bluuebunny/crossref_metadata_2025 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

Background

The 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.

Aim

To evaluate the predictive ability of caIMR of MVO after ST-segment elevation myocardial infarction (STEMI).

Methods

CaIMR 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.

Results

Fifty-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).

Conclusions

CaIMR 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.
Pore heterogeneity analysis and control mechanisms in Cambrian shale of the Shuijingtuo Formation, Yichang area, China
Authors: An Zhengzhen , Zhao Yue , Zhang Yanfei
Published: April 2024

This study focuses on understanding the fractal characteristics and controlling factors of micropore structures within organic-rich shale of the Cambrian Shuijingtuo Formation in the Yichang area of Hubei Province. Mineralogy, petrology, and organogeochemical characteristics were confirmed through comprehensive testing methods, including whole-rock X-ray diffraction and organic geochemical analyses. Additional experiments included low-temperature carbon dioxide adsorption, low-temperature nitrogen adsorption, and high-pressure mercury injection. Fractal dimensions of micropores, mesopores, and macropores were calculated using the V-S, FHH, and MENGER sponge models, respectively. Results indicate that the Cambrian Shuijingtuo Formation represents a typical deposit from an alkaline water body, resulting in high-calcareous shale. Fractal dimensions were as follows: micropores (D1) ranged from 2.1138 to 2.3475 (average 2.2342), mesopores (D2) ranged from 2.5327 to 2.7162 (average 2.6171), and macropores (D3) ranged from 2.7361 to 2.9316 (average 2.82905). Correlations were observed between total organic carbon (TOC) content and Ro with D1 and D2 (positive) and D3 (negative). Shale pore volume and specific surface area exhibited positive correlations with D1 and D2 but negative correlations with D3. High bio-deposited silica positively influenced micropore and mesopore development, while clay mineral compaction and dehydration transformations favored macropore development. Carbonate minerals primarily contributed to regular macropores, with complex correlations involving fractal dimensions D1, D2, and D3. The research results provide theoretical support for analyzing pore fractal characteristics of shallow old Marine shale reservoirs and the prediction and development plan of high-quality reservoirs of the Shuijingtuo Formation in the Yichang area.
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

Purpose

A 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).

Methods

PubMed, 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.

Results

A 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<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.

Conclusion

Elevated 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 registration

https://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

Objective

The present study aimed to evaluate the association of plasma trans fatty acids (TFAs) biomarkers with the risk of hypertension.

Methods

Using 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.

Results

The 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 < 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).

Conclusion

Our 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

Objectives

We 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.

Design

The design is a longitudinal study using data from the Health and Retirement Study.

Setting and participants

Data 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.

Methods

Longitudinal 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.

Results

Women 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 implications

The 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.
Resilience-oriented repair crew and network reconfiguration coordinated operational scheduling for post-event restoration
Authors: Zhou Fuju , Zhou Peng , Shi Tianchen , Jing Jiangping , Liang Gaige , Xu Shengrong , Zhou Jianda , Yang Kai
Published: April 2024

This paper introduces a post-disaster load restoration approach for the distribution grid, utilizing network reconfiguration (NR) and dispatching of repair crews (RCs) to significantly enhance grid resilience. We propose an RC–NR coordinated model that leverages diverse flexible resources within the active distribution network (ADN), aimed at not only enhancing the grid’s resilience level but also efficiently mending the fault lines. The model introduces fault repairing and sequential NR coupled constraints to devise an optimal resilience strategy within temporal domain cooperation, focusing on minimizing repair and penalty costs associated with the restoration process. To tackle the challenge of computational complexity, the nonlinear model is reformulated into a mixed-integer second-order cone programming model. The efficacy of the approach is validated through case studies on an IEEE 33-bus system, in which simulation results demonstrate a considerable improvement in grid resilience, achieving optimal load recovery with reduced restoration time and costs. The proposed approach outperforms traditional methods with optimal repair sequence and RC scheduling, aligned with NR efforts, and contributes to an improved system resilience level.
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

Introduction

Modified 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.

Methods

To 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.

Results

We 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.

Discussion

We 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

Background

Autoinflammation 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.

Methods

We 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.

Results

Significant 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 <0.001). There were significant positive correlations between serum Gal-3 levels and AOSD disease activity score (Pouchot score, r=0.66, p <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).

