Miracle-dz/UniFAR-FTUs huggingface dataset:
How Epstein-Barr Virus Induces the Reorganization of Cellular Chromatin

Five families of viruses support the reorganization of cellular chromatin (ROCC), the compaction and margination of host chromatin, upon their productive infection. That they all share this phenotype implies the importance of ROCC in viral life cycles. ABSTRACT We have discovered how Epstein-Barr virus (EBV) induces the reorganization of cellular chromatin (ROCC), in which host chromatin is compacted and marginated within the nucleus, with viral DNA replication occurring in the chromatin-free regions. Five families of DNA viruses induce ROCC: herpesviruses, adenoviruses, parvoviruses, baculoviruses, and geminiviruses. These families infect a variety of hosts, including vertebrates, insects, and plants. They also share several characteristics: they replicate and encapsidate their genomes in the host nucleus and package their genomes unbound by histones. We have identified the viral genes and processes required for EBV’s ROCC. Each of EBV’s seven core DNA synthesis genes and its origin of lytic replication (oriLyt), in trans, are required, while its protein kinase, BGLF4, and its true late genes are not. Following these findings, we tested the role of EBV lytic DNA amplification in driving ROCC. Surprisingly, the inhibition of EBV’s lytic DNA synthesis still supports chromatin compaction but blocks its margination. We propose a two-step model for ROCC. First, the initiation of viral lytic DNA synthesis induces a cellular response that results in global chromatin compaction. Second, the histone-free, productive viral DNA synthesis leads to the margination of compacted chromatin to the nuclear periphery. We have tested this model by asking if the histone-associated simian virus 40 (SV40) DNA synthesis could substitute for oriLyt-mediated synthesis and found that EBV’s ROCC is incompatible with SV40 DNA replication. Elucidating EBV’s induction of ROCC both illuminates how other viruses can do so and indicates how this spatial control of cellular chromatin benefits them. IMPORTANCE Five families of viruses support the reorganization of cellular chromatin (ROCC), the compaction and margination of host chromatin, upon their productive infection. That they all share this phenotype implies the importance of ROCC in viral life cycles. With Epstein-Barr virus (EBV), a herpesvirus, we show that the viral replication complex and origin of lytic replication (oriLyt) are essential for ROCC. In contrast, its protein kinase and true late genes are not. We show that, unexpectedly, the viral lytic amplification is not required for chromatin compaction but is required for its margination. We propose a two-step model for ROCC: first, global chromatin compaction occurs as a cellular response to the initiation of viral DNA synthesis; then, the accumulation of newly synthesized, histone-free viral DNA leads to cellular chromatin margination. Taken together, our findings provide insights into a process contributing to the productive phase of five families of viruses.
Complete genome analyses of G12P[8] rotavirus strains from hospitalized children in Surabaya, Indonesia, 2017–2018

Rotavirus A (RVA) is a major viral cause of acute gastroenteritis (AGE) worldwide. G12 RVA strains have emerged globally since 2007. There has been no report of the whole genome sequences of G12 RVAs in Indonesia. We performed the complete genome analysis by the next‐generation sequencing of five G12 strains from hospitalized children with AGE in Surabaya from 2017 to 2018. All five G12 strains were Wa‐like strains (G12‐P[8]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1) and were clustered into lineage‐III of VP7 gene phylogenetic tree. STM430 sample was observed as a mixed‐infection between G12 and G1 strains: G12/G1‐P[8]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1. A phylogenetic tree analysis revealed that all five Indonesian G12 strains (SOEP379, STM371, STM413, STM430, and STM433) were genetically close to each other in all 11 genome segments with 98.0%–100% nucleotide identities, except VP3 and NSP4 of STM430, suggesting that these strains have originated from a similar ancestral G12 RVA. The VP3 and NSP4 genome segments of STM430‐G12P[8] were separated phylogenetically from those of the other four G12 strains, probably due to intra‐genotype reassortment between the G12 and G1 Wa‐like strains. The change from G12P[6] lineage‐II in 2007 to G12P[8] lineage‐III 2017–2018 suggests the evolution and diversity of G12 RVAs in Indonesia over the past approximately 10 years.
Effect of combining UV-C irradiation and vacuum sealing on the shelf life of fresh strawberries and tomatoes.

