bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell expressions of aberrant gene signatures and Co-inhibitory receptors (Co-IRs) as predictors of renal damage and lupus disease activity
Authors: Wang Chin-Man , Jan Wu Yeong-Jian , Zheng Jian-Wen , Huang Li Yu , Tan Keng Poo , Chen Ji-Yih 
Published: April 2024

Background
Systemic lupus erythematosus (SLE) is distinguished by an extensive range of clinical heterogeneity with unpredictable disease flares and organ damage. This research investigates the potential of aberrant signatures on T cell genes, soluble Co-IRs/ligands, and Co-IRs expression on T cells as biomarkers for lupus disease parameters.

Methods
Comparative transcriptome profiling analysis of non-renal and end-stage renal disease (ESRD) phenotypes of SLE was performed using CD4 + and CD8 + cDNA microarrays of sorted T cells. Comparing the expression of Co-IRs on T cells and serum soluble mediators among healthy and SLE phenotypes.

Results
SLE patients with ESRD were downregulated CD38, PLEK, interferon-γ, CX3CR1, FGFBP2, and SLCO4C1 transcripts on CD4 + and CD8 + T cells simultaneously and NKG7, FCRL6, GZMB/H, FcγRIII, ITGAM, Fas ligand, TBX21, LYN, granulysin, CCL4L1, CMKLR1, HLA-DRβ, KIR2DL3, and KLRD1 in CD8 T cells. Pathway enrichment and PPI network analyses revealed that the overwhelming majority of Differentially Expressed Genes (DEGs) have been affiliated with novel cytotoxic, antigen presentation, and chemokine-cell migration signature pathways. CD8 + GZMK + T cells that are varied in nature, including CD161 + Mucosal-associated invariant T (MAIT) cells and CD161- aged-associated T (Taa) cells and CD161-GZMK + GZMB + T cells might account for a higher level of GZMK in CD8 + T cells associated with ESRD. SLE patients have higher TIGIT + , PD1 + , and lower CD127 + cell percentages on CD4 + T cells, higher TIM3 + , TIGIT + , HLA-DR + cell frequency, and lower MFI expression of CD127, CD160 in CD8 T cells. Co-IRs expression in T cells was correlated with soluble PD-1, PDL-2, and TIM3 levels, as well as SLE disease activity, clinical phenotypes, and immune-therapy responses.

Conclusion
The signature of dysfunctional pathways defines a distinct immunity pattern in LN ESRD patients. Expression levels of Co-IRs in peripheral blood T cells and serum levels of soluble PD1/PDL-2/TIM3 can serve as biomarkers for evaluating clinical parameters and therapeutic responses.
Nursing labor supply in Iran: a survey in Shiraz public hospitals in 2022
Authors: Keshavarzi Ali , Delavari Sajad , Lotfi Farhad , Goudarzi Zahra , Bashiri Faezeh , Bayati Mohsen 
Published: April 2024

Abstract
Background
The labor supply of nurses, as one of the main healthcare workers, is an important issue in health human resources planning in all health systems. Finding the factors affecting it, could help policymakers to solve the shortage of nursing work supply. The present study aimed to investigating the quantity and factors affecting the nurses' labor supply in Iran.

Method
In this cross-sectional study, a sample of 598 nurses working in public hospitals of Shiraz (Iran) were selected via proportionate stratified random sampling method. The required data was collected using a structured questionnaire which asked working hours and other related factors. To analyze the data, descriptive statistics, univariate analysis and multivariate linear regression were performed using STATA 15. The multivariate labor supply model was estimated separately for married and single nurses.

Results
The average weekly working hours of nurses was 54.65 h in all medical centers and 50.28 h in the main hospital. The regression results showed that the labor supply of nurses with work experience (β = − 0.368, P = 0.014), satisfaction with work shift arrangement (β = − 2.473, P = 0.001), income between 60-89 million rial (β = − 14.046, P = 0.002), income between 90-119 million rial(β = − 12.073, P = 0.012), and working in the emergency department (β = − 5.043, P = 0.017) had negative and significant relationship; But there was a positive and significant relationship with satisfaction of the work environment (β = 1.86, P = 0.011), workload at work (β = 1.951, P = 0.023) and employment status (contractual employees) (β = 4.704, P = 0.004).

