bluuebunny/crossref_metadata_2025 huggingface dataset:
The application of corneal biomechanical interocular asymmetry for the diagnosis of keratoconus and subclinical keratoconus
Authors: Dong Ruilan , Liu Yan , Zhang Yu , Chen Yueguo
Published: October 2023

Purpose: To evaluate the interocular consistency of biomechanical properties in normal, keratoconus (KC) and subclinical keratoconus (SKC) populations and explore the application of interocular asymmetry values in KC and SKC diagnoses.

Methods: This was a retrospective chart-review study of 331 ametropic subjects (control group) and 207 KC patients (KC group, including 94 SKC patients). Interocular consistency was evaluated using the intraclass correlation coefficient (ICC). Interocular asymmetry was compared between the control and KC groups and its correlation with disease severity was analyzed. Three logistic models were constructed using biomechanical monocular parameters and interocular asymmetry values. The diagnostic ability of interocular asymmetry values and the newly established models were evaluated using receiver operating characteristic curves and calibration curves. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were also estimated.

Results: The interocular consistency significantly decreased and the interocular asymmetry values increased in KC patients compared with those in control individuals. In addition, the interocular asymmetry values increased with respect to the severity of KC. The binocular assisted biomechanical index (BaBI) had an area under the curve (AUC) of 0.998 (97.8% sensitivity, 99.2% specificity; cutoff 0.401), which was statistically higher than that of the Corvis biomechanical index [CBI; AUC = 0.935, p < 0.001 (DeLong’s test), 85.6% sensitivity]. The optimized cutoff of 0.163 provided an AUC of 0.996 for SKC with 97.8% sensitivity, which was higher than that of CBI [AUC = 0.925, p < 0.001 (DeLong’s test), 82.8% sensitivity].

Conclusion: Biomechanical interocular asymmetry values can reduce the false-negative rate and improve the performance in KC and SKC diagnoses.
Different seminal ejaculated fractions in artificial insemination condition the protein cargo of oviductal and uterine extracellular vesicles in pig
Authors: Toledo-Guardiola S. M. , Luongo C. , Abril-Parreño L. , Soriano-Úbeda C. , Matás C.
Published: October 2023

The seminal plasma (SP) is the liquid component of semen that facilitates sperm transport through the female genital tract. SP modulates the activity of the ovary, oviductal environment and uterine function during the periovulatory and early pregnancy period. Extracellular vesicles (EVs) secreted in the oviduct (oEVs) and uterus (uEVs) have been shown to influence the expression of endometrial genes that regulate fertilization and early embryo development. In some species, semen is composed of well-separated fractions that vary in concentration of spermatozoa and SP composition and volume. This study aimed to investigate the impact of different accumulative fractions of the porcine ejaculate (F1, composed of the sperm-rich fraction, SRF; F2, composed of F1 plus the intermediate fraction; F3, composed of F2 plus the post-SRF) on oEVs and uEVs protein cargo. Six days after the onset of estrus, we determined the oEVs and uEVs size and protein concentration in pregnant sows by artificial insemination (AI-sows) and in non-inseminated sows as control (C-sows). We also identified the main proteins in oEVs and uEVs, in AI-F1, AI-F2, AI-F3, and C-sows. Our results indicated that although the size of EVs is similar between AI- and C-sows, the protein concentration of both oEVs and uEVs was significantly lower in AI-sows (p < 0.05). Proteomic analysis identified 38 unique proteins in oEVs from AI-sows, mainly involved in protein stabilization, glycolytic and carbohydrate processes. The uEVs from AI-sows showed the presence of 43 unique proteins, including already-known fertility-related proteins (EZR, HSPAA901, PDS). We also demonstrated that the protein composition of oEVs and uEVs differed depending on the seminal fraction(s) inseminated (F1, F2, or F3). In conclusion, we found specific protein cargo in oEVs and uEVs according to the type of semen fraction the sow was inseminated with and whose functions these specific EVs proteins are closely associated with reproductive processes.
Cell lipid biology in infections: an overview
Authors: Prado Luan Gavião , Camara Niels Olsen Saraiva , Barbosa Angela Silva
Published: October 2023

Lipids are a big family of molecules with a vast number of functions in the cell membranes, within the cytoplasm, and extracellularly. Lipid droplets (LDs) are the most common storage organelles and are present in almost every tissue type in the body. They also have structural functions serving as building blocks of cellular membranes and may be precursors of other molecules such as hormones, and lipoproteins, and as messengers in signal transduction. Fatty acids (FAs), such as sterol esters and triacylglycerols, are stored in LDs and are used in β-oxidation as fuel for tricarboxylic acid cycle (TCA) and adenosine triphosphate (ATP) generation. FA uptake and entrance in the cytoplasm are mediated by membrane receptors. After a cytoplasmic round of α- and β-oxidation, FAs are guided into the mitochondrial matrix by the L-carnitine shuttle system, where they are fully metabolized, and enter the TCA cycle. Pathogen infections may lead to impaired lipid metabolism, usage of membrane phospholipids, and LD accumulation in the cytoplasm of infected cells. Otherwise, bacterial pathogens may use lipid metabolism as a carbon source, thus altering the reactions and leading to cellular and organelles malfunctioning. This review aims to describe cellular lipid metabolism and alterations that occur upon infections.
Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial
Authors: Mohammadnia Niekbachsh , Los Jan , Opstal Tjerk S. J. , Fiolet Aernoud T. L. , Eikelboom John W. , Mosterd Arend , Nidorf Stefan M. , Budgeon Charley A. , Tijssen Jan G. P. , Thompson Peter L. , Tack Cees J. , Simsek Suat , Bax Willem A. , Cornel Jan H. , El Messaoudi Saloua
Published: October 2023

Introduction

Despite optimal treatment, patients with chronic coronary artery disease (CAD) and diabetes mellitus (DM) are at high risk of cardiovascular events, emphasizing the need for new treatment options. The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD. This analysis determines the efficacy of colchicine in patients with chronic CAD and DM as well as the effect of colchicine on the development of new-onset type 2 diabetes mellitus (T2DM).

