bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why mothers continue to die in Pakistan: a nested case-control study of predictors of maternal mortality
Authors: Ahmad Ahsan Maqbool , Shah Iqbal H. , Mir Ali Muhammad , Sadiq Maqsood , Bosan Muddassir Altaf 
Published: August 2023

AbstractBackgroundMaternal mortality ratio (MMR) declined in Pakistan from 276 maternal deaths per 100,000 live births in 2006-07 to 186 (confidence interval: 138-234) in 2019. Despite this decline, reasons why mothers continue to die, the inequity in the burden of maternal mortality and its predictors largely remain unknown. We investigate the levels and predictors of maternal mortality in Pakistan.MethodsThe in-depth analysis of Pakistan Maternal Mortality Survey (PMMS) 2019 was undertaken using the nested case-control design. We matched 147 maternal deaths that occurred during three years prior to PMMS 2019, defined as “cases”, with 724 women who delivered during the same period, defined as “controls”. We compared socio-demographic background characteristics of cases and controls and performed multivariate regression to investigate the predictors of maternal mortality in Pakistan.ResultsCases and controls were similar on access to antenatal care (ANC) and ANC provider, but differed on age, education, number of pregnancies, type of delivery, tetanus toxoid vaccination during last pregnancy, and ever using a contraceptive method. More of the cases had their last delivery by a skilled birth attendant (83% compared to 63% among controls) and delivered at the government hospital (43% compared to 33% among controls) while home delivery was relatively more common among controls (32% compared to 25% among cases). Odds of maternal death were lowest for women giving birth during age 20-29 (odds ratio – OR: 0.5; 95% CI 0.23-1.07) as compared to women in age 15-19 and those age 30-39 (OR: 1.34; 95% CI 0.61-2.95) and 40-49 (OR: 1.21; 95% CI 0.42-3.45), and among women with secondary or higher education (OR: 0.35; 95% CI 0.17-0.74) compared to women with no education. Surprisingly, women who had their delivery by a skilled birth attendant experienced higher odds of maternal death (OR: 4.07; 95% CI 2.19- 7.57) compared to those who did not. Whereas women having had tetanus injection during last pregnancy (OR: 0.1; 95% CI 0.0-0.96) and ever-used contraceptives (OR: 0.23; 95% CI 0.11-0.39) tend to have reduced odds of maternal death compared to women who did not have the injection and who never used contraceptives, respectively.ConclusionsWomen in certain sub-groups confront higher risks of maternal death. Increasing female education, preventing early and late childbearing through contraceptive use, increasing tetanus vaccination during pregnancy, improving providers’ skills, and quality of health care are required to eliminate preventable maternal deaths in Pakistan.
Scaling laws of human transcriptional activity
Authors: Hong Jiayin , Cavga Ayse Derya , Shah Devina , Laue Ernest , Taipale Jussi 
Published: August 2023

AbstractEach human chromosome maintains its individuality during the cell cycle, and occupies a spatially limited volume, termed chromosome territory. Each linear chromosomal DNA is folded into multiple loops in the three dimensional space, and further organized into densely packed heterochromatin, less dense euchromatin and nucleosome-free regions that are accessible for transcription factor binding. As the average density of chromatin in the nucleus is very high, size exclusion potentially restricts access of large macromolecules such as RNA polymerase II and Mediator to DNA buried in chromosomal interiors. To examine this idea, we investigated whether increase in chromosome size leads to relative decrease in transcriptional activity of larger chromosomes. We found that the scaling of gene expression relative to chromosome size follows exactly the surface-area-to-volume ratio, suggesting that active genes are located at chromosomal surfaces. To directly test this hypothesis, we developed a scalable probe to assess chromatin accessibility to macromolecules of different sizes. We show that, at the chromosomal level, open chromatin landscapes of small and large molecules are strikingly similar. However, at a finer locus level, regions accessible to small transcription factors were primarily enriched around promoters, whereas regions accessible to large molecules were dispersed along gene bodies. Collectively, our results indicate that DNA accessibility is controlled at two different scales, and suggest that making chromatin accessible to large molecules is a critical step in the control of gene expression.
MetaCerberus: distributed highly parallelized scalable HMM-based implementation for robust functional annotation across the tree of life
Authors: Figueroa Jose L. , Dhungel Eliza , Brouwer Cory R. , White Richard Allen 
Published: August 2023