Conclusion
The labor supply function of nurses is affected by demographic, economic and non-economic factors. The most contributing factors were related to non-economic variables. It seems that the non-financial cost and benefits related to the job as well as internal factors have more important role on the nurses' labor supply.
Interleukin-4 protects retinal ganglion cells and promotes axon regeneration
Authors: Zuo Zhaoyang , Fan Bin , Zhang Ziyuan , Liang Yang , Chi Jing , Li Guangyu 
Published: April 2024

Abstract
Background
The preservation of retinal ganglion cells (RGCs) and the facilitation of axon regeneration are crucial considerations in the management of various vision-threatening disorders. Therefore, we investigate the efficacy of interleukin-4 (IL-4), a potential therapeutic agent, in promoting neuroprotection and axon regeneration of retinal ganglion cells (RGCs) as identified through whole transcriptome sequencing in an in vitro axon growth model.

Methods
A low concentration of staurosporine (STS) was employed to induce in vitro axon growth. Whole transcriptome sequencing was utilized to identify key target factors involved in the molecular mechanism underlying axon growth. The efficacy of recombinant IL-4 protein on promoting RGC axon growth was validated through in vitro experiments. The protective effect of recombinant IL-4 protein on somas of RGCs was assessed using RBPMS-specific immunofluorescent staining in mouse models with optic nerve crush (ONC) and N-methyl-D-aspartic acid (NMDA) injury. The protective effect on RGC axons was evaluated by anterograde labeling of cholera toxin subunit B (CTB), while the promotion of RGC axon regeneration was assessed through both anterograde labeling of CTB and immunofluorescent staining for growth associated protein-43 (GAP43).

Results
Whole-transcriptome sequencing of staurosporine-treated 661 W cells revealed a significant upregulation in intracellular IL-4 transcription levels during the process of axon regeneration. In vitro experiments demonstrated that recombinant IL-4 protein effectively stimulated axon outgrowth. Subsequent immunostaining with RBPMS revealed a significantly higher survival rate of RGCs in the rIL-4 group compared to the vehicle group in both NMDA and ONC injury models. Axonal tracing with CTB confirmed that recombinant IL-4 protein preserved long-distance projection of RGC axons, and there was a notably higher number of surviving axons in the rIL-4 group compared to the vehicle group following NMDA-induced injury. Moreover, intravitreal delivery of recombinant IL-4 protein substantially facilitated RGC axon regeneration after ONC injury.

Conclusion
The recombinant IL-4 protein exhibits the potential to enhance the survival rate of RGCs, protect RGC axons against NMDA-induced injury, and facilitate axon regeneration following ONC. This study provides an experimental foundation for further investigation and development of therapeutic agents aimed at protecting the optic nerve and promoting axon regeneration.
Pathological high intraocular pressure induces glial cell reactive proliferation contributing to neuroinflammation of the blood-retinal barrier via the NOX2/ET-1 axis-controlled ERK1/2 pathway
Authors: Shi Xin , Li Panpan , Herb Marc , Liu Hanhan , Wang Maoren , Wang Xiaosha , Feng Yuan , van Beers Tim , Xia Ning , Li Huige , Prokosch Verena 
Published: April 2024

Abstract
Background
NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat.

Methods
Ex vivo cultures of retinal explants from wildtype C57BL/6J and Nox2−/− mice were subjected to normal and high hydrostatic pressure (Pressure 60 mmHg) for 24 h. In vivo, high intraocular pressure (H-IOP) was induced in C57BL/6J mice for two weeks. Both Pressure 60 mmHg retinas and H-IOP mice were treated with either gp91ds-tat (a NOX2-specific inhibitor). Proteomic analysis was performed on control, H-IOP, and treatment with gp91ds-tat retinas to identify differentially expressed proteins (DEPs). The study also evaluated various glaucoma phenotypes, including IOP, retinal ganglion cell (RGC) functionality, and optic nerve (ON) degeneration. The superoxide (O2-) levels assay, blood-retinal barrier degradation, gliosis, neuroinflammation, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative PCR were performed in this study.