Methods

The LoDoCo2 trial randomized 5,522 patients to placebo or colchicine 0.5 mg once daily, with a median follow-up of 28.6 months. The primary composite endpoint was cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven revascularization. The effect of its treatment in patients with and without DM was evaluated by including an interaction term in the model.

Results

A total of 1,007 participants (18.2%) had T2DM at baseline. The adjusted hazard ratio (HR) [(95% confidence interval (CI)] for the primary endpoint in the T2DM group was 1.52 (1.15–2.01, p < 0.01) compared with the group without T2DM. The HR for the treatment effect on the primary endpoint was 0.87 (0.61–1.25) in participants with T2DM and 0.64 (0.51–0.80) in participants without diabetes (pinteraction = 0.14). The incidence of new-onset T2DM was 1.5% (34 out of 2,270) in the colchicine group and 2.2% (49 out of 2,245) in the placebo group (p = 0.10).

Discussion

In conclusion, based on the current evidence, the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The potential benefits of colchicine in preventing new-onset DM need further investigation. These findings are only hypothesis-generating and require larger prospective trials to confirm the results.
Prioritization of risk genes for Alzheimer’s disease: an analysis framework using spatial and temporal gene expression data in the human brain based on support vector machine
Authors: Wang Shiyu , Fang Xixian , Wen Xiang , Yang Congying , Yang Ying , Zhang Tianxiao
Published: October 2023

Background: Alzheimer’s disease (AD) is a complex disorder, and its risk is influenced by multiple genetic and environmental factors. In this study, an AD risk gene prediction framework based on spatial and temporal features of gene expression data (STGE) was proposed.

Methods: We proposed an AD risk gene prediction framework based on spatial and temporal features of gene expression data. The gene expression data of providers of different tissues and ages were used as model features. Human genes were classified as AD risk or non-risk sets based on information extracted from relevant databases. Support vector machine (SVM) models were constructed to capture the expression patterns of genes believed to contribute to the risk of AD.

Results: The recursive feature elimination (RFE) method was utilized for feature selection. Data for 64 tissue-age features were obtained before feature selection, and this number was reduced to 19 after RFE was performed. The SVM models were built and evaluated using 19 selected and full features. The area under curve (AUC) values for the SVM model based on 19 selected features (0.740 [0.690–0.790]) and full feature sets (0.730 [0.678–0.769]) were very similar. Fifteen genes predicted to be risk genes for AD with a probability greater than 90% were obtained.

Conclusion: The newly proposed framework performed comparably to previous prediction methods based on protein-protein interaction (PPI) network properties. A list of 15 candidate genes for AD risk was also generated to provide data support for further studies on the genetic etiology of AD.
Prognostic risk of immune-associated signature in the microenvironment of brain gliomas
Authors: Tao Yaling , Zhu Junqi , Yu Xiaoling , Cong Huaiwei , Li Jinpeng , Cai Ting , Chen Qian
Published: October 2023

Understanding the key factors in the tumor microenvironment (TME) that affect the prognosis of gliomas is crucial. In this study, we sought to uncover the prognostic significance of immune cells and immune-related genes in the TME of gliomas. We incorporated data of 970 glioma patient samples from the Chinese Glioma Genome Atlas (CGGA) database as the training set, and an additional set of 666 samples from The Cancer Genome Atlas (TCGA) database served as the validation set. From our analysis, we identified 21 immune-related differentially expressed genes (DEGs) in the TME, which holds implications for glioma prognosis. Based on these genes, we constructed a prognostic risk model on the 21 genes. The prognostic risk model demonstrated robust performance with an area under the curve (AUC) value of 0.848. Notably, the risk score derived from the model emerged as an independent prognostic factor of gliomas, with high risk scores indicative of an unfavorable prognosis. Furthermore, we observed that high infiltration levels of certain immune cells, namely, activated dendritic cells, M0 macrophages, M2 macrophages, and regulatory T cells (Tregs), correlated with an unfavorable glioma prognosis. In conclusion, our findings suggested that the TME of gliomas harbored a distinct immune-associated signature, comprising 21 immune-related genes and specific immune cells. These elements significantly influence the prognosis and present potential as novel indicators in the clinical assessment of glioma patient outcomes.
Novel Siglec-15-Sia axis inhibitor leads to colorectal cancer cell death by targeting miR-6715b-3p and oncogenes
Authors: Ahmad Mohammed Saqif , Braoudaki Maria , Patel Hershna , Ahmad Irshad , Shagufta  , Siddiqui Shoib Sarwar
Published: October 2023