Conclusions

Although 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.
Measuring canopy morphology of saltmarsh plant patches using UAV-based LiDAR data
Authors: Hong Qiuxin , Ge Zhenpeng , Wang Xinkai , Li Yan , Xia Xiaoming , Chen Yining
Published: April 2024

Plant patches play a crucial role in understanding the biogeomorphology of saltmarshes. Although two-dimensional optical remote sensing has long been applied to the study of saltmarsh plant patches, studies focusing on the canopy features at a patch-scale remain limited. Therefore, a simple and efficient method is needed to capture three-dimensional patch features and their relationship to habitat. This study utilized UAV-based LiDAR to obtain three-dimensional patch features of the native species S. mariqueter and the invasive species S. alterniflora in Andong Shoal, Hangzhou Bay, and examine the relationship between patch distribution and geomorphological characteristics. A workflow was established to overcome the inability of low-cost LiDAR sensor to penetrate dense vegetation, resulting in no ground return. Results showed that S. alterniflora patches were smaller in size but taller in canopy height than S. mariqueter patches. Regarding morphological patterns of patch canopy, S. alterniflora exhibited single-arch patterns (29%) and double-arch patterns (16%), whereas S. mariqueter exhibited only single-arch patterns (83%). The presence of double-arch patches suggested the development of fairy circles, indicating that the invasive S. alterniflora exhibits greater ecological resilience compared to the native S. mariqueter. Furthermore, this study explored the ecological niches of the two species in the pioneer zone of Andong Shoal. The ecological niches for S. alterniflora were 2.00-2.25 m, whereas that for S. mariqueter were 1.85-2.00 m and 2.25-2.40 m. Distance from the tidal creeks significantly moderated the number and area of patches for both species. This study demonstrated that UAV-based LiDAR technology can provide high-quality three-dimensional information about the pioneer zone of saltmarsh, thus helping to understand biogeomorphological processes in this region.
Current status of artificial intelligence methods for skin cancer survival analysis: a scoping review
Authors: Schreidah Celine M. , Gordon Emily R. , Adeuyan Oluwaseyi , Chen Caroline , Lapolla Brigit A. , Kent Joshua A. , Reynolds George Bingham , Fahmy Lauren M. , Weng Chunhua , Tatonetti Nicholas P. , Chase Herbert S. , Pe’er Itsik , Geskin Larisa J.
Published: April 2024

Skin cancer mortality rates continue to rise, and survival analysis is increasingly needed to understand who is at risk and what interventions improve outcomes. However, current statistical methods are limited by inability to synthesize multiple data types, such as patient genetics, clinical history, demographics, and pathology and reveal significant multimodal relationships through predictive algorithms. Advances in computing power and data science enabled the rise of artificial intelligence (AI), which synthesizes vast amounts of data and applies algorithms that enable personalized diagnostic approaches. Here, we analyze AI methods used in skin cancer survival analysis, focusing on supervised learning, unsupervised learning, deep learning, and natural language processing. We illustrate strengths and weaknesses of these approaches with examples. Our PubMed search yielded 14 publications meeting inclusion criteria for this scoping review. Most publications focused on melanoma, particularly histopathologic interpretation with deep learning. Such concentration on a single type of skin cancer amid increasing focus on deep learning highlight growing areas for innovation; however, it also demonstrates opportunity for additional analysis that addresses other types of cutaneous malignancies and expands the scope of prognostication to combine both genetic, histopathologic, and clinical data. Moreover, researchers may leverage multiple AI methods for enhanced benefit in analyses. Expanding AI to this arena may enable improved survival analysis, targeted treatments, and outcomes.
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

Background

Limited 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.

Methods

We 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.

Results

Among 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 < 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 < 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 < 0.001).

Conclusion

Overt 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

Objective

Brucellosis, 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.

Methods

The 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.

Results

We 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.

Conclusion

This 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.
Colonic epithelial cell-specific TFEB activation: a key mechanism promoting anti-bacterial defense in response to Salmonella infection
Authors: Rao Shanshan , Huang Pu , Qian Yi-Yu , Xia Yu , Zhang Hongfeng
Published: April 2024

