bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifunctional hyaluronic acid-based biomimetic/pH-responsive hybrid nanostructured lipid carriers for treating bacterial sepsis
Authors: Elhassan Eman , Omolo Calvin A. , Gafar Mohammed A. , Ismail Eman A. , Ibrahim Usri H. , Khan Rene , Lesouhaitier Mathieu , Kubes Paul , Govender Thirumala 
Published: February 2025

Abstract

Introduction
The application of biomimetic and stimuli-responsive nanocarriers displays considerable promise in improving the management of bacterial sepsis and overcoming antimicrobial resistance. Therefore, the study aimed to synthesize a novel hyaluronic acid-lysine conjugate (HA-Lys) and to utilize the attributes of the synthesized HA-Lys with Tocopherol succinate (TS) and Oleylamine (OLA) in the formulation of multifunctional biomimetic pH-responsive HNLCs loaded with vancomycin (VCM-HNLCs), to combat bacterial sepsis.

Methods
A novel hyaluronic acid-lysine conjugate (HA-Lys) was synthesized and characterized using FTIR and 1H NMR spectroscopy. Vancomycin-loaded hybrid nanosystems (VCM-HNLCs) were prepared through hot homogenization ultrasonication and evaluated for particle size, polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE%). In vitro biocompatibility was assessed via MTT assay and red blood cell hemolysis test. The binding affinity to TLR2 and TLR4 was measured using microscale thermophoresis (MST). Drug release was evaluated using the dialysis bag method. Antimicrobial activity against MRSA and efflux pump inhibition were also determined. Efficacy was demonstrated in an MRSA-induced sepsis mice model.

Results
The VCM-HNLCs, produced via hot homogenization ultrasonication, exhibited particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE%) of 110.77 ± 1.692 nm, 0.113 ± 0.022, − 2.92 ± 0.210 mV, and 76.27 ± 1.200%, respectively. In vitro, biocompatibility was proven by hemolysis and cytotoxicity studies. The VCM-HNLCs demonstrated targetability to human Toll-like receptors (TLR 2 and 4) as validated by microscale thermophoresis (MST). VCM-HNLCs showed a twofold reduction in MIC values at physiological pH compared to the bare VCM against S. aureus and MRSA for 48 h. While at pH 6.0, MIC values were reduced by fourfold in the first 24 h and by eightfold in the subsequent 48 and 72 h against tested strains. Furthermore, VCM-HNLCs showed inhibitory effects against MRSA efflux pumps, reactive oxygen species (ROS), and lipopolysaccharide (LPS)-induced hyperinflammation. In an MRSA-induced sepsis mice model, VCM-HNLCs demonstrated superior efficacy compared to free VCM, significantly eliminated bacteria and improved survival rates.

Conclusions
Overall, these results highlight the potential of VCM-HNLCs as novel multifunctional nanocarriers to combat antimicrobial resistance (AMR) and enhance sepsis outcomes.

Graphical Abstract
Populist attitudes and belief in conspiracy theories: anti-elitist attitudes and the preference for unrestricted popular sovereignty reduce the positive impact of an analytical thinking style on conspiracy beliefs
Authors: Mehl Stephanie , Rief Winfried , Soll Daniel , Pytlik Nico 
Published: February 2025

Abstract

Objective
Populist attitudes and the tendency to believe in specific conspiracy theories (conspiracy beliefs) are often exploited by extremist or populist parties. However, more scientific research is needed to scrutinize this association. Consequently, the present non-preregistered exploratory online study assessed whether and how conspiracy beliefs and populist attitudes are associated and whether populist attitudes moderate the association between the preference for an analytical or intuitive thinking style and conspiracy beliefs.

Results
We assessed 483 nonclinical individuals regarding their conspiracy beliefs, populist attitudes, and thinking styles and found a moderate correlation between populist attitudes and conspiracy beliefs. Conspiracy beliefs were significantly predicted by three facets of populist attitudes (anti-elitism, preference for unrestricted popular sovereignty, and belief in the homogeneity and virtuousness of the people). Anti-elitist attitudes and a preference for unrestricted popular sovereignty significantly moderated (reduced) the impact of an analytical thinking style on conspiracy beliefs. Anti-elitism and a preference for popular sovereignty might enhance a person’s vulnerability to conspiracy beliefs. We assume that these populistic attitudes reduce a person’s motivation to use a more effortful thinking style to reinterpret ideology-inconsistent information to protect existing conspiracy beliefs. Our results provide new insights into the interplay between conspiracy beliefs, populism, and a preference for an analytical/more effortful thinking style.
Moisturizer induced contact anaphylaxis
Authors: Jeffrey Bronte , Gardner Logan , Le Michelle , Frost Julie , Lin Ming Wei 
Published: February 2025

Abstract

Background
Contact allergens typically trigger localised reactions, but systemic Type I hypersensitivity from skin contact reactions are rare.

