bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges of Proper Disposal of Old Long-Lasting Insecticidal Nets and its Alternative Uses in Rural South-Eastern Tanzania
Authors: Salum Sheila J. , Mponzi Winifrida P. , Muyaga Letus L. , Nkya Joel D. , Mwalugelo Yohana A. , Finda Marceline F. , Msuya Hajirani M. , Lwetoijera Dickson W. , Kaindoa Emmanuel W. 
Published: December 2022

AbstractIntroductionInsecticide-treated nets (ITNs) specifically long-lasting insecticidal nets (LLINs) are one of the most commonly used, scalable and cost-effective tools for controlling malaria transmission in sub-Saharan Africa. However, multiple alternative uses of retired LLINs have been observed and are associated with poor disposal practices. Nevertheless, the World Health Organisation (WHO) provided guidelines and recommendations for proper management of worn-out LLINs. This study assessed the existing alternative uses and disposal practices of old LLINs.MethodsAn explanatory sequential mixed-methods approach was used to assess LLINs existing alternative uses, disposal practices, knowledge and perceptions regarding WHO recommendations on proper disposal of old LLINs among stakeholders in Kilombero and Ulanga districts, southe-astern Tanzania. A survey questionnaire was administered to 384 respondents, Focus Group Discussions (FGD) and Key Informant Interviews (KII) were conducted to clarify responses regarding existing disposal practices with associated challenges and alternative uses of the LLINs. Findings from both study components were used to draw inferences.ResultsA total of 384 people surveyed, 97% were not aware of the WHO recommendation on proper disposal of old LLINs. The common methods used to dispose LLINs were burning 30.73%, disposing of into garbage pit 14.84% and alternative uses 12.24 %. Of respondents with LLINs (239); 41% had alternative uses while 59% had no alternative uses. The common alternative uses were ropes for tying or covering items 20.92%, garden fencing 7.53%, chicken coops 5.02% and 7.53% for other minor alternative uses. All key informants reported being unaware of the WHO guideline on the proper disposal of the old LLINs.ConclusionThis study demonstrates that despite participant’s limited knowledge on WHO guidelines for proper disposal of old LLINs, after presenting these guidelines, majority are willing to comply. Comprehensive efforts are therefore needed to address challenges associated with poor disposal, alternative uses and awareness about WHO guidelines among key stakeholders. Collection strategies should be agreed upon within the community members prior to replacement. Since alternative uses sometimes referred to as repurposing of old nets, proper guidelines should be developed to ensure that repurposing of old LLINs do not cause harm to human health and the environment.
Development of an Ectopic huLiver Model forPlasmodiumLiver Stage Infection
Authors: Reyes Gabriela Samayoa , Flaherty Siobhan , Wickham Kristina S. , Viera-Morilla Sara , Strauch Pamela , Roth Alison , Padrón Laura , Jackson Conner , Meireles Patricia , Calvo David , Roobsoong Wanlapa , Kangwanrangsan Niwat , Sattabongkot Jetsumon , Reichard Gregory , Lafuente-Monasterio Maria José , Rochford Rosemary 
Published: December 2022

AbstractEarlyPlasmodium falciparumandP. vivaxinfection requires parasite replication within host hepatocytes, referred to as liver stage (LS). However, limited understanding of infection dynamics in human LS exists due to species-specificity challenges. Reported here is a reproducible, easy-to-manipulate, and moderate-costin vivomodel to study human Plasmodium LS in mice; the ectopic huLiver model. Ectopic huLiver tumors were generated through subcutaneous injection of the HC-04 cell line and shown to be infectible by both freshly dissected sporozoites and through the bite of infected mosquitoes. Evidence for complete LS development was supported by the transition to blood-stage infection in mice engrafted with human erythrocytes. Additionally, this model was successfully evaluated for its utility in testing antimalarial therapeutics, as supported by primaquine acting as a causal prophylactic againstP. falciparum.Presented here is a new platform for the study of humanPlasmodiuminfection with the potential to aid in drug discovery.
Gemigliptin alleviates succinate induced endoplasmic reticulum stress and activation of hepatic stellate cells
Authors: Do Dinh-Vinh , Nguyen Giang , Park So Young , Cho Eun-Hee 
Published: December 2022

