bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipocyte dysfunction promotes lung inflammation and aberrant repair: a potential target of COPD
Authors: Zhang Si-jin , Qin Xian-zheng , Zhou Jie , He Bin-feng , Shrestha Surendra , Zhang Jing , Hu Wei-ping
Published: October 2023

Background

Obesity and chronic obstructive pulmonary disease (COPD) are prevailing worldwide, bringing a heavy medical burden. Clinical and pathophysiological relationship between obesity and COPD is paradoxical and elusive. We aim to explore their inherent associations from clinical, genetic, and animal levels.

Methods

We performed literature review and cohort analysis of patients with COPD to compare lung function, symptom, and prognosis among different weight groups. After retrieving datasets of obesity and COPD in Gene Expression Omnibus (GEO) database, we carried out differentially expressed gene analysis, functional enrichment, protein–protein interactions network, and weighted gene co-expression network analysis. Then, we acquired paraffin-embedded lung tissues of fatty acid–binding protein 4–Cre-BMPR2fl/fl conditional knockout (CKO) mice that were characterized by adipocyte-specific knockout of bone morphogenetic protein receptor 2 (BMPR2) for staining and analysis.

Results

Our cohort study reports the effect of obesity on COPD is inconsistent with previous clinical studies. Lung function of overweight group was statistically superior to that of other groups. We also found that the inflammatory factors were significantly increased hub genes, and cytokine-associated pathways were enriched in white adipose tissue of patients with obesity. Similarly, injury repair–associated genes and pathways were further enhanced in the small airways of patients with COPD. CKO mice spontaneously developed lung injury, emphysema, and pulmonary vascular remodeling, along with increased infiltration of macrophages. BMPR2-defiecient adipocytes had dysregulated expression of adipocytokines.

Conclusion

Inflammation and abnormal repair might be potential mechanisms of the pathological association between obesity and COPD. BMPR2-associated adipocyte dysfunction promoted lung inflammation and aberrant repair, in which adipocytokines might play a role and thus could be a promising therapeutic target.
HbA1c: an independent risk factor for dysthyroid optic neuropathy
Authors: Wang Xing , Ye Huijing , Chen Rongxin , Yang Shenglan , Zhang Te , Xiao Wei , Yang Huasheng
Published: October 2023

Background

We aimed to explore the frequencies of islet β-cell autoantibodies and insulin resistance (IR) in thyroid-associated ophthalmopathy (TAO) and identify specific diabetes mellitus (DM) indicators as early predictors for dysthyroid optic neuropathy (DON).

Methods

Ninety-eight TAO patients (57 DON and 41 non-DON patients) and 48 healthy control (HC) participants were recruited for this prospective cross-sectional study. Serum thyroxine, serum thyroid autoantibodies, serum humoral immune markers against islet β-cell, fasting plasma glucose (FPG), fasting serum insulin (FINS), fasting c-peptide (FCP), and glycosylated hemoglobin A1 (HbA1c) were measured. Logistic regression analysis was used to evaluate the correlation of patients’ age, body mass index (BMI), FPG, HbA1c, and related indexes of islet β-cell function to the occurrence of DON.

Results

The DON group had higher FPG (P<0.001, 0.016) and HbA1c (P<0.0001, P<0.001) levels than the HC and non-DON groups. The homeostasis model assessment (HOMA)-IR level was the highest in the DON group (HC 2.15 ± 0.89, non-DON 2.41 ± 1.24, and DON 2.82 ± 2.65), while the HOMA-β level was the lowest (HC 101.8 ± 44.75%, non-DON 102.9 ± 54.61%, and DON 88.29 ± 52.75%), with no significant differences (P=1, P>0.05). On univariate analysis, age (P=0.006), BMI (P=0.022), history of steroid use (P=0.014), FPG (P=0.013), and HbA1c (P=0.001) levels were significantly associated with the presence/absence of DON. In addition, after adjusting for potential confounds, the HbA1c level was an independent factor associated with DON (P=0.009, OR=4.012).

Conclusions

HbA1c is an independent risk factor for DON. Given the interconnected link between thyroid dysfunction and DM, the use of HbA1c as a potential biomarker for DON warrants further investigation.
Study on the economic benefits of carbon-neutral digital platforms for sustainable development based on the GPT-QRCNN model
Authors: Yang Huifang , Zhou Xiang
Published: October 2023

Introduction

This article proposes a method for assessing the economic benefits of carbon-neutral digital platforms, which promote sustainable development by reducing carbon emissions through digital technology and data platforms.

Methods

The proposed method combines the GPT (Generative Pre-trained Transformer) and QRCNN (Quantile Regression Convolutional Neural Network) models. Firstly, the GPT model is utilized to extract features from platform data. Then, these features are combined with the QRCNN model for sequence modeling, enhancing prediction accuracy and generalization ability.

Results

The method's effectiveness is demonstrated through experimental verification using actual platform data. The results highlight the practical significance and application value of the proposed method in evaluating the economic benefits of carbon-neutral digital platforms.

