bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes-based dual drug-loaded nanocarrier for targeted and multiple proliferative vitreoretinopathy therapy
Authors: Zhao Peiyi , Wang Jiahao , Huang Huiying , Chen Zhirong , Wang Hui , Lin Quankui 
Published: June 2024

Abstract
Proliferative vitreoretinopathy (PVR) is a common cause of vision loss after retinal reattachment surgery and ocular trauma. The key pathogenic mechanisms of PVR development include the proliferation, migration and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPEs) activated by the growth factors and cytokines after surgery. Although some drugs have been tried in PVR treatments as basic investigations, the limited efficacy remains an obstacle, which may be due to the single pharmacological action and lack of targeting. Herein, the anti-proliferative Daunorubicin and anti-inflammatory Dexamethasone were co-loaded in the RPEs-derived exosomes (Exos), obtaining an Exos-based dual drug-loaded nanocarrier (Exos@D-D), and used for multiple PVR therapy. Owing to the advantages of homologous Exos and the dual drug loading, Exos@D-D showed good RPEs targeting as well as improved uptake efficiency, and could inhibit the proliferation, migration, as well as EMT of RPEs effectively. The animal studies have also demonstrated that Exos@D-D effectively inhibits the production of proliferative membranes and prevents the further development of inflammation, shows significant therapeutic effects on PVR and good biocompatibility. Such Exos-based dual drug-loaded nanocarrier investigation not only provides a promising approach for multifunctional exosome drug delivery systems construction, but also has great potential in PVR clinical therapy application.
Truly at home? Perceived belonging and immigrant incorporation
Authors: Ocampo Angela X 
Published: June 2024

Abstract
A significant amount of research has been devoted to studying the sociopolitical incorporation of immigrants and their descendants both socially and structurally. However, questions remain about how psychological mechanisms play a role in the incorporation process. While some immigrants might internalize a sense of social alienation, others might be able to overcome the detrimental impact of historical and present-day exclusion and develop a psychological notion of belonging to US society. To test the role of a psychological mechanism in the incorporation process, I rely on national survey data from the 2016 Collaborative Multiracial Post-Election Survey and a novel survey experiment. By leveraging these data, I examine the determinants of perceptions of inclusion in the United States among Latinos. The findings present a mixed picture of incorporation. I find that as Latinos become more familiarized with the United States culturally and socially, they are more likely to develop a sense of belonging. However, both experiencing discrimination and perceiving that the in-group faces discrimination negatively shape Latinos’ psychological sense of belongingness. Furthermore, receiving hostile messaging causes Latinos to feel less included in the US society. This paper highlights a social psychological mechanism of racialized incorporation, capturing whether immigrants and their descendants feel that they belong and are part of the host society.
Association between sleep microarchitecture and cognition in obstructive sleep apnea
Authors: Beaudin Andrew E , Younes Magdy , Gerardy Bethany , Raneri Jill K , Hirsch Allen A J Marcus , Gomes Teresa , Gakwaya Simon , Sériès Frédéric , Kimoff John , Skomro Robert P , Ayas Najib T , Smith Eric E , Hanly Patrick J 
Published: June 2024

Abstract

Study Objectives
Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication.

Methods
Participants with suspected OSA (n = 1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit–Symbol Coding, DSC). Associations between cognitive scores and stage 2 non-rapid eye movement (NREM) sleep spindle density, power, frequency and %-fast (12–16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP), and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition.

Results
All spindle characteristics were lower in participants with moderate and severe OSA (p ≤ .001, vs. no/mild OSA) and positively associated with MoCA, RAVLT, and DSC scores (false discovery rate corrected p-value, q ≤ 0.026), except spindle power which was not associated with RAVLT (q = 0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p ≤ .001) but neither ORPNREM (q ≥ 0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q ≥ 0.166). In mediation analyses, spindle density and EEGNP (p ≥ .048) mediated moderate-to-severe OSA’s negative effect on MoCA scores while ORPNREM, spindle power, and %-fast spindles mediated OSA’s negative effect on DSC scores (p ≤ .018).

Conclusions
Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.
Snoring and risk of dementia: a prospective cohort and Mendelian randomization study
Authors: Gao Yaqing , Andrews Shea , Daghlas Iyas , Brenowitz Willa D , Raji Cyrus A , Yaffe Kristine , Leng Yue 
Published: June 2024

Abstract

Study Objectives
The association between snoring, a very common condition that increases with age, and dementia risk is controversial. We aimed to investigate the observational and causal relationship between snoring and dementia, and to elucidate the role of body mass index (BMI).

Methods
Using data from 451 250 participants who were dementia-free at baseline, we examined the association between self-reported snoring and incident dementia using Cox proportional-hazards models. Causal relationship between snoring and Alzheimer’s disease (AD) was examined using bidirectional two-sample Mendelian randomization (MR) analysis.