Results
We found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst.

Conclusions
Collectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management.
The potency of mesenchymal stem/stromal cells: does donor sex matter?
Authors: Maged Ghada , Abdelsamed Menna A. , Wang Hongjun , Lotfy Ahmed 
Published: April 2024

AbstractMesenchymal stem/stromal cells (MSCs) are a promising therapeutic tool in cell therapy and tissue engineering because of their multi-lineage differentiation capacity, immunomodulatory effects, and tissue protective potential. To achieve optimal results as a therapeutic tool, factors affecting MSC potency, including but not limited to cell source, donor age, and cell batch, have been investigated. Although the sex of the donor has been attributed as a potential factor that can influence MSC potency and efficacy, the impact of donor sex on MSC characteristics has not been carefully investigated. In this review, we summarize published studies demonstrating donor-sex-related MSC heterogeneity and emphasize the importance of disclosing donor sex as a key factor affecting MSC potency in cell therapy.
RecSOI: recommending research directions using statements of ignorance
Authors: Bibal Adrien , Salem Nourah M. , Cardon Rémi , White Elizabeth K. , Acuna Daniel E. , Burke Robin , Hunter Lawrence E. 
Published: April 2024

AbstractThe more science advances, the more questions are asked. This compounding growth can make it difficult to keep up with current research directions. Furthermore, this difficulty is exacerbated for junior researchers who enter fields with already large bases of potentially fruitful research avenues. In this paper, we propose a novel task and a recommender system for research directions, RecSOI, that draws from statements of ignorance (SOIs) found in the research literature. By building researchers’ profiles based on textual elements, RecSOI generates personalized recommendations of potential research directions tailored to their interests. In addition, RecSOI provides context for the recommended SOIs, so that users can quickly evaluate how relevant the research direction is for them. In this paper, we provide an overview of RecSOI’s functioning, implementation, and evaluation, demonstrating its effectiveness in guiding researchers through the vast landscape of potential research directions.
Interruptible demyelination in avian riboflavin deficient neuropathy
Authors: Cai Zhao 
Published: April 2024

Abstract
Background and aims
The evolution of demyelination in individual internodes remains unclear although it has been noticed the paranodal demyelination precedes internodal demyelination in neuropathies with diverse aetiologies. For therapeutic purpose, it is fundamental to know whether the demyelinating procedure in affected internodes can be interrupted. This study aimed to delineate the development of demyelination in individual internodes in avian riboflavin deficient neuropathy.

Methods
Newborn broiler meat chickens were maintained either on a routine diet containing 5.0 mg/kg riboflavin, a riboflavin deficient diet containing 1.8 mg/kg riboflavin, or initially a riboflavin deficient diet for 11 days and then routine diet plus riboflavin repletion from day 12. Evolution of demyelination in individual internodes was analyzed by teased nerve fibre studies from day 11 to 21.

Results
In riboflavin deficient chickens, demyelination was the predominant feature: it was mainly confined to the paranodal region at day 11; extended into internodal region, but less than half of the internodal length in most affected internodes at day 16; involved more than half or whole internode at day 21. In the internode undergoing demyelination, myelin degeneration of varying degrees was noticed in the cytoplasm of the Schwann cell wrapping the internode. Two days after riboflavin repletion, co-existence of remyelination and active demyelination within individual internodes was noticed. Remyelination together with preserved short original internodes was the characteristic feature 4 and 9 days after riboflavin repletion.

Conclusion
Riboflavin repletion interrupts the progression from paranodal to internodal demyelination in riboflavin deficient chickens and promotes remyelination before complete internodal demyelination.
Childhood migration experience and adult health: evidence from China’s rural migrants
Authors: Li Xiaohong , Qiao Shiyan , Zhang Dongying 
Published: April 2024

Abstract
Background
Place of residence plays an influential role in shaping individual development, and studies have established links between Childhood migration experience (CME) and health outcomes through maturity. Over the past three decades, China has undergone one of the largest rural-to-urban migrations, however, little is known about the effect of CME on rural migrants’ adult health in China.

