bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for erectile dysfunction in diabetes mellitus: a systematic review and meta-analysis
Authors: Dilixiati Diliyaer , Waili Alapati , Tuerxunmaimaiti Aizihaier , Tao Liwen , Zebibula Abudureheman , Rexiati Mulati
Published: April 2024

Background

Previous studies have established that diabetes mellitus (DM) markedly raises the risk of developing erectile dysfunction (ED). Despite extensive investigations, the risk factors associated with ED in diabetic men have yet to be unequivocally determined, owing to incongruent and inconclusive results reported in various studies.

Objective

The objective of this systematic review and meta-analysis was to assess the risk factors for ED in men with DM.

Methods

A comprehensive systematic review was conducted, encompassing studies published in the PubMed, Scopus and Embase databases up to August 24th, 2023. All studies examining the risk factors of ED in patients with DM were included in the analysis. To identify significant variations among the risk factors, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were employed. The risk of bias was evaluated using the Newcastle-Ottawa Scale(NOS) for longitudinal studies and the Agency for Healthcare Research and Quality Scale(AHRQ) for cross-sectional studies.

Results

A total of 58 studies, including a substantial participant pool of 66,925 individuals diagnosed with DM, both with or without ED, were included in the meta-analysis. Mean age (OR: 1.31, 95% CI=1.24-1.37), smoking status (OR: 1.32, 95% CI=1.18-1.47), HbA1C (OR: 1.44, 95% CI=1.28-1.62), duration of DM (OR: 1.39, 95% CI=1.29-1.50), diabetic neuropathy (OR: 3.47, 95% CI=2.16-5.56), diabetic retinopathy (OR: 3.01, 95% CI=2.02-4.48), diabetic foot (OR: 3.96, 95% CI=2.87-5.47), cardiovascular disease (OR: 1.92, 95% CI=1.71-2.16), hypertension (OR: 1.74, 95% CI=1.52-2.00), microvascular disease (OR: 2.14, 95% CI=1.61-2.85), vascular disease (OR: 2.75, 95% CI=2.35-3.21), nephropathy (OR: 2.67, 95% CI=2.06-3.46), depression (OR: 1.82, 95% CI=1.04-3.20), metabolic syndrome (OR: 2.22, 95% CI=1.98-2.49), and diuretic treatment (OR: 2.42, 95% CI=1.38-4.22) were associated with increased risk factors of ED in men with DM.

Conclusion

Our study indicates that in men with DM, several risk factors for ED have been identified, including mean age, HbA1C, duration of DM, diabetic neuropathy, diabetic retinopathy, diabetic foot, cardiovascular disease, hypertension, microvascular disease, vascular disease, nephropathy, depression, metabolic syndrome, and diuretic treatment. By clarifying the connection between these risk factors and ED, clinicians and scientific experts can intervene and address these risk factors, ultimately reducing the occurrence of ED and improving patient management.
A climate analog approach to evaluate seed transfer and vegetation transitions
Authors: Richardson Bryce A. , Rehfeldt Gerald E. , Sáenz-Romero Cuauhtémoc , Milano Elizabeth R.
Published: April 2024

Introduction

There is growing recognition that restoring species diversity is crucial to maintaining ecological functions and services. Increasing the diversity of species used in restoration programs has placed greater emphasis on determining the seed transfer needs for a wider array of plants. However, many plants, outside of commercial forestry, lack information that would provide guidance on seed transfer for current or future climates. Generalized seed transfer approaches use climate partitioning to approximate adaptive differentiation among populations and provide an estimation of seed transfer distance for such species.

Methods

Herein, we describe a generalized seed transfer approach that uses Euclidean distance of 19 climate variables within North America (from northern Honduras to the Arctic). Euclidean distances are used to identify climate analogs from vegetation databases of about 685,000 plots, an average density of 1 plot per 32 km2. Analogs are classified into three thresholds (strong, moderate, and weak) that correspond to altitudinal climate gradients and are guided by the scientific literature of observed adaptive variation of natural tree populations and seed transfer limits.

Results

For strong threshold observations, about 97% of the analogs had climate distances equivalent to ≤300 m elevation, whereas for the weak threshold observations, 53% had an elevation equivalence of ≤300 m. On average 120, 267, and 293 m elevation separated two points under strong, moderate, and weak thresholds, respectively. In total, threshold classification errors were low at 13.9%.

Discussion

We use examples of plot data identified from a reference period (1961–1990) and mid-century (2056–2065) analogs across North American biomes to compare and illustrate the outcomes of projected vegetation change and seed transfer. These examples showcase that mid-century analogs may be located in any cardinal direction and vary greatly in spatial distance and abundance from no analog to hundreds depending on the site. The projected vegetative transitions will have substantial impacts on conservation programs and ecosystem services. Our approach highlights the complexity that climate change presents to managing ecosystems, and the need for predictive tools in guiding land management decisions to mitigate future impacts caused by climate change.
Beyond 40 fluorescent probes for deep phenotyping of blood mononuclear cells, using spectral technology
Authors: Schmutz Sandrine , Commere Pierre-Henri , Montcuquet Nicolas , Cumano Ana , Ait-Mansour Cédric , Novault Sophie , Hasan Milena
Published: April 2024

