bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic dispatch of generation load aggregators based on two-stage robust optimization
Authors: Zhang Haonan , Tian Youwen , Zhao Yi , Liu Qingyu , Zhang Nannan
Published: August 2023

Introduction: In recent years, with the rapid development of renewable energy generation, the stability of the power grid has been greatly reduced. In response to this problem, integrating the user side transferable load into the power market has become the key to the development of future power grid. At present, large transferable loads have entered the electricity market in some pilot areas of China, but the relevant research on small and medium-sized transferable users entering the electricity market is still few.

Methods: This paper proposes the concept of generation load aggregators. A two-stage generation load aggregator robust optimization model is developed to obtain the scheduling scheme with the lowest operating cost under the worst scenario. The model consists of distributed renewable power, transferable load, self-provided power, energy storage, etc. Uncertainties of renewable energy and load are introduced in the model. By using the column constraint generation algorithm and strong pairwise theory, the original problem is decomposed into the main problem and sub-problems to be solved alternately, so as to obtain the scheduling scheme with the lowest operating cost in the worst scenario under different conservatism.

Results: The solved results are compared with those without the generation load aggregator, illustrating the role of the generation load aggregator in relieving peak and valley pressure on the grid from the load side, reducing the cost of electricity for loads, and promoting the consumption of renewable energy. The comparison with the deterministic optimization algorithm shows a significant decrease in the total cost and validates the performance of the selected solution algorithm. The boundary conditions for the use of energy storage by generation load aggregators for peak and valley reduction under the time-sharing tariff mechanism are also derived.

Discussion: This study can provide reference for the investors of generation load aggregators when planning whether to install energy storage or the scale of energy storage, and also help the power market management department to design a reasonable incentive mechanism.
Bacterial community responses of the hydrothermal vent crab Xenograpsus testudinatus fed on microplastics
Authors: Muthu Priyanka , Lee Yun-Cheng , Girija Gowri Krishna , Chen Yu-Ling , Ho Ying-Ning , Hwang Jiang-Shiou
Published: August 2023

Microplastics (MPs) provide persistent contaminants in freshwaters and the oceans from anthropogenic sources worldwide. MP contamination in ecosystems has emerged as a global environmental issue. While increasing research focused on the ecological consequences of plastic pollution, health-related implications of plastic pollution have been somewhat overlooked. In this study, we evaluated the effects of polyethylene MP contamination on microbial, physical, and biochemical characteristics of the hydrothermal vent crab Xenograpsus testudinatus over a 7-day food exposure. Different concentrations (0%, 0.3%, 0.6%, and 1.0%) of polyethylene MPs were used for feed intake experiments. Oxford Nanopore Technologies’ full-length sequencing of the 16S rDNA gene was used to explore the changes of the microbial composition in vent crab tissues. At the phylum level, the content of Firmicutes significantly decreased in the digestive gland tissue. Furthermore, the predicted functions of genes in the microbial community were significantly influenced by MPs. In contrast, there were eight functions in gill and 11 functions in digestive gland tissues identified at low and high intake levels. The dominant functions of methylotrophy, dark thiosulfate oxidation, dark oxidation of sulfur compounds, aromatic hydrocarbon degradation, and aromatic compound degradation were significantly increased at high intake levels in the digestive gland. These findings indicate that MP ingestion causes not only a short-term decrease in energy intake for crustaceans but also a change in microbial communities and their functions. This study provided a first account on the toxicity of MPs in a hydrothermal vent crab to aid in the assessment of health risks provided by polyethylene MP to marine invertebrates.
Prediction of distinct populations of innate lymphoid cells by transcriptional profiles
Authors: Dong Haiyao , Du Zhenguang , Ma Haoming , Zhou Zhicheng , Yang Haitao , Wang Zhenyuan
Published: August 2023

Innate lymphoid cells (ILCs) are a unique type of lymphocyte that differ from adaptive lymphocytes in that they lack antigen receptors, which primarily reside in tissues and are closely associated with fibers. Despite their plasticity and heterogeneity, identifying ILCs in peripheral blood can be difficult due to their small numbers. Accurately and rapidly identifying ILCs is critical for studying homeostasis and inflammation. To address this challenge, we collect single-cell RNA-seq data from 647 patients, including 26,087 transcripts. Background screening, Lasso analysis, and principal component analysis (PCA) are used to select features. Finally, we employ a deep neural network to classify lymphocytes. Our method achieved the highest accuracy compared to other approaches. Furthermore, we identified four genes that play a vital role in lymphocyte development. Adding these gene transcripts into model, we were able to increase the model’s AUC. In summary, our study demonstrates the effectiveness of using single-cell transcriptomic analysis combined with machine learning techniques to accurately identify congenital lymphoid cells and advance our understanding of their development and function in the body.
Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion in vivo
Authors: Nelson Adam G. , Wang Huimeng , Dewar Phoebe M. , Eddy Eleanor M. , Li Songyi , Lim Xin Yi , Patton Timothy , Zhou Yuchen , Pediongco Troi J. , Meehan Lucy J. , Meehan Bronwyn S. , Mak Jeffrey Y. W. , Fairlie David P. , Stent Andrew W. , Kjer-Nielsen Lars , McCluskey James , Eckle Sidonia B. G. , Corbett Alexandra J. , Souter Michael N. T. , Chen Zhenjun
Published: August 2023

Introduction

Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease.

