bluuebunny/crossref_metadata_2025 huggingface dataset:
Untangling the relationship between bempedoic acid and gout: results from a systematic literature review
Authors: Alunno Alessia , Carubbi Francesco , Campanozzi Elena , Bellisario Federico , Schoones Jan W. , Mariani Francesco Maria , Di Ruscio Evy , Altieri Piera , Ferri Claudio
Published: October 2023

Background

Bempedoic acid (BA) is a small-molecule first-in-class of inhibitor of ATP citrate lyase that significantly lowers low-density lipoproteins cholesterol (LDL-c) in statin-intolerant and inadequate responders. Increased serum uric acid (SUA) levels and gout incidence have been described in BA-treated patients. The aim of this systematic review was to investigate the safety of BA regarding SUA levels and gout in randomised controlled trials (RCTs).

Methods

A search on 7 databases was performed from inception to May 4, 2023. RCTs of BA monotherapy or combination with other lipid-lowering treatment (LLT) in patients with increased LDL-c were included. Dual data extraction was performed with disagreements resolved through consensus. Due to the methodological purpose of this review risk-of-bias assessment of studies was not performed.

Results

6 Phase 3 RCTs (N = 17,975 patients of which 9,635 received BA) 9 Phase 2 RCTs (N = 362 patients of which 170 received BA) and an open-label extension of a Phase 3 RCT were included. Gout and/or hyperuricemia were not mentioned as exclusion criteria, previous/current use of urate-lowering therapies (ULT) and/or colchicine and/or dietary patterns were not reported. Phase 3 RCTs: 2 studies specified the number of patients experiencing hyperuricemia over the study period (BA: 4.9%–11%; placebo: 1.9%–5.6%) and the effect size was significant only in 1 study (OR = 2.0, 95% CI 1.8–2.3). Four RCTs reported a higher incidence of gout in the BA arm however, when we calculated the effect size, it was small and often not significant. Two studies reported 0 cases of gout. The paucity of information about SUA levels at baseline and/or at the end of follow-up do not allow us to quantify the effect sizes for BA-induced SUA elevation. Data on gout from Phase 2 RCTs is scant.

Conclusions

Data from phase 2 and 3 RCTs do not allow for confirming a clear association between BA and gout. It is conceivable that a careful assessment of SUA levels/history of gout at baseline and the concomitant use of urate-lowering agents may be instrumental to minimise the risk of new-onset gout/gout flares in patients treated with BA.
Benefits and geography of international collaboration for PhD students in biology from four global south countries
Authors: Mahdjoub Hayat , Baaloudj Afef , Chaib Sara , Ramírez-Castañeda Valeria , Contreras Leidy Alejandra Barragan , González-Tokman Daniel , Villada-Bedoya Sebastián , Rocha-Ortega Maya , Córdoba-Aguilar Alex , Khelifa Rassim
Published: October 2023

Collaboration is a fundamental aspect of scientific research and innovation. Fair collaborations between scientists from different identities or positions of power (e.g., Global North and Global South scientists) could have a great impact on scientific knowledge and exchange. However, there are existing limitations to the potential of Global South scientists to collaborate fairly. Here we assess the impact and geographic distribution of international collaborations for PhD students in biological sciences in four Global South countries (two from Africa: Algeria and Morocco, and two from the Americas: Colombia and Mexico), where students typically have low English proficiency. We show that overall international collaboration, particularly with the Global North, increased the probability of publishing in a journal with an impact factor and achieved more citations. Most international collaborators were affiliated with French-speaking countries for Algerian and Moroccan students and Spanish and English-speaking countries for Colombian and Mexican universities, suggesting that language and geopolitical history might play a role in shaping the selection of international collaborators. While the results highlight the benefit of international collaboration for researchers in the Global South, we discuss that the current metrics of scientific success could maintain the dependence of Global South scientists on the Global North.
Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study
Authors: García de Lucas María Dolores , Caballero Irene , Fernández-García José Carlos , Domínguez-Rodríguez Manuel , Moreno-Moreno Paloma , Jiménez-Millán Anabel , Botana-López Manuel , Avilés Beatriz , Merino-Torres Juan Francisco , Soto Alfonso , Tejera Cristina , Morales Cristóbal
Published: October 2023

Objectives

Semaglutide is a glucagon-like peptide 1 receptor agonist that improves glycemic control and achieves weight loss in type 2 diabetes (T2D) patients. Subcutaneous (s.c.) semaglutide at 1 mg once weekly (OW) is safe in T2D patients with chronic kidney disease (CKD). Whether or not CKD and its severity influence treatment response remains undetermined.

Method

This is an observational, ambispective, multicenter, nationwide, real-world study designed to compare safety/efficacy of OW s.c. 1 mg semaglutide in T2D patients with or without CKD. The influence of CKD severity was also addressed. Patients were followed up for 12 months. Primary end-points were glycosylated hemoglobin (HbA1c), weight, and renal outcomes. Secondary end-points included insulin resistance, atherogenic and hepatic steatosis indexes, and changes in antihyperglycemic medications.

