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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 FROM AUTHOR]

Ecuadorian asphalt has the particularity of being prone to premature aging; therefore, the asphalt pavements have insufficient durability. The objective of this experimental work is to assess the effect that a modification with the rejuvenating agent Sylvaroad RP-1000 produces on the properties of AC 20 asphalt from the Esmeraldas Refinery, as well as evaluating its impact on the quality of a typical asphalt mix, without reclaimed asphalt pavement, prepared with modified and unmodified asphalt. The asphalt used is also classified as PG 64-22 and when mixed with 2.5% by weight of the rejuvenator, the grade changed to PG 58-28. Additional studies were carried out using the ?Tc, Glover-Rowe parameters and the corresponding transition temperatures, showing improvements in the results. At that point, a dense mix with 5.5% asphalt was designed. Stiffness modulus, cyclic compression and fatigue modulus tests were applied with the NAT equipment to the specimens. When using modified asphalt, the fatigue behavior improved remarkably. Additionally, an aging process in oven at 85 ° C was applied to both mixtures, measuring the stiffness modulus and fatigue at 8 days, which demonstrated an adequate behavior only in the mixture made with rejuvenator. El asfalto ecuatoriano tiene la particularidad de ser proclive al envejecimiento prematuro incidiendo en que los pavimentos asfálticos presenten una insuficiente durabilidad. El objetivo de este trabajo experimental es valorar el efecto que produce en las propiedades del asfalto AC 20, procedente de la Refinería de Esmeraldas, su modificación con el agente rejuvenecedor Sylvaroad RP-1000; así como evaluar su incidencia en la calidad de una mezcla asfáltica típica, sin material fresado, preparada con asfalto sin modificar y modificado con rejuvenecedor. El asfalto utilizado clasifica como PG 64-22 y al ser mezclado con 2.5% en peso del rejuvenecedor, su grado cambió a PG 58-28. Se realizaron estudios adicionales empleando los parámetros ?Tc, Glover-Rowe y las temperaturas de transición, evidenciándose mejoras en los resultados. Luego se diseñó una mezcla densa con 5.5% de asfalto; a las briquetas confeccionadas se le aplicaron pruebas de módulo de rigidez, compresión cíclica y fatiga con el equipo NAT. Al emplear asfalto modificado el comportamiento a la fatiga mejoró notablemente. Adicionalmente, se aplicó un proceso de envejecimiento en horno a 85°C a ambas mezclas, valorándose el módulo y la fatiga a los 8 días, que demostraron un buen comportamiento solo en la mezcla con rejuvenecedor. [ABSTRACT FROM AUTHOR]

The article discusses point-of-care test which are performed at or near patient care facilities and their results lead directly to a diagnosis, from which a therapeutic consequence can then be derived. Topics discussed include use of antibiotics, which leads to increasing resistance rates; use of selection of molecular biological methods for the diagnostic amplification of pathogen DNA or RNA; and focus to improve patient care, antibiotic management, and infection prevention.

Although rates of organ donation and solid organ transplantation have been increasing over the last few decades, demand for organs still greatly exceeds supply. Several strategies have been utilised to increase organ supply, including utilisation of high-risk (e.g. HCV antibody-positive) donors. In this context, organs from HCV antibody-positive donors have been used in recipients with chronic HCV since the early 1990s. Recently, transplantation of HCV-viraemic organs into HCV-naïve recipients has garnered significant interest, owing to the development of safe and highly effective direct-acting antivirals and increased experience of treating HCV in the post-transplant setting. Preliminary studies based largely in the US have shown excellent outcomes in kidney, liver, heart, and lung transplantation. This practice has the potential to significantly increase transplantation rates and decrease waitlist mortality; however, intentionally transmitting an infectious disease to recipients has important practical and ethical implications. Further, the generalisability of the US experience to other countries is limited by significant differences in HCV-viraemic donor populations. This review summarises the current data on this practice, discusses barriers to implementation, and highlights areas that warrant further study. [ABSTRACT FROM AUTHOR]

Background: Gray zone samples with optical density (OD) lying between cutoff OD and 10% below the cutoff OD (cutoff OD × 0.9) were identified during routine Transfusion Transmissible Infections (TTI) screening. Enzyme-linked immunosorbent assay (ELISA) used for this purpose can sometimes fail to detect blood donors who are recently infected or possessing the low viremia. Estimation of a gray zone in ELISA testing and repeat testing of gray zone samples can further help in reducing the risks of TTI in countries where nucleic acid amplification testing for TTIs is not feasible. Methods: Repeat ELISA testing was done on gray zone samples in duplicate, the samples showing both OD values below gray zone were marked nonreactive, and samples showing one or both OD values in the gray zone were marked indeterminate. The samples on repeat testing showing one or both OD above cutoff values were labeled reactive. Results: Out of the 196 gray zone samples, 33 samples turned out to be reactive (as shown in the table), 39 samples were nonreactive, and 124 samples were again in the gray zone and were labeled as indeterminate. Conclusion: Estimation of gray zone samples with repeat testing can further enhance the safety of blood transfusion in resource-poor developing nations where more sophisticated and sensitive methods such as nucleic acid amplification test (NAT) is not available in all the blood banks. [ABSTRACT FROM AUTHOR]

