bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights into β-glucan-enhanced immunity in largemouth bass Micropterus salmoides by transcriptome and intestinal microbial composition
Authors: Zhang Yuexing , Guo Mingyu , Li Ning , Dong Zhiyong , Cai Linwei , Wu Bowen , Xie Jianjun , Liu Liang , Ren Lina , Shi Bo
Published: December 2022

β-glucan is widely used in aquaculture due to its immunostimulatory effects, but the specific effect and potential regulatory mechanism on largemouth bass (Micropterus salmoides) are still unclear. Here, we evaluated the effects of β-glucan on growth, resistance to Aeromonas schubertii, intestinal health, and transcriptome of largemouth bass to reveal the potential regulators, metabolic pathways, and altered differential microbiota. Four experimental diets were designed with β-glucan supplementation levels of 0 (control), 100 (LA-100), 200 (MA-200), and 300 (HA-300) mg kg-1, and each diet was fed to largemouth bass (79.30 ± 0.50 g) in triplicate for 70 days, followed by a 3-day challenge experiment. Results showed that different β-glucan supplementations had no significant effects on growth performance and whole-body composition. Fish fed a diet with 300 mg kg-1 β-glucan significantly increased the activity of lysozyme than those fed diets with 0 and 100 mg kg-1 β-glucan. In addition, the survival rate of largemouth bass in β-glucan supplementation groups was significantly higher than the control group at 12- and 24-h challenge by Aeromonas schubertii. Transcriptome analysis showed that a total of 1,245 genes were differentially expressed [|log2(fold change)| ≥1, q-value ≤0.05], including 109 immune-related differentially expressed genes (DEGs). Further analysis revealed that significantly upregulated and downregulated DEGs associated with immunity were mapped into 12 and 24 pathways, respectively. Results of intestinal microflora indicated that fish fed a diet with 300 mg kg-1 β-glucan had higher bacterial richness and diversity as evaluated by Sobs, Chao, Ace, and Simpson indices, but no significant differences were found in the comparison groups. Furthermore, 300 mg kg-1 β-glucan significantly increased the relative abundance of Mycoplasma and decreased Proteobacteria (mainly Escherichia-Shigella and Escherichia coli) and Bacillus anthracis in largemouth bass intestinal microflora. The findings of this study provided new insights that will be valuable in future studies to elucidate the mechanism of immunity enhancement by β-glucan.
The analysis and design of deep-sea lighting field based on spectral transfer function
Authors: Quan Xiangqian , Wei Yucong , Liu Kaibin , Li Bo
Published: December 2022

Due to the attenuation of light in water, the deep-sea optical imaging system needs an active lighting system to provide the light source. However, because of the nonlinearity of light attenuation in spatial dimension and spectral dimension, the deep-sea lighting differs from terrestrial lighting. In order to quantitatively analyze and design deep-sea lighting system, we proposed a precise deep-sea lighting field simulation model and design method based on spectral transfer function. Firstly, with the analysis of deep-sea lighting-imaging process, the spectral transfer function in lighting field was analyzed and the deep-sea lighting model was built. Then, the platform used to study light attenuation was set up and the attenuation characteristics of light in water were derived. Moreover, the deep-sea lighting field simulation model was built with the computer program. Finally, the experiment platform for testing the underwater lighting field was set up in test pool. The experimental results show that the deep-sea lighting field computational model is accurate. In addition, the optimal deep-sea lighting system design was proposed. This study provides the theoretical basis and experimental data for the design of a deep-sea lighting system which has far-reaching significance for improving the efficiency of deep-sea scientific research.
Contrast-enhanced ultrasonography for the management of portal hypertension in cirrhosis
Authors: Maruyama Hitoshi , Tobari Maki , Nagamatsu Hiroaki , Shiina Suichiro , Yamaguchi Tadashi
Published: December 2022

Portal hypertension is a major pathophysiological condition in patients with cirrhosis. This accounts for the occurrence and severity of the various manifestations. The degree is determined by the portal pressure or hepatic venous pressure gradients, both of which are obtained by invasive interventional radiological procedures. Ultrasound (US) is a simple and minimally invasive imaging modality for the diagnosis of liver diseases. Owing to the availability of microbubble-based contrast agents and the development of imaging modes corresponding to contrast effects, contrast-enhanced US (CEUS) has become popular worldwide for the detailed evaluation of hepatic hemodynamics, diffuse liver disease, and focal hepatic lesions. Recent advancements in digital technology have enabled contrast-based demonstrations with improved resolution, leading to a wider range of applications. This review article describes the current role, benefits, and limitations of CEUS in the management of portal hypertension.
The role of artificial intelligence in surgical simulation
Authors: Park Jay J. , Tiefenbach Jakov , Demetriades Andreas K.
Published: December 2022