Results

A total of 296 and 190 T2D patients without or with CKD, respectively, were recruited. Baseline CKD risk was moderate, high, or very high in 82, 53, and 45 patients, respectively. Treatment reduced HbA1c by 0.90%–1.20%. Relevant differences were seen neither between non-CKD and CKD patients nor among CKD subgroups. Notable weight losses were achieved in both non-CKD and CKD patients. The median reduction was higher in the former at 6 months (5.90 kg vs. 4.50 kg, P = 0.008) and at end of study (6.90 kg vs. 5.00 kg, P = 0.087). A trend toward slightly lower weight losses as CKD severity increased was observed. CKD markers improved across all CKD subgroups. Relevant differences were not observed for other variables, either between non-CKD and CKD patients, or among CKD subgroups. Safety concerns were not reported.

Conclusion

The safety/efficacy of OW s.c. semaglutide to improve glycemic control and weight in T2D patients with CKD is not notably lower than that in T2D patients without renal failure. CKD severity barely influences treatment response. OW s.c. semaglutide can be useful to manage T2D patients with CKD in daily clinical practice.
Low voltage protection method of DFIG based on rotor-side double current limiting circuit
Authors: Yang Hongyu , Yuan Chao , Liu Yanan , Mei Rui
Published: October 2023

A doubly fed induction generator (DFIG) configured for crowbar protection faces the following problems during low voltage ride through (LVRT): delayed input of crowbar protection and the difficulty in coordinating current limiting targets and DC voltage overrun with constant resistance rectification. A low voltage protection method of a DFIG based on a rotor-side double current limiting circuit is proposed. The rotor current characteristics during a fault are analyzed from a time domain perspective and used as a basis for resistance setting. The transient response characteristics of a resistive superconducting fault current limiter (RSFCL) are used for fast initial suppression of rotor currents. The adaptive crowbar resistance adjustment method is used to realize the coordinated consideration of current limiting and DC voltage non-overrun. The simulation results show that the proposed protection method effectively shortens the actual input time of the current limiting circuit and has good suppression ability for the rotor current at the early stage of fault. The adaptive and flexible resistance setting of the controllable crowbar circuit ensures that the DC voltage does not exceed the limit during the fault current limiting period, which helps improve the LVRT capability of doubly fed wind turbines.
Utilization of intestinal organoid models for assessment of micro/nano plastic-induced toxicity
Authors: Yuan Qinqin , Liu Yajing
Published: October 2023

Micro/nano plastics (M/NPs) are emerging pollutants that have extensively infiltrated various aspects of human life, posing a significant threat to the natural ecological systems. M/NPs can enter the digestive system through the oral cavity and accumulate in various organs. The current research on M/NPs primarily relies on model organisms, and there remains a dearth of direct evidence concerning the impact of M/NPs on human health. Commonly utilized specific two dimensional (2D) cultured cell lines exhibit substantial disparities in physiological functions when compared to multicellular tissues in vivo. The conduct of animal experiments is a time-consuming process, constrained by ethical considerations, and also confronted with interspecies variations. A significant breakthrough in biology is the development of organoids derived from stem cells. Intestinal organoids can mimic the complex structure and functionality of tissue, and can generate cell-cell and cell-matrix interactions that closely resemble physiological responses in the body. As a result, they provide a more accurate reflection of toxic effects and mechanisms, and hold great potential for applications in the environmental toxicology assessment. However, the current research on the toxic mechanisms of M/NPs using intestinal organoids is still in its early stages. The focus of this review is on the application of intestinal organoids in toxicology studies of M/NPs, assessing the correlation between M/NPs and diseases, as well as elucidating the molecular mechanisms underlying toxic effects. Ultimately, we present the challenges and potential solutions for utilizing intestinal organoids as models to evaluate M/NPs-induced toxicity, aiming to provide valuable insights for future research.
Genetically predicted levels of circulating cytokines and the risk of six immune skin diseases: a two-sample Mendelian randomization study
Authors: Luo Qinghua , Cao Qiurui , Guo Jinyan , Chang Shuangqing , Wu Yunxiang
Published: October 2023

Background

Circulating cytokines play a crucial role in the onset and progression of immune skin diseases. However, the causal relationships and the direction of causal effects require further investigation.

Methods

Two-sample Mendelian randomization (MR) analyses were conducted to assess the causal relationships between 41 circulating cytokines and six immune skin diseases including alopecia areata, chloasma, hidradenitis suppurativa (HS), lichen planus (LP), seborrheic dermatitis, and urticaria, using summary statistics from genome-wide association studies. Reverse MR analyses was performed to test for the reverse causation. Pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings.

Results

Twelve unique cytokines showed a suggestive causal relationship with the risk of six immune skin diseases. Among them, the causal effects between 9 unique cytokines and immune skin diseases have strong statistical power. Additionally, the concentrations of six cytokines might be influenced by LP and urticaria. After Bonferroni correction, the following associations remained significant: the causal effect of beta-nerve growth factor on HS (odds ratio [OR] = 1.634, 95% confidence interval [CI] = 1.226-2.177, p = 7.97e-04), interleukin (IL)-6 on LP (OR = 0.615, 95% CI = 0.481-0.786, p = 1.04e-04), IL-4 on LP (OR = 1.099. 95% CI = 1.020-1.184, p = 1.26e-02), and IL-2 on urticaria (OR = 0.712, 95% CI = 0.531-0.955, p = 2.33e-02).