Ephrin type-A receptor 2 (EPHA2) is a receptor tyrosine kinase (RTK), whose over-expression has been observed in a variety of cancers, including breast cancer. EPHA2 expression may be causally related to tumorigenesis; therefore, it is important to understand how EPHA2 gene (EPHA2) expression is regulated. Here, we report that EPHA2 antisense RNA (EPHA2-AS), a natural antisense transcript, is an important modulator of EPHA2 mRNA levels. EPHA2-AS is a ∼1.8 kb long non-coding RNA (lncRNA) with a poly(A) tail that encodes two splice variants, EPHA2-AS1/2. They are constitutively expressed in a concordant manner with EPHA2 mRNA in human breast adenocarcinoma cell lines and in patient samples, with the highest levels detected in the triple-negative breast cancer (TNBC) subtype. The silencing of EPHA2-AS1/2 by a sense oligonucleotide or over-expression of an antisense oligoribonucleotide, which were both designed from the EPHA2 mRNA region (nt 2955–2974) targeted by AS1/2, showed that EPHA2-AS1/2 modulated EPHA2 mRNA levels by interacting with the specific AS1/2-complementary region in the mRNA. The EPHA2-AS1/2 did not prevent microRNAs from acting on the relevant microRNA response elements shared by EPHA2-AS1/2 and EPHA2 mRNA. Our studies demonstrate a crucial role played by EPHA2-AS1/2 in modulating EPHA2 mRNA levels, and hence production of EPHA2 protein, a key oncogenic RTK that contributes to the tumorigenesis of TNBC cells. • EPHA2 antisense RNA (AS), a natural AS transcript, modulates EPHA2 mRNA levels. • EPHA2 AS is constitutively expressed in human breast cancer cell lines. • EPHA2 AS is expressed in patient samples. • EPHA2 AS is most highly expressed in the triple-negative breast cancer subtype. • EPHA2 AS works by targeting the specific secondary structure of EPHA2 mRNA. [ABSTRACT FROM AUTHOR]

Background: This study analyzes the regulation of and developments in blood donation in China from 1996 to 2019, and demonstrates the government's efforts to improve blood safety.Results: Since the implementation of the Blood Donation Law in 1998, the number of blood donors in China increased by 275% from 1998 to 2018 (from 4 million to 15 million). The principle of no-fault liability was proposed and has been applied since 2010 to the tort liability related to blood transfusion malpractice. In 2015, mutual blood donation accounted for 4.2% of the national collection. However, in some provinces of China, the percentage of mutual blood donation increased from 9.3 to 35.6% in 2016. The National Health Commission canceled mutual blood donation in March of 2018. Since 2015, nucleic acid amplification testing has become a routine test item for screening blood.Conclusions: The Chinese government institutionalized the voluntary non-remunerated donation principle, enacted regulations for the management of blood transfusion, and adopted advanced blood testing technology to sustain blood supply and ensure blood safety. Despite increased blood donation, blood shortages persist. The quality and safety of blood collection can be further improved through the cancellation of mutual blood donation and incentive measures for voluntary non-remunerated donation of blood, which needs facilitation by governmental legislation. [ABSTRACT FROM AUTHOR]

The article focuses on the laboratory diagnostics for suspected Clostridioides difficile-associated Diarrhea (CDAD). It highlights the efforts of the European Society of Clinical Microbiology and Infectious Diseases to conduct test algorithms for acute diagnosis of the CDAD, as of January 2021. It discusses risk factors, mortality and morbidity and treatments associated with the CDAD.