ABSTRACTBackgroundHepatic stellate cells (HSCs) activation is the principal event in the development of liver fibrosis in which succinate-GPR91 signaling has recently been shown to be a contributor. Moreover, endoplasmic reticulum (ER) stress has been reported to involve in HSC activation, but its association with succinate in pathogenesis of liver fibrosis remains scarce. In this study, we investigated the role of gemigliptin, an antidiabetic DDP-4 inhibitor, in the succinate-induced ER stress and activation of HSCs.MethodsLX-2 cells, the immortalized human HSCs, were treated with succinate and gemigliptin. For animal experiments, C57BL/6N mice were divided into 3 groups: control diet, high-fat high-cholesterol (HFHC) diet, and HFHC diet mixed with gemigliptin.ResultsSuccinate significantly induced HSC activation and increased expression of inflammatory markers and the increase in the migration of HSCs. The treatment of succinate also caused ER dilation and activated the unfolded protein response (UPR) signaling as PERK, eIF2alpha, Bip, suggesting increasing ER stress in HSCs. All responses of HSCs to succinate were attenuated with the co-treatment of gemigliptin. Moreover, the exposure of HSCs to tunicamycin, an inducer of ER stress, promoted the expression of α-SMA, proliferation and migration of HSCs. In vivo, the level of fibrotic and ER stress markers was increased in mice fed with HFHC diet and the administration of gemigliptin improved these changes in HFHC-induced mice.ConclusionThis study showed the involvement of ER stress in the activation of succinate-induced LX-2 HSCs and gemigliptin significantly reduced ER stress in HSC activation. Therefore, gemigliptin may become an anti-fibrotic agent and targeting to succinate and ER stress may be a promising therapeutic in the management of liver fibrosis.
WITHDRAWN: Isolation and Characterization of the Lytic Bacteriophages and Its Application in Combination with Amoxicillin against Aeromonas dhakensis
Authors: Sawaengwong Thanchanok , Sunthornthummas Sirinthorn , Wongyoo Rinratree , Surachat Komwit , Rangsiruji Achariya , Atithep Thassanant , Sarawaneeyaruk Siriruk , Doi Katsumi , Nantavisai Kwannan , Insian Kedvadee , Pomwised Rattanaruji , Pringsulaka Onanong 
Published: December 2022

Withdrawal StatementThe authors have withdrawn their manuscript owing to self-plagiarism concerns. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Effects of Low-level Persistent Infection on maintenance of immunity by CD4 T cell subsets and Th1 cytokines
Authors: Ibitokou Samad A. , Gbedande Komi , Opata Michael M. , Carpio Victor H. , Marshall Karis M. , Stephens Robin 
Published: December 2022

ABSTRACTCD4 T cells are required, along with antibodies, for complete protection from blood-stage infection withPlasmodium spp., which cause malaria. Without continuous exposure, as on emigration of people from endemic areas, protection from malaria decays. As in other persistent infections, low-levelP. chabaudiprotects the host from re-infection at two months post-infection, a phenomenon termed premunition. Premunition is correlated with T cell responses, rather than antibody levels. We previously showed that while both effector T cells (Teff) and memory T cells (Tmem) are present after infection, Teff protect better than Tmem. Here we studied T cell kinetics post-infection by labelling dividingIfng+T cells with BrdU in infectedIfng-reporter mice. A large drop in specific T cell numbers andIfng+cells upon clearance of parasite suggest a mechanism for decay of protection. Although protection decays, CD4 Tmem persist, including a highly-differentiated CD27-Effector Memory (Tem) subset that maintains someIfngexpression. In addition, pre-treatment of chronically-infected animals with neutralizing antibody to IFN-γ, or clodronate liposomes before re-infection decrease premonition supporting a role for Th1-type immunity to re-infection. A pulse/chase experiment comparing chronically infected to treated animals showed that recently dividedIfng+T cells, particularly IFN-γ+TNF+IL-2-T cells, are promoted by persistent infection. These data suggest that low-level persistent infection reduces CD4+Tmem survival and multi-functional Teff but promotes IFN-γ+TNF+IL-2-Late Effector Memory and Terminally Differentiated Effector T cells and prolongs immunity.
Running Kinesin-1 shapes the microtubule acetylation gradient
Authors: Andreu-Carbó Mireia , Egoldt Cornelia , Velluz Marie-Claire , Aumeier Charlotte 
Published: December 2022