Methods

Here, we outline three methods to increase the abundance of MAIT cells in C57BL/6 mice using a combination of inflammatory stimuli, 5-A-RU and MG.

Results

Our data demonstrate that the administration of synthetic 5-A-RU in combination with one of three different inflammatory stimuli is sufficient to increase the frequency and absolute numbers of MAIT cells in C57BL/6 mice. The resultant boosted MAIT cells are functional and can provide protection against a lethal infection of Legionella longbeachae.

Conclusion

These results provide alternative methods for expanding MAIT cells with high doses of commercially available 5-A-RU (± MG) in the presence of various danger signals.
Combining single-cell sequencing and spatial transcriptome sequencing to identify exosome-related features of glioblastoma and constructing a prognostic model to identify BARD1 as a potential therapeutic target for GBM patients
Authors: Zhao Songyun , Wang Qi , Ni Kaixiang , Zhang Pengpeng , Liu Yuan , Xie Jiaheng , Ji Wei , Cheng Chao , Zhou Qiang
Published: August 2023

Background

Glioblastoma (GBM) is a malignant primary brain tumor. This study focused on exploring the exosome-related features of glioblastoma to better understand its cellular composition and molecular characteristics.

Methods

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptome RNA sequencing (stRNA-seq) were used to analyze the heterogeneity of glioblastomas. After data integration, cell clustering, and annotation, five algorithms were used to calculate scores for exosome-related genes(ERGs). Cell trajectory analysis and intercellular communication analysis were performed to explore exosome-related communication patterns. Spatial transcriptome sequencing data were analyzed to validate the findings. To further utilize exosome-related features to aid in clinical decision-making, a prognostic model was constructed using GBM’s bulk RNA-seq.

Results

Different cell subpopulations were observed in GBM, with Monocytes/macrophages and malignant cells in tumor samples showing higher exosome-related scores. After identifying differentially expressed ERGs in malignant cells, pseudotime analysis revealed the cellular status of malignant cells during development. Intercellular communication analysis highlighted signaling pathways and ligand-receptor interactions. Spatial transcriptome sequencing confirmed the high expression of exosome-related gene features in the tumor core region. A prognostic model based on six ERGs was shown to be predictive of overall survival and immunotherapy outcome in GBM patients. Finally, based on the results of scRNA-seq and prognostic modeling as well as a series of cell function experiments, BARD1 was identified as a novel target for the treatment of GBM.

Conclusion

This study provides a comprehensive understanding of the exosome-related features of GBM in both scRNA-seq and stRNA-seq, with malignant cells with higher exosome-related scores exhibiting stronger communication with Monocytes/macrophages. In terms of spatial data, highly scored malignant cells were also concentrated in the tumor core region. In bulk RNA-seq, patients with a high exosome-related index exhibited an immunosuppressive microenvironment, which was accompanied by a worse prognosis as well as immunotherapy outcomes. Prognostic models constructed using ERGs are expected to be independent prognostic indicators for GBM patients, with potential implications for personalized treatment strategies for GBM. Knockdown of BARD1 in GBM cell lines reduces the invasive and value-added capacity of tumor cells, and thus BARD1-positively expressing malignant cells are a risk factor for GBM patients.
Interannual eddy variability in the eastern Ryukyu Island chain
Authors: Zhang Zhen-Long , Nakamura Hirohiko , Kako Shin’ichiro , Zhu Xiao-Hua
Published: August 2023

Interannual eddy variability in the eastern Ryukyu Island chain (RIC) was analyzed based on eddy trajectories and assimilation data. Analysis of the eddy trajectory data suggested a predominance of eddies originating near the study area. The occurrence frequency of eddies has interannual variability, but it demonstrates a different tendency with eddy kinetic energy (EKE): few eddies appear when EKE is high; however, they are strong with fast rotation speeds and increase in size. The EKE variability was correlated with the baroclinic conversion rates, suggesting a vital role of baroclinic instability in the study area. Baroclinic instability was found to be affected by the North Equatorial Current (NEC), during which more NEC water entered the eastern RIC, intensifying the vertical velocity shear between the upper and lower oceans. Consequently, baroclinic instability in the study area was enhanced.
A program quality framework: a collaborative teaching team approach to quality assurance, quality enhancement and staff capacity building
Authors: van de Mortel Thea , Mitchell Creina , Shuker Mary-Ann , Needham Judith , Kain Victoria , Sanger Georgina , Pierce Beth
Published: August 2023

