bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the role of sex in hospitalizations among people with and without HIV in British Columbia, Canada
Authors: Naidu Nicholas , Kooij Katherine W. , Budu Michael , Ye Monica , Lu Michelle , Ding Erin , Mcclean Alison , Guillemi Silvia , Hull Mark , Barrios Rolando , Montaner Julio S.G. , Hogg Robert S. 
Published: January 2025

Objective:
We assessed sex differences in hospitalization rates among people with HIV (PWH) and people without HIV (PWoH) in British Columbia (BC).

Methods:
PWH and a 10% random sample of PWoH in BC aged ≥19 were followed from 04/01/2002 to 03/31/2020, using linked administrative Comparative Outcomes and Service Utilization Trends (COAST) study data. Hospitalizations were categorized by discharge diagnosis, using broad International Classification of Diseases-classes. Using Poisson regression, we modelled the association between sex, HIV-status, their interaction, and hospitalization rates adjusting for confounders.

Results:
Among 12,635 PWH (17.81% females) and 548,992 PWoH (49.34% females), age-adjusted hospitalization rates per 100 person-years were highest among females with HIV (incidence rate [IR] 34.25), followed by males with HIV (IR 21.49), females (IR 7.10), and males (IR 7.06) without HIV. Hospitalization rates for all causes declined from 2002-2022 across all subgroups but remained consistently higher among females with HIV, except for circulatory diseases and neoplasms. Adjusted for socio-structural factors, being male (rate ratio [RR] 1.92) or female with HIV (RR 2.66) was significantly associated with a higher hospitalization rate compared to males without HIV. Among PWH, female sex remained significantly associated with a higher hospitalization rate, after adjusting for HIV- and disease-related factors.

Conclusions:
We found a higher hospitalization rate among PWH than PWoH in BC, with the highest rate among females with HIV. This could partially be explained by socio-structural factors. Addressing these disparities and improving our understanding of the underlying mechanisms is critical to enhance health outcomes for women with HIV.
Clinical and sociodemographic characteristics of alzheimer's disease and related dementias (AD/ADRD) among people living with HIV: a cross-sectional analysis
Authors: Brown Monique J. , Murtala Nyame Mustapha , Amoatika Daniel , Kaur Amandeep , Addo Prince Nii Ossah , Osinubi Medinat Omobola , Miller Maggi , Ingram Lucy A. 
Published: January 2025

Introduction:
Alzheimer's disease and related dementias (AD/ADRD) continue to be a public health challenge. People living with HIV (PLWH) are at risk for neurocognitive disorders and may be at risk for AD/ADRD. However, studies examining clinical and sociodemographic factors associated with AD/ADRD among PLWH are lacking. Therefore, the aim of this cross-sectional study was to determine the association between selected sociodemographic (age, gender, race and rurality) and clinical (depression and encephalopathy) factors with (AD/ADRD) among PLWH.

Methods:
Data were obtained from the South Carolina Revenue and Fiscal Affairs (RFA) Office and the South Carolina Alzheimer's Disease Registry (N = 13,390). Multivariable logistic regression models were used to determine the association between age, gender, race, rurality, depression and encephalopathy, and AD/ADRD among PLWH.

Results:
Among the study population (N = 13,390), 5% (n = 601) were found to have AD/ADRD. There was a dose-response relationship between age group and AD/ADRD whereas the age group increased, the association increased. For example, those who were aged 80 years and older were 80 times more likely to have AD/ADRD compared to those aged 18–29 years (aOR: 80.4; 95% CI: 40.2–160.8). Additionally, male sex (aOR: 1.3; 95% CI: 1.9–1.6) and encephalopathy (aOR: 2.4; 95% CI: 1.9–3.2) were positively associated with AD/ADRD for PLWH.

