bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebellar contributions to fear-based emotional processing: relevance to understanding the neural circuits involved in autism
Authors: Couto-Ovejero Sabina , Ye Jingjing , Kind Peter C. , Till Sally M. , Watson Thomas C.
Published: November 2023

Cerebellar networks have traditionally been linked to sensorimotor control. However, a large body of evidence suggests that cerebellar functions extend to non-motor realms, such as fear-based emotional processing and that these functions are supported by interactions with a wide range of brain structures. Research related to the cerebellar contributions to emotional processing has focussed primarily on the use of well-constrained conditioning paradigms in both human and non-human subjects. From these studies, cerebellar circuits appear to be critically involved in both conditioned and unconditioned responses to threatening stimuli in addition to encoding and storage of fear memory. It has been hypothesised that the computational mechanism underlying this contribution may involve internal models, where errors between actual and expected outcomes are computed within the circuitry of the cerebellum. From a clinical perspective, cerebellar abnormalities have been consistently linked to neurodevelopmental disorders, including autism. Importantly, atypical adaptive behaviour and heightened anxiety are also common amongst autistic individuals. In this review, we provide an overview of the current anatomical, physiological and theoretical understanding of cerebellar contributions to fear-based emotional processing to foster further insights into the neural circuitry underlying emotional dysregulation observed in people with autism.
Efficacy and safety of tyrosine kinase inhibitors plus PD-1 inhibitor in patients with transarterial chemoembolization- refractory hepatocellular carcinoma: a two-center retrospective study
Authors: Gao Ya , Lu Haohao , Xiong Zhifan
Published: November 2023

Object

To investigate the efficacy and safety of tyrosine kinase inhibitors (TKIs: sorafenib and lenvatinib) plus PD-1 inhibitor (camrelizumab) versus TKIs alone in transarterial chemoembolization-refractory (TACE-refractory) hepatocellular carcinoma (HCC).

Materials and methods

Data of TACE-refractory HCC patients treated with TACE+TKIs+PD-1 inhibitor (TACE+TKIs+PD-1group) (n=57) or TACE+TKIs (TACE+TKIs group) (n=50) from January 2019 to January 2022 were retrospectively collected and analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were evaluated by univariate and multivariate analyses.

Results

Compared with the TKIs group, both PFS and OS were prolonged in the TACE+TKIs+PD-1 group (median PFS: 7 months vs. 5 months, P=0.007; median OS: 17 months vs. 11 months, P=0.002). In multivariate analysis, tumor size and treatment were independent prognostic factors for PFS and OS. The incidence and severity of AEs related to the treatment between the two groups showed no significant difference.

Conclusion

The treatment of TACE combined with TKIs plus camrelizumab demonstrated promising efficacy and safety in TACE-refractory HCC.
Latest advances in the study of non-coding RNA-mediated circadian rhythm disorders causing endometrial cancer
Authors: Zheng Ling-tao , Chen Shao-rong , Zhou Liang-yu , Huang Qiao-yi , Chen Jia-ming , Chen Wei-hong , Lin Shu , Shi Qi-yang
Published: November 2023

Endometrial cancer (EC) is one of the most common gynecological cancers, and its risk factors include obesity and metabolic, genetic, and other factors. Recently, the circadian rhythm has also been shown to be associated with EC, as the severity of EC was found to be related to night work and rhythm disorders. Therefore, circadian rhythm disorders (CRDs) may be one of the metabolic diseases underlying EC. Changes in the circadian rhythm are regulated by clock genes (CGs), which in turn are regulated by non-coding RNAs (ncRNAs). More importantly, the mechanism of EC caused by ncRNA-mediated CRDs is gradually being unraveled. Here, we review existing studies and reports and explore the relationship between EC, CRDs, and ncRNAs.
The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cells
Authors: Nguyen Mai R. , Ma Emily , Wyatt Debra , Knight Katherine L. , Osipo Clodia
Published: November 2023

Introduction

Many well-known risk factors for breast cancer are associated with dysbiosis (an aberrant microbiome). However, how bacterial products modulate cancer are poorly understood. In this study, we investigated the effect of an exopolysaccharide (EPS) produced by the commensal bacterium Bacillus subtilis on breast cancer phenotypes. Although B. subtilis is commonly included in probiotic preparations and its EPS protects against inflammatory diseases, it was virtually unknown whether B. subtilis-derived EPS affects cancer.

Methods

This work investigated effects of EPS on phenotypes of breast cancer cells as a cancer model. The phenotypes included proliferation, mammosphere formation, cell migration, and tumor growth in two immune compromised mouse models. RNA sequencing was performed on RNA from four breast cancer cells treated with PBS or EPS. IKKβ or STAT1 signaling was assessed using pharmacologic or RNAi-mediated knock down approaches.

Results

Short-term treatment with EPS inhibited proliferation of certain breast cancer cells (T47D, MDA-MB-468, HCC1428, MDA-MB-453) while having little effect on others (MCF-7, MDA-MB-231, BT549, ZR-75-30). EPS induced G1/G0 cell cycle arrest of T47D cells while increasing apoptosis of MDA-MB-468 cells. EPS also enhanced aggressive phenotypes in T47D cells including cell migration and cancer stem cell survival. Long-term treatment with EPS (months) led to resistance in vitro and promoted tumor growth in immunocompromised mice. RNA-sequence analysis showed that EPS increased expression of pro-inflammatory pathways including STAT1 and NF-κB. IKKβ and/or STAT1 signaling was necessary for EPS to modulate phenotypes of EPS sensitive breast cancer cells.