The analytical capability of flow cytometry is crucial for differentiating the growing number of cell subsets found in human blood. This is important for accurate immunophenotyping of patients with few cells and a large number of parameters to monitor. Here, we present a 43-parameter panel to analyze peripheral blood mononuclear cells from healthy individuals using 41 fluorescence-labelled monoclonal antibodies, an autofluorescent channel, and a viability dye. We demonstrate minimal population distortions that lead to optimized population identification and reproducible results. We have applied an advanced approach in panel design, in selection of sample acquisition parameters and in data analysis. Appropriate autofluorescence identification and integration in the unmixing matrix, allowed for resolution of unspecific signals and increased dimensionality. Addition of one laser without assigned fluorochrome resulted in decreased fluorescence spill over and improved discrimination of cell subsets. It also increased the staining index when autofluorescence was integrated in the matrix. We conclude that spectral flow cytometry is a highly valuable tool for high-end immunophenotyping, and that fine-tuning of major experimental steps is key for taking advantage of its full capacity.
Donor KIR genotype based outcome prediction after allogeneic stem cell transplantation: no land in sight
Authors: Schetelig Johannes , Baldauf Henning , Heidenreich Falk , Hoogenboom Jorinde D. , Spellman Stephen R. , Kulagin Alexander , Schroeder Thomas , Sengeloev Henrik , Dreger Peter , Forcade Edouard , Vydra Jan , Wagner-Drouet Eva Maria , Choi Goda , Paneesha Shankara , Miranda Nuno A. A. , Tanase Alina , de Wreede Liesbeth C. , Lange Vinzenz , Schmidt Alexander H. , Sauter Jürgen , Fein Joshua A. , Bolon Yung-Tsi , He Meilun , Marsh Steven G. E. , Gadalla Shahinaz M. , Paczesny Sophie , Ruggeri Annalisa , Chabannon Christian , Fleischhauer Katharina
Published: April 2024

Optimizing natural killer (NK) cell alloreactivity could further improve outcome after allogeneic hematopoietic cell transplantation (alloHCT). The donor’s Killer-cell Immunoglobulin-like Receptor (KIR) genotype may provide important information in this regard. In the past decade, different models have been proposed aiming at maximizing NK cell activation by activating KIR-ligand interactions or minimizing inhibitory KIR-ligand interactions. Alternative classifications intended predicting outcome after alloHCT by donor KIR-haplotypes. In the present study, we aimed at validating proposed models and exploring more classification approaches. To this end, we analyzed samples stored at the Collaborative Biobank from HLA-compatible unrelated stem cell donors who had donated for patients with acute myeloid leukemia (AML) or myelodysplastic neoplasm (MDS) and whose outcome data had been reported to EBMT or CIBMTR. The donor KIR genotype was determined by high resolution amplicon-based next generation sequencing. We analyzed data from 5,017 transplants. The median patient age at alloHCT was 56 years. Patients were transplanted for AML between 2013 and 2018. Donor-recipient pairs were matched for HLA-A, -B, -C, -DRB1, and -DQB1 (79%) or had single HLA mismatches. Myeloablative conditioning was given to 56% of patients. Fifty-two percent of patients received anti-thymocyte-globulin-based graft-versus-host disease prophylaxis, 32% calcineurin-inhibitor-based prophylaxis, and 7% post-transplant cyclophosphamide-based prophylaxis. We tested several previously reported classifications in multivariable regression analyses but could not confirm outcome associations. Exploratory analyses in 1,939 patients (39%) who were transplanted from donors with homozygous centromeric (cen) or telomeric (tel) A or B motifs, showed that the donor cen B/B-tel A/A diplotype was associated with a trend to better event-free survival (HR 0.84, p=.08) and reduced risk of non-relapse mortality (NRM) (HR 0.65, p=.01). When we further dissected the contribution of B subtypes, we found that only the cen B01/B01-telA/A diplotype was associated with a reduced risk of relapse (HR 0.40, p=.04) while all subtype combinations contributed to a reduced risk of NRM. This exploratory finding has to be validated in an independent data set. In summary, the existing body of evidence is not (yet) consistent enough to recommend use of donor KIR genotype information for donor selection in routine clinical practice.
PyPop: a mature open-source software pipeline for population genomics
Authors: Lancaster Alexander K. , Single Richard M. , Mack Steven J. , Sochat Vanessa , Mariani Michael P. , Webster Gordon D.
Published: April 2024

Python for Population Genomics (PyPop) is a software package that processes genotype and allele data and performs large-scale population genetic analyses on highly polymorphic multi-locus genotype data. In particular, PyPop tests data conformity to Hardy-Weinberg equilibrium expectations, performs Ewens-Watterson tests for selection, estimates haplotype frequencies, measures linkage disequilibrium, and tests significance. Standardized means of performing these tests is key for contemporary studies of evolutionary biology and population genetics, and these tests are central to genetic studies of disease association as well. Here, we present PyPop 1.0.0, a new major release of the package, which implements new features using the more robust infrastructure of GitHub, and is distributed via the industry-standard Python Package Index. New features include implementation of the asymmetric linkage disequilibrium measures and, of particular interest to the immunogenetics research communities, support for modern nomenclature, including colon-delimited allele names, and improvements to meta-analysis features for aggregating outputs for multiple populations.