Siglecs are well known immunotherapeutic targets in cancer. Current checkpoint inhibitors have exhibited limited efficacy, prompting a need for novel therapeutics for targets such as Siglec-15. Presently, small molecule inhibitors targeting Siglec-15 are not explored alongside characterised regulatory mechanisms involving microRNAs in CRC progression. Therefore, a small molecule inhibitor to target Siglec-15 was elucidated in vitro and microRNA mediated inhibitor effects were investigated. Our research findings demonstrated that the SHG-8 molecule exerted significant cytotoxicity on cell viability, migration, and colony formation, with an IC50 value of approximately 20µM. SHG-8 exposure induced late apoptosis in vitro in SW480 CRC cells. Notably, miR-6715b-3p was the most upregulated miRNA in high-throughput sequencing, which was also validated via RT-qPCR. MiR-6715b-3p may regulate PTTG1IP, a potential oncogene which was validated via RT-qPCR and in silico analysis. Additionally, molecular docking studies revealed SHG-8 interactions with the Siglec-15 binding pocket with the binding affinity of -5.4 kcal/mol, highlighting its role as a small molecule inhibitor. Importantly, Siglec-15 and PD-L1 are expressed on mutually exclusive cancer cell populations, suggesting the potential for combination therapies with PD-L1 antagonists.
Mechanisms and regulations of ferroptosis
Authors: Zhang Xu-Dong , Liu Zhong-Yuan , Wang Mao-Sen , Guo Yu-Xiang , Wang Xiang-Kun , Luo Kai , Huang Shuai , Li Ren-Feng
Published: October 2023

Regulation of cell mortality for disease treatment has been the focus of research. Ferroptosis is an iron-dependent regulated cell death whose mechanism has been extensively studied since its discovery. A large number of studies have shown that regulation of ferroptosis brings new strategies for the treatment of various benign and malignant diseases. Iron excess and lipid peroxidation are its primary metabolic features. Therefore, genes involved in iron metabolism and lipid metabolism can regulate iron overload and lipid peroxidation through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) is the body’s primary non-enzymatic antioxidants and plays a pivotal role in the struggle against lipid peroxidation. GSH functions as an auxiliary substance for glutathione peroxidase 4 (GPX4) to convert toxic lipid peroxides to their corresponding alcohols. Here, we reviewed the researches on the mechanism of ferroptosis in recent years, and comprehensively analyzed the mechanism and regulatory process of ferroptosis from iron metabolism and lipid metabolism, and then described in detail the metabolism of GPX4 and the main non-enzymatic antioxidant GSH in vivo.
Occupational physical activity: the good, the bad, and the proinflammatory
Authors: Jordakieva Galateja , Hasenoehrl Timothy , Steiner Margarete , Jensen-Jarolim Erika , Crevenna Richard
Published: October 2023

Background

Physical activity (PA) is beneficial for preventing several conditions associated with underlying chronic inflammation, e. g., cardiovascular disease (CVD) and cancer. While an active lifestyle appears to have anti-inflammatory effects, high levels of occupational PA (OPA) were associated with inflammation and elevated mortality risks. We aimed to summarize the current knowledge (1) on the association between inflammation and OPA and (2) its implications for health and mortality.

Methods and results

This mini-review summarized relevant literature published before January 2023 using established scientific databases and sources. For the primary outcome, observational studies (S) reporting immunological effects (O) in subjects (P), with high (I) vs. low OPA (C), were included. For secondary outcomes, i.e., morbidity and mortality associated with inflammatory processes, (systematic) reviews were included. While “active” occupations and “moderate” OPA appear to have beneficial effects, low (particularly sedentary) and “high-intensity” OPA (particularly including heavy lifting tasks) were associated with inflammation and (CVD and cancer-related) mortality; higher leisure-time PA has been almost consistently associated with lower proinflammatory markers and all-cause mortality risks. Workplace interventions appear to counter some of the observed health effects of unfavorable work strain.

Conclusion

The few studies addressing OPA “intensity” and inflammatory markers are largely heterogeneous regarding OPA classification and confounder control. Sedentary and “heavy” OPA appear to promote proinflammatory effects. In addition to targeted management of work-related physical strain and hazardous environmental co-factors, occupational health providers should focus on employer-initiated exercise interventions and the promotion of leisure-time PA.
Effectiveness of an image analyzing AI-based Digital Health Technology to identify Non-Melanoma Skin Cancer and other skin lesions: results of the DERM-003 study
Authors: Marsden Helen , Morgan Caroline , Austin Stephanie , DeGiovanni Claudia , Venzi Marcello , Kemos Polychronis , Greenhalgh Jack , Mullarkey Dan , Palamaras Ioulios
Published: October 2023

Introduction

Identification of skin cancer by an Artificial Intelligence (AI)-based Digital Health Technology could help improve the triage and management of suspicious skin lesions.

Methods

The DERM-003 study (NCT04116983) was a prospective, multi-center, single-arm, masked study that aimed to demonstrate the effectiveness of an AI as a Medical Device (AIaMD) to identify Squamous Cell Carcinoma (SCC), Basal Cell Carcinoma (BCC), pre-malignant and benign lesions from dermoscopic images of suspicious skin lesions. Suspicious skin lesions that were suitable for photography were photographed with 3 smartphone cameras (iPhone 6S, iPhone 11, Samsung 10) with a DL1 dermoscopic lens attachment. Dermatologists provided clinical diagnoses and histopathology results were obtained for biopsied lesions. Each image was assessed by the AIaMD and the output compared to the ground truth diagnosis.