Discussion

These results demonstrate a multifaceted role for an EPS molecule secreted by the probiotic bacterium B. subtilis on breast cancer cell phenotypes. These results warrant future studies in immune competent mice and different cancer models to fully understand potential benefits and/or side effects of long-term use of probiotics.
Long-term follow-up after retrosternal ileocolic esophagoplasty in two cases of long-gap esophageal atresia: why it is still a valid option as a rescue strategy
Authors: Léonard Matthieu , Deswysen Yannick , Scheers Isabelle , Thoma Maximilien , de Magnée Catherine , Stephenne Xavier , Dumitriu Dana , Menten Renaud , Reding Raymond , Tambucci Roberto
Published: November 2023

Introduction

Esophageal replacement surgery in children is sometimes necessary for long-gap esophageal atresia. Ileocolic esophagoplasty in the retrosternal space can serve as a good alternative technique in case of hostile posterior mediastinum. We present two cases of successful ileocolic transposition performed at 6 months of age.

Methods

Esophageal replacement was performed through a midline laparotomy incision associated with a left cervical approach. The ileocolic transplant was pediculized on the right superior colic artery after ligating the right colic and ileocolic vessels. A retrosternal tunnel was created, and the ileocolic transplant pulled through it to reach the cervical region. Proximally, esophageal-ileal anastomosis and, distally, colonic–gastric anastomosis were performed. Ileocolic continuity was repaired.

Results

There were no early postoperative complications. In both cases, the patients presented oral feeding difficulties during the first 6 postoperative months. Thereafter, full oral feeding was achieved, and both patients were clinically asymptomatic during the following 18 and 20 years, respectively, with satisfactory oral radiological assessments, showing no redundancy or inappropriate growth of the graft and no anastomotic stricture. Currently, these patients do not complain of dysphagia, pathological reflux, or respiratory symptoms.

Conclusion

When native esophagus preservation in long-gap esophageal atresia is estimated unfeasible, ileocolic transposition in the retrosternal space might be considered a good and safe option, particularly in those difficult cases after multiple previous surgical attempts and mediastinitis. This technique is putatively associated with a beneficial anti-reflux effect, thanks to the presence of the ileocecal valve, in preventing cervical peptic esophagitis. Long-term follow-up confirms that the transposed colon in the retrosternal space did not suffer any abnormal modification in size and growth.
Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells
Authors: Wan Xingyang , Zhou Qian , Chen Huaxian , Li Zhen , Mo Mianling , Liu Zhimin , Zhang Heng , He Zhuojie , Xiao Guozhong , Zheng Yihui , Lin Hongcheng , Ren Donglin
Published: November 2023

Purpose: Slow transit constipation (STC) is a common gastrointestinal disorder characterized by altered gut microbiota and reduced number of enterochromaffin cells (ECs). Astragaloside IV (AS-IV), a low drug permeability saponin, has showed beneficial effects on patients with STC. However, the specific mechanism by which AS-IV regulates STC remains unclear. In this study, we aimed to investigate the effect of AS-IV on STC and its associated mechanisms involving gut microbiota.

Methods: The effect of AS-IV on STC was evaluated on STC mice induced with loperamide. We measured defecation frequency, intestinal mobility, ECs loss, and colonic lesions in STC mice treated with AS-IV. We also analyzed the changes in gut microbiota and metabolites after AS-IV treatment. Moreover, we investigated the relationship between specific gut microbes and altered fecal metabolites, such as 3-bromotyrosine (3-BrY). We also conducted in vitro experiments to investigate the effect of 3-BrY on caspase-dependent apoptosis of ECs and the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.

Results: AS-IV treatment promoted defecation, improved intestinal mobility, suppressed ECs loss, and alleviated colonic lesions in STC mice. AS-IV treatment also affected gut microbiota and metabolites, with a significant correlation between specific gut microbes and altered fecal metabolites such as 3-BrY. Furthermore, 3-BrY may potentially reduce caspase-dependent apoptosis of ECs and protect cell survival by inhibiting the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.

Conclusion: Our findings suggest that changes in gut microbiota and ECs mediated the therapeutic effect of STC by AS-IV. These results provide a basis for the use of AS-IV as a prebiotic agent for treating STC. The specific mechanism by which AS-IV regulates gut microbiota and ECs warrants further investigation.
Total flavonoids extracted from Penthorum chinense Pursh mitigates CCl4-induced hepatic fibrosis in rats via inactivation of TLR4-MyD88-mediated NF-κB pathways and regulation of liver metabolism
Authors: Wang Sujuan , Li Wenqing , Liu Wenxiu , Yu Lei , Peng Fu , Qin Junyuan , Pu Lin , Tang Yunli , Xie Xiaofang , Peng Cheng
Published: November 2023

Background:Penthorum chinense Pursh (PCP) is widely utilized in China to treat a variety of liver diseases. It has been shown that flavonoids inhibit inflammation and have the potential to attenuate tissue damage and fibrosis. However, the mechanisms underlying how total flavonoids isolated from PCP (TFPCP) exert their anti-fibrotic effects remain unclear.