Results
During a median follow-up of 13.6 years, 8325 individuals developed dementia. Snoring was associated with a lower risk of all-cause dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.89 to 0.98) and AD (HR 0.91; 95% CI 0.84 to 0.97). The association was slightly attenuated after adjusting for BMI, and was stronger in older individuals, APOE ε4 allele carriers, and during shorter follow-up periods. MR analyses suggested no causal effect of snoring on AD; however, genetic liability to AD was associated with a lower risk of snoring. Multivariable MR indicated that the effect of AD on snoring was primarily driven by BMI.

Conclusions
The phenotypic association between snoring and lower dementia risk likely stems from reverse causation, with genetic predisposition to AD associated with reduced snoring. This may be driven by weight loss in prodromal AD. Increased attention should be paid to reduced snoring and weight loss in older adults as potential early indicators of dementia risk.
Impaired cognition in narcolepsy: clinical and neurobiological perspectives
Authors: Cano Christopher A , Harel Brian T , Scammell Thomas E 
Published: June 2024

Abstract
In addition to well-known symptoms such as sleepiness and cataplexy, many people with narcolepsy have impaired cognition, reporting inattention, poor memory, and other concerns. Unfortunately, research on cognition in narcolepsy has been limited. Strong evidence demonstrates difficulties with sustained attention, but evidence for executive dysfunction and impaired memory is mixed. Animal research provides some insights into how loss of the orexin neurons in narcolepsy type 1 may give rise to impaired cognition via dysfunction of the prefrontal cortex, and cholinergic and monoaminergic systems. This paper reviews some of these clinical and preclinical findings, provides a neurobiological framework to understand these deficits, and highlights some of the many key unanswered questions.
The meaning of trust in good public governance
Authors: Liechtenstein H S H Prince Michael of 
Published: June 2024

Abstract
‘Perhaps the most important lesson is that trust is not only an indicator of success; it is, more significantly, one of the ingredients that make success—for a business or for a government—possible.’ This quote originally stems from a publication of the Organisation for Economic Co-operation and Development and confirms the results of a study conducted in Liechtenstein on the importance of institutional trust. The article discusses the interdependence of trust in state institutions and economic success and sets the context for the foundation and trust sector.
Discrete Correlate Summation Clustering of a Dopamine-Angiotensin Network
Authors: Westwood Brian M. , Yamaleyeva Liliya M. , Chen Rong 
Published: June 2024

ABSTRACTWe present a model of directed investigation of KEGG pathway analysis, beginning with discrete correlate summation (DCS) clustering of Swiss-Prot sets. Dopamine and angiotensin related proteins define the boundary for pathway analyses upon a network of proteins also associated with a compositely defined matrix of Swiss-Prot keywords to provide a framework for their biological indices (Figure 1).
Phosphoglycerate mutase regulates Treg differentiation through control of serine synthesis and one-carbon metabolism
Authors: Godfrey Wesley H. , Cho Kaho , Deng Xiaojing , Ambati Chandra Shekar R. , Putluri Vasanta , Mostafa Kamal Abu Hena , Putluri Nagireddy , Kornberg Michael D. 
Published: June 2024

AbstractThe differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3PG), the PGAM substrate, to de novo serine synthesis. Blocking de novo serine synthesis from 3PG reversed the effect of PGAM inhibition on Treg polarization, while exogenous serine directly inhibited Treg polarization. Additionally, altering serine levelsin vivowith a serine/glycine-free diet increased peripheral Tregs and attenuated autoimmunity in a murine model of multiple sclerosis. Mechanistically, we found that serine limits Treg polarization by contributing to one-carbon metabolism and methylation of Treg-associated genes. Inhibiting one-carbon metabolism increased Treg polarization and suppressive function bothin vitroandin vivoin a murine model of autoimmune colitis. Our study identifies a novel physiologic role for PGAM and highlights the metabolic interconnectivity between glycolysis, serine synthesis, one-carbon metabolism, and epigenetic regulation of Treg differentiation and suppressive function.
The Incisive Duct as a Pathway for Early Vomeronasal Communication in Neonatal Dogs
Authors: Vázquez Eva Sanmartín , Ortiz-Leal Irene , Torres Mateo V. , Kalak Patrycja , Kubiak-Nowak Dominika , Dzięcioł Michał , Sanchez-Quinteiro Pablo 
Published: June 2024