Artificial Intelligence (AI) plays an integral role in enhancing the quality of surgical simulation, which is increasingly becoming a popular tool for enriching the training experience of a surgeon. This spans the spectrum from facilitating preoperative planning, to intraoperative visualisation and guidance, ultimately with the aim of improving patient safety. Although arguably still in its early stages of widespread clinical application, AI technology enables personal evaluation and provides personalised feedback in surgical training simulations. Several forms of surgical visualisation technologies currently in use for anatomical education and presurgical assessment rely on different AI algorithms. However, while it is promising to see clinical examples and technological reports attesting to the efficacy of AI-supported surgical simulators, barriers to wide-spread commercialisation of such devices and software remain complex and multifactorial. High implementation and production costs, scarcity of reports evidencing the superiority of such technology, and intrinsic technological limitations remain at the forefront. As AI technology is key to driving the future of surgical simulation, this paper will review the literature delineating its current state, challenges, and prospects. In addition, a consolidated list of FDA/CE approved AI-powered medical devices for surgical simulation is presented, in order to shed light on the existing gap between academic achievements and the universal commercialisation of AI-enabled simulators. We call for further clinical assessment of AI-supported surgical simulators to support novel regulatory body approved devices and usher surgery into a new era of surgical education.
Livestock-associated methicillin-resistant Staphylococcus aureus epidemiology, genetic diversity, and clinical characteristics in an urban region
Authors: Konstantinovski Maria M. , Schouls Leo M. , Witteveen Sandra , Claas Eric C. J. , Kraakman Margriet E. , Kalpoe Jayant , Mattson Eva , Hetem David J. , van Elzakker Erika P. M. , Kerremans Jos , Hira Vishal , Bosch Thijs , Gooskens Jairo
Published: December 2022

Objectives

While Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), defined as CC398, is a well-known pathogen among those working with livestock, there are indications that LA-MRSA prevalence among the general population is increasing. However, the clinical impact in urban areas remains unknown. The aim of this study was to assess the genetic epidemiology and clinical characteristics of LA-MRSA in an urban area with a limited livestock population.

Methods

In this retrospective study, we evaluated LA-MRSA strains that were collected between 2014 and 2018 from patients who received clinical care in a single urban area in Netherlands. Patient files were assessed for livestock exposure data, clinical findings, and contact tracing information. Next-generation sequencing (NGS) analysis in combination with wgMLST was conducted to assess genetic diversity and relatedness and to detect virulence and resistance genes.

Results

LA-MRSA strains were cultured from 81 patients, comprising 12% of all the MRSA strains found in seven study laboratories between 2014 and 2018. No livestock link was found in 76% of patients (n = 61), and 28% of patients (n = 23) had an infection, mostly of the skin or soft tissue. Contact tracing had been initiated in 14 cases, leading to the identification of two hospital transmissions: a cluster of 9 cases and one of 2 cases. NGS data were available for 91% (n = 75) of the patients. wgMLST confirmed the clusters detected via contact tracing (n = 2) and identified 5 additional clusters without a known epidemiological link. Relevant resistance and virulence findings included the PVL virulence gene (3 isolates) and tetracycline resistance (79 isolates).

Conclusion

LA-MRSA may cause a relevant burden of disease in urban areas. Surprisingly, most infections in the present study occurred in the absence of a livestock link, suggesting inter-human transmission. These findings and the presence of PVL and other immune evasive complex virulence genes warrant future surveillance and preventative measures.
From DNA-protein interactions to the genetic circuit design using CRISPR-dCas systems
Authors: Shaytan A. K. , Novikov R. V. , Vinnikov R. S. , Gribkova A. K. , Glukhov G. S.
Published: December 2022

In the last decade, the CRISPR-Cas technology has gained widespread popularity in different fields from genome editing and detecting specific DNA/RNA sequences to gene expression control. At the heart of this technology is the ability of CRISPR-Cas complexes to be programmed for targeting particular DNA loci, even when using catalytically inactive dCas-proteins. The repertoire of naturally derived and engineered dCas-proteins including fusion proteins presents a promising toolbox that can be used to construct functional synthetic genetic circuits. Rational genetic circuit design, apart from having practical relevance, is an important step towards a deeper quantitative understanding of the basic principles governing gene expression regulation and functioning of living organisms. In this minireview, we provide a succinct overview of the application of CRISPR-dCas-based systems in the emerging field of synthetic genetic circuit design. We discuss the diversity of dCas-based tools, their properties, and their application in different types of genetic circuits and outline challenges and further research directions in the field.
Case Report: Deep brain stimulation improves tremor in FGF-14 associated spinocerebellar ataxia
Authors: Loeffler Moritz A. , Synofzik Matthis , Cebi Idil , Klocke Philipp , Hormozi Mohammad , Gasser Thomas , Gharabaghi Alireza , Weiss Daniel
Published: December 2022

Objectives

Spinocerebellar ataxia 27 (SCA 27) is a rare heredodegenerative disorder caused by mutations in the fibroblast growth factor 14 (FGF14) and characterized by early-onset tremor and progressive ataxia later during the disease course. We investigated the effect of deep brain stimulation (DBS) of the ventralis intermedius nucleus of the thalamus (VIM) and subthalamic projections on tremor and ataxia.

Methods

At baseline, we studied the effects of high-frequency VIM stimulation and low-frequency stimulation of subthalamic projections on tremor and ataxia. The patient then adopted the best individual high-frequency stimulation programme at daytime and either 30 Hz-stimulation of the subthalamic contacts or StimOFF at night during two separate 5-weeks follow-up intervals. Both patient and rater were blinded to the stimulation settings.