Methods: The chemical composition of TFPCP was determined using UHPLC–Q-Orbitrap HRMS. Subsequently, rats were randomly assigned to a control group (Control), a carbon tetrachloride (CCl4)-induced hepatic fibrosis model group (Model), a positive control group [0.2 mg/(kg∙day)] of Colchicine), and three TFPCP treatment groups [50, 100, and 150 mg/(kg∙day)]. All substances were administered by gavage and treatments lasted for 9 weeks. Simultaneously, rats were intraperitoneally injected with 10%–20% CCl4 for 9 weeks to induce liver fibrosis. At the end of the experiment, the liver ultrasound, liver histomorphological, biochemical indicators, and inflammatory cytokine levels were tested respectively. The underlying mechanisms were assessed using Western blot, immunohistochemistry, immunofluorescence, RT-qPCR, and metabolomics.

Results: Fourteen flavonoids were identified in TFPCP. Compared with control animals, CCl4-treated rats demonstrated obvious liver injury and fibrosis, manifested as increases in gray values, distal diameter of portal vein (DDPV) and a decrease in blood flow velocity (VPV) in the ultrasound analysis; increased biochemical index values (serum levels of ALT, AST, TBIL, and ALP); marked increases in the contents of fibrotic markers (PC III, COL4, LN, HA) and inflammatory factors (serum TNF-α, IL-6, and IL-1β); and significant pathological changes. However, compared with the Model group, the ultrasound parameters were significantly improved and the serum levels of inflammatory cytokines were reduced in the TFPCP group. In contrast, the expression of TGF-β1, TLR4, and MyD88, as well as the p-P65/P65 and p-IκBα/IκBα ratios, were considerably reduced following TFPCP treatment. In addition, we identified 32 metabolites exhibiting differential abundance in the Model group. Interestingly, TFPCP treatment resulted in the restoration of the levels of 20 of these metabolites.

Conclusion: Our findings indicated that TFPCP can ameliorate hepatic fibrosis by improving liver function and morphology via the inactivation of the TLR4/MyD88-mediated NF-κB pathway and the regulation of liver metabolism.
Pharmacokinetics, pharmacodynamics, and safety of ciprofol emulsion in Chinese subjects with normal or impaired renal function
Authors: Tao Jun , Liu Shuaibing , Zhao Ying Ying , Qi Lei , Yan Pangke , Wu Nan , Liu Xiao , Liu Dongwei , Tian Xin
Published: November 2023

Background: Ciprofol, a novel sedative–hypnotic drug, has been approved for its use in inducing and maintaining general anesthesia, as well as for providing sedation.

Methods: In this phase I, single-center, parallel, controlled, open-label clinical trial, our objective was to analyze the pharmacokinetics (PK), pharmacodynamics (PD), and safety of ciprofol emulsion in 24 participants with mild and moderate renal impairment (n = 8 per group) and matched healthy participants (n = 8). An initial loading infusion of ciprofol was administered at 0.4 mg/kg for 1 min, followed by a maintenance infusion at a rate of 0.4 mg/kg/h for 30 min. We collected plasma and urine samples from the participants to assess the PK of ciprofol and its metabolite M4. The evaluation of PD involved using a modified observer’s alertness/sedation scale (MOAA/S) in combination with bispectral index (BIS) monitoring. Safety assessments were conducted throughout the trial process.

Results: The plasma concentration–time curve of ciprofol in participants with renal impairment was similar to that in participants with normal kidney function. The area under the curve (AUC) and maximum concentration (Cmax) of total and unbound ciprofol in plasma for participants with renal impairment were only slightly higher (0.7–1.2-fold) than those in participants with normal renal function. In contrast, for the metabolite M4, AUC values were 1.3- and 2.1-fold greater in participants with mild and moderate renal impairment, respectively, than in healthy controls. However, renal impairment had no significant impact on the PD parameters. The study found that ciprofol was well-tolerated, with all adverse events (AEs) reported being mild or moderate in severity.

Conclusion: Based on these findings, we can conclude that no dosage adjustment of ciprofol is necessary for patients with mild–moderate renal impairment who receive the injection.

Clinical Trial Registration:https://clinicaltrials.gov, identifier NCT04142970.
Genome-wide CRISPR/Cas9 screening for drug resistance in tumors
Authors: Zhang Zhongyan , Wang Hailiang , Yan Qian , Cui Jinwei , Chen Yubin , Ruan Shiye , Yang Jiayu , Wu Zelong , Han Mingqian , Huang Shanzhou , Zhou Qi , Zhang Chuanzhao , Hou Baohua
Published: November 2023

Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9) screening is a simple screening method for locating loci under specific conditions, and it has been utilized in tumor drug resistance research for finding potential drug resistance-associated genes. This screening strategy has significant implications for further treatment of malignancies with acquired drug resistance. In recent years, studies involving genome-wide CRISPR/Cas9 screening have gradually increased. Here we review the recent application of genome-wide CRISPR/Cas9 screening for drug resistance, involving mitogen-activated protein kinase (MAPK) pathway inhibitors, poly (ADP-ribose) polymerase inhibitors (PARPi), alkylating agents, mitotic inhibitors, antimetabolites, immune checkpoint inhibitors (ICIs), and cyclin-dependent kinase inhibitors (CDKI). We summarize drug resistance pathways such as the KEAP1/Nrf2 pathway MAPK pathway, and NF-κB pathway. Also, we analyze the limitations and conditions for the application of genome-wide CRISPR/Cas9 screening techniques.
Gut microbiome and metabolome in aneurysm rat with hypertension after ginsenoside Rb1 treatment
Authors: Zeng Zhaobin , Wang Haibin , Yi Renhui , Lou Jianyun , Wen Shuting , Hu Zheng
Published: November 2023

Introduction: Hypertension is a well-known risk factor for aneurysms, as high blood pressure can worsen the development and rupture of aneurysms. Ginsenoside, derived from ginseng and widely used in traditional herbal medicine, is believed to have antihypertensive properties. Recent research has also shown a connection between gut microbiota and various diseases, including hypertension. However, the relationship between ginsenosides, gut microbiota, blood pressure, and intracranial aneurysms needs further exploration.

Methods: In this study, a rat model was used to investigate the effects of ginsenosides on both blood pressure and intracranial arteries. Comparative analysis was conducted, and 16S rRNA sequencing was employed to identify marker genera within the gut microbiota. Metabolites were also analyzed to uncover potential mediators of blood pressure regulation.

Results and Discussion: The results of this study revealed that ginsenosides, particularly ginsenoside Rb1, demonstrated positive effects in reducing both blood pressure and the development of intracranial aneurysms in rats. Furthermore, the analysis of gut microbiota showed that certain genera, including Clostridium, Roseburia, Ruminococcus, and Treponema, were significantly influenced by ginsenoside treatment. Several metabolites, such as behenic acid, N-Acetylserotonin, Prostaglandin F2a, and Vitamin D2, were also detected, all of which play a role in regulating blood pressure. These findings provide valuable insights into the potential benefits of ginsenosides in hypertension and atheroma development. Furthermore, they suggest a possible link between ginsenosides, gut microbiota, and blood pressure regulation. Further research is needed to fully understand the mechanisms underlying these effects and to determine the clinical implications for treating hypertension and reducing the risk of aneurysm development.
Predictive modeling of Alfvén eigenmode stability in inductive scenarios in JT-60SA
Authors: Coelho R. , Vincenzi P. , Vallar M. , Rodrigues P. , Tholerus E. , Särkimäki K. , Garcia J. , Borba D. , Nabais F. , Calado R. , Ferreira J. , Figueiredo A.
Published: November 2023

The JT-60SA device offers unique conditions before ITER for the study of the interaction of energetic particles with plasma waves. With similar dimensions to JET, e.g., a major radius but with a slightly more elongated plasma volume, JT-60SA is used as a high-power device where additional heating power (including 10 MW of the 500 keV Neutral Beam Injection) of up to 41 MW and the potential for high non-inductive plasma current operation pave the path for numerous challenges in physics on MHD stability, in particular, when considering the effects of energetic particles. Several operational scenarios with ITER and DEMO-relevant plasma regimes, in terms of non-dimensional plasma parameters, are anticipated. In this work, the stability of Alfvén eigenmodes (AEs) in variants of two of the most relevant operational scenarios with single null is analyzed: a full Ip inductive scenario at high density (1.1 × 1020 m−3 on-axis electron density) and 5.48MA/2.05T toroidal plasma current and magnetic field, and an advanced (hybrid) scenario with an ion energy transport barrier (ITB) and 3.5MA/2.28T toroidal plasma current and magnetic field. The workflow included the CRONOS code to establish the scenario, the ASCOT code to calculate the slowing-down energetic particle distributions for a positive/negative ion source-based neutral beam, and the MISHKA/CASTOR-K suite to calculate the MHD spectra of AEs and the associated drive/damping contributions from the NBI energetic ions, as well as the thermal ion landau damping. The systematic analysis, over a large Fourier space of the toroidal mode number/mode frequency, provides evidence that although a significant fraction of supra-Alfvénic particles stemming from the negative ion source-based neutral beam (500 keV) can, in some cases, drive to AEs in both scenarios, it is not enough to overcome the thermal ion landau damping. In addition, the advanced scenario with ITB is shown to be stable against AEs localized in the vicinity of the barrier as well, offering good prospects of sustainability of the plasma performance and of ITB. Finally, some sensitivity scan results are shown on the influence of fast ion density and q-profile on the AE mode spectra and stability.
A range ambiguity classification algorithm for automotive LiDAR based on FPGA platform acceleration
Authors: Li Haoyu , Xiang Sihua , Zhang Lu , Zhu Jianzhong , Wang Song , Wang You
Published: November 2023