ABSTRACTThe properties of single microtubules within the microtubule network can be modulated through posttranslational modifications (PTMs), including acetylation within the lumen of microtubules. To access the lumen, the enzymes could either enter through the microtubule ends or at damage sites along the microtubule shaft. Here we show that the acetylation profile depends on damage sites, which can be caused by the motor protein kinesin-1. Indeed, the entry of the deacetylase HDAC6 into the microtubule lumen depends on kinesin-1-induced damage sites. In contrast, activity of the microtubule acetylase αTAT1 is independent of kinesin-1 and shaft damage. On a cellular level, our results show that microtubule acetylation distributes in an exponential gradient. This gradient results from tight regulation of microtubule (de-)acetylation and scales with the size of the cells. The control of shaft damage represents a novel mechanism to regulate PTM inside the microtubule by giving access to the lumen.
Associations between area-level health-related social factor indices and risk of acute COVID-19: An EHR-based cohort study from the RECOVER program
Authors: Chisolm Deena J. , Webb Ryan , Salamon Katherine S. , Schuchard Julia , Mendonca Eneida A , Sills Marion R. , Patel Payal B , Musante Jordan , Forrest Christopher B. , Jhaveri Ravi , Pajor Nathan M , Rao Suchitra , Lee Grace M. , Mejias Asuncion 
Published: December 2022

ABSTRACTBackgroundResearch demonstrates that SARS-CoV-2 infection (COVID-19) among adults disproportionately impacts racial and ethnic minorities and those living in lower-income communities. Similar research in children is limited due, in part, to the relatively low COVID-19 incidence in children compared to adults. This analysis, conducted as part of the RECOVER Initiative, explores this question.MethodsElectronic health record (EHR) data from PEDSnet, a multi-institutional research network of pediatric healthcare organizations, were geocoded and linked to two indices of contextual social deprivation: the Area Deprivation Index and the Child Opportunity Index. Univariate statistics were employed to test the association between each index and COVID19 positivity among children ages 0-20 tested at one of six Children’s hospitals. Multivariate logistic regression was used to explore the relationship between these social context indices and racial disparities in positivity, controlling co-variates.ResultsBoth ADI and COI were significantly associated with COVID-19 positivity in univariate and adjusted models, particularly in the pre-delta and delta variant waves. ADI showed a stronger association. Higher rates of positivity were found for non-Hispanic Black, Hispanic, and multi-racial children compared to non-Hispanic White children. These racial disparities remained significant after control for either index and for other variables.ConclusionADI and COI are significantly associated with COVID-19 test positivity in a population of children and adolescents tested in children’s hospital settings. These social contextual variables do not fully explain racial disparities, arguing that racial disparities are not solely a reflection of socioeconomic status. Future disparities research should consider both race and social context.
High prevalence of low high-density lipoprotein cholesterol and insulin resistance among children and adolescents living with HIV in Uganda: Harbinger for metabolic syndrome?
Authors: Kisitu Grace , Shabanova Veronika , Naiga Fairuzi , Nakagwa Mary , Kekitiinwa Adeodata R , Elyanu Peter J. , Paintsil Elijah 
Published: December 2022

AbstractBackgroundAntiretroviral Therapy-associated adverse effects and comorbidities are still pervasive in people living with HIV, especially metabolic syndrome (MetS), which is on the rise and occurring at early age. However, there is paucity of data on MetS in children and adolescents living with HIV (CALWH), particularly in sub-Saharan Africa. We investigated the age-dependent prevalence of components of MetS in this population.MethodsA cross-sectional pilot study of CALWH treated at the Baylor Uganda Clinical Centre of Excellence in Kampala, Uganda. Using stratified by age group and sex random sampling, participants were recruited from May to August 2021. At enrollment, we collected data on participant demographics, anthropometric measurements, HIV disease characteristics, and past medical history and obtained blood for fasting levels of glucose, insulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL) cholesterol. The primary outcome of MetS was defined by both the International Diabetes Federation (IDF) and Adult Treatment Panel (ATPIII) criteria. We estimated the prevalence of MetS and its components for all participants and by the stratification factors.ResultsWe enrolled 90 children and adolescents: <10 y/o (N=30), 10 to <16 y/o (N=30), and ≥16 (N=30) y/o. Fifty-one percent were females. The prevalence of MetS was 1.11% (1 of 90) using either IDF or ATPIII criteria for all participants, and 3.33% for ≥16-year group. Over 55% of participants had ≥1 IDF component, with 47% having low HDL cholesterol; 14% of participants had early insulin resistance using the HOMA index. The proportion of early insulin resistance was 6.67%, 23.33%, and 13.33% for the three age groups, respectively. Two participants (6.67%) in the 10 to <16 years group had significant insulin resistance. For every 1-year increase in age, HOMA index increased by 0.04 (95% Confidence Interval 0.01, 0.08), p=0.02.ConclusionsThe high prevalence of components of MetS, particularly low HDL and early insulin resistance, are of concern. With increasing survival of CALWH into adulthood and increased lifetime exposure to ART, the frequency of MetS in this population may rise, increasing the lifetime risk for associated health problems, such as type 2 diabetes, myocardial infarction, stroke, and nonalcoholic fatty liver disease.
Large-scale duplication events underpin population-level flexibility in tRNA gene copy number inPseudomonas fluorescensSBW25
Authors: Khomarbaghi Zahra , Ngan Wing Y. , Ayan Gökçe B. , Lim Sungbin , Dechow-Seligmann Gunda , Nandy Pabitra , Gallie Jenna 
Published: December 2022