Results

High-frequency stimulation of the VIM effectively attenuated tremor. At follow-up, intermittent 30 Hz-stimulation at night resulted in a superior tremor response compared to StimOFF at night. Ataxia was not affected.

Discussion

Stimulation of the VIM and adjacent subthalamic projections effectively attenuated tremor in a patient with confirmed SCA 27. Cycling between daytime high-frequency and night-time low-frequency stimulation led to a more sustained tremor response. This suggests to study in future if low-frequency stimulation of the subthalamic projection fibers may help overcome tolerance of tremor that is observed as a long-term limitation of VIM-DBS.
Neuroimaging biomarkers of cognitive recovery after ischemic stroke
Authors: Tahmi Mouna , Kane Veronica A. , Pavol Marykay A. , Naqvi Imama A.
Published: December 2022

Post-stroke cognitive impairment affects more than one-third of patients after an ischemic stroke (IS). Identifying markers of potential cognitive recovery after ischemic stroke can guide patients' selection for treatments, enrollment in clinical trials, and cognitive rehabilitation methods to restore cognitive abilities in post-stroke patients. Despite the burden of post-stroke cognitive impairment, biomarkers of cognitive recovery are an understudied area of research. This narrative review summarizes and critically reviews the current literature on the use and utility of neuroimaging as a predictive biomarker of cognitive recovery after IS. Most studies included in this review utilized structural Magnetic Resonance Imaging (MRI) to predict cognitive recovery after IS; these studies highlighted baseline markers of cerebral small vessel disease and cortical atrophy as predictors of cognitive recovery. Functional Magnetic Resonance Imaging (fMRI) using resting-state functional connectivity and Diffusion Imaging are potential biomarkers of cognitive recovery after IS, although more precise predictive tools are needed. Comparison of these studies is limited by heterogeneity in cognitive assessments. For all modalities, current findings need replication in larger samples. Although no neuroimaging tool is ready for use as a biomarker at this stage, these studies suggest a clinically meaningful role for neuroimaging in predicting post-stroke cognitive recovery.
Endovascular treatment of acute ischemic stroke with a fully radiopaque retriever: A randomized controlled trial
Authors: Zhang Yongxin , Liu Pei , Li Zifu , Peng Ya , Chen Wenhuo , Zhang Liyong , Chu Jianfeng , Kuai Dong , Chen Zhen , Wu Wei , Xu Yun , Zhang Yong , Zhou Bin , Geng Yu , Yin Congguo , Li Jiang , Wang Ming , Zhai Naichi , Peng Xiaoxiang , Ji Zhong , Xiao Yaping , Zhu Xingen , Cai Xueli , Zhang Lei , Hong Bo , Xing Pengfei , Shen Hongjian , Zhang Yongwei , Li Minghua , Shang Meixia , Liu Jianmin , Yang Pengfei
Published: December 2022

Objective

The Neurohawk retriever is a new fully radiopaque retriever. A randomized controlled non-inferiority trial was conducted to compare the Neurohawk and the Solitaire FR in terms of safety and efficacy. In order to evaluate the efficacy and safety of endovascular treatment in acute ischemic stroke (AIS) caused by intracranial atherosclerotic disease (ICAD) larger vessel occlusion (LVO), a sub-analysis was performed.

Methods

Acute ischemic stroke patients aged 18–80 years with LVO in the anterior circulation were randomly assigned to undergo thrombectomy with either the Neurohawk or the Solitaire FR. The primary efficacy endpoint was successful reperfusion (mTICI 2b-3) rate by the allocated retriever. A relevant non-inferiority margin was 12.5%. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and all-cause mortality within 90 days. Secondary endpoints included first-pass effect (FPE), modified FPE, and favorable outcomes at 90 days. In subgroup analysis, the patients were divided into the ICAD group and non-ICAD group according to etiology, and baseline characteristics, angiographic, and clinical outcomes were compared.

Results

A total of 232 patients were involved in this analysis (115 patients in the Neurohawk group and 117 in the Solitaire group). The rates of successful reperfusion with the allocated retriever were 88.70% in the Neurohawk group and 90.60% in the Solitaire group (95%CI of the difference, −9.74% to 5.94%; p = 0.867). There were similar results in FPE and mFPE in both groups. The rate of sICH seemed higher in the Solitaire group (13.16% vs. 7.02%, p = 0.124). All-cause mortality and favorable outcome rates were comparable as well. In subgroup analysis, 58 patients were assigned to the ICAD group and the remaining 174 to the non-ICAD group. The final successful reperfusion and favorable outcome rates showed no statistically significant differences in two groups. Mortality within 90 days was relatively lower in the ICAD group (6.90% vs. 17.24%; p = 0.054).

Conclusion

The Neurohawk retriever is non-inferior to the Solitaire FR in the mechanical thrombectomy of large vessel occlusion-acute ischemic stroke (LVO-AIS). The sub-analysis suggested that endovascular treatment including thrombectomy with the retriever and essential rescue angioplasty is effective and safe in AIS patients with intracranial atherosclerotic disease-larger vessel occlusion (ICAD-LVO).

