roche Diagnostics) and the Procleix Dengue Virus Assay (Grifols) were compared. In addition, CHIKV‐RNA LOD of the cobas CHIKV/DENV assay was evaluated. Results: For dengue, the 95% LOD of the cobas assay ranged between 4.10 [CI95%: 2.70–8.19] IU/mL (DENV‐2) and 7.07 [CI95%: 4.34–14.89] IU/mL (DENV‐4), and between 2.19 [CI95%: 1.53–3.83] IU/mL (DENV‐3) and 5.84 [CI95%: 3.84–10.77] IU/mL (DENV‐1) for Procleix assay. The Procleix assay had a significant lower LOD for DENV‐3 (2.19 vs. 5.89 IU/mL) when compared to the cobas assay (p = 0.005). The 95% LOD for CHIKV‐RNA detection of the cobas assay was 4.76 [CI95%: 3.08–8.94] IU/mL. Discussion: The two NAT assays developed for blood donor screening evaluated in this study demonstrated high and similar analytical performance. Subject to an appropriate risk‐benefit assessment, they can be used to support blood safety during outbreaks in endemic areas or in non‐endemic areas as an alternative to deferring blood donors during local transmission likely to affect the blood supply. The development of multiplex assays is expected to optimize laboratory organization. [ABSTRACT FROM AUTHOR]

Summary: Background: External quality assessment (EQA) schemes provide objective feedback to participating laboratories about the performance of their analytical systems and information about overall regional analytical performance. The EQAs are particularly important during pandemics as they also assess the reliability of individual test results and show opportunities to improve test strategies. With the end of the COVID-19 pandemic, the testing frequency significantly decreased in Austria. Here, we analyzed whether this decrease had an effect on participation and/or performance in SARS-CoV‑2 virus detection EQAs, as compared to the pandemic era. Material and methods: Identical samples were sent to all participating laboratories, and the EQA provider evaluated the agreement of the reported results with defined targets. The EQA was operated under two schemes with identical samples and therefore we analyzed it as a single EQA round. The performance of testing was reported as true positive ratios, comparing the post-pandemic data to previous rounds. Furthermore, subgroups of participants were analyzed stratified by laboratory type (medical or nonmedical) and the test system format (fully automated or requiring manual steps). Results: While the frequency of false negative results per sample did not change during the 3 years of the pandemic (5.7%, 95% confidence interval [CI] 3.1–8.4%), an average per sample false negative ratio of 4.3% was observed in the first post-pandemic EQA (0%, 1.8%, and 11% for the 3 positive samples included in the test panel, n = 109 test results per sample). In this first post-pandemic EQA medical laboratories (average 0.4% false negative across 3 samples, n = 90) and automated test systems (average 1.2% false negative, n = 261) had lower false negative ratios than nonmedical laboratories (22.8%, n = 19) and manual test systems (16.7%, n = 22). These lower average ratios were due to a low concentration sample, where nonmedical laboratories reported 36.8% and manual test systems 54.5% true positive results. Conclusion: Overall ratios of true positive results were below the mean of all results during the pandemic but were similar to the first round of the pandemic. A lower post-pandemic true positive ratio was associated with specific laboratory types and assay formats, particularly for samples with low concentration. The EQAs will continue to monitor the laboratory performance to ensure the same quality of epidemiological data after the pandemic, even if vigilance has decreased. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi‐regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking‐associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra‐patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra‐patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD‐L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis‐to‐metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

[2,3-diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide], named as ETN101, is a novel therapeutic agent for hepatocellular carcinoma. In vitro studies examined ETN101 metabolites in human, mouse, rat, dog, and monkey hepatocytes and identified the drug-metabolizing enzymes involved using cDNA-expressed human recombinant cytochrome P450s (CYPs), carboxylesterases (CESs), N-acetyltransferase (NAT) 1, and human liver cytosol. ETN101 showed similar metabolic stability across hepatocytes from five species, with particularly comparable stability in humans, rats, and monkeys. Its half-life was 75.0 min in humans, 68.9 in rats, 73.1 in monkeys, 120.4 in mice, and 112.7 in dogs. Thirty-four ETN101 metabolites, including the major metabolite M1, were identified using liquid chromatography–high-resolution mass spectrometry. ETN101 was primarily metabolized to M1 and CYP1A2 is exclusively responsible for M1 metabolism. Both NAT1 and NAT2 were responsible for the N-acetylation of M1 to M2. ETN101 remained stable in human CESs. In conclusion, this study provides comprehensive insights into the metabolic characteristics of ETN101, valuable for its toxicological and clinical development. [ABSTRACT FROM AUTHOR]

Background and Objectives: Nucleic acid‐amplification testing (NAT) is used for screening blood donations/donors for blood‐borne viruses. We reviewed global viral NAT characteristics and NAT‐yield confirmatory testing used by blood operators. Materials and Methods: NAT characteristics and NAT‐yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion‐Transmitted Infectious Diseases. Reported characteristics are presented herein. Results: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini‐pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT‐yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow‐up sample. Conclusion: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT‐yields, potentially benefitting blood operators seeking to implement NAT. [ABSTRACT FROM AUTHOR]

The object detection model in UAV aerial image scenes faces challenges such as significant scale changes of certain objects and the presence of complex backgrounds. This paper aims to address the detection of small objects in aerial images using NATCA (neighborhood attention Transformer coordinate attention) YOLO. Specifically, the feature extraction network incorporates a neighborhood attention transformer (NAT) into the last layer to capture global context information and extract diverse features. Additionally, the feature fusion network (Neck) incorporates a coordinate attention (CA) module to capture channel information and longer-range positional information. Furthermore, the activation function in the original convolutional block is replaced with Meta-ACON. The NAT serves as the prediction layer in the new network, which is evaluated using the VisDrone2019-DET object detection dataset as a benchmark, and tested on the VisDrone2019-DET-test-dev dataset. To assess the performance of the NATCA YOLO model in detecting small objects in aerial images, other detection networks, such as Faster R-CNN, RetinaNet, and SSD, are employed for comparison on the test set. The results demonstrate that the NATCA YOLO detection achieves an average accuracy of 42%, which is a 2.9% improvement compared to the state-of-the-art detection network TPH-YOLOv5. [ABSTRACT FROM AUTHOR]