A global shortage of registered nurses provides a further impetus to retain nursing students and graduate safe nurses. While various frameworks support curriculum design and describe the need for ongoing curriculum evaluation and monitoring, there is little in the literature to support the enactment and ongoing quality enhancement of curricula. Translation of the curriculum plan into the delivered curriculum relies on academics who may or may not be adequately prepared for course writing and teaching in higher education settings, despite their discipline expertise. Additionally, there are well recognized issues of curriculum drift where curriculum innovations and changes are whittled away over time by incremental changes to courses that interfere with the integrity of the accredited curriculum. We propose an evidence-based Program Quality (ProQual) Framework that takes a holistic, collaborative, and systematic approach to monitoring and enhancing curriculum quality and program delivery over the life of the curriculum while developing staff capability and scholarship.
Disconnectome associated with progressive white matter hyperintensities in aging: a virtual lesion study
Authors: Li Meng , Habes Mohamad , Grabe Hans , Kang Yan , Qi Shouliang , Detre John A.
Published: August 2023

Objective

White matter hyperintensities (WMH) are commonly seen on T2-weighted magnetic resonance imaging (MRI) in older adults and are associated with an increased risk of cognitive decline and dementia. This study aims to estimate changes in the structural connectome due to age-related WMH by using a virtual lesion approach.

Methods

High-quality diffusion-weighted imaging data of 30 healthy subjects were obtained from the Human Connectome Project (HCP) database. Diffusion tractography using q-space diffeomorphic reconstruction (QSDR) and whole brain fiber tracking with 107 seed points was conducted using diffusion spectrum imaging studio and the brainnetome atlas was used to parcellate a total of 246 cortical and subcortical nodes. Previously published WMH frequency maps across age ranges (50’s, 60’s, 70’s, and 80’s) were used to generate virtual lesion masks for each decade at three lesion frequency thresholds, and these virtual lesion masks were applied as regions of avoidance (ROA) in fiber tracking to estimate connectivity changes. Connections showing significant differences in fiber density with and without ROA were identified using paired tests with False Discovery Rate (FDR) correction.

Results

Disconnections appeared first from the striatum to middle frontal gyrus (MFG) in the 50’s, then from the thalamus to MFG in the 60’s and extending to the superior frontal gyrus in the 70’s, and ultimately including much more widespread cortical and hippocampal nodes in the 80’s.

Conclusion

Changes in the structural disconnectome due to age-related WMH can be estimated using the virtual lesion approach. The observed disconnections may contribute to the cognitive and sensorimotor deficits seen in aging.
Linking temporal coordination of hippocampal activity to memory function
Authors: Etter Guillaume , Carmichael James E. , Williams Sylvain
Published: August 2023

Oscillations in neural activity are widespread throughout the brain and can be observed at the population level through the local field potential. These rhythmic patterns are associated with cycles of excitability and are thought to coordinate networks of neurons, in turn facilitating effective communication both within local circuits and across brain regions. In the hippocampus, theta rhythms (4–12 Hz) could contribute to several key physiological mechanisms including long-range synchrony, plasticity, and at the behavioral scale, support memory encoding and retrieval. While neurons in the hippocampus appear to be temporally coordinated by theta oscillations, they also tend to fire in sequences that are developmentally preconfigured. Although loss of theta rhythmicity impairs memory, these sequences of spatiotemporal representations persist in conditions of altered hippocampal oscillations. The focus of this review is to disentangle the relative contribution of hippocampal oscillations from single-neuron activity in learning and memory. We first review cellular, anatomical, and physiological mechanisms underlying the generation and maintenance of hippocampal rhythms and how they contribute to memory function. We propose candidate hypotheses for how septohippocampal oscillations could support memory function while not contributing directly to hippocampal sequences. In particular, we explore how theta rhythms could coordinate the integration of upstream signals in the hippocampus to form future decisions, the relevance of such integration to downstream regions, as well as setting the stage for behavioral timescale synaptic plasticity. Finally, we leverage stimulation-based treatment in Alzheimer's disease conditions as an opportunity to assess the sufficiency of hippocampal oscillations for memory function.
An improved fused feature residual network for 3D point cloud data
Authors: Gezawa Abubakar Sulaiman , Liu Chibiao , Jia Heming , Nanehkaran Y. A. , Almutairi Mubarak S. , Chiroma Haruna
Published: August 2023

Point clouds have evolved into one of the most important data formats for 3D representation. It is becoming more popular as a result of the increasing affordability of acquisition equipment and growing usage in a variety of fields. Volumetric grid-based approaches are among the most successful models for processing point clouds because they fully preserve data granularity while additionally making use of point dependency. However, using lower order local estimate functions to close 3D objects, such as the piece-wise constant function, necessitated the use of a high-resolution grid in order to capture detailed features that demanded vast computational resources. This study proposes an improved fused feature network as well as a comprehensive framework for solving shape classification and segmentation tasks using a two-branch technique and feature learning. We begin by designing a feature encoding network with two distinct building blocks: layer skips within, batch normalization (BN), and rectified linear units (ReLU) in between. The purpose of using layer skips is to have fewer layers to propagate across, which will speed up the learning process and lower the effect of gradients vanishing. Furthermore, we develop a robust grid feature extraction module that consists of multiple convolution blocks accompanied by max-pooling to represent a hierarchical representation and extract features from an input grid. We overcome the grid size constraints by sampling a constant number of points in each grid using a simple K-points nearest neighbor (KNN) search, which aids in learning approximation functions in higher order. The proposed method outperforms or is comparable to state-of-the-art approaches in point cloud segmentation and classification tasks. In addition, a study of ablation is presented to show the effectiveness of the proposed method.
Toward the use of novel alternative methods in epilepsy modeling and drug discovery
Authors: Miguel Sanz Claudia , Martinez Navarro Miriam , Caballero Diaz Daniel , Sanchez-Elexpuru Gentzane , Di Donato Vincenzo
Published: August 2023

