bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal spirometric patterns and respiratory symptoms in HIV patients with no recent pulmonary infection in a periurban hospital in Ghana
Authors: Yeboah Kwame , Musa Latif , Bedu-Addo Kweku 
Published: August 2022

AbstractBackgroundHuman immunodeficiency virus (HIV) infection is associated with chronic pulmonary diseases, even in those with viral suppression by highly active antiretroviral treatment (HAART). Spirometry is an accurate method of diagnosing pulmonary dysfunction in people living with HIV (PLWH).AimTo compare the prevalence of spirometric abnormalities among HAART-treated HIV patients and HAART naïve HIV patients with non-HIV controls with no recent history of pulmonary infection in a peri-urban hospital in Ghana.MethodsIn a case-control design, we recruited 158 HAART-treated HIV patients, 150 HAART-naïve HIV patients and 156 non-HIV controls for the study. Clinical, sociodemographic data and respiratory symptoms were collected using a structured questionnaire. Spirometry was performed in all participants and abnormalities were categorised as obstructive (OSP) or restrictive (RSP) spirometric patterns based on the GLI definition.ResultsThe prevalence of OSP was similar among the HAART treated, HAART naïve HIV patients and non-HIV controls (10.1% vs 9.3% vs 9% respectively, p=0.994), whereas that of RSP was higher in HAART-treated HIV patients compared to HAART-naïve HIV patients and non-HIV controls (51.9% vs 32.1% vs 32% respectively, p=0.013). Respiratory symptoms were common among HAART-treated and HAART-naïve HIV patients compared to non-HIV controls (48.1% vs 40% vs 19.2% respectively, p<0.001). The major determinants of OSP were female gender, exposure to medium-to-high levels of biomass, presence of a respiratory symptom, unemployment and underweight, and that of RSP were age, female gender, being unmarried, medium-to-high biomass exposure and being self-employed or unemployed.ConclusionIn HIV patients without any recent pulmonary infection in a peri-urban area of Ghana, there was no difference in the prevalence of OSP among HAART-treated and HAART naïve HIV patients compared to the non-HIV control. However, the prevalence of RSP was higher in HAART-treated HIV patients compared to the other groups.
Geospatial disparities in federal COVID-19 test-to-treat program
Authors: Smith Emily R. , Oakley Erin M. 
Published: August 2022

AbstractBackgroundPaxlovid is authorized for the treatment of COVID-19 and must be used within the first 5 days of symptom onset. This limited window for initiating treatment makes rapid access critical. Federal Test-to-Treat programs provide tests, prescriptions, and medication in one visit3.ObjectiveThe objective of this study was to map the location of and identify disparities in access to Test-to-Treat programs in the United States (U.S.).MethodsWe obtained location data for public providers of Paxlovid and Test-to-Treat programs in the contiguous U.S. and examined their spatial distribution at the zip code tabulation area level. We defined zip codes as underserved if there was no Test-to-Treat program located within the zip code or within 20 miles of its boundaries.ResultsMore than 52,000,000 people—representing 16% of the continental U.S. population—do not have access to a Test-to-Treat program in their zip code or within 20 miles. The majority of zip codes representing metropolitan areas have a Test-to-Treat program within 20 miles (77%). In contrast, only 30% of small towns and 23% of rural areas have nearby access. Zip codes with a high proportion of Hispanic and Black residents were likely to have access to nearby Test-to-Treat programs (72%, 70%). In contrast, zip codes with a high proportion of Native American residents were likely to be underserved (70%). About half of high-poverty zip codes do not have access to a Test-to-Treat program within 20 miles.DiscussionDisparities in outcomes related to COVID-19 have been apparent since the beginning of the pandemic and continue to grow. While the multi-dimensional measure of social vulnerability was used to expand the federal Test-to-Treat program, some populations remain without access.
Estimating temporally variable selection intensity from ancient DNA data with the flexibility of modelling linkage and epistasis
Authors: He Zhangyi , Dai Xiaoyang , Lyu Wenyang , Beaumont Mark , Yu Feng 
Published: August 2022