Case presentation
We present the case of a 69-year-old non-atopic male who developed anaphylaxis following the application of moisturizer to an area of chemical burns. Skin testing showed a strong positive result to moisturizer. Whilst not all ingredients were available for testing, phenoxyethanol was thought to be the likely culprit agent based on literature review and a weakly positive skin test result.

Conclusion
Products such as moisturizers can rarely trigger anaphylaxis, especially when applied to damaged skin which may favor systemic absorption. This case highlights the need for careful consideration of cosmetic application when discerning culprit allergens.
Development of a novel chimeric lysin to combine parental phage lysin and cefquinome for preventing sow endometritis after artificial insemination
Authors: Li Xin-xin , Hong Zi-qiang , Xiong Zhi-xuan , Zhang Li-wen , Wang Shuang , Tao Pan , Chen Pin , Li Xiang-min , Qian Ping 
Published: February 2025

Abstract
Sow endometritis is usually caused by multiple species of pathogenic bacteria. Numerous isolates from endometritis patients have developed antimicrobial resistance. Thus, novel antibacterial agents and strategies to combat endometritis are needed. A total of 526 bacteria, including Staphylococcus spp. (26.3%), Streptococcus spp. (12.3%), E. coli (28.9%), Enterococcus spp. (20.1%), Proteus spp. (9.5%), and Corynebacterium spp. (2.8%), were isolated from sows with endometritis. We constructed a novel chimeric lysin, ClyL, which is composed of a cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP) catalytic domain from the phage lysin LysGH15 and a cell wall-binding domain (CBD) from the prophage lysin Lys0859. The activities of ClyL and Lys0859 were most pronounced for the Staphylococcus and Streptococcus strains isolated from sow endometritis and bovine mastitis, respectively. ClyL and Lys0859 were combined to create a phage lysin cocktail, which demonstrated a synergistic effect against the coinfection of Staphylococcus and Streptococcus in vitro and in vivo. Furthermore, the combination of phage lysin cocktail and cefquinome had a synergistic bactericidal effect on boar semen that did not influence the activity of sperm. Remarkably, the incidence rate of sow endometritis was 0% (0/7) when the combination of phage lysin cocktail and cefquinome was used in semen via artificial insemination compared with 50% (3/6) when PBS was administered. Overall, the administration of a phage lysin cocktail and cefquinome in semen via artificial insemination is a promising novel strategy to prevent sow endometritis after artificial insemination.
The intestinal microbiome and metabolome discern disease severity in cytotoxic T-lymphocyte-associated protein 4 deficiency
Authors: Chandrasekaran Prabha , Krausz Máté , Han Yu , Mitsuiki Noriko , Gabrysch Annemarie , Nöltner Christina , Proietti Michele , Heller Theo , Grou Caroline , Calderon Virginie , Subramanian Poorani , Jones Drew R. , Siu Yik , Deming Clayton , Conlan Sean , Holland Steven M. , Segre Julia A. , Uzel Gulbu , Grimbacher Bodo , Falcone Emilia Liana 
Published: February 2025

Abstract

Background
Cytotoxic T-lymphocyte-associated protein 4 deficiency (CTLA4-D) is an inborn error of immunity (IEI) caused by heterozygous mutations, and characterized by immune cell infiltration into the gut and other organs, leading to intestinal disease, immune dysregulation and autoimmunity. While regulatory T-cell dysfunction remains central to CTLA4-D immunopathogenesis, mechanisms driving disease severity and intestinal pathology are unknown but likely involve intestinal dysbiosis. We determined whether the intestinal microbiome and metabolome could distinguish individuals with severe CTLA4-D and identify biomarkers of disease severity.