Code available at: https://zenodo.org/records/10080668 and https://github.com/alexlancaster/pypop
Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation
Authors: Sun Qin , Song Si-Yuan , Ma Jiabao , Li Danni , Wang Yiping , Yang Zhengteng , Wang Yi
Published: April 2024

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of xenotransplantation research. It begins by examining the mechanisms through which xenotransplantation activates both the classical and alternative complement pathways. It then assesses the current landscape of xenotransplantation from donor pigs, with a particular emphasis on the innovative strides made in genetically engineering pigs to evade complement system activation. These modifications are critical in mitigating the discordance between pig endogenous retroviruses and human immune molecules. Additionally, the review discusses pharmacological interventions designed to support transplantation. By exploring the intricate relationship between the complement system and xenotransplantation, this retrospective analysis not only underscores the scientific and clinical importance of this field but also sheds light on the potential pathways to overcoming one of the major barriers to the success of xenografts. As such, the insights offered here hold significant promise for advancing xenotransplantation from a research concept to a viable clinical reality.
Current knowledge of Holothuriida (Holothuroidea: Echinodermata) from Brazil
Authors: Prata Jéssica , Christoffersen Martin Lindsey
Published: April 2024

Sea cucumbers are the second most diverse class among echinoderms. They are characterized by an elongated body and dermal ossicles in the body wall. Among the included groups in that class, the order Holothuriida encompasses many species of commercial interest. Faced with the threats of biodiversity loss resulting from the climate crisis and the advancement of cities, this study provides an overview of recent research involving the Holothuriida of the Brazilian Coast. Searches were carried out in the main periodical databases, using appropriate keywords, targeting publications on the subject in the period between 2000 and 2023. In total, 69 publications were found, most of them corresponding to scientific articles in international journals. Most of the studies come from the Northeast region in Brazil (56.52%). Regarding lines of research, those involving taxonomy and molecular analysis were the most prevalent. Over these 20 years, seven species constituted new occurrences. Of note are the studies focused onHolothuria(Halodeima)grisea, which makes up 39.13% of papers. Despite progress, little is known about morphological variations, genetic distance between populations, population densities, and on reproductive biology of species. Brazil has a vast, heterogeneous coastal area, with unique characteristics to which the species are adapted. The findings reinforce the importance to expand studies aiming on knowing the biodiversity, reproductive biology, and population densities of species. Such data are essential for the creation of public policies aimed at the conservation of species of Holothuriida and their habitats.
Wave-induced residual response and liquefaction of a nonhomogeneous layered seabed
Authors: Sui Titi , Yang Musheng , Peng Li , Chen Jiandong , Zhang Chi , Zheng Jinhai
Published: April 2024

Numerical studies were conducted on the wave-induced residual liquefaction of a silt–coarse sand layered seabed. Fully dynamic soil equations and residual seabed response equations were incorporated into the development of a numerical model. The numerical results were compared with theoretical solutions and experimental data from previous studies. Relatively good agreement was found in this comparison, validating the reliability of the proposed numerical model. The present model was applied to systematically investigate the wave-induced residual response with a silt–coarse sand layered seabed. The effects of coverage thickness, permeability, Young’s modulus in the upper silt layer on the residual response of the seabed were carefully examined. Numerical simulations indicate that the potential liquefaction is prone to occur with low permeability of the upper silt layer and shallower water depth, and the effect of coverage thickness of the silt layer on pore pressure and liquefaction potential is determined by shear stress ratio (χ) and effective normalized spreading parameter (Se) which represent the “generation power” and “dissipation potential” for residual pore pressure. The performance of the pore pressure and liquefaction in the layered seabed is the result of a trade-off between two non-dimensional parameters.
Value of carotid corrected flow time or changes value of FTc could be more useful in predicting fluid responsiveness in patients undergoing robot-assisted gynecologic surgery: a prospective observational study
Authors: Tang Xixi , Liang Jingqiu , Tan Dongling , Chen Qi , Zhou Chengfu , Yang Tingjun , Liu Hongliang
Published: April 2024

Background

The aim of this study was to evaluate the ability of point-of-care Doppler ultrasound measurements of carotid corrected flow time and its changes induced by volume expansion to predict fluid responsiveness in patients undergoing robot-assisted gynecological surgery.

Methods

In this prospective study, carotid corrected flow time was measured using Doppler images of the common carotid artery before and after volume expansion. The stroke volume index at each time point was recorded using noninvasive cardiac output monitoring with MostCare. Of the 52 patients enrolled, 26 responded.

Results

The areas under the receiver operating characteristic curves of the carotid corrected flow time and changes in carotid corrected flow time induced by volume expansion were 0.82 and 0.67, respectively. Their optimal cut-off values were 357 and 19.5 ms, respectively.