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT04995757, number: NCT04995757.
Hyperactivity of the default mode network in schizophrenia and free energy: A dialogue between Freudian theory of psychosis and neuroscience
Authors: Tran The Jessica , Ansermet Jean-Philippe , Magistretti Pierre J. , Ansermet Francois
Published: December 2022

The economic conceptualization of Freudian metapsychology, based on an energetics model of the psyche's workings, offers remarkable commonalities with some recent discoveries in neuroscience, notably in the field of neuroenergetics. The pattern of cerebral activity at resting state and the identification of a default mode network (DMN), a network of areas whose activity is detectable at baseline conditions by neuroimaging techniques, offers a promising field of research in the dialogue between psychoanalysis and neuroscience. In this article we study one significant clinical application of this interdisciplinary dialogue by looking at the role of the DMN in the psychopathology of schizophrenia. Anomalies in the functioning of the DMN have been observed in schizophrenia. Studies have evidenced the existence of hyperactivity in this network in schizophrenia patients, particularly among those for whom a positive symptomatology is dominant. These data are particularly interesting when considered from the perspective of the psychoanalytic understanding of the positive symptoms of psychosis, most notably the Freudian hypothesis of delusions as an “attempt at recovery.” Combining the data from research in neuroimaging of schizophrenia patients with the Freudian hypothesis, we propose considering the hyperactivity of the DMN as a consequence of a process of massive reassociation of traces occurring in schizophrenia. This is a process that may constitute an attempt at minimizing the excess of free energy present in psychosis. Modern models of active inference and the free energy principle (FEP) may shed some light on these processes.
The emerging roles of ferroptosis in cells of the central nervous system
Authors: Li Yuyao , Xiao Dongqiong , Wang Xiaodong
Published: December 2022

Ferroptosis is morphologically characterized by shrunken mitochondria and biochemically characterized by iron overload, lipid peroxidation and lipid reactive oxygen species (ROS) accumulation; these phenomena are suppressed by iron chelation, genetic inhibition of cellular iron uptake, and intervention on other pathways such as lipid metabolism. The induction of ferroptosis may be related to pathological cellular conditions in the central nervous system (CNS); thus, ferroptosis may cause disability via CNS damage. Here, we review the role of ferroptosis in the main cells of the CNS, including glial cells, neurons, and pericytes; in various diseases of the CNS; and in the interaction of glia and neurons in CNS diseases. Some small molecules and traditional Chinese drugs which inhibit ferroptosis in cells of the CNS are shown as potential therapeutic strategies for neurological diseases.
Phase-dependent modulation of the vestibular–cerebellar network via combined alternating current stimulation influences human locomotion and posture
Authors: Nakazono Hisato , Taniguchi Takanori , Mitsutake Tsubasa , Takeda Akinori , Yamada Emi , Ogata Katsuya
Published: December 2022

Background

Human locomotion induces rhythmic movements of the trunk and head. Vestibular signaling is relayed to multiple regions in the brainstem and cerebellum, and plays an essential role in maintaining head stability. However, how the vestibular–cerebellar network contributes to the rhythmic locomotor pattern in humans is unclear. Transcranial alternating current stimulation (tACS) has been used to investigate the effects of the task-related network between stimulation regions in a phase-dependent manner. Here, we investigated the relationship between the vestibular system and the cerebellum during walking imagery using combined tACS over the left cerebellum and alternating current galvanic vestibular stimulation (AC-GVS).

Methods

In Experiment 1, we tested the effects of AC-GVS alone at around individual gait stride frequencies. In Experiment 2, we then determined the phase-specificity of combined stimulation at the gait frequency. Combined stimulation was applied at in-phase (0° phase lag) or anti-phase (180° phase lag) between the left vestibular and left cerebellar stimulation, and the sham stimulation. We evaluated the AC-GVS-induced periodic postural response during walking imagery or no-imagery using the peak oscillatory power on the angular velocity signals of the head in both experiments. In Experiment 2, we also examined the phase-locking value (PLV) between the periodic postural responses and the left AC-GVS signals to estimate entrainment of the postural response by AC-GVS.

Results

AC-GVS alone induced the periodic postural response in the yaw and roll axes, but no interactions with imagery walking were observed in Experiment 1 (p > 0.05). By contrast, combined in-phase stimulation increased yaw motion (0.345 ± 0.23) compared with sham (−0.044 ± 0.19) and anti-phase stimulation (−0.066 ± 0.18) during imaginary walking (in-phase vs. other conditions, imagery: p < 0.05; no-imagery: p ≥ 0.125). Furthermore, there was a positive correlation between the yaw peak power of actual locomotion and in-phase stimulation in the imagery session (imagery: p = 0.041; no-imagery: p = 0.177). Meanwhile, we found no imagery-dependent effects in roll peak power or PLV, although in-phase stimulation enhanced roll motion and PLV in Experiment 2.