Discussion

By leveraging digital technology and data platforms, carbon-neutral digital platforms aim to reduce carbon emissions and promote sustainable development. The proposed method provides a means to accurately predict and analyze the economic benefits associated with these platforms. The combination of the GPT and QRCNN models enhances the accuracy and generalization ability of economic benefit predictions, enabling informed decision-making and policy formulation.
Possible contribution of rare alleles of human ACE2 in the emergence of SARS-CoV-2 variants escaping the immune response
Authors: Devaux Christian A. , Fantini Jacques
Published: October 2023

Since the start of the SARS-CoV-2 pandemic, the rapid replacement of one lineage by another has been observed. Indeed, SARS-CoV-2 is evolving through a quasispecies mechanism leading to post-infection mutation selection under positive evolutionary pressure (host-driven viral evolution). These mutations may reduce the effectiveness of the specific neutralizing immune response against the virus. We provide here evidence that apart from the selection of SARS-CoV-2 variants by the immune system, selection by the cellular receptor can just as well select variants which escape neutralization.
Retrospective analysis of autoimmune bullous diseases in Middle Franconia
Authors: Sollfrank Lukas , Schönfelder Valerie , Sticherling Micheal
Published: October 2023

Introduction

Autoimmune bullous diseases (AIBDs) are a group of rare cutaneous disorders affecting cornified skin and mucous membranes. They are characterized by tense or flaccid blistering and erosions due to autoantibodies against desmosomal and hemidesmosomal structural proteins of the skin. This group of disorders can be divided into those of pemphigoid and those of pemphigus diseases. If left untreated, these autoimmune diseases can cause serious or even life-threatening complications such as loss of fluid, superinfections or impaired food intake. Due to modern standardized serological assays, the diagnosis of AIBDs can usually be confirmed in combination with their clinical appearance. Whereas for a long time corticosteroids were the major players in the treatment of these diseases, with the approval of rituximab and other immunosuppressive agents, the therapy has increasingly improved.

Methods

In this study, we aimed to investigate epidemiologic and clinical features as well as diagnostics and therapy of bullous autoimmune diseases in Middle Franconia, a governorate within the German federal state of Bavaria. Patients diagnosed or treated because of a AIBDs between 01.04.2013 and 31.03.2019 at the dermatological department of the university hospital Erlangen were included in this retrospective study (n = 242). Patients were either diagnosed for the first time (n=176) or the diagnosis has been confirmed (n=66) at the department. The respective incidence was calculated among the 176 subjects who had been diagnosed at the center in this period. Data was taken from patient records and analyzed with Microsoft® Excel. The evaluation included the diagnoses of pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), linear IgA dermatosis (LAD), epidermolysis bullosa acquisita (EBA), and dermatitis herpetiformis (DH).

Results

This study shows that the incidence of each AIBDs in Middle Franconia is low and comparable (PV, PF, LAD, EBA) or lower (BP, MMP, DH) than in other studies and regions. BP is the most common newly diagnosed AIBD in Middle Franconia.

Discussion

Due to the chronic and sometimes severe course of AIBDs, repeated in-house treatments are often necessary. To date, mainly topically and systemically applied corticosteroids in combination with immunomodulators are used as first-line therapy.
L-methionine supplementation modulates IgM+ B cell responses in rainbow trout
Authors: Martín Diana , Ordás M. Camino , Carvalho Inês , Díaz-Rosales Patricia , Nuñez-Ortiz Noelia , Vicente-Gil Samuel , Arrogante Aitor , Zarza Carlos , Machado Marina , Costas Benjamín , Tafalla Carolina
Published: October 2023

The interest in dietary amino acids (AAs) as potential immunomodulators has been growing the recent years, since specific AAs are known to regulate key metabolic pathways of the immune response or increase the synthesis of some immune-related proteins. Methionine, tryptophan and lysine are among the ten essential AAs for fish, meaning that they cannot be produced endogenously and must be provided through the diet. To date, although dietary supplementation of fish with some of these AAs has been shown to have positive effects on some innate immune parameters and disease resistance, the effects that these AAs provoke on cells of the adaptive immune system remained unexplored. Hence, in the current study, we have investigated the effects of these three AAs on the functionality of rainbow trout (Oncorhynchus mykiss) IgM+ B cells. For this, splenic leukocytes were isolated from untreated adult rainbow trout and incubated in culture media additionally supplemented with different doses of methionine, tryptophan or lysine in the presence or absence of the model antigen TNP-LPS (2,4,6-trinitrophenyl hapten conjugated to lipopolysaccharide). The survival, IgM secreting capacity and proliferation of IgM+ B cells was then studied. In the case of methionine, the phagocytic capacity of IgM+ B cells was also determined. Our results demonstrate that methionine supplementation significantly increases the proliferative effects provoked by TNP-LPS and also up-regulates the number of cells secreting IgM, whereas tryptophan or lysine have either minor or even negative effects on rainbow trout IgM+ B cells. This increase in the number of IgM-secreting cells in response to methionine surplus was further verified in a feeding experiment, in which the beneficial effects of methionine on the specific response to anal immunization were also confirmed. The results presented demonstrate the beneficial effects of dietary supplementation with methionine on the adaptive immune responses of fish.
The nexus of dynamic T cell states and immune checkpoint blockade therapy in the periphery and tumor microenvironment
Authors: Luo Hong , Wang Wenxiang , Mai Jia , Yin Rutie , Cai Xuyu , Li Qintong
Published: October 2023