Introduction: Hemotherapy consists of therapeutic treatment using blood transfusion. Because of the vast amount of bloodborne infectious diseases, highly sensitive laboratory tests must be conducted to minimize the transfusion risks for donors and recipients. Thus, the present study aimed to evaluate the prevalence of hepatitis B and C serological markers in samples from a blood bank in Porto Alegre, southern Brazil, as well as the correlation between serology and nucleic acid amplification testing (NAT). Methods: A quantitative, descriptive, retrospective study was conducted to analyze blood donor information obtained from a blood bank database in Porto Alegre, southern Brazil, concerning 2017 and 2018. Serology and NAT results for hepatitis B and C were examined. Results: Of 17,181 blood donations, the total number of serologically reactive samples was 162 (0.94%) for anti-HBc, 20 (0.12%) for HbsAg, and 62 (0.36%) for anti-HCV. Only 4 (0.02%) samples were simultaneously reactive for anti-HBc and HbsAg, being also positive in NAT. The number of samples reactive to hepatitis C in NAT was 18 (0.10%). Conclusions: Biotechnological evolution has contributed to biosafety in blood transfusions. Considering that NAT is relatively recent in blood banks, further studies using different time periods are suggested for yielding satisfactory results for transfusion safety and elucidating the combination of serological testing and NAT at blood banks. [ABSTRACT FROM AUTHOR]

Transporters are transmembrane proteins that mediate the selective translocation of solutes across biological membranes. Recently, we have shown that specific interactions with plasma membrane phospholipids are essential for the formation and/or stability of functional dimers of the purine transporter UapA, a prototypic eukaryotic member of the ubiquitous nucleobase ascorbate transporter (NAT) family. Here, we provide strong evidence that distinct interactions of UapA with membrane lipids are essential for ab initio formation of functional dimers in the ER, or ER exit and further subcellular trafficking. Through genetic screens, we identify mutations that restore defects in dimer formation and/or trafficking. Suppressors of defective dimerization restore ab initio formation of UapA dimers in the ER. Most of these suppressors are located in the movable core domain, but also in the core-dimerization interface and in residues of the dimerization domain exposed to lipids. Molecular dynamics suggest that the majority of suppressors stabilize interhelical interactions in the core domain and thus assist the formation of functional UapA dimers. Among suppressors restoring dimerization, a specific mutation, T401P, was also isolated independently as a suppressor restoring trafficking, suggesting that stabilization of the core domain restores function by sustaining structural defects caused by the abolishment of essential interactions with specific lipids. Importantly, the introduction of mutations topologically equivalent to T401P into a rat homolog of UapA, namely rSNBT1, permitted the functional expression of a mammalian NAT in Aspergillus nidulans. Thus, our results provide a potential route for the functional expression and manipulation of mammalian transporters in the model Aspergillus system. [ABSTRACT FROM AUTHOR]

• Hepatitis E virus (HEV) is the most common cause of acute hepatitis worldwide. • Nucleic acid testing (NAT) is important for the confirmation of acute hepatitis E infection • A World Health Organization International Reference Panel (IRP) for HEV genotypes NAT has been established. • The IRP contains all four major genotypes of HEV that infect humans, including clinically important sub-genotypes. • The IRP is an important resource for HEV NAT assay validation. Globally, hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Epidemiology and clinical presentation of hepatitis E vary greatly by location and are affected by the HEV genotype. Nucleic acid amplification technique (NAT)-based assays are important for the detection of acute HEV infection as well for monitoring chronic cases of hepatitis E. The aim of the study was to evaluate a panel of samples containing different genotypes of HEV for use in nucleic NAT-based assays. The panel of samples comprises eleven different members including HEV genotype 1a (2 strains), 1e, 2a, 3b, 3c, 3e, 3f, 4c, 4g as well as a human isolate related to rabbit HEV. Each laboratory assayed the panel members directly against the 1st World Health Organization (WHO) International Standard (IS) for HEV RNA (6329/10) which is based upon a genotype 3 a strain. The samples for evaluation were distributed to 24 laboratories from 14 different countries and assayed on three separate days. Of these, 23 participating laboratories returned a total of 32 sets of data; 17 from quantitative assays and 15 from qualitative assays. The assays used consisted of a mixture of in-house developed and commercially available assays. The results showed that all samples were detected consistently by the majority of participants, although in some cases, some samples were detected less efficiently. Based on the results of the collaborative study the panel (code number 8578/13) was established as the "1st International Reference Panel (IRP) for all HEV genotypes for NAT-based assays" by the WHO Expert Committee on Biological Standardization. This IRP will be important for assay validation and ensuring adequate detection of different genotypes and clinically important sub-genotypes of HEV. [ABSTRACT FROM AUTHOR]

