bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell RNA-seq reveals cellular and transcriptional heterogeneity in the splenic CD11b+Ly6Chigh monocyte population expanded in sepsis-surviving mice
Authors: Watanabe Haruki , Rana Minakshi , Son Myoungsun , Chiu Pui Yan , Fei-Bloom Yurong , Choi Kwangmin , Diamond Betty , Sherry Barbara 
Published: November 2024

Abstract
Background
Sepsis survivors exhibit immune dysregulation that contributes to poor long-term outcomes. Phenotypic and functional alterations within the myeloid compartment are believed to be a contributing factor. Here we dissect the cellular and transcriptional heterogeneity of splenic CD11b+Ly6Chigh myeloid cells that are expanded in mice that survive the cecal ligation and puncture (CLP) murine model of polymicrobial sepsis to better understand the basis of immune dysregulation in sepsis survivors.

Methods
Sham or CLP surgeries were performed on C57BL/6J and BALB/c mice. Four weeks later splenic CD11b+Ly6Chigh cells from both groups were isolated for phenotypic (flow cytometry) and functional (phagocytosis and glycolysis) characterization and RNA was obtained for single-cell RNA-seq (scRNA-seq) and subsequent analysis.

Results
CD11b+Ly6Chigh cells from sham and CLP surviving mice exhibit phenotypic and functional differences that relate to immune function, some of which are observed in both C57BL/6J and BALB/c strains and others that are not. To dissect disease-specific and strain-specific distinctions within the myeloid compartment, scRNA-seq analysis was performed on CD11b+Ly6Chigh cells from C57BL/6J and BALB/c sham and CLP mice. Uniform Manifold Approximation and Projection from both strains identified 13 distinct clusters of sorted CD11b+Ly6Chigh cells demonstrating significant transcriptional heterogeneity and expressing gene signatures corresponding to classical-monocytes, non-classical monocytes, M1- or M2-like macrophages, dendritic-like cells, monocyte-derived dendritic-like cells, and proliferating monocytic myeloid-derived suppressor cells (M-MDSCs). Frequency plots showed that the percentages of proliferating M-MDSCs (clusters 8, 11 and 12) were increased in CLP mice compared to sham mice in both strains. Pathway and UCell score analysis in CLP mice revealed that cell cycle and glycolytic pathways were upregulated in proliferating M-MDSCs in both strains. Notably, granule protease genes were upregulated in M-MDSCs from CLP mice. ScRNA-seq analyses also showed that phagocytic pathways were upregulated in multiple clusters including the classical monocyte cluster, confirming the increased phagocytic capacity in CD11b+Ly6Chigh cells from CLP mice observed in ex vivo functional assays in C57BL/6J mice.

Conclusion
The splenic CD11b+Ly6Chigh myeloid populations expanded in survivors of CLP sepsis correspond to proliferating cells that have an increased metabolic demand and gene signatures consistent with M-MDSCs, a population known to have immunosuppressive capacity.
The need for implementing a standardized, evidence-based emergency department discharge plan for optimizing adult asthma patient outcomes in the UAE, expert meeting report
Authors: Buhumaid Rasha , Alzaabi Ashraf , Mahboub Bassam , Iqbal Mohamed Nizam , Alhameli Hamad Alhay , Al-Mafrachi Mohamed Ghazi , Dittrich Kenneth Charles , Jaiganesh Thiagarajan 
Published: November 2024

Abstract
Background
Asthma is a common chronic respiratory inflammatory disease that adversely affects patients’ quality of life (QoL) and overall well-being. When asthma is not adequately controlled, there is a higher risk of exacerbations and hospitalizations, thereby increasing the direct and indirect costs associated with the treatment and productivity loss. Overreliance on SABA and underutilization of ICS in the management of asthma can result in suboptimal treatment and poor asthma control. Patients who visit the emergency department are more likely to have poorly controlled asthma. Ensuring that these patients are provided with an evidence-based treatment plan during discharge can help reduce the risk of future exacerbations and consequently reduce the burden on the UAE healthcare system.

Methods
A joint task force comprising experts from the Emirates Society of Emergency Medicine (ESEM) and Emirates Thoracic Society (ETS) reviewed published evidence and updated guidelines in asthma management to optimize the post-discharge recommendations.