AbstractInnovations in ancient DNA (aDNA) preparation and sequencing technologies have exponentially increased the quality and quantity of aDNA data extracted from ancient biological materials. The additional temporal component from the incoming aDNA data can provide improved power to address fundamental evolutionary questions like characterising selection processes that shape the phenotypes and genotypes of contemporary populations or species. However, utilising aDNA to study past selection processes still involves considerable hurdles like how to eliminate the confounding factor of genetic interactions in the inference of selection. To address this issue, we extend the approach of He et al. (2022) to infer temporally variable selection from the aDNA data in the form of genotype likelihoods with the flexibility of modelling linkage and epistasis in this work. Our posterior computation is carried out by a robust adaptive version of the particle marginal Metropolis-Hastings algorithm with a coerced acceptance rate. Our extension inherits the desirable features of He et al. (2022) such as modelling sample uncertainty resulting from the damage and fragmentation of aDNA molecules and reconstructing underlying gamete frequency trajectories of the population. We evaluate its performance through extensive simulations and show its utility with an application to the aDNA data from pigmentation loci in horses.
Lipid Oxidation Controls Peptide Self-Assembly near Membranes
Authors: John Torsten , Piantavigna Stefania , Dealey Tiara J. A. , Abel Bernd , Risselada Herre Jelger , Martin Lisandra L. 
Published: August 2022

AbstractThe self-assembly of peptides into supramolecular fibril structures has been linked to neurodegenerative diseases such as Alzheimer’s disease but has also been observed in functional roles. Peptides are physiologically exposed to crowded environments of biomacromolecules, and particularly membrane lipids, within a cellular milieu. Previous research has shown that membranes can both accelerate and inhibit peptide self-assembly. Here, we studied the impact of biomimetic membranes that mimic cellular oxidative stress and compared this to mammalian and bacterial membranes. Using molecular dynamics simulations and experiments, we propose a model that explains how changes in peptide-membrane binding, electrostatics, and peptide secondary structure stabilization determine the nature of peptide self-assembly. We explored the influence of zwitterionic (POPC), anionic (POPG) and oxidized (PazePC) phospholipids, as well as cholesterol, and mixtures thereof, on the self-assembly kinetics of the amyloid β (1–40) peptide (Aβ40), linked to Alzheimer’s disease, and the amyloid-forming antimicrobial peptide uperin 3.5 (U3.5). We show that the presence of an oxidized lipid had similar effects on peptide self-assembly as the bacterial mimetic membrane. While Aβ40fibril formation was accelerated, U3.5 aggregation was inhibited by the same lipids at the same peptide-to-lipid ratio. We attribute these findings and peptide-specific effects to differences in peptide-membrane adsorption with U3.5 being more strongly bound to the membrane surface and stabilized in an α-helical conformation compared to Aβ40. Different peptide-to-lipid ratios resulted in different effects. Molecular dynamics simulations provided detailed mechanistic insights into the peptide-lipid interactions and secondary structure stability. We found that electrostatic interactions are a primary driving force for peptide-membrane interaction, enabling us to propose a model for predictions how cellular changes might impact peptide self-assemblyin vivo, and potentially impact related diseases.
Pantothenate Kinase 4 Governs Lens Epithelial Fibrosis by Negatively Regulating Pyruvate Kinase M2-Related Glycolysis
Authors: Li Xue , Luo Lin-Lin , Li Rui-Feng , Chen Chun-Lin , Sun Min , Lin Sen 
Published: August 2022