Conclusion

Carotid corrected flow time was superior to changes in carotid corrected flow time induced by volume expansion for predicting fluid responsiveness in this population.
Epiphytic microbiota source stimulates the fermentation profile and bacterial community of alfalfa-corn mixed silage
Authors: Tang Xiaolong , Liao Chaosheng , Huang Xiaokang , Chen Cheng , Xu Duhan , Chen Chao
Published: April 2024

The epiphytic microbiota source on plants plays a crucial role in the production of high-quality silage. To gain a better understanding of its contribution, the microbiota of alfalfa (M1C0), corn (M0C1) and the resulting mixture (M1C1) was applied in alfalfa-corn mixed silage production system. M1C0 decreased ammonia-N levels in terms of total nitrogen (57.59–118.23 g/kg TN) and pH (3.59–4.40) values (p < 0.01), which increased lactic acid (33.73–61.89 g/kg DM) content (p < 0.01). Consequently, this resulted in higher residual water-soluble carbohydrate (29.13–41.76 g/kg DM) and crude protein (152.54–167.91 g/kg DM) contents, as well as lower NDF (427.27 g/kg DM) and ADF (269.53 g/kg DM) contents in the silage compared to M1C1- and M0C1-treated samples. Moreover, M1C0 silage showed significantly higher bacterial alpha diversity indices (p < 0.05), including the number of observed species and Chao1 and Shannon diversity indices, at the later stages of ensiling. Lactobacillus, Kosakonia and Enterobacter were the dominant bacterial species in silages, with a relative abundance of >80%. However, the abundance of Lactobacillus amylovorus in M0C1- and M1C1-treated silage increased (p < 0.01) in the late stages of ensiling. These findings confirmed that the epiphytic microbiota source exerts competitive effects during anaerobic storage of alfalfa-corn mixed silage.
Novel microbiota Mesosutterella faecium sp. nov. has a protective effect against inflammatory bowel disease
Authors: Yu Seung Yeob , Oh Byeong Seob , Ryu Seoung Woo , Bak Jeong Eun , Heo Eun Seo , Moon Jeong Chan , Jeong Jae-Ho , Lee Ju Huck
Published: April 2024

A novel Gram-negative, obligate anaerobe, non-motile, flagella-lacking, catalase- and oxidase-negative, coccobacilli-shaped bacterial strain designated AGMB02718T was isolated from swine feces. The 16S rRNA gene analysis indicated that strain AGMB02718T belonged to the genus Mesosutterella with the highest similarity to M. multiformis 4NBBH2T (= DSM 106860T) (sequence similarity of 96.2%), forming a distinct phylogenetic lineage. Its growth occurred at 25–45°C (optimal 37°C) and in 0.5–1% NaCl (optimal 0.5%). Strain AGMB02718T was asaccharolytic and contained menaquinone 6 (MK-6) and methylmenaquinone 6 (MMK-6) as the predominant respiratory quinones. The major cellular fatty acids in the isolate were C18:1ω9c and C16:0. Based on the whole-genome sequencing analysis, strain AGMB02718T had a 2,606,253 bp circular chromosome with a G + C content of 62.2%. The average nucleotide identity value between strain AGMB02718T and M. multiformis 4NBBH2T was 72.1%, while the digital DNA–DNA hybridization value was 20.9%. Interestingly, genome analysis suggested that strain AGMB02718T possessed a low-toxicity lipopolysaccharide (LPS) because the genome of the isolate does not include lpxJ and lpxM genes for Kdo2-Lipid A (KLA) assembly, which confers high toxicity to LPS. Moreover, in vitro macrophage stimulation assay confirmed that AGMB02718T produced LPS with low toxicity. Because the low-toxicity LPS produced by the Sutterellaceae family is involved in regulating host immunity and low-toxicity LPS-producing strains can help maintain host immune homeostasis, we evaluated the anti-inflammatory activity of strain AGMB02718T against inflammatory bowel disease (IBD). As a result, strain AGMB02718T was able to prevent the inflammatory response in a dextran sulfate sodium (DSS)-induced colitis model. Therefore, this strain represents a novel species of Mesosutterella that has a protective effect against DSS-induced colitis, and the proposed name is Mesosutterella faecium sp. nov. The type strain is AGMB02718T (=GDMCC 1.2717T = KCTC 25541T).
Roles of gut microbiota in androgenetic alopecia: insights from Mendelian randomization analysis
Authors: Fu Haijing , Xu Tianyi , Zhao Wumei , Jiang Leiwei , Shan Shijun
Published: April 2024

Background

Androgenetic alopecia (AGA) is the most common type of androgen-associated hair loss. Previous studies have indicated an association between the gut microbiota and AGA. To delve deeper, we executed a two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between the gut microbiota and AGA.

Methods

A two-sample MR investigation was utilized to delve into the intricate interplay between gut microbiota and AGA. Information regarding 211 gut microbial taxa was sourced from the MiBioGen consortium. The summary statistics of the genome-wide association studies (GWAS) for AGA were obtained from the FinnGen biobank, which included 195 cases and 201,019 controls. Various analytical approaches, including Inverse Variance Weighting (IVW), Weighted Median, MR-Egger, Weighted Mode, and Simple Mode were employed to evaluate the causal impact of gut microbiota on AGA. Sensitivity analyses were subsequently conducted to affirm the robustness of the findings.