The emergence of Zika virus (ZIKV) in the Americas has resulted in increased nucleic acid amplification testing (NAT) of clinical samples and blood donations. New molecular diagnostic assays have been developed resulting in a corollary requirement for ZIKV reference material. To address this we have produced and calibrated two African lineage ZIKV reference materials: a highly concentrated secondary standard (NIBSC: 16/110) and a lower concentration external quality control (QC) reagent (NIBSC: 16/124) and compared their performance in three ZIKV NAT assays in relation with the First International Standard (IS) for Zika Virus NAT assays (PEI: 11468/16). In summary the African lineage ZIKV reference materials were detected by all three assays. The ZIKV lineage did not affect the performance of the secondary standard. The external QC reagent (16/124) was detected by all three assays highlighting its suitability for use as a low positive control to monitor assay performance on a regular basis. The relative potency of 16/110 to the IS was 5.49E+06IU/mL (95% CI: 1.46E+06–2.06E+07) and 16/124 to 16/110 was 8.36E+03 (95% CI: 7.83E+03–8.92E+03). The global availability of African lineage ZIKV reference materials will facilitate standardization of ZIKV molecular diagnostic assays between and within laboratories whilst preserving the IS. [ABSTRACT FROM AUTHOR]

Background: over the two last decades, much attention has been given to the prevention of transfusion-transmitted viral infections. Given the potential transmission of viruses during the window period, novel non-serology based approaches such as viral nucleic acid testing (NAT) have been established. Objective: a comparative study of different methods to detect transfusion transmitted viral infections. Materials and methods: this cross-sectional study was conducted at the Egyptian National Blood Transfusion Center (NBTC), Giza. The duration of the research was 2 months from June 2018 to august 2018. In our study 1000 donor samples were tested by ELISA and NAT tests for HBV, HCV and HIV. Results: regarding ELISA tests of the three viruses, only 14 (1.4%) samples were finally HBsAg reactive. Finally, reactive HCVAb were 22 (2.2%) samples, while only 4 (0.4%) samples were HIV Ag-Ab finally reactive. We found highly statistical significant difference between initial and final results of ELISA (p<0.001). Regarding NAT testing of the three viruses. HBV: 5 (0.5%) samples were NAT and ELISA reactive, 1 was NAT yield. HCV: 9 (0.9%) samples were NAT and ELISA reactive. HIV one sample (0.1%) was NAT and ELISA reactive, one (0.1%) was NAT yield. Statistical significant difference was found in comparison between NAT and ELISA in HBV, HCV, and HIV p values <0.001, <0.001, and = 0,008 respectively. Conclusion: we concluded that NAT and ELISA are complementary to each other. NAT is an effective method for safeguarding the blood supply. [ABSTRACT FROM AUTHOR]

Here we have explored the effect of neoagarotetraose (NAT) on liver injury caused by intense exercise. Our results showed that NAT treatment obviously decreased liver weight (p < 0.01), improved the liver morphological structure, decreased ALT level (p < 0.05) and endotoxin (LPS) (p < 0.01). In addition, NAT could regulate bile acid profiles in feces and serum of mice, which indicated the potential of liver function, suggesting that NAT was effective to relieve intense exercise-induced liver injury. NAT could regulate the expression of colon genes. NAT tended to alter the microbial composition of mice under intense exercise. We uncovered the network interactions between liver traits and microbial communities in NAT treatment mice. Interestingly, our data indicated that intense exercise-induced liver injury may be related to Clostridiales. In summary, these results demonstrated that NAT relieved liver injury induced by intense exercise may be related to gut microbiota. NAT can effectively relieve liver injury induced by intense exercise. We uncovered the network interactions between liver traits and microbial communities in NAT treatment mice. [ABSTRACT FROM AUTHOR]

Immunocompromised patients are at significant risk from BKV reactivation, causing allograft dysfunction or loss. Patient management relies on viral DNA monitoring, using a viral load cut-off to reduce immunosuppression. However, consistency between viral load detection assays cannot be achieved without an effective means of standardisation. We have worked with the WHO's Expert Committee on Biological Standardisation to develop suitable reference materials and undertake an international collaborative study to establish the 1st WHO International Standard for BKV detection assays. We report on the evaluation of two lyophilised candidate cell culture derived, whole virus preparations, undertaken by 33 expert laboratories. By employing the principles of biological standardisation, we show improved agreement across laboratories, demonstrating the suitability of either candidate for use as a primary order calibrant. Candidate 14/212 was established by the WHO ECBS with an assigned potency of 7.2 log 10 International Units/mL intended for the calibration of BKV secondary reference materials. [ABSTRACT FROM AUTHOR]