Immune checkpoint blockade (ICB) therapies, that is, using monoclonal antibodies to reinvigorate tumor-reactive, antigen-specific T cells from the inhibitory effects of CTLA-4, PD-1 and PD-L1 immune checkpoints, have revolutionized the therapeutic landscape of modern oncology. However, only a subset of patients can benefit from the ICB therapy. Biomarkers associated with ICB response, resistance and prognosis have been subjected to intensive research in the past decade. Early studies focused on the analysis of tumor specimens and their residing microenvironment. However, biopsies can be challenging to obtain in clinical practice, and do not reflect the dynamic changes of immunological parameters during the ICB therapy. Recent studies have investigated profiles of antigen-specific T cells derived from the peripheral compartment using multi-omics approaches. By tracking the clonotype and diversity of tumor-reactive T cell receptor repertoire, these studies collectively establish that de novo priming of antigen-specific T cells in peripheral blood occurs throughout the course of ICB, whereas preexisting T cells prior to ICB are exhausted to various degrees. Here, we review what is known about ICB-induced T cell phenotypic and functional changes in cancer patients both within the tumor microenvironment and in the peripheral compartment. A better understanding of parameters influencing the response to ICBs will provide rationales for developing novel diagnostics and combinatorial therapeutic strategies to maximize the clinical efficacies of ICB therapies.
Accuracy of new intraocular lens calculation formulas in Chinese eyes with short axial lengths
Authors: Ma Yueting , Lin Yongdong , Li Yuancun , Hu Zhuoyi , Qiu Kunliang
Published: October 2023

Purpose

To compare the measurement accuracy of new/updated intraocular lens (IOL) power calculation methods, namely, Kane, Emmetropia Verifying Optical (EVO), with existing methods (Barrett Universal II, Olsen, Haigis, Hoffer Q, Holladay 1, SRK/T) in Chinese eyes with axial lengths ≤ 22.5 mm.

Methods

The study included data from patients who underwent uneventful cataract surgery with the insertion of ZCB00 IOL. Refractive prediction errors were determined by calculating the difference between postoperative refraction and the predicted refraction using each formula. Various parameters were evaluated, including mean prediction error (ME), mean absolute error (MAE), median absolute error (MedAE), and the percentage of eyes with prediction errors (PE) within different ranges.

Results

The study enrolled 38 eyes of 38 patients, and the Barrett Universal II formula demonstrated the lowest MAE and MedAE among the tested formulas. Post hoc analysis using Wilcoxon signed-rank pairwise comparisons for non-parametric samples with Bonferroni correction revealed no significant difference in postoperative refractive prediction among all the formulas (P > 0.05). The percentage of eyes with PE within ± 0.5 D was as follows: Barrett Universal II, 81.58%; Haigis, 78.95%; EVO, 76.32%; Olsen, 76.32%; Holladay I, 73.68%; SRK/T, 71.05%; Kane, 68.42%; and Hoffer Q, 65.79%.

Conclusion

The Barrett Universal II formula was more accurate than the other formulas for Chinese eyes with AL ≤ 22.5 mm.
Identification of acacia gum fermenting bacteria from pooled human feces using anaerobic enrichment culture
Authors: Rawi Muhamad Hanif , Tan Hui Yan , Sarbini Shahrul Razid
Published: October 2023

Commercial acacia gum (AG) used in this study is a premium-grade free-flowing powder. It is a gummy exudate composed of arabinogalactan branched polysaccharide, a biopolymer of arabinose and galactose. Also known as food additive, acacia gum (E414), which is presently marketed as a functional dietary fiber to improve overall human gut health. The health effects may be related to the luminal pH regulation from the short-chain fatty acids (SCFA) production. Studies suggested that amylolytic and butyrogenic pathways are the major factors determining the SCFA outcome of AG in the lower gut. However, the primary bacteria involved in the fermentation have not been studied. This study aimed to investigate the putative primary degraders of acacia gum in the gut ecosystem. Isolation and identification of gum-fermenting bacteria were performed through enrichment culture fermentation. The experiment was conducted in an anaerobic chamber for 144 h in three stages. The study was conducted in triplicate using an anaerobic chamber system. This culture system allows specific responses to support only bacteria that are responsible for gum fermentation among the gut microbiota. Five bacterial strains were isolated and found to be gum-fermenting bacteria. Based on the 16s RNA sequence, the isolates matched to butyrate-producing Escherichia fergusonii, ATCC 35469.
Construction of pseudorabies virus variant attenuated vaccine: codon deoptimization of US3 and UL56 genes based on PRV gE/TK deletion strain
Authors: Xu Mengwei , Zhu Laixu , Ge Aimin , Liu Yamei , Chen Saisai , Wei Ziwen , Zheng Yating , Tong Ling , Wang Zhisheng , Fei Rongmei , Wang Jichun , Zhang Chuanjian
Published: October 2023