Results

572 patients (49.5% female, mean age 68.5 years, 96.9% Fitzpatrick skin types I-III) were recruited from 4 UK NHS Trusts, providing images of 611 suspicious lesions. 395 (64.6%) lesions were biopsied; 47 (11%) were diagnosed as SCC and 184 (44%) as BCC. The AIaMD AUROC on images taken by iPhone 6S was 0.88 (95% CI: 0.83–0.93) for SCC and 0.87 (95% CI: 0.84–0.91) for BCC. For Samsung 10 the AUROCs were 0.85 (95% CI: 0.79–0.90) and 0.87 (95% CI, 0.83–0.90), and for the iPhone 11 they were 0.88 (95% CI, 0.84–0.93) and 0.89 (95% CI, 0.86–0.92) for SCC and BCC, respectively. Using pre-determined diagnostic thresholds on images taken on the iPhone 6S the AIaMD achieved a sensitivity and specificity of 98% (95% CI, 88–100%) and 38% (95% CI, 33–44%) for SCC; and 94% (95% CI, 90–97%) and 28% (95 CI, 21–35%) for BCC. All 16 lesions diagnosed as melanoma in the study were correctly classified by the AIaMD.

Discussion

The AIaMD has the potential to support the timely diagnosis of malignant and premalignant skin lesions.
Rapid inactivation and sample preparation for SARS-CoV-2 PCR-based diagnostics using TNA-Cifer Reagent E
Authors: Pollak Nina M. , Rawle Daniel J. , Yan Kexin , Buckley Cameron , Le Thuy T. , Wang Claire Y. T. , Ertl Nicole G. , van Huyssteen Karla , Crkvencic Nicole , Hashmi Misha , Lyons Russell E. , Whiley David M. , Suhrbier Andreas , Macdonald Joanne
Published: October 2023

RT-qPCR remains a key diagnostic methodology for COVID-19/SARS-CoV-2. Typically, nasal or saliva swabs from patients are placed in virus transport media (VTM), RNA is extracted at the pathology laboratory, and viral RNA is measured using RT-qPCR. In this study, we describe the use of TNA-Cifer Reagent E in a pre-clinical evaluation study to inactivate SARS-CoV-2 as well as prepare samples for RT-qPCR. Adding 1 part TNA-Cifer Reagent E to 5 parts medium containing SARS-CoV-2 for 10 min at room temperature inactivated the virus and permitted RT-qPCR detection. TNA-Cifer Reagent E was compared with established column-based RNA extraction and purification methodology using a panel of human clinical nasal swab samples (n = 61), with TNA-Cifer Reagent E showing high specificity (100%) and sensitivity (97.37%). Mixtures of SARS-CoV-2 virus and TNA-Cifer Reagent E could be stored for 3 days at room temperature or for 2 weeks at 4°C without the loss of RT-qPCR detection sensitivity. The detection sensitivity was preserved when TNA-Cifer Reagent E was used in conjunction with a range of VTM for saliva samples but only PBS (Gibco) and Amies Orange for nasal samples. Thus, TNA-Cifer Reagent E improves safety by rapidly inactivating the virus during sample processing, potentially providing a safe means for molecular SARS-CoV-2 testing outside traditional laboratory settings. The reagent also eliminates the need for column-based and/or automated viral RNA extraction/purification processes, thereby providing cost savings for equipment and reagents, as well as reducing processing and handling times.
plASgraph2: using graph neural networks to detect plasmid contigs from an assembly graph
Authors: Sielemann Janik , Sielemann Katharina , Brejová Broňa , Vinař Tomáš , Chauve Cedric
Published: October 2023

Identification of plasmids from sequencing data is an important and challenging problem related to antimicrobial resistance spread and other One-Health issues. We provide a new architecture for identifying plasmid contigs in fragmented genome assemblies built from short-read data. We employ graph neural networks (GNNs) and the assembly graph to propagate the information from nearby nodes, which leads to more accurate classification, especially for short contigs that are difficult to classify based on sequence features or database searches alone. We trained plASgraph2 on a data set of samples from the ESKAPEE group of pathogens. plASgraph2 either outperforms or performs on par with a wide range of state-of-the-art methods on testing sets of independent ESKAPEE samples and samples from related pathogens. On one hand, our study provides a new accurate and easy to use tool for contig classification in bacterial isolates; on the other hand, it serves as a proof-of-concept for the use of GNNs in genomics. Our software is available at https://github.com/cchauve/plasgraph2 and the training and testing data sets are available at https://github.com/fmfi-compbio/plasgraph2-datasets.
Longitudinal MR imaging after unilateral MR-guided focused ultrasound thalamotomy: clinical and radiological correlation
Authors: Blitz Sarah E. , Chua Melissa M. J. , Ng Patrick , Segar David J. , Jha Rohan , McDannold Nathan J. , DeSalvo Matthew N. , Rolston John D. , Cosgrove G. Rees
Published: October 2023

Introduction

Magnetic-resonance-guided focused ultrasound (MRgFUS) thalamotomy uses multiple converging high-energy ultrasonic beams to produce thermal lesions in the thalamus. Early postoperative MR imaging demonstrates the location and extent of the lesion, but there is no consensus on the utility or frequency of postoperative imaging. We aimed to evaluate the evolution of MRgFUS lesions and describe the incidence, predictors, and clinical effects of lesion persistence in a large patient cohort.