Summary Recent studies of N-terminal acetylation have identified new N-terminal acetyltransferases (NATs) and expanded the known functions of these enzymes beyond their roles as ribosome-associated co-translational modifiers. For instance, the identification of Golgi- and chloroplast-associated NATs shows that acetylation of N termini also happens post-translationally. In addition, we now appreciate that some NATs are highly specific; for example, a dedicated NAT responsible for post-translational N-terminal acetylation of actin was recently revealed. Other studies have extended NAT function beyond Nt acetylation, including functions as lysine acetyltransferases (KATs) and non-catalytic roles. Finally, emerging studies emphasize the physiological relevance of N-terminal acetylation, including roles in calorie-restriction-induced longevity and pathological α-synuclein aggregation in Parkinson's disease. Combined, the NATs rise as multifunctional proteins, and N-terminal acetylation is gaining recognition as a major cellular regulator. N-terminal acetylation, long considered a co-translational and static modification, recently stepped into the post-translational world, and several reports now suggest regulation and crosstalk with other modifications as well as moonlighting functions. Aksnes et al. review novel functions of N-terminal acetyltransferases, including the most recently described Nt acetylation of actin. [ABSTRACT FROM AUTHOR]

• Nt-acetylation is affects the stability, degradation, interaction, and translocation of cellular proteins. • Alterations in the NATs or Nt-acetylation lead to cancer, genetic, neurodegenerative and cardiovascular diseases. • NAT-mediated epigenetic modifications control mitochondrial function, which may lead to inflammatory diseases. Protein N-terminal (Nt) acetylation is an essential post-translational process catalysed by N-acetyltransferases or N-terminal acetyltransferases (NATs). Over the past several decades, several types of NATs (NatA- NatH) have been identified along with their substrates, explaining their significance in eukaryotes. It affects protein stability, protein degradation, protein translocation, and protein–protein interaction. NATs have recently drawn attention as they are associated with the pathogenesis of human diseases. In particular, NAT-induced epigenetic modifications play an important role in the control of mitochondrial function, which may lead to inflammatory diseases. NatC knockdown causes a marked reduction in mitochondrial membrane proteins, impairing their functions, and NatA affects mitophagy via reduced phosphorylation and transcription of the autophagy receptor. However, the NAT-mediated mitochondrial epigenetic mechanisms involved in the inflammatory process remain unexplored. The current review will impart an overview of the biological functions and aberrations of various NAT, which may provide a novel therapeutic strategy for inflammatory disorders. [ABSTRACT FROM AUTHOR]

Smoking plays an important role in carcinogenesis, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the association between smoking status and prognosis in resected PDAC. All patients who underwent resection for PDAC were identified from two prospective institutional databases. Clinicopathologic data as well as demographics including smoking status were extracted. Survival analysis and multivariable Cox regression modelling was performed. Restricted cubic splines were used for linear data to define cut-off points. Out of 848 patients, 357 (42.1%) received neoadjuvant treatment (NAT), 491 upfront resection (57.9%), and 475 (56%) adjuvant therapy. The median overall survival (OS) was 27.8 months, 36.1 months, and 23.0 months for the entire cohort, after NAT and upfront resection. 464 patients were never smokers (54.7%), 250 former smokers (29.5%), and 134 active smokers (15.8%). In the multivariable model, the interaction of neoadjuvant FOLFIRINOX and active smoking was associated with the highest risk for decreased OS (harzard ratio (HR) 2.35; 95% confidence interval 1.13–4.90) and strongly mitigated the benefit of FOLFIRNOX (HR 0.40; 95% CI 0.25–0.63). Adjusted median OS in NAT patients with FOLFIRINOX was not reached for never and former smokers, compared to 26.2 months in active smokers. Based on the model, a nomogram was generated to illustrate the probability of 5-year survival after PDAC resection. The present study confirms that neoadjuvant FOLFIRINOX is associated with excellent survival and demonstrates that active smoking reduces its benefit. The nomogram can assist in daily clinical practice and emphasises the importance of smoking cessation in patients with PDAC, especially prior to NAT with FOLFIRINOX. • Neoadjuvant FOLFIRINOX was associated with excellent overall survival. • Active smoking impaired the benefit of neoadjuvant FOLFIRINOX. • No interactions between smoking status and non-FOLFIRINOX regimens were observed. [ABSTRACT FROM AUTHOR]