In the past decade, the automotive light detection and ranging (LiDAR) has been experiencing a rapid expansion stage. Many researchers have been involved in the research of LiDARs and have installed it in vehicles as a means of enhancing autopilot capabilities. Compared with a traditional millimeter wave radar, LiDARs have many advantages such as the high imaging resolution, long measurement range, and the ability to reconstruct 3D information around the vehicle. These features make LiDARs one of the crucial research hotspots in the field of autopilot. The basic principles of LiDARs are the same as those of a laser rangefinder. The distance information can be obtained by locating the echo instant corresponding to the laser emission moment. But if the interval between two adjacent laser pulses is extremely narrow, the regions of the light emission and echo will be overlapped. Therefore, a range ambiguity will occur and the distance information calculation process will become abnormal. Besides, the high resolution of LiDARs is also characterized by its extremely high emissions frequency. Whilst the information about the surrounding environment of an automotive car can be retrieved more accurately, it means that the possibility of range ambiguity is also increasing at the same time. In this paper, we propose an algorithm for solving the range ambiguity problem of the LiDARs based on the concept of classification and can be accelerated by the FPGA approach, for the first time in the field of an automotive LiDAR. The algorithm can be performed by employing a single wavelength pulsed laser and can be specifically optimized for the demands of field programmable gate arrays (FPGAs). While guaranteeing the high resolution of LiDARs, the attenuation of the measurement ability should exceed due to the occurrence of range ambiguity. It can also match the demand for the processing speed of large amounts of point cloud information data. Through controlling the cost of the whole device, the performance of the LiDAR can be greatly improved. The result of this paper might provide a bright future of automotive LiDARs with the high data processing efficiency and the high resolution at the same time.
Global tendencies and frontier topics in hemodynamics research of intracranial aneurysms: a bibliometric analysis from 1999 to 2022
Authors: Chen Bo , Huang Siting , Zhang Liyang , Yang Liting , Liu Yuanyuan , Li Chuntao
Published: November 2023

Background: Hemodynamics plays a crucial role in the initiation, enlargement, and rupture of intracranial aneurysms (IAs). This bibliometric analysis aimed to map the knowledge network of IA hemodynamic research.

Methods: Studies on hemodynamics in IAs published from 1999 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The contributions of countries, institutions, authors, and journals were identified using VOSviewer, Scimago Graphica, and Microsoft Excel. Tendencies, frontier topics, and knowledge networks were analyzed and visualized using VOSviewer and CiteSpace.

Results: We identified 2,319 publications on hemodynamics in IAs. The annual number of publications exhibited an overall increasing trend. Among these, the United States, Japan, and China were the three major contributing countries. Capital Medical University, State University of New York (SUNY) Buffalo University, and George Mason University were the three most productive institutions. Meng H ranked first among authors regarding the number of articles and citations, while Cebral JR was first among co-cited authors. The American Journal of Neuroradiology was the top journal in terms of the number of publications, citations, and co-citations. In addition, the research topics can be divided into three clusters: hemodynamics itself, the relationship of hemodynamics with IA rupture, and the relationship of hemodynamics with IA treatment. The frontier directions included flow diverters, complications, morphology, prediction, recanalization, and four-dimensional flow magnetic resonance imaging (4D flow MRI).

Conclusion: This study drew a knowledge map of the top countries, institutions, authors, publications, and journals on IA hemodynamics over the past 2 decades. The current and future hotspots of IA hemodynamics mainly include hemodynamics itself (4D flow MRI), its relationship with IA rupture (morphology and prediction), and its relationship with IA treatment (flow diverters, complications, and recanalization).
The role of cellular senescence in skin aging and age-related skin pathologies
Authors: Chin Toby , Lee Xin Er , Ng Pei Yi , Lee Yaelim , Dreesen Oliver
Published: November 2023

Aging is the result of a gradual functional decline at the cellular, and ultimately, organismal level, resulting in an increased risk of developing a variety of chronic illnesses, such as cardiovascular disease, stroke, cancer and diabetes. The skin is the largest organ of the human body, and the site where signs of aging are most visible. These signs include thin and dry skin, sagging, loss of elasticity, wrinkles, as well as aberrant pigmentation. The appearance of these features is accelerated by exposure to extrinsic factors such as ultraviolet (UV) radiation or pollution, as well as intrinsic factors including time, genetics, and hormonal changes. At the cellular level, aging is associated with impaired proteostasis and an accumulation of macromolecular damage, genomic instability, chromatin reorganization, telomere shortening, remodelling of the nuclear lamina, proliferation defects and premature senescence. Cellular senescence is a state of permanent growth arrest and a key hallmark of aging in many tissues. Due to their inability to proliferate, senescent cells no longer contribute to tissue repair or regeneration. Moreover, senescent cells impair tissue homeostasis, promote inflammation and extracellular matrix (ECM) degradation by secreting molecules collectively known as the “senescence-associated secretory phenotype” (SASP). Senescence can be triggered by a number of different stimuli such as telomere shortening, oncogene expression, or persistent activation of DNA damage checkpoints. As a result, these cells accumulate in aging tissues, including human skin. In this review, we focus on the role of cellular senescence during skin aging and the development of age-related skin pathologies, and discuss potential strategies to rejuvenate aged skin.
Assistive diagnostic technology for congenital heart disease based on fusion features and deep learning
Authors: Wang Yuanlin , Yang Xuankai , Qian Xiaozhao , Wang Weilian , Guo Tao
Published: November 2023

Introduction:Congenital heart disease (CHD) is a cardiovascular disorder caused by structural defects in the heart. Early screening holds significant importance for the effective treatment of this condition. Heart sound analysis is commonly employed to assist in the diagnosis of CHD. However, there is currently a lack of an efficient automated model for heart sound classification, which could potentially replace the manual process of auscultation.