Although various pathological grading systems are available for evaluating the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant therapy (NAT), their prognostic value has not been thoroughly validated. This study examined whether microscopic tumor mapping of post-NAT specimens could predict tumor recurrence. This prospective study enrolled 52 patients who underwent pancreaticoduodenectomy after NAT for PDAC between 2019 and 2021. Microscopic mapping was performed to identify residual tumor loci within the tumor bed using 4 mm2 pixels. Patients were divided into small extent (SE; n = 26) and large extent (LE; n = 26) groups using a cutoff value of 226 mm2. The diagnostic performance for predicting tumor recurrence was evaluated using receiver operating characteristic (ROC) curves. Carbohydrate antigen 19-9 levels were normalised after NAT in more patients in the SE group (SE 21 [80.8%] vs. LE 13 [50.0%]; P = 0.041). Tumor size (P < 0.001), T stage (P < 0.001), positive lymph node yield (P = 0.024), and perineural invasion rate (P = 0.018) were significantly greater in the LE group. The 3-year disease-free survival rate was significantly lower in the LE group (SE 83.3% vs. LE 50.0%, P = 0.004). The area under the ROC curve for mapping extent was 0.743, which was greater than that of the other tumor response scoring systems. Microscopic tumor mapping of the residual tumor in post-NAT specimens is a significant predictor of post-surgical recurrence, and offers better prognostic performance than the current grading systems. [ABSTRACT FROM AUTHOR]

India is home to a wide range of ethnic groups. Each group has unique characteristics. The Nat, for instance, is a nomadic tribe and is known for its specialized acrobatic and musical skills. The associated traditional occupations, however, have proved restrictive to the socio-economic mobility of the tribe. This study, therefore, is an attempt to develop an understanding of the ways in which the Nat situate themselves within the changing social dynamics by addressing the following questions: How do members of the Nat community evolve in response to changing societal dynamics? Has the change been restrictive to the tribe’s social and economic mobility? In order to find answers to these questions 31 case studies were conducted of the Nat from four states in India who had gathered at a famous fair organized annually in Chhattisgarh state. Analysis of the data collected followed Wolcott’s and Biggam’s iterative approach to the description and interpretation of the field notes and case studies. The findings of the study suggest that in order to survive, the Nat community has significantly assimilated with mainstream society by adopting social differentiation based on caste and religion. Instead of reaping positive results, this process has proved detrimental to the socio-economic situation of the Nat. While other communities reap the benefits of the developmental processes, the Nat nomadic tribe continues to be stigmatized and marginalized. Social and economic mobility is significantly lacking and the few measures taken for their welfare have not improved their situation. Efforts from both the researchers and the major stakeholders are indispensable so that relevant policy measures may be introduced for their welfare. [ABSTRACT FROM AUTHOR]

Background and Objectives: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion‐transmitted infections. This project reviewed NAT for screening blood donations globally. Materials and Methods: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion‐transmitted Infectious Diseases (ISBT WP‐TTID), was distributed through ISBT WP‐TTID members. Data were analysed using descriptive statistics. Results: Forty‐three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT‐positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT‐positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT‐positivity rate was higher in first‐time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). Conclusion: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT. [ABSTRACT FROM AUTHOR]

Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children. [ABSTRACT FROM AUTHOR]

The rapid economic growth has created many environmental problems. These problems include global warming and natural resource depletion. South Asian countries are rich in NAT, and these countries are moving toward ECG. Despite the availability of rich literature, very few studies have investigated the associations of NAT, ECG, and CO2 emissions in South Asian nations. Therefore, this research probes this association in the presence of urbanization and trade. For this purpose, yearly data from 1980 to 2019 are investigated with the help of second-generation methodologies like cross-sectional autoregressive distributed lag (CS-ARDL). CS-ARDL results show that ECG and economic growth are improving air quality in India, Pakistan, Sri Lanka, and Bangladesh. Urbanization, NAT, and trade are contaminating the environmental quality. In light of these findings, some important policy recommendations are provided to grasp sustainable development in South Asian nations. [ABSTRACT FROM AUTHOR]

[2,3-diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide], named as ETN101, is a novel therapeutic agent for hepatocellular carcinoma. In vitro studies examined ETN101 metabolites in human, mouse, rat, dog, and monkey hepatocytes and identified the drug-metabolizing enzymes involved using cDNA-expressed human recombinant cytochrome P450s (CYPs), carboxylesterases (CESs), N-acetyltransferase (NAT) 1, and human liver cytosol. ETN101 showed similar metabolic stability across hepatocytes from five species, with particularly comparable stability in humans, rats, and monkeys. Its half-life was 75.0 min in humans, 68.9 in rats, 73.1 in monkeys, 120.4 in mice, and 112.7 in dogs. Thirty-four ETN101 metabolites, including the major metabolite M1, were identified using liquid chromatography–high-resolution mass spectrometry. ETN101 was primarily metabolized to M1 and CYP1A2 is exclusively responsible for M1 metabolism. Both NAT1 and NAT2 were responsible for the N-acetylation of M1 to M2. ETN101 remained stable in human CESs. In conclusion, this study provides comprehensive insights into the metabolic characteristics of ETN101, valuable for its toxicological and clinical development.

The object detection model in UAV aerial image scenes faces challenges such as significant scale changes of certain objects and the presence of complex backgrounds. This paper aims to address the detection of small objects in aerial images using NATCA (neighborhood attention Transformer coordinate attention) YOLO. Specifically, the feature extraction network incorporates a neighborhood attention transformer (NAT) into the last layer to capture global context information and extract diverse features. Additionally, the feature fusion network (Neck) incorporates a coordinate attention (CA) module to capture channel information and longer-range positional information. Furthermore, the activation function in the original convolutional block is replaced with Meta-ACON. The NAT serves as the prediction layer in the new network, which is evaluated using the VisDrone2019-DET object detection dataset as a benchmark, and tested on the VisDrone2019-DET-test-dev dataset. To assess the performance of the NATCA YOLO model in detecting small objects in aerial images, other detection networks, such as Faster R-CNN, RetinaNet, and SSD, are employed for comparison on the test set. The results demonstrate that the NATCA YOLO detection achieves an average accuracy of 42%, which is a 2.9% improvement compared to the state-of-the-art detection network TPH-YOLOv5.