Results
The ESEM-ETS experts’ joint task force has developed a step-by-step plan for emergency department/hospital discharge, which is based on the GINA 2023 guideline recommendations and the medications available in the UAE. By adhering to this structured plan, emergency department physicians can play a crucial role in improving asthma care, long-term patient outcomes, and the utilization of healthcare resources.

Conclusions
Prioritizing patient education and ensuring patients are equipped with the best-suited asthma treatment plans prior to discharge can help ED physicians improve patient outcomes and reduce healthcare resource utilization in UAE hospitals.
Molecular evolution of toothed whale genes reveals adaptations to echolocating in different environments
Authors: Magpali L. , Ramos E. , Picorelli A. , Freitas L. , Nery M. F. 
Published: November 2024

Abstract
Background
Echolocation was a key development in toothed whale evolution, enabling their adaptation and diversification across various environments. Previous bioacoustic and morphological studies suggest that environmental pressures have influenced the evolution of echolocation in toothed whales. This hypothesis demands further investigation, especially regarding the molecular mechanisms involved in the adaptive radiation of toothed whales across multiple habitats. Here we show that the coding sequences of four hearing genes involved in echolocation (CDH23, prestin, TMC1, and CLDN14) have different signatures of molecular evolution among riverine, coastal, and oceanic dolphins, suggesting that the evolutionary constraints of these habitats shaped the underlying genetic diversity of the toothed whale sonar.

Results
Our comparative analysis across 37 odontocete species revealed patterns of accelerated evolution within coastal and riverine lineages, supporting the hypothesis that shallow habitats pose specific selective pressures to sonar propagation, which are not found in the deep ocean. All toothed whales with genes evolving under positive selection are shallow coastal species, including three species that have recently diverged from freshwater lineages (Cephalorhynchus commersonii, Sotalia guianensis, and Orcaella heinsohni - CDH23), and three species that operate specialized Narrow Band High Frequency (NBHF) Sonars (Phocoena sinus - prestin, Neophocaena phocaenoides - TMC1 and Cephalorhynchus commersonii - CDH23). For river dolphins and deep-diving toothed whales, we found signatures of positive selection and molecular convergence affecting specific sites on CDH23, TMC1, and prestin. Positively selected sites (PSS) were different in number, identity, and substitution rates (dN/dS) across riverine, coastal, and oceanic toothed whales.

Conclusion
Here we shed light on potential molecular mechanisms underlying the diversification of toothed whale echolocation. Our results suggest that toothed whale hearing genes changed under different selective pressures in coastal, riverine, and oceanic environments.
Molecular cloning of PRD-like homeobox genes expressed in bovine oocytes and early IVF embryos
Authors: Yaşar Barış , Boskovic Nina , Ivask Marilin , Weltner Jere , Jouhilahti Eeva-Mari , Vill Piibe , Skoog Tiina , Jaakma Ülle , Kere Juha , Bürglin Thomas R. , Katayama Shintaro , Org Tõnis , Kurg Ants 
Published: November 2024

Abstract
Background
Embryonic genome activation (EGA) is a critical step in early embryonic development, as it marks the transition from relying on maternal factors to the initiation of transcription from embryo’s own genome. The factors associated with EGA are not well understood and need further investigation. PRD-like (PRDL) homeodomain transcription factors (TFs) are considered to play crucial roles in this early event during development but these TFs have evolved differently, even within mammalian lineages. Different numbers of PRDL TFs have been predicted in bovine (Bos taurus); however, their divergent evolution requires species-specific confirmation and functional investigations.

Results
In this study, we conducted molecular cloning of mRNAs for the PRDL TFs ARGFX, DUXA, LEUTX, NOBOX, TPRX1, TPRX2, and TPRX3 in bovine oocytes or in vitro fertilized (IVF) preimplantation embryos. Our results confirmed the expression of PRDL TF genes in early bovine development at the cDNA level and uncovered their structures. For each investigated PRDL TF gene, we isolated at least one homeodomain-encoding cDNA fragment, indicative of DNA binding and thus potential role in transcriptional regulation in developing bovine embryos. Additionally, our cDNA cloning approach allowed us to reveal breed-related differences in bovine, as evidenced by the identification of a high number of single nucleotide variants (SNVs) across the PRDL class homeobox genes. Subsequently, we observed the prediction of the 9aa transactivation domain (9aaTAD) motif in the putative protein sequence of TPRX3 leading us to conduct functional analysis of this gene. We demonstrated that the TPRX3 overexpression in bovine fibroblast induces not only protein-coding genes but also short noncoding RNAs involved in splicing and RNA editing. We supported this finding by identifying a shared set of genes between our and published bovine early embryo development datasets.