Conclusion

These findings suggest that combined stimulation can influence vestibular–cerebellar network activity, and modulate postural control and locomotion systems in a temporally sensitive manner. This novel combined tACS/AC-GVS stimulation approach may advance development of therapeutic applications.
Gene editing in monogenic autism spectrum disorder: animal models and gene therapies
Authors: Wang Na , Lv Longbao , Huang Xiaoyi , Shi Mingqin , Dai Youwu , Wei Yuanyuan , Xu Bonan , Fu Chenyang , Huang Haoyu , Shi Hongling , Liu Yun , Hu Xintian , Qin Dongdong
Published: December 2022

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disease, and its diagnosis is dependent on behavioral manifestation, such as impaired reciprocal social interactions, stereotyped repetitive behaviors, as well as restricted interests. However, ASD etiology has eluded researchers to date. In the past decades, based on strong genetic evidence including mutations in a single gene, gene editing technology has become an essential tool for exploring the pathogenetic mechanisms of ASD via constructing genetically modified animal models which validates the casual relationship between genetic risk factors and the development of ASD, thus contributing to developing ideal candidates for gene therapies. The present review discusses the progress in gene editing techniques and genetic research, animal models established by gene editing, as well as gene therapies in ASD. Future research should focus on improving the validity of animal models, and reliable DNA diagnostics and accurate prediction of the functional effects of the mutation will likely be equally crucial for the safe application of gene therapies.
The critical periods of cerebral plasticity: A key aspect in a dialog between psychoanalysis and neuroscience centered on the psychopathology of schizophrenia
Authors: Tran The Jessica , Magistretti Pierre J. , Ansermet Francois
Published: December 2022

Through research into the molecular and cellular mechanisms that occur during critical periods, recent experimental neurobiological data have brought to light the importance of early childhood. These have demonstrated that childhood and early environmental stimuli play a part not only in our subjective construction, but also in brain development; thus, confirming Freud’s intuition regarding the central role of childhood and early experiences of the environment in our psychological development and our subjective outcomes. “Critical periods” of cerebral development represent temporal windows that mark favorable, but also circumscribed, moments in developmental cerebral plasticity. They also vary between different cortical areas. There are, therefore, strictly defined temporal periods for learning language, music, etc., after which this learning becomes more difficult, or even impossible, to acquire. Now, research into these critical periods can be seen as having a significant part to play in the interdisciplinary dialog between psychoanalysis and neurosciences with regard to the role of early experiences in the etiology of some psychopathological conditions. Research into the cellular and molecular mechanisms controlling the onset and end of these critical periods, notably controlled by the maturation of parvalbumin-expressing basket cells, have brought to light the presence of anomalies in the maturation of these neurons in patients with schizophrenia. Starting from these findings we propose revisiting the psychoanalytic theories on the etiology of psychosis from an interdisciplinary perspective. Our study works from the observation, common to both psychoanalysis and neurosciences, that experience leaves a trace; be it a “psychic” or a “synaptic” trace. Thus, we develop a hypothesis for an “absence of trace” in psychosis; reexamining psychosis through the prism of the biological theory of critical periods in plasticity.
Assessment of non-linearity in calorie–income relationship in Pakistan
Authors: Shabnam Nadia
Published: December 2022

This article considers the issue of assessing non-linearity in the relationship between calorie consumption and income using non-parametric and semi-parametric approaches. These methodologies are implemented on the cross-sectional household survey data conducted in Pakistan in 2010–2011. This framework takes account of the heterogeneity among families and potential non-linearity in the relationship. The findings show that the calorie–income elasticity is considerable and statistically significant across estimating methodologies. The results also demonstrate that the elasticity is larger for the substantially poorer households of the sample. By incorporating the explanatory variables in a manageable way in the parametric section of regression procedures, the semi-parametric analysis also reveals a slight increase in calorie response to increases in income at various income levels.
Decreased circulating branched-chain amino acids are associated with development of Alzheimer’s disease in elderly individuals with mild cognitive impairment
Authors: Ikeuchi Takeshi , Kanda Mayuka , Kitamura Hitomi , Morikawa Fumiyoshi , Toru Shuta , Nishimura Chika , Kasuga Kensaku , Tokutake Takayoshi , Takahashi Tetsuya , Kuroha Yasuko , Miyazawa Nobuhiko , Tanaka Shin , Utsumi Kumiko , Ono Kenjiro , Yano Satoshi , Hamano Tadanori , Naruse Satoshi , Yajima Ryuji , Kawashima Noriko , Kaneko Chikako , Tachibana Hisatsugu , Yano Yuki , Kato Yumiko , Toue Sakino , Jinzu Hiroko , Kitamura Akihiko , Yokoyama Yuri , Kaneko Eiji , Yamakado Minoru , Nagao Kenji
Published: December 2022

Background

Nutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants.

Method

In a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal (“MCI-stable,” N = 87) and converted to Alzheimer’s disease (AD) (“AD-convert,” N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted.

Results

Plasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group.

Conclusion

The PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status.