Methods:This study introduces an innovative and efficient screening and classification model, combining a locally concatenated fusion approach with a convolutional neural network based on coordinate attention (LCACNN). In this model, Mel-frequency spectral coefficients (MFSC) and envelope features are locally fused and employed as input to the LCACNN network. This model automatically analyzes feature map energy information, eliminating the need for denoising processes.

Discussion:The proposed classification model in this study demonstrates a robust capability for identifying congenital heart disease, potentially substituting manual auscultation to facilitate the detection of patients in remote areas.

Results:This study introduces an innovative and efficient screening and classification model, combining a locally concatenated fusion approach with a convolutional neural network based on coordinate attention (LCACNN). In this model, Mel-frequency spectral coefficients (MFSC) and envelope features are locally fused and employed as input to the LCACNN network. This model automatically analyzes feature map energy information, eliminating the need for denoising processes. To assess the performance of the classification model, comparative ablation experiments were conducted, achieving classification accuracies of 91.78% and 94.79% on the PhysioNet and HS databases, respectively. These results significantly outperformed alternative classification models.
Quantifying the effects of plant density on soybean lodging resistance and growth dynamics in maize-soybean strip intercropping
Authors: Wang Li , Cheng Bin , Zhou Tao , Jing Shuzhong , Liu Ranjin , Gao Yang , Deng Chaoyang , Ye Wenwei , Luo Zhigang , Raza Ali , Xu Mei , Wang Wenyan , Liu Weiguo , Yang Wenyu
Published: November 2023

Shading-induced soybean stem lodging is a prevalent concern in the maize (Zea mays L.)-soybean (Glycine max L. Merr.) strip intercropping system, leading to a substantial decline in yield. Nevertheless, the associations between soybean growth, stem lodging, and yield formation in this scenario remain unclear. To investigate this, the logistic and beta growth models were utilized to analyze the growth process of soybean organs (stems, leaves, branches, and pods) and the accumulation of carbohydrates (lignin, cellulose, and sucrose) at three planting densities (8.5, 10, and 12.5 plants m−2) in both strip intercropping and skip strip monoculture systems. The results indicate that shading stress caused by maize in the intercropping system reduced lignin and cellulose accumulation in soybean stems, thus decelerating soybean organ growth compared to monoculture. Furthermore, intercropped soybean at higher planting density (PD3) exhibited a 28% reduction in the maximum dry matter growth rate (cm) and a 11% decrease in the time taken to reach the maximum dry matter growth rate (te) compared to the lower planting density (PD1). Additionally, a 29% decrease in the maximum accumulation rate (cmax) of sucrose, lignin, and cellulose was observed, along with a 13% decrease in the continuous accumulation time (tc) of these carbohydrates in intercropped soybean at PD3. Interspecific and intraspecific shading stress led to a preferential allocation of assimilates into soybean stems, enhancing plant height during the initial stage, while at later stages, a greater proportion of sucrose was allocated to leaves. Consequently, this hindered the conversion of sucrose into lignin and cellulose within the stems, ultimately resulting in a reduction in the lodging resistance index (LRI). Overall, this study provides valuable insights into the effects of shading stress on soybean growth and yield. It also emphasizes how optimizing planting density in intercropping systems can effectively alleviate shading stress and enhance crop productivity.
Genome-wide analysis reveals regulatory mechanisms and expression patterns of TGA genes in peanut under abiotic stress and hormone treatments
Authors: Zhong Chao , Liu Yu , Li Zhao , Wang Xiaoguang , Jiang Chunji , Zhao Xinhua , Kang Shuli , Liu Xibo , Zhao Shuli , Wang Jing , Zhang He , Huang Yuning , Yu Haiqiu , Xue Renfeng
Published: November 2023

Introduction

The TGA transcription factors, plays a crucial role in regulating gene expression. In cultivated peanut (Arachis hypogaea), which faces abiotic stress challenges, understanding the role of TGAs is important.

Methods

In this study, we conducted a comprehensive in analysis of the TGA gene family in peanut to elucidate their regulatory mechanisms and expression patterns under abiotic stress and hormone treatments. Furthermore, functional studies on the representative AhTGA gene in peanut cultivars were conducted using transgenic Arabidopsis and soybean hair roots.

Results

The genome-wide analysis revealed that a total of 20 AhTGA genes were identified and classified into five subfamilies. Collinearity analysis revealed that AhTGA genes lack tandem duplication, and their amplification in the cultivated peanut genome primarily relies on the whole-genome duplication of the diploid wild peanut to form tetraploid cultivated peanut, as well as segment duplication between the A and B subgenomes. Promoter and Protein-protein interaction analysis identified a wide range of cis-acting elements and potential interacting proteins associated with growth and development, hormones, and stress responses. Expression patterns of AhTGA genes in different tissues, under abiotic stress conditions for low temperature and drought, and in response to hormonal stimuli revealed that seven AhTGA genes from groups I (AhTGA04, AhTGA14 and AhTGA20) and II (AhTGA07, AhTGA11, AhTGA16 and AhTGA18) are involved in the response to abiotic stress and hormonal stimuli. The hormone treatment results indicate that these AhTGA genes primarily respond to the regulation of jasmonic acid and salicylic acid. Overexpressing AhTGA11 in Arabidopsis enhances resistance to cold and drought stress by increasing antioxidant activities and altering endogenous hormone levels, particularly ABA, SA and JA.