Conclusion:
AD/ADRD interventions may be warranted among PLWH, especially among older adults, men, and those with encephalopathy. Future studies should examine potential pathways between clinical and sociodemographic characteristics and AD/ADRD among PLWH.
Campylobacter fetus subspecies fetus; an unforeseen cause of abortion in Regional Australia.
Authors: Owusu-Ansa Immanuella , Ramadas Manjeera , Jacob Nikhitha , Ayeni Femi E. 
Published: January 2025

Campylobacter fetus (C.fetus) subspecies fetus, a gram-negative bacterium, is an established cause of abortion and infertility in cattle, sheep and goats. Human infections have been rarely reported. In contrast to TORCH infections, this campylobacter species is hardly recognised as a cause of abortion in humans. Since 1947 after the first case report in France, there are only 11 reported cases in pregnant women worldwide and no published reports in Australia, pregnant or otherwise. The case in this study was compared to the first reported infection of C.fetus in 1947 to raise awareness and educate doctors and midwives, subsequently impacting prenatal and antenatal counselling in these regions.
A Venn diagram was constructed to highlight the similarities between this and the index case. The similarities found included the clinical state of the patient post-abortion and the all-important history of exposure to farm animals that suffered recent deaths on the farms of both patients. Some of the differences included the time of onset of symptoms to the time of abortion, the choice of antibiotics by both treating teams and the presentation of sepsis, suggesting the importance of Campylobacter fetus subspecies fetus as a perinatal infection.
scAGG: Sample-level embedding and classification of Alzheimer’s disease from single-nucleus data
Authors: Verlaan T. , Bouland G. , Mahfouz A. , Reinders M.J.T. 
Published: January 2025

AbstractIdentifying key cell types and genes in Alzheimer’s Disease (AD) is crucial for understanding its pathogenesis and discovering therapeutic targets. Single cell RNA sequencing technology (scRNAseq) has provided unprecedented opportunities to study the molecular mechanisms that underlie AD at the cellular level. In this study, we address the problem of sample-level classification of AD using scRNAseq data, where we predict the disease status of entire samples from the gene expression profiles of their cells, which are not necessarily all affected by the disease. We introduce scAGG, a sample-level classification model which uses a sample-level pooling mechanism to aggregate single-cell embeddings, and show that it can accurately classify AD individuals and healthy controls. We then investigate the latent space learnt by the model and find that the model learns an ordering of the cells corresponding to disease severity. Genes associated with this ordering are enriched in AD-linked pathways, including cytokine signalling, apoptosis, and metal ion response. We also evaluate two attention-based models that perform on par with scAGG, but entropy analysis of their attention scores reveals limited interpretability value. As scRNAseq is increasingly applied to large cohorts, our approach provides a way to link individual phenotypes to single-cell measurements. Our cell- and sample-level severity scores may enable identification of AD-associated cell subtypes, paving the way for targeted drug development and personalized treatment strategies in AD.A Python implementation of scAGG is available athttp://github.com/timoverlaan/scAGG
Distinct localization patterns of actin microfilaments during early cell plate formation in plants through deep learning-based image restoration
Authors: Kikuchi Suzuka , Kotaka Takumi , Hanaki Yuga , Ueda Minako , Higaki Takumi 
Published: January 2025

AbstractPhragmoplasts are plant-specific intracellular structures composed of microtubules, actin microfilaments (AFs), membranes, and associated proteins. Importantly, they are involved in the formation and expansion of cell plates that partition daughter cells during cell division. While previous studies have revealed the important role of cytoskeletal dynamics in the proper functioning of the phragmoplast, the localization and role of AFs in the initial phase of cell plate formation remain controversial. Here, we used deep learning-based image restoration to achieve high-resolution 4D imaging with minimal laser-induced damage, enabling us to investigate the dynamics of AFs during the initial phase of cell plate formation in transgenic tobacco BY-2 cells labeled with Lifeact-RFP or RFP-ABD2 (actin binding domain 2). This computational approach overcame the limitation of conventional imaging, namely laser-induced photobleaching and phototoxicity. The restored images indicated that RFP-ABD2 labeled AFs were predominantly localized near the daughter nucleus, whereas Lifeact-RFP labeled AFs were found not only near the daughter nucleus but also around the initial cell plate. These findings, validated by imaging with a long exposure time, highlight distinct localization patterns between the two AF probes and suggest that Lifeact-RFP labeled AFs play a role in initiating cell plate formation.
An integrative molecular systems approach unravels mechanisms underlying biphasic nitrate uptake by plant nitrate transporter NRT1.1
Authors: Subhadarshini Seemadri , Sahoo Sarthak , Jolly Mohit Kumar , Rashid Mubasher 
Published: January 2025