Since 2011, pseudorabies based on the pseudorabies virus (PRV) variant has emerged as a serious health issue in pig farms in China. The PRV gE/TK or gE/gI/TK deletion strains protect against emerging PRV variants. However, these variants may cause lethal infections in newborn piglets without PRV antibodies. Previous studies have shown that codon deoptimization of a virulence gene causes virus attenuation. Accordingly, we deoptimized US3-S (US3 gene encoding a short isoform that represents approximately 95% of the total US3 transcription) and UL56 genes (first 10 or all codons) of PRV gE/TK deletion strain (PRVΔTK&gE−AH02) to generate six recombinant PRVs through bacterial artificial chromosome technology. In swine testicular cells, recombinant PRVs with all codon deoptimization of US3-S or UL56 genes were grown to lower titers than the parental virus. Notably, US3-S or UL56 with all codon deoptimization reduced mRNA and protein expressions. Subsequently, the safety and immunogenicity of recombinant PRVs with codon deoptimization of US3-S or UL56 are evaluated as vaccine candidates in mice and piglets. The mice inoculated with recombinant PRVs with codon deoptimization of US3-S or UL56 showed exceptional survival ability without severe clinical signs. All codons deoptimized (US3-S and UL56) significantly decreased virus load and attenuated pathological changes in the brains of the mice. Moreover, the protection efficiency offered by recombinant PRVs with codon deoptimization of US3-S or UL56 showed similar effects to PRVΔTK&gE−AH02. Remarkably, the 1-day-old PRV antibody-negative piglets inoculated with PRVΔTK&gE-US3-ST−CD (a recombinant PRV with all codon deoptimization of US3-S) presented no abnormal clinical symptoms, including fever. The piglets inoculated with PRVΔTK&gE-US3-ST−CD showed a high serum neutralization index against the PRV variant. In conclusion, these results suggest using codon deoptimization to generate innovative live attenuated PRV vaccine candidates.
Enhanced brain functional connectivity and activation after 12-week Tai Chi-based action observation training in patients with Parkinson’s disease
Authors: Meng Lin , Wang Deyu , Shi Yu , Li Zhuo , Zhang Jinghui , Lu Hanna , Zhu Xiaodong , Ming Dong
Published: October 2023

Introduction

Motor-cognitive interactive interventions, such as action observation training (AOT), have shown great potential in restoring cognitive function and motor behaviors. It is expected that an advanced AOT incorporating specific Tai Chi movements with continuous and spiral characteristics can facilitate the shift from automatic to intentional actions and thus enhance motor control ability for early-stage PD. Nonetheless, the underlying neural mechanisms remain unclear. The study aimed to investigate changes in brain functional connectivity (FC) and clinical improvement after 12 weeks of Tai Chi-based action observation training (TC-AOT) compared to traditional physical therapy (TPT).

Methods

Thirty early-stage PD patients were recruited and randomly assigned to the TC-AOT group (N = 15) or TPT group (N = 15). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after 12 weeks of training and clinical assessments. The FCs were evaluated by seed-based correlation analysis based on the default mode network (DMN). The rehabilitation effects of the two training methods were compared while the correlations between significant FC changes and clinical improvement were investigated.

Results

The results showed that the TC-AOT group exhibited significantly increased FCs between the dorsal medial prefrontal cortex and cerebellum crus I, between the posterior inferior parietal lobe and supramarginal gyrus, and between the temporal parietal junction and clusters of middle occipital gyrus and superior temporal. Moreover, these FC changes had a positive relationship with patients’ improved motor and cognitive performance.

Discussion

The finding supported that the TC-AOT promotes early-stage PD rehabilitation outcomes by promoting brain neuroplasticity where the FCs involved in the integration of sensorimotor processing and motor learning were strengthened.
Development and evaluation of a robotic system for lumbar puncture and epidural steroid injection
Authors: Lu Jiaxin , Huang Zekai , Zhuang Baiyang , Cheng Zhuoqi , Guo Jing , Lou Haifang
Published: October 2023

Introduction

Lumbar puncture is an important medical procedure for various diagnostics and therapies, but it can be hazardous due to individual variances in subcutaneous soft tissue, especially in the elderly and obese. Our research describes a novel robot-assisted puncture system that automatically controls and maintains the probe at the target tissue layer through a process of tissue recognition.

Methods

The system comprises a robotic system and a master computer. The robotic system is constructed based on a probe consisting of a pair of concentric electrodes. From the probe, impedance spectroscopy measures bio-impedance signals and transforms them into spectra that are communicated to the master computer. The master computer uses a Bayesian neural network to classify the bio-impedance spectra as corresponding to different soft tissues. By feeding the bio-impedance spectra of unknown tissues into the Bayesian neural network, we can determine their categories. Based on the recognition results, the master computer controls the motion of the robotic system.

Results

The proposed system is demonstrated on a realistic phantom made of ex vivo tissues to simulate the spinal environment. The findings indicate that the technology has the potential to increase the precision and security of lumbar punctures and associated procedures.

Discussion

In addition to lumbar puncture, the robotic system is suitable for related puncture operations such as discography, radiofrequency ablation, facet joint injection, and epidural steroid injection, as long as the required tissue recognition features are available. These operations can only be carried out once the puncture needle and additional instruments reach the target tissue layer, despite their ensuing processes being distinct.
Progression events defined by home-based assessment of motor function in multiple sclerosis: protocol of a prospective study
Authors: Dorsch Eva-Maria , Röhling Hanna Marie , Zocholl Dario , Hafermann Lorena , Paul Friedemann , Schmitz-Hübsch Tanja
Published: October 2023

Background

This study relates to emerging concepts of appropriate trial designs to evaluate effects of intervention on the accumulation of irreversible disability in multiple sclerosis (MS). Major starting points of our study are the known limitations of current definitions of disability progression by rater-based clinical assessment and the high relevance of gait and balance dysfunctions in MS. The study aims to explore a novel definition of disease progression using repeated instrumental assessment of relevant motor functions performed by patients in their home setting.

