bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel GCaMP6f-RCS rat model for studying electrical stimulation in the degenerated retina
Authors: Azrad Leibovitch Tamar , Farah Nairouz , Markus Amos , Mandel Yossi 
Published: April 2024

Background: Retinal prostheses aim to restore vision by electrically stimulating the remaining viable retinal cells in Retinal Degeneration (RD) cases. Research in this field necessitates a comprehensive analysis of retinal ganglion cells’ (RGCs) responses to assess the obtained visual acuity and quality. Here we present a novel animal model which facilitates the optical recording of RGCs activity in an RD rat. This model can significantly enhance the functional evaluation of vision restoration treatments.Methods: The development of the novel rat model is based on crossbreeding a retinal degenerated Royal College of Surgeons (RCS) rat with a transgenic line expressing the genetic calcium indicator GCaMP6f in the RGCs. Characterization of the model was achieved using Optical Coherence Tomography (OCT) imaging, histology, and electroretinography (ERG) at the ages of 4, 8, and 12 weeks. Additionally, optical recordings of RGCs function in response to ex-vivo subretinal electrical stimulations were performed.Results: Histological investigations confirmed the high expression of GCaMP6f in the RGCs and minimal expression in the inner nuclear layer (INL). OCT imaging and histological studies revealed the expected gradual retinal degeneration, as evident by the decrease in retinal thickness with age and the formation of subretinal debris. This degeneration was further confirmed by ERG recordings, which demonstrated a significant decrease in the b-wave amplitude throughout the degeneration process, culminating in its absence at 12 weeks in the GCaMP6f-RCS rat. Importantly, the feasibility of investigating subretinal stimulation was demonstrated, revealing a consistent increase in activation threshold throughout degeneration. Furthermore, an increase in the diameter of the activated area with increasing currents was observed. The spatial spread of the activation area in the GCaMP6f-RCS rat was found to be smaller and exhibited faster activation dynamics compared with the GCaMP6f-LE strain.Conclusion: This novel animal model offers an opportunity to deepen our understanding of prosthetically induced retinal responses, potentially leading to significant advancements in prosthetic interventions in visual impairments.
Ability of the coronary angiography-derived index of microcirculatory resistance to predict microvascular obstruction in patients with ST-segment elevation
Authors: Wen Xinyan , Wang Zhi , Zheng Bo , Gong Yanjun , Huo Yong 
Published: April 2024

BackgroundThe coronary angiography-derived index of microvascular resistance (caIMR) correlates well with the index of microcirculatory resistance (IMR), which predicts microvascular obstruction (MVO). However, the relationship between caIMR and MVO remains unclear.AimTo evaluate the predictive ability of caIMR of MVO after ST-segment elevation myocardial infarction (STEMI).MethodsCaIMR was calculated using computational flow and pressure simulation in patients with STEMI in whom MVO status had been assessed by cardiac magnetic resonance (CMR) after successful primary percutaneous intervention at Peking University First Hospital between December 2016 and August 2019. The clinical, biochemical, echocardiographic, and CMR characteristics were assessed according to MVO status. The predictive value of the clinical parameters and caIMR was evaluated.ResultsFifty-three eligible patients were divided into an MVO group (n = 32) and a no-MVO group (n = 21). The caIMR tended to be higher in the MVO group (41.6 U vs. 30.1 U; p = 0.136). CaIMR and peak cardiac troponin-I (cTNI) were independent predictors of MVO (per 1-U increment in caIMR: odds ratio [OR] 1.044, 95% confidence interval [CI] 1.004–1.086, p = 0.030; per 1 ng/L increase in peak cTNI: OR 1.018, 95% CI 1.003–1.033, p = 0.022). In receiver-operating characteristic curve analysis, when a cut-off value of 45.17 U was used, caIMR had some ability to predict MVO (area under the curve 0.622, 95% CI 0.478–0.752, p = 0.127).ConclusionsCaIMR and peak cTNI were independent predictors of short-term MVO in patients with STEMI who had undergone successful primary percutaneous coronary intervention and may help to identify those at high risk of MVO.
Meta-analysis of the relationship between ocular and peripheral serum IL-17A and diabetic retinopathy
Authors: Li Xiaodong , Qin Wei , Qin Xuewei , Wu Dandan , Gao Chenyuan , Luo Yinyue , Xu Mingchao 
Published: April 2024