Conclusion

This study provides novel perspectives on the relationship between circulating cytokines and immune skin diseases, potentially providing valuable insights into their etiology, diagnostic approaches, and treatment.
Emerging insights into inflammatory bowel disease from the intestinal microbiota perspective: a bibliometric analysis
Authors: Zhang Anqi , Wang Fang , Li Delong , Wang Chong-Zhi , Yao Haiqiang , Wan Jin-Yi , Yuan Chun-Su
Published: October 2023

Background

Inflammatory bowel disease (IBD) has caused severe health concerns worldwide. Studies on gut microbiota have provided new targets for preventing and treating IBD. Therefore, it is essential to have a comprehensive understanding of the current status and evolution of gut microbiota and IBD studies.

Methods

A bibliometric analysis was performed on documents during 2003-2022 retrieved from the Scopus database, including bibliographical profiles, citation patterns, and collaboration details. Software programs of VOSviewer, CiteSpace, and the Bibliometrix R package visually displayed the mass data presented in the scientific landscapes and networks.

Results

10479 publications were retrieved, showing a steadily growing tendency in interest. Xavier Ramnik J. group led the total number of publications (73 papers) and 19787 citations, whose productive work aroused widespread concern. Among the 1977 academic journals, the most prolific ones were Inflammatory Bowel Diseases, Frontiers in Immunology, and Nutrients. Research outputs from the United States (US, 9196 publications), China (5587), and Italy (2305) were highly ranked.

Conclusion

Our bibliometric study revealed that the role of gut microbiota has become a hot topic of IBD research worldwide. These findings are expected to improve understanding of research characteristics and to guide future directions in this field.
Neural control of redox response and microbiota-triggered inflammation in Drosophila gut
Authors: Fuse Naoyuki , Hashiba Haruka , Ishibashi Kentaro , Suzuki Takuro , Nguyen Quang-Dat , Fujii Kiho , Ikeda-Ohtsubo Wakako , Kitazawa Haruki , Tanimoto Hiromu , Kurata Shoichiro
Published: October 2023

Background

The neural system plays a critical role in controlling gut immunity, and the gut microbiota contributes to this process. However, the roles and mechanisms of gut-brain-microbiota interactions remain unclear. To address this issue, we employed Drosophila as a model organism. We have previously shown that NP3253 neurons, which are connected to the brain and gut, are essential for resistance to oral bacterial infections. Here, we aimed to investigate the role of NP3253 neurons in the regulation of gut immunity.

Methods

We performed RNA-seq analysis of the adult Drosophila gut after genetically inactivating the NP3253 neurons. Flies were reared under oral bacterial infection and normal feeding conditions. In addition, we prepared samples under germ-free conditions to evaluate the role of the microbiota in gut gene expression. We knocked down the genes regulated by NP3253 neurons and examined their susceptibility to oral bacterial infections.

Results

We found that immune-related gene expression was upregulated in NP3253 neuron-inactivated flies compared to the control. However, this upregulation was abolished in axenic flies, suggesting that the immune response was abnormally activated by the microbiota in NP3253 neuron-inactivated flies. In addition, redox-related gene expression was downregulated in NP3253 neuron-inactivated flies, and this downregulation was also observed in axenic flies. Certain redox-related genes were required for resistance to oral bacterial infections, suggesting that NP3253 neurons regulate the redox responses for gut immunity in a microbiota-independent manner.

Conclusion

These results show that NP3253 neurons regulate the appropriate gene expression patterns in the gut and contribute to maintain homeostasis during oral infections.
The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials
Authors: Zhao Fang , He Yini , Zhao Zhihao , He Jiarong , Huang Hong , Ai Kelong , Liu Liang , Cai Xiong
Published: October 2023

Angiogenesis plays a key role in the pathological process of inflammation and invasion of the synovium, and primarily drives the progression of rheumatoid arthritis (RA). Recent studies have demonstrated that the Notch signaling may represent a new therapeutic target of RA. Although the Notch signaling has been implicated in the M1 polarization of macrophages and the differentiation of lymphocytes, little is known about its role in angiogenesis in RA. In this review, we discourse the unique roles of stromal cells and adipokines in the angiogenic progression of RA, and investigate how epigenetic regulation of the Notch signaling influences angiogenesis in RA. We also discuss the interaction of the Notch-HIF signaling in RA’s angiogenesis and the potential strategies targeting the Notch signaling to improve the treatment outcomes of RA. Taken together, we further suggest new insights into future research regarding the challenges in the therapeutic strategies of RA.
The role and mechanisms of macrophage polarization and hepatocyte pyroptosis in acute liver failure
Authors: Xie Dan , Ouyang Shi
Published: October 2023

Acute liver failure (ALF) is a severe liver disease caused by disruptions in the body’s immune microenvironment. In the early stages of ALF, Kupffer cells (KCs) become depleted and recruit monocytes derived from the bone marrow or abdomen to replace the depleted macrophages entering the liver. These monocytes differentiate into mature macrophages, which are activated in the immune microenvironment of the liver and polarized to perform various functions. Macrophage polarization can occur in two directions: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. Controlling the ratio and direction of M1 and M2 in ALF can help reduce liver injury. However, the liver damage caused by pyroptosis should not be underestimated, as it is a caspase-dependent form of cell death. Inhibiting pyroptosis has been shown to effectively reduce liver damage induced by ALF. Furthermore, macrophage polarization and pyroptosis share common binding sites, signaling pathways, and outcomes. In the review, we describe the role of macrophage polarization and pyroptosis in the pathogenesis of ALF. Additionally, we preliminarily explore the relationship between macrophage polarization and pyroptosis, as well as their effects on ALF.
Interactive effects of ocean acidification and temperature on oxygen uptake rates in Calanus hyperboreus nauplii
Authors: Espinel-Velasco Nadjejda , Gawinski Christine , Kohlbach Doreen , Pitusi Vanessa , Graeve Martin , Hop Haakon
Published: October 2023