Colitis caused by infections, especially Salmonella, has long been a common disease, underscoring the urgency to understand its intricate pathogenicity in colonic tissues for the development of effective anti-bacterial approaches. Of note, colonic epithelial cells, which form the first line of defense against bacteria, have received less attention, and the cross-talk between epithelial cells and bacteria requires further exploration. In this study, we revealed that the critical anti-bacterial effector, TFEB, was primarily located in colonic epithelial cells rather than macrophages. Salmonella-derived LPS significantly promoted the expression and nuclear translocation of TFEB in colonic epithelial cells by inactivating the mTOR signaling pathway in vitro, and this enhanced nuclear translocation of TFEB was also confirmed in a Salmonella-infected mouse model. Further investigation uncovered that the infection-activated TFEB contributed to the augmentation of anti-bacterial peptide expression without affecting the intact structure of the colonic epithelium or inflammatory cytokine expression. Our findings identify the preferential distribution of TFEB in colonic epithelial cells, where TFEB can be activated by infection to enhance anti-bacterial peptide expression, holding promising implications for the advancement of anti-bacterial therapeutics.
Gut microbiome is associated with personality traits of free-ranging Tibetan macaques (Macaca thibetana)
Authors: Xia Mengyi , Xia Yingna , Sun Yu , Wang Jingjing , Lu Jiakai , Wang Xi , Xia Dongpo , Xu Xiaojuan , Sun Binghua
Published: April 2024

Recent studies have emphasized that there is a strong link between the gut microbiome and the brain that affects social behavior and personality in animals. However, the interface between personality and the gut microbiome in wild primates remains poorly understood. Here, we used high-throughput sequencing and ethological methods in primate behavioral ecology to investigate the relationship between gut microbiome and personality in Tibetan macaques (Macaca thibetana). The behavioral assessment results indicated three personality dimensions including socialization, shyness, and anxiety. There was significant variation in alpha diversity only for shyness, with a significantly lower alpha diversity indices (including Shannon, Chao1, and PD) for bold individuals than for shy individuals. Using regression models to control for possible confounding factors, we found that the relative abundance of three genera, Akkermansia, Dialister, and Asteroleplasma, was significantly and positively correlated with the sociability scores in the macaques. In addition, Oscillospiraceae exhibited a positive correlation with scores for Shy Dimension. Furthermore, we found that the predicted functional genes for propionate and pyruvate, porphyrin and chlorophyll metabolic pathways related to animal behavior, were significant enriched in shyness group. We propose that the gut microbiome may play an important role in the formation of personality of Tibetan macaques.
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

Introduction

This study explored the causal connections between gut microbiota (GM), urinary tract infection (UTI), and potential metabolite mediators using Mendelian randomization (MR).

Methods

We 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.

Results

Our 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%.

Discussion

This MR study provides compelling evidence supporting the existence of causal relationships between specific GM taxa and UTI, along with potential mediating metabolites.
Impact of renal function variability on long-term prognosis in ischemic stroke patients with atrial fibrillation
Authors: Wang Xiao , Sin Chun-fung , Teo Kay-Cheong , Leung William C. Y. , Wong Yuen-Kwun , Liu Roxanna K. C. , Fok Joshua W. , Ip Bonaventure Y. , Kwan Hon Hang , Lee Tsz Ching , Sheng Bun , Yip Edwin Kin-Keung , Yap Desmond Y. H. , Luo Hao , Lau Kui-Kai
Published: April 2024

Background

Although renal dysfunction is associated with adverse clinical outcomes in patients with atrial fibrillation (AF) following stroke, the impact of renal function variability is unclear.

Aim

This study aimed to assess the association between renal function variability and various adverse clinical outcomes in patients with transient ischemic attack (TIA)/ischemic stroke and atrial fibrillation (AF).

Methods

We conducted a population-based study and retrospectively identified patients hospitalized with a diagnosis of TIA/ischemic stroke and AF during 2016–2020 using the Clinical Data Analysis and Reporting System of Hong Kong. Serial serum creatinine tested upon the onset of TIA/ischemic stroke and during their subsequent follow-up was collected. Renal function variability was calculated using the coefficient of variation of the estimated glomerular filtration rate (eGFR). Clinical endpoints that occurred during the study period were captured and included ischemic stroke/systemic embolism, intracerebral hemorrhage (ICH), total bleeding, major adverse cardiovascular events (MACE), cardiovascular, non-cardiovascular, and all-cause mortality. Competing risk regression and Cox proportional hazard regression models were used to assess the associations of renal function variability with the outcomes of interest.