AbstractSummaryMetaCerberus is an exclusive HMM/HMMER-based tool that is massively parallel, on low memory, and provides rapid scalable annotation for functional gene inference across genomes to metacommunities. It provides robust enumeration of functional genes and pathways across many current public databases including KEGG (KO), COGs, CAZy, FOAM, and viral specific databases (i.e., VOGs and PHROGs). In a direct comparison, MetaCerberus was twice as fast as EggNOG-Mapper, and produced better annotation of viruses, phages, and archaeal viruses than DRAM, PROKKA, or InterProScan. MetaCerberus annotates more KOs across domains when compared to DRAM, with a 186x smaller database and a third less memory. MetaCerberus is fully integrated with differential statistical tools (i.e., DESeq2 and edgeR), pathway enrichment (GAGE R), and Pathview R for quantitative elucidation of metabolic pathways. MetaCerberus implements the key to unlocking the biosphere across the tree of life at scale.Availability and implementationMetaCerberus is written in Python and distributed under a BSD-3 license. The source code of MetaCerberus is freely available athttps://github.com/raw-lab/metacerberus. Written in python 3 for both Linux and Mac OS X. MetaCerberus can also be easily installed using mamba create –n metacerberus –c bioconda –c conda-forge metacerberus
RNA binding limits the ligand induced transcriptional potential of estrogen receptor-alpha (ERα)
Authors: Soota Deepanshu , Saravanan Bharath , Mann Rajat , Kharbanda Tripti , Notani Dimple 
Published: August 2023

AbstractTranscription factors (TFs) primarily regulate gene expression by binding to DNA through their DNA binding domains (DBD). Additionally, approximately half of these TFs also interact with RNA. However, the role of RNA in enabling TF binding on chromatin and subsequent transcription is poorly understood. Estrogen receptor-α (ERα) is one such TF that activates genes in response to estrogen stimulation. Here, we report that ERα interacts with various types of RNAs in ligand dependent manner via its RNA binding motif in hinge region. RNA binding defects lead to a global loss of ERα binding in the genome, particularly at weaker ERα motifs. In the absence of RNA binding, the ERα exhibits dynamic behavior in the nucleus and unexpectedly, the dynamic binding coincides with robust polymerase loading on ERα bound chromatin regions. The higher occupancy of PolII was recapitulated by robust ligand induced transcription of ERα-regulated genes. Collectively, our results suggest that RNA interactions strengthen ERα binding to chromatin limiting the ligand-dependent transcriptional upregulation of estrogen-induced genes.
Intracellular mechanical fingerprint reveals cell type specific mechanical tuning
Authors: Muenker Till M. , Vos Bart E. , Betz Timo 
Published: August 2023

AbstractLiving cells are complex entities that perform many different complex tasks with astonishing robustness. While the direct dependence of biological processes on controlled protein expression is well established, we only begin to understand how intracellular mechanical characteristics guide and support biological function. This is in stark contrast to the expected functional role that intracellular mechanical properties should have for many core cellular functions such as organization, homeostasis and transport. From a mechanical point of view, cells are complex viscoelastic materials that are continuously driven out of thermodynamic equilibrium, which makes both a physical measurement and mathematical modeling of its properties difficult. Here, we define a “mechanical fingerprint” that can not only characterize the intracellular mechanical state, but also carve out the mechanical differences between cell types with the potential to relate these to proper cell function. By analyzing the frequency-dependent viscoelastic properties and intracellular activity of cells using microrheology, we distilled the complex active mechanical state into just 6 parameters that comprise the mechanical fingerprint. The systematic investigation of the fingerprint illustrates a parameter tuning that can be explained by the functional cellular requirements. However, the full potential of the mechanical fingerprint is given by a statistical analysis of its parameters across all investigated cell types, which suggests that cells adjust mechanical parameters in a correlated way to position their intracellular mechanical properties within a well defined phase-space that is spanned between activity, mechanical resistance and fluidity. This paves the way for a systematic study of the interdependence of biological function and intracellular active mechanics.
Transferrin Receptor Targeting Chimeras (TransTACs) for Membrane Protein Degradation
Authors: Zhang Dingpeng , Duque-Jimenez Jhoely , Brixi Garyk , Facchinetti Francesco , Rhee Kaitlin , Feng William W. , Jänne Pasi A. , Zhou Xin 
Published: August 2023