Introduction: Blood transfusions began to be performed in Brazil in the twentieth century as a form of therapeutic treatment. With the discovery of the HIV, the safety of donated blood became a priority. Therefore, candidates for blood donation are subjected to clinical and serological screening, in addition to the nucleic acid test (NAT), which has been mandatory since 2014 in blood banks. Methods: We conducted a retrospective study using data from blood donors at one hemotherapy service in Porto Alegre, state of Rio Grande do Sul, from 2015 to 2017. Serological and NAT results for HIV were evaluated. Results: Of the 28,625 samples of users of the hemotherapy service, 41 (0.14%) were HIV reagents and 21 (0.07%) had a reagent result for the NAT test. These data demonstrate a two-fold higher reactivity in the samples of serologically tested units as compared to the methodology used in NAT. Conclusions: Studies with different time periods are needed to further explain this association. The NAT test had a significant increase in the search for viruses and the safety in the release of blood components. The test was introduced in the blood bank routines in order to reduce the window period when compared to serological tests, a fact that was not observed in the years of data collection in the hemotherapy service referred to in this study. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a serious major health concern that has existed from millennia. According to annual WHO report 2016, it is considered as world's ninth highest killer disease by single infectious agent, ranking above HIV/AIDS. To worsen the scenario the development of multi-drug resistant tuberculosis (MDR-TB) and extremely drug-resistant tuberculosis (XDR-TB) have significantly reduced the success rate of TB treatment. Several efforts are being made to handle pharmacodynamic resistance (MDR and XDR-TB) involving designing of new inhibitors, targeting mutated target or by multi-targeting agents. However, the issue of pharmacokinetic resistance in TB is not being addressed appropriately till date. Pharmacokinetic mode of resistance involves an intrinsic mechanism of bacterial drug resistance via expression of various enzymes and efflux pumps that are responsible for the loss of activity of the therapeutic agents. Mycobacterium tuberculosis is also intrinsically resistant to various approved agents via pharmacokinetic mechanism of resistance. Several bacterial enzymes are encoded that either degrade or modifies the drugs and renders them ineffective. Targeting such inactivating bacterial enzymes provides a novel approach to make the current therapy effective and combat the problem of resistance. This review provides an insight into different bacterial enzymes which are responsible for pharmacokinetic drug resistance in TB. The structure attributes and mechanism of catalysis employed by these enzymes to inactivate drug have also been discussed which may provide basis for developing novel therapeutic agents for resistant TB. [ABSTRACT FROM AUTHOR]

Abstract: Kidney transplant from donors with hepatitis C virus (HCV) antibody has been limited to HCV viremic recipients only, due to concern of the HCV transmission. However, the new antiviral medications provide an opportunity to expand the utilization of these donors. To study the risk of HCV transmission in kidney transplantation, we used discarded donor kidneys and determined HCV RNA levels by quantitative real‐time PCR in bilateral (right and left) kidney biopsies and plasma from 14 HCV antibody‐positive donors (sensitivity: 15 international unit (IU)/mL plasma; 1.8 IU/50 nL kidney). In three NAT‐negative donors, HCV RNA was negative in plasma and kidney. In all 11 NAT‐positive donors, HCV RNA was positive in plasma (range: 5807‐19 134 177 IU/mL) but negative in six kidneys from four donors with plasma HCV RNA <1.5 million IU/μL. HCV RNA correlated between right and left kidneys (P = 0.75) and between kidney and plasma (r = 0.86). When normalized by volume, HCV RNA median (range) was 49 (0‐957) IU/50 nL plasma and 1.0 (0‐103) IU/50 nL kidney, significantly lower in kidney (P = 0.005) than in plasma (14‐fold). Plasma HCV RNA can be used to predict the kidney HCV load. Future studies are needed if plasma/kidney HCV levels can be used to stratify donors for transmission risk and recipients for post‐transplant management in extended utilization of HCV antibody‐positive donors. [ABSTRACT FROM AUTHOR]

In November 2017, the deferral on blood donations from highrisk groups in Great Britain was changed to 3 months from last at-risk sexual contact following recommendations from the Advisory Committee on the Safety of Blood, Tissues and Organs. This represented a reduction from 12 months for men who have sex with men, and from a lifetime ban for sex workers. This is a step forward for equality and for reducing stigma around these groups. However, one argument for deferral is the prevalence of infections, which may not be identifi ed due to the fallibility of current testing approaches. Clearly it is vital that the welfare of blood transfusion recipients is prioritised and they are not exposed to unacceptable risks. However, with the increasingly sophisticated technology used to screen blood, it can be argued that the evidence shows that the reduction in deferral does not go far enough. [ABSTRACT FROM AUTHOR]

The assumption that IPv6 will inevitably replace IPv4 as the dominant network layer protocol on the Internet is almost universal. A failure of IPv6 to diffuse is thought to have far-reaching and long-lasting economic and social consequences, yet there have been no prior analyses of the dual-stacking transition mechanism by which IPv6 diffusion is expected to be achieved in order to understand whether it is likely to succeed. Guided by economic theory, this paper presents such an analysis, and concludes that the dual-stacking transition strategy is unlikely to work, leaving the Internet with no workable means of achieving migration to IPv6. The paper concludes with a number of recommendations for regulatory and policy bodies, end-user organisations and network operators. [ABSTRACT FROM AUTHOR]

