bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Heart Rate Variability Buffers the Effect of Attachment Insecurity on Sleep Quality
Authors: Paoletti-Hatcher Jensine , Argueta Daniel L. , Wu-Chung E. Lydia , Chen Michelle A. , Brown Ryan L. , LeRoy Angie S. , Murdock Kyle W. , Thayer Julian F. , Fagundes Christopher P. 
Published: March 2024

Objective
Sleep quality is an important health-protective factor. Psychosocial factors, including attachment orientation, may be valuable for understanding who is at risk of poor sleep quality and associated adverse health outcomes. High attachment anxiety is reliably associated with adverse health outcomes, whereas high attachment avoidance is associated with adverse health outcomes when co-occurring with poor self-regulatory capacity, indexed by heart rate variability (HRV). We examined the associations between attachment anxiety, attachment avoidance, HRV, and sleep quality.

Methods
Using longitudinal data from a sample of 171 older adults measured four times over 1 year (M = 66.18 years old; 67.83% women), we separated the between-person variance (which we call “trait”) and within-person variance (which we call “state”) for attachment anxiety, attachment avoidance, and HRV (via the root mean square of successive differences). Sleep quality was measured with the Pittsburgh Sleep Quality Index.

Results
Higher trait attachment anxiety was associated with poorer global sleep quality (B = 0.22, p = .005). Higher state attachment avoidance was associated with poorer sleep quality (B = −0.13, p = .01), except for those with higher trait HRV. Higher state attachment anxiety was associated with poorer sleep quality (B = −0.15, p = .002), except for those with higher or mean trait HRV. Higher trait attachment anxiety was associated with poorer sleep quality (B = −0.31, p = .02), except for those with higher trait HRV.

Conclusions
High trait HRV mitigated the adverse effects of attachment insecurity on sleep quality. Our results suggest that people with high trait HRV had greater self-regulation capacity, which may enable them to enact emotion regulation strategies effectively.
Impact of Collaborative Nursing Care Delivery on Patient Safety Events in an Emergency Intensive Care Unit: A Retrospective Observational Study
Authors: Obayashi Masato , Shimoyama Keiichiro , Ono Koji 
Published: March 2024

Objectives
Patient safety events (PSEs) have detrimental consequences for patients and healthcare staff, highlighting the importance of prevention. Although evidence shows that nurse staffing affects PSEs, the role of an appropriate nursing care delivery system remains unclear. The current study aimed to investigate whether nursing care delivery systems could prevent PSEs.

Methods
This retrospective study was conducted in Japan. The study examined the collaborative 4:2 nursing care delivery system in which 2 nurses are assigned to care for 4 patients, collaborating to perform tasks, and provide care. The cohort receiving care from a collaborative 4:2 nursing care delivery system was labeled the postintervention, whereas the cohort receiving care from a conventional individualized system, in which one nurse provides care for 2 patients, was labeled the preintervention. The primary outcome was the occurrence of PSEs.

Results
The preintervention and postintervention comprised 561 and 401 patients, respectively, with the latter consisting of a younger and more critically ill population. The number of PSEs per 1000 patient-days was not significantly different between the 2 groups (10.3 [95% confidence interval, 7.1–13.5] versus 6.0 [95% confidence interval, 3.2–8.9], P = 0.058). Multiple logistic regression analysis showed that the collaborative 4:2 nursing care delivery system was significantly associated with PSEs (adjusted odds ratio, 0.53; 95% confidence interval, 0.29–0.95; P = 0.037).

Conclusions
These findings suggest that in an emergency intensive care unit, a collaborative nursing care delivery system was associated with a decrease in PSEs.
Seminal root angle is associated with root system architecture in durum wheat
Authors: Kang Yichen , Rambla Charlotte , Haeften Shanice V. , Fu Brendan , Akinlade Oluwaseun , Potgieter Andries B. , Borrell Andrew K. , Mace Emma , Jordan David R. , Alahmad Samir , Hickey Lee T. 
Published: March 2024