AbstractCancer cells require high levels of iron for rapid proliferation, leading to a significant upregulation of the iron carrier protein Transferrin Receptor (TfR) on their cell surface. Leveraging this phenomenon and the exceptionally fast endocytosis rate of TfR, we introduce Transferrin Receptor TArgeting Chimeras (TransTAC), a novel molecular archetype for membrane protein degradation in cancers and other cell types. TransTACs repurpose the naturally recycling receptor TfR1 for protein degradation. To accomplish this, we utilized a combination of protein engineering strategies to redirect the target protein from recycling-endosome trafficking to lysosomal degradation. We show that TransTACs can highly efficiently degrade a diverse range of single-pass, multi-pass, native, or synthetic membrane proteins, establishing new possibilities for targeted cancer therapy.
Increased tolerance to commonly used antibiotics in aPseudomonas aeruginosa ex vivoporcine keratitis model
Authors: Okurowska K. , Monk P. N. , Karunakaran E. 
Published: August 2023

AbstractAntibiotics in development are usually tested on rapidly dividing cells in a culture medium and do not reflect the complexity of infectionsin vivo, while testingin vivois limited, expensive and ethically concerning. This often results in the development and subsequent prescription of antibiotics only targeting infections in which pathogens are undergoing rapid cell division and in case of persistent infections like keratitis leads to poor clinical outcomes such as impaired vision or loss of an eye. In this study, we demonstrate antibiotic tolerance ofPseudomonas aeruginosastrains PA01 and PA14 using theex vivoporcine keratitis model in which bacterial physiology more closely mimics infectionsin vivothan in a culture medium.MBEC and MIC were used as a guideline to establish the concentration of applied antibiotics on tissue. Infectedex vivoporcine corneas were treated with therapeutically relevant concentrations of gentamicin, ciprofloxacin and chloramphenicol. Ciprofloxacin was the most potent across all tests demonstrating a positive correlation with MIC but not MBEC. Nonetheless, the results demonstrated that MIC and MBEC concentrations were not sufficient to clear infection even after 18 hours of continuous exposure to the tested antibiotics reflecting the need for novel antibiotics that can target the persistent subpopulation of these pathogens and the ability of theex vivokeratitis model to be a relevant platform to identify novel antibiotics with suitable activities. There was a clear visual distinction between corneas infected with cytotoxic strain PA14 and invasive strain PA01. In this study, both strains PA14 and PA01 showed a high level of antibiotic tolerance, which suggests that in clinical settings the treatment approach could be similar regardless of the causative strain.Data summaryThe authors confirm all supporting data and protocols have been provided within the article or through supplementary data files.
Downstream effects of dre-miR-210-5p in zebrafish primary ovarian cell culture
Authors: van Gelderen T.A. , Ribas L. 
Published: August 2023