AbstractElucidating the mechanisms of transport kinetics in plants is crucial to develop crops that can use nutrients efficiently. The plant nitrate transporter NRT1.1 rapidly switches between high- and low-affinity transport modes to maintain an optimal uptake amidst fluctuations in nitrate levels. This functional switch is regulated by NRT1.1 phosphorylation, but the precise mechanisms remain poorly understood. Here, using an integrated molecular and systems-level modeling, we identify mechanisms underlying biphasic behaviour of NRT1.1. Phosphorylation of NRT1.1 and its binding to nitrate impacts its overall flexibility and synergistically modulates its global conformation, impacting the nitrate transport rate. Integrating these observations with a regulatory network involving kinases CIPK8/CIPK23 and calcium binding proteins CBL1/9, reveals that in high nitrate conditions, CIPK8-mediated sequestration of CBL1 disrupts the CIPK23-CBL complex required for NRT1.1 phosphorylation, switching NRT1.1 to a low-affinity mode. Together, our findings untangle the molecular complexity enabling NRT1.1 phosphorylation switch with broader implications in nitrate sensing and molecular-level adaption to fluctuating external nutrient levels.
Functional Modulation of Retrotrapezoid Neurons Drives Fentanyl-Induced Respiratory Depression
Authors: Moreira Thiago S. , Burgraff Nicholas J. , Takakura Ana C. , Oliveira Luiz M. , Araujo Emmanuel V. , Guan Steven , Ramirez Jan-Marino 
Published: January 2025

AbstractThe primary cause of death from opioid overdose is opioid-induced respiratory depression (OIRD), characterized by severe suppression of respiratory rate, destabilized breathing patterns, hypercapnia, and heightened risk of apnea. The retrotrapezoid nucleus (RTN), a critical chemosensitive brainstem region in the rostral ventrolateral medullary reticular formation contains Phox2b+/Neuromedin-B (Nmb) propriobulbar neurons. These neurons, stimulated by CO2/H+, regulate breathing to prevent respiratory acidosis. Since the RTN shows limited expression of opioid-receptors, we expected that opioid-induced hypoventilation should activate these neurons to restore ventilation and stabilize arterial blood gases. However, the ability of the RTN to stimulate ventilation during OIRD has never been tested. We used optogenetic and pharmacogenetic approaches, to activate and inhibit RTN Phox2B+/Nmb+neurons before and after fentanyl administration. As expected, fentanyl (500 µg/kg, ip) suppressed respiratory rate and destabilized breathing. Before fentanyl, optogenetic stimulation of Phox2b+/Nmb+or chemogenetic inhibition ofNmb+cells increased and decreased breathing activity, respectively. Surprisingly, optogenetic stimulation after fentanyl administration caused a significantly greater increase in breathing activity compared to pre-fentanyl levels. By contrast chemogenetic ablation of RTNNmbneurons caused profound hypoventilation and breathing instability after fentanyl. The results suggest that fentanyl does not inhibit the ability of Phox2b+/Nmb+cells within the RTN region to stimulate breathing. Thus, this study highlights the potential of stimulating RTN neurons as a therapeutic approach to restore respiratory function in cases of OIRD.
Complex exchanges among plasmids and clonal expansion of lineages shape the population structure and virulence ofBorrelia burgdorferi
Authors: Laing Rachel A. , Foster Michael J. , Hassani M. Amine , Kotzen Benjamin , Huang Weihua , Shea Terrence , Schaffner Stephen F. , Cerar Tjasa , Freimark Lisa , Ruzic-Sabljic Eva , Liveris Dionysios , Reed Kurt D. , Branda John A. , Steere Allen C. , Wormser Gary P. , Strle Franc , Sabeti Pardis C. , Earl Ashlee , Schwartz Ira , Strle Klemen , Lemieux Jacob E. 
Published: January 2025

