bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of cardiovascular disease associated with long-term use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis
Authors: Kim Ji-Won , Yoon Jun Sik , Park Sojeong , Kim Hasung , Kim Bo young , Lee Hwajeong , Park Sung-Hoon , Kim Seong-Kyu , Choe Jung-Yoon 
Published: January 2024

Abstract

Objective
To examine the risk of cardiovascular disease associated with long-term use of NSAIDs in a large real-world AS cohort.

Methods
This nationwide population-based cohort study used data from the Korean National Health Insurance Database. Patients aged ≥18 years old who were newly diagnosed with AS without prior cardiovascular disease between January 2010 and December 2018 were included in this study. Controls without AS were randomly selected by age, sex and index year. The primary outcome was cardiovascular disease, a composite outcome of ischaemic heart disease, stroke or congestive heart failure. Long-term use of NSAIDs was defined as use of NSAIDs for &gt;365 cumulative defined daily doses. The association between long-term use of NSAIDs and incident cardiovascular disease was examined in both AS and non-AS populations.

Results
Among 19 775 patients with AS and 59 325 matched controls without AS, there were 1663 and 4308 incident cases of cardiovascular disease, showing an incidence of 16.9 and 13.8 per 1000 person-years, respectively. Long-term use of NSAIDs was associated with increased risk of cardiovascular disease in non-AS controls [adjusted hazard ratio (aHR) 1.64; 95% CI 1.48–1.82]. In contrast, long-term use of NSAIDs did not increase the risk of cardiovascular disease in AS patients (aHR 1.06; 95% CI 0.94–1.20; adjusted for age, sex, socioeconomic status, BMI, smoking status, hypertension, diabetes, hyperlipidemia and TNF inhibitor use).

Conclusion
Prolonged NSAID treatment in AS patients may not be as harmful as in the general population regarding cardiovascular risk.
Predictors of renal flares in systemic lupus erythematosus: a post-hoc analysis of four phase III clinical trials of belimumab
Authors: Jägerback Sandra , Gomez Alvaro , Parodis Ioannis 
Published: January 2024

Abstract

Objective
The objective of this study was to identify predictors of renal flares in patients with SLE treated for active extra-renal disease.

Methods
Data from four clinical trials of belimumab in SLE (BLISS-52, NCT00424476; BLISS-76, NCT00410384; BLISS-NEA, NCT01345253; BLISS-SC, NCT01484496) were used. Patients were assigned to belimumab or placebo on top of standard therapy. We investigated the performance of predictors of renal flares through weeks 52–76 using proportional hazards regression analysis.

Results
Of 3225 participants, 192 developed at least one renal flare during follow-up, with the first occurring after a median time of 197 days. Current/former renal involvement [hazards ratio (HR): 15.4; 95% CI: 8.3–28.2; P &lt; 0.001], low serum albumin levels (HR 0.9; 95% CI: 0.8–0.9; P &lt; 0.001), proteinuria (HR: 1.6; 95% CI: 1.5–1.7; P &lt; 0.001), and low C3 levels (HR: 2.9; 95% CI: 2.1–4.1; P &lt; 0.001) at baseline appeared robust determinants of impending renal flares. Anti-dsDNA positivity yielded an increased hazard for renal flares (HR: 2.1; 95% CI: 1.4–3.2; P &lt; 0.001), which attenuated after adjustments. Anti-Sm positivity was associated with renal flares in the placebo (HR: 3.7; 95% CI: 2.0–6.9; P &lt; 0.001) but not in the belimumab subgroup, whereas anti-ribosomal P positivity was associated with renal flares in the belimumab subgroup only (HR: 2.8; 95% CI: 1.5–5.0; P = 0.001).

Conclusion
A history of renal involvement, high baseline proteinuria, hypoalbuminaemia, and C3 consumption were robust determinants of impending renal flares. In addition to anti-dsDNA, anti-Sm and anti-ribosomal P protein antibody positivity may have value in surveillance of renal SLE.
Disease activity trajectories in juvenile dermatomyositis from childhood to adulthood
Authors: Nozawa Tomo , Pullenayegum Eleanor M , Bell-Peter Audrey , Marcuz Jo-Anne , Whitney Kristi , Vinik Ophir , Shupak Rachel , Dover Saunya , Feldman Brian M 
Published: January 2024

Abstract

Objectives
To assess whether there are identifiable subgroups of disease activity trajectory in a population of JDM patients—followed throughout childhood and into adulthood—and determine factors that predict those trajectory groupings.