PurposeA systematic evaluation and Meta-analysis were performed to determine the relationship between IL-17A levels in ocular aqueous and peripheral venous serum samples and diabetic retinopathy (DR).MethodsPubMed, Embase, Web of Science, and CNKI databases were searched from the time of library construction to 2023-09-20.The results were combined using a random-effects model, sensitivity analyses were performed to determine whether the arithmetic was stable and reliable, and subgroup analyses were used to look for possible sources of heterogeneity.ResultsA total of 7 case-control studies were included. The level of IL-17A was higher in the Nonproliferative DR(NPDR) group than in the Non-DR(NDR) group [SMD=2.07,95%CI(0.45,3.68),P=0.01], and the level of IL-17A in the proliferating DR(PDR) group was higher than that of the NDR group [SMD=4.66,95%CI(1.23,8.08),P&lt;0.00001]. IL-17A levels in peripheral serum and atrial fluid were significantly higher in NPDR and PDR patients than in non-DR patients in subgroup analyses, and detection of peripheral serum IL-17A concentrations could help to assess the risk of progression from NPDR to PDR. Sensitivity analyses suggested that the results of the random-effects arithmetic were stable and reliable. Subgroup analyses based on assay method and sample source showed that the choice of these factors would largely influence the relationship between IL-17A levels and DR.ConclusionElevated peripheral serum and ocular aqueous humor IL-17A levels in diabetic patients are associated with the risk of DR, IL-17A may serve as a potential predictor or therapeutic target for DR, and IL-17A may be an important predictor of inflammation for the progression of NPDR to PDR.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024532900.
Association of plasma trans fatty acid concentrations with blood pressure and hypertension in U.S. adults
Authors: Luan Min , Tian Youping , Yan Dandan , Liang Shuang 
Published: April 2024

ObjectiveThe present study aimed to evaluate the association of plasma trans fatty acids (TFAs) biomarkers with the risk of hypertension.MethodsUsing data from the National Health and Nutrition Examination Surveys (NHANES 2009-2010), we conducted a thorough analysis using both the traditional regression model and the Bayesian Kernel Machine Regression (BKMR) model to investigate the associations of individual TFAs and their mixtures with systolic blood pressure (SBP), diastolic blood pressure (DBP), and the risk of hypertension in a sample of 1,970 American adults.ResultsThe concentrations of TFAs were natural logarithms (ln) transformed to approximate a normal distribution. Multivariate linear regression models showed that each 1-unit increase in ln-transformed plasma concentrations of palmitelaidic, elaidic, vaccenic, and linolelaidic acids was associated with separate 2.94-, 3.60-, 2.46- and 4.78-mm Hg and 2.77-, 2.35-, 2.03-, and 3.70- mm Hg increase in SBP and DBP, respectively (P &lt; 0.05). The BKMR model showed positive associations between the four TFAs mixtures and SBP and DBP. In addition, linolelaidic acid contributed the most to an increased blood pressure. Similar results were observed with the threshold of hypertension (≥130/80 mm Hg).ConclusionOur findings provide preliminary evidence that plasma TFA concentrations are associated with increased blood pressure and the risk of hypertension in US adults. This study also suggests that linolelaidic acid might exhibit more deleterious effects on hypertension than other TFAs. Further studies should be conducted to validate these results.
Terminal trajectory of HbA1c for 10 years supports the HbA1c paradox: a longitudinal study using Health and Retirement Study data
Authors: Zhang Zeyi , Yang Longshan , Cao Heng 
Published: April 2024