Epilepsy is a chronic brain disease and, considering the amount of people affected of all ages worldwide, one of the most common neurological disorders. Over 20 novel antiseizure medications (ASMs) have been released since 1993, yet despite substantial advancements in our understanding of the molecular mechanisms behind epileptogenesis, over one-third of patients continue to be resistant to available therapies. This is partially explained by the fact that the majority of existing medicines only address seizure suppression rather than underlying processes. Understanding the origin of this neurological illness requires conducting human neurological and genetic studies. However, the limitation of sample sizes, ethical concerns, and the requirement for appropriate controls (many patients have already had anti-epileptic medication exposure) in human clinical trials underscore the requirement for supplemental models. So far, mammalian models of epilepsy have helped to shed light on the underlying causes of the condition, but the high costs related to breeding of the animals, low throughput, and regulatory restrictions on their research limit their usefulness in drug screening. Here, we present an overview of the state of art in epilepsy modeling describing gold standard animal models used up to date and review the possible alternatives for this research field. Our focus will be mainly on ex vivo, in vitro, and in vivo larval zebrafish models contributing to the 3R in epilepsy modeling and drug screening. We provide a description of pharmacological and genetic methods currently available but also on the possibilities offered by the continued development in gene editing methodologies, especially CRISPR/Cas9-based, for high-throughput disease modeling and anti-epileptic drugs testing.
Initiation of combined antiretroviral therapy confers suboptimal beneficial effects on neurovascular function in people with HIV
Authors: Singh Meera V. , Uddin Md Nasir , Singh Vir B. , Peterson Angelique N. , Murray Kyle D. , Zhuang Yuchuan , Tyrell Alicia , Wang Lu , Tivarus Madalina E. , Zhong Jianhui , Qiu Xing , Schifitto Giovanni
Published: August 2023

Introduction

Due to advances in combined anti-retroviral treatment (cART), there is an increased burden of age-related cerebrovascular disease (CBVD), in people living with HIV (PWH). The underlying CNS injury can be assessed by measuring cerebral blood flow (CBF) and cerebrovascular reactivity (CVR).

Methods

35 treatment-naïve PWH and 53 HIV negative controls (HC) were enrolled in this study. Study participants underwent T1-weighted anatomical, pseudo-continuous arterial spin labeling, and resting-state functional MRI to obtain measures of CBF and CVR prior to starting cART treatment and at two-time points (12 weeks and 2 years) post-cART initiation. Controls were scanned at the baseline and 2-year visits. We also measured plasma levels of microparticles of endothelial and glial origin and well-known endothelial inflammation markers, ICAM-1 and VCAM-1, to assess HIV-associated endothelial inflammation and the interaction of these peripheral markers with brain neurovascular function.

Results

HIV infection was found to be associated with reduced CVR and increased levels of endothelial and glial microparticles (MPs) prior to initiation of cART. Further, CVR correlated negatively with peripheral MP levels in PWH.

Discussion

Our results suggest that while cART treatment has a beneficial effect on the neurovascular function after initiation, these benefits are suboptimal over time.
Prediction models for post-thrombectomy brain edema in patients with acute ischemic stroke: a systematic review and meta-analysis
Authors: Liu Lei , He Chun-yu , Yang Jia-xin , Zheng Si-ting , Zhou Jun , Kong Ye , Chen Wen-bo , Xie Yan
Published: August 2023

Objective

The objective of this study is to systematically evaluate prediction models for post-thrombectomy brain edema in acute ischemic stroke (AIS) patients. This analysis aims to equip clinicians with evidence-based guidance for the selection of appropriate prediction models, thereby facilitating the early identification of patients at risk of developing brain edema post-surgery.

Methods

A comprehensive literature search was conducted across multiple databases, including PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang, and Vip, aiming to identify studies on prediction models for post-thrombectomy brain edema in AIS patients up to January 2023. Reference lists of relevant articles were also inspected. Two reviewers independently screened the literature and extracted data. The Prediction Model Risk of Bias Assessment Tool (PROBAST) and the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines were employed to assess study bias and literature quality, respectively. We then used random-effects bivariate meta-analysis models to summarize the studies.

Results

The review included five articles, yielding 10 models. These models exhibited a relatively high risk of bias. Random effects model demonstrated that the AUC was 0.858 (95% CI 0.817–0.899).