The Arctic region is undergoing rapid and significant changes, characterized by high rates of acidification and warming. These transformations prompt critical questions about the resilience of marine communities in the face of environmental change. In the Arctic, marine zooplankton and in particular calanoid copepods play a vital role in the food web. Changes in environmental conditions could disrupt zooplankton communities, posing detrimental consequences for the entire ecosystem. Copepod early-life stages have been shown to be particularly sensitive to environmental stressors since they represent a bottleneck in the life cycle. Here, we investigated the responses of 4-day old Calanus hyperboreus nauplii when exposed to acidification (pH 7.5 and 8.1) and warming (0 and 3°C), both independently and in combination. Naupliar respiration rates increased when exposed to a combination of acidification and warming, but not when exposed to the stressors individually. Moreover, we found no discernible differences in lipid content and fatty acid (FA) composition of the nauplii across the different experimental treatments. Wax esters accounted for approximately 75% of the lipid reserves, and high amounts of long chain fatty acids 20:1 and 22:1, crucial for the reproduction cycle in copepods, were also detected. Our results indicate a sensitivity of these nauplii to a combination of acidification and warming, but not to the individual stressors, aligning with a growing body of evidence from related studies. This study sheds light on the potential implications of global change for Arctic copepod populations by elucidating the responses of early-life stages to these environmental stressors.
Changes in species compositions of fish in the bays of the Northwestern Gulf of Mexico
Authors: Torres Ceron Milton , Fujiwara Masami , Martinez-Andrade Fernando
Published: October 2023

Introduction

Local biodiversity is increasing in many temperate and subtropical waters due to climate change. It is often caused by shifting fish distributions, thus the biodiversity gradient, from lower to higher latitudes. However, these shifts in distributions do not occur uniformly across all species. Consequently, communities are not only shifting their spatial distributions, but species compositions are also changing. We investigated spatiotemporal differences in the compositions of fish species in the bays of the northeastern Gulf of Mexico and identified species that contribute to the temporal changes.

Methods

We used fish count data collected using gillnets in eight major bays, encompassing over 600 km of coastline, during spring and fall seasons from 1982 to 2019. The nonmetric multidimensional scaling (NMDS) on the Bray-Curtis dissimilarity index among species composition vectors was used to detect the differences in species composition, and the similarity percentages (SIMPER) were used to determine the contribution of species to the differences.

Results

The result shows there was a gradual change in species composition in all bays over the years, and the composition was different among bays and seasons. The species contributing to the temporal changes included those that are expanding (e.g., Common snook, Centropomus undecimalis, and Smallscale fat snook, C. parallelus) as well as retracting (e.g., Southern flounder, Paralichthys lethostigma, and Spanish mackerel, Scomberomorus maculatus) their distributions toward the north. The species observed only in recent years in these bays tended to have a preference for warmer water (e.g., Gulf pipefish, Syngnathus scovelli, and Chain pipefish, S. louisiana).

Discussion

The results are consistent with the potential effects of climate change. However, the salinity of the bays in the study area generally exhibits an increasing trend from the northern to southern bays. The spatial salinity gradient has a substantial impact on species compositions, indicating that species distributions are influenced by multiple environmental conditions. This complexity makes our ability to accurately predict future species compositions under changing environmental conditions challenging.
A vendor-agnostic, PACS integrated, and DICOM-compatible software-server pipeline for testing segmentation algorithms within the clinical radiology workflow
Authors: Zhang Lei , LaBelle Wayne , Unberath Mathias , Chen Haomin , Hu Jiazhen , Li Guang , Dreizin David
Published: October 2023

Background

Reproducible approaches are needed to bring AI/ML for medical image analysis closer to the bedside. Investigators wishing to shadow test cross-sectional medical imaging segmentation algorithms on new studies in real-time will benefit from simple tools that integrate PACS with on-premises image processing, allowing visualization of DICOM-compatible segmentation results and volumetric data at the radiology workstation.

Purpose

In this work, we develop and release a simple containerized and easily deployable pipeline for shadow testing of segmentation algorithms within the clinical workflow.

Methods

Our end-to-end automated pipeline has two major components- 1. A router/listener and anonymizer and an OHIF web viewer backstopped by a DCM4CHEE DICOM query/retrieve archive deployed in the virtual infrastructure of our secure hospital intranet, and 2. An on-premises single GPU workstation host for DICOM/NIfTI conversion steps, and image processing. DICOM images are visualized in OHIF along with their segmentation masks and associated volumetry measurements (in mL) using DICOM SEG and structured report (SR) elements. Since nnU-net has emerged as a widely-used out-of-the-box method for training segmentation models with state-of-the-art performance, feasibility of our pipleine is demonstrated by recording clock times for a traumatic pelvic hematoma nnU-net model.