Methods

A total of 215 unilateral MRgFUS thalamotomy procedures for essential tremor (ET) by a single surgeon were retrospectively analyzed. All patients had MR imaging 1 day postoperatively; 106 had imaging at 3 months and 32 had imaging at 1 year. Thin cut (2 mm) axial and coronal T2-weighted MRIs at these timepoints were analyzed visually on a binary scale for lesion presence and when visible, lesion volumes were measured. SWI and DWI sequences were also analyzed when available. Clinical outcomes including tremor scores and side effects were recorded at these same time points. We analyzed if patient characteristics (age, skull density ratio), preoperative tremor score, and sonication parameters influenced lesion evolution and if imaging characteristics correlated with clinical outcomes.

Results

Visible lesions were present in all patients 1 day post- MRgFUS and measured 307.4 ± 128.7 mm3. At 3 months, residual lesions (excluding patients where lesions were not visible) were 83.6% smaller and detectable in only 54.7% of patients (n = 58). At 1 year, residual lesions were detected in 50.0% of patients (n = 16) and were 90.7% smaller than 24 h and 46.5% smaller than 3 months. Lesions were more frequently visible on SWI (100%, n = 17), DWI (n = 38, 97.4%) and ADC (n = 36, 92.3%). At 3 months, fewer treatment sonications, higher maximum power, and greater distance between individual sonications led to larger lesion volumes. Volume at 24 h did not predict if a lesion was visible later. Lesion visibility at 3 months predicted sensory side effects but was not correlated with tremor outcomes.

Discussion

Overall, lesions are visible on T2-weighted MRI in about half of patients at both 3 months and 1 year post-MRgFUS thalamotomy. Certain sonication parameters significantly predicted persistent volume, but residual lesions did not correlate with tremor outcomes.
The ego in psychedelic drug action – ego defenses, ego boundaries, and the therapeutic role of regression
Authors: Buchborn Tobias , Kettner Hannes S. , Kärtner Laura , Meinhardt Marcus W.
Published: October 2023

The ego is one of the most central psychological constructs in psychedelic research and a key factor in psychotherapy, including psychedelic-assisted forms of psychotherapy. Despite its centrality, the ego-construct remains ambiguous in the psychedelic literature. Therefore, we here review the theoretical background of the ego-construct with focus on its psychodynamic conceptualization. We discuss major functions of the ego including ego boundaries, defenses, and synthesis, and evaluate the role of the ego in psychedelic drug action. According to the psycholytic paradigm, psychedelics are capable of inducing regressed states of the ego that are less protected by the ego’s usual defensive apparatus. In such states, core early life conflicts may emerge that have led to maladaptive ego patterns. We use the psychodynamic term character in this paper as a potential site of change and rearrangement; character being the chronic and habitual patterns the ego utilizes to adapt to the everyday challenges of life, including a preferred set of defenses. We argue that in order for psychedelic-assisted therapy to successfully induce lasting changes to the ego’s habitual patterns, it must psycholytically permeate the characterological core of the habits. The primary working principle of psycholytic therapy therefore is not the state of transient ego regression alone, but rather the regressively favored emotional integration of those early life events that have shaped the foundation, development, and/or rigidification of a person’s character – including his or her defense apparatus. Aiming for increased flexibility of habitual ego patterns, the psycholytic approach is generally compatible with other forms of psychedelic-assisted therapy, such as third wave cognitive behavioral approaches.
An experimental platform for stochastic analyses of single serotonergic fibers in the mouse brain
Authors: Mays Kasie C. , Haiman Justin H. , Janušonis Skirmantas
Published: October 2023

The self-organization of the serotonergic matrix, a massive axon meshwork in all vertebrate brains, is driven by the structural and dynamical properties of its constitutive elements. Each of these elements, a single serotonergic axon (fiber), has a unique trajectory and can be supported by a soma that executes one of the many available transcriptional programs. This “individuality” of serotonergic neurons necessitates the development of specialized methods for single-fiber analyses, both at the experimental and theoretical levels. We developed an integrated platform that facilitates experimental isolation of single serotonergic fibers in brain tissue, including regions with high fiber densities, and demonstrated the potential of their quantitative analyses based on stochastic modeling. Single fibers were visualized using two transgenic mouse models, one of which is the first implementation of the Brainbow toolbox in this system. The trajectories of serotonergic fibers were automatically traced in the three spatial dimensions with a novel algorithm, and their properties were captured with a single parameter associated with the directional von Mises-Fisher probability distribution. The system represents an end-to-end workflow that can be imported into various studies, including those investigating serotonergic dysfunction in brain disorders. It also supports new research directions inspired by single-fiber analyses in the serotonergic matrix, including supercomputing simulations and modeling in physics.
Beneficial effects of silibinin on serum lipids, bile acids, and gut microbiota in methionine-choline-deficient diet-induced mice
Authors: Wang Wei , Zhai Ting , Luo Ping , Miao Xiaolei , Wang Junjun , Chen Yong
Published: October 2023

Background and purpose

Silibinin (SIL) is a flavonoid lignin isolated from the fruit and seeds of silybum marianum that exhibits good therapeutic potential for NASH. However, the effects of SIL on serum lipids, bile acids (BAs), and gut microbiota (GM) in NASH mice remain unknown. The present work aimed to explore the beneficial effects of SIL supplementation on serum lipids, bile acids, and gut microbiota in MCD mice.