Methods
This is a retrospective, longitudinal inception cohort of patients with idiopathic inflammatory myopathies, largely JDM. We sought to identify baseline factors that predict membership into different groups (latent classes) of disease activity trajectory.

Results
A total of 172 patients (64% females), with median age at diagnosis of 7.7 years, were analysed. We studied 4725 visits (1471 patient-years). We identified three latent classes of longitudinal disease activity, as measured by the modified DAS (DASm), with distinct class trajectories predicted by DASm at baseline, and by the changes of DASm from either baseline to 3 months or baseline to 6 months (early response to therapy). In the analysis in which DASm at baseline and the changes of DASm from baseline to 6 months are included as predictors, Class 1 (10%) has persistently high disease activity, Class 2 (34%) is characterized by moderate disease activity and Class 3 (56%) is characterized by individuals with a high early disease activity but an apparently good response to treatment and long-term low disease activity.

Conclusion
High early disease activity, and treatment resistance in the first few months, predict a more chronic longitudinal course of JDM.
First-time orgasm in a young man with lifelong anorgasmia after flibanserin use: a case report
Authors: Saffati Gal , Naeem Taher , Kaaki Basil , Khera Mohit 
Published: January 2024

Abstract

Introduction
Anorgasmia is a poorly understood phenomenon defined as either a lifelong or acquired consistent inability to achieve ejaculation. Despite the prevalence of anorgasmia, there is currently no established treatment for the condition.

Aims
To report a unique case of a patient with lifelong anorgasmia who was able to achieve his first orgasm with off-label use of flibanserin.

Methods
The present case study relies on the patient’s self-report and a review of the relevant literature. The patient provided written informed consent.

Results
A 28-year-old male presented to our office with complaints of lifelong anorgasmia, without any signs of erectile dysfunction. He reported good libido and energy levels and denied any urinary symptoms or history of depression. The patient failed medical management with numerous off-label medications, including bupropion and bremelanotide. Despite having received 4 or 5 sex therapy sessions over 3 months, the patient reported that this treatment approach was not effective. Off-label use of flibanserin was then initiated, and after 28 to 32 doses over 4 weeks, he achieved his first orgasm. Notably, the patient experienced nocturia and insomnia. The follow-up International Index of Erectile Function score marginally improved by 2 points without any improvement in the overall satisfaction subdomain.

Conclusion
This case highlights the challenges of managing anorgasmia and anejaculation in a young male patient. A stepwise approach involving pharmacotherapy and sex therapy was not successful. However, the off-label use of flibanserin ultimately resulted in the patient achieving his first orgasm, albeit with some side effects. Further studies are needed to evaluate the efficacy and safety of flibanserin in men for this indication.
A propensity score–matched analysis of intra- and postoperative penile prosthetic complications in the solid organ transplant population
Authors: Johnson John C , Venna Rahul , Alzweri Laith 
Published: January 2024

Abstract

Introduction
Solid organ transplant (SOT) has an anticipated higher risk of penile prosthesis (PP) complications related to immunosuppression and surgical approach post-SOT. It is still not determined if PP surgery in the SOT population incurs these same higher risks.

Objectives
To observe differences in intra- and postoperative PP complications between SOT and non-SOT cases from the TriNetX US Collaborative Network, a large real-world database of deidentified patient data from 56 health care organizations within the United States.

Methods
We used the TriNetX database to perform a propensity score–matched cohort study comparing 10-year outcomes between patients with and without a SOT (kidney, heart, lung, liver, pancreas, and intestine) who underwent a PP procedure. Cohorts were matched on age, race/ethnicity, history of pelvic and abdominal surgery, overweight and obesity status, type 2 diabetes mellitus, atherosclerosis, substance use disorders, socioeconomic difficulties, anticoagulant/antiplatelet medications, and spinal cord injury. Outcomes included intra- and perioperative complications as well as prosthetic complications (mechanical malfunction, fibrosis, displacement, hemorrhage, pain, stenosis, removal with or without replacement, and complex [all postoperative complications]).