AbstractMicroRNAs (miRNAs) are small, non-coding RNAs that are involved in post-transcriptional gene regulation in many cellular functions and are highly conserved throughout evolution. In teleost fish species, miRNAs are believed to play a role in the reproductive system, but more research is needed to better understand the functions of miRNAs in fish gonads. Furthermore, miR-210 has previously been described to be involved in many processes, such as hypoxia response, angiogenesis, cell proliferation and male infertility. The aim of this study was, first, to develop anin vitromodel in fish to study the functions of miRNAs and second, to identify target genes of dre-miR-210-5p by establishing a primary ovarian cell culture in zebrafish (Danio rerio). The cell culture was performed by isolating ovaries from adult female fish (n=4) which were incubated with dre-miR-210-5p mimic or scramble miRNA mimic. Cell survival was studied by flow cytometry analysis and fluorescent microscopy. Following, the effect of dre-miR-210-5p on ovarian cells was uncovered by RNA-sequencing, identifying ∼6,000 targeted-genes differentially expressed (DEGs), of which ∼2,600 downregulated and ∼3,400 upregulated. GO term and KEGG pathway analyses showed downregulated genes involved in cell cycle processes and reproduction-related pathways while, in contrast, immune-related pathways were upregulated after miR-210 mimic treatment in the ovarian cells. To provide the molecular mechanisms triggered by miRNA-210, seed regions of targeted genes were identified andin silicoanalysis classified DEGs as potential biomarkers in reproduction or immune cell types. These results support the crosstalk between the reproductive and immune system in which dre-miR-210-5p plays a key role in the transcriptomic alteration in the fish ovaries.Take home messagemiR-210 promotes the immune response and suppresses oocyte meiosis in the ovarian cells in zebrafish
Is it what’s inside that matters? A conserved microbiome in woody tissues ofPinus radiata
Authors: Daley Kaitlyn , Eslami Yeganeh , Armstrong Charlotte , Wigley Kathryn , Wakelin Steven A. 
Published: August 2023

AbstractUnderstanding the interaction of endophytic microbiomes and their tree hosts may provide insights into wood formation and quality. Given the role of wood in carbon and nutrient cycling, this will provide valuable insights for forest growth and carbon cycling globally. Furthermore, the management of these interactions may add new value to wood-and fibre-based forest products. We assessed the microbiome of outer and inner bark, cambium tissue, year 2-8 wood increments, and the pith of 11Pinus radiatatrees, a widely planted, model conifer species. Diverse prokaryotic and fungal microbiomes were present in all trees, with communities structured by tissue type (p<0.001). Inner and outer bark tissues had high richness and the most distinct communities. Microbiome richness was lowest in year 2 through to year 8 wood, and the communities in these samples had similar composition. Prokaryote communities were dominated by Alpha-Beta-, and Gamma-proteobacteria, Actinobacteria, Firmicutes (Clostridia and Bacilli). Within fungal communities, Sordariomycetes comprised over 90% of the taxa present. Microbiomes of cambial and pith tissues were distinct to those niches. Overall, we provide further support that the wood of conifers is host to distinct microbiome communities. Microbiomes in these niches are profoundly placed to impact tree physiology, health, and fitness, through to ecosystem function and global carbon cycles.
Association of coffee consumption in metabolic syndrome: a cross-sectional and Mendelian randomization study in UK Biobank
Authors: Wong Tommy Hon Ting , Luo Shan , Au Yeung Shiu Lun , Louie Jimmy Chun Yu 
Published: August 2023

AbstractObjectiveTo investigate the associations between coffee consumption and metabolic syndrome and its component conditions, as well as the effect of using milk, sugar, and artificial sweetener on these associations.Research Design and MethodsThe cross-sectional analysis included 351,805 participants from the UK Biobank. Coffee consumption data was obtained using food frequency questionnaire and 24-hour recall and metabolic syndrome was ascertained based on blood biochemistry results and self-reported medication use. Odds ratios were calculated using multivariable logistic regression adjusted for lifestyle and socioeconomic factors, with verification using two-sample Mendelian randomization.ResultsCoffee consumption up to 2 cups per day was inversely associated with metabolic syndrome (1 cup/day, OR: 0.88, 95% CI: 0.85, 0.92; 2 cups/day, OR: 0.90, 95% CI: 0.86, 0.93) while associations at higher intakes were near null. Mendelian randomization did not support a causal association between coffee intake and metabolic syndrome. Both self-reported and genetically predicted high coffee consumption (4 cups per day or more) were associated with central obesity. The inverse association between coffee consumption and metabolic syndrome was more profound among drinkers of ground coffee than those of instant coffee. Results were similar when stratified by the use of milk and sugar, yet the use of artificial sweetener with coffee was positively associated with metabolic syndrome and all component conditions.ConclusionsCoffee consumption likely increase the risk of central obesity but unlikely impact risk of metabolic syndrome. The possible health effect of using artificial sweetener with coffee warrant investigations in future studies.
Elevated pre-treatment Neutrophil-to-lymphocyte and neutrophil-to-lymphocyte-platelet ratios are associated with a high risk of in-hospital death among patients with prostate cancer in Nigeria
Authors: Okoye Jude Ogechukwu , Ogbonnaya Vivian Ifunanya , Chiemeka Michael Emeka , Ogenyi Samuel Ifedioranma 
Published: August 2023