ObjectivesWe aimed to assess the potential time-varying associations between HbA1c and mortality, as well as the terminal trajectory of HbA1c in the elderly to reveal the underlying mechanisms.DesignThe design is a longitudinal study using data from the Health and Retirement Study.Setting and participantsData were from the Health and Retirement Study. A total of 10,408 participants aged ≥50 years with available HbA1c measurements at baseline (2006/2008) were included.MethodsLongitudinal HbA1c measured at 2010/2012 and 2014/2016 were collected. HbA1c values measured three times for their associations with all-cause mortality were assessed using Cox regression and restricted cubic splines. HbA1c terminal trajectories over 10 years before death were analyzed using linear mixed-effect models with a backward time scale.ResultsWomen constitute 59.6% of the participants with a mean age of 69 years, with 3,070 decedents during the follow-up (8.9 years). The mortality rate during follow-up was 29.5%. Increased mortality risk became insignificant for the highest quartile of HbA1c compared to the third quartile (aHR 1.148, 1.302, and 1.069 for a follow-up of 8.9, 6.5, and 3.2 years, respectively) with a shorter follow-up, while it became higher for the lowest quartile of HbA1c (aHR 0.986, 1.068, and 1.439 for a follow-up of 8.9, 6.5, and 3.2 years, respectively). Accordingly, for both decedents with and without diabetes, an initial increase in HbA1c was followed by an accelerating terminal decline starting 5–6 years before death.Conclusions and implicationsThe time-varying association between HbA1c and mortality mapped to the terminal trajectory in HbA1c. High and low HbA1c may have different clinical relationships with mortality. The HbA1c paradox may be partially explained by reverse causation, namely, early manifestation of death.
Solubility of H2-CH4 mixtures in brine at underground hydrogen storage thermodynamic conditions
Authors: Tawil Michel , Salina Borello Eloisa , Bocchini Sergio , Pirri Candido Fabrizio , Verga Francesca , Coti Christian , Scapolo Matteo , Barbieri Donatella , Viberti Dario 
Published: April 2024

Concerning the emerging power-to-gas technologies, which are considered the most promising technology for seasonal renewable energy storage, Underground Hydrogen Storage (UHS) has gained attention in the last few years. For safe and efficient storage, possible hydrogen losses due to dissolution into the aquifer must be estimated accurately. Due to safety concerns, experimental measurements of hydrogen solubility in brine at reservoir conditions are limited. In this study, a PVT cell is used to characterize the solubility of hydrogen and its mixtures with methane in saline water/brine. The experiments were carried out at 45, 50, and 55°C and from 1 bar up to 500 bar, mimicking a significant range of possible reservoir conditions. Two brine samples representative of two different reservoirs were tested. Two mixtures of methane and hydrogen (10 mol% H2 and 50 mol% H2, respectively) were considered, along with pure hydrogen, to account for the presence of methane in the primary phase of hydrogen storage in a depleted gas reservoir. In the current paper, a comparison of the experimental results with literature models is provided. At the experiment conditions, the impact of the differences in the composition of the two analyzed brines as well as the impact of the analyzed range of temperatures was not significant. Conversely, a non-negligible variation in terms of the slope of the solubility curve was observed as a function of the gas mixture composition: the curve increased more steeply as the percentage of hydrogen reduced.
The purinergic receptor P2X7 as a modulator of viral vector-mediated antigen cross-presentation
Authors: Longo Ylenia , Mascaraque Sara Moreno , Andreacchio Giuseppe , Werner Julia , Katahira Ichiro , De Marchi Elena , Pegoraro Anna , Lebbink Robert Jan , Köhrer Karl , Petzsch Patrick , Tao Ronny , Di Virgilio Francesco , Adinolfi Elena , Drexler Ingo 
Published: April 2024

IntroductionModified Vaccinia Virus Ankara (MVA) is a safe vaccine vector inducing long- lasting and potent immune responses. MVA-mediated CD8+T cell responses are optimally induced, if both, direct- and cross-presentation of viral or recombinant antigens by dendritic cells are contributing.MethodsTo improve the adaptive immune responses, we investigated the role of the purinergic receptor P2X7 (P2RX7) in MVA-infected feeder cells as a modulator of cross-presentation by non-infected dendritic cells. The infected feeder cells serve as source of antigen and provide signals that help to attract dendritic cells for antigen take up and to license these cells for cross-presentation.ResultsWe demonstrate that presence of an active P2RX7 in major histocompatibility complex (MHC) class I (MHCI) mismatched feeder cells significantly enhanced MVA-mediated antigen cross-presentation. This was partly regulated by P2RX7-specific processes, such as the increased availability of extracellular particles as well as the altered cellular energy metabolism by mitochondria in the feeder cells. Furthermore, functional P2RX7 in feeder cells resulted in a delayed but also prolonged antigen expression after infection. DiscussionWe conclude that a combination of the above mentioned P2RX7-depending processes leads to significantly increased T cell activation via cross- presentation of MVA-derived antigens. To this day, P2RX7 has been mostly investigated in regards to neuroinflammatory diseases and cancer progression. However, we report for the first time the crucial role of P2RX7 for antigen- specific T cell immunity in a viral infection model.
Serum Mac-2 binding protein glycosylation isomer and galectin-3 levels in adult-onset Still’s disease and their association with cytokines
Authors: Yoshida Shuhei , Koga Tomohiro , Fujita Yuya , Yatsuhashi Hiroshi , Matsumoto Haruki , Sumichika Yuya , Saito Kenji , Sato Shuzo , Asano Tomoyuki , Kobayakawa Masao , Ohira Hiromasa , Mizokami Masashi , Sugiyama Masaya , Migita Kiyoshi 
Published: April 2024