Clinical trial registration

[https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].
Antioxidant, anti-inflammatory and immunomodulatory effects of spirulina in exercise and sport: A systematic review
Authors: Calella Patrizia , Cerullo Giuseppe , Di Dio Mirella , Liguori Fabrizio , Di Onofrio Valeria , Gallè Francesca , Liguori Giorgio
Published: December 2022

Arthrospira platensis, also known as spirulina, is currently one of the most well-known algae supplements, mainly due to its high content of bioactive compounds that may promote human health. Some authors have hypothesized that spirulina consumption could protect subjects from exercise-induced oxidative stress, accelerate recovery by reducing muscle damage, and stimulate the immune system. Based on this, the main goal of this review was to critically analyze the effects of spirulina on oxidative stress, immune system, inflammation and performance in athletes and people undergoing exercise interventions. Of the 981 articles found, 428 studies were considered eligible and 13 met the established criteria and were included in this systematic review. Most recently spirulina supplementation has demonstrated ergogenic potential during submaximal exercise, increasing oxygen uptake and improving exercise tolerance. Nevertheless, spirulina supplementation does not seem to enhance physical performance in power athletes. Considering that data supporting benefits to the immune system from spirulina supplementation is still lacking, overall evidence regarding the benefit of spirulina supplementation in healthy people engaged in physical exercise is scarce and not consistent. Currently, spirulina supplementation might be considered in athletes who do not meet the recommended dietary intake of antioxidants. Further high-quality research is needed to evaluate the effects of spirulina consumption on performance, the immune system and recovery in athletes and active people.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=262896], identifier [CRD42021262896].
Case Report: Bronchial artery embolization and chemoradiotherapy for central squamous cell lung carcinoma with rapid regression
Authors: Zhou Siqi , Zhang Jianxin , Meng Xue , Meng Yingtao , Han Xiao
Published: December 2022

Background

Interventional embolization is a common treatment for hemoptysis, one of the complications of lung cancer. However, there are no official guidelines for the use of this method in antitumor therapy.

Case Description

Herein, we describe a case of a patient who was pathologically diagnosed as central squamous cell lung cancer. The patient received chemotherapy, interventional embolization and radiotherapy successively. The tumor regressed rapidly within 48 hours of receipt of interventional embolization. Furthermore, the tumor decreased by more than 50% in size within 7 days during radiotherapy. Unfortunately, the patient has since developed lymph node metastases and remains under treatment.

Conclusions

Thus, finding the suitable blood vessel embolized may be a suitable option to reduce the local tumor load and can be considered as antitumor therapy in combination with other treatments. The patient’s theoretical hypoxia state after interventional therapy still produced a good tumor regression after radiotherapy. However, so far, no related studies have reported the changes of tumor immune microenvironment in human body after intervention and radiotherapy.
Screening of an individualized treatment strategy for an advanced gallbladder cancer using patient-derived tumor xenograft and organoid models
Authors: Tan Dengxu , An Jiaze , Gong Miaomiao , Wang Huihui , Li Han , Meng Han , Zhang Caiqin , Zhao Yong , Ge Xu , Shi Changhong
Published: December 2022

Gallbladder cancer is a highly aggressive malignancy with poor sensitivity to postoperative radiotherapy or chemotherapy; therefore, the development of individualized treatment strategies is paramount to improve patient outcomes. Both patient-derived tumor xenograft (PDX) and patient-derived tumor organoid (PDO) models derived from surgical specimens can better preserve the biological characteristics and heterogeneity of individual original tumors, display a unique advantage for individualized therapy and predicting clinical outcomes. In this study, PDX and PDO models of advanced gallbladder cancer were established, and the consistency of biological characteristics between them and primary patient samples was confirmed using pathological analysis and RNA-sequencing. Additionally, we tested the efficacy of chemotherapeutic drugs, targeted drugs, and immune checkpoint inhibitors using these two models. The results demonstrated that gemcitabine combined with cisplatin induced significant therapeutic effects. Furthermore, treatment with immune checkpoint inhibitors elicited promising responses in both the humanized mice and PDO immune models. Based on these results, gemcitabine combined with cisplatin was used for basic treatment, and immune checkpoint inhibitors were applied as a complementary intervention for gallbladder cancer. The patient responded well to treatment and exhibited a clearance of tumor foci. Our findings indicate that the combined use of PDO and PDX models can guide the clinical treatment course for gallbladder cancer patients to achieve individualized and effective treatment.
BTG2 suppresses renal cell carcinoma progression through N6-methyladenosine
Authors: Qi Fuming , Liu Wenlong , Tan Bo , Zhang Juan , Ma Yan , Cao Congcong , Ma Fujun , Zhu Bo , Yang Jinhui , Liu Xiaoyun
Published: December 2022

The biological functions of N6-methyladenosine (m6A) modification of mRNA have recently received a great deal of attention. In previous studies, m6A methylation modification has been shown to regulate mRNA fate and to be crucial for the progression and development of tumors. BTG2 (B-cell translocation gene 2) is a member of BTG/TOB anti-proliferative protein family. BTG2 could inhibit cell proliferation and migration and regulate the cell cycle progression. In this study, we confirm that BTG2 is frequently down-regulated in renal cell carcinoma (RCC) tissues and its low expression is associated with unfavorable prognosis and decreased m6A level. Moreover, we found that m6A methylation modifies the 5’UTR of BTG2 to promote its mRNA stability by binding to IGF2BP2. It has been shown that CRISPR/dCas13b-METLL3 can specifically increase BTG2 m6A modification to significantly increase its m6A and expression levels. Then m6A hypermethylation in BTG2 mRNA could dramatically inhibit RCC cells proliferation and migration, and induce cells apoptosis. Taken together, our data show that BTG2 functions as a tumor suppressor and is frequently silenced via m6A modification in RCC.
MicroRNAs (miRNAs): Novel potential therapeutic targets in colorectal cancer
Authors: Yang Ying , Meng Wen-Jian , Wang Zi-Qiang
Published: December 2022