Nucleic acid testing (NAT) for pathogenic filoviruses plays a key role in surveillance and to control the spread of infection. As they share clinical features with other pathogens, the initial spread of these viruses can be misdiagnosed. Tests that can identify a pathogen in the initial stages of infection are essential to control outbreaks. Since the Ebola virus disease (EVD) outbreak in 2014–2016 several tests have been developed that are faster than previous tests and more suited for field use. Furthermore, the ability to test for a range of pathogens simultaneously has been expanded to improve clinical pathway management of febrile syndromes. This review provides an overview of these novel diagnostic tests. [ABSTRACT FROM AUTHOR]

Actin, one of the most abundant proteins in nature, participates in countless cellular functions ranging from organelle trafficking and pathogen motility to cell migration and regulation of gene transcription. Actin's cellular activities depend on the dynamic transition between its monomeric and filamentous forms, a process exquisitely regulated in cells by a large number of actin-binding and signaling proteins. Additionally, several posttranslational modifications control the cellular functions of actin, including most notably N-terminal (Nt)- acetylation, a prevalent modification throughout the animal kingdom. However, the biological role and mechanism of actin Nt-acetylation are poorly understood, and the identity of actin's N-terminal acetyltransferase (NAT) has remained a mystery. Here, we reveal that NAA80, a suggested NAT enzyme whose substrate specificity had not been characterized, is Nt-acetylating actin. We further show that actin Ntacetylation plays crucial roles in cytoskeletal assembly in vitro and in cells. The absence of Nt-acetylation leads to significant differences in the rates of actin filament depolymerization and elongation, including elongation driven by formins,whereas filament nucleation by the Arp2/ 3 complex is mostly unaffected. NAA80-knockout cells display severely altered cytoskeletal organization, including an increase in the ratio of filamentous to globular actin, increased filopodia and lamellipodia formation, and accelerated cellmotility. Together, the results demonstrate NAA80's role as actin's NAT and reveal a crucial role for actin Ntacetylation in the control of cytoskeleton structure and dynamics. [ABSTRACT FROM AUTHOR]

With the rapid growth of Infrastructure as a Service (IaaS), it becomes more important to increase reliability and availability of a service. In our patent, called Connector in the paper, we allow a server to be live migrated to another physical host with a different Internet Protocol (IP) address; meanwhile, all existing clients still can use their original connections to connect to the new server. However, a client sitting behind a network address translator cannot use Connector directly. In this research, we propose a new mechanism, called Handover , to allow a client sitting behind a network address translator to use Connector. We apply a fake three-way handshake to prevent the redirected traffic from being blocked by a network address translator router. Experimental results show that Handover is effective and the overhead of this changeover process is less than 0.2 s. Furthermore, it may be integrated into a Distributed Denial of Service (DDoS) defense system to guard a host against DDoS attacks. [ABSTRACT FROM AUTHOR]

Abstract: Background: Evaluation of assay performance on postmortem blood specimens (obtained after cessation of the heartbeat) presents unique scientific and regulatory challenges. In the United States, assay performance is evaluated in part by spiking postmortem specimens. Methods: Fifty‐four specimens obtained from decedents known to be infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV), including some coinfections, were tested for each virus using Food and Drug Administration (FDA)‐licensed donor screening tests for nucleic acid, antibody, and antigen. Results: For each disease, >95% of subjects who were reported to have an infection at the time of death had a positive test result on at least one of the donor screening assays for that infection. Conclusion: Licensed donor screening tests were positive on postmortem specimens obtained within 24 hours of death from individuals dying with HIV, HCV, and/or HBV, and were able to detect presence of the virus. The use of multiple tests (including antibody and direct viral detection methods) is necessary to adequately evaluate donors. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effects of neoagarotetraose (NAT) on gut microbiota composition and inflammation after antibiotic treatment. Our results showed that NAT significantly increased the length of colon (P < .01) and decreased the ileocecal valve index (P < .05), and reduced IFN-γ content (P < .01) and downregulated the IFN-γ/IL-4 ratio (P < .01), suggesting that NAT mediated the balance of the Th1/Th2 ratio to maintain the immune equilibrium of the intestinal mucosa. Our data showed that NAT prohibited intestinal inflammation by increasing antimicrobial peptides and gut integrity. Furthermore, NAT administration significantly increased the fecal concentration of total short-chain fatty acids. In addition, NAT had the ability to modulate gut microbiota composition and diversity. In our study, significantly increasedBifidobacterium,LactobacillusandPrevotellawere observed in the NAT group (P < .01). In summary, all of these results demonstrated that NAT was a potential prebiotic for modulating intestinal microbiota and promoting host health. [ABSTRACT FROM PUBLISHER]