ABSTRACTThe detection of chemical signals by the vomeronasal organ (VNO) is critical for communication among mammals from an early age, influencing behaviors such as suckling and recognition of the mother and conspecifics. Located in a concealed position at the base of the nasal cavity, the VNO features a duct covered with a sensory epithelium rich in neuroreceptors. A critical aspect of VNO functionality is the efficient access of stimuli from the nasal and oral cavities to the receptors. In adult dogs, it has been demonstrated through in vivo magnetic resonance imaging and anatomically postmortem how the VNO duct (VD) communicates to the environment through the incisive duct (ID). However, in newborn puppies, the existence of functional communication between the ID and the VD has not been confirmed to date, raising doubts about the potential physiological obliteration of the ID due to its small size and the degree of immaturity of the puppies at birth. Determining this aspect is necessary to evaluate the role played by chemical communication in this critical phase for the survival and socialization of puppies. This study employs serial histological staining techniques to examine the presence and functionality of the incisive duct in neonatal dogs. The serial histological sections have confirmed both the existence of functional communication between both the vomeronasal and incisive ducts in perinatal puppies, and the dual functional communication of the incisive duct with the oral and nasal cavities. The ID shows an uninterrupted lumen along its path and is associated with a sophisticated cartilaginous complex that prevents its collapse, as well as erectile tissue rich in blood vessels and connective tissue that acts as a cushion, facilitating its action under pressure induced by sampling behaviors such as tonguing. This investigation demonstrates the communicative capabilities of the VNO during the perinatal stage in dogs.
Between-day reliability of local and global muscle-tendon unit assessments in female athletes whilst controlling for menstrual cycle phase
Authors: Newbould Scott , Walker Josh , Dinsdale Alexander J , Whitehead Sarah , Nicholson Gareth 
Published: June 2024

AbstractMeasurements of muscle-tendon unit (MTU) function can be categorised into local (e.g. tendon strain) or global (e.g. jump height) assessments. Although menstrual cycle phase may be a key consideration when implementing these assessments in female athletes, the reliability of many MTU assessments is not well defined within female populations. Therefore, the purpose of this study was to report the test-retest reliability of local and global MTU function assessments during the early follicular phase of the menstrual cycle. Seventeen naturally menstruating females (age 28.5 ± 7.3 years) completed local and global assessments of MTU function during two testing sessions separated over 24-72 hours. Local tests included Achilles’ tendon mechanical testing and isometric strength of ankle plantar flexors and knee extensors, whereas global tests included countermovement, squat, and drop jumps, and the isometric midthigh pull. Based on intraclass correlation coefficient (ICC) statistics,poortoexcellentreliability was found for local measures (ICC: 0.096-0.936).Goodtoexcellentreliability was found for all global measures (ICC: 0.788-0.985), excluding the eccentric utilisation ratio (ICC 0.738) and most rate of force development metrics (ICC: 0.635-0.912). Isometric midthigh pull peak force displayedexcellentreliability (ICC: 0.966), whereas force-time metrics ranged frommoderatetoexcellent(ICC: 0.635-0.970). Excluding rate of force development (coefficient of variation [CV]: 10.6-35.9%), global measures (CV: 1.6-12.9%) were more reproducible than local measures (CV: 3.6-64.5%). However, local metrics directly measure specific aspects of MTU function, and therefore provide valuable information despite lower reproducibility. The novel data reported here provides insight into the natural variability of MTU function within female athletes, which can be used to enhance the interpretation of other female athlete data, especially that which aims to investigate other aspects of variability, such as the menstrual cycle.
PIN2-mediated self-organizing transient auxin flow contributes to auxin maxima at the tip of Arabidopsis cotyledons
Authors: Pérez-Henríquez Patricio , Nagawa Shingo , Liu Zhongchi , Pan Xue , Michniewicz Marta , Tang Wenxin , Rasmussen Carolyn , Van Norman Jaimie , Strader Lucia , Yang Zhenbiao 
Published: June 2024

AbstractDirectional auxin transport and formation of auxin maxima are critical for embryogenesis, organogenesis, pattern formation, and growth coordination in plants, but the mechanisms underpinning the initiation and establishment of these auxin dynamics are not fully understood. Here we show that a self-initiating and - terminating transient auxin flow along the marginal cells (MCs) contributes to the formation of an auxin maximum at the tip of Arabidopsis cotyledon that globally coordinates the interdigitation of puzzle-shaped pavement cells in the cotyledon epidermis. Prior to the interdigitation, indole butyric acid (IBA) is converted to indole acetic acid (IAA) to induce PIN2 accumulation and polarization in the marginal cells, leading to auxin flow toward and accumulation at the cotyledon tip. When IAA levels at the cotyledon tip reaches a maximum, it activates pavement cell interdigitation as well as the accumulation of the IBA transporter TOB1 in MCs, which sequesters IBA to the vacuole and reduces IBA availability and IAA levels. The reduction of IAA levels results in PIN2 down-regulation and cessation of the auxin flow. Hence, our results elucidate a self-activating and self-terminating transient polar auxin transport system in cotyledons, contributing to the formation of localized auxin maxima that spatiotemporally coordinate pavement cell interdigitation.
G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer
Authors: Robinson Jenna , Flint Gem , Garner Ian , Galli Silvia , Maher Thomas E. , Kuimova Marina K. , Vilar Ramon , McNeish Iain A. , Brown Robert , Keun Hector , Di Antonio Marco 
Published: June 2024