This research presents the effect of combining UV-C irradiation and vacuum sealing on the shelf life of strawberries and quartered tomatoes and compares it with the effect of the sole use of UV-C irradiation or vacuum sealing. A constant UV-C dose of 360 J/m2 was used for the samples' irradiation, and all the vacuum-sealed samples were stored at a reduced pressure of 40 kPa. Organoleptic analysis, microbial population quantification of yeast and mold, Pseudomonas sp. , weight loss, and pH measurements were obtained to identify the spoilage occurrence, monitor the samples' quality, and quantify the shelf life. Sensory evaluation was conducted by 12 consumer panelists to evaluate the aroma, taste, color, texture, and the overall acceptance of the samples. The results revealed that the combination of UV-C irradiation and vacuum sealing prolongs the shelf life of perishables more than the sole use of UV-C irradiation or vacuum sealing. The achieved shelf-life increase using this combination was 124.41% and 54.41% for strawberries and quartered tomatoes, respectively, while acceptable sensory characteristics were maintained throughout the storage period. Hence, this food preservation method can be further improved and integrated in the daily life of modern consumers and the operations of fresh produce retailers, as it could effectively reduce the spoilage rates of fresh produce and help achieve the UN SDG 12.3, which aims to reduce food loss and waste by 50% by 2030 at the consumer and retail levels. PRACTICAL APPLICATION: The system can be further developed and introduced to the market as a kitchen appliance for households or as a predistribution step for fresh produce distribution centers. The shelf-life extension capability of this system, which does not involve any use of chemical substances, would make it an attractive solution for households and food retailers.
SPECTROSCOPIC OBSERVATIONS OF 22 QUASI-STELLAR OBJECTS.

Spectroscopic observations of 22 QSOs are described, and redshifts of 20 are given. A corrected redshift for 3C 407 is included, and an error in that published for PKS 0226-038 is pointed out. The variability of the large-redshift 5C 2.56 is discussed. Lines of Si II have been found in OI 318.
Broadly neutralizing antibody-mediated protection against simian-HIV infection among macaques with vaginal sexually transmitted infections

Objective: Sexually transmitted infections (STIs) increase mucosal HIV infection risk and have the potential to reduce preexposure prophylaxis efficacy. Clinical trials of a broadly neutralizing antibody (bNAb) provided proof-of-concept that passive immunization against HIV can be efficacious in people. We sought to evaluate preclinically the protective efficacy of passive bNAb immunization against simian-human immunodeficiency virus (SHIV) infection in the context of concurrent vaginal STIs. Design: Using a macaque model of combined ulcerative and nonulcerative vaginal STIs caused by Treponema pallidum, Chlamydia trachomatis, and Trichomonas vaginalis, we determined the protection that passively administered bNAb 10-1074 conferred against repeated vaginal SHIV challenges and compared correlates of protection to contemporaneous and historical controls without STIs. Methods: Plasma viremia was monitored via RT-qPCR assay. Concentrations of 10-1074 were determined longitudinally in plasma samples via TZM-bl pseudovirus neutralization assay. Results: Among macaques with vaginal STIs, a single subcutaneous injection of 10-1074 durably protected against vaginal SHIV acquisition, as compared with untreated controls. Interestingly, the median plasma concentration of 10-1074 at the time of SHIV breakthrough among macaques with STIs was significantly higher (10-fold) than that previously observed among 10-1074-treated macaques in the absence of STIs. Conclusion: Passive immunization with 10-1074 conferred significant protection against repeated vaginal SHIV challenges among macaques harboring vaginal STIs. However, our findings suggest that higher bNAb concentrations may be required for prophylaxis when STIs are present. Our findings potentially impact dose selection for the clinical development of bNAbs and highlight the importance of additional preclinical efficacy testing in STI models.
Chemical abundances determined from meteor spectra: II. Evidence for enlarged sodium abundances in meteoroids