Methods

The study is a prospective single-center observational cohort study with the primary outcome acquired by participants themselves, a home-based assessment of motor functions based on an RGB-Depth (RGB-D) camera, a camera that provides both depth (D) and color (RGB) data. Participants are instructed to perform and record a set of simple motor tasks twice a day over a one-week period every 6 months. Assessments are complemented by a set of questionnaires. Annual research grade assessments are acquired at dedicated study visits and include clinical ratings as well as structural imaging (MRI and optical coherence tomography). In addition, clinical data from routine visits is provided semiannually by treating neurologists. The observation period is 24 months for the primary endpoint with an additional clinical assessment at 27 month to confirm progression defined by the Expanded Disability Status Scale (EDSS). Secondary analyses aim to explore the time course of changes in motor parameters and performance of the novel definition against different alternative definitions of progression in MS. The study was registered at Deutsches Register für Klinische Studien (DRKS00027042).

Discussion

The study design presented here investigates disease progression defined by marker-less home-based assessment of motor functions against 3-month confirmed disease progression (3 m-CDP) defined by the EDSS. The technical approach was chosen due to previous experience in lab-based settings. The observation time per participant of 24, respectively, 27 months is commonly conceived as the lower limit needed to study disability progression. Defining a valid digital motor outcome for disease progression in MS may help to reduce observation times in clinical trials and add confidence to the detection of progression events in MS.
New insights and potential clinical implications of the odds ratio product
Authors: Younes Magdy
Published: October 2023

The odds ratio product (ORP) is a continuous metric of sleep depth that ranges from 0 (very deep sleep) to 2. 5 (full wakefulness). Its advantage over the conventional method recommended by AASM is that it discloses different levels of stage wake (sleep propensity) and different sleep depths within the same sleep stage. As such, it can be used to identify differences in sleep depth between subjects, and in the same subjects under different circumstances, when differences are not discernible by conventional staging. It also identifies different sleep depths within stage rapid-eye-movement sleep, with possible implications to disorders during this stage. Epoch-by-epoch ORP can be displayed graphically across the night or as average values in conventional sleep stages. In addition, ORP can be reported as % of recording time in specific ORP ranges (e.g., deciles of the total ORP range) where it produces distinct distribution patterns (ORP-architecture) that have been associated with different clinical disorders and outcomes. These patterns offer unique research opportunities to identify different mechanisms and potential therapy for various sleep complaints and disorders. In this review I will discuss how ORP is measured, its validation, differences from delta power, and the various phenotypes, and their postulated mechanisms, identified by ORP architecture and the opportunities for research to advance management of sleep-disordered breathing, insomnia and idiopathic hypersomnia.
Astaxanthin promotes locomotor function recovery and attenuates tissue damage in rats following spinal cord injury: a systematic review and trial sequential analysis
Authors: Zhou Long-yun , Wu Zi-ming , Chen Xu-qing , Yu Bin-bin , Pan Meng-xiao , Fang Lu , Li Jian , Cui Xue-jun , Yao Min , Lu Xiao
Published: October 2023

Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant activities, is finding its new application in the field of SCI. Here, we performed a systematic review to assess the neurological roles of AST in rats following SCI, and assessed the potential for clinical translation. Searches were conducted on PubMed, Embase, Cochrane Library, the Web of Science, China National Knowledge Infrastructure, WanFang data, Vip Journal Integration Platform, and SinoMed databases. Animal studies that evaluated the neurobiological roles of AST in a rat model of SCI were included. A total of 10 articles were included; most of them had moderate-to-high methodological quality, while the overall quality of evidence was not high. Generally, the meta-analyses revealed that rats treated with AST exhibited an increased Basso, Beattie, and Bresnahan (BBB) score compared with the controls, and the weighted mean differences (WMDs) between those two groups showed a gradual upward trend from days 7 (six studies, n = 88, WMD = 2.85, 95% CI = 1.83 to 3.87, p < 0.00001) to days 28 (five studies, n = 76, WMD = 6.42, 95% CI = 4.29 to 8.55, p < 0.00001) after treatment. AST treatment was associated with improved outcomes in spared white matter area, motor neuron survival, and SOD and MDA levels. Subgroup analyses indicated there were differences in the improvement of BBB scores between distinct injury types. The trial sequential analysis then firmly proved that AST could facilitate the locomotor recovery of rats following SCI. In addition, this review suggested that AST could modulate oxidative stress, neuroinflammation, neuron loss, and autophagy via multiple signaling pathways for treating SCI. Collectively, with a protective effect, good safety, and a systematic action mechanism, AST is a promising candidate for future clinical trials of SCI. Nonetheless, in light of the limitations of the included studies, larger and high-quality studies are needed for verification.
Mediterranean diet affects the metabolic outcome of metabolic dysfunction-associated fatty liver disease
Authors: Xiao Yuji , Zhang Xue , Yi Dongxin , Qiu Fangyi , Wu Lei , Tang Yiyong , Wang Ningning
Published: October 2023