Conclusions
Providing full-length cDNA evidence for previously predicted homeobox genes that belong to PRDL class improves the annotation of the bovine genome. Updating the annotation with seven developmentally-important genes will enhance the accuracy of RNAseq analysis with datasets derived from bovine preimplantation embryos. In addition, the absence of TPRX3 in humans highlights the species-specific and TF-specific regulation of biological processes during early embryo development.
Isolation and characterization of non-rhizobial bacteria and arbuscular mycorrhizal fungi from legumes
Authors: Abd-Alla Mohamed Hemida , Nafady Nivien A. , Hassan Amany A. , Bashandy Shymaa R. 
Published: November 2024

AbstractThis study investigates non-rhizobial endophytic bacteria in the root nodules of chickpea (Cicer arietinum L), faba bean (Vicia faba), and cowpea (Vigna unguiculata L. Walp), as well as arbuscular mycorrhizal fungi in the rhizospheric soil of chickpea and faba bean. Out of the 34 endophytic bacterial populations examined, 31 strains were identified as non-rhizobial based on nodulation tests. All strains were assessed for their plant growth-promoting (PGP) activities in vitro. The results revealed that most isolates exhibited multiple PGP activities, such as nitrogen fixation, indole-3-acetic acid (IAA) and ammonia (NH3) production, phosphate solubilization, and exopolysaccharide production. The most effective PGP bacteria were selected for 16S rRNA analysis. Additionally, a total of 36 species of native arbuscular mycorrhizal fungi (AMF) were identified. Acaulospora (100%) and Scutellospora (91.66%) were the most prevalent genera in Cicer arietinum L. and Vicia faba L. plants, respectively. Acaulospora also exhibited the highest spore density and relative abundance in both plants. Moreover, the root colonization of Cicer arietinum L. and Vicia faba L. plants by hyphae, vesicles, and arbuscules (HVA) was significant. The findings of this study provide valuable insights into non-rhizobial endophytic bacteria associated with legume root nodules and the diversity of AMF. These organisms have great potential for PGP and can be manipulated by co-inoculation with rhizobia to enhance their biofertilizer effectiveness. This manipulation is crucial for promoting sustainable agriculture, improving crop growth, and advancing biofertilizer technology.
Exploring the response of yellow lupine (Lupinus luteus L.) root to drought mediated by pathways related to phytohormones, lipid, and redox homeostasis
Authors: Burchardt Sebastian , Czernicka Małgorzata , Kućko Agata , Pokora Wojciech , Kapusta Małgorzata , Domagalski Krzysztof , Jasieniecka-Gazarkiewicz Katarzyna , Karwaszewski Jacek , Wilmowicz Emilia 
Published: November 2024

Abstract
Background
Yellow lupine (Lupinus luteus L.) is a high-protein crop of considerable economic and ecological significance. It has the ability to fix atmospheric nitrogen in symbiosis with Rhizobium, enriching marginal soils with this essential nutrient and reducing the need for artificial fertilizers. Additionally, lupine produces seeds with a high protein content, making it valuable for animal feed production. However, drought negatively affects lupine development, its mutualistic relationship with bacteria, and overall yield. To understand how lupine responds to this stress, global transcriptome sequencing was conducted, along with in-depth biochemical, chromatography, and microscopy analyses of roots subjected to drought. The results presented here contribute to strategies aimed at mitigating the effects of water deficit on lupine growth and development.