Methods
Data from 7035 members of the 2016 and 2018 China Labor-force Dynamics Survey were analyzed. CME was measured by whether the place of residence and place of birth changed at the age of 14 years. Three measures of health (self-assessed health, BMI, and mental health scale) were obtained. Causal inferential analysis was performed, using the Probit model, the OLS model and the Propensity Score Matching (PSM) method, to explore the impact of CME on the adult health of rural migrants.

Results
Overall, compared to individuals who did not migrate in childhood, the probability of reporting “very unhealthy”, “rather unhealthy”, and “fair” in the self-assessed health of the rural migrants with CME decreased by 0.23%, 1.55%, and 5.53%, the probability of reporting “healthy” and “very healthy” increased by 1.94% and 5.38%, the probability of BMI within the normal range was higher by 7.32%, and the mental health test scores were 0.2591 points higher significantly. Furthermore, in comparison with childhood non-migration, both cross-county and cross-city migration promoted the health status of rural migrants, but the positive effect of cross-province migration was not significant; from the gender perspective, CME could more dramatically improve rural women’s adult health than men, especially in mental health.

Conclusion
CME can significantly improve adult health, including physical and mental health, and the positive effect is more obvious among women, helping to reduce gender differences in health. For the migration distance, attention can be focused on the long-distance migrating individuals, who should get more support.
The effect of colchicine on cancer risk in patients with immune-mediated inflammatory diseases: a time-dependent study based on the Taiwan’s National Health Insurance Research Database
Authors: Yeh Jun-Jun , Liw Pei-Xuan , Wong Yi-Sin , Kao Husan-Min , Lee Chia-Hsun , Lin Cheng-Li , Kao Chia-Hung 
Published: April 2024

Abstract
Background
To determine the effect of colchicine on cancer risk in patients with the immune-mediated inflammatory diseases (IMIDs)-related to colchicine use.

Methods
This is a time-dependent propensity-matched general population study based on the National Health Insurance Research Database (NHIRD) of Taiwan. We identified the IMIDs patients (n = 111,644) newly diagnosed between 2000 and 2012 based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)—274,712, 135, 136.1, 279.49, 518.3, 287.0, 696.0, 696.1, 696.8, 420, 429.4, 710.0, 710.1, 710.3, 710.4, 714.0, 720, 55.0, 55.1, 55.9, 556. Inclusion criteria: aged ≧ 20 years, if a patient had at least these disease diagnosis requirements within 1 year of follow-up, and, these patients had at least two outpatient visits or an inpatient visit. After propensity-matched according to age, sex, comorbidities, medications and index date, the IMIDs patients enter into colchicine users (N = 16,026) and colchicine nonusers (N = 16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (95% CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for smoking cessation such as nicotine replacement medicines (the nicotine patch) and pill medicines (varenicline), anti-inflammatory drugs and immunosuppressant drugs.

Results
Comparing the colchicine nonusers, all cancer risk were mildly attenuated, the (aHR (95% CI)) of all cancer is (0.84 (0.55, 0.99)). Meanwhile, the colchicine users were associated with the lower incidence of the colorectal cancer, the (aHRs (95% CI)) is (0.22 (0.19, 0.89)). Those aged < 65 years and male/female having the colchicine users were associated with lower risk the colorectal cancer also. Moreover, the colchicine > 20 days use with the lower aHR for colorectal cancer.