Experimental approach

After male C57BL/6 mice were fed with a methionine-choline deficient (MCD) diet and simultaneously gavaged with SIL (20 mg/kg. d) for 8 weeks, the pathological changes of liver tissue were observed by oil red O, haematoxylin-eosin, and Masson tricolor staining; the levels of serum AST and ALT, and liver TG and MDA were detected by assay kits; metabonomics and 16S rDNA sequencing were used to analyze the composition of serum lipids and BAs and the abundance of GM; and the mRNA expression levels of hepatic genes related to BAs homeostasis were detected by RT-qPCR.

Results

The results indicated that SIL treatment decreased the levels of 26 lipids (including four arachidonic acids, seven FFAs, 12 acyl carnitines, and three GPs) and two BAs (23-DCA, GLCA), while Dubosiella increased the levels of 10 lipids (including TxB3, PG16:0_18:1, Cer t18:0/24:0 and 7 TGs), five BAs (β-MCA, α-MCA, UDCA, 3-oxo-DCA and HCA), and two GMs (Verrucomicrobiota and Akkermansiaceae) of MCD mice, but had no significant effect on the mRNA expression of CYP7A1, CYP27A1, Bsep, Mrp2, Ntcp, or Oatp1b2. Therefore, influencing GM composition and then regulating the levels of serum lipids and BAs through enterohepatic axis should be an important mechanism of SIL-induced alleviative effect on MCD mice. More importantly, we found that SIL had a good coordination in regulating the abundance of GM and the contents of serum lipids and BAs in MCD mice, that is, when the abundance of probiotics was up-regulated, the content of beneficial unsaturated fatty acids in serum was up-regulated, while the serum levels of harmful lipids and BAs were down-regulated.

Conclusion

The alleviating effect of SIL on NASH may be closely related to the correction of intestinal bacteria disorder, serum bile acid, and lipid metabolic disturbance in mice.
Ecological stoichiometry and homeostasis characteristics of plant-litter-soil system with vegetation restoration of the karst desertification control
Authors: Hu Tinghui , Xiong Kangning , Yu Yanghua , Wang Jun , Wu Yawei
Published: October 2023

It is of great significance to clarify the ecologically chemical stoichiometric characteristics of plant-litter-soil in vegetation restoration process for elucidating the nutrient cycling law and soil nutrient management of karst ecosystem. The carbon (C), nitrogen (N) and phosphorus (P) contents of leaves, litter and soil and their stoichiometry were determined in loquat (Eribotrya japonica) plantations in a karst plateau canyon after 3, 6, 10 and 15 years of restoration. The homeostasis characteristics of leaf N, P, and N:P with the change in soil nutrients during restoration were revealed. The results showed that leaf C, N, and P contents initially increased and then decreased with increasing years of restoration at the same sampling time. The contents of nutrients in soil and litter varied with increasing restoration years, with the highest values mostly appearing in May and July. This could be due to greater moisture in May and July, which helps with nutrient absorption and transformation. The leaf N:P ratio of loquat with different restoration years was 35.76-47.39, with an average of 40.06. Therefore, loquat leaves may experience P limitation in the growth process. The relationships between N, P and N:P in leaves and soil indexes could be simulated by a homeostasis model. Except for the weak sensitivity of loquat leaf N in 10 years, the other indexes and treatments had a certain homeostasis. Plants maintain homeostasis by regulating physiological responses in vivo in response to soil nutrient changes, indicating that loquat has good adaptability in karst desertification environments, but attention should focus on the management of soil P in the field as part of the vegetation restoration process. Therefore, in future research, we should combine the soil water and fertilizer conditions of different growing seasons in karst rocky desertification areas and provide scientific field management to ensure that the results of rocky desertification management can play a role in rural revitalization.
The nature and organization of satellite DNAs in Petunia hybrida, related, and ancestral genomes
Authors: Alisawi Osamah , Richert-Pöggeler Katja R. , Heslop-Harrison J.S. (Pat) , Schwarzacher Trude
Published: October 2023

Introduction

The garden petunia, Petunia hybrida (Solanaceae) is a fertile, diploid, annual hybrid species (2n=14) originating from P. axillaris and P. inflata 200 years ago. To understand the recent evolution of the P. hybrida genome, we examined tandemly repeated or satellite sequences using bioinformatic and molecular cytogenetic analysis.

Methods

Raw reads from available genomic assemblies and survey sequences of P. axillaris N (PaxiN), P. inflata S6, (PinfS6), P. hybrida (PhybR27) and the here sequenced P. parodii S7 (PparS7) were used for graph and k-mer based cluster analysis of TAREAN and RepeatExplorer. Analysis of repeat specific monomer lengths and sequence heterogeneity of the major tandem repeat families with more than 0.01% genome proportion were complemented by fluorescent in situ hybridization (FISH) using consensus sequences as probes to chromosomes of all four species.