Results
Based on RNA-seq, drought-specific genes were identified and annotated to biological pathways involved in phytohormone biosynthesis/signaling, lipid metabolism, and redox homeostasis. Our findings indicate that drought-induced disruption of redox balance characterized by the upregulation of reactive oxygen species (ROS) scavenging enzymes, coincided with the accumulation of lipid-metabolizing enzymes, such as phospholipase D (PLD) and lipoxygenase (LOX). This disruption also led to modifications in lipid homeostasis, including increased levels of triacylglycerols (TAG) and free fatty acids (FFA), along with a decrease in polar lipid content. Additionally, the stress response involved alterations in the transcriptional regulation of the linolenic acid metabolism network, resulting in changes in the composition of fatty acids containing 18 carbons.

Conclusion
The first comprehensive global transcriptomic profiles of lupine roots, combined with the identification of key stress-responsive molecules, represent a significant advancement in understanding lupine’s responses to abiotic stress. The increased expression of the Δ12DESATURASE gene and enhanced PLD activity lead to higher level of linoleic acid (18:2), which is subsequently oxidized by LOX, resulting in membrane damage and malondialdehyde (MDA) accumulation. Oxidative stress elevates the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT), while the conversion of FFAs into TAGs provides protection against ROS. This research offers valuable molecular and biochemical candidates with significant potential to enhance drought tolerance . It enables innovative strategies in lupine breeding and crop improvement to address critical agricultural challenges.
Perspectives of midwives on respectful maternity care
Authors: Lunda Petronella , Minnie Catharina Susanna , Lubbe Welma 
Published: November 2024

Abstract
Background
Respectful maternity care forms the foundation of maternity services; however, delivery of dignified, efficient, and effective care in these settings remains inconsistent. Research has identified several factors that influence respectful maternity care. To understand the South African context, these factors were explored and described from the perspectives of midwives.

Methods
A qualitative descriptive inquiry was conducted, with participants recruited through snowball sampling on the social networking site Facebook. Semi-structured questions were used to collect data, to which participants responded in writing, detailing factors that influenced respectful care, including words and practices they associated with respectful maternity care. The data was analyzed using content analysis to identify common categories.

Results
Twenty-five responses from participants were analyzed; four categories and six sub-categories emerged as representations of respectful maternity care. The categories and sub-categories were as follows: healthcare professional behavior (ethical conduct and professional attributes related to education and training), managerial support (conducive work environment), interpersonal facet of care (characteristics of healthcare providers), and the birth environment (caring within the birth environment and client-centered care).

Conclusion
Midwives emphasized the importance of understanding respectful maternity care to ensure optimal outcomes for women, families, and communities. However, given the complexity of maternity care, it is crucial for policymakers, administrators, and midwives to comprehend and appreciate the various elements that define respectful care, as this understanding can significantly enhance its successful implementation.
A study of the enablers and barriers to the collection of sociodemographic data by public health units in Ontario, Canada during the COVID-19 pandemic
Authors: Komeiha Menna , Kujbida Gregory , Reynolds Aideen , Mbagwu Ikenna , Dojeiji Laurie , O’Rourke Joseph J. , Raju Shilpa , Varia Monali , Stylianou Helen , Burgess Sydnee , Ogundele Oluwasegun Jko , Pinto Andrew D. 
Published: November 2024

Abstract
Background
Collection and use of sociodemographic data (SDD), including race, ethnicity and income, are foundational to understanding health inequities. Ontario’s public health units collected SDD as part of COVID-19 case management and vaccination activities. This research aimed to identify enablers and barriers to collecting SDD during COVID-19 case management and vaccination.

Methods
As part of a larger mixed-method research study [1], qualitative methods were used to identify enablers and barriers to SDD collection during the COVID-19 pandemic. Purposive sampling was used to recruit participants from Ontario’s 34 public health units. Sixteen focus groups and eight interviews were conducted virtually using Zoom. Interview data were transcribed and analyzed using inductive and deductive qualitative description.

Results
SDD collection enablers included: legally mandating SDD collection and having dedicated data systems, technological and legal supports, senior management championing SDD collection, establishing rapport and trust between staff and clients, and gaining insight from the experiences from local communities and other jurisdictions. Identified barriers to SDD collection included: provincial data systems being perceived as lacking user-friendliness, SDD collection “was not a priority,” time and other constraints on building staff and client rapport, and perceived discomfort with asking and answering personal SDD questions.