ABSTRACTThe complement of tRNA genes within a genome is typically considered to be a (relatively) stable characteristic of an organism. Here we demonstrate that bacterial tRNA gene set composition can be more flexible than previously appreciated, particularly regarding tRNA gene copy number. We report the high-rate occurrence of spontaneous, large-scale, tandem duplication events in laboratory populations of the bacteriumPseudomonas fluorescensSBW25. The identified duplications are up to ∼1 Mb in size (∼15 % of the wildtype genome) and are predicted to change the copy number of up to 917 genes, including several tRNA genes. The observed duplications are inherently unstable: they occur, and are subsequently lost, at extremely high rates. We propose that this unusually plastic type of mutation provides a mechanism by which tRNA gene set diversity can be rapidly generated, while simultaneously preserving the underlying tRNA gene set in the absence of continued selection. That is, if a tRNA set variant provides no fitness advantage, then high-rate segregation of the duplication ensures the maintenance of the original tRNA gene set. However, if a tRNA gene set variant is beneficial, the underlying duplication fragment(s) may persist for longer and provide raw material for further, more stable, evolutionary change.
Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis
Authors: Roth-Carter Quinn R. , Burks Hope E. , Ren Ziyou , Koetsier Jennifer L. , Tsoi Lam C. , Harms Paul W. , Xing Xianying , Kirma Joseph , Harmon Robert M. , Godsel Lisa M. , Perl Abbey L. , Gudjonsson Johann E. , Green Kathleen J. 
Published: December 2022

AbstractBackgroundDarier, Hailey-Hailey, and Grover’s diseases are rare non-autoimmune acantholytic skin diseases. While these diseases have different underlying causes, they share defects in cell-cell adhesion in the epidermis and desmosome organization.ObjectiveTo better understand the underlying mechanisms leading to disease in these conditions we performed RNA-seq on lesional skin samples from Darier, Hailey-Hailey, and Grover’s disease patients.MethodsRNA-seq and bioinformatics analyses were performed on banked paraffin embedded diagnostic samples from each disease. For detailed Methods, please see the Methods section in this article’s Online Repository atwww.jacionline.org.ResultsThe transcriptomic profiles of Darier, Hailey-Hailey, and Grover’s disease were found to share a remarkable overlap, which did not extend to other common inflammatory skin diseases, psoriasis and atopic dermatitis. Analysis of enriched pathways showed a shared upregulation in keratinocyte differentiation and Th17 inflammatory pathways, and a decrease in cell adhesion and actin organization pathways in Darier, Hailey-Hailey, and Grover’s disease. Direct comparison to atopic dermatitis and psoriasis showed that the downregulation in actin organization pathways was a unique feature in Darier, Hailey-Hailey, and Grover’s disease.Further, upstream regulator analysis suggests that a decrease in SRF/MRTF activity may be responsible for the downregulation of actin organization pathways. Staining for MRTFA in lesional skin samples showed a decrease in nuclear MRTFA in patient skin compared to normal skin.ConclusionThese findings highlight the significant level of similarity in the transcriptome of Darier, Hailey-Hailey, and Grover’s disease, and identify decreases in actin organization pathways as a unique signature present in these conditions.Key MessagesDarier Disease, Hailey-Hailey Disease, and Grover’s Disease share similar transcriptional profiles suggesting common mechanisms of pathogenesis.SRF/MRTFA activity is reduced in Darier Disease, Hailey-Hailey Disease and Grover’s disease, implicating actin organization in acantholysis.
Autophagy degrades immunogenic endogenous retroelements induced by 5-azacytidine in acute myeloid leukemia
Authors: Noronha Nandita , Durette Chantal , Silva Bianca E , Courtois Justine , Humeau Juliette , Sauvat Allan , Hardy Marie-Pierre , Vincent Krystel , Laverdure Jean-Philippe , Lanoix Joël , Baron Frédéric , Thibault Pierre , Perreault Claude , Ehx Gregory 
Published: December 2022