Results

Seven repeat families, PSAT1, PSAT3, PSAT4, PSAT5 PSAT6, PSAT7 and PSAT8, shared high consensus sequence similarity and organisation between the four genomes. Additionally, many degenerate copies were present. FISH in P. hybrida and in the three wild petunias confirmed the bioinformatics data and gave corresponding signals on all or some chromosomes. PSAT1 is located at the ends of all chromosomes except the 45S rDNA bearing short arms of chromosomes II and III, and we classify it as a telomere associated sequence (TAS). It is the most abundant satellite repeat with over 300,000 copies, 0.2% of the genomes. PSAT3 and the variant PSAT7 are located adjacent to the centromere or mid-arm of one to three chromosome pairs. PSAT5 has a strong signal at the end of the short arm of chromosome III in P. axillaris and P.inflata, while in P. hybrida additional interstitial sites were present. PSAT6 is located at the centromeres of chromosomes II and III. PSAT4 and PSAT8 were found with only short arrays.

Discussion

These results demonstrate that (i) repeat families occupy distinct niches within chromosomes, (ii) they differ in the copy number, cluster organization and homogenization events, and that (iii) the recent genome hybridization in breeding P. hybrida preserved the chromosomal position of repeats but affected the copy number of repetitive DNA.
Inhibition of ethylene involved in resistance to E. turcicum in an exotic-derived double haploid maize population
Authors: Lipps Sarah , Lipka Alexander E. , Mideros Santiago , Jamann Tiffany
Published: October 2023

Northern corn leaf blight (NCLB) is an economically important disease of maize. While the genetic architecture of NCLB has been well characterized, the pathogen is known to overcome currently deployed resistance genes, and the role of hormones in resistance to NCLB is an area of active research. The objectives of the study were (i) to identify significant markers associated with resistance to NCLB, (ii) to identify metabolic pathways associated with NCLB resistance, and (iii) to examine role of ethylene in resistance to NCLB. We screened 252 lines from the exotic-derived double haploid BGEM maize population for resistance to NCLB in both field and greenhouse environments. We used a genome wide association study (GWAS) and stepwise regression to identify four markers associated with resistance, followed by a pathway association study tool (PAST) to identify important metabolic pathways associated with disease severity and incubation period. The ethylene synthesis pathway was significant for disease severity and incubation period. We conducted a greenhouse assay in which we inhibited ethylene to examine the role of ethylene in resistance to NCLB. We observed a significant increase in incubation period and a significant decrease in disease severity between plants treated with the ethylene inhibitor and mock-treated plants. Our study confirms the potential of the BGEM population as a source of novel alleles for resistance. We also confirm the role of ethylene in resistance to NCLB and contribute to the growing body of literature on ethylene and disease resistance in monocots.
The MISLI-Drive, a modular sterilizable robotic driver for steerable laparoscopic instruments
Authors: Lenssen Tomas , Bîrjac Radu , Dankelman Jenny , Horeman Tim
Published: October 2023

Introduction:Based on the success of the former “Shaft-Actuated, Tip-Articulated” SATA-Drive, a prototype robotic instrument driver for modular, steerable, laparoscopic instruments, a new driver is designed and tested to improve previously lacking features concerning cleanability, instrument adaptation, practical application and control. The design of the driver engages these issues with a modular design aimed at re-use of both the instrument and the driver, for which a set of design requirements are established.

Methods:A new modular design has been developed to improve cleanability through separation of the electro-motors and the instrument mechanism which clutches the instrument. Contamination of the driver’s robotic side is prevented though a combination of a drape and a Sterile barrier interface, while the instrument side is made sterilizable. A novel instrument clutching mechanism enables quick-release features, while a motor-axis latching mechanism enables plug-and-play assembly. Embedded sensors allow precise and fast control. A user-experiment was conducted on instrument exchange and assembly time, while mechanical and electrical tests were conducted on the driver’s responsiveness.

Results:The driver has proven its ability to control the instrument, after which it can be disassembled for cleaning and inspection. The driver is designed for re-use through disassembled sterilization where all possibly contaminated surfaces are exposable for cleaning and inspection. The new standardized instrument clutches allow easy instrument (dis-)assembly. Instrument exchange is possible in two methods, the fastest of which is a median of 11 (6.3–14.6) seconds. The driver’s instrument mechanism is separated in a median of 3.7 (1.8–8.1) seconds. After assembly, the driver is operational in less than 2 s.

Discussion:Instrument exchange times are similar to the semi-reusable Da Vinci systems, yet the MISLI-Drive is designed for sterilization, inspection and continual re-use. The modular build of the driver also allows easier parts replacement during maintenance, and requires minimal adaptation to different future scenarios, which is expected to reduce the overall cost of use.
Exploring the effects of lysozyme dietary supplementation on laying hens: performance, egg quality, and immune response
Authors: Sindaye Daniel , Xiao Zaili , Wen Chaoyu , Yang Kang , Zhang Limeng , Liao Pinfeng , Zhang Fan , Xin Zhongquan , He Shansong , Ye Shibin , Guo Dan , Hang Suqin , Zeid Shehata , Deng Baichuan
Published: October 2023