ABSTRACTBackgroundIn the United States,Borrelia burgdorferi(Bb) is the principal etiologic agent of Lyme disease. The complex structure ofBbgenomes has posed challenges for genomic studies because homology among the bacterium’s many plasmids, which account for ∼40% of the genome by length, has made them difficult to sequence and assemble.ResultsWe used long-read sequencing to generate near-complete assemblies of 62 isolates of human-derivedBband collected public genomes with plasmid sequences. We characterized genetic diversity and population structure in the resulting set of 82 plasmid-completeBorrelia burgdorferisensu stricto genomes. TheBbcore genome is encoded by a chromosome and the conserved plasmids cp26, lp54, and lp17; the accessory genome is encoded by all other plasmids and the distal arm of the chromosome. Near-complete genomes reveal that the most granularBbgenotypes are clonal expansions of complex rearrangements among accessory genome elements. Ribosomal spacer types (RST) represent multiple collections of such genotypes, whereas OspC types are usually clonal. Structural rearrangements are non-randomly distributed throughout the genome, with cp32 plasmids undergoing dense exchanges and most linear plasmids, except lp54, sharing blocks among themselves and with the distal arm of the chromosome. OspC type A strains, known to possess greater virulence in humans, are distinguished by the presence of lp28-1 and lp56. Rearrangements among plasmids tended to preserve gene content, suggesting functional constraints among gene networks. Using k-partite graph decompositions, we identified gene sets with correlation patterns suggestive of conserved functional modules.ConclusionsLong-read assemblies reveal thatBbpopulation genetic structure results from clonal expansion of lineages that have undergone complex rearrangements among plasmid-encoded accessory genome elements. Genetic structure is preserved among genes even when plasmid rearrangements occur, suggesting that selection among epistatic loci maintains functional genetic networks. The analysis of near-complete genomes assembled using long-read sequencing methods advances our understanding ofBbbiology and Lyme disease pathogenesis by providing the first detailed view of population variation in previously inaccessible areas of theBbgenome.
ChiraKit, an online tool for the analysis of circular dichroism spectroscopy data
Authors: Burastero Osvaldo , Jones Nykola C. , Defelipe Lucas A. , Zavrtanik Uroš , Hadži San , Hoffmann Søren Vrønning , Garcia-Alai Maria M. 
Published: January 2025

AbstractCircular dichroism (CD) spectroscopy is an established biophysical technique to study chiral molecules. CD allows investigating conformational changes under varying experimental conditions and has been used to understand secondary structure, folding and binding of proteins and nucleic acids. Here, we present ChiraKit, a user-friendly, online, open-source tool to process raw CD data and perform advanced analysis. ChiraKit features include the calculation of protein secondary structure with the SELCON3 and SESCA algorithms, estimation of peptide helicity using the helix-ensemble model, the fitting of thermal/chemical unfolding or user-defined models, and the decomposition of spectra through singular value decomposition (SVD) or principal component analysis (PCA). ChiraKit can be accessed athttps://spc.embl-hamburg.de/.
Single-AAV CRISPR editing of skeletal muscle in non-human primates with NanoCas, an ultracompact nuclease
Authors: Rauch Benjamin J. , DeLoughery Aaron , Sper Renan , Chen Sean , Yunanda Sophia , Masnaghetti Megan , Chai Ning , Lin Jason Chen , Neckelmann Alexander , Bjornson Ymer , Espino David Paez , Sancio Alyssa , Schmitt Christopher , Scholes Clarissa , Shah Ria , Narendra Pooja Kyatsandra , Ansaloni Sara , Tan SiuSze , Rukmini Subhadra Jayaraman , Somaiah Sahana , Suresh Shravanti , Minami Shiaki , Tymoshenko Stepan , Wright Will , Xu Siming , Broughton James , Retwitzer Matan Drory , Bobbin Maggie , Yuan Dave , Abe Keith , DeWitt Mark , Zhang Bohong , Harrington Lucas B. 
Published: January 2025