Results
The genera Veillonella and Streptococcus emerged as biomarkers that distinguished CTLA4-D from healthy cohorts from both the National Institutes of Health (NIH) Clinical Center, USA (NIH; CTLA-D, n = 32; healthy controls, n = 16), and a geographically distinct cohort from the Center for Chronic Immunodeficiency (CCI) of the Medical Center - University of Freiburg, Germany (CCI; CTLA4-D, n = 25; healthy controls, n = 24). Since IEIs in general may be associated with perturbations of the microbiota, a disease control cohort of individuals with common variable immunodeficiency (CVID, n = 20) was included to evaluate for a CTLA4-D-specific microbial signature. Despite common IEI-associated microbiome changes, the two bacterial genera retained their specificity as biomarkers for CTLA4-D. We further identified intestinal microbiome and metabolomic signatures that distinguished patients with CTLA4-D having severe vs. mild disease. Microbiome changes were associated with distinct stool metabolomic profiles and predicted changes in metabolic pathways. These differences were impacted by the presence of gastrointestinal manifestations and were partially reversed by treatment with abatacept and/or sirolimus.

Conclusions
Loss of intestinal microbial diversity and dysbiosis causing metabolomic changes was observed in CTLA4-D. Albeit some of these features were shared with CVID, the distinct changes associated with CTLA4-D highlight the fact that IEI-associated microbiome changes likely reflect the underlying immune dysregulation. Identified candidate intestinal microbial and metabolic biomarkers distinguishing individuals with CTLA4-D based on severity should be studied prospectively to determine their predictive value, and investigated as potential therapeutic ta.
Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids
Authors: Athanasiou Dimitra , Afanasyeva Tess A. V. , Chai Niuzheng , Ziaka Kalliopi , Jovanovic Katarina , Guarascio Rosellina , Boldt Karsten , Corral-Serrano Julio C. , Kanuga Naheed , Roepman Ronald , Collin Rob W. J. , Cheetham Michael E. 
Published: February 2025

Abstract
Bialleleic pathogenic variants in LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. Here, we report the use of gene editing to generate isogenic LCA5 knock-out (LCA5 KO) induced pluripotent stem cells (iPSC) and their differentiation to retinal organoids. The molecular and cellular phenotype of the LCA5 KO retinal organoids was studied in detail and compared to isogenic controls as well as patient-derived retinal organoids. The absence of LCA5 was confirmed in retinal organoids by immunohistochemistry and western blotting. There were no major changes in retinal organoid differentiation or ciliation, however, the localisation of CEP290 and IFT88 was significantly altered in LCA5 KO and patient photoreceptor cilia with extension along the axoneme. The LCA5-deficient organoids also had shorter outer segments and rhodopsin was mislocalised to the outer nuclear layer. We also identified transcriptomic and proteomic changes associated with the loss of LCA5. Importantly, treatment with the small molecules eupatilin, fasudil or a combination of both drugs reduced CEP290 and IFT88 accumulation along the cilia. The treatments also improved rhodopsin traffic to the outer segment and reduced mislocalisation of rhodopsin in the outer nuclear layer (ONL). The improvements in cilia-associated protein localisation and traffic were accompanied by significant changes in the transcriptome towards control gene expression levels in many of the differentially expressed genes. In summary, iPSC-derived retinal organoids are a powerful model for investigating the molecular and cellular changes associated with loss of LCA5 function and highlight the therapeutic potential of small molecules to treat retinal ciliopathies.
Taxonomy of digital curation activities that promote critical thinking
Authors: Gadot Rivka , Tsybulsky Dina 
Published: February 2025

Abstract
Critical thinking (CT) consists of a deliberate and reflective process that can lead to informed decisions. It involves scrutinizing the trustworthiness and consistency of underlying assumptions, the sources of data, and the validity of other information. CT embodies deliberate, self-regulated judgment incorporating cognitive abilities such as analysis, evaluation, and inference. In this follow-up study to Gadot & Tsybulsky (2023), we confirm the role of Digital Curation (DC) as a catalyst for CT and present a structured taxonomy of DC practices that enhance CT. This taxonomy is designed to act as a systematic framework for categorizing DC tasks while capturing the personal and social facets of curation activities. The curation workflow is broken down into the acquisition and assimilation stages and incorporates the level of complexity. This classification can thus be harnessed by educators and practitioners to define the aims and competencies that are critical to fostering CT skills through DC practices.
SGLT2 inhibitors for prevention and management of cancer treatment-related cardiovascular toxicity: a review of potential mechanisms and clinical insights
Authors: Simela Carl , Walker J Malcolm , Ghosh Arjun K. , Chen Daniel H. 
Published: February 2025