Discussion

The AhTGA genes plays a crucial role in hormone regulation and stress response during peanut growth and development. The findings provide insights into peanut's abiotic stress tolerance mechanisms and pave the way for future functional studies.
Genetic breakthroughs in the Brassica napus–Sclerotinia sclerotiorum interactions
Authors: Chen Rong-Shi , Wang Ji-Yi , Sarwar Rehman , Tan Xiao-Li
Published: November 2023

Sclerotinia sclerotiorum (Lib.) de Bary is a highly destructive fungal pathogen that seriously damages the yield and quality of Brassica napus worldwide. The complex interaction between the B. napus and S. sclerotiorum system has presented significant challenges in researching rapeseed defense strategies. Here, we focus on the infection process of S. sclerotiorum, the defense mechanisms of rapeseed, and recent research progress in this system. The response of rapeseed to S. sclerotiorum is multifaceted; this review aims to provide a theoretical basis for rapeseed defense strategies.
Deciphering the roles of unknown/uncharacterized genes in plant development and stress responses
Authors: Wang Xi , Wang Baoshan , Yuan Fang
Published: November 2023

In recent years, numerous genes that encode proteins with specific domains that participate in different biological processes or have different molecular functions have been identified. A class of genes with typical domains whose function has rarely been identified and another type of genes with no typical domains have attracted increasing attentions. As many of these so-called as unknown/uncharacterized (U/U) genes are involved in important processes, such as plant growth and plant stress resistance, there is much interest in deciphering their molecular roles. Here, we summarize our current understanding of these genes, including their structures, classifications, and roles in plant growth and stress resistance, summarize progress in the methods used to decipher the roles of these genes, and provide new research perspectives. Unveiling the molecular functions of unknown/uncharacterized genes may suggest strategies to fine-tune important physiological processes in plants, which will enrich the functional network system of plants and provide more possibilities for adaptive improvement of plants.
Energy transfer from phycobilisomes to photosystem I at 77 K
Authors: van Stokkum Ivo H. M. , Akhtar Parveen , Biswas Avratanu , Lambrev Petar H.
Published: November 2023

Phycobilisomes serve as a light-harvesting antenna of both photosystem I (PSI) and II (PSII) in cyanobacteria, yet direct energy transfer from phycobilisomes to PSI is not well documented. Here we recorded picosecond time-resolved fluorescence at wavelengths of 605–760 nm in isolated photosystem I (PSI), phycobilisomes and intact cells of a PSII-deficient mutant of Synechocystis sp. PCC 6803 at 77 K to study excitation energy transfer and trapping. By means of a simultaneous target analysis of the kinetics of isolated complexes and whole cells, the pathways and dynamics of energy transfer in vitro and in vivo were established. We establish that the timescale of the slowest equilibration between different terminal emitters in the phycobilisome is ≈800 ps. It was estimated that the terminal emitter in about 40% of the phycobilisomes transfers its energy with a rate constant of 42 ns−1 to PSI. This energy transfer rate is higher than the rates of equilibration within the phycobilisome – between the rods and the core or between the core cylinders – and is evidence for the existence of specific phycobilisome-PSI interactions. The rest of the phycobilisomes remain unconnected or slowly transferring energy to PSI.
Advantages and pitfalls of machine translation for party research: the translation of party manifestos of European parties using DeepL
Authors: Plenter Johanna Ida
Published: November 2023

Parties are the central actors in representative democracies as they perform important democratic functions. Thus, the identification of party positions is a crucial concern. Party researchers mainly rely on party manifestos to estimate policy positions. However, the analysis of manifestos is accompanied by challenges—one of the biggest being cross-national comparisons because of different institutional settings and languages. This article discusses machine translation (MT) as a new option for party research, and reports on the author's experiences with the translation of more than 200 party manifestos using the commercial artificial intelligence (AI) translation tool DeepL. To make this approach widely applicable, the (technical) procedure, including its problems and workarounds for large-scale projects, is presented as a step-by-step guide using R. Additionally, drawing on the most recent German, Estonian, Italian and Polish parliamentary election manifestos this article evaluates the quality of the DeepL translations by applying both back translation and Wordfish analyses. The main findings indicate that DeepL offers high-quality translations as more than 90% of the checked sentences are reproduced word-for-word or at least synonymously and with stable positioning on the left-right scale of both original and English translation. The results have greater implications for political science research as they speak to the reliability of machine translation for political texts.
Predicting online information seeking on Douyin, Baidu, and other Chinese search engines among gynecologic oncology patients: a cross-sectional study
Authors: Xiong Wenli , Li Xiaohong , Han Yun , He Lijuan
Published: November 2023

Objective

The rise of online platforms like Douyin, Baidu, and other Chinese search engines has changed how gynecologic oncology patients seek information about their diagnosis or condition. This study aimed to investigate the factors associated with information seeking among these patients and to evaluate their predictive performance.