Conclusion

Despite the promising discriminative ability shown by studies on prediction models for post-thrombectomy brain edema in AIS patients, concerns related to a high risk of bias and limited external validation remain. Future research should prioritize the external validation and optimization of these models. There is an urgent need for large-scale, multicenter studies to develop robust, user-friendly models for real-world clinical application.

Systematic review registration

https://www.crd.york.ac.uk, unique Identifier: CRD42022382790.
Fine scale hippocampus morphology variation cross 552 healthy subjects from age 20 to 80
Authors: Yang Qinzhu , Cai Shuxiu , Chen Guojing , Yu Xiaxia , Cattell Renee F. , Raviv Tammy Riklin , Huang Chuan , Zhang Nu , Gao Yi
Published: August 2023

The cerebral cortex varies over the course of a person's life span: at birth, the surface is smooth, before becoming more bumpy (deeper sulci and thicker gyri) in middle age, and thinner in senior years. In this work, a similar phenomenon was observed on the hippocampus. It was previously believed the fine-scale morphology of the hippocampus could only be extracted only with high field scanners (7T, 9.4T); however, recent studies show that regular 3T MR scanners can be sufficient for this purpose. This finding opens the door for the study of fine hippocampal morphometry for a large amount of clinical data. In particular, a characteristic bumpy and subtle feature on the inferior aspect of the hippocampus, which we refer to as hippocampal dentation, presents a dramatic degree of variability between individuals from very smooth to highly dentated. In this report, we propose a combined method joining deep learning and sub-pixel level set evolution to efficiently obtain fine-scale hippocampal segmentation on 552 healthy subjects. Through non-linear dentation extraction and fitting, we reveal that the bumpiness of the inferior surface of the human hippocampus has a clear temporal trend. It is bumpiest between 40 and 50 years old. This observation should be aligned with neurodevelopmental and aging stages.
Altered static and dynamic intrinsic brain activity in unilateral sudden sensorineural hearing loss
Authors: Li Jing , Yu Xiaocheng , Zou Yan , Leng Yangming , Yang Fan , Liu Bo , Fan Wenliang
Published: August 2023

Introduction

Sudden sensorineural hearing loss (SSHL) is a critical otologic emergency characterized by a rapid decline of at least 30 dB across three consecutive frequencies in the pure-tone audiogram within a 72-hour period. This audiological condition has been associated with alterations in brain cortical and subcortical structures, as well as changes in brain functional activities involving multiple networks. However, the extent of cerebral intrinsic brain activity disruption in SSHL remains poorly understood. The aimed of this study is to investigate intrinsic brain activity alterations in SSHL using static and dynamic fractional amplitude of low-frequency fluctuation (fALFF) analysis.

Methods

Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a cohort of SSHL patients (unilateral, n = 102) and healthy controls (n = 73). Static and dynamic fALFF methods were employed to analyze the acquired fMRI data, enabling a comprehensive examination of intrinsic brain activity changes in SSHL.

Results

Our analysis revealed significant differences in static fALFF patterns between SSHL patients and healthy controls. SSHL patients exhibited decreased fALFF in the left fusiform gyrus, left precentral gyrus, and right inferior frontal gyrus, alongside increased fALFF in the left inferior frontal gyrus, left superior frontal gyrus, and right middle temporal gyrus. Additionally, dynamic fALFF analysis demonstrated elevated fALFF in the right superior frontal gyrus and right middle frontal gyrus among SSHL patients. Intriguingly, we observed a positive correlation between static fALFF in the left fusiform gyrus and the duration of hearing loss, shedding light on potential temporal dynamics associated with intrinsic brain activity changes.

Discussion

The observed disruptions in intrinsic brain activity and temporal dynamics among SSHL patients provide valuable insights into the functional reorganization and potential compensatory mechanisms linked to hearing loss. These findings underscore the importance of understanding the underlying neural alterations in SSHL, which could pave the way for the development of targeted interventions and rehabilitation strategies aimed at optimizing SSHL management.
Post-activation depression of the Hoffman reflex is not altered by galvanic vestibular stimulation in healthy subjects
Authors: Alvarado-Navarrete Mónica del Carmen , Pliego-Carrillo Adriana C. , Ledesma-Ramírez Claudia Ivette , Cuellar Carlos A.
Published: August 2023