Abstract
More evidence-based strategies are needed for preventing and managing cancer treatment-related cardiovascular toxicity (CTR-CVT). Owing to the growing body of evidence supporting their cardioprotective role in several cardiac injury scenarios, sodium-glucose cotransporter 2 inhibitors (SGLT2i) may be beneficial for preventing and treating CTR-CVT. In October 2024, a search was conducted of the PubMed database to review full studies investigating the cardioprotective role of SGLT2i against CTR-CVT. We identified 44 full published/pre-print studies and 3 ongoing randomised controlled trial across eight types of cancer treatment (anthracyclines, platinum-containing therapy, immune checkpoint inhibitors, HER2-targeted therapies, kinase inhibitors, androgen deprivation therapies, multiple myeloma therapies and 5-fluorouracil). Most studies used animal models and focussed on primary prevention. 43 of the 44 studies found some cardioprotective effect of SGLT2i against CTR-CVT, which in some cases included preventing ejection fraction decline and aberrations in cardiac electrophysiological parameters. Some studies also observed beneficial effects on mortality. A central triad of anti-inflammatory, anti-oxidative and anti-apoptotic mechanisms likely underlie SGLT2i-mediated cardioprotection against CTR-CVT. Overall, this growing body of research suggests that SGLT2i may be a promising candidate for preventing CTR-CVT either as monotherapy or in combination with other cardioprotective drugs. However, the literature is limited in that no prospective randomised controlled trials investigating SGLT2i for the prevention and management of CTR-CVT exist and most existing human retrospective data is based on diabetic populations. Future work must focus on addressing these limitations of the current literature.
Deciphering single-cell genomic architecture: insights into cellular heterogeneity and regulatory dynamics
Authors: Kang Byunghee , Lee Hyeonji , Roh Tae-Young 
Published: February 2025

Abstract

Background
The genomic architecture of eukaryotes exhibits dynamic spatial and temporal changes, enabling cellular processes critical for maintaining viability and functional diversity. Recent advances in sequencing technologies have facilitated the dissection of genomic architecture and functional activity at single-cell resolution, moving beyond the averaged signals typically derived from bulk cell analyses.

Main body
The advent of single-cell genomics and epigenomics has yielded transformative insights into cellular heterogeneity, behavior, and biological complexity with unparalleled genomic resolution and reproducibility. This review summarizes recent progress in the characterization of genomic architecture at the single-cell level, emphasizing the impact of structural variation and chromatin organization on gene regulatory networks and cellular identity.

Conclusion
Future directions in single-cell genomics and high-resolution epigenomic methodologies are explored, focusing on emerging challenges and potential impacts on the understanding of cellular states, regulatory dynamics, and the intricate mechanisms driving cellular function and diversity. Future perspectives on the challenges and potential implications of single-cell genomics, along with high-resolution genomic and epigenomic technologies for understanding cellular states and regulatory dynamics, are also discussed.
Prenatal Testosterone Exposure Is Linked to Sexually Dimorphic Changes in Body Composition in 7-Year-Old Children
Authors: Palm Camilla Viola Buskbjerg , Grøntved Anders , Jensen Dorte Møller , Hansen Freja Pelck , Jørgensen Jan Stener , Christesen Henrik Thybo , Glintborg Dorte , Andersen Marianne Skovsager 
Published: February 2025

Abstract

Context
Maternal free testosterone (FT) increases during the third trimester and FT is higher in pregnant women with polycystic ovary syndrome (PCOS) compared to women without PCOS. Higher prenatal androgen exposure has previously been associated with increased catch-up growth in boys.

Objective
This work aimed to examine associations between maternal third-trimester testosterone and body composition in boys and girls.

Methods
This study comprised 1008 mother-child pairs (boys, n = 520) in the Odense Child Cohort (maternal PCOS, n = 101). Maternal FT was calculated from total testosterone (TT) analyzed by mass spectrometry at gestational week 28. Body composition assessments were performed in 7-year-old children by whole-body dual x-ray absorptiometry (DXA, n = 897) measuring body fat (fat mass index [FMI = fat mass(kg)/height(m)2]), percentages of total fat mass, gynoid, and android fat mass) and lean body mass, body weight, body mass index (BMI and BMI z scores), and abdominal circumference. The main outcome was body fat at age 7 years.