Results

A total of 3,809 patients (mean age 80 ± 10 years, 43% men) who satisfied the inclusion and exclusion criteria were followed up for a mean of 2.5 ± 1.5 years (9,523 patient-years). The mean eGFR was 66 ± 22 mL/min/1.73 m2 at baseline, and the median number of renal function tests per patient during the follow-up period was 20 (interquartile range 11–35). After accounting for potential confounders, a greater eGFR variability was associated with increased risks of recurrent ischemic stroke/systemic embolism [fully adjusted subdistribution hazard ratio 1.11, 95% confidence interval (CI) 1.03–1.20], ICH (1.17, 1.01–1.36), total bleeding (1.13, 1.06–1.21), MACE (1.22, 1.15–1.30), cardiovascular (1.49, 1.32–1.69), non-cardiovascular (1.43, 1.35–1.52), and all-cause mortality (fully adjusted hazard ratio 1.44, 1.39–1.50).

Conclusion

Visit-to-visit renal function variability is independently associated with adverse clinical outcomes in TIA/ischemic stroke patients with AF. Further large-scale studies are needed to validate our results.
A study on the association between prefrontal functional connectivity and non-suicidal self-injury in adolescents with depression
Authors: Guo Yan , Lu Ruoxi , Ou Yiwen , Huang Yuxin , Li Jianyu , Cui Ying , Li Danian , Zheng Yanting , Liang Xinyu , Qiu Shijun , Liu Yujie
Published: April 2024

Objective

Among adolescents with depression, the occurrence of non-suicidal self-injury (NSSI) behavior is prevalent, constituting a high-risk factor for suicide. However, there has been limited research on the neuroimaging mechanisms underlying adolescent depression and NSSI behavior, and the potential association between the two remains unclear. Therefore, this study aims to investigate the alterations in functional connectivity (FC) of the regions in the prefrontal cortex with the whole brain, and elucidates the relationship between these alterations and NSSI behavior in adolescents with depression.

Methods

A total of 68 participants were included in this study, including 35 adolescents with depression and 33 healthy controls. All participants underwent assessments using the 17-item Hamilton Depression Rating Scale (17-HAMD) and the Ottawa Self-Harm Inventory. In addition, functional magnetic resonance imaging (fMRI) data of the participants’ brains were collected. Subsequently, the FCs of the regions in the prefrontal cortex with the whole brain was calculated. The FCs showing significant differences were then subjected to correlation analyses with 17-HAMD scores and NSSI behavior scores.

Result

Compared to the healthy control group, the adolescent depression group exhibited decreased FCs in several regions, including the right frontal eye field, left dorsolateral prefrontal cortex, right orbitofrontal cortex, left insula and right anterior cingulate coetex. The 17-HAMD score was positively correlated with the frequency of NSSI behavior within 1 year (rs = 0.461, p = 0.005). The FC between the right anterior cingulate cortex and the right precuneus showed a negative correlation with the 17-HAMD scores (rs = −0.401, p = 0.023). Additionally, the FC between the right orbitofrontal cortex and the right insula, demonstrated a negative correlation with the frequency of NSSI behavior within 1 year (rs = −0.438, p = 0.012, respectively).

Conclusion

Adolescents with depression showed decreased FCs of the prefrontal cortex with multiple brain regions, and some of these FCs were associated with the NSSI frequency within 1 year. This study provided neuroimaging evidence for the neurophysiological mechanisms underlying adolescent depression and its comorbidity with NSSI behavior.
Research status and prospects of pituitary adenomas in conjunction with neurological and psychiatric disorders and the tumor microenvironment
Authors: Cui Siyuan , Chen Sainan , Wu Xuechao , Wang Qing
Published: April 2024

Patients with pituitary neuroendocrine tumors (PitNETs) often experience neuropsychiatric disorders due to factors such as hormonal imbalances, and inadequate management of medications, surgeries, and radiation therapies. Commonly observed disorders include depression, anxiety, and cognitive dysfunction, which significantly impact patients’ quality of life and prognosis. PitNETs have a significant presence of immune cells within the tumor microenvironment (TME), predominantly macrophages and T lymphocytes. These immune cells secrete a variety of cytokines, growth factors, and chemokines, which regulate the biological behaviors of PitNETs, including tumor initiation, proliferation, migration, invasion, and angiogenesis. In addition, this review provides a pioneering summary of the close relationships between the aberrant secretion of proinflammatory cytokines within the TME of PitNETs and the occurrence of neuropsychiatric disorders, along with their potential underlying mechanisms. The cytokines produced as a result of TME dysregulation may affect various aspects of the central nervous system, including neurotransmitter metabolism, neuroendocrine function, and neurovascular plasticity, thereby leading to a higher susceptibility to neurobehavioral disorders in PitNET patients.
Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing
Authors: Zhou Jianbiao , Chng Wee-Joo
Published: April 2024