Conclusion
A combination of provincial and local organizational strategies including supportive data systems, training, and frameworks for data collection and use, are needed to normalize and scale up SDD collection by local health units beyond the context of the COVID-19 pandemic.
Diagnosis and treatment of patients with gastroesophageal reflux disease – a systematic review of cost-effectiveness and economic burden
Authors: Maresova Petra , Rezny Lukas , Hruska Jan , Klimova Blanka , Swanstrom Lee L , Kuca Kamil 
Published: November 2024

Abstract
Background
This study aims to review the existing knowledge on the cost-effectiveness and item costs related to the diagnosis and treatment of gastroesophageal reflux disease (GERD) patients at different stages.

Methods
The study adhered to the PRISMA guidelines. The systematic search involved several steps: finding and identifying relevant articles, filtering them according to the set criteria, and examining the final number of selected articles to obtain the primary information. The number of articles published between 2013 and September 2024 in the Web of Science and PubMed databases was considered. The CHEERS checklist was used for the risk of bias assessment. Ultimately, 36 studies were included.

Results
Regarding the cost-effectiveness of GERD treatment, Proton pump inhibitors (PPIs) appeared to be the dominant solution for non-refractory patients. However, this might change with the adoption of the novel drug vonoprazan, which is more effective and cheaper. With advancements in emerging technologies, new diagnostic and screening approaches such as Endosheath, Cytosponge, and combined multichannel intraluminal impedance and pH monitoring catheters should be considered, with potential implications for optimal GERD management strategies.

Discussion
The new diagnostic methods are reliable, safe, and more comfortable than standard procedures. PPIs are commonly used as the first line of treatment for GERD. Surgery, such as magnetic sphincter augmentation or laparoscopic fundoplication, is only recommended for patients with treatment-resistant GERD or severe symptoms.

Other
Advances in emerging technologies for diagnostics and screening may lead to a shift in the entire GERD treatment model, offering less invasive options and potentially improving patients’ quality of life.
Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial
Authors: Connon Roisin , Olupot-Olupot Peter , Pistorius Arthur M. A. , Okiror William , Ssenyondo Tonny , Muhindo Rita , Uyoga Sophie , Mpoya Ayub , Williams Thomas N. , Gibb Diana M. , Walker A. Sarah , ter Heine Rob , George Elizabeth C. , Maitland Kathryn 
Published: November 2024

Abstract
Background
African children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection.

Methods
We conducted a phase I/II trial in Ugandan children with severe malaria comparing a 5-day course of azithromycin: 10, 15 and 20 mg/kg of azithromycin (prescribed by weight bands) spanning the dose-range effective for other salmonellae infection. We generated relevant pharmacokinetic (PK) data by sparse sampling during dosing intervals and investigated associations between azithromycin exposure and potential mechanisms (PK-pharmacodynamics) using change in C-reactive protein (CRP), a putative marker of sepsis, at 72 h (continuous) and microbiological cure (7-day) (binary), alone and as a composite with 7-day and 90-day survival. To assess whether clinical or biomarkers could identify those at risk of sepsis, a non-severe malaria control was concurrently enrolled.

Results
Between January 2020 and January 2022, 105 cases were randomised azithromycin doses: 35 to 10 mg/kg, 35 to 15 mg/kg and 35 to 20 mg/kg. Fifty non-severe malaria controls were concurrently enrolled. CRP reduced in all arms by 72 h with a mean reduction of 65.8 mg/L (95% CI 57.1, 74.5) in the 10 mg/kg arm, 64.8 mg/L (95% CI 56.5, 73.1; p = 0.87) in the 20 mg/kg arm and a smaller reduction 51.2 mg/L (95% CI 42.9, 59.5; p = 0.02) in the 15 mg/kg arm. Microbiological cure alone outcome was not analysed as only one pathogen was found among cases. Three events contributed to the composite outcome of 7-day survival and microbiological cure, with no events in the 15 mg/kg arm. The odds ratio comparing 20 vs 10 mg/kg was 0.50 (95% CI 0.04, 5.79); p = 0.58. Due to the low number of pathogens identified, it was not possible to identify better methods for targeting antibiotics including both the cases and controls.

Conclusions
We found no evidence for an association between systemic azithromycin exposure and reduction in CRP. Further work is needed to better identify children at highest risk from bacterial co-infection.

Trial registration
ISRCTN49726849 (registered on 27th October 2017).