Colorectal cancer (CRC) is the most common malignant tumor and one of the most lethal malignant tumors in the world. Despite treatment with a combination of surgery, radiotherapy, and/or systemic treatment, including chemotherapy and targeted therapy, the prognosis of patients with advanced CRC remains poor. Therefore, there is an urgent need to explore novel therapeutic strategies and targets for the treatment of CRC. MicroRNAs (miRNAs/miRs) are a class of short noncoding RNAs (approximately 22 nucleotides) involved in posttranscriptional gene expression regulation. The dysregulation of its expression is recognized as a key regulator related to the development, progression and metastasis of CRC. In recent years, a number of miRNAs have been identified as regulators of drug resistance in CRC, and some have gained attention as potential targets to overcome the drug resistance of CRC. In this review, we introduce the miRNAs and the diverse mechanisms of miRNAs in CRC and summarize the potential targeted therapies of CRC based on the miRNAs.
Post-operative ctDNA monitoring in stage I colon cancer: A case report
Authors: Alden Stephanie L. , Dhani Harmeet , Palsuledesai Charuta C. , Krinshpun Shifra , Jurdi Adham , Christenson Eric , Browner Ilene , Rosner Samuel
Published: December 2022

Circulating tumor DNA (ctDNA) level monitoring after surgery for colon cancer has been studied in stage II and III colon cancer to risk-stratify patients for adjuvant therapy. However, there is less data regarding the role of this diagnostic tool in the management of stage I disease, where current recommended surveillance is limited to screening colonoscopy at one year. In this report, we describe the case of a 57-year-old man with stage I colon cancer who underwent complete resection with adequate lymph node surgical sampling, normal preoperative CEA and no evidence of metastatic disease on initial imaging. The patient elected to undergo serial ctDNA monitoring after surgery. Rising ctDNA levels, five months after resection, prompted cross-sectional imaging which demonstrated metastatic disease to the liver. The patient subsequently received five cycles of leucovorin, 5-fluorouracil, oxaliplatin, and irinotecan with bevacizumab (FOLFOXIRI-Bev) and definitive microwave ablation to the liver metastases, with resulting undetectable ctDNA levels. The patient’s imaging and colonoscopy one-year post-operatively showed no evidence of disease, with ctDNA levels remaining undetectable. This report highlights the value of ctDNA monitoring in patients with early-stage colon cancer and suggests that further, large-scale studies may be warranted to determine its appropriate clinical use.
Evidence of somatic hypermutation in the antigen binding sites of patients with CLL harboring IGHV genes with 100% germline identity
Authors: Sofou Electra , Zaragoza-Infante Laura , Pechlivanis Nikolaos , Karakatsoulis Georgios , Notopoulou Sofia , Stavroyianni Niki , Psomopoulos Fotis , Georgiou Elisavet , de Septenville Anne Langlois , Davi Frederic , Agathangelidis Andreas , Chatzidimitriou Anastasia , Stamatopoulos Kostas
Published: December 2022

Classification of patients with chronic lymphocytic leukemia (CLL) based on the somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene has established predictive and prognostic relevance. The SHM status is assessed based on the number of mutations within the IG heavy variable domain sequence, albeit only over the rearranged IGHV gene excluding the variable heavy complementarity determining region 3 (VH CDR3). This may lead to an underestimation of the actual impact of SHM, in fact overlooking the most critical region for antigen-antibody interactions, i.e. the VH CDR3. Here we investigated whether SHM may be present within the VH CDR3 of cases bearing ‘truly unmutated’ IGHV genes (i.e. 100% germline identity across VH FR1-VH FR3) employing Next Generation Sequencing. We studied 16 patients bearing a ‘truly unmutated’ CLL clone assigned to stereotyped subsets #1 (n=12) and #6 (n=4). We report the existence of SHM within the germline-encoded 3’IGHV, IGHD, 5’IGHJ regions of the VH CDR3 in both the main IGHV-IGHD-IGHJ gene clonotype and its variants. Recurrent somatic mutations were identified between different patients of the same subset, supporting the notion that they represent true mutational events rather than technical artefacts; moreover, they were located adjacent to/within AID hotspots, pointing to SHM as the underlying mechanism. In conclusion, we provide immunogenetic evidence for intra-VH CDR3 variations, attributed to SHM, in CLL patients carrying ‘truly unmutated’ IGHV genes. Although the clinical implications of this observation remain to be defined, our findings offer a new perspective into the immunobiology of CLL, alluding to the operation of VH CDR3-restricted SHM in U-CLL.
Plasma exosomal miR-320d, miR-4479, and miR-6763-5p as diagnostic biomarkers in epithelial ovarian cancer
Authors: Wang Shiwen , Song Xingguo , Wang Kangyu , Zheng Baibing , Lin Qinghai , Yu Miao , Xie Li , Chen Liang , Song Xianrang
Published: December 2022

Background

Exosomal miRNA had been proved as the promising biomarkers for multiple cancers including epithelial ovarian cancer (EOC). This study aimed to validate the diagnostic accuracy of exosomal miR-320d, miR-4479, and miR-6763-5p for EOC.