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is on the rise globally. It is currently one of the most prevalent liver diseases and one of the world’s important public health problems. At present, there is no consensus on a pharmacological treatment for MAFLD. By contrast, lifestyle interventions based on exercise and a balanced diet are considered to be the cornerstone of MAFLD management. Mediterranean diet (MD) have a large content of polyphenols, polyunsaturated fatty acids, oleic acid, carotenoids and fiber, which carry out antioxidant, anti-inflammatory and antibacterial benefits. It has been considered to reduce the incidence rate of cardiovascular disease and type 2 diabetes. The purpose of this narrative review is therefore to summarize and analyze the evidence for the effect of MD on metabolic outcomes in MAFLD patients.
Combined effect of serum carcinoembryonic antigen and hepatic steatosis on new-onset ischemic heart disease among middle-aged and older Korean adults: a cohort study
Authors: Kwak Ji Won , Lee Yong Jae , Park Byoungjin , Jung Dong Hyuk
Published: October 2023

Background

Carcinoembryonic antigen (CEA) is a commonly used tumor marker in cancer screening. However, it has also been associated with metabolic alterations. Hepatic steatosis, the accumulation of fat in liver cells, is associated with various cardiovascular risk factors. This study investigated the risk of ischemic heart disease (IHD) in individuals with elevated CEA levels, hepatic steatosis, and their co-occurrence.

Methods

The study cohort comprised 5,580 Korean adults who underwent health examinations between November 2006 and June 2010. Data regarding baseline CEA levels, hepatic steatosis status, and development of IHD were collected. Hepatic steatosis was defined as more than two findings: deep attenuation, vascular blurring, and increased liver echogenicity on abdominal ultrasound. Participants were divided into four groups based on their CEA and hepatic steatosis status: no hepatic steatosis and low CEA (group 1), no hepatic steatosis and elevated CEA (group 2), low CEA and hepatic steatosis (group 3), and elevated CEA and hepatic steatosis (group 4).

Results

A total of 226 (4.1%) participants developed IHD during the follow-up period. Participants with elevated CEA levels and hepatic steatosis (group 4) had the highest cumulative incidence of IHD in comparison to other groups (p < 0.001). The combined effect of elevated CEA levels and hepatic steatosis showed significantly greater area under the receiver operating characteristic curve than hepatic steatosis alone (p < 0.001). Furthermore, participants with elevated CEA and hepatic steatosis (group 4) had higher risk of developing IHD compared to those with low CEA and no hepatic steatosis (group 1) (hazard ratio: 1.63, 95% confidence interval: 1.04–2.55, p = 0.034).

Conclusion

Co-occurrence of elevated CEA levels and hepatic steatosis increases the risk of IHD. Comprehensive risk assessment is crucial to guide interventions and improve cardiovascular health in individuals with both the conditions.
VRK3 depletion induces cell cycle arrest and metabolic reprogramming of pontine diffuse midline glioma - H3K27 altered cells
Authors: Menez Virginie , Kergrohen Thomas , Shasha Tal , Silva-Evangelista Claudia , Le Dret Ludivine , Auffret Lucie , Subecz Chloé , Lancien Manon , Ajlil Yassine , Vilchis Irma Segoviano , Beccaria Kévin , Blauwblomme Thomas , Oberlin Estelle , Grill Jacques , Castel David , Debily Marie-Anne
Published: October 2023

We previously identified VRK3 as a specific vulnerability in DMG-H3K27M cells in a synthetic lethality screen targeting the whole kinome. The aim of the present study was to elucidate the mechanisms by which VRK3 depletion impact DMG-H3K27M cell fitness. Gene expression studies after VRK3 knockdown emphasized the inhibition of genes involved in G1/S transition of the cell cycle resulting in growth arrest in G1. Additionally, a massive modulation of genes involved in chromosome segregation was observed, concomitantly with a reduction in the level of phosphorylation of serine 10 and serine 28 of histone H3 supporting the regulation of chromatin condensation during cell division. This last effect could be partly due to a concomitant decrease of the chromatin kinase VRK1 in DMG following VRK3 knockdown. Furthermore, a metabolic switch specific to VRK3 function was observed towards increased oxidative phosphorylation without change in mitochondria content, that we hypothesized would represent a cell rescue mechanism. This study further explored the vulnerability of DMG-H3K27M cells to VRK3 depletion suggesting potential therapeutic combinations, e.g. with the mitochondrial ClpP protease activator ONC201.
Optimization of therapeutic strategies for selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in patients with rectal cancer with clinical suspected lateral lymph node metastasis
Authors: Liu Yuan , Bao Mandoula , Jiang Yujuan , Li Feng , Xing Wei , Yang Zhufeng , Liu Qian
Published: October 2023

Background

Selective lateral lymph node (LLN) dissection with total mesorectal excision after neoadjuvant chemoradiotherapy (nCRT) is pointed out to reduce lateral compartment recurrence and to improve survival in patients with rectal cancer with LLN metastases. This study aimed to explore the safety, surgical indications, and survival outcomes of LLN dissection after nCRT.