ABSTRACTThe hypomethylating agent 5-azacytidine (AZA) is the first-line therapy for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. Evidence suggests that the anti-tumor effect of AZA results partly from T-cell cytotoxic responses against MHC-I-associated peptides (MAPs) whose expression is induced by hypomethylation. Through a proteogenomic approach, we analyzed the impact of AZA on the transcriptome and MAP repertoire of four AML cell lines and validated salient findings in the transcriptome of 437 primary AML samples. We demonstrate that AZA caused pleiotropic changes in AML cells via perturbation of transcription, translation, and protein degradation. Overall, 1,364 MAPs were upregulated in AZA-treated cells, including several cancer-testis antigens. Increased MAP abundance was due to the upregulation of corresponding transcripts in a minority of cases and post-translational events in most cases. Furthermore, AZA-induced hypomethylation increased the abundance of numerous transcripts, of which 38% were endogenous retroelements (EREs). Upregulated ERE transcripts triggered innate immune responses but were degraded by autophagy and not processed into MAPs. Autophagy resulted from the formation of protein aggregates caused by AZA-dependent inhibition of DNMT2, a tRNA-methyl transferase enzyme. We found that autophagy inhibition had a synergistic effect with AZA on AML cell proliferation and survival, increased ERE levels and triggered pro-inflammatory responses. Finally, autophagy gene signatures were associated with a lower abundance of CD8+T-cell markers in AML patients expressing high levels of EREs. Altogether, this work demonstrates that the impact of AZA is regulated at several levels and suggests that inhibiting autophagy could improve the immune recognition of AML blasts in patients.
Species-dependent actions of the Goαb selective adenosine A1receptor agonist BnOCPA
Authors: Hill Emily , Huang Xianglin , Del Popolo Ivana , Mache Circe La , Lochner Martin , Ladds Graham , Frenguelli Bruno G. , Wall Mark J. 
Published: December 2022

SummaryWe have previously reported that in rat hippocampal area CA1, the A1R-selective agonist, BnOCPA, potently inhibited excitatory synaptic transmission but did not cause membrane hyperpolarisation in CA1 pyramidal neurons, as would be expected of A1R agonists. This functional discrimination by BnOCPA may arise from its ability, in cAMP inhibition assays, to selectively activate only Gob out of the six Gαi/o subtypes. This may explain why BnOCPA is a potent analgesic that does not cause sedation or cardiorespiratory depression in the rat. Since many preclinical studies are performed using mice, we have here investigated whether BnOCPA’s functional discrimination extends to the mouse. While the potency of BnOCPA against the inhibition of hippocampal synaptic transmission was comparable between rats and mice, we discovered that low concentrations of BnOCPA hyperpolarised mouse CA1 neurons and reduced both their input resistance and firing rate in an A1R-dependent manner. In interleaved experiments we confirmed our previous observations in the rat that concentrations of BnOCPA equivalent to those tested in the mouse had little or no effect on membrane potential or input resistance. Using NanoBRET binding we established that BnOCPA had similar affinity at the mouse and rat A1Rs, and displayed little difference in G protein coupling, as determined using the TRUPATH assay. Thus, although the mechanism for the loss of BnOCPA functional selectivity between pre- and postsynaptic receptors in the mouse hippocampus is currently unclear, it may stem from differences in expression of the individual G proteins subunits or the coupling to murine K+channels.Short summaryWe describe the differential actions of the selective A1R agonist BnOCPA in mouse vs rat hippocampus. In mice, BnOCPA does not show a selectivity between pre and postsynaptic A1Rs, unlike in rats. This may stem from differences in the G protein coupling to K+channels.