Results
There were 233 patients in each group after matching (SOT and non-SOT). The mean ± SD age at the prosthesis procedure was 59.7 ± 9.89 years, and 44% of patients were White (P &gt; .05). There was no significant difference for incidence of intra- and perioperative complications (2.62% vs 2.19%, P = .76). The SOT group did not have a higher 10-year incidence of complex complications (30.58% vs 27.51%, P = .11) or mechanical malfunction (10.35% vs 11.62%, P = .25) when compared with the non-SOT group. No difference was found for other prosthetic-related complications (P &gt; .05).

Conclusion
In our analysis, patients with a SOT were not more likely to experience long-term complications related to PP. Surgeons performing PP surgery in the SOT population may consider this procedure a potentially safe and viable option for restoring erectile function.
Human immunodeficiency virus dynamics in secondary lymphoid tissues and the evolution of cytotoxic T lymphocyte escape mutants
Authors: Chung Wen-Jian , Connick Elizabeth , Wodarz Dominik 
Published: January 2024

Abstract
In secondary lymphoid tissues, human immunodeficiency virus (HIV) can replicate in both the follicular and extrafollicular compartments. Yet, virus is concentrated in the follicular compartment in the absence of antiretroviral therapy, in part due to the lack of cytotoxic T lymphocyte (CTL)–mediated activity there. CTLs home to the extrafollicular compartment, where they can suppress virus load to relatively low levels. We use mathematical models to show that this compartmentalization can explain seemingly counter-intuitive observations. First, it can explain the observed constancy of the viral decline slope during antiviral therapy in the peripheral blood, irrespective of the presence of CTL in Simian Immunodeficiency Virus (SIV)-infected macaques, under the assumption that CTL-mediated lysis significantly contributes to virus suppression. Second, it can account for the relatively long times it takes for CTL escape mutants to emerge during chronic infection even if CTL-mediated lysis is responsible for virus suppression. The reason is the heterogeneity in CTL activity and the consequent heterogeneity in selection pressure between the follicular and extrafollicular compartments. Hence, to understand HIV dynamics more thoroughly, this analysis highlights the importance of measuring virus populations separately in the extrafollicular and follicular compartments rather than using virus load in peripheral blood as an observable; this hides the heterogeneity between compartments that might be responsible for the particular patterns seen in the dynamics and evolution of the HIV in vivo.
SARS-CoV-2 lineage assignments using phylogenetic placement/UShER are superior to pangoLEARN machine-learning method
Authors: de Bernardi Schneider Adriano , Su Michelle , Hinrichs Angie S , Wang Jade , Amin Helly , Bell John , Wadford Debra A , O’Toole Áine , Scher Emily , Perry Marc D , Turakhia Yatish , De Maio Nicola , Hughes Scott , Corbett-Detig Russ 
Published: January 2024

AbstractWith the rapid spread and evolution of SARS-CoV-2, the ability to monitor its transmission and distinguish among viral lineages is critical for pandemic response efforts. The most commonly used software for the lineage assignment of newly isolated SARS-CoV-2 genomes is pangolin, which offers two methods of assignment, pangoLEARN and pUShER. PangoLEARN rapidly assigns lineages using a machine-learning algorithm, while pUShER performs a phylogenetic placement to identify the lineage corresponding to a newly sequenced genome. In a preliminary study, we observed that pangoLEARN (decision tree model), while substantially faster than pUShER, offered less consistency across different versions of pangolin v3. Here, we expand upon this analysis to include v3 and v4 of pangolin, which moved the default algorithm for lineage assignment from pangoLEARN in v3 to pUShER in v4, and perform a thorough analysis confirming that pUShER is not only more stable across versions but also more accurate. Our findings suggest that future lineage assignment algorithms for various pathogens should consider the value of phylogenetic placement.
Oxaloacetic acid induces muscle energy substrate depletion and fatigue by JNK‐mediated mitochondrial uncoupling
Authors: Yin Cong , Qin Rui , Ma Zewei , Li Fan , Liu Jiao , Liu Hong , Shu Gang , Xiong Hairong , Jiang Qingyan 
Published: January 2024