The comprehension of the neural elements interacting in the spinal cord affected by vestibular input will contribute to the understanding of movement execution in normal and pathological conditions. In this context, Hoffman’s reflex (H-reflex) has been used to evaluate transient excitability changes on the spinal cord descending pathways. The post-activation depression (P-AD) of the H-reflex consists of evoking consecutive responses (>1 Hz) provoking an amplitude depression, which has been shown to diminish in pathological conditions (i.e., spasticity, diabetic neuropathy). Galvanic Vestibular Stimulation (GVS) is a non-invasive method that activates the vestibular afferents and has been used to study the excitability of the H-reflex applied as a conditioning pulse. To our knowledge, there are no reports evaluating the P-AD during and after GVS. Our primary aim was to determine if GVS alters the P-AD evoked by stimulating the tibial nerve at 0.1, 1, 5, and 10 Hz, recording in the gastrocnemius and soleus muscles. Direct current stimulation of 2.0 ± 0.6 mA with the cathode ipsilateral (Ipsi) or contralateral (Contra) to the H-reflex electrode montage was applied bilaterally over the mastoid process in 19 healthy subjects. The P-AD’s immediate post-GVS response (P Ipsi, P Contra) was also analyzed. Secondarily, we analyzed the excitability of the H-reflex during GVS. Responses evoked at 0.1 Hz with GVS, post-GVS, and a Control (no GVS) condition were used for comparisons. Our results show that P-AD persisted in all subjects despite increased excitability induced by GVS: statistical significance was found when comparing P-AD at 1, 5, and 10 Hz with the corresponding condition (Control, Ipsi, P Ipsi, Contra, P Contra) at 0.1 Hz (p < 0.001). Additionally, the increase in excitability produced by GVS was quantified for the first H-reflex of each P-AD stimulation frequency. The percentage change for all GVS conditions surpassed the Control by at least 20%, being statistically significant for Contra compared to Control (p < 0.01). In summary, although GVS increases the excitability of the vestibulospinal pathway at a premotor level, the neural inhibitory mechanism present in P-AD remains unaltered in healthy subjects.
Differential optogenetic activation of the auditory midbrain in freely moving behaving mice
Authors: Rogalla Meike M. , Seibert Adina , Sleeboom Jana M. , Hildebrandt K. Jannis
Published: August 2023

Introduction

In patients with severe auditory impairment, partial hearing restoration can be achieved by sensory prostheses for the electrical stimulation of the central nervous system. However, these state-of-the-art approaches suffer from limited spectral resolution: electrical field spread depends on the impedance of the surrounding medium, impeding spatially focused electrical stimulation in neural tissue. To overcome these limitations, optogenetic activation could be applied in such prostheses to achieve enhanced resolution through precise and differential stimulation of nearby neuronal ensembles. Previous experiments have provided a first proof for behavioral detectability of optogenetic activation in the rodent auditory system, but little is known about the generation of complex and behaviorally relevant sensory patterns involving differential activation.

Methods

In this study, we developed and behaviorally tested an optogenetic implant to excite two spatially separated points along the tonotopy of the murine inferior colliculus (ICc).

Results

Using a reward based operant Go/No-Go paradigm, we show that differential optogenetic activation of a sub-cortical sensory pathway is possible and efficient. We demonstrate how animals which were previously trained in a frequency discrimination paradigm (a) rapidly respond to either sound or optogenetic stimulation, (b) generally detect optogenetic stimulation of two different neuronal ensembles, and (c) discriminate between them.

Discussion

Our results demonstrate that optogenetic excitatory stimulation at different points of the ICc tonotopy elicits a stable response behavior over time periods of several months. With this study, we provide the first proof of principle for sub-cortical differential stimulation of sensory systems using complex artificial cues in freely moving animals.
Efficacy of thoracoscopic segmentectomy versus lobectomy in the treatment of early invasive lung adenocarcinoma: a propensity score matching study
Authors: Ding Congyi , Jia Qiyu , Wu Zhongjie , Zhang Yanfei , Hu Yi , Wang Jingyu , Wei Dahai
Published: August 2023

Objective

This study aimed to investigate and analyze the clinical application value of thoracoscopic segmentectomy and lobectomy in patients with invasive pulmonary adenocarcinoma.

Methods

286 patients with invasive pulmonary adenocarcinoma who underwent segmentectomy or lobectomy at the First Hospital of Jiaxing City from January 2018 to June 2020 were retrospectively analyzed. Patients were divided into a thoracoscopic segmentectomy group(n=97) and a lobectomy group (n=189). Patients were compared after obtaining 1:1 propensity score-matched cohorts. Outcome indicators included surgery-related indicators, immune-inflammation-related indicators, postoperative complications, recurrence, and metastasis.

Results

After 1:1 propensity score matching, 93 patients were included in each group. We found that the volume of intraoperative blood loss in the segmentectomy group was significantly less than in the lobectomy group (P=0.014). The duration of postoperative drainage (P = 0.005) and hospitalization (P=0.002) in the segmentectomy group were significantly shorter than in the lobectomy group. In terms of immunoinflammatory response, compared with the lobectomy group, white blood cells, neutrophils, SII, and NLR in the segmentectomy group were significantly lower than in the lobectomy group (P< 0.05). The recurrence-free survival (RFS) rates in the segmentectomy and lobectomy were 80.5% and 88.2% at 1 year and 35.1% and 52.6% at 3 years, respectively, and the difference was statistically significant (P<0.05). The segmentectomy group achieved similar outcomes to the lobectomy group at 1 year and 3 years (P > 0.05). Multivariate COX regression analysis showed that CAR was an independent risk factor for RFS in patients undergoing invasive adenocarcinoma surgery.