AbstractOptimal root system architecture (RSA) is critical for efficient resource capture in soils, hence being an interest in crop breeding. Seminal root angle (SRA) at the seedling stage in durum wheat has been suggested to be a good indicator of RSA. However, research on correlating such lab-based seedling root phenotyping to RSA at later phases of plant growth is limited, resulting in the importance of root trait variation seen in seedlings often being overstated. To explore the role of SRA in modifying RSA at later phases of plant growth, we assessed 11 genotypes contrasting in SRA (wide and narrow), grown in a rhizobox designed for phenotyping root systems of plants during late-tillering. Above-ground traits and root dry mass in different soil depths and across the entire soil volume were measured manually, while root architectural traits were extracted using image analysis and summarised by multiple factor analysis to describe RSA. When comparing the wide and narrow genotypes, no differences were detected for above-ground traits and total root dry mass. However, differences were observed in the allocation of root dry mass at different depths. The wide and narrow genotypes showed distinct RSAs, particularly in the upper soil (0 ‒ 30 cm). The wide genotypes exhibited a ‘spread-out’ root system with dense and thin roots, whereas the narrow genotypes had a compact root system with fewer but thicker roots. Our study demonstrated a clear difference in RSA between the wide and narrow genotypes, highlighting the association between SRA on the direction and distribution of root growth in plants at later growth stages.
Aberrant cytoplasmic localization of MLH1 characterizes a sub-clonal breast cancer cell population that seeds recurrence
Authors: Mazumder A , DeWitt JT , Oropeza E , Punturi N , Lozano D , Raghunathan M , Piscitelli JM , Sajjadi E , Guerini-Rocco E , Venetis K , Ivanova M , Mane E , Fusco N , Bainbridge MN , Manhart CM , Haricharan S 
Published: March 2024

AbstractEstrogen receptor positive (ER+) breast cancer is one of the most common causes of cancer-related death in women. Mortality is largely driven by recurrence of treatment-resistant disease after many years of apparent response, making the molecular events that cause recurrence a critical area of investigation. Loss of expression ofMLH1, a tumor suppressor best studied in its role in mismatch repair, induces resistance of ER+ breast cancer cells to standard estrogen-targeting therapies. It does so by delinking cell cycle progression from estrogen regulation, a role distinct from its function in mismatch repair. MLH1 loss, as currently clinically diagnosed by detecting genomic instability or by immunohistochemistry for absence of protein, occurs in 12-15% of all cancers. Here, we demonstrate that sub-clonal, patient-derived mutations inMLH1, which neither impact protein abundance nor contribute sufficiently to genomic instability to be detected diagnostically, seed endocrine treatment resistance by enabling estrogen-independent growthin vitro,ex vivoin patient-derived organoids (p=0.005) andin vivo(p=0.0001). The mechanism underlying this endocrine treatment resistance is aberrant localization of MLH1 to the cytoplasmin vitroandin vivo(p=0.04), which precludes cell cycle arrest in response to endocrine therapy while simultaneously rendering cells acutely dependent on CDK4/6 activity. Consequently, administration of CDK4/6 inhibitors causes extreme regression in cells with cytoplasmic MLH1 compared to control cell populations with nuclear localization of MLH1in vitro(p=0.00000009),ex vivo(p=0.01) andin vivo(p=0.01). As aberrant cytoplasmic localization occurs in an additional ∼12% of ER+ breast cancer patients, it constitutes a new, major contributor to MLH1 dysregulation. The potential applicability of cytoplasmic MLH1 as a predictor of responsiveness to existing targeted therapies in a hard-to-treat breast cancer subtype posits an update of current clinical diagnostic criteria and therapeutic strategies. This is particularly important in the adjuvant setting where identification of biomarkers predicting responsiveness to CDK4/6 inhibitors remains an urgent, unmet clinical need.
Promoting Longevity in Aged Liver through NLRP3 Inflammasome Inhibition Using Tauroursodeoxycholic Acid (TUDCA) and SCD Probiotics
Authors: Baba Burcu , Ceylani Taha , Acikgoz Eda , Gurbanov Rafig , Keskin Seda , Samgane Gizem , Tombuloglu Huseyin , Teker Hikmet Taner 
Published: March 2024