Results

A two-sample MR investigation unveiled the genus Olsenella, genus Ruminococcaceae UCG-004, and genus Ruminococcaceae UCG-010 were identified as risk factors associated with AGA. In contrast, the family Acidaminococcaceae and genus Anaerofilum, along with the genus Ruminiclostridium 9, demonstrated a protective effect. The sensitivity analyses provided additional assurance that the findings of the current study were less susceptible to the influence of confounding variables and biases.

Conclusion

The MR study has established a link between specific gut microbiota and AGA, offering evidence for the identification of more precisely targeted probiotics. This discovery has the potential to aid in the prevention, control, and reversal of AGA progression.
Global research trends and hotspots of artificial intelligence research in spinal cord neural injury and restoration—a bibliometrics and visualization analysis
Authors: Tao Guangyi , Yang Shun , Xu Junjie , Wang Linzi , Yang Bin
Published: April 2024

Background

Artificial intelligence (AI) technology has made breakthroughs in spinal cord neural injury and restoration in recent years. It has a positive impact on clinical treatment. This study explores AI research’s progress and hotspots in spinal cord neural injury and restoration. It also analyzes research shortcomings related to this area and proposes potential solutions.

Methods

We used CiteSpace 6.1.R6 and VOSviewer 1.6.19 to research WOS articles on AI research in spinal cord neural injury and restoration.

Results

A total of 1,502 articles were screened, in which the United States dominated; Kadone, Hideki (13 articles, University of Tsukuba, JAPAN) was the author with the highest number of publications; ARCH PHYS MED REHAB (IF = 4.3) was the most cited journal, and topics included molecular biology, immunology, neurology, sports, among other related areas.

Conclusion

We pinpointed three research hotspots for AI research in spinal cord neural injury and restoration: (1) intelligent robots and limb exoskeletons to assist rehabilitation training; (2) brain-computer interfaces; and (3) neuromodulation and noninvasive electrical stimulation. In addition, many new hotspots were discussed: (1) starting with image segmentation models based on convolutional neural networks; (2) the use of AI to fabricate polymeric biomaterials to provide the microenvironment required for neural stem cell-derived neural network tissues; (3) AI survival prediction tools, and transcription factor regulatory networks in the field of genetics were discussed. Although AI research in spinal cord neural injury and restoration has many benefits, the technology has several limitations (data and ethical issues). The data-gathering problem should be addressed in future research, which requires a significant sample of quality clinical data to build valid AI models. At the same time, research on genomics and other mechanisms in this field is fragile. In the future, machine learning techniques, such as AI survival prediction tools and transcription factor regulatory networks, can be utilized for studies related to the up-regulation of regeneration-related genes and the production of structural proteins for axonal growth.
Prospective observational study to evaluate treatment satisfaction and effectiveness in patients with relapsing multiple sclerosis starting cladribine tablets (CLADREAL) in Italy
Authors: Filippi Massimo , Ferrè Laura , Zanetta Chiara , Rizzi Caterina , Pessina Gabriella , Assogna Francesco , Rocca Maria A.
Published: April 2024

Disease-modifying therapies (DMTs) for multiple sclerosis (MS) reduce relapse frequency, magnetic resonance imaging (MRI) activity, and slow disability progression. Numerous DMTs are approved for relapsing forms of MS although real-world data on patient-reported outcomes (PROs) and quality of life (QoL) are needed to inform treatment choice. Immune reconstitution therapy with cladribine tablets is a highly effective treatment for relapsing MS (RMS). We present the protocol for an observational study to prospectively assess the effectiveness of cladribine tablets on clinical and MRI parameters as well as on PROs, including treatment satisfaction, QoL, sleep quality, self-perceived health, fatigue, and physical function. Enrolled patients at study sites in Italy will be adults with RMS (including relapsing–remitting and active secondary progressive MS) who are either treatment naïve or have received at least one first-line disease modifying DMT or no more than one second-line DMT. The primary objective will be change in global treatment satisfaction measured with the Treatment Satisfaction Questionnaire for Medication Version 1.4 approximately 24 months after initiating cladribine tablets in patients switching from previous DMTs. Secondary objectives will include global treatment satisfaction at earlier timepoints, will comprise treatment naïve patients, and will quantify treatment effectiveness and tolerability. We will also assess relapses, disability progression, MRI activity, and other PROs at approximately 12 and 24 months. The findings will provide insight from daily clinical practice into the patient’s experience to complement data from controlled trials and inform treatment choice. EU PAS Registration Number EUPAS49334 filed 17/10/2022.
Non-invasive suppression of the human nucleus accumbens (NAc) with transcranial focused ultrasound (tFUS) modulates the reward network: a pilot study
Authors: Peng Xiaolong , Connolly Dillon J. , Sutton Falon , Robinson John , Baker-Vogel Brenna , Short Edward B. , Badran Bashar W.
Published: April 2024

Background

The nucleus accumbens (NAc) is a key node of the brain reward circuit driving reward-related behavior. Dysregulation of NAc has been demonstrated to contribute to pathological markers of addiction in substance use disorder (SUD) making it a potential therapeutic target for brain stimulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation approach that can modulate deep brain regions with a high spatial resolution. However, there is currently no evidence showing how the brain activity of NAc and brain functional connectivity within the reward network neuromodulated by tFUS on the NAc.