Conclusion

Compared with lobectomy, thoracoscopic segmentectomy can effectively reduce the postoperative inflammatory response in patients with early invasive lung adenocarcinoma and promote patient recovery. Although segmentectomy is associated with a higher recurrence rate in the short term for patients with early invasive lung adenocarcinoma, the associated survival rate is similar to the lobectomy group. Segmentectomy should be considered in the treatment of early invasive lung adenocarcinoma. Meanwhile, postoperative CAR represents an independent risk factor for early postoperative recurrence in patients with IAC.
Systemic treatment of patients with locally advanced or metastatic cholangiocarcinoma – an Austrian expert consensus statement
Authors: Taghizadeh Hossein , Djanani Angela , Eisterer Wolfgang , Gerger Armin , Gruenberger Birgit , Gruenberger Thomas , Rumpold Holger , Weiss Lukas , Winder Thomas , Wöll Ewald , Prager Gerald W.
Published: August 2023

Locally advanced or metastatic cholangiocarcinoma is an aggressive carcinoma with a dismal prognosis. For the first-line treatment of locally advanced or metastatic cholangiocarcinoma, cisplatin/gemcitabine has been the standard of care for more than 10 years. Its combination with the immune checkpoint inhibitor durvalumab resulted in an efficiency improvement in the phase III setting. Regarding the use of chemotherapy in the second line, positive phase III data could only be generated for FOLFOX. The evidence base for nanoliposomal irinotecan (Nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) is contradictory. After the failure of first-line treatment, targeted therapies can be offered if the molecular targets microsatellite instability-high (MSI-H), IDH1, FGFR2, BRAF V600E, and NTRK are detected. These targeted agents are generally preferable to second-line chemotherapy. Broad molecular testing should be performed, preferably from tumor tissue, at the initiation of first-line therapy to timely identify potential molecular targets.
Temporal muscle thickness has no prognostic relevance in patients with high-grade glioma compared to functional scales
Authors: Klingenschmid Julia , Krigers Aleksandrs , Schön Victoria , Pinggera Daniel , Kerschbaumer Johannes , Grams Astrid E. , Thomé Claudius , Freyschlag Christian F.
Published: August 2023

Background

GBM research is constantly assessing potential valuable prognostic biomarkers to better understand the disease and prognosticate future outcomes. Measuring temporal muscle thickness (TMT) has appeared to be a promising new surrogate marker for skeletal muscle mass and sarcopenia, which further indicates frailty and predicts overall survival (OS). The aim of this study was to determine its usefulness as a prognostic marker in patients with high-grade glioma compared to functional status scales.

Methods

TMT was measured in preoperative axial T1-weighted contrast-enhanced magnetic resonance images in 277 patients who received surgical treatment of newly diagnosed WHO III and IV gliomas in our institution between 2015 and 2020. Clinical Frailty Scale (CFS) and Karnofsky Performance Scale (KPS) were assessed preoperatively and during a follow-up visit.

Results

Female gender has shown significant correlation with TMT, while TMT did not correlate with preoperative and follow-up functional scores, age, WHO classification, IDH mutation, MGMT promoter methylation, EGFR and ATRX expression, or 1p/19q co-deletion. No significant prognostic value of TMT could be shown in 6, 12, and 24 months OS, while changes in CFS and KPS proved to have a significant impact.

Conclusion

Only female gender, but no other clinical, histological, or molecular marker showed any interrelation with TMT. Functional scores outclass measuring TMT as a reliable prognostic factor for predicting OS in patients with high-grade glioma.
Safety and economic analysis of the EasyEndo disposable endoscopic cutting and stapling device for VATS lobectomy or segmentectomy in lung cancer patients: a retrospective study
Authors: Han Ziyang , Lu Jieming , Chen Shuchen , Yu Shaobin , Zhang Peipei , Kang Mingqiang
Published: August 2023

Objective

The aim of this retrospective study was to investigate the safety and economic aspects of using the EasyEndo disposable endoscopic cutting and stapling device for video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy in patients with lung cancer. The choice between the two staplers was influenced by changes in our hospital’s procurement policy; Johnson EC45A was used before January 2022 and was then replaced by the EasyEndo stapler.

Methods

We reviewed and analyzed consecutive patients with lung cancer who underwent VATS segmentectomy from March 2021 to December 2022. Inclusion criteria included patients with suspected non-small cell lung cancer (NSCLC) who were eligible for surgical resection. The surgical procedures were performed using either the EasyEndo or Johnson EC45A staplers. Intraoperative variables, postoperative outcomes, and cost analysis were compared between the two groups.

Results

A total of 1556 patients were included in the study, with 775 patients in the Control group and 781 patients in the EasyEndo group. There were no significant differences in patient characteristics between the two groups. Intraoperative variables, including blood loss, blood transfusion, and operation time, showed no significant differences between the groups. Postoperative outcomes, such as hospital stay, drainage tube placement time, and incidence of complications, were also comparable between the two groups. However, there was a significant difference in the cost of stapler usage, with the EasyEndo group showing a lower cost compared to the Control group.