AbstractEpigenetic evolution is a common mechanism used by cancer cells to evade the therapeutic effects of drug treatment. In ovarian cancers, epigenetically-driven resistance may be responsible for a large number of late-stage patient deaths. Here, we describe the first investigation into the role of G-quadruplex (G4) DNA secondary structures in mediating epigenetic regulation in drug-resistant ovarian cancer cells. Through genome-wide mapping of G4s in paired drug-sensitive and drug-resistant cell lines, we find that increased G4 formation is associated with significant increase in gene expression, with high enrichment in signalling pathways previously established to promote drug-resistant states. However, in contrast to previous studies, the expression-enhancing effects of G4s were not found at gene promoters, but intergenic and intronic regions, indicating that G4s promote long-range transcriptional regulation in drug-resistant cells. Furthermore, we discovered that clusters of G4s (super-G4s) are associated with particularly high levels of transcriptional enhancement that surpass the effects of super-enhancers, which act as well established regulatory sites in many cancers. Finally, we demonstrate that targeting G4s with small molecules results in significant down-regulation of pathways associated with drug-resistance, which results in resensitisation of resistant cells to chemotherapy agents. These findings indicate that G4 structures are critical for the epigenetic regulatory networks of drug-resistant cells and may represent a promising target to treat drug-tolerant ovarian cancer.
Synovial fluid transcriptome dynamics in osteoarthritis progression: Implications in pathogenesis
Authors: Sharma Rinkle , Rana Diksha , Kumar Rahul , Narula Sakshi , Chaudhary Alpa , Kaur Bhavneet , Kaur Khushpreet , Dhillon Mandeep , Chauhan Devendra K , Saini Uttam Chand , Sharma Sadhna , Kaur Jyotdeep , Verma Indu 
Published: June 2024

AbstractBackgroundOsteoarthritis, a degenerative joint disease associated with various pathological manifestations in the joint including cartilage loss, alterations in subchondral bone and synovial inflammation.ObjectiveThis study aimed to elucidate the transcriptional and molecular changes in synovial fluid associated with OA progression, focusing on differential gene expression and pathway enrichment across OA grades.MethodologyPatients with different OA grades were recruited from PGIMER, Chandigarh, following the KL classification. Microarray analysis was conducted to study the transcriptional profiles in different OA grades using a fold-change (FC) cutoff of 2 and a p-value cutoff of 0.05, followed by pathway analysis performed using GSEA and STRING database. Selected genes from microarray and pathway analysis were validated using qRT-PCR.ResultsMicroarray analysis reveals distinct gene expression patterns corresponding to different OA stages (KL grade 2 to KL grade 4). Notably, the upregulation ofAMTNandDKK2, alongside the downregulation ofMSLN, highlighted their roles in pathological mineralization and disrupted bone remodeling in OA. Pathway enrichment analysis revealed significant changes in immune response, inflammation related pathways and cellular processes such as autophagy and programmed cell death, indicating their involvement in disease progression. Furthermore, mitochondrial dysfunction and impaired autophagy were linked to increased inflammation in advanced OA.ConclusionThese findings suggest that targeting mineralization and inflammatory pathways could offer novel therapeutic avenues for OA management.
GeneRAG: Enhancing Large Language Models with Gene-Related Task by Retrieval-Augmented Generation
Authors: Lin Xinyi , Deng Gelei , Li Yuekang , Ge Jingquan , Ho Joshua Wing Kei , Liu Yi 
Published: June 2024

AbstractLarge Language Models (LLMs) like GPT-4 have revolutionized natural language processing and are used in gene analysis, but their gene knowledge is incomplete. Fine-tuning LLMs with external data is costly and resource-intensive. Retrieval-Augmented Generation (RAG) integrates relevant external information dynamically. We introduce GeneRAG, a frame-work that enhances LLMs’ gene-related capabilities using RAG and the Maximal Marginal Relevance (MMR) algorithm. Evaluations with datasets from the National Center for Biotechnology Information (NCBI) show that GeneRAG outperforms GPT-3.5 and GPT-4, with a 39% improvement in answering gene questions, a 43% performance increase in cell type annotation, and a 0.25 decrease in error rates for gene interaction prediction. These results highlight GeneRAG’s potential to bridge a critical gap in LLM capabilities for more effective applications in genetics.