AbstractLens fibrosis is one of the leading causes of cataract in the elderly population. The primary energy substrate of the lens is glucose from the aqueous humor, and the transparency of mature lens epithelial cells (LECs) is dependent on glycolysis for ATP. Therefore, the deconstruction of reprogramming of glycolytic metabolism can contribute to further understanding of LEC epithelial–mesenchymal transition (EMT). In the present study, we found a novel pantothenate kinase 4 (PANK4)-related glycolytic mechanism that regulates LEC EMT. The PANK4 level was correlated with aging in cataract patients and mice. Loss of function of PANK4 significantly contributed to alleviating LEC EMT by upregulating pyruvate kinase M2 isozyme (PKM2), which was phosphorylated at Y105, thus switching oxidative phosphorylation to glycolysis. However, PKM2 regulation did not affect PANK4, demonstrating the downstream role of PKM2. Inhibition of PKM2 inPank4−/−mice caused lens fibrosis, which supports the finding that the PANK4–PKM2 axis is required for LEC EMT. Glycolytic metabolism-governed hypoxia inducible factor (HIF) signaling is involved in PANK4–PKM2-related downstream signaling. However, HIF-1α elevation was independent of PKM2 (S37) but PKM2 (Y105) when PANK4 was deleted, which demonstrated that PKM2 and HIF-1α were not involved in a classic positive feedback loop. Collectively, these results indicate a PANK4-related glycolysis switch that may contribute to HIF-1 stabilization and PKM2 phosphorylation at Y105 and inhibit LEC EMT. The mechanism elucidation in our study may also shed light on fibrosis treatments for other organs.
Soil microbiota and herbivory drive the assembly of plant-associated microbial communities through different mechanisms
Authors: Malacrinò Antonino , Bennett Alison E. 
Published: August 2022

AbstractPlant-associated microbial communities are key to shaping many aspects of plant biology. In this study, we tested whether soil microbial communities and herbivory influence the bacterial community of tomato plants and whether their influence in different plant compartments is driven by microbial spillover between compartments or whether plants are involved in mediating this effect. We grew our plants in soils hosting three different microbial communities and covered (or not) the soil surface to prevent (or allow) passive microbial spillover between compartments, and we exposed them (or not) to herbivory byManduca sexta. The results showed that the soil-driven effect on aboveground compartments was consistently detected regardless of soil coverage, whereas soil cover influenced the herbivore-driven effect on belowground microbiota. Together, our results suggest that the soil microbiota influences aboveground plant and insect microbial communities via changes in plant metabolism and physiology or by sharing microorganisms via xylem sap. In contrast, herbivores influence the belowground plant microbiota via a combination of microbial spillover and changes in plant metabolism. These results demonstrate the important role of plants in linking aboveground and belowground microbiota, and can foster further research on soil microbiota manipulation for sustainable pest management.
Prevalent regulation of GATA2/3 and MSX2 on endogenous retrovirus-derived regulatory elements in human trophoblast stem cells
Authors: Du Cui , Jiang Jing , Li Yuzhuo , Yu Miao , Jin Jian , Chen Shuai , Fan Hairui , Macfarlan Todd S. , Cao Bin , Sun Ming-an 
Published: August 2022

AbstractThe placenta is an organ with extraordinary phenotypic diversity in eutherian mammals. Recent evidence suggests that numerous human placental enhancers are evolved from lineage-specific insertions of endogenous retroviruses (ERVs), yet the transcription factors (TFs) underlying their regulation remain largely elusive. Here, by first focusing on MER41, a primate-specific ERV family previously linked to placenta and innate immunity, we uncover the binding motifs of multiple crucial trophoblast TFs (GATA2/3, MSX2, GRHL2) in addition to innate immunity TFs STAT1 and IRF1. Integration of ChIP-Seq data confirms the binding of GATA2/3, MSX2 and their related factors on the majority of MER41-derived enhancers in human trophoblast stem cells (TSCs). Notably, MER41-derived enhancers that are constitutively active in human TSCs are distinct from those activated upon interferon stimulation, which is determined by the binding of relevant TFs and their sub-family compositions. We further demonstrate that GATA2/3 and MSX2 have prevalent binding on numerous other ERV families – indicating their broad impact on ERV-derived enhancers. Functionally, the derepression of many syncytiotrophoblast genes after disruption of MSX2 is likely to be mediated by regulatory elements derived from ERVs – suggesting ERVs are also important for mediating transcriptional repression. Overall, this study characterized the prevalent regulation of GATA2/3, MSX2 and their co-factors on ERV-derived regulatory elements in human TSCs and provided mechanistic insights into the importance of ERVs in human trophoblast regulatory network.
Low photosynthetic rate under low light stress inhibited sucrose distribution and transportation to grain
Authors: Sun Zhichao , Geng Wenjie , Ren Baizhao , Zhao Bin , Liu Peng , Zhang Jiwang 
Published: August 2022