Materials and methods

Exosomes isolated from the plasma by ultracentrifugation were verified using TEM, qNano and western blot. MiRNAs sequencing was used to screen out the differential exosomal miRNAs and miR-320d, miR-4479, and miR-6763-5p were selected as candidates, which were further verified by RT-qPCR in 168 healthy donors and 161 primary EOC patients. Besides, the diagnostic accuracy of these three exosomal miRNAs were evaluated using the receiver operating characteristic curve (ROC).

Results

MiRNAs sequencing revealed 95 differential exosomal miRNAs between EOC patients and healthy donors. Subsequently, exosomal miR-320d, miR-4479, and miR-6763-5p were significantly down regulated in EOC patients compared with healthy controls and benign patients. More importantly, these three miRNAs could serve as circulating diagnostics biomarkers for EOC, possessing areas under the curve (AUC) of 0.6549, 0.7781, and 0.6834, respectively. Moreover, these three exosomal miRNAs levels were closely associated with lymph node metastasis, meanwhile exosomal miR-320d and miR-4479 expression was related to tumor stage.

Conclusion

Exosomal miR-320d, miR-4479, and miR-6763-5p might serve as potential biomarkers for EOC.
Multicenter validation of PIM3 and PIM2 in Brazilian pediatric intensive care units
Authors: Genu Daniel Hilário Santos , Lima-Setta Fernanda , Colleti José , de Souza Daniela Carla , Gama Sérgio D’Abreu , Massaud-Ribeiro Letícia , Pistelli Ivan Pollastrini , Proença Filho José Oliva , Bernardi Thaís de Mello Cesar , de Castilho Taísa Roberta Ramos Nantes , Clemente Manuela Guimarães , Borsetto Cibele Cristina Manzoni Ribeiro , de Oliveira Luiz Aurelio , Alves Thallys Ramalho Suzart , Pedroso Diogo Botelho , La Torre Fabíola Peixoto Ferreira , Borges Lunna Perdigão , Santos Guilherme , Mello e Silva Juliana Freitas de , de Magalhães-Barbosa Maria Clara , da Cunha Antonio José Ledo Alves , Soares Marcio , Prata-Barbosa Arnaldo ,   The Brazilian Research Network in Pediatric Intensive Care (BRnet-PIC)
Published: December 2022

Objective

To validate the PIM3 score in Brazilian PICUs and compare its performance with the PIM2.

Methods

Observational, retrospective, multicenter study, including patients younger than 16 years old admitted consecutively from October 2013 to September 2019. We assessed the Standardized Mortality Ratio (SMR), the discrimination capability (using the area under the receiver operating characteristic curve – AUROC), and the calibration. To assess the calibration, we used the calibration belt, which is a curve that represents the correlation of predicted and observed values and their 95% Confidence Interval (CI) through all the risk ranges. We also analyzed the performance of both scores in three periods: 2013–2015, 2015–2017, and 2017–2019.

Results

41,541 patients from 22 PICUs were included. Most patients aged less than 24 months (58.4%) and were admitted for medical conditions (88.6%) (respiratory conditions = 53.8%). Invasive mechanical ventilation was used in 5.8%. The median PICU length of stay was three days (IQR, 2–5), and the observed mortality was 1.8% (763 deaths). The predicted mortality by PIM3 was 1.8% (SMR 1.00; 95% CI 0.94–1.08) and by PIM2 was 2.1% (SMR 0.90; 95% CI 0.83–0.96). Both scores had good discrimination (PIM3 AUROC = 0.88 and PIM2 AUROC = 0.89). In calibration analysis, both scores overestimated mortality in the 0%–3% risk range, PIM3 tended to underestimate mortality in medium-risk patients (9%–46% risk range), and PIM2 also overestimated mortality in high-risk patients (70%–100% mortality risk).

Conclusions

Both scores had a good discrimination ability but poor calibration in different ranges, which deteriorated over time in the population studied.
Accurate and stable measurement of ash in coal by X-ray fluorescence spectrometry based on partial least squares
Authors: Guo Rui , Zhang Lei , Zheng Yaohui , Yao Hui
Published: December 2022

Coal resources play a very important role in the energy structure, especially in the field of thermal power generation. However, in thermal power generation, coal resources can’t be used efficiently for various reasons, resulting in a waste of energy. Due to the advantages of many kinds of elements and rapid measurement, X-fluorescence spectroscopy (XRF) can rapid measurement a variety of metal elements in coal. Combined with partial least squares (PLS), the relationship between a variety of elements and ash in coal can be established, and the ash value in the measured coal can be quickly obtained, which can effectively guide the coal combustion process of power plant, so as to improve the utilization rate of coal. The experimental results show that under the PLS model, XRF technology has good measurement results for the ash content of 45 calibration set coal samples, in which the determination coefficient of the fitting curve (R2) reaches 0.946, and the root mean square error (RMSE) is only 1.177%. The accuracy of the model is further predicted under a cross validation. 15 validation set coal samples are brought into the model for prediction. According to the prediction results, the R2 reaches 0.982, and RMSE is only 0.726%. Finally, four of the 60 samples are randomly selected for stability test, and the relative standard deviation (RSD) is less than 1%. Therefore, the quantitative analysis method of XRF method based on PLS model has high accuracy and stability, which can provide guidance for rapid online measurement of coal ash and coal blending.