The hepatitis B virus (HBV), comprising of ten genotypes (A-J), has been a silent threat against humanity, constituting a public health problem worldwide. In 2016, the World Health Organization set forth an impressive initiative for the global elimination of viral hepatitis by 2030. As the target date approaches, many nations, particularly in the Latin American region, face challenges in designing and implementing their respective elimination plan. This review aimed to portray the state of knowledge about the epidemiological, molecular, and clinical characteristics of HBV genotype H (HBV/H), endemic to Mexico. PubMed, Scopus, Web of Science, and Google Scholar were searched to compile scientific literature over 50 years (1970–2022). A total of 91 articles were organized into thematic categories, addressing essential aspects such as epidemiological data, risk factors, HBV genotype distribution, HBV mixed infections, clinical characteristics, and vaccination. The prevalence and its associated 95% confidence interval (95% CI) were estimated using the Metafor package in R programming language (version 4.1.2). We provide insights into the strengths and weaknesses in diagnostics and prevention measures that explain the current epidemiological profile of HBV/H. Training, research, and awareness actions are required to control HBV infections in Mexico. These actions should contribute to creating more specific clinical practice guides according to the region's characteristics. Mexico's elimination plan for HBV will require teamwork among the government health administration, researchers, physicians, specialists, and civil society advocates to overcome this task jointly. [ABSTRACT FROM AUTHOR]

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The human immunodeficiency virus (HIV) attacks the immune system to cause a lifelong severe illness called AIDS (acquired immunodeficiency syndrome). The HIV infection is a serious condition associated with high costs of therapy and care. Since the beginning of the AIDS/HIV epidemic the number of HIV infected people worldwide has exceeded 84 million, and about 40 million have already died of AIDS. Transfusion of blood and blood components is one of the transmission routes for HIV infection. The risk of transmission of infection by this route has been significantly reduced e.g. by introducing mandatory screening tests for blood donors. There are still however reports of sporadic cases of transfusion transmitted infections related to the so-called diagnostic window and virus polymorphism. In Poland, mandatory testing of anti-HIV were introduced for all blood donors in 1987, and HIV RNA in 2005. Enzyme immunoassays (EIA) have gradually been improved and currently all Polish Blood Transfusion Centers (BTCs) analyze both IgG and IgM antibodies as well as p24 antigen (IV generation tests) in donors. HIV RNA is tested in individual donations (IDT) or in mini pools (MP); the sensitivity expressed as 95% limit of detection [95% LOD] is 45-18 IU/mL and 1469 IU/mL -- 302 IU/mL, respectively. Verification tests were always performed at the Department of Virology of the Institute of Hematology and Transfusion Medicine (IHTM) with Western blot (WB) and molecular biology methods: transcription mediated amplification (TMA) and real-time polymerase chain reaction (RT-PCR). This publication presents detailed strategy and methodology for conducting screening and verification tests for HIV in Polish blood donors in the years 2005-2022. The study is an extension and update of a part of the author's doctoral dissertation and initiates a discussion on the donor qualification process and the effectiveness of screening studies. [ABSTRACT FROM AUTHOR]

Background: A sensitive and specific donor screening strategy is essential for the prevention of transfusion-transmitted infections (TTI). The study was conducted to ascertain the comparative efficacy of ICT, CLIA and NAT methods. Methods: This cross-sectional analytical study was conducted in Regional Blood Center Abbottabad, Pakistan from 1st April to 25 August 2022. 6233 donors were screened for Hep B, C, and HIV by testing simultaneously with ICT, CLIA and NAT. Results: Active Hep B, C and HIV Infection was present in 0.51%, 0.28% and 0.00048% donors respectively. The sensitivity was found to be higher for HBV and HIV with CLIA as compared to ICT but was equal for HCV with both. whereas specificity was the same with both CLIA and ICT for all three viruses. PPV was higher with ICT for HBV and HCV, but for HIV it was found higher by CLIA. NPV was higher for all three viruses by CLIA as compared to ICT. Conclusion: In case rapid testing devices are used for the initial screening of blood in countries with limited resources, positive cases must be confirmed by CLIA and if possible, then by NAT because of missing cases in the window period and false positive cases. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prevalence and trends of transfusion-transmitted infections (TTIs) in two hospitals in Riyadh, as well as to judge the best type of tests to ensure blood transfusion safety. By using serological and nucleic acid test (NAT) tests, these donors were screened for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), human T-lymphotropic virus type 1 (HTLV-1), human T-lymphotropic virus type 2 (HTLV-2), syphilis, and malaria infection as a first time of donation. Out of 58,898 blood units, 336 units were reacted for HBsAg, 5,318 units for HBcAbs, 506 units for HCV antibodies, 214 units for HIV Ab/Ag combinations, 206 units for HTLV antibodies, 355 units for syphilis antibodies, and 81 units for malaria. Moreover, the genotypic prevalence of these products showed that 349 units reacted for HBV DNA, HCV RNA, and HIV RNA in blood donation. This study reflects the seriousness of the residual risk of TTI, which is still a threat factor for the transmission of blood-borne infectious diseases. It was discovered that utilising (NAT) could increase test sensitivities while also lowering residual TTI risks, improving blood safety, and being cost-effective.

Objective To compare the performance and cost-effectiveness between ID-NAT (individual detection of NAT) mode and MP-NAT (mini-pool nucleic acid test) mode in blood screening, and to provide reference for blood sample detection. Methods The results of 95 895 NAT-samples completed in 2021 were analyzed, and the Ct values of MP-NAT positive/ID-NAT negative group, MP-NAT positive/ID-NAT positive group, MP-NAT negative/ID-NAT positive group were compared. The amplification efficiency of MP-NAT and ID-NAT mode was estimated by PCR. Twelve samples from MP-NAT negative/ ID-NAT positive group were simulated by MP-NAT for 5 to 10 times. Results The Ct values of samples by MP-NAT were significantly higher than those by ID-NAT(P