AbstractUnder the condition of low light, the yield of summer maize decreased significantly, but the decrease of yield under low light stress was not only caused by the lack of photosynthetic assimilates in leaves, but also the transportation and utilization of assimilates by stems and grains. In this study, we investigated the effects of low light stress on leaves, stems and grains of summer maize and the relationship between them. The results showed that the synthesis ability of sucrose and export sucrose to grains ability in leaves decreased under low light. Due to dry matter transfer, the number and area of small vascular bundles in spike node and shank decreased, which restricted the translocation of photoassimilates to grains at filling stage. The activities of SUS and AGPase was decreased in grains under low light stress, which limited the availability of sucrose. The process of leaf synthesis, sucrose loading and sucrose utilization in grains was affected under low light, resulting in relatively higher sucrose concentration in grains than in leaves, forming a “leaf low” - “grain high” sugar concentration gradient, resulting in the opposite hydrostatic pressure, and then feedback inhibition of sucrose output in leaves, reducing sucrose loading and transportation rate.HightlightThe key factor of low light stress reducing summer maize yield was the decrease of leaf photosynthetic rate, resulting in insufficient grain dry matter supply. The sugar concentration gradient between leaves and grains further restricted the sucrose transport from leaves to grains.
A universal influenza mRNA vaccine candidate boosts T-cell responses and reduces zoonotic influenza virus disease in ferrets
Authors: van de Ven Koen , Lanfermeijer Josien , van Dijken Harry , Muramatsu Hiromi , de Melo Caroline Vilas Boas , Lenz Stefanie , Peters Florence , Beattie Mitchell B , Lin Paulo J C , Ferreira José A. , van den Brand Judith , van Baarle Debbie , Pardi Norbert , de Jonge Jørgen 
Published: August 2022

AbstractUniversal influenza vaccines have the potential to protect against continuously evolving and newly emerging influenza viruses. T cells may be an essential target of such vaccines as they can clear infected cells through recognition of conserved influenza virus epitopes. We evaluated a novel T cell-inducing nucleoside-modified mRNA vaccine that encodes the conserved nucleoprotein, matrix protein 1 and polymerase basic protein 1 of an H1N1 influenza virus. To mimic the human situation, we applied the mRNA vaccine as a prime-boost regimen in naïve ferrets (mimicking young children) and as a booster in influenza-experienced ferrets (mimicking adults). The vaccine induced and boosted broadly-reactive T cells in the circulation, bone marrow and respiratory tract. Booster vaccination enhanced protection against heterosubtypic infection with potential pandemic H7N9 influenza virus in influenza-experienced ferrets. Our findings show that mRNA vaccines encoding internal influenza virus proteins are a promising strategy to induce broadly-protective T-cell immunity against influenza viruses.
Prevalence and Determinant of Adverse Drug Reactions Among MDR-TB Patients Attending St. Peter’s TB Specialized Hospital, Addis Ababa, Ethiopia
Authors: Shararo Fikru Letose , Asebe Degemu Sahlu , Teshome Hawine Teshome , Jabo Sahle Asfaw 
Published: August 2022