AbstractThis study investigates the combined impact of SCD Probiotics and tauroursodeoxycholic acid (TUDCA) on the biomolecular makeup, histological changes and levels of inflammasome in the liver tissue of 24-month-old male Sprague-Dawley rats. By administering TUDCA (300 mg/kg, intravenously) and SCD Probiotics (3 mL (1 x 108 CFU), orally) daily for a week, the researchers employed ATR-FTIR spectroscopy along with machine learning approaches such as Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) to analyze the biomolecular profiles. In addition, the study measured the expression levels of inflammasome markers NLRP3, ASC, Caspase-1, IL18, and IL1β using RT-qPCR and examined liver sections for histopathological changes and NLRP3 inflammasome activation. The results revealed significant differences in the levels of lipids, proteins, and nucleic acids, with TUDCA having a noteworthy impact on enhancing lipid bands and reducing cholesterol ester bands, while SCD Probiotics showed the opposite effects. Furthermore, TUDCA was found to decrease the acyl chain length of fatty acids and improve protein conformation, whereas SCD Probiotics increased both the acyl chain length and protein phosphorylation ratio, suggesting a decrease in lipid and protein dynamics from both treatments. The histological assessments showed significant reductions in cellular degeneration, lymphatic infiltration, hepatic fibrosis, and the immunoreactivity of NLRP3 and ASC in the treated groups. SCD Probiotics exhibited a marked reduction in inflammasome-related gene expressions, and the lowest gene expression levels were observed in the group receiving both treatments. Despite an increase in serum AST and LDH levels across all groups, only the SCD Probiotics group showed an increase in albumin levels. The findings suggest that SCD Probiotics, TUDCA, and their combined administration may provide a promising avenue for therapeutic interventions in age-associated liver conditions and may mitigate age-related liver fibrosis while enhancing liver functionality.
Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic
Authors: Bach Emil , Ghanizada Mustafa , Kirkby Nikolaj , Buus Søren , Østerbye Thomas 
Published: March 2024

AbstractBackgroundAntibodies play a key role in the immune defence against infectious pathogens. Understanding the underlying process of B cell recognition is not only of fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas the nature of conformational B cell epitope recognition is inherently complicated, linear B cell epitopes offer a straightforward approach that potentially can be reduced to one of peptide recognition.MethodsUsing an overlapping peptide approach representing the entire proteomes of the seven main coronaviruses known to infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents and eight pre-pandemic controls. Using a high-density peptide microarray platform, 13-mer peptides overlapping by 11 amino acids were in situ synthesised and incubated with the pooled primary serum samples, followed by development with secondary fluorochrome-labelled anti-IgG and -IgA antibodies. Interactions were detected by fluorescence detection. Strong Ig interactions encompassing consecutive peptides were considered to represent “high-fidelity regions” (HFRs). These were mapped to the coronavirus proteomes using a 60% homology threshold for clustering.ResultsWe identified 333 human coronavirus derived HFRs. Among these, 98 (29%) mapped to SARS-CoV-2, 144 (44%) mapped to one or more of the four circulating common cold coronaviruses (CCC), and 54 (16%) cross-mapped to both SARS-CoV-2 and CCCs. The remaining 37 (11%) mapped to either SARS-CoV or MERS-CoV. Notably, the COVID-19 serum was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas the pre-pandemic was skewed towards recognising CCC-mapped HFRs. In terms of absolute numbers of linear B cell epitopes, the primary targets are the ORF1ab protein (60%), the spike protein (21%), and the nucleoprotein (15%) in that order; however, in terms of epitope density the order would be reversed.ConclusionWe identified linear B cell epitopes across coronaviruses, highlighting pan-, alpha-, beta-, or SARS-CoV-2-corona-specific B cell recognition patterns. These findings could be pivotal in deciphering past and current exposures to epidemic and endemic coronavirus. Moreover, our results suggest that pre-pandemic anti-CCC antibodies may cross-react against SARS-CoV-2, which could explain the highly variable outcome of COVID-19. Finally, the methodology used here offers a rapid and comprehensive approach to high-resolution linear B-cell epitope mapping, which could be vital for future studies of emerging infectious diseases.
NEK1 haploinsufficiency impairs ciliogenesis in human iPSC-derived motoneurons and brain organoids
Authors: Nice Sorce Marta , Sabrina Invernizzi , Valeria Casiraghi , Serena Santangelo , Chiara Lattuada , Paola Podini , Alberto Brusati , Alessio Silva , Silvia Peverelli , Angelo Quattrini , Vincenzo Silani , Patrizia Bossolasco , Antonia Ratti 
Published: March 2024