BackgroundAutoinflammation with cytokine dysregulation may be implicated in the pathophysiology of adult-onset Still’s disease (AOSD); however, the relationship between galectins and cytokines in patients with active AOSD remains unknown. We aimed to examine the relationship between circulating cytokines/chemokines and galectin-3 (Gal-3) or its ligand, Mac-2 binding protein glycosylation isomer (M2BPGi), in Japanese patients with AOSD.MethodsWe recruited 44 consecutive patients diagnosed with AOSD according to the Yamaguchi criteria, 50 patients with rheumatoid arthritis (RA) as disease controls, and 27 healthy participants. Serum M2BPGi levels were directly measured using a HISCL M2BPGi reagent kit and an automatic immunoanalyzer (HISCL-5000). Serum Gal-3 concentrations were measured by enzyme-linked immunosorbent assay. The serum levels of 69 cytokines were analyzed in patients with AOSD using a multi-suspension cytokine array. We performed a cluster analysis of each cytokine expressed in patients with AOSD to identify specific molecular networks.ResultsSignificant increases in the serum concentrations of Gal-3 and M2BPGi were found in the serum of patients with AOSD compared with patients with RA and healthy participants (both p &lt;0.001). There were significant positive correlations between serum Gal-3 levels and AOSD disease activity score (Pouchot score, r=0.66, p &lt;0.001) and serum ferritin levels. However, no significant correlations were observed between serum M2BPGi levels and AOSD disease activity scores (Pouchot score, r = 0.32, p = 0.06) or serum ferritin levels. Furthermore, significant correlations were observed between the serum levels of Gal-3 and various inflammatory cytokines, including interleukin-18, in patients with AOSD. Immunosuppressive treatment in patients with AOSD significantly reduced serum Gal-3 and M2BPGi levels (p = 0.03 and 0.004, respectively).ConclusionsAlthough both Gal-3 and M2BPGi were elevated in patients with AOSD, only Gal-3 was a useful biomarker for predicting disease activity in AOSD. Our findings suggest that circulating Gal-3 reflects the inflammatory component of AOSD, which corresponds to proinflammatory cytokine induction through inflammasome activation cascades.
Overt disseminated intravascular coagulation and antithrombin III predict bleeding and in-hospital mortality in patients undergoing extracorporeal membrane oxygenation
Authors: Kim Tae Wan , Ko Ryoung-Eun , Choi Ki Hong , Chung Chi Ryang , Cho Yang Hyun , Yang Jeong Hoon 
Published: April 2024

BackgroundLimited data are available on the relationship of disseminated intravascular coagulation (DIC) with mortality in patients receiving extracorporeal membrane oxygenation (ECMO). Thus, we investigated the association of DIC score and antithrombin (AT) III with clinical outcomes in patients undergoing ECMO.MethodsWe analyzed 703 patients who underwent ECMO between January 2014 and May 2022 at Samsung Medical Center. The DIC score was calculated using laboratory findings within 24 h of the ECMO initiation, and ≥ 5 was defined as overt DIC. In addition, the AT III level was measured to identify the correlation with the DIC score.ResultsAmong the study patients, 169 (24.0%) were diagnosed with overt DIC (DIC group) during early maintenance therapy. In-hospital mortality was significantly higher in the DIC group than in the non-DIC group (55.0% vs. 36.5%, p &lt; 0.001). Bleeding events were significantly higher in the group of patients with a DIC score of 7 or 8 than in the other group (20.8% vs. 8.4%, p = 0.038). DIC score negatively correlated with AT III level (r = −0.417, p &lt; 0.001). The predictive performance of AT III for overt DIC had statistical significance with a c-static of 0.81 (95% confidence interval (CI), 0.77–0.84, p &lt; 0.001).ConclusionOvert DIC was associated with higher in-hospital mortality and a tendency to bleed in ECMO patients. Furthermore, AT III plasma levels can easily predict overt DIC in patients undergoing ECMO. These findings suggest that monitoring AT III plasma levels may be important in the management of ECMO.
Investigating the mechanism of rough phenotype in a naturally attenuated Brucella strain: insights from whole genome sequencing
Authors: Han Wendong , Wei Dong , Sun Zhiping , Qu Di 
Published: April 2024