Results

Mean total clock time from PACS send by user to completion of transfer to the DCM4CHEE query/retrieve archive was 5 min 32 s (± SD of 1 min 26 s). This compares favorably to the report turnaround times for whole-body CT exams, which often exceed 30 min, and illustrates feasibility in the clinical setting where quantitative results would be expected prior to report sign-off. Inference times accounted for most of the total clock time, ranging from 2 min 41 s to 8 min 27 s. All other virtual and on-premises host steps combined ranged from a minimum of 34 s to a maximum of 48 s.

Conclusion

The software worked seamlessly with an existing PACS and could be used for deployment of DL models within the radiology workflow for prospective testing on newly scanned patients. Once configured, the pipeline is executed through one command using a single shell script. The code is made publicly available through an open-source license at “https://github.com/vastc/,” and includes a readme file providing pipeline config instructions for host names, series filter, other parameters, and citation instructions for this work.
Risk of transient vision loss after intravitreal aflibercept using vial-prepared vs. the novel prefilled syringe formulation
Authors: Klaas Julian E. , Bui Vinh , Maierhofer Niklas , Schworm Benedikt , Maier Mathias , Priglinger Siegfried G. , Siedlecki Jakob
Published: October 2023

Purpose

To compare the risk of transient vision loss (TVL) probably attributable to a severe intraocular pressure spike after intravitreal aflibercept application using the novel prefilled syringe (PFS) vs. the established vial system (VS).

Methods

Datasets of the intravitreal injection service of the Ludwig Maximilians-University Munich and the Technical University Munich, Germany, were screened for documentation of TVL after intravitreal injection of aflibercept. The observation period included two full months prior to the introduction of the novel PFS and two months afterwards. TVL was defined as loss of perception of hand motion for a duration of >30 s.

Results

Over a period of four months, 1720 intravitreal injections of aflibercept were administered in 672 patients. There were 842 injections with the old VS, and 878 injections using the novel PFS. Using the VS, TVL was noted during two injections (0.24%) in two patients, as compared to 11 cases of TVL (1.25%) in 10 patients with the PFS (p = 0.015). Using the PFS, patients had a 5.3-fold risk of TVL as compared to the VS (OR: 5.33; 95% CI: 1.2–24.1; p = 0.0298).

Conclusion

There was a more than five-fold risk of TVL using the novel pre-filled aflibercept syringe as compared to the established vial system. During informed consent, this risk should be discussed.
Common and unique testosterone and 17 beta-estradiol degradation mechanisms in Comamonas testosteroni JLU460ET by transcriptome analysis
Authors: Wang Ze , Chen Mingming , Liu Na , Zhao Yongkang , Ru Jintao , Qin Chuanyu , Zhang Tingdi
Published: October 2023

Strain C. testosteroni JLU460ET was isolated for testosterone and 17 beta-estradiol degradation by our group. In this study, strain C. testosteroni JLU460ET was induced by testosterone and 17 beta-estradiol and then subjected to transcriptome analysis. There were 2,047 upregulated genes after 3 h of testosterone induction, 2,040 upregulated genes after 13 h of testosterone induction, 2,078 upregulated genes after 3 h of 17 beta-estradiol induction, and 2,095 upregulated genes after 13 h of 17 beta-estradiol induction. Significantly upregulated genes were mainly involved in steroid and aromatic compound degradation. A 100 kb steroid-degrading gene cluster was found by transcriptome analysis, which included 92 annotated genes and 58 novel genes. Among them, MucB/RseB and Fiu are secretory proteins for sensing substrates in the environment. MFS-1 and TonB are transporters of testosterone and 17 beta-estradiol. Ring-cleavage enzymes and beta-oxidation enzymes are important for degradation. The genes upregulated by both substrates were almost the same, but the degree of induction by testosterone was higher than that by 17 beta-estradiol. Nine upregulated genes were selected for verification by quantitative real-time polymerase chain reaction (qRT–PCR). The qRT-PCR results were consistent with the transcriptome sequencing results. In this study, the common and unique metabolic mechanisms of testosterone and 17 beta-estradiol were compared by transcriptome analysis in C. testosteroni JLU460ET for the first time.
Microclimate shapes the phylosymbiosis of rodent gut microbiota in Jordan’s Great Rift Valley
Authors: Al-khlifeh Enas , Khadem Sanaz , Hausmann Bela , Berry David
Published: October 2023

Host phylogeny and the environment play vital roles in shaping animal microbiomes. However, the effects of these variables on the diversity and richness of the gut microbiome in different bioclimatic zones remain underexplored. In this study, we investigated the effects of host phylogeny and bioclimatic zone on the diversity and composition of the gut microbiota of two heterospecific rodent species, the spiny mouse Acomys cahirinus and the house mouse Mus musculus, in three bioclimatic zones of the African Great Rift Valley (GRV). We confirmed host phylogeny using the D-loop sequencing method and analyzed the influence of host phylogeny and bioclimatic zone parameters on the rodent gut microbiome using high-throughput amplicon sequencing of 16S rRNA gene fragments. Phylogenetic analysis supported the morphological identification of the rodents and revealed a marked genetic difference between the two heterospecific species. We found that bioclimatic zone had a significant effect on the gut microbiota composition while host phylogeny did not. Microbial alpha diversity of heterospecific hosts was highest in the Mediterranean forest bioclimatic zone, followed by the Irano–Turanian shrubland, and was lowest in the Sudanian savanna tropical zone. The beta diversity of the two rodent species showed significant differences across the Mediterranean, Irano–Turanian, and Sudanian regions. The phyla Firmicutes and Bacteroidetes were highly abundant, and Deferribacterota, Cyanobacteria and Proteobacteria were also prominent. Amplicon sequence variants (ASVs) were identified that were unique to the Sudanian bioclimatic zone. The core microbiota families recovered in this study were consistent among heterospecific hosts. However, diversity decreased in conspecific host populations found at lower altitudes in Sudanian bioclimatic zone. The composition of the gut microbiota is linked to the adaptation of the host to its environment, and this study underscores the importance of incorporating climatic factors such as elevation and ambient temperature, in empirical microbiome research and is the first to describe the rodent gut microbiome from the GRV.
Comparison of clinical outcomes in patients with acute ischemic stroke who underwent endovascular treatment using different perfusion modalities: a real-world multicenter study
Authors: Gao Jiali , Jing Zhen , Huang Shengming , Yang Jiajie , Guan Min , Zhang Shijun , Li Hao , Li Yongxin , Lu Kui , Yang Ming , Huang Li’an
Published: October 2023