ABSTRACTPrimary cilia are microtubule-based organelles acting as specialized signalling antennae that respond to specific stimuli to maintain cellular integrity and homeostasis. Recent studies indicate defective primary cilia in post-mortem human brains and animal models of neurodegenerative conditions, including Amyotrophic Lateral Sclerosis (ALS). Heterozygous loss-of-function mutations (LOF) inNEK1gene are present in about 1% of familial and sporadic ALS cases. The protein kinase NEK1 regulates various cellular processes, including ciliogenesis, but a clear link betweenNEK1LOF mutation in ALS and primary cilia is unknown. In this study we generated a human iPSC line carrying aNEK1LOF mutation by gene editing, leading to NEK1 protein haploinsufficiency. In differentiated iPSC-motoneurons (MNs) we observed that primary cilia were significantly shorter inNEK1-LOF iPSC-MNs compared to wild-type (WT) iPSC-MNs and that also the percentage of ciliated iPSC-MNs was significantly decreased inNEK1-LOF cells. We also investigated ciliogenesis inNEK1-LOF iPSC-brain organoids confirming that primary cilia were thinner with no apparent alteration in the ultrastructure by transmission electron microscopy.Our data suggest that NEK1 protein plays a role in regulating ciliogenesis in both 2D and 3D human iPSC-derived neuronal models and thatNEK1LOF mutations associated to ALS, leading toNEK1haploinsufficiency and likely to reduced kinase activity, impair primary cilium formation. The involvement of ciliogenesis dysfunction in ALS deserves further investigation providing novel therapeutic targets and strategies to be addressed for this incurable disease.
Sputum Production and Salivary Microbiome in COVID-19 Patients Reveals Oral-Lung Axis
Authors: Lu Korina Yun-Fan , Alqaderi Hend , Hasan Saadoun Bin , Alhazmi Hesham , Alghounaim Mohammad , Devarajan Sriraman , Freire Marcelo , Altabtbaei Khaled 
Published: March 2024

AbstractObjectiveSARS-CoV-2 is a severe respiratory disease that primarily targets the lungs and was the leading cause of death worldwide during the pandemic. Investigating the intricate interplay between the oral microbiome and inflammatory cytokines during the acute phase of infection is crucial for understanding host immune responses. This study aimed to explore the relationship between the oral microbiome and cytokines in COVID-19 patients, specifically examining those with and without sputum production.MethodsSaliva and blood samples from 50 COVID-19 patients were subjected to 16S ribosomal RNA gene sequencing to analyze the oral microbiome. Additionally, 65 saliva and serum cytokines were assessed using Luminex multiplex analysis. The Mann-Whitney test compared cytokine levels between individuals with and without sputum production.ResultsOur study revealed significant differences in the membership (Jaccard dissimilarity: p=0.016) and abundance (PhILR dissimilarity: p=0.048; metagenomeSeq) of salivary microbial communities between COVID-19 patients with and without sputum production. Seven bacterial genera, including Prevotella, Streptococcus, Actinomyces, Atopobium, Filifactor, Leptotrichia, and Selenomonas, were present in statistically higher proportions of patients with sputum production (p<0.05, Fisher’s exact test). Eight bacterial genera, including Prevotella, Megasphaera, Stomatobaculum, Leptotrichia, Veillonella, Actinomyces, Atopobium, and Corynebacteria were significantly more abundant in the sputum-producing group, while Lachnoacaerobaculum was notably more prevalent in the non-sputum-producing group (p<0.05, ANCOM-BC).We observed a significant positive correlation between salivary IFN-gamma (Interferon-gamma) and Eotaxin2/CCL24 (chemokine ligand 24) with sputum production. Conversely, negative correlations were noted in serum MCP3/CCL7 (monocyte-chemotactic protein 3/Chemokine ligand 7), MIG/CXCL9 (Monokine induced by gamma/Chemokine ligand 9), IL1 beta (interleukin 1 beta), and SCF (stem cell factor) with sputum production (p<0.05, Mann-Whitney test).ConclusionSubstantial distinctions in salivary microbial communities were evident between COVID-19 patients with and without sputum production, emphasizing the notable impact of sputum production on the oral microbiome and cytokine levels during the acute phase of infection.
5’-untranslated region sequences enhance plasmid-based protein production inSulfolobus acidocaldarius
Authors: Kuschmierz Laura , Wagner Alexander , Busche Tobias , Kalinowski Jörn , Bräsen Christopher , Siebers Bettina 
Published: March 2024