AbstractFatigue is a common phenomenon closely related to physical discomfort and numerous diseases, which is severely threatening the life quality and health of people. However, the exact mechanisms underlying fatigue are not fully characterized. Herein, we demonstrate that oxaloacetic acid (OAA), a crucial tricarboxylic acid cycle intermediate, modulates the muscle fatigue. The results showed that serum OAA level was positively correlated with fatigue state of mice. OAA‐treated induced muscle fatigue impaired the exercise performance of mice. Mechanistically, OAA increased the c‐Jun N‐terminal kinase (JNK) phosphorylation and uncoupling protein 2 (UCP2) levels in skeletal muscle, which led to decreased energy substrate and enhanced glycolysis. On the other hand, OAA boosted muscle mitochondrial oxidative phosphorylation uncoupled with energy production. In addition, either UCP2 knockout or JNK inhibition totally reversed the effects of OAA on skeletal muscle. Therein, JNK mediated UCP2 activation with OAA‐treated. Our studies reveal a novel role of OAA in skeletal muscle metabolism, which would shed light on the mechanism of muscle fatigue and weakness.
Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis
Authors: Pekayvaz Kami , Joppich Markus , Brambs Sophia , Knottenberg Viktoria , Eivers Luke , Martinez-Navarro Alejandro , Kaiser Rainer , Meißner Nina , Kilani Badr , Stockhausen Sven , Janjic Aleksandar , Polewka Vivien , Wendler Franziska , Droste zu Senden Augustin , Leunig Alexander , Voelkl Michael , Engelmann Bernd , Hernandez Petzsche Moritz R , Boeckh-Behrens Tobias , Liebig Thomas , Dichgans Martin , Enard Wolfgang , Zimmer Ralf , Tiedt Steffen , Massberg Steffen , Nicolai Leo , Stark Konstantin 
Published: January 2024

AbstractThrombotic diseases remain the major cause of death and disability worldwide with insufficient preventive and therapeutic strategies available. In the last decades a prominent inflammatory component has been identified as a key driver in the initiation and propagation of thrombosis – named thromboinflammation. However, a comprehensive investigation of the human immune system in thromboinflammation, beyond histological quantification, is lacking, which is essential for the development of novel therapeutic approaches. We therefore mapped the trajectories, functional states, and intercommunication of immune cells in stroke thrombi, retrieved by thrombectomy, at single-cell resolution. We reveal distinct leukocyte subpopulations with prothrombotic and, surprisingly, prominent fibrinolytic properties characterized by aberrant activation of intracellular host defense as well as hypoxia induced pathways. A prominent thrombolytic PLAUhigh, PLAURhigh, THBDhighthrombus neutrophil subset, also expressing high levels of pro-recanalizing VEGFA and VEGFB, dominated the thrombus neutrophil environment. On the other hand CD16highNR4A1highnon-classical monocytes with strong CXCL8, CXCL2, CXCL1 and CXCL16 mediated neutrophil- attracting and PLAU, PLAUR, THBD and TFPI mediated thrombolytic properties defined the thrombus monocyte environment. These thrombus monocyte subsets were characterized by high expression of TIMP1 and TREM1. These novel innate immune- cell subsets provide insights into the thrombogenic and pro-resolving properties of innate immune-cells. To provide mechanistic insight into these multi-omic findings, we utilized reverse translation approaches.In vitroas well as murinein vivothrombosis models underlined the causal relevance of these immune-cell axes for thrombolysis: NR4A1highthrombus monocytes acquired a neutrophil-chemoattractive transcriptomic phenotype, neutrophils continuously infiltrated established murine thrombiin vivoand acquired a HIF1α-mediated thrombolytic phenotypein vitro. A depletion of NR4A1highthrombus monocytes reduced thrombus neutrophil influx and exacerbated thrombosisin vivo.Together, this unravels cross-communicating monocyte and neutrophil subsets with thrombus-resolving properties and provide a publicly accessible immune-landscape of thrombosis. This provides a valuable resource for future research on thrombo- inflammation and might pave the way for novel immune-modulatory approaches for prevention or resolution of thrombosis.
Spiking Neuron-Astrocyte Networks for Image Recognition
Authors: Lorenzo Jhunlyn , Rico-Gallego Juan-Antonio , Binczak Stéphane , Jacquir Sabir 
Published: January 2024