Methods

In this pilot study, we carried out a single-blind, sham-controlled clinical trial using functional magnetic resonance imaging (fMRI) to investigate the underlying mechanism of tFUS neuromodulating the reward network through NAc in ten healthy adults. Specifically, the experiment consists of a 20-min concurrent tFUS/fMRI scan and two 24-min resting-state fMRI before and after the tFUS session.

Results

Firstly, our results demonstrated the feasibility and safety of 20-min tFUS on NAc. Additionally, our findings demonstrated that bilateral NAc was inhibited during tFUS on the left NAc compared to sham. Lastly, increased functional connectivity between the NAc and medial prefrontal cortex (mPFC) was observed after tFUS on the left NAc, but no changes for the sham group.

Conclusion

Delivering tFUS to the NAc can modulate brain activations and functional connectivity within the reward network. These preliminary findings suggest that tFUS could be potentially a promising neuromodulation tool for the direct and non-invasive management of the NAc and shed new light on the treatment for SUD and other brain diseases that involve reward processing.
Characterization of the neural circuitry of the auditory thalamic reticular nucleus and its potential role in salicylate-induced tinnitus
Authors: Dai Qian , Qu Tong , Shen Guoming , Wang Haitao
Published: April 2024

Introduction

Subjective tinnitus, the perception of sound without an external acoustic source, is often subsequent to noise-induced hearing loss or ototoxic medications. The condition is believed to result from neuroplastic alterations in the auditory centers, characterized by heightened spontaneous neural activities and increased synchrony due to an imbalance between excitation and inhibition. However, the role of the thalamic reticular nucleus (TRN), a structure composed exclusively of GABAergic neurons involved in thalamocortical oscillations, in the pathogenesis of tinnitus remains largely unexplored.

Methods

We induced tinnitus in mice using sodium salicylate and assessed tinnitus-like behaviors using the Gap Pre-Pulse Inhibition of the Acoustic Startle (GPIAS) paradigm. We utilized combined viral tracing techniques to identify the neural circuitry involved and employed immunofluorescence and confocal imaging to determine cell types and activated neurons.

Results

Salicylate-treated mice exhibited tinnitus-like behaviors. Our tracing clearly delineated the inputs and outputs of the auditory-specific TRN. We discovered that chemogenetic activation of the auditory TRN significantly reduced the salicylate-evoked rise in c-Fos expression in the auditory cortex.

Discussion

This finding posits the TRN as a potential modulatory target for tinnitus treatment. Furthermore, the mapped sensory inputs to the auditory TRN suggest possibilities for employing optogenetic or sensory stimulations to manipulate thalamocortical activities. The precise mapping of the auditory TRN-mediated neural pathways offers a promising avenue for designing targeted interventions to alleviate tinnitus symptoms.
The neuroimmune pathway of high-altitude adaptation: influence of erythrocytes on attention networks through inflammation and the autonomic nervous system
Authors: Wang Nian-Nian , Yu Si-Fang , Dang Peng , Su Rui , Li Hao , Ma Hai-Lin , Liu Ming , Zhang De-Long
Published: April 2024

Introduction

Many studies have shown that the functional adaptation of immigrants to high-altitude is closely related to oxygen transport, inflammatory response and autonomic nervous system. However, it remains unclear how human attention changes in response to hypoxia-induced neurophysiological activity during high-altitude exposure.

Methods

In the present study, we analyzed the relationship between hypoxic-induced neurophysiological responses and attention networks in 116 immigrants (3,680 m) using an attention network test to simultaneously record electroencephalogram and electrocardiogram in combination with specific routine blood markers.

Results

Our analysis revealed that red blood cells exert an indirect influence on the three attention networks, mediated through inflammatory processes and heart rate variability.

Discussion

The present study provides experimental evidence for the role of a neuroimmune pathway in determining human attention performance at high- altitude. Our findings have implications for understanding the complex interactions between physiological and neurocognitive processes in immigrants adapting to hypoxic environments.
The effect of electromyographic feedback functional electrical stimulation on the plantar pressure in stroke patients with foot drop
Authors: Li Xiaoting , Li Hanting , Liu Yu , Liang Weidi , Zhang Lixin , Zhou Fenghua , Zhang Zhiqiang , Yuan Xiangnan
Published: April 2024

Purpose

The purpose of this study was to observe, using Footscan analysis, the effect of electromyographic feedback functional electrical stimulation (FES) on the changes in the plantar pressure of drop foot patients.

Methods

This case–control study enrolled 34 stroke patients with foot drop. There were 17 cases received FES for 20 min per day, 5 days per week for 4 weeks (the FES group) and the other 17 cases only received basic rehabilitations (the control group). Before and after 4 weeks, the walking speed, spatiotemporal parameters and plantar pressure were measured.

Results

After 4 weeks treatments, Both the FES and control groups had increased walking speed and single stance phase percentage, decreased step length symmetry index (SI), double stance phase percentage and start time of the heel after 4 weeks (p < 0.05). The increase in walking speed and decrease in step length SI in the FES group were more significant than the control group after 4 weeks (p < 0.05). The FES group had an increased initial contact phase, decreased SI of the maximal force (Max F) and impulse in the medial heel after 4 weeks (p < 0.05).