Background: The rapid detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is vital for patient care. The LumiraDx™ SARS-CoV-2 RNA Star Complete (RSC) is an Emergency Use Authorization-recognized molecular test using nasal/nasopharyngeal swabs immersed in a viral/universal transport medium (VTM/UTM). However, there is a critical need for an alternative medium for point-of-care testing (POCT). This study aimed to investigate Xtract-Free (XF), a novel collection medium for transport and direct (extraction-free) use with nucleic acid tests. Methods: Using serially diluted SARS-CoV-2 viral RNA (vRNA) in a routine UTM and XF, a limit of detection (LOD) was established via an RSC test and a quantitative reverse transcription PCR (RT-qPCR). Additionally, the results obtained from a panel of 108 clinical "car-side" nasal swabs collected in XF during the coronavirus pandemic and assessed using the "gold-standard" RT-qPCR assay were compared to Lumira's RSC assay. Results: The average replicate RT-qPCR cycle threshold (CT) values for vRNA in XF and UTM were observed to be equivalent. An LOD for which five out of five replicates were detected using XF or VTM was approximately 2000 copies/mL. The nasal swabs collected in XF exhibited 93.9% positive percent agreement (sensitivity) and 100% negative percent agreement (specificity) compared to the RT-qPCR. Three specimens tested positive via an RT-qPCR were negative when tested via RSC; however, all three samples had CT values ≥ 36.4. Conclusions: XF is equivalent to VTM/UTM and is compatible for use with the RSC test. Furthermore, XF can be used directly with RT-qPCRs and rapid antigen testing without the requirement for separate nucleic acid extraction (an extraction-free process), making it ideal for cost-effective high-throughput and decentralized respiratory testing. Impact Statement: This study is the first to evaluate LumiraDx's SARS-CoV-2 RNA Star Complete assay in concert with Xtract-Free (XF), a novel collection medium containing a proprietary RNase-inactivating technology for the rapid, "extraction-free" detection of SARS-CoV-2 RNA from clinical nasal swabs. Specimens collected in XF combined with rapid LumiraDx detection provide a safe and sensitive alternative to VTM/UTM, and Molecular Transport medium (MTM) for high throughput, "extraction-free" molecular detection. [ABSTRACT FROM AUTHOR]

Nucleic acid testing (NAT) is used to screen transfusiontransmittable infections (TTIs) in donated blood samples and provide an additional layer of blood safety. In this study, we describe our experience in screening viral TTIs using two formats of NAT: cobas® MPX2 polymerase chain reaction- based minipool NAT (PCR MP-NAT) and Procleix Utrio Plus transcription-mediated amplificationbased individual donor-NAT (TMA ID-NAT). Data routinely collected as a part of blood bank operations were retrospectively analysed over a period of 70 months for TTIs. Blood samples were initially screened for HIV, HBV, HCV, syphillis by chemiluminescence and malaria by Rapid card test. In addition to serological testing, all samples were further screened by TMA-based ID-NAT (ProcleixUltrio Plus Assay) during Jan 2015–Dec 2016, and by PCR-based MP-NAT (Cobas® TaqScreen MPX2) during Jan 2017–Oct 2020. RESULTS: A total of 48,151 donations were processed over 70 months, of which 16,212 donations were screened by ProcleixUtrio Plus TMA ID-NAT and 31,939 donations by cobas® MPX2 PCR MP-NAT. Replacement donors and male donors outnumbered voluntary donors and female donors respectively. The overall NAT yield rate of MP-NAT was 1:2281 compared to 1:3242 with ID-NAT, during the respective time period. ID-NAT detected 5 HBV infections missed by serology, whereas MP-NAT detected 13 HBV infections and 1 HCV infection missed by serology. The proportion of donations that were both seroreactive and NAT reactive was higher with MP-NAT (59.8%) compared to ID-NAT (34.6%). Cobas® MPX2MP-NAT had higher overall NAT yield rate compared to ProcleixUtrio Plus ID-NAT and confirmed a higher proportion of seroreactive donations. Due to the ease of operation, simple algorithm, cobas® MPX2 PCR based MP-NAT can be an effective solution for blood screening in India. [ABSTRACT FROM AUTHOR]

Objective To investigate the effectiveness of current indicators in initial screening and retest before donation and access the optimal testing strategies. Methods Data of initial screening (rate method for ALT, colloidal gold method for HBsAg) and retest (rate method for ALT, ELISA for HBsAg) of 18 510 platelet donors in our center from January 2019 to December 2021 were collected, and the results were retrospectively analyzed and compared in terms of different years and number of donations. Results From 2019 to 2021, data of initial screening and retest of platelet donors were as follows: 1) the deferral rate of ALT and HBsAg was 12.98% (2 403/18 510) vs 0.26%(40/15 412); 2) the deferral rate of ALT was 13.19% (712/5 398) vs 0.20%(9/4 410)in 2019, 13.33% (873/6 549) vs 0.06%(3/5 387)in 2020 and 11.05% (725/6 563) vs 0.07%(4/5 615)in 2021; for initial screening, significant difference was noticed in ALT reactivity in 2021 as in comparison to other two years(P

Objective To investigate the characteristics of HBV serological markers of NAT reactive blood donors under different HBsAg status. Methods NAT reactive samples, with HBsAg-, HBsAg+ /retest - and HBsAg+ by single reagent were collected from September 2021 to May 2022 in our laboratory. The TMA non-reactive samples were retested by Roche PCR, then HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were detected by ECLI for statistical analysis. Results A total of 66 samples were collected, among which 55 were HBsAg-/NAT+. The positive rate of anti-HBc, anti-HBs+ anti-HBc, anti-HBe+ anti-HBc was 87.3% (48/55), 43.6% (24/55) and 45.5% (25/55), respectively. The positive rate of anti-HBs was 10.9% (6/55) and the overall negative rate was 1.8% (1/55). In 7 HBsAg+ initially/retest -/NAT+ samples, the positive rate of anti-HBc was 100%(7/7), and the positive rate of anti-HBe+ anti-HBc was 71.4%(5/7). In 4 HBsAg+ /NAT+ samples by single reagent, the positive rate of HBsAg+ anti-HBs+ anti-HBe+ anti-HBc was 50% (2/4), and positive rate of anti-HBe+ anti-HBc was100% (4/4). Samples, not reactive to TMA discriminatory and anti-HBc negative, were also non-reactive to individual PCR retest. There were significant differences in the positive rates of anti-HBe+ anti-HBc between HBsAg-/NAT+ samples and HBsAg+ /NAT+ (single reagent) samples (P

Background: Hepatitis B virus (HBV)‐positive individuals with isolated anti‐HBs are found among HBV vaccine recipients and healthy blood donors with no vaccination history. HBV infectivity from blood transfusions derived from such individuals remains unclear. Case Presentation: A male patient who received transfusion with blood negative for individual donation‐NAT, HBsAg and anti‐HBc but weakly positive for anti‐HBs developed typical transfusion‐transmitted (TT)‐HBV with anti‐HBc response. The responsible blood donor was a frequent repeat donor showing a marked increase in anti‐HBs titer without anti‐HBc response 84 days after index donation. Test results for his past donations showed transient viremia with very low viral load and fluctuating low‐level anti‐HBs. The HBV vaccination history of this donor was unknown. Discussion: Anti‐HBs and anti‐HBc kinetics of the donor suggest a second antibody response to new HBV challenge, representing a vaccine breakthrough case. On the other hand, transient low‐level viremia and fluctuating anti‐HBs in the test results of past donations suggested chronic occult HBV infection with isolated anti‐HBs. Conclusion: Whatever the basic infection state, blood donors with isolated weak anti‐HBs may include a small population with a risk of causing TT‐HBV. Identifying individuals harboring such TT‐HBV risk among individuals positive only for anti‐HBs is difficult under current screening strategies. Active surveillance for the occurrence of TT‐HBV with blood positive only for anti‐HBs is necessary. [ABSTRACT FROM AUTHOR]