Background

Advanced perfusion modalities are increasingly popular for various diseases. However, few studies have focused on contrasting perfusion patterns.

Objective

This study aimed to compare the time efficiency and clinical outcomes of patients with acute ischemic stroke (AIS) who underwent endovascular treatment (EVT) before one-stop arterial spin labeling (ASL) and computed tomography perfusion (CTP) protocols.

Methods

This study retrospectively included 326 patients with AIS who had accepted EVT within 24 h of onset from four comprehensive stroke centers between October 2017 and September 2022. After 1:1 matching of the propensity scores, 202 patients were separated into two groups: the ASL group (n = 101) and the CTP group (n = 101).

Results

Functional independence at 90 days (modified Rankin Scale [mRS] 0–2; p = 0.574), onset-to-puncture time (p = 0.231), door-to-puncture time (p = 0.136), and door-to-perfusion time (p = 0.646) were not significantly different between the two groups. The proportion of EVT complications (31.7% in the ASL group vs. 14.9% in the CTP group, p = 0.005) and symptomatic intracranial hemorrhage (sICH) at 24 h (23.8% in the ASL group vs. 9.9% in the CTP group, p = 0.008) in the CTP group were lower than the ASL group. The ischemic core volume was a common predictor of favorable outcomes in both ASL (p < 0.001) and CTP (p < 0.001) groups.

Conclusion

There were no significant differences in time efficiency and efficacy outcomes between the two groups of patients receiving one-stop ASL and CTP. The proportion of sICH at 24 h and EVT complications of patients in the CTP group was lower than the ASL group. The ischemic core volume was an independent predictor for favorable outcomes.
Transcriptional and bioinformatic analysis of GABAA receptors expressed in oligodendrocyte progenitor cells from the human brain
Authors: Gutierrez Berenice A. , González-Coronel José Manuel , Arellano Rogelio O. , Limon Agenor
Published: October 2023

Introduction

Oligodendrocyte progenitor cells (OPCs) are vital for neuronal myelination and remyelination in the central nervous system. While the molecular mechanisms involved in OPCs’ differentiation and maturation are not completely understood, GABA is known to positively influence these processes through the activation of GABAA receptors (GABAARs). The molecular identity of GABAARs expressed in human OPCs remains unknown, which restricts their specific pharmacological modulation to directly assess their role in oligodendrocytes’ maturation and remyelination.

Methods

In this study, we conducted a transcriptomic analysis to investigate the molecular stoichiometry of GABAARs in OPCs from the human brain. Using eight available transcriptomic datasets from the human brain cortex of control individuals, we analyzed the mRNA expression of all 19 known GABAARs subunit genes in OPCs, with variations observed across different ages.

Results

Our analysis indicated that the most expressed subunits in OPCs are α1–3, β1–3, γ1–3, and ε. Moreover, we determined that the combination of any α with β2 and γ2 is likely to form heteropentameric GABAARs in OPCs. Importantly, we also found a strong correlation between GABAAR subunits and transcripts for postsynaptic scaffold proteins, suggesting the potential postsynaptic clustering of GABAARs in OPCs.

Discussion

This study presents the first transcriptional-level identification of GABAAR subunits expressed in human OPCs, providing potential receptor combinations. Understanding the molecular composition of GABAARs in OPCs not only enhances our knowledge of the underlying mechanisms in oligodendrocyte maturation but also opens avenues for targeted pharmacological interventions aimed at modulating these receptors to promote remyelination in neurological disorders.
RETRACTED: A 1 year course of starch- and sucrose-reduced diet used by irritable bowel syndrome patients with diarrhoea and the effect of genetic variants
Authors: Garcia-Etxebarria Koldo , Gayoso Lucía , Arzallus Teresa , Montalvo Isabel , Lizasoain Jacobo , Izagirre Arantzazu , Ezkurra Ander , D’Amato Mauro , Etxeberria Usune , Bujanda Luis
Published: October 2023

Background

Irritable bowel syndrome is a heterogeneous syndrome and it is difficult to find an effective treatment. Previously, a starch- and sucrose-reduced diet (SSRD) demonstrated promising short-term outcomes. It was proposed that genetic variants in the sucrose-isomaltase gene might influence this success. Our aim in this work was to extend the follow-up study to 1 year and to analyse the effect of the genetic variants of genes involved in starch and sucrose metabolism.