Conclusion
Colchicine was associated with the lower aHR of the all cancer and colorectal cancer formation in patients with the IMIDs.
Carrageenan maintains the contractile phenotype of vascular smooth muscle cells by increasing macromolecular crowding in vitro
Authors: Liu Qing , Jiang Hong-Jing , Wu Yin-Di , Li Jian-Dong , Sun Xu-Heng , Xiao Cong , Xu Jian-Yi , Lin Zhan-Yi 
Published: April 2024

Abstract
Background
The contractile phenotype of vascular smooth muscle cells (VSMCs) results in good diastolic and contractile capacities, and its altered function is the main pathophysiological basis for diseases such as hypertension. VSMCs exist as a synthetic phenotype in vitro, making it challenging to maintain a contractile phenotype for research. It is widely recognized that the common medium in vitro is significantly less crowded than in the in vivo environment. Additionally, VSMCs have a heightened sense for detecting changes in medium crowding. However, it is unclear whether macromolecular crowding (MMC) helps maintain the VSMCs contractile phenotype.

Purpose
This study aimed to explore the phenotypic, behavioral and gene expression changes of VSMCs after increasing the crowding degree by adding carrageenan (CR).

Methods
The degree of medium crowding was examined by a dynamic light scattering assay; VSMCs survival and activity were examined by calcein/PI cell activity and toxicity and CCK-8 assays; VSMCs phenotypes and migration were examined by WB and wound healing assays; and gene expression was examined by transcriptomic analysis and RT-qPCR.

Results
Notably, 225 μg/mL CR significantly increased the crowding degree of the medium and did not affect cell survival. Simultaneously, CR significantly promoted the contraction phenotypic marker expression in VSMCs, shortened cell length, decreased cell proliferation, and inhibited cell migration. CR significantly altered gene expression in VSMCs. Specifically, 856 genes were upregulated and 1207 genes were downregulated. These alterations primarily affect the cellular ion channel transport, microtubule movement, respiratory metabolism, amino acid transport, and extracellular matrix synthesis. The upregulated genes were primarily involved in the cytoskeleton and contraction processes of VSMCs, whereas the downregulated genes were mainly involved in extracellular matrix synthesis.

Conclusions
The in vitro study showed that VSMCs can maintain the contractile phenotype by sensing changes in the crowding of the culture environment, which can be maintained by adding CR.

Graphical Abstract
Respiratory drive: a journey from health to disease
Authors: Georgopoulos Dimitrios , Bolaki Maria , Stamatopoulou Vaia , Akoumianaki Evangelia 
Published: April 2024

Abstract
Respiratory drive is defined as the intensity of respiratory centers output during the breath and is primarily affected by cortical and chemical feedback mechanisms. During the involuntary act of breathing, chemical feedback, primarily mediated through CO2, is the main determinant of respiratory drive. Respiratory drive travels through neural pathways to respiratory muscles, which execute the breathing process and generate inspiratory flow (inspiratory flow-generation pathway). In a healthy state, inspiratory flow-generation pathway is intact, and thus respiratory drive is satisfied by the rate of volume increase, expressed by mean inspiratory flow, which in turn determines tidal volume. In this review, we will explain the pathophysiology of altered respiratory drive by analyzing the respiratory centers response to arterial partial pressure of CO2 (PaCO2) changes. Both high and low respiratory drive have been associated with several adverse effects in critically ill patients. Hence, it is crucial to understand what alters the respiratory drive. Changes in respiratory drive can be explained by simultaneously considering the (1) ventilatory demands, as dictated by respiratory centers activity to CO2 (brain curve); (2) actual ventilatory response to CO2 (ventilation curve); and (3) metabolic hyperbola. During critical illness, multiple mechanisms affect the brain and ventilation curves, as well as metabolic hyperbola, leading to considerable alterations in respiratory drive. In critically ill patients the inspiratory flow-generation pathway is invariably compromised at various levels. Consequently, mean inspiratory flow and tidal volume do not correspond to respiratory drive, and at a given PaCO2, the actual ventilation is less than ventilatory demands, creating a dissociation between brain and ventilation curves. Since the metabolic hyperbola is one of the two variables that determine PaCO2 (the other being the ventilation curve), its upward or downward movements increase or decrease respiratory drive, respectively. Mechanical ventilation indirectly influences respiratory drive by modifying PaCO2 levels through alterations in various parameters of the ventilation curve and metabolic hyperbola. Understanding the diverse factors that modulate respiratory drive at the bedside could enhance clinical assessment and the management of both the patient and the ventilator.