Copyright of Bouhouth is the property of London Research & Consulting Center and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Fusarium endophytes damage cereal crops and contaminate produce with mycotoxins. Those fungi overcome the main chemical defence of host via detoxification by a malonyl‐CoA‐dependent enzyme homologous to xenobiotic metabolizing arylamine N‐acetyltransferase (NAT). In Fusarium verticillioides (teleomorph Gibberella moniliformis, GIBMO), this N‐malonyltransferase activity is attributed to (GIBMO)NAT1, and the fungus has two additional isoenzymes, (GIBMO)NAT3 (N‐acetyltransferase) and (GIBMO)NAT2 (unknown function). We present the crystallographic structure of (GIBMO)NAT1, also modelling other fungal NAT homologues. Monomeric (GIBMO)NAT1 is distinctive, with access to the catalytic core through two "tunnel‐like" entries separated by a "bridge‐like" helix. In the quaternary arrangement, (GIBMO)NAT1 monomers interact in pairs along an extensive interface whereby one entry of each monomer is covered by the N‐terminus of the other monomer. Although monomeric (GIBMO)NAT1 apparently accommodates acetyl‐CoA better than malonyl‐CoA, dimerization changes the active site to allow malonyl‐CoA to reach the catalytic triad (Cys110, His158 and Asp173) via the single uncovered entry, and anchor its terminal carboxyl‐group via hydrogen bonds to Arg109, Asn157 and Thr261. Lacking a terminal carboxyl‐group, acetyl‐CoA cannot form such stabilizing interactions, while longer acyl‐CoAs enter the active site but cannot reach catalytic Cys. Other NAT isoenzymes lack such structural features, with (GIBMO)NAT3 resembling bacterial NATs and (GIBMO)NAT2 adopting a structure intermediate between (GIBMO)NAT1 and (GIBMO)NAT3. Biochemical assays confirmed differential donor substrate preference of (GIBMO)NAT isoenzymes, with phylogenetic analysis demonstrating evolutionary separation. Given the role of (GIBMO)NAT1 in enhancing Fusarium pathogenicity, unravelling the structure and function of this enzyme may benefit research into more targeted strategies for pathogen control. [ABSTRACT FROM AUTHOR]

Histone acetylation involves the addition of acetyl groups to specific amino acid residues. This chemical histone modification is broadly divided into two types - acetylation of the amino group found on the side chain of internal lysine residues (lysine acetylation) or acetylation of the α-amino group at the N-terminal amino acid residue (N-terminal acetylation). Although the former modification is considered a classic epigenetic mark, the biological importance of N-terminal acetylation has been mostly overlooked in the past, despite its widespread occurrence and evolutionary conservation. However, recent studies have now conclusively demonstrated that histone N-terminal acetylation impacts important cellular processes, such as controlling gene expression and chromatin function, and thus ultimately affecting biological phenotypes, such as cellular ageing, metabolic rewiring and cancer. In this Review, we provide a summary of the literature, highlighting current knowledge on the function of this modification, as well as allude to open questions we expect to be the focus of future research on histone N-terminal acetylation. [ABSTRACT FROM AUTHOR]

Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.

Objective To establish a reasonable and effective blood screening strategy for Hepatitis C virus (HCV), so as to reduce the risk of blood transfusion transmission, ensure blood safety and improve the quality of blood screening. Methods In order to evaluate HCV screening strategies comprehensively, the unqualified blood donations due to anti-HCV alone positivity in Dalian from 2017 to 2021 was tracked, with combined detection methods of electro-chemiluminescence immunoassay (ECLIA) and HCV-RNA nucleic acid test (NAT). Results A total of 851 (0.20%) unqualified donations due to anti-HCV alone positivity were screened from 2017 to 2021, with a decreasing trend in both numbers and rate. Among them, the unqualified rate of samples with anti-HCV reactivity in both dural-ELISA-reagent and NAT decreased significantly (P