The relative abundances of sodium in meteoroids have been estimated by averaging the composition of the radiating gas along the fireball path produced during their atmospheric entry. We used the method of thermal equilibrium for 13 fireballs produced by meteoroids mainly of cometary origin. The results show greater sodium abundances than those expected for interplanetary dust particles and chondritic meteorites, and interesting differences from the sodium abundance of 1P/Halley comet dust were also found.
Biotransformation of Efavirenz and Proteomic Analysis of Cytochrome P450s and UDP-Glucuronosyltransferases in Mouse, Macaque, and Human Brain-Derived In Vitro Systems

Antiretroviral drugs such as efavirenz (EFV) are essential to combat human immunodeficiency virus (HIV) infection in the brain, but little is known about how these drugs are metabolized locally. In this study, the cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT)-dependent metabolism of EFV was probed in brain microsomes from mice, cynomolgus macaques, and humans as well as primary neural cells from C57BL/6N mice. Utilizing ultra high performance liquid chromatography high-resolution mass spectrometry (uHPLC-HRMS), the formation of 8-hydroxyefavirenz (8-OHEFV) from EFV and the glucuronidation of P450-dependent metabolites 8-OHEFV and 8,14-dihydroxyefavirenz (8,14-diOHEFV) were observed in brain microsomes from all three species. The direct glucuronidation of EFV, however, was only detected in cynomolgus macaque brain microsomes. In primary neural cells treated with EFV, microglia were the only cell type to exhibit metabolism, forming 8-OHEFV only. In cells treated with the P450-dependent metabolites of EFV, glucuronidation was detected only in cortical neurons and astrocytes, revealing that certain aspects of EFV metabolism are cell type specific. Untargeted and targeted proteomics experiments were used to identify the P450s and UGTs present in brain microsomes. Eleven P450s and 11 UGTs were detected in human brain microsomes, whereas seven P450s and 14 UGTs were identified in mouse brain microsomes and 15 P450s and four UGTs, respectively, were observed in macaque brain microsomes. This was the first time many of these enzymes have been noted in brain microsomes at the protein level. This study indicates the potential for brain metabolism to contribute to pharmacological and toxicological outcomes of EFV in the brain. SIGNIFICANCE STATEMENT Metabolism in the brain is understudied, and the persistence of human immunodeficiency virus (HIV) infection in the brain warrants the evaluation of how antiretroviral drugs such as efavirenz are metabolized in the brain. Using brain microsomes, the metabolism of efavirenz by both cytochrome P450s (P450s) and UDP-glucuronosyltransferases (UGTs) is established. Additionally, proteomics of brain microsomes characterizes P450s and UGTs in the brain, many of which have not yet been noted in the literature at the protein level.
Effectiveness of exercise in improving quality of life in patients with traumatic brain injury: A systematic review and meta-analysis

ABSTRACT Background Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. People with TBI exhibit poor quality of life (QOL). Exercise is considered a possible intervention for improving cognitive function and mood, helping improve QOL in patients with TBI. According to our review of the relevant literature, meta-analyses have yet to explore the effect of exercise on QOL in patients with TBI. Objectives To determine by meta-analysis of relevant studies whether physical exercise could promote QOL in patients with TBI. Methods A systematic review and meta-analysis of intervention studies involving physical exercise for improving QOL outcomes in TBI populations were conducted according to the PRISMA guideline. Our inclusion criteria were as follows: being randomized or nonrandomized controlled trials with quantitative designs that included patients diagnosed with TBI. Results Thus, six studies met the inclusion criteria. The interventions in four of the six studies had statistically significant effects on QOL improvement. Our meta-analysis revealed a moderate effect size of physical exercise on QOL promotion in patients with TBI. Conclusion For TBI, exercise seems to improve QOL. More research with long-term follow-up should be conducted to assess the effect of exercise on patients with TBI.
Cannabis companies and the sponsorship of scientific research: A cross-sectional Canadian case study