AbstractIntroductionIn the last decade, there is an increasing mortality rate among patients diagnosed with prostate cancer (PCa) in West Africa. To identify the causes of the high mortality rate, this study analyzed the occurrence of high-grade tumours and the presence of BRCA2 mutation. It also assessed the systemic inflammatory indices as prognostic tools in low-resource settings.MethodsThis study included 72 cases of PCa diagnosed from Jan. 2017 to Dec. 2020. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelets-neutrophils-to-lymphocytes ratio (PNLR), and neutrophils-to-lymphocytes platelets ratio (NLPR) were assessed and analyzed accordingly. Significance was set at p< 0.05.ResultsThe prevalence of Gleason grades (G) 1 to 5 was 9.3%, 16.3%, 16.3%, 25.6, and 32.6%, respectively. There was a high frequency of BRCA2 mutation (58.3%) and the frequency was higher among patients with G4/5 tumours (59.5%) than in patients with G1-G3 tumours (46.7%) at p= 0.347. A high frequency of G4/5 tumours was observed among patients within the age group of 50-59 years (n= 7/8; 87.5%) and patients with castration-resistant PCa (n= 12/17; 70.6%). The pre-treatment PLR and calcium concentration were higher among patients with G4/5 tumours compared to patients with G1-G3 tumours (p= 0.046 and < 0.001, respectively.) There were direct relationships between BRCA2 expression and age (p= 0.019), tumour grade and calcium (p= 0.000), BRCA2 and calcium expression (p= 0.027), unemployment and G4/5 (p< 0.001), and education status and G4/5 (p= 0.020). The pretreatment NLR and NLPR were 2.0 and 4.7 times higher in in-hospital deaths than in stable discharges at p= 0.005 and 0.001, respectively.ConclusionThis study revealed high frequencies of BRCA2 mutation and high-grade PCa in Southern Nigeria. It also suggests that pre-treatment PLR could be used to identify patients with G4/5 while pretreatment NLR and NLPR could be used to predict treatment outcomes.
Reproduction Number EXCEL Model of COVID-19 for predictive calculation of nearby trend up to the end of infection
Authors: Matsuda Shinzaburo , Toki Hiroshi 
Published: August 2023

AbstractReproduction Number (RN-)EXCEL Model has been developed on an EXCEL sheet to provide important characteristics of COVID-19 infectious disease for practical use. The model is developed based only on observed data to predict future infection toward herd immunity threshold and until the end stage of the infection. Basic equations are simple and constructed in analogy with neutron multiplication reactions in nuclear reactor. To know the next day infection, we calculate an exponential increase in one day step with a rate obtained from nearby PCR positive infectious numbers, which are daily input in the EXCEL sheet. In a closed community, main players are non-immune holders and immune holders, where total number of immune holders derived from infection and vaccination plays an essential role. In traditional SIR model, infection behavior is characterized by the reproduction rate in differential equation where social actions such as governmental regulations or vaccinations are included as constant breaking term for infection spread. However, in actual situation these terms are time dependent and is difficult to solve by a set of differential equations. In contrast, RN-EXCEL model deals with infection by defining successive reproduction number for each time interval as inchworm that represents a clear physical picture of the virus infectivity. Using this model, a lot of predictions were made for semi-closed communities domestically and world-wide, timely for practical use.