Results
In boys, a doubling in FT was associated with a 4.2% increase in FMI (P = .04) and an increase in BMI and BMI z score of 0.2 and 0.1 (P = .05 and .04), respectively. In girls, no statistically significant association was observed between maternal FT and body composition.

Conclusion
Boys exposed to higher prenatal levels of FT had higher fat mass, whereas no relation was seen in girls, suggesting a sex-specific susceptibility to prenatal testosterone exposure on child body composition.
Global Burden of Complex Regional Pain Syndrome in At-Risk Populations: Estimates of Prevalence From 35 Countries Between 1993 and 2023
Authors: D’Souza Ryan S. , Klasova Johana , Saini Chandan , Chang Albert , Music Stephen , Shah Jay D. , Elmati Praveen Reddy , Chitneni Ahish , To Jimmy , Prokop Larry J. , Hussain Nasir 
Published: February 2025

BACKGROUND:
Complex regional pain syndrome (CRPS) is a debilitating and painful condition accompanied by sensory, autonomic, trophic, and/or motor abnormalities. Although CRPS is rare in the general population, the prevalence among individuals at higher risk, particularly posttraumatic and postsurgical patients, remains unknown. This study aims to provide a benchmark that quantifies CRPS prevalence in high-risk groups, and offers insights on potential predictors of developing CRPS.

METHODS:
We conducted a systematic review and meta-analysis to identify studies reporting prevalence of CRPS after an inciting event (eg, fracture, surgery), specifically 12-month and 24-month prevalence (primary outcomes), as well as 3-month and 6-month prevalence (secondary outcomes). Estimates from individual studies were transformed using double-arcsine transformation, and the resulting estimates with 95% confidence interval (CI) were pooled in a meta-analysis using a random-effects model.

RESULTS:
We included 214 articles with data from 2491,378 participants worldwide (35 countries), of which 16,873 had CRPS. The pooled 12-month and 24-month global prevalence was 3.04% (95% CI, 2.64–3.48) and 6.46% (95% CI, 5.46–7.53), respectively. Subgroup analysis and meta-regression were performed to understand the impact of population-dependent (mechanism of injury, type of CRPS), contextual-dependent (socioeconomic status), and methodological-dependent (study design, publication year) factors. The 12-month prevalence was higher in countries with a high human development index (HDI) compared to those with a medium or very high HDI, was higher in participants with a traumatic inciting injury only versus those with surgical injury only or traumatic/surgical injury, and was higher in prospective versus retrospective studies. Meta-regression analysis showed that publication year was a significant moderator, with more recent articles reporting lower 12-month prevalence.

CONCLUSIONS:
This study provides a benchmark of the global prevalence of CRPS, which anesthesiologists and pain specialists can use to prioritize early diagnosis and identify those at the highest risk for CRPS.
Plant-like heliotropism in a photosymbiotic animal
Authors: Lintnerova Eliska , Shaw Callum , Keys Matthew , Brownlee Colin , Modepalli Vengamanaidu 
Published: February 2025

ABSTRACT
As in plants, photosynthesis also represents a key energy source in photosymbiotic cnidarians bearing microalgae. We observed that the cnidarian sea anemone Anemonia viridis, commonly known as the snakelocks anemone, displayed heliotropism or solar tracking in their natural habitats. When exposed to sunlight, A. viridis point their tentacles towards the sun while remaining sessile, facing east at dawn and west at dusk as they track the sun's relative position through the day. This phenomenon was previously only observed in plants. Solar tracking movements in A. viridis are driven by peak wavelengths that prompt photosynthesis in their endosymbionts. The heliotropic response was absent in both bleached (aposymbiotic) A. viridis and in symbiotic A. viridis with chemically inhibited photosynthesis. We revealed a direct correlation between heliotropism and symbiont oxygen production in A. viridis and showed how photosymbiotic A. viridis utilises this mechanism to modulate exposure to solar irradiation. Our study exemplifies how photosynthetic organisms such as plants and symbiotic sea anemones, display similar behaviour in response to similar environmental pressures.