Corporations across sectors engage in the conduct, sponsorship, and dissemination of scientific research. Industry sponsorship of research, however, is associated with research agendas, outcomes, and conclusions that are favourable to the sponsor. The legalization of cannabis in Canada provides a useful case study to understand the nature and extent of the nascent cannabis industry’s involvement in the production of scientific evidence as well as broader impacts on equity-oriented research agendas. We conducted a cross-sectional, descriptive, meta-research study to describe the characteristics of research that reports funding from, or author conflicts of interest with, Canadian cannabis companies. From May to August 2021, we sampled licensed, prominent Canadian cannabis companies, identified their subsidiaries, and searched each company name in the PubMed conflict of interest statement search interface. Authors of included articles disclosed research support from, or conflicts of interest with, Canadian cannabis companies. We included 156 articles: 82% included at least one author with a conflict of interest and 1/3 reported study support from a Canadian cannabis company. More than half of the sampled articles were not cannabis focused, however, a cannabis company was listed amongst other biomedical companies in the author disclosure statement. For articles with a cannabis focus, prevalent topics included cannabis as a treatment for a range of conditions (15/72, 21%), particularly chronic pain (6/72, 8%); as a tool in harm reduction related to other substance use (10/72, 14%); product safety (10/72, 14%); and preclinical animal studies (6/72, 8%). Demographics were underreported in empirical studies with human participants, but most included adults (76/84, 90%) and, where reported, predominantly white (32/39, 82%) and male (49/83, 59%) participants. The cannabis company-funded studies included people who used drugs (37%) and people prescribed medical cannabis (22%). Canadian cannabis companies may be analogous to peer industries such as pharmaceuticals, alcohol, tobacco, and food in the following three ways: sponsoring research related to product development, expanding indications of use, and supporting key opinion leaders. Given the recent legalization of cannabis in Canada, there is ample opportunity to create a policy climate that can mitigate the harms of criminalization as well as impacts of the “funding effect” on research integrity, research agendas, and the evidence base available for decision-making, while promoting high-priority and equity-oriented independent research.
Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients receiving secukinumab: a literature review

Abstract Purpose: There is a paucity of evidence on the impact of immune-mediated inflammatory disease (IMID) treatments on the immunogenicity of SARS-CoV-2 vaccination. The purpose of this literature review is to address the question of whether patients with IMIDs receiving secukinumab, a fully human anti–interleukin-17A monoclonal antibody, have an adequate immune response after SARS-CoV-2 vaccination. Materials and Methods: Clinical studies that evaluated the effect of secukinumab on immune responses in patients with IMIDs after SARS-CoV-2 vaccination were searched in publication databases, including Medline and Embase, until May 2022. Results: From the 53 articles identified, a total of 11 articles were included. Overall, the majority of the patients treated with secukinumab elicited an adequate immune response to SARS-CoV-2 vaccines. Patients receiving secukinumab for IMIDs developed cellular immune responses following vaccination with the BNT162b2 vaccine, and there were no significant differences in the overall humoral and cellular immune responses between patients and healthy individuals. The third dose of the BNT162b2 mRNA vaccine resulted in a positive antibody response in secukinumab-treated patients. Conclusion: The available data provide no evidence of impairment in immunological response to SARS-CoV-2 vaccines by secukinumab in patients with IMIDs.
Proactive personality and organizational support in television industry: Their roles in creativity

Employee creativity is important for TV companies because it can improve organizational performance and increase success and survival based on the ability to create innovations. In response to this, field reporters who work for TV companies also need high creativity in facing the challenges of their work and in creating innovations. This research aims to test the roles of perceived organizational support, proactive personality, the meaning of work, and work engagement in affecting employee creativity. The total numbers of respondents were 119 selected from 14 private television companies in Indonesia. The method in this study is a quantitative approach using the Partial Least Square (PLS) analysis tool with the SmartPls 3.0 application. Most of the hypotheses of this study show significant results. However, there is one finding that a proactive personality is not able to strengthen employee creativity. This indicates that employees’ behavior at work is sometimes different from the personality. This study is the first to look at news reporters’ employee creativity using the suggested model. As a result, organizations can use the study’s findings as a starting point to determine the best strategy for fostering creativity within their workforce.
Clinical Evidence and Practice-Based Guidelines on the Utility of Basal Insulin Combined Oral Therapy (Metformin and Glimepiride) in the Current Era