This talk outlines a vision for Common European Data Spaces, proposed by the European Commission, where FAIR principles (Wilkinson et al. 2016) and FAIR Digital Objects (FDOs) (De Smedt et al. 2020, Schwardmann 2020) can play a role in bringing together research infrastructures, data aggregators and other stakeholders working with curated objects in museums, herbaria, libraries and archives. The organisations and stakeholders involved represent a wide range of disciplines and data types including biodiversity, ecology, anthropology, archaeology, cultural history, digital storytelling, art conservation, and history of science among others (ICEDIG 2020, Ortolja-Baird and Nyhan 2021). The context and the history of the curated objects also span the natural sciences and cultural heritage domains (Nadim 2021, Weber 2021). Despite this heterogeneity, various common themes in the area of digital curation, open access, and data usage (Tasovac et al. 2020) appear where FDOs and Common European Data Spaces can be a useful venue for supporting the European Strategy for Data. In particular, FDOs, as an abstraction mechanism to structure and describe digital artefacts from a specific domain yet at the same time provide interoperability (De Smedt et al. 2020), can help realise the vision behind a common data space to “bring together relevant data infrastructures and governance frameworks in order to facilitate data pooling and sharing” (European Commission 2022:2).A May 2022 report on the challenges and opportunities of European Common Data Spaces highlights the following points:Open data holders have extensive experience in data publishing, metadata management, data quality, dataset discovery, data federation, as well as tried-and-tested standards (e.g. DCAT) and technologies. There seems to be very little knowledge/technology transfer from the open data community to the data spaces community, which is a missed opportunity. Data space implementations should not reinvent wheels that the open data community has already developed, tested, and used extensively.Whether the data is private, shared, or open, using data from multiple sources requires interoperability at several levels, from identifiers to vocabularies. The question of which data intermediaries will act as neutral agents to ensure interoperability is underexplored in the data space context. Public administrations, building on their experience of publishing open data, are best placed to take on such rolesBuilding on previous conversations facilitated by DiSSCo, DARIAH, Europeana, and Archives Portal Europe Foundation, (Europeana Conference 2021, DARIAH Annual Event 2022), this talk will address the above points from the perspective of bringing together the domains of natural history museums, cultural heritage, and digital humanities. Within our collaboration, we have identified several common areas such as data discoverability, linking, and providing contextual information, which align with the goal of FDO implementation. DiSSCo and DARIAH as European infrastructures, on the one hand, and Europeana and Archives Portal as data aggregators, on the other hand, are involved in improving access to data and the researchers' capacity to work with heterogeneous data sources. One of the biggest shared challenges across the diverse workflows in the arts and humanities and natural history domains is that the data curation processes form a natural continuum between a range of different actors working either in cultural heritage institutions or in academia. In reality, these different layers of curation, enrichment and analysis are separated by legal, institutional, infrastructural and even funding silos (as in many countries, these institutions belong to different ministries, and fall under different legislative frameworks). How can this continuum, from a scholarly point of view, be supported within common data space and FDO framework? At the same time, implementing a common data space requires not just interoperability but stewardship and strategy for sharing resources (Keller 2021).The data infrastructure and FAIR related activities explored in our collaboration are of strategic importance to help Europe and the rest of the world deal with important societal issues. Therefore, bringing this collaboration within the context of FDO provides an ideal avenue to explore potential data, policy, and implementation matters, in order to address the two gaps outlined above for Common Data Spaces. Furthermore, the ideas expressed in Common European Data Space for Cultural Heritage (with Europeana as the core stakeholder) and Green Deal Data Spaces need further clarification concerning implementation planning and most importantly, how multiple commons would work together. With DARIAH coming from the humanities and DiSSCo from the natural sciences side, such collaborations and synergy should align with the Common Data Spaces vision. The philosophy and ideas behind data and digital commons are not new (Fuchs 2020, Kashwan et al. 2021). However, it is crucial to contextualise the implementation strategy and benefits within data intensive, multidisciplinary research and FAIR principles.Given that curated objects are informational resources for the researchers, but can also provide contexts, and make visible the relationships between artefacts, people, publications, organisations, provenance, and events, it is important to think of them as much more than just records in a database. Additionally, FDOs as the digital representations of the curated objects have the potential of fostering cross-disciplinary collaborations (such as between biology, history, art or anthropology) and of providing a wider lens for understanding materiality and the role of data (Ribes 2019). As interdisciplinarity and data-driven foci are gaining traction via applications of artificial intelligence and machine learning, it is vital to understand what FDO adoption and implementation can contribute to common data spaces. We believe FDOs can be a successful foundation for Common European Data Spaces because they can can connect multiple commons -- from Green Deal to Cultural Heritage -- in order to drive forward the vision for interdisciplinary collaboration.

Erythema infectiosum, caused by human parvovirus B19 (B19V), is difficult to diagnose by its clinical symptoms and is often misdiagnosed as measles or rubella. Timely confirmation of measles/rubella or other viral etiologies via laboratory tests can provide an accurate picture of the infection status, which can appropriate response. The purpose of this study was to determine the contribution of B19V as an etiological agent for fever‐rash in suspected cases of measles and rubella in Osaka Prefecture between 2011 and 2021. Of 1356 suspected cases, 167 were confirmed with measles and 166 with rubella using nucleic acid testing (NAT). Of the remaining 1023 cases, 970 from which blood specimens could be obtained were screened by real‐time polymerase chain reaction for B19V, from which 136 (14%) tested positive. Of the positives cases, 21% were young children (9 years and younger), while 64% were adults (20 years and older). Phylogenetic tree analysis showed that 93 samples belonged to genotype 1a. The importance of B19V in the etiology of fever‐rash illness was revealed in this study. The importance of laboratory diagnosis by NAT in maintaining the status of measles elimination and to eliminate rubella was reaffirmed. [ABSTRACT FROM AUTHOR]

The hepatitis B virus (HBV), comprising of ten genotypes (A-J), has been a silent threat against humanity, constituting a public health problem worldwide. In 2016, the World Health Organization set forth an impressive initiative for the global elimination of viral hepatitis by 2030. As the target date approaches, many nations, particularly in the Latin American region, face challenges in designing and implementing their respective elimination plan. This review aimed to portray the state of knowledge about the epidemiological, molecular, and clinical characteristics of HBV genotype H (HBV/H), endemic to Mexico. PubMed, Scopus, Web of Science, and Google Scholar were searched to compile scientific literature over 50 years (1970–2022). A total of 91 articles were organized into thematic categories, addressing essential aspects such as epidemiological data, risk factors, HBV genotype distribution, HBV mixed infections, clinical characteristics, and vaccination. The prevalence and its associated 95% confidence interval (95% CI) were estimated using the Metafor package in R programming language (version 4.1.2). We provide insights into the strengths and weaknesses in diagnostics and prevention measures that explain the current epidemiological profile of HBV/H. Training, research, and awareness actions are required to control HBV infections in Mexico. These actions should contribute to creating more specific clinical practice guides according to the region’s characteristics. Mexico’s elimination plan for HBV will require teamwork among the government health administration, researchers, physicians, specialists, and civil society advocates to overcome this task jointly.

Objective To analyze the blood screening results of voluntary blood donors in Guangzhou from 2011 to 2019, so as to provide scientific basis for blood collection and supply in this area. Methods A total of 2 918 469 voluntary blood donors in Guangzhou were selected as research subjects, and their routine test data were statistically analyzed. Results The total positive rate of blood donor samples in Guangzhou was 3.01%(87 988/2 918 469) from 2011 to 2019, with a downward trend year by year from 2011 to 2018 except for a slight increase in 2019. The difference of total positive rate in each year was statistically significant (P

Derzeit werden viele neue Analysetechniken und Anwendungen für die patientennahe Labordiagnostik angeboten. Dies kann insbesondere im Krankenhaus bedeuten, dass das Nichtlaborpersonal eine Reihe verschiedener Geräte bedienen muss, wodurch unter Umständen die Patientensicherheit gefährdet wird. Daher gibt es verschiedene Ansätze, die Point-of-Care-Gerätelandschaft zu konsolidieren. Neben Geräten, die mithilfe verschiedener Kartuschensysteme unterschiedliche Analysemethoden vereinen, werden hier in Zukunft auch neuartige Systemarchitekturen für mehrere Analysesysteme eines Herstellers mit einem gemeinsamen Intelligent Device Management zum Einsatz kommen. [ABSTRACT FROM AUTHOR]