Methods

This multicenter retrospective study included patients with rectal cancer with clinical evidence of LLN metastases (n = 466) treated across three hospitals in China. Patients who underwent total mesorectal excision and LLN dissection were grouped into nCRT (n = 155) and non-nCRT (n = 291), respectively. Propensity score matching was used to minimize selection bias.

Results

After matching, nCRT did not significantly increase the surgery duration, intraoperative blood loss or postoperative complications (P > 0.05). In a multivariate logistic regression analysis, poor/mucinous/signet adenocarcinoma (P = 0.042) and post-nCRT LLN short diameter ≥7 mm (P < 0.001) were independent risk factors for pathological LLN metastasis after nCRT. Overall survival (P < 0.001) and disease-free survival (P < 0.001) were significantly worse in patients with LLN metastasis, which was, however, not an independent risk factor for survival after eliminating confounders. Multivariate prognostic analysis of 40-patient subset with pathological LLN metastasis showed that distant metastasis, metastasis beyond the obturator or internal iliac region, and ≥2 LLN metastasis were independent predictors of poor overall survival.

Conclusions

Selective LLN dissection after nCRT is safe and feasible with acceptable perioperative outcomes. Patients with a post-nCRT LLN short diameter ≥7 mm or poor/mucinous/signet adenocarcinoma should receive supplementary LLN dissection after nCRT. However, patients with distant metastasis, metastasis beyond the obturator or internal iliac region, and involvement of ≥2 LLN may not benefit from LLN dissection, and LLN dissection should be carefully considered in such patients.
Fragment-pair based drug molecule solubility prediction through attention mechanism
Authors: Liu Jianping , Lei Xiujuan , Ji Chunyan , Pan Yi
Published: October 2023

The purpose of drug discovery is to identify new drugs, and the solubility of drug molecules is an important physicochemical property in medicinal chemistry, that plays a crucial role in drug discovery. In solubility prediction, high-precision computational methods can significantly reduce the experimental costs and time associated with drug development. Therefore, artificial intelligence technologies have been widely used for solubility prediction. This study utilized the attention layer in mechanism in the deep learning model to consider the atomic-level features of the molecules, and used gated recurrent neural networks to aggregate vectors between layers. It also utilized molecular fragment technology to divide the complete molecule into pairs of fragments, extracted characteristics from each fragment pair, and finally fused the characteristics to predict the solubility of drug molecules. We compared and evaluated our method with five existing models using two performance evaluation indicators, demonstrating that our method has better performance and greater robustness.
Impairment of exocytotic transmitter release by decynium-22 through an inhibition of ion channels
Authors: Haar Gabriele , Hrachova Katsiaryna , Wagner Tanja , Boehm Stefan , Schicker Klaus
Published: October 2023

Introduction: In addition to members of the family of Na+/Cl− dependent monoamine transporters, organic cation transporters (OCTs), in particular OCT3, as well as the plasma membrane monoamine transporter (PMAT) may contribute to neuronal reuptake of according neurotransmitters. As opposed to the numerous blockers of monoamine transporters, only a very limited number of specific blockers of OCT3 and PMAT are available. In fact, decynium-22 is the only blocking agent with micromolar affinities for both transport proteins, and this molecule is frequently used to establish roles of OCT3 and/or PMAT as targets for antidepressant drugs and psychostimulants, respectively.

Methods/Results: To test for a function of these transporters in the sympathetic nervous system, uptake and release of [3H]1-methyl-4-phenylpyridinium (MPP+) was investigated in primary cultures of rat superior cervical ganglia. Uptake was reduced by cocaine or desipramine, blockers of the noradrenaline transporter, by about 70% and by corticosterone or β-estradiol, blockers of OCT3, by about 30%; decynium-22 achieved complete inhibition of uptake with half maximal effects at 3 μM. Depolarization dependent release was enhanced by corticosterone or β-estradiol, but reduced by decynium-22. As the latter effect is unlikely to be related to actions at OCT3 and/or PMAT, electrophysiological recordings were performed to reveal that decynium-22 inhibits action potential firing and currents through voltage activated calcium channels in superior cervical ganglion neurons.

Discussion: These results demonstrate that decynium-22 can impair exocytotic neurotransmitter release by interfering with several types of ion channels. Such transporter-independent effects of decynium-22 that my interfere with basic neuronal functions need to be considered when interpreting results obtained with decynium-22 as prototypic inhibitor of transmitter reuptake via OCT3 and/or PMAT.
Effects of postponing nitrogen topdressing on starch structural properties of superior and inferior grains in hybrid indica rice cultivars with different taste values
Authors: Yuan Xiaojuan , Luo Yongheng , Yang Yonggang , Chen Kairui , Wen Yanfang , Luo Yinghan , Li Bo , Ma Yangming , Guo Changchun , Chen Zongkui , Yang Zhiyuan , Sun Yongjian , Ma Jun
Published: October 2023

Introduction

Nitrogen (N) fertilizer management, especially postponing N topdressing can affect rice eating quality by regulating starch quality of superior and inferior grains, but the details are unclear. This study aimed to evaluate the effects of N topdressing on starch structure and properties of superior and inferior grains in hybrid indica rice with different tastes and to clarify the relationship between starch structure, properties, and taste quality.