AbstractSulfolobus acidocaldarius, a thermoacidophilic archaeon of the phylum Thermoproteota (former Crenarchaeota), is a widely used model organism for gene deletion studies and recombinant protein production. Previous research has demonstrated the efficacy of thesaci_2122promoter (Para), providing low basal activity and high pentose-dependent induction. However, available expression vectors lack a 5’-terminal untranslated region (5’-UTR), which is a typical element in bacterial expression vectors, usually significantly enhancing protein production in bacteria. To establishS. acidocaldariusas a production strain in biotechnology in the long-term, it is intrinsically relevant to optimize its tools and capacities to increase production efficiencies. Here we show that protein production is increased by the integration ofS. acidocaldarius5’-UTRs into Paraexpression plasmids. Using the esterase Saci_1116 as a reporter protein, we observed a fourfold increase in soluble and active protein yield upon insertion of thesaci_1322(alba) 5’-UTR. Screening of four additional 5’-UTRs from other highly abundant proteins (thα,slaA,slaB, saci_0330) revealed a consistent enhancement in target protein production. Additionally, site-directed mutagenesis of the Shine-Dalgarno (SD) motif within thealba5’-UTR revealed its significance for protein synthesis. Ultimately, thealba5’-UTR optimized expression vector demonstrated successful applicability in expressing various proteins, exemplified by its utilization for archaeal glycosyltransferases. Our results demonstrate that the integration of SD-motif containing 5’-UTRs significantly boosted plasmid-based protein production inS. acidocaldarius. This advancement in recombinant expression not only broadens the utility ofS. acidocaldariusas an archaeal expression platform but also marks a significant step toward potential biotechnological applications.
Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques
Authors: Tong Xin , Wang Qixin , Jung Wonyeong , Chicz Taras M. , Blanc Ross , Parker Lily J. , Barouch Dan H. , McNamara Ryan P. 
Published: March 2024

AbstractAntibodies represent a primary mediator of protection against respiratory viruses such as SARS-CoV-2. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are not well understood. Here we show that antibody correlates of protection against SARS-CoV-2 challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, neutralizing antibodies were the strongest correlate of protection and were linked to Spike-specific binding antibodies and other extra-neutralizing antibody functions that create a larger protective network. In contrast, in bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal Spike-specific IgG, IgA/secretory IgA, and Fcγ-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites. The correlation of ADCP and other Fc functional antibody responses with protection in BAL suggests that these antibody responses may be critical for protection against SARS-CoV-2 Omicron challenge in mucosa.
The antifungal activity of cymoxanil is associated with proton pump inhibition and disruption of plasma membrane potential
Authors: Mendes Filipa , Meyer Hadar , Amaral Leslie , Castro Bruno B. , Schuldiner Maya , Sousa Maria João , Chaves Susana R. 
Published: March 2024

AbstractWorldwide use of agrochemicals, particularly pesticides, is necessary to increase agricultural production to feed the ever-growing population. However, despite widespread use, the biochemical mode of action of many agrochemicals and their potential deleterious effects on the environment are poorly characterized. Cymoxanil (CYM) is a fungicide used to combat downy mildew diseases in grapevine cultures and late blight diseases in tomato and potato cultures caused by the oomycetesPlasmopara viticolaandPhytophthora infestans, respectively. Previous reports indicate that CYM affects growth, DNA and RNA synthesis inPhytophthoraand inhibits cell growth, biomass production and respiration rate in the well-characterized fungal modelSaccharomyces cerevisiae. We therefore used this model to further dissect mechanisms underlying the toxicological effects of CYM. We found that CYM induced genome-wide alterations, particularly in membrane transporter systems. These alterations were associated with perturbations in lipid-raft organization and inhibition of Pma1p, leading to a decrease in plasma membrane potential and intracellular acidification. Altogether, these findings identify the plasma membrane as one of the targets of CYM and proposes a mode of action underlying its antifungal activity.