Chromatin structural organization, gene expression and proteostasis are intricately regulated in a wide range of biological processes, both physiological and pathological. Protein acetylation, a major post-translational modification, is tightly involved in interconnected biological networks, modulating the activation of gene transcription and protein action in cells. A very large number of studies describe the pivotal role of the so-called acetylome (accounting for more than 80% of the human proteome) in orchestrating different pathways in response to stimuli and triggering severe diseases, including cancer. NAA60/NatF (N-terminal acetyltransferase F), also named HAT4 (histone acetyltransferase type B protein 4), is a newly discovered acetyltransferase in humans modifying N-termini of transmembrane proteins starting with M–K/M-A/M-V/M-M residues and is also thought to modify lysine residues of histone H4. Because of its enzymatic features and unusual cell localization on the Golgi membrane, NAA60 is an intriguing acetyltransferase that warrants biochemical and clinical investigation. Although it is still poorly studied, this review summarizes current findings concerning the structural hallmarks and biological role of this novel targetable epigenetic enzyme. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with non-metastatic breast cancer may achieve partial or complete response after neoadjuvant treatment. Early response to treatment after two cycles of chemotherapy has been associated with complete pathological response, longer disease-free interval and better overall survival. We aimed to investigate the role of morphologic, functional and relaxometry MR characteristics in predicting early response to neoadjuvant treatment. Tumor size, estrogen and progesterone receptors, HER2 status, Ki67%, tumor margins, enhancement type or ADC values were not associated with response. The T2 min relaxometry parameter and nodal stage were associated with early response, achieving an AUC of 0.826 [95% CI: 0.66–0.90, p-value < 0.001]. Aim: To evaluate the role of MR relaxometry and derived proton density analysis in the prediction of early treatment response after two cycles of neoadjuvant therapy (NAT), in patients with breast cancer. Methods: This was a prospective study that included 59 patients with breast cancer, who underwent breast MRI prior (MRI1) and after two cycles of NAT (MRI2). The MRI1 included a sequential acquisition with five different TE's (50, 100, 150, 200 and 250 ms) and a TR of 5000 ms. Post-processing was used to obtain the T2 relaxometry map from the MR acquisition. The tumor was delineated and seven relaxometry and proton density parameters were extracted. Additional histopathology data, T2 features and ADC were included. The response to NAT was reported based on the MRI2 as responders: partial response (>30% decreased size) and complete response (no visible tumor stable disease (SD); and non-responders: stable disease or progression (>20% increased size). Statistics was done using Medcalc software. Results: There were 50 (79.3%) patients with response and 13 (20.7%) non-responders to NAT. Age, histologic type, "in situ" component, tumor grade, estrogen and progesterone receptors, ki67% proliferation index and HER2 status were not associated with NAT response (all p > 0.05). The nodal status (N) 0 was associated with early response, while N2 was associated with non-response (p = 0.005). The tumor (T) and metastatic (M) stage were not statistically significant associated with response (p > 0.05). The margins, size and ADC values were not associated with NAT response (p-value > 0.05). The T2 min relaxometry value was associated with response (p = 0.017); a cut-off value of 53.58 obtained 86% sensitivity (95% CI 73.3–94.2), 69.23 specificity (95% CI 38.6–90.9), with an AUC = 0.715 (p = 0.038). The combined model (T2 min and N stage) achieved an AUC of 0.826 [95% CI: 0.66–0.90, p-value < 0.001]. Conclusions: MR relaxometry may be a useful tool in predicting early treatment response to NAT in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: The risk of a blood donation contaminated with hepatitis E virus (HEV) entering the blood supply before introducing universal HEV‐RNA screening in France was estimated to assess the benefit of such a measure. Materials and Methods: The results of selective HEV nucleic acid testing (HEV‐NAT) performed in mini pool of six plasma donations between 2018 and 2020 were extrapolated to the whole blood donor (BD) population after adjustment on three variables: regional establishment, sex and age group. Results: Among the 246,285 plasma donations collected from 172,635 BDs tested for HEV‐RNA, 248 (10.1/10,000) were positive. The extrapolation to all BDs led to an estimated rate of 5.9/10,000 donations (95% confidence interval [CI]: 4.5–7.4) which would be positive to HEV‐RNA and a prevalence of 9.9/10,000 BDs (95% CI: 7.5–12.3). This prevalence was 4.4 times higher in males than females (16.8/10,000 vs. 3.8/10,000, p < 10−4). The highest prevalence was observed in males in the 30–39 age group (20.5/10,000) and the lowest in females in the 50–70 age group (2.8/10,000). Conclusion: The risk of an HEV‐RNA‐positive donation entering the blood supply was estimated at 1 in 1682 donations. This risk does not translate directly to the risk of HEV transfusion transmission, which mainly depends on the total number of viral particles in the transfused blood component and the sensitivity of NAT. [ABSTRACT FROM AUTHOR]

Background: Estimation of residual risk (RR) is necessary to understand status of blood safety with current testing strategies and need to improve it further. These estimates from India are lacking till date. Present study was aimed to estimate RR and incident rate (IR) of transfusion transmitted infectious disease (TTIDs) in Indian setting. Study Design and Methods: Blood donor demographic data, serological testing results and nucleic acid testing (NAT) screening results were collected retrospectively from January 2015 to June 2017. Mathematical modelling using NAT yield/window period model was done to estimate IR and RR of TTIDs. Data was compared between different groups based on age‐group, gender, donation repeatability and type of donor. Results: A total 106 119 blood donors donated 109 441 units with overall TTID reactivity of 2.22%. HBV was most prevalent TTID (1.26%) with RR of 16.1 per million followed by HCV and HIV with RR of 4.4 and 3.1 per million donations, respectively. NAT testing variably reduced RR ranging from 69.4% to 96.1% depending on TTID. Younger, repeat and voluntary donors had significantly lower prevalence of TTIDs compared to older, first time and replacement donors. Discussion: Gaps in the blood safety could be bridged significantly by implementing NAT testing and using quality serological assays. Comparatively high RR despite using quality serological assays and ID‐NAT testing highlights need to develop long term strategies to improve blood safety by focusing on improving donor pool by recruiting regular voluntary donors among youth and imparting knowledge of healthy practices. [ABSTRACT FROM AUTHOR]