Conclusion

The advantages of FES were: the improvement of gait speed, step length SI, and the enhancement of propulsion force were more significant. The initial contact phase was closer to the normal range, which implies that the control of ankle dorsiflexion was improved. The plantar dynamic parameters between the two sides of the foot were more balanced than the control group. FES is more effective than basic rehabilitations for stroke patients with foot drop based on current spatiotemporal parameters and plantar pressure results.
KANPHOS: Kinase-associated neural phospho-signaling database for data-driven research
Authors: Kannon Takayuki , Murashige Satoshi , Nishioka Tomoki , Amano Mutsuki , Funahashi Yasuhiro , Tsuboi Daisuke , Yamahashi Yukie , Nagai Taku , Kaibuchi Kozo , Yoshimoto Junichiro
Published: April 2024

Protein phosphorylation, a key regulator of cellular processes, plays a central role in brain function and is implicated in neurological disorders. Information on protein phosphorylation is expected to be a clue for understanding various neuropsychiatric disorders and developing therapeutic strategies. Nonetheless, existing databases lack a specific focus on phosphorylation events in the brain, which are crucial for investigating the downstream pathway regulated by neurotransmitters. To overcome the gap, we have developed a web-based database named “Kinase-Associated Neural PHOspho-Signaling (KANPHOS).” This paper presents the design concept, detailed features, and a series of improvements for KANPHOS. KANPHOS is designed to support data-driven research by fulfilling three key objectives: (1) enabling the search for protein kinases and their substrates related to extracellular signals or diseases; (2) facilitating a consolidated search for information encompassing phosphorylated substrate genes, proteins, mutant mice, diseases, and more; and (3) offering integrated functionalities to support pathway and network analysis. KANPHOS is also equipped with API functionality to interact with external databases and analysis tools, enhancing its utility in data-driven investigations. Those key features represent a critical step toward unraveling the complex landscape of protein phosphorylation in the brain, with implications for elucidating the molecular mechanisms underlying neurological disorders. KANPHOS is freely accessible to all researchers at https://kanphos.jp.
Progress and hotspot of diet or exercise therapy in the treatment of non-alcoholic fatty liver disease
Authors: Shi Xinyu , Xiong Yalan , Song Hualing , Rong Fen , Tang Nan , Zhu Leping , Li Shenyu , Wang Jianying , Zhang Lei , You Shengfu , Ji Guang , Liu Baocheng , Wu Na
Published: April 2024

Introduction

The primary treatment for non-alcoholic fatty liver disease (NAFLD) is modifying lifestyle through dietary or exercise interventions. In recent decades, it has received increasing attention. However, the lack of bibliometric analysis has posed a challenge for researchers seeking to understand the overall trends in this field.

Methods

As of February 3rd, 2024, 876 articles on treating NAFLD through diet or exercise therapy from 2013 to 2023 had been retrieved. Two software tools, VOSviewer and CiteSpace, were utilized to analyze the growth of publications, countries, institutions, authors, journals, citations, and keywords. Additionally, the keywords with strong citation burstiness were identified to determine the changes and future trends of research hotspots in this field.

Results

China had the highest number of articles, followed by the United States and South Korea. Yonsei University and Nutrients were the institutions and journals with the most significant contributions. Professor Younossi Zobair M, from the United States, is the most prolific author in this field. Through analyzing the keywords, three research hotspots were identified: research on the pathogenesis of NAFLD, research on the treatment modalities of NAFLD, and research on the risk factors and diagnosis methods of NAFLD. In recent years, the research emphasis in this field has changed, suggesting that future research will focus on two frontier keywords: “oxidative stress” and “aerobic capacity.”

Conclusion

In the past eleven years, the attention in this field was still rising, and the authors, journals, countries and so on had formed a considerable cooperative relationship. There were also many highly influential and productive researchers in this field. It is speculated that new research will continue around “aerobic exercise” and “oxidative stress” in the future.
Comparison of nutritional, bioactive potential and antioxidant properties of Saba senegalensis fruit pulps from five regions of Burkina Faso
Authors: Tiendrebeogo Salamata , Compaoré Clarisse Sidbewendé , Barry Raymond Poussian , Oboulbiga Edwige Bahanla , Hama Dicko Mamoudou
Published: April 2024

Introduction

The fruit of Saba senegalensis plays an important role in household nutrition. It is an important source of sweet carbohydrates, minerals, vitamin C, provitamin A and has many biological properties. It is also of economical importance and employment for rural populations, through the processing of fruit. Unfortunately, the lack of exhaustive data on the composition and properties of the fruit and its derivatives limits processing and marketing. The species is widespread in different climatic zones.

Methods

Therefore, its composition and biological properties may vary, offering a variety of processing products to meet the specific nutritional needs. This study aimed to characterize the bioactive potential and antioxidant properties of fruit pulps of S. senegalensis in order to increase its value-added processing. Pulp samples of fruits were sampled from five regions of Burkina Faso, namely the Cascades, Sud-Ouest, Boucle du Mouhoun, Nord and Centre-Sud regions.