Methods

IBS-SSS questionnaire, IBS-QoL questionnaire and questionnaires about adherence, difficulty and food assessment were sent to 34 patients after 6 months and 1 year after the end of the dietary intervention. In addition, 11 genes involved in sucrose and starch metabolism were sequenced.

Results

Twenty-three participants responded to the 6 months follow-up and 16 to the 1 year follow-up. IBS-SSS total value increased 59.71% in the 6 months follow-up compared with the end of the intervention (p = 0.0018), and 55.39% in the 1 year follow-up (p = 0.0166); while IBS-QoL score decreased 24.09% (p = 0.0002) and 18.07% (p = 0.0022), respectively. The adherence decreased by 29.11% (p = 4.8 × 10−5) and 27.21% (p = 0.0054), respectively. In addition, carriers of pathogenic variants on the SI gene showed a slightly better performance than non-carriers. Finally, the participants showed less satisfaction over time with 18 allowed foods in the diet.

Conclusion

Over time the SSRD is difficult to follow and the genotype might affect the performance of the diet. Since this diet could be a promising therapeutic option, a larger cohort needs to be analysed to validate the results and to compare it with other diets.
Application of DKI and IVIM imaging in evaluating histologic grades and clinical stages of clear cell renal cell carcinoma
Authors: Cheng QiChao , Ren AnLi , Xu XingHua , Meng Zhao , Feng Xue , Pylypenko Dmytro , Dou WeiQiang , Yu DeXin
Published: October 2023

Purpose

To evaluate the value of quantitative parameters derived from diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) in differentiating histologic grades and clinical stages of clear cell renal cell carcinoma (ccRCC).

Materials and methods

A total of 65 patients who were surgically and pathologically diagnosed as ccRCC were recruited in this study. In addition to routine renal magnetic resonance imaging examination, all patients underwent preoperative IVIM and DKI. The corresponding diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean diffusivity (MD), kurtosis anisotropy (KA), and mean kurtosis (MK) values were obtained. Independent-samples t-test or Mann–Whitney U test was used for comparing the differences in IVIM and DKI parameters among different histologic grades and clinical stages. The diagnostic efficacy of IVIM and DKI parameters was evaluated using the receiver operating characteristic (ROC) curve. Spearman’s correlation analysis was used to separately analyze the correlation of each parameter with histologic grades and stages of ccRCC.

Results

The D and MD values were significantly higher in low-grade ccRCC than high-grade ccRCC (all p < 0.001) and in low-stage than high-stage ccRCC (all p < 0.05), and the f value of high-stage ccRCC was lower than that of low-stage ccRCC (p = 0.007). The KA and MK values were significantly higher in low-grade than high-grade ccRCC (p = 0.000 and 0.000, respectively) and in low-stage than high-stage ccRCC (p = 0.000 and 0.000, respectively). The area under the curve (AUC) values of D, D*, f, MD, KA, MK, DKI, and IVIM+DKI values were 0.825, 0.598, 0.626, 0.792, 0.750, 0.754, 0.803, and 0.857, respectively, in grading ccRCC and 0.837, 0.719, 0.710, 0.787, 0.796, 0.784, 0.864, 0.823, and 0.916, respectively, in staging ccRCC. The AUC of IVIM was 0.913 in staging ccRCC. The D, D*, and MD values were negatively correlated with the histologic grades and clinical stages (all p < 0.05), and the KA and MK values showed a positive correlation with histologic grades and clinical stages (all p < 0.05). The f value was also negatively correlated with the ccRCC clinical stage (p = 0.008).

Conclusion

Both the IVIM and DKI values can be used preoperatively to predict the degree of histologic grades and stages in ccRCC, and the D and MD values have better diagnostic performance in the grading and staging. Also, further slightly enhanced diagnostic efficacy was observed in the model with combined IVIM and DKI parameters.
Elastic–plastic intermittent re-arrangements of frictionless, soft granular matter under very slow isotropic deformations
Authors: Luding Stefan
Published: October 2023

How do soft granular materials (or dense amorphous systems) respond to externally applied deformations at different rates and for different system sizes? This long-standing question was intensively studied for shear deformations but only more recently for isotropic deformations, like compression–decompression cycles. For moderate strain rates, in the solid-like state, above jamming, the system appears to evolve more or less smoothly in time/strain, whereas for slow enough deformations, the material flips intermittently between the elastic, reversible base state and plastic, dynamic “events.” Only during the latter events, the microstructure re-arranges irreversibly. The reversible base state involves both affine and non-affine deformations, while the events are purely non-affine. The system size and rate dependence of the events are studied, providing reference data for comparison in future studies evaluating materials like hydrogel particles.
Total and component forest aboveground biomass inversion via LiDAR-derived features and machine learning algorithms
Authors: Ma Jiamin , Zhang Wangfei , Ji Yongjie , Huang Jimao , Huang Guoran , Wang Lu
Published: October 2023