Copyright of Iskolakultúra is the property of University of Szeged, Faculty of Arts & Social Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Dengue, chikungunya and zika infections occur in tropical and subtropical regions of the world. We describe the utilization of an in-house nucleic acid test (NAT) targeting all three viruses for febrile returning travelers in Alberta, Canada. Methods NAT was performed until 40 days from symptom onset or exposure due to the prolonged duration of zika virus RNA detection. From Sept 1, 2017 to August 31, 2019, 2552 specimens from 1932 patients were tested. Results Approximately 2% of patients tested were NAT positive for dengue virus (n = 42), chikungunya virus (n = 4), and zika virus (n = 1). The majority presented with fever, myalgia and rash. Regions with the most frequent travel included SouthEast Asia (68.5%), South America (25%) and the Caribbean (6.5%). Ct values were stronger (~ 1.5 logs) for patients within 1–3 days following onset of clinical symptoms than those presenting later. Nineteen patients had urine and plasma submitted; 5 were positive for both specimens and 2 were positive only for dengue virus in the urine. Also, Ct values were lower for plasma when compared to the corresponding urine. RNA was detected until 10 days and 5 days post-exposure in plasma and urine respectively for dengue virus. Conclusions Owing to dengue viremia detected beyond the conventional 7 days and low levels of circulating zika virus globally, a cutoff of 14 days from symptom onset to NAT is sufficient to diagnose acute cases. Inclusion of a zoonotic history form that collects appropriate clinical history results in improved test utilization.

Abstract Background The purpose of this study was to determine whether advanced quantitative magnetic resonance imaging (MRI) can be deployed outside of large, research-oriented academic hospitals and into community care settings to predict eventual pathological complete response (pCR) to neoadjuvant therapy (NAT) in patients with locally advanced breast cancer. Methods Patients with stage II/III breast cancer (N = 28) were enrolled in a multicenter study performed in community radiology settings. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW)-MRI data were acquired at four time points during the course of NAT. Estimates of the vascular perfusion and permeability, as assessed by the volume transfer rate (K trans) using the Patlak model, were generated from the DCE-MRI data while estimates of cell density, as assessed by the apparent diffusion coefficient (ADC), were calculated from DW-MRI data. Tumor volume was calculated using semi-automatic segmentation and combined with K trans and ADC to yield bulk tumor blood flow and cellularity, respectively. The percent change in quantitative parameters at each MRI scan was calculated and compared to pathological response at the time of surgery. The predictive accuracy of each MRI parameter at different time points was quantified using receiver operating characteristic curves. Results Tumor size and quantitative MRI parameters were similar at baseline between groups that achieved pCR (n = 8) and those that did not (n = 20). Patients achieving a pCR had a larger decline in volume and cellularity than those who did not achieve pCR after one cycle of NAT (p

As IPv4 address became exhausted even sooner, China Telecom had been speeding up the IPv4/IPv6 dual IP stack construction before the final large scale application of IPv6.Meanwhile, emphasis of IPv4 address privatize modification was placed on following schedule at this very moment to ensure the smooth transition and public IPv4 address providing.By studying the trace-back model of IPv6 and private IPv4 dual stack IP address in typical telecom business scenarios, the way to separate IP address trace-back model from traditional broadband AAA platform and migrated into cloud deployment were acquired , thus provided a reference for the AAA entirety reconstruction.

The tropospheric and stratospheric nitrate aerosol is simulated by a sectional aerosol model coupled to the Community Earth System Model. The simulated nitrate mass fractional contribution to aerosols is significantly higher in the upper troposphere and lower stratosphere (UTLS) than that at the surface. Both in situ measurements and simulations show that nitrate aerosol accounts for about 30%–40% of the aerosol mass at the tropopause of the Asian summer monsoon (ASM) region. Furthermore, simulated condensed nitric acid particles account for ∼20% of the annual mean aerosol mass at the tropical tropopause, and over 95% in the UTLS at the South Pole in June‐July‐August. Our study suggests that the extremely cold ambient conditions in the UTLS of the tropics, ASM and polar regions thermodynamically favor the condensation of ammonia and nitric acid. The widely distributed nitrate aerosol in the global UTLS may be overlooked by climate models. Plain Language Summary: The tropospheric and stratospheric nitrate aerosol is simulated by a sectional aerosol model coupled to the Community Earth System Model. Simulated nitrate aerosol mass concentrations are evaluated with observations at the surface and the upper troposphere and lower stratosphere (UTLS). At the global surface, simulated nitrate aerosols account for 6% of non‐dust and non‐sea salt aerosol mass. Significantly higher mass fractions of nitrate are simulated in the UTLS. Our study shows that nitrate accounts for about 30%–40% of the aerosol mass in the Asian tropopause aerosol layer. Furthermore, the model simulations suggested that condensed HNO3 particles contribute to about 20% of the annual mean aerosol burden in the tropical tropopause layer and over 95% in the UTLS of the South Pole in June‐July‐August. We find that the cold conditions in the global UTLS thermodynamically favors the condensation of ammonia and nitric acid. The widely distributed nitrate aerosol in the global UTLS may be overlooked by climate models. Key Points: Nitrate and nitric acid aerosol contribute significantly to the tropical upper troposphere and lower stratosphere (UTLS), Asian summer monsoon and polar regionsThe cold ambient conditions in the UTLS thermodynamically favor the condensation of nitric acidThe simulated aerosol in the global UTLS is primarily composed of the secondarily formed nitrate, sulfate and organics [ABSTRACT FROM AUTHOR]

Most eukaryotic proteins are N-terminally acetylated by a set of Nα acetyltransferases (NATs). This ancient and ubiquitous modification plays a fundamental role in protein homeostasis, while mutations are linked to human diseases and phenotypic defects. In particular, Naa50 features species-specific differences, as it is inactive in yeast but active in higher eukaryotes. Together with NatA, it engages in NatE complex formation for cotranslational acetylation. Here, we report Naa50 homologs from the filamentous fungi Chaetomium thermophilum and Neurospora crassa with significant N- and C-terminal extensions to the conserved GNAT domain. Structural and biochemical analyses show that CtNaa50 shares the GNAT structure and substrate specificity with other homologs. However, in contrast to previously analyzed Naa50 proteins, it does not form NatE. The elongated N-terminus increases Naa50 thermostability and binds to dynein light chain protein 1, while our data suggest that conserved positive patches in the C-terminus allow for ribosome binding independent of NatA. Our study provides new insights into the many facets of Naa50 and highlights the diversification of NATs during evolution. [ABSTRACT FROM AUTHOR]