An experiment was conducted to evaluate the dietary supplementation with lysozyme's impacts on laying performance, egg quality, biochemical analysis, body immunity, and intestinal morphology. A total of 720 Jingfen No. 1 laying hens (53 weeks old) were randomly assigned into five groups, with six replicates in each group and 24 hens per replicate. The basal diet was administered to the laying hens in the control group, and it was supplemented with 100, 200, 300, or 400 mg/kg of lysozyme (purity of 10% and an enzyme activity of 3,110 U/mg) for other groups. The preliminary observation of the laying rate lasted for 4 weeks, and the experimental period lasted for 8 weeks. The findings demonstrated that lysozyme might enhance production performance by lowering the rate of sand-shelled eggs (P < 0.05), particularly 200 and 300 mg/kg compared with the control group. Lysozyme did not show any negative effect on egg quality or the health of laying hens (P > 0.05). Lysozyme administration in the diet could improve intestinal morphology, immune efficiency, and nutritional digestibility in laying hens when compared with the control group (P < 0.05). These observations showed that lysozyme is safe to use as a feed supplement for the production of laying hens. Dietary supplementation with 200 to 300 mg/kg lysozyme should be suggested to farmers as a proper level of feed additive in laying hens breeding.
Relationship Between Effort-Reward Imbalance, Over-Commitment and Occupational Burnout in the General Population: A Prospective Cohort Study
Authors: Shoman Yara , Ranjbar Setareh , Strippoli Marie-Pierre , von Känel Roland , Preisig Martin , Guseva Canu Irina
Published: October 2023

Objectives: To prospectively investigate the association between Effort-Reward Imbalance (ERI) and over-commitment and the scores of the burnout dimensions over a 4 years follow-up period considering potential confounders.

Methods: Data stemmed from CoLaus|PsyCoLaus, a population-based cohort study including 575 participants (mean age 55 years, 50% men). Participants completed the Maslach Burnout Inventory-General Survey, ERI and over-commitment questionnaires at baseline (T1) and after a 4 years follow-up (T2), and provided demographic, behavioral, psychiatric, personality and social support information through self-reported questionnaires and semi-structured interviews. Serially adjusted linear regression models were used.

Results: ERI and over-commitment were not associated longitudinally with any of the burnout dimensions when controlling for confounders. One standard deviation increases in the scores of exhaustion, cynicism and professional efficacy were associated with one standard deviation increase in the scores of the same burnout dimensions longitudinally, and these associations were independent of the effects of ERI and over-commitment.

Conclusion: Future studies should re-examine the effect of ERI and over-commitment on workers’ burnout, considering the effects of confounders.
Metabolomic Analysis of Arabidopsis ost1-4 Mutant Revealed the Cold Response Regulation Mechanisms by OPEN STOMATA 1 (OST1) at Metabolic Level
Authors: Wu Fangming , Du Zhimin , Hu Zhengrong , Gan Lu , Khaldun Abul Bashar Mohammad , Amombo Erick , Huang Xuebing , Fan Jibiao
Published: October 2023

Cold stress is one of the major abiotic stresses that limits the growth and development of plants. Improving the cold tolerance of plants is essential to enhance crop productivity in the changing environment. OPEN STOMATA 1 (OST1), also known as sucrose non-fermenting 1 related protein kinases 2.6/2E (SnRK2.6/SnRK2E), has been reported to involved in cold stress response in plants. This interesting protein is confined to expressed in guard cells and vascular system. However, the detailed mechanism of how OST1 regulates cold stress, especially at the metabolomic level is largely unknown. In this study, metabolomic profiling of ost1 mutant and WT Arabidopsis plants under cold stress was investigated. The results showed that ost1-4 mutants displayed cold sensitive phenotypes compared with the WT plant, as evidenced by higher MDA content and electrolyte leakage and lower photosynthetic characteristics. Next, the metabolic changes between ost1-4 and WT plants in response to cold stress was analyzed by using the GC-TOF-MS system. The results showed that numbers of metabolites were identified to be related to OST1 regulated cold stress response. A large portion of the metabolites were carbohydrates and organic acids. The KEGG enrichment analysis revealed that the alanine, aspartate and glutamate metabolism, cyanoamino acid metabolism and citrate cycle (TCA cycle) were presumptive pathways that most related to OST1 regulated cold stress response. Gene expression such as AtGDHs, AtPPC1 and AtAK1 was also in line with the metabolic changes in the presumed pathways. Overall, this study provides fundamental knowledge for understanding the underlying metabolic mechanisms of OST1 mediated cold stress response in plants.
Blood-Based Markers for Skeletal and Cardiac Muscle Function in Eventing Horses before and after Cross-Country Rides and How They Are Influenced by Plasma Volume Shift
Authors: Giers Johanna , Bartel Alexander , Kirsch Katharina , Müller Simon Franz , Horstmann Stephanie , Gehlen Heidrun
Published: October 2023

Horses competing in cross-country tests are subjected to high physical demands. Within the scope of this prospective longitudinal study, blood values of 20 elite eventing horses were examined before and after two- to four-star cross-country rides. The aim was to find out whether blood-based markers for skeletal muscle and cardiac muscle function change after cross-country exercise. Parameters that provide information about fluid balance, muscle enzymes, metabolites and cardiac muscle-specific markers were investigated. We developed an approach to eliminate the concentration changes caused by reduced plasma volume. Parameters were measured pre, 10 and 30 min post exercise and the next morning and were evaluated using a mixed model. Thirty minutes after exercise, most parameter concentrations changed in an exercise-dependent manner. The next morning, most exercise-related markers recovered rapidly, while creatine kinase (CK) (26% increase; p = 0.008) and lactate dehydrogenase (LDH) (15% increase; p < 0.001) showed a declining but sustained increase. Cardiac troponin I (cTnI) increased above the reference range in 40 of the 55 rides (73%) and in 18 of 20 horses in the morning after exercise.