ObjectiveBrucellosis, a significant zoonotic disease, not only impacts animal health but also profoundly influences the host immune responses through gut microbiome. Our research focuses on whole genome sequencing and comparative genomic analysis of these Brucella strains to understand the mechanisms of their virulence changes that may deepen our comprehension of the host immune dysregulation.MethodsThe Brucella melitensis strain CMCC55210 and its naturally attenuated variant CMCC55210a were used as models. Biochemical identification tests and in vivo experiments in mice verified the characteristics of the strain. To understand the mechanism of attenuation, we then performed de novo sequencing of these two strains.ResultsWe discovered notable genomic differences between the two strains, with a key single nucleotide polymorphism (SNP) mutation in the manB gene potentially altering lipopolysaccharide (LPS) structure and influencing host immunity to the pathogen. This mutation might contribute to the attenuated strain's altered impact on the host's macrophage immune response, overing insights into the mechanisms of immune dysregulation linked to intracellular survival. Furthermore, we explore that manipulating the Type I restriction-modification system in Brucella can significantly impact its genome stability with the DNA damage response, consequently affecting the host's immune system.ConclusionThis study not only contributes to understanding the complex relationship between pathogens, and the immune system but also opens avenues for innovative therapeutic interventions in inflammatory diseases driven by microbial and immune dysregulation.
Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study
Authors: He Yining , Han Chao , Li Chengjuan , Yin Xiaofan , Wang Jiawen , Gu Lina , Yan Ruxue , Liu Buhui , Zhou Xuan , He Weiming 
Published: April 2024

IntroductionThis study explored the causal connections between gut microbiota (GM), urinary tract infection (UTI), and potential metabolite mediators using Mendelian randomization (MR).MethodsWe utilized summary statistics from the most comprehensive and extensive genome-wide association studies (GWAS) available to date, including 196 bacterial traits for GM, 1,091 blood metabolites, 309 metabolite ratios, alongside UTI data from ukb-b-8814 and ebi-a-GCST90013890. Bidirectional MR analyses were conducted to investigate the causal links between GM and UTI. Subsequently, two MR analyses were performed to identify the potential mediating metabolites, followed by a two-step MR analysis to quantify the mediation proportion.ResultsOur findings revealed that out of the total 15 bacterial traits, significant associations with UTI risk were observed across both datasets. Particularly, taxon g_Ruminococcaceae UCG010 displayed a causal link with a diminished UTI risk in both datasets (ukb-b-8814: odds ratio [OR] = 0.9964, 95% confidence interval [CI] = 0.9930–0.9997, P = 0.036; GCST90013890: OR = 0.8252, 95% CI = 0.7217–0.9436, P = 0.005). However, no substantial changes in g_Ruminococcaceae UCG010 due to UTI were noted (ukb-b-8814: β = 0.51, P = 0.87; ebi-a-GCST90013890: β = −0.02, P = 0.77). Additionally, variations in 56 specific metabolites were induced by g_Ruminococcaceae UCG010, with N-acetylkynurenine (NAK) exhibiting a causal correlation with UTI. A negative association was found between g_Ruminococcaceae UCG010 and NAK (OR: 0.8128, 95% CI: 0.6647–0.9941, P = 0.044), while NAK was positively associated with UTI risk (OR: 1.0009; 95% CI: 1.0002–1.0016; P = 0.0173). Mediation analysis revealed that the association between g_Ruminococcaceae UCG010 and UTI was mediated by NAK with a mediation proportion of 5.07%.DiscussionThis MR study provides compelling evidence supporting the existence of causal relationships between specific GM taxa and UTI, along with potential mediating metabolites.