Methods

A cross-sectional study was conducted among 199 gynecologic oncology patients at a single hospital in China. The patients’ demographic characteristics and scores on the State–Trait Anxiety Inventory (STAI-S and STAI-T) and the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) were compared between those who sought information online and those who did not. Logistic regression analyses and receiver operating characteristic (ROC) curve analyses were performed.

Results

The patients’ age, marital status, STAI-S scores, and HADS-A scores were significantly associated with online information seeking. The combined model that included these factors showed good predictive performance with an area under the ROC curve of 0.841.

Conclusion

The combination of demographic and psychological factors can be used to predict the likelihood of gynecologic oncology patients seeking information online. These findings can help healthcare providers understand their patients’ information-seeking behaviors and tailor their communication strategies accordingly.
What can we learn from COVID-19?: examining the resilience of primary care teams
Authors: Hughes Ashley M. , Arredondo Kelley , Lester Houston F. , Oswald Frederick L. , Pham Trang N. D. , Jiang Cheng , Hysong Sylvia J.
Published: November 2023

Introduction

The COVID-19 pandemic continues to place an unprecedented strain on the US healthcare system, and primary care is no exception. Primary care services have shifted toward a team-based approach for delivering care in the last decade. COVID-19 placed extraordinary stress on primary care teams at the forefront of the pandemic response efforts. The current work applies the science of effective teams to examine the impact of COVID-19—a crisis or adverse event—on primary care team resilience.

Methods

Little empirical research has been done testing the theory of team resilience during an extremely adverse crisis event in an applied team setting. Therefore, we conducted an archival study by using large-scale national data from the Veterans Health Administration to understand the characteristics and performance of 7,023 Patient Aligned Care Teams (PACTs) during COVID-19.

Results

Our study found that primary care teams maintained performance in the presence of adversity, indicating possible team resilience. Further, team coordination positively predicted team performance (B = 0.53) regardless of the level of adversity a team was experiencing.

Discussion

These findings in turn attest to the need to preserve team coordination in the presence of adversity. Results carry implications for creating opportunities for teams to learn and adjust to an adverse event to maintain performance and optimize team-member well-being. Teamwork can act as a protective factor against high levels of workload, burnout, and turnover, and should be studied further for its role in promoting team resilience.
Trust in automated vehicles: constructs, psychological processes, and assessment
Authors: Walker Francesco , Forster Yannick , Hergeth Sebastian , Kraus Johannes , Payre William , Wintersberger Philipp , Martens Marieke
Published: November 2023

There is a growing body of research on trust in driving automation systems. In this paper, we seek to clarify the way trust is conceptualized, calibrated and measured taking into account issues related to specific levels of driving automation. We find that: (1) experience plays a vital role in trust calibration; (2) experience should be measured not just in terms of distance traveled, but in terms of the range of situations encountered; (3) system malfunctions and recovery from such malfunctions is a fundamental part of this experience. We summarize our findings in a framework describing the dynamics of trust calibration. We observe that methods used to quantify trust often lack objectivity, reliability, and validity, and propose a set of recommendations for researchers seeking to select suitable trust measures for their studies. In conclusion, we argue that the safe deployment of current and future automated vehicles depends on drivers developing appropriate levels of trust. Given the potentially severe consequences of miscalibrated trust, it is essential that drivers incorporate the possibility of new and unexpected driving situations in their mental models of system capabilities. It is vitally important that we develop methods that contribute to this goal.
5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case study
Authors: Ragnhildstveit Anya , Khan Ryan , Seli Paul , Bass Lisa Claire , August River Jude , Kaiyo Miriam , Barr Nathaniel , Jackson Laura Kate , Gaffrey Michael Santo , Barsuglia Joseph Peter , Averill Lynnette Astrid
Published: November 2023

Psychedelic therapy is, arguably, the next frontier in psychiatry. It offers a radical alternative to longstanding, mainstays of treatment, while exciting a paradigm shift in translational science and drug discovery. There is particular interest in 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)—a serotonergic psychedelic—as a novel, fast-acting therapeutic. Yet, few studies have directly examined 5-MeO-DMT for trauma- or stress-related psychopathology, including post-traumatic stress disorder (PTSD). Herein, we present the first longitudinal case study on 5-MeO-DMT for chronic refractory PTSD, in a 23-year-old female. A single dose of vaporized bufotoxin of the Sonoran Desert Toad (Incilius alvarius), containing an estimated 10−15 mg of 5-MeO-DMT, led to clinically significant improvements in PTSD, with next-day effects. This was accompanied by marked reductions in hopelessness and related suicide risk. Improvements, across all constructs, were sustained at 1-, 3-, 6-, and 12-months follow-up, as monitored by a supporting clinician. The subject further endorsed a complete mystical experience, hypothesized to underly 5-MeO-DMT’s therapeutic activity. No drug-related, serious adverse events occurred. Together, results showed that 5-MeO-DMT was generally tolerable, safe to administer, and effective for PTSD; however, this was not without risk. The subject reported acute nausea, overwhelming subjective effects, and late onset of night terrors. Further research is warranted to replicate and extend these findings, which are inherently limited, non-generalizable, and rely on methods not clinically accepted.