Results and Discussion

Qualitative analysis showed the presence of alkaloids, saponins, terpenoids and steroids, anthocyanins and tannins. Quantitative analyses showed a significant variation in phenolics, tannins, lycopene, vitamin C, β-carotene and antioxidant activity among samples. However, this variation was not region-dependent. Indeed, some fruits from same region showed both the highest and lowest values for the assessed parameters. Fruits from regions of Centre-Sud and Sud-Ouest and displayed the highest and lowest levels of total phenolics (877.48 and 1142.33 mg GAE/100 g) and tannins (42.38 and 55.64 mg TAE/100 g), respectively. The high potential of S. senegalensis fruits pulp in nutritional and bioactive compounds, and antioxidant properties recorded in this study suggests that they can be used as a dietary supplement or in the formulation of energy foods and nutraceutical containing foods.
The agreement of low lean mass with obesity using different definitions and its correlation with hyperuricemia
Authors: Xiao Huan , Hu Longxiangfeng , Xie Mengyu , Du Yunfei , Liao Dan
Published: April 2024

Background

The agreement on the identification of sarcopenic obesity remains elusive, and its association with hyperuricemia remains unestablished. This study sought to evaluate the agreement of low lean mass (LLM) with obesity and its correlation with hyperuricemia.

Methods

A total of 25,252 study participants, comprising 4,597 individuals with hyperuricemia, were obtained from the National Health and Nutrition Examination Survey spanning the years 1999–2006 and 2011–2018. LLM with obesity was characterized by the coexistence of LLM, determined by the ratio of appendicular lean mass to body mass index (BMI), and three categories of obesity including BMI, body fat percentage (BF%), and waist circumference (WC). We employed Cohen’s kappa to evaluate the agreement among the different diagnostic criteria and implemented survey multiple logistic regression and stratified analyses to explicate the connection between LLM with obesity and the risk of hyperuricemia.

Results

When defining obesity using BF%, BMI, and WC, the prevalence of LLM with obesity varied from 6.6 to 10.1%, with moderate-to-strong agreement. In the fully adjusted model, individuals with LLM or any of the three types of obesity exhibited notably elevated odds of developing hyperuricemia. Likewise, participants with LLM and obesity had 2.70 (LLM + BMI), 2.44 (LLM + BF%), and 3.12 (LLM + WC) times the risk of hyperuricemia, respectively, compared with healthy individuals. The association between LLM with obesity and hyperuricemia remained stable and significant across different age and sex subgroups.

Conclusion

When employing the three definitions of obesity, the incidence of LLM with obesity was not high, and the diagnostic agreement was relatively good. The participants with LLM and obesity exhibited an increased risk of hyperuricemia.
Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target
Authors: Zhao Zekun , Cui Tenglu , Wei Fengxian , Zhou Zhiming , Sun Yuan , Gao Chaofeng , Xu Xiaodong , Zhang Huihan
Published: April 2024

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and one of the leading causes of cancer-related deaths worldwide. The Wnt/β-Catenin signaling pathway is a highly conserved pathway involved in several biological processes, including the improper regulation that leads to the tumorigenesis and progression of cancer. New studies have found that abnormal activation of the Wnt/β-Catenin signaling pathway is a major cause of HCC tumorigenesis, progression, and resistance to therapy. New perspectives and approaches to treating HCC will arise from understanding this pathway. This article offers a thorough analysis of the Wnt/β-Catenin signaling pathway’s function and its therapeutic implications in HCC.
Potential antidepressant effects of Traditional Chinese botanical drug formula Chaihu-Shugan-San and its active ingredients
Authors: Guo Ziyi , Long Tianjian , Yao Jianping , Li Yamin , Xiao Lu , Chen Min
Published: April 2024

Background: Depression is a severe mental disorder that poses a significant threat to both the physical and mental wellbeing of individuals. Currently, there are various methods for treating depression, including traditional Chinese herbal formulations like Chaihu-Shugan-San (CSS), which have shown effective antidepressant effects in both clinical and animal research.

Objective: This review aims to provide a comprehensive synthesis of evidence related to CSS, considering both preclinical and clinical studies, to uncover its potential multi-level, multi-pathway, and multi-target mechanisms for treating depression and identify its active ingredients.

Methods: A thorough search was conducted in electronic databases, including PubMed, MEDLINE, Web of Science, Google Scholar, CNKI, and Wanfang, using keywords such as “Chaihu Shugan” and “depression” to retrieve relevant literature on CSS and its active ingredients. The review process adhered to the PRISMA guidelines.

Results: This review consolidates the mechanisms underlying antidepressant effects of CSS and its active ingredients. It emphasizes its involvement in the regulation of monoaminergic neurotransmitter systems, synaptic plasticity, and the hypothalamic-pituitary-adrenal axis, among other aspects.

Conclusion: CSS exerts a pivotal role in treating depression through various pathways, including the monoaminergic neurotransmitter system, the hypothalamic-pituitary-adrenal axis, synaptic plasticity, inflammation, brain-derived neurotrophic factor levels, and the brain-gut axis. This review facilitates a comprehensive understanding of the current state of CSS research, fostering an in-depth exploration of the etiological mechanisms of depression and the potential discovery of novel antidepressant drugs.