AbstractCRISPR gene editing is a transformative technology for addressing genetic diseases, but delivery constraints have largely limited its therapeutic applications to liver-targeted andex vivotherapies. Here, we present the discovery and engineering of NanoCas, an ultracompact CRISPR nuclease capable of extending CRISPR’s reachin vivobeyond liver targets. We experimentally screened 176 ultracompact CRISPR systems found in metagenomic data and applied protein engineering approaches to enhance the editing efficiency of NanoCas. The optimized NanoCas exhibits potent editing capabilities across various cell systems and tissuesin vivowhen administered via adeno-associated viral (AAV) vectors. This is accomplished despite NanoCas being approximately one-third the size of conventional CRISPR nucleases. In proof-of-concept experiments, we observed robust editing with our optimized NanoCas in mouse models targeting Pcsk9, a gene involved in cholesterol regulation, and targeting exon splice sites in dystrophin to address Duchenne muscular dystrophy (DMD) mutations. We further tested the efficacy of our NanoCas systemin vivoin non-human primates (NHPs) resulting in editing levels above 30% in muscle tissues. The compact size of NanoCas, in combination with robust nuclease editing, opens the door for single-AAV editing of non-liver tissuesin vivo, including the use of newer editing modalities such as reverse transcriptase (RT) editing, base editing, and epigenetic editing.
Three-dimensional cellularization in chytrid fungi uses distinct mechanisms from those driving one- and two-dimensional cytokinesis in animals and yeast
Authors: Medina Edgar M , Elting Mary W , Fritz-Laylin Lillian 
Published: January 2025

ABSTRACTChytrid fungi offer a unique opportunity to study three-dimensional cellularization, where nuclei that start out homogeneously distributed throughout the cytoplasm are synchronously compartmentalized into daughter cells. This process addresses geometric challenges not encountered in conventional cytokinesis, where nuclei are organized in a one-dimensional line, or inDrosophilacellularization, which is organized in a two-dimensional plane—both of which allow nuclei direct access to cytokinetic cues placed at the plasma membrane. Here, we show that three-dimensional cellularization in the chytridSpizellomyces punctatusproceeds through a stepwise program, beginning with the transient migration of nuclei and their associated centrosomes to the plasma membrane. At this point, centrosome-associated vesicles form and initiate membrane invagination, establishing tubular furrows that expand and branch, ultimately creating a foam-like tessellation of tightly packed polyhedral compartments, each containing a single nucleus and bearing a cilium. Using a combination of small molecule inhibitors and laser ablation, we demonstrate that, similar to cytokinesis andDrosophilacellularization, chytrid cellularization is powered by actomyosin networks. We also show that while microtubules are important for patterning, they appear dispensable for cellularization. Finally, we suggest that chytrids may have incorporated mechanisms associated with ciliogenesis in animals to coordinate the association of internal nuclei with actomyosin networks and membranes. These data highlight the value of using chytrid fungi to study the unique geometric problems associated with three-dimensional cellularization.
Haplotype rather than single causal variants effects contribute to regulatory gene expression associations in human myeloid cells
Authors: Greenwood Emily , Cao Mingming , Lee Ciaran M. , Liu Aidi , Moyo Buhle , Bao Gang , Gibson Greg 
Published: January 2025

ABSTRACTGenome-wide association studies typically identify hundreds to thousands of loci, many of which harbor multiple independent peaks, each parsimoniously assumed to be due to the activity of a single causal variant. Fine-mapping of such variants has become a priority and since most associations are located within regulatory regions, it is also assumed that they colocalize with regulatory variants that influence the expression of nearby genes. Here we examine these assumptions by using a moderate throughput expression CROPseq protocol in which Cas9 nuclease is used to induce small insertions and deletions across the credible set of SNPs that may account for expression quantitative trait loci (eQTL) for genes associated with inflammatory bowel disease (IBD). Of the 4,384 SNPs targeted in 88 loci (an average of 50 per locus), 439 were significant and further examined for validation. From these, 98 significantly altered target gene expression in HL-60 myeloid cell line, 74 in induced macrophages from these HL-60 cells, and 78 in induced neutrophils for a total of 201 validated effects (46%), 43 of which were observed in at least two of the cell types. Considering the observed sensitivity and specificity of the controls, we estimate that there are at least 150 true positives per cell type, an average of almost 2.4 for each of the 64 eQTL for which putative causal variants have been fine-mapped. This implies that haplotype effects are likely to explain many of the associations. We also demonstrate that the same approach can be used to investigate the activity of very rare variants in regulatory regions for 89 genes, providing a rapid strategy for establishing clinical relevance of non-coding mutations.