Forest aboveground biomass (AGB) and its biomass components are key indicators for assessing forest ecosystem health, productivity, and carbon stocks. Light Detection and Ranging (LiDAR) technology has great advantages in acquiring the vertical structure of forests and the spatial distribution characteristics of vegetation. In this study, the 56 features extracted from airborne LiDAR point cloud data were used to estimate forest total and component AGB. Variable importance–in–projection values calculated through a partial least squares regression algorithm were utilized for LiDAR-derived feature ranking and optimization. Both leave-one-out cross-validation (LOOCV) and cross-validation methods were applied for validation of the estimated results. The results showed that four cumulative height percentiles (AIH30,AIH40, AIH20, and AIH25), two height percentiles (H8 and H6), and four height-related variables (Hmean, Hsqrt, Hmad, and Hcurt) are ranked more frequently in the top 10 sensitive features for total and component forest AGB retrievals. Best performance was acquired by random forest (RF) algorithm, with R2 = 0.75, root mean square error (RMSE) = 22.93 Mg/ha, relative RMSE (rRMSE) = 25.30%, and mean absolute error (MAE) = 19.26 Mg/ha validated by the LOOCV method. For cross-validation results, R2 is 0.67, RMSE is 24.56 Mg/ha, and rRMSE is 25.67%. The performance of support vector regression (SVR) for total AGB estimation is R2 = 0.66, RMSE = 26.75 Mg/ha, rRMSE = 28.62%, and MAE = 22.00 Mg/ha using LOOCV validation and R2 = 0.56, RMSE = 30.88 Mg/ha, and rRMSE = 31.41% by cross-validation. For the component AGB estimation, the accuracy from both RF and SVR algorithms was arranged as stem > bark > branch > leaf. The results confirmed the sensitivity of LiDAR-derived features to forest total and component AGBs. They also demonstrated the worse performance of these features for retrieval of leaf component AGB. RF outperformed SVR for both total and component AGB estimation, the validation difference from LOOCV and cross-validation is less than 5% for both total and component AGB estimated results.
Rosin from Pinus pinaster Portuguese forests shows a regular profile of resin acids
Authors: Pinheiro Ângela , Martins Isabel , Bento Artur , Escórcio Rita , Nunes Carolina , Varela Adélia , Nunes João , Afonso Carlos A.M. , Silva Pereira Cristina
Published: October 2023

Pinus pinaster forestry occupies >20% of the forest ecosystem area in the continental territory of Portugal with a high impact on the national economy. This species’ major derived non-wood product is oleoresin, the raw material for rosin production. Rosin comprises mainly a blend of resin acids and has broad industrial and pharmaceutical applications. Oleoresin production in Portugal has been progressively reduced due to low-cost producers in other countries; currently, it reaches only 2% of the existing P. pinaster trees. To support this value chain, the chemical fingerprint of rosin derived from the national forest requires focused analysis. In the present study, we collected oleoresin within seven geographically distinct pure P. pinaster forests in two consecutive collection years. A high-resolution nuclear magnetic resonance (NMR) method was used to quantify the diversity of resin acids in the corresponding rosin samples. Overall, the acquired data highlighted that the profile of resin acids in P. pinaster rosin produced in Portugal is highly regular, regardless of the forest location, having as the major constituents abietic acid and dehydroabietic acid. The diversity of resin acids is possibly influenced, to a minor extent, by some edaphoclimatic factors.
Physiological responses and transcriptome analysis of soybean under gradual water deficit
Authors: Xu Yuwen , Song Di , Qi Xingliang , Asad Muhammad , Wang Sui , Tong Xiaohong , Jiang Yan , Wang Shaodong
Published: October 2023

Soybean is an important food and oil crop widely cultivated globally. However, water deficit can seriously affect the yield and quality of soybeans. In order to ensure the stability and increase of soybean yield and improve agricultural water use efficiency (WUE), research on improving drought tolerance and the efficiency of water utilization of soybeans under drought stress has become particularly important. This study utilized the drought-tolerant variety Heinong 44 (HN44) and the drought-sensitive variety Suinong 14 (SN14) to analyze physiological responses and transcriptome changes during the gradual water deficit at the early seed-filling stage. The results indicated that under drought conditions, HN44 had smaller stomata, higher stomatal density, and lower stomatal conductance (Gs) and transpiration rate as compared to SN14. Additionally, HN44 had a higher abscisic acid (ABA) content and faster changes in stomatal morphology and Gs to maintain a dynamic balance between net photosynthetic rate (Pn) and Gs. Additionally, drought-tolerant variety HN44 had high instantaneous WUE under water deficit. Further, HN44 retained a high level of superoxide dismutase (SOD) activity and proline content, mitigating malondialdehyde (MDA) accumulation and drought-induced damage. Comprehensive analysis of transcriptome data revealed that HN44 had fewer differentially expressed genes (DEGs) under light drought stress, reacting insensitivity to water deficit. At the initial stage of drought stress, both varieties had a large number of upregulated DEGs to cope with the drought stress. Under severe drought stress, HN44 had fewer downregulated genes enriched in the photosynthesis pathway than SN14, while it had more upregulated genes enriched in the ABA-mediated signaling and glutathione metabolism pathways than SN14. During gradual water deficit, HN44 demonstrated better drought-tolerant physiological characteristics and water use efficiency than SN14 through key DEGs such as GmbZIP4, LOC100810474, and LOC100819313 in the major pathways. Key transcription factors were screened and identified, providing further clarity on the molecular regulatory pathways responsible for the physiological differences in drought tolerance among these varieties. This study deepened the understanding of the drought resistance mechanisms in soybeans, providing valuable references for drought-resistant soybean breeding.