Methods

Two hybrid indica rice varieties, namely the low-taste Fyou 498 and high-taste Shuangyou 573, were used as experimental materials. Based on 150 kg·N hm-2, three N fertilizer treatments were established: zero N (N0), local farmer practice (basal fertilizer: tillering fertilizer: panicle fertilizer=7:3:0) (N1), postponing N topdressing (basal fertilizer: tillering fertilizer: panicle fertilizer=3:1:6) (N2).

Results

The starch granules of superior grains were more complete, and the decrease in small granules content and the stability of starch crystals were a certain extent less than those of inferior grains. Compared with N1, under N2, low-taste and high-taste varieties large starch granules content were significantly reduced by 6.89%, 0.74% in superior grains and 4.26%, 2.71% in inferior grains, the (B2 + B3) chains was significantly reduced by 1.61%, 0.98% in superior grains, and 1.18%, 0.97% in inferior grains, both reduced the relative crystallinity and 1045/1022 cm-1, thereby decreasing the stability of the starch crystalline region and the orderliness of starch granules. N2 treatment reduced the ΔHgel of two varieties. These changes ultimately contributed to the enhancement of the taste values in superior and inferior grains in both varieties, especially the inferior grains. Correlation analysis showed that the average starch volume diameter (D[4,3]) and relative crystallinity were significantly positively correlated with the taste value of superior and inferior sgrains, suggesting their potential use as an evaluation index for the simultaneous enhancement of the taste value of rice with superior and inferior grains.

Discussion

Based on 150 kg·N hm-2, postponing N topdressing (basal fertilizer: tillering fertilizer: panicle fertilizer=3:1:6) promotes the enhancement of the overall taste value and provides theoretical information for the production of rice with high quality
Human-like interactions prompt people to take a robot’s perspective
Authors: Ye Tian , Minato Takashi , Sakai Kurima , Sumioka Hidenobu , Hamilton Antonia , Ishiguro Hiroshi
Published: October 2023

The increasing need for human-robot interaction requires not only robots to understand how humans think, but also humans to understand robots. Interestingly, little attention has been given to how humans interpret robots’ behaviors. In this study, we adopted a social mental rotation task and investigated whether socially engaging behaviors could influence how people take a robot’s perspectives. In a real lab, two android robots with neutral appearance sat opposite each other by a table with conflicting perspectives. Before the participant started the experiment, one of the robots behaved more interactively than the other by showing more socially engaging behaviors. Then the participant was required to identify rotated normal or mirrored digits presented inbetween the two robots. Results revealed a significant interactive effect between the digits type (normal; mirrored) and robot type (interactive; noninteractive). When digits were oriented to the interactive robot, we found a larger RT difference between normal and mirrored digits. In general, these findings suggested that robots’ interactive behaviors could influence how people spontaneously consider the robot’s perspective. Future studies may further consider how interactive behaviors can shape human-robot relationships and facilitate human-robot interaction.
Workplace coaching: a meta-analysis and recommendations for advancing the science of coaching
Authors: Cannon-Bowers Janis A. , Bowers Clint A. , Carlson Catherine E. , Doherty Shannon L. , Evans Jocelyne , Hall Julie
Published: October 2023

Workplace coaching has experienced a dramatic rise in popularity over the past decade and is one of the fastest growing performance-enhancing interventions used by modern organizations. Yet, despite its popularity, workplace coaching has not been the subject of much empirical research and a true science of coaching has yet to be developed. The purpose of this research was to update prior meta-analyzes that investigated the impact of coaching on organizational outcomes and to provide recommendations for how the field needs to evolve. Results indicated that, consistent with prior meta-analyzes, workplace coaching is effective in achieving positive organizational outcomes. The effects of several moderators were also investigated. Finally, we discuss the results in terms of recommendations for future directions that we believe will establish and advance the science of coaching.
The complex relation between obstructive sleep apnoea syndrome, hypogonadism and testosterone replacement therapy
Authors: Graziani Andrea , Grande Giuseppe , Ferlin Alberto
Published: October 2023

Obstructive sleep apnoea syndrome (OSAS) is an under-recognized medical disease. The main risk factors for OSAS are male sex, older age, obesity, and metabolic syndrome, that are also associated with male hypogonadism (MH). Therefore, obesity has been classically identified as the most evident link between OSAS and MH. However, OSAS is per se linked to the development of MH by a combined effect of hypoxia, increased night-time awakenings, reduced sleep efficiency and fragmented sleep. Similarly, MH might represent a risk factor for OSAS, mainly related to sleep disturbances that are frequently associated with low testosterone. Data on testosterone replacement therapy (TRT) in patients with OSAS are limited. Nevertheless, TRT is generally contraindicated by guidelines in the presence of untreated or severe OSAS. TRT might in fact worse OSAS symptoms in different ways. Furthermore, OSAS has been proposed to be a risk factor for secondary polycythaemia and TRT might exacerbate polycythaemia. Therefore, TRT in hypogonadal men affected by untreated OSAS or severe OSAS should be considered with caution and in a personalised way. Nevertheless, the type and dosage of TRT should be considered, as short-term high-dose TRT might worsen OSAS, whereas long-term lower doses could eventually determine a clinical improvement of symptoms of OSAS. Here we reviewed the data on the association between OSAS, MH and TRT, including the opportunity of assessment of patients who develop signs and symptoms of OSAS during TRT by polysomnography.