Acute myeloid leukemia (AML) is a complex and heterogeneous group of aggressive hematopoietic stem cell disease. The presence of diverse and functionally distinct populations of leukemia cells within the same patient’s bone marrow or blood poses a significant challenge in diagnosing and treating AML. A substantial proportion of AML patients demonstrate resistance to induction chemotherapy and a grim prognosis upon relapse. The rapid advance in next generation sequencing technologies, such as single-cell RNA-sequencing (scRNA-seq), has revolutionized our understanding of AML pathogenesis by enabling high-resolution interrogation of the cellular heterogeneity in the AML ecosystem, and their transcriptional signatures at a single-cell level. New studies have successfully characterized the inextricably intertwined interactions among AML cells, immune cells and bone marrow microenvironment and their contributions to the AML development, therapeutic resistance and relapse. These findings have deepened and broadened our understanding the complexity and heterogeneity of AML, which are difficult to detect with bulk RNA-seq. This review encapsulates the burgeoning body of knowledge generated through scRNA-seq, providing the novel insights and discoveries it has unveiled in AML biology. Furthermore, we discuss the potential implications of scRNA-seq in therapeutic opportunities, focusing on immunotherapy. Finally, we highlight the current limitations and future direction of scRNA-seq in the field.
The non-clinical burden of febrile seizures: a systematic review
Authors: Marangoni Maria Beatrice , Corsello Antonio , Cozzi Laura , Agostoni Carlo , Santangelo Andrea , Milani Gregorio Paolo , Dilena Robertino
Published: April 2024

Febrile seizures (FS) can be frightening for parents, even though they are usually harmless. Various questionnaires have been used to assess parental reactions and awareness about FS, revealing insufficient knowledge. Studies have shown that educational interventions significantly reduce parental concerns, improve knowledge, and promote better first-aid measures. Providing clear information and emotional support to parents is important to reduce their concerns and improve FS management. Healthcare providers should give comprehensive information about FS, including the risk of recurrence, and provide clear instructions on their management. The economic impact of FS includes direct and indirect costs. Studies have shown a decrease of hospitalizations and associated costs due to improved clinical adherence to guidelines, which also reduces the inappropriate use of healthcare resources. This systematic review provides a comprehensive overview of the existing literature on parental anxiety and education about FS, as well as their economic impact, aiming at identifying areas for improvement in the management of FS and providing valuable insights for healthcare providers and policymakers to better address the non-clinical burden of this condition.
Ophiocordyceps sinensis preparations combined with the renin–angiotensin system inhibitor for diabetic kidney disease treatment: an umbrella review of systematic reviews and network meta-analysis
Authors: Xue Xue , Jin Xin-Yan , Ye Xing-Lan , Li Ke-Ying , Li Jia-Xuan , Liu Xue-Han , Bai Juan , Liu Qiang , Zhang Bing-Rui , Zou Xin-Rong , Yuan Jun , Lu Chun-Li , Zhao Fang-Fang , Liu Jian-Ping , Wang Xiao-Qin
Published: April 2024

Aims:

This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin–angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD).

Methods:

Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Results:

Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi.

Conclusion:

Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm.

Systematic Review Registration:

INPASY202350066.
Malware traffic detection based on type II fuzzy recognition
Authors: Zhang Weisha , Liu Jiajia , Peng Jimin , Liu Qiang , Yu Kun
Published: April 2024

In recent years, a surge in malicious network incidents and instances of network information theft has taken place, with malware identified as the primary culprit. The primary objective of malware is to disrupt the normal functioning of computers and networks, all the while surreptitiously gathering users’ private and sensitive information. The formidable concealment and latency capabilities of malware pose significant challenges to its detection. In light of the operational characteristics of malware, this paper conducts an initial analysis of prevailing malware detection schemes. Subsequently, it extracts fuzzy features based on the distinct characteristics of malware traffic. The approach then integrates traffic detection techniques with Type II fuzzy recognition theory to effectively monitor malware-related traffic. Finally, the paper classifies the identified malware instances according to fuzzy association rules. Experimental results showcase that the proposed method achieves a detection accuracy exceeding 90%, with a remarkably low false alarm rate of approximately 5%. This method adeptly addresses the challenges associated with malware detection, thereby making a meaningful contribution to enhancing our country’s cybersecurity.