Of the 40 million donations screened with Nucleic acid testing (NAT) between July 2001 and December 2015 in France, 20 HIV-positive, 13 HCV-positive and 17 HBV (HBV-NAT was initiated in 2005 and extended to the whole country in 2010) donations were discarded thanks to NAT. The main benefit in terms of discarded donations is related to HBV with a yield of 0.88 per million donations, which is 12.5 and 1.8 times higher than for HCV and HIV respectively. The main risk factor found in these donors during the post donation interview was having sex with men for males ( n = 11, all repeat blood donors), having a partner HCV positive ( n = 6) or at-risk partner (originated from endemic area or HBV positive) for HBV ( n = 8) for HIV, HCV and HBV, respectively. Although the mean viral load was high for HIV (5.6 log copies/mL) and HCV (7 log IU/mL), HBV cases show low level of DNA (1.8 log IU/mL) demonstrating the need of a highly sensitive NAT assay. Overall, the clinical benefit for recipients remains those related to the prevention of HIV contaminations since HCV avoided transmissions are extremely rare (only one case in the last 5 years thanks to NAT) and the potential infectivity of HBV-NAT only positive cases is questionable due to the low level of HBV DNA and the presence of anti-HBs in more than a half of DNA positive/HBsAg and anti-HBc negative donors. [ABSTRACT FROM AUTHOR]

Teaching informatics is inevitable in economics higher education as well as in higher education as a whole. However, defining the content of this education is a hard and rather complex task. In the current study, as part of a larger research project, the author wishes to illustrate what kind of preliminary knowledge the education of informatics can rely on. Since the National Core Curriculum of 1995 took effect, the law made the teaching of informatics compulsory in public education, and the students themselves also come across lots of computer science information in a number of areas. The analysis built on questionnaire-based research points out that, in spite of the legal obligation, the students entering higher education do not possess a homogeneous preliminary knowledge of infomatics, at the same time on some areas they complete the knowledge they acquired at school on their own. The analysis also discusses the suitability of ECDL and GCSE certificates to indicate the level of informatics knowledge. [ABSTRACT FROM AUTHOR]

HBV still represents a global risk factor in transfusion medicine. The residual risk of HBV is not limited to preseroconversion window period but it extends to donors with occult HBV infection (OBI) characterized by the presence of HBV DNA in liver and by the absence of the virus surface antigen. Each country developed an appropriate blood screening policy according to local HBV prevalence, yields of infectious units per different screening methods and cost-effectiveness. We underline the need of maintaining a high level of attention for OBI carrier identification in all blood banks worldwide where the screening procedures are generally based on a combination of both serological markers and nucleic acid amplification test. In this context, markers such as hepatitis B surface antibodies and hepatitis B core antibodies (anti-HBc) might be useful, although the use of this latter is highly debated and still controversial. Our aim is to give an overview on the relevant diagnostic approaches for the routine screening for HBV focusing on the feasi-bility of anti-HBc testing as precautionary measure in preventing OBI transmission worldwide. In our tailored algorithm, the loss of about 1% of 'anti-HBc only' donors, does not significantly affect the blood supply while improving recipient safety. [ABSTRACT FROM AUTHOR]

Background: Mollicutes detection can be cumbersome due to their slow growth in vitro. For this reason, the use of DNA based on generic molecular tests represents an alternative for rapid, sensitive and specific detection of these microorganism. For this reason, six previously described nucleic acid testing assays were compared to evaluate their ability to detect microorganisms belonging to the class Mollicutes. Methods: A panel of 61 mollicutes, including representatives from the Mycoplasma, Acholeplasma, Mesoplasma, Spiroplasma and Ureaplasma genus, were selected to evaluate the sensitivity and specificity of these assays. A total of 21 non-mollicutes, including closely related non-mollicutes species, were used to evaluate specificity. Limits of detection were calculated to determine the analytical sensitivity of the assays. The two best performing assays were subsequently adapted into real-time PCR format, followed by melting curve analysis. Results: Both assays performed satisfactorily, with a 100% specificity described for both assays. The detection limits were found to be between 10-4 and 10-5 dilutions, equivalent to 15 to 150 genome copies approximately. Based on our work, both van Kuppeveld and Botes real-time PCR assays were found to be the best performing tests in terms of sensitivity and specificity. Furthermore, Botes real-time PCR assay could detect phytoplasmas as well. Conclusions: These assays can be very useful for the rapid, specific and sensitive screening cell line contaminants, clinical samples as well as detecting non-culturable, unknown species of mollicutes or mollicutes whose growth is slow or difficult. [ABSTRACT FROM AUTHOR]