Conclusion

The EasyEndo disposable endoscopic cutting and stapling device demonstrated comparable safety and effectiveness to the Johnson EC45A stapler in VATS segmentectomy for lung cancer patients. Moreover, the use of the EasyEndo stapler resulted in cost savings, indicating its potential economic benefits for healthcare institutions.
Metabolic-suppressed cancer-associated fibroblasts limit the immune environment and survival in colorectal cancer with liver metastasis
Authors: Wu Chenghao , Yu Shaobo , Wang Yanzhong , Gao Yuzhen , Xie Xinyou , Zhang Jun
Published: August 2023

Background: Colorectal cancer liver metastasis is a major risk factor of poor outcomes, necessitating proactive interventions and treatments. Cancer-associated fibroblasts (CAFs) play essential roles in metastasis, with a focus on metabolic reprogramming. However, knowledge about associations between Cancer-associated fibroblasts metabolic phenotypes and immune cell is limited. This study uses single-cell and bulk transcriptomics data to decode roles of metabolism-related subtype of Cancer-associated fibroblasts and immune cells in liver metastasis, developing a CAF-related prognostic model for colorectal cancer liver metastases.

Methods: In this study, Cancer-associated fibroblasts metabolism-related phenotypes were screened using comprehensive datasets from The Cancer Genome Atlas and gene expression omnibus (GEO). Cox regression and Lasso regression were applied to identify prognostic genes related to Cancer-associated fibroblasts, and a model was constructed based on the Cancer-associated fibroblasts subtype gene score. Subsequently, functional, immunological, and clinical analyses were performed.

Results: The study demonstrated the metabotropic heterogeneity of Cancer-associated fibroblasts cells. Cancer-associated fibroblasts cells with varying metabolic states were found to exhibit significant differences in communications with different immune cells. Prognostic features based on Cancer-associated fibroblasts signature scores were found to be useful in determining the prognostic status of colorectal cancer patients with liver metastases. High immune activity and an enrichment of tumor-related pathways were observed in samples with high Cancer-associated fibroblasts signature scores. Furthermore, Cancer-associated fibroblasts signature score could be practical in guiding the selection of chemotherapeutic agents with higher sensitivity.

Conclusion: Our study identified a prognostic signature linked to metabotropic subtype of Cancer-associated fibroblasts. This signature has promising clinical implications in precision therapy for colorectal cancer liver metastases.
CU06-1004 as a promising strategy to improve anti-cancer drug efficacy by preventing vascular leaky syndrome
Authors: Park Songyi , Lee Sunghye , Kim Dongyeop , Kim Hyejeong , Kwon Young-Guen
Published: August 2023

Background: Interleukin-2 (IL-2) is the first cancer therapeutic agent with an immunomodulatory function. Although it has been experimentally proven to be effective against metastatic renal cell carcinoma and metastatic melanoma, the clinical application of high-dose IL-2 (HDIL-2) has been limited because of its short half-life and severe side effects, such as vascular leakage syndrome (VLS) or capillary leaky syndrome (CLS). However, methods for overcoming this issue have not yet been identified.

Methods: We discovered CU06-1004, an endothelial dysfunction blocker, through a previous study, and co-treated with IL-2 immunotherapy to confirm its inhibitory effect on HDIL-2-induced endothelial permeability. CU06-1004 was co-administered with HDIL-2 for 4 days in an in vivo mouse model. After drug injection, the mice were sacrificed, and Evans blue staining was performed.

Results:In vitro, HDIL-2 treatment decreased HUVEC stability, which was rescued by co-treatment with CU06-1004. In our mouse model, co-administration of CU06-1004 and HDIL-2 prevented HDIL-2-induced vascular leakage by normalizing endothelial cells. Notably, the HDIL-2 and CU06-1004 combination therapy considerably reduced tumor growth in the B16F10 melanoma mouse model.

Conclusion: Our data suggest that CU06-1004 acts as a potential anticancer drug candidate, not only by preventing HDIL-2-induced VLS but also by enhancing the anticancer effects of HDIL-2 immunotherapy.
Densities and excess molar volumes of the binary systems of the ionic liquid trihexyl(tetradecyl)phosphonium bromide mixed with acetonitrile or tetrahydrofuran at temperatures from 293.15 to 313.15 K
Authors: Elizalde-Solis Octavio , Zúñiga-Moreno Abel , Camacho-Camacho Luis E. , García-Morales Ricardo , González-Arias Sandro , Verónico-Sánchez Francisco J.
Published: August 2023

Experimental densities and excess molar volumes of two binary mixtures composed of the ionic liquid trihexyl(tetradecyl)phosphonium bromide ([THTDP][Br]) mixed with acetonitrile (ACN) or tetrahydrofuran (THF) are reported in this work. Measurements were made using a vibrating tube densimeter at temperatures from 293.15 to 323.15 K. Both binary systems were studied in the whole composition range along with the pure compounds. Excess molar volumes were calculated from the experimental densities and were fitted with the Redlich–Kister polynomial equation. Excess molar volumes were negative for the mixtures and became more negative as the temperature increased. In addition, the ERAS model was applied for the modeling of excess molar volumes.