AbstractBackgroundTuberculosis is one of a major public health problem throughout the world. About 9.6 million people were estimated to have Tuberculosis in 2014. Out of this, 480 000 cases were multidrug-resistant Tuberculosis. Thus, it has to be identified, focused and prioritized for subsequent and targeted interventions. Therefore, the aim this study was to assess the prevalence and factors affecting adverse drug reaction among multidrug-resistant Tuberculosis patients.MethodInstitution based retrospective cross sectional study design was included all patients with Multi Drug Resistant who were registered and treated from 9 January 2020 to 30 March 2020. Data abstraction form was used to obtain patient information from their cards. Data were collected by trained nurses who have been working at multidrug-resistant Tuberculosis treatment service. Data were entered, cleaned and checked using Epi Data version 4.6 statistical software and analyzed by SPSS version 23. Bivariate and multivariate logistic regression analyses were used to examine the association between independent and dependent variables. The results were presented as Odds Ratio with 95% CI.ResultA total of 286 patients were included in the study. The prevalence of adverse drug reaction in this study were 169 (59.1%). Factors such as Treatment outcome and comorbidity were significantly associated with adverse drug reaction among multidrug-resistant Tuberculosis patients.Conclusion and RecommendationThere was high prevalence of adverse drug reaction among multidrug-resistant Tuberculosis patients. Comorbidity and treatment outcome were the independent determinants. Patients who are identified with adverse drug events need special attention enhanced clinical management.
Structure of a volume-regulated heteromeric LRRC8A/C channel
Authors: Rutz Sonja , Deneka Dawid , Dittmann Antje , Sawicka Marta , Dutzler Raimund 
Published: August 2022

AbstractVolume-regulated anion channels participate in the cellular response to osmotic swelling. These heteromeric membrane proteins consist of LRRC8 family members, where the subunit composition determines permeation properties. Although structures of the obligatory LRRC8A subunit have previously defined the architecture of VRACs, the organization of heteromeric channels has remained elusive. Here we have closed this gap by the structural characterization of channels consisting of LRRC8A and LRRC8C. Like homomeric LRRC8A, these proteins assemble as hexamers. Despite twelve possible arrangements, we find a single predominant organization with an A:C ratio of two. In this assembly, four LRRCA subunits cluster in their preferred conformation observed in homomers as pairs of closely interacting proteins that stabilize a closed state of the channel. In contrast, the two interacting LRRC8C subunits show a larger flexibility, underlining their role in the destabilization of the tightly packed A subunits, thereby enhancing the activation properties of the protein.
Disputed interpretations and active strategies of resistance during an audit regulatory debate
Authors: Harber Michael , Verhoef Grietjie , de Villiers Charl 
Published: August 2022

PurposeThe paper aims to examine disputed interpretations of “key meanings” between the audit regulator and Big 4 firms during a highly contentious regulatory debate, showcasing their use of “strategies of resistance” to achieve their intended outcomes.Design/methodology/approachA qualitative analysis is performed of the discourse in a South African audit regulatory debate, set within the country's unique political and historical context. The analysis is informed by the theoretical construct of a “regulatory space” and an established typology of strategic responses to institutional pressures.FindingsThe study’s findings show how resistance to regulatory intentions from influential actors, notably the Big 4 firms, was dispelled. This was achieved by the regulator securing oversight independence, co-opting political support, shortening the debate timeline and unilaterally revising the interpretation of its statutory mandate. The regulator successfully incorporated race equality into its interpretation of how the public interest is advanced (in addition to audit quality). The social legitimacy of the Big 4 was then further undermined. The debate was highly contentious and unproductive and likely contributed to overall societal concerns regarding the legitimacy of, and the value ascribed to, the audit function.Practical implicationsA deeper appreciation of vested interests and differing interpretations of key concepts and regulatory logic could help to promote a less combative regulatory environment, in the interest of enhanced audit quality and the sustainability and legitimacy of the audit profession.Originality/valueThe context provides an example, contrary to that observed in many jurisdictions, where the Big 4 fail to actively resist or even dilute significant regulatory reform. Furthermore, the findings indicate that traditional conceptions of what it means to serve “the public interest” may be evolving in favour of a more liberal social democratic interpretation.