AbstractFrom biological and artificial network perspectives, researchers have started acknowledging astrocytes as computational units mediating neural processes. Here, we propose a novel biologically-inspired neuron-astrocyte network model for image recognition, one of the first attempts at implementing astrocytes in Spiking Neuron Networks (SNNs) using a standard dataset. The architecture for image recognition has three primary units: the pre-processing unit for converting the image pixels into spiking patterns, the neuron-astrocyte network forming bipartite (neural connections) and tripartite synapses (neural and astrocytic connections), and the classifier unit. In the astrocyte-mediated SNNs, an astrocyte integrates neural signals following the simplified Postnov model. It then modulates the Integrate-and-Fire (IF) neurons via gliotransmission, thereby strengthening the synaptic connections of the neurons within the astrocytic territory. We develop an architecture derived from a baseline SNN model for unsupervised digit classification. The Spiking Neuron-Astrocyte Networks (SNANs) display better network performance with an optimal variance-bias trade-off than SNN alone. We demonstrate that astrocytes promote faster learning, support memory formation and recognition, and provide a simplified network architecture. Our proposed SNAN can serve as a benchmark for future researchers on astrocyte implementation in artificial networks, particularly in neuromorphic systems, for its simplified design.
Dynamic coexistence driven by physiological transitions in microbial communities
Authors: Narla Avaneesh V. , Hwa Terence , Murugan Arvind 
Published: January 2024

AbstractMicrobial ecosystems are commonly modeled by fixed interactions between species in steady exponential growth states. However, microbes often modify their environments so strongly that they are forced out of the exponential state into stressed or non-growing states. Such dynamics are typical of ecological succession in nature and serial-dilution cycles in the laboratory. Here, we introduce a phenomenological model, the Community State model, to gain insight into the dynamic coexistence of microbes due to changes in their physiological states. Our model bypasses specific interactions (e.g., nutrient starvation, stress, aggregation) that lead to different combinations of physiological states, referred to collectively as “community states”, and modeled by specifying the growth preference of each species along a global ecological coordinate, taken here to be the total community biomass density. We identify three key features of such dynamical communities that contrast starkly with steady-state communities: increased tolerance of community diversity to fast growth rates of species dominating different community states, enhanced community stability through staggered dominance of different species in different community states, and increased requirement on growth dominance for the inclusion of late-growing species. These features, derived explicitly for simplified models, are proposed here to be principles aiding the understanding of complex dynamical communities. Our model shifts the focus of ecosystem dynamics from bottom-up studies based on idealized inter-species interaction to top-down studies based on accessible macroscopic observables such as growth rates and total biomass density, enabling quantitative examination of community-wide characteristics.
Idiosyncratic pupil regulation in autistic children
Authors: Bleimeister Isabel , Avni Inbar , Granovetter Michael , Meiri Gal , Ilan Michal , Michaelovski Analya , Menashe Idan , Behrmann Marlene , Dinstein Ilan 
Published: January 2024

AbstractRecent neuroimaging and eye tracking studies have suggested that children with autism spectrum disorder (ASD) may exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here we extended this research for the first time to pupillometry recordings. We successfully completed pupillometry recordings with 103 children (66 with ASD), 4.5-years-old on average, who viewed three 90 second movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group. ASD participants exhibited significantly weaker inter-subject correlations than TD participants, reliably across all three movies. Differences across groups were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. This measure enabled classification of ASD and TD children with a sensitivity of 0.82 and specificity of 0.73 when trained and tested on independent datasets. Using the largest ASD pupillometry dataset to date, we demonstrate the utility of a new technique for measuring the idiosyncrasy of pupil regulation, which can be completed even by young children with co-occurring intellectual disability. These findings reveal that a considerable subgroup of ASD children have significantly more unstable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.