Background and Aim Basal insulin combined oral therapy consisting of insulin and oral anti-diabetic drugs (OADs) is recommended for type 2 diabetes uncontrolled on OADs. There is a lack of clear evidence and recommendations on the combined use of basal insulin analogues to more than one OADs (glimepiride plus metformin) in effective control of glycemic parameters and its safety in terms of reduced hypoglycemic events, weight gain and cardiovascular risk. In this context, a group of clinical experts discussed the utility of basal insulin combined oral therapy with metformin and glimepiride in the current era. Methods The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists and diabetologists from India and Nepal. Results The panel thoroughly reviewed existing literature on the subject and proposed clinical evidence and practice-based guidelines. Conclusion These current clinical practice guidelines highlight the efficacy and safety of basal insulin combination therapy with various available basal insulins including neutral protamine hagedorn, detemir, glargine and degludec in addition to metformin and glimepiride therapy.
Sexual selection in females and the evolution of polyandry

Over the last decades, the field of sexual selection underwent a paradigm shift from sexual-stereotype thinking of “eager” males and “coy” females towards a more nuanced perspective acknowledging that not only males but also females can benefit from multiple mating and compete for mating partners. Yet, sexual selection in females is still considered a peculiarity, and the evolution of polyandry is often viewed to result from a higher mating interest of males. Here, we present meta-analytic evidence from 77 species across a broad range of animal taxa to demonstrate that female reproductive success is overall positively correlated with mating success, suggesting that females typically benefit from multiple mating. Importantly, we found that these fitness gains likely promote the evolution of polyandry. Our findings offer support for the idea that sexual selection is widespread in females and to play a key role for the evolution of animal mating systems. Thereby, our results extend our understanding of the evolutionary consequences of sexual reproduction and contribute to a more balanced view of how sexual selection operates in males and females.
Jackknife Empirical Likelihood

Empirical likelihood has been found very useful in many different occasions. However, when applied directly to some more complicated statistics such as U-statistics, it runs into serious computational difficulties. In this paper, we introduce a so-called jackknife empirical likelihood (JEL) method. The new method is extremely simple to use in practice. In particular, the JEL is shown to be very effective in handling one and two-sample U-statistics. The JEL can be potentially useful for other nonlinear statistics.
Dr.Nod: computational framework for discovery of regulatory non-coding drivers in tissue-matched distal regulatory elements

Abstract The discovery of cancer driver mutations is a fundamental goal in cancer research. While many cancer driver mutations have been discovered in the protein-coding genome, research into potential cancer drivers in the non-coding regions showed limited success so far. Here, we present a novel comprehensive framework Dr.Nod for detection of non-coding cis-regulatory candidate driver mutations that are associated with dysregulated gene expression using tissue-matched enhancer-gene annotations. Applying the framework to data from over 1500 tumours across eight tissues revealed a 4.4-fold enrichment of candidate driver mutations in regulatory regions of known cancer driver genes. An overarching conclusion that emerges is that the non-coding driver mutations contribute to cancer by significantly altering transcription factor binding sites, leading to upregulation of tissue-matched oncogenes and down-regulation of tumour-suppressor genes. Interestingly, more than half of the detected cancer-promoting non-coding regulatory driver mutations are over 20 kb distant from the cancer-associated genes they regulate. Our results show the importance of tissue-matched enhancer-gene maps, functional impact of mutations, and complex background mutagenesis model for the prediction of non-coding regulatory drivers. In conclusion, our study demonstrates that non-coding mutations in enhancers play a previously underappreciated role in cancer and dysregulation of clinically relevant target genes.