bluuebunny/crossref_metadata_2025 huggingface dataset:
The application of Interleukin-2 family cytokines in tumor immunotherapy research
Authors: Zhou Yangyihua , Quan Guiqi , Liu Yujun , Shi Ning , Wu Yahui , Zhang Ran , Gao Xiang , Luo Longlong
Published: March 2023

The Interleukin-2 Family contains six kinds of cytokines, namely IL-2, IL-15, IL-4, IL-7, IL-9, and IL-21, all of which share a common γ chain. Many cytokines of the IL-2 family have been reported to be a driving force in immune cells activation. Therefore, researchers have tried various methods to study the anti-tumor effect of cytokines for a long time. However, due to the short half-life, poor stability, easy to lead to inflammatory storms and narrow safety treatment window of cytokines, this field has been tepid. In recent years, with the rapid development of protein engineering technology, some engineered cytokines have a significant effect in tumor immunotherapy, showing an irresistible trend of development. In this review, we will discuss the current researches of the IL-2 family and mainly focus on the application and achievements of engineered cytokines in tumor immunotherapy.
Nocardia rubra cell-wall skeleton activates an immune response in cervical tissue via stimulating FPR3 to enhance dendritic cell-mediated Th1 differentiation
Authors: Guo Qianyu , Chen Wei , Sun Junyi , Zhao Chunfang , Bai Xue , Zhang Yanan , Liu Ke , Zhang Lei , Shao Suxia
Published: March 2023

Nocardia rubra cell wall skeleton (Nr-CWS) has proven to be a successful medicine for therapy of cervical human papillomavirus infection. The mechanism of action of Nr-CWS is unclear but may involve a stimulatory effect on the host immune system. We previously found that CD4+ T cells were increased in cervical tissue after Nr-CWS treatment. Microarray data from these cervical tissues revealed the significant upregulation of formylated peptide receptor 3 (FPR3). This study aimed to explore the role of Nr-CWS in immunomodulatory based on these findings. Examination of CD4+ T cell subsets in cervical tissue from patients who received Nr-CWS revealed substantial increases in Th1 cytokines and transcription factors. The regulatory effects of Nr-CWS on the function and phenotype of dendritic cells (DCs) were assessed in comparison with the traditional DC maturation inducer lipopolysaccharide (LPS). Similar to LPS, Nr-CWS potently induced DC maturation and interleukin-12 (IL-12) secretion. Differentiation of T cells induced by Nr-CWS stimulated DCs was assessed using the mixed lymphocyte reaction assay. Significant differentiation towards Th1 was evident. Finally, FPR3 expression in DCs in response to Nr-CWS and LPS was measured. Nr-CWS potently upregulated FPR3 expression, while the LPS did not. Silencing FPR3 in DCs reduced Nr-CWS-induced IL-12 production and Th1 cell polarization in co-cultured T cells. The collective findings indicate that Nr-CWS may target FPR3 on the surface of DC cells and activate a Th1-type immune response. The findings clarify the basis of the antiviral immune effects of Nr-CWS on human papillomavirus.
Study on feeding behavior and biological sound of Sebastes schlegelii
Authors: Song Mingyuan , Gong Dehua , Cui Xiaojie , Yu Xiaoming , Xu Pengxiang , Xing Binbin , Yin Leiming
Published: March 2023

The construction of marine ranches can enrich and conserve the fishery resources and improve the marine ecosystem, which helps realize the sustainable utilization of these resources. Sebastes schlegelii is a major breeding and releasing fish species in the marine ranches of North China. Its behavioral characteristics can be understood better by researching its vocalization, which will provide data support for constructing acoustic taming marine ranches with S. schlegelii as the target fish species. However, there are few studies focusing on its sounds and behaviors. Therefore, based on the passive acoustic monitoring technology, the audios of underwater noises made by S. schlegelii were extracted using an AQH hydrophone. The high-definition internet protocol camera was used to monitor the behavior change of S. schlegelii. Then, by collating and replaying the collected audios and videos, the feeding behavior and biological noises of S. schlegelii were matched to analyze their relationship. Results are as follows: (1) The noise of chewing settling granular baits (Φ5.0 mm) has a main frequency band and sound pressure level of 2000~4500 Hz and 96.53 ± 0.65 dB, respectively; in this feeding process, the main frequency band and sound pressure level of the swimming noise are 25~400 Hz and 95.63 ± 0.38 dB, respectively; the values are 500~700 Hz and 97.34 ± 4.91 dB, respectively, for the noise of flapping the water with the tail. (2) The sound signals emitted by S. schlegelii are mostly presented as single pulses during normal habitation or ingestion of baits on the surface of the water tank. However, S. schlegelii will attack and fight against each other when scrambling for baits, during which these signals are presented as continuous pulses. To sum up, the vocalization of S. schlegelii is closely related to feeding activities, and the sounds produced under different behaviors have specific biological significance.
Uncovering the link between environmental factors and coral immunity: A study of fluorescent protein expression and phenoloxidase activity in Acropora cervicornis
Authors: Toledo-Hernández Carlos , Ruiz-Diaz Claudia Patricia , Ramírez-Lugo Juan Sebastian , Torres-Díaz Marielys , Santiago-Pagán Lisby , Bruno-Chardón Andrea , Díaz-Vázquez Liz M.
Published: March 2023

Worsening environmental conditions due to climate change have profoundly affected the health of coral reefs worldwide. Thus, understanding how corals respond to fluctuating and/or extreme levels of temperature and solar irradiation will guide future protection and restoration efforts of this valuable ecosystem. Herein, we present a study of the immune responses of the endangered coral Acropora cervicornis to seasonal fluctuations in water temperature (WT), light intensity (LI), and water depth. Immune responses were observed by measuring the concentration of green and cyan fluorescent proteins (GFP and CyFP) and the activity of phenoloxidase (PO), an enzyme involved in the biosynthesis of the photoprotective protein melanin. To study these responses, visually healthy A. cervicornis fragments were placed at 8, and 12 m depth, and GFP, CyPF, and PO activity were measured at three-month intervals over a 12-month period. Seawater temperature and light intensity were also measured at each depth during this period. A general linear mixed model was used to determine the effects of seasonal variations of WT, LI, and water depth on the immune proteins. GFP, CyFP, and PO activity varied significantly across time – all higher in late summer/early fall and lower in late winter/early spring. Likewise, WT and LI significantly affected GFP, CyFP, and PO activity. On the other hand, water depth only had a significant effect on fluorescent protein concentrations but not PO activity. Our study demonstrates that corals can modulate these key immune-related proteins throughout natural seasonal fluctuations. That is, increasing in months of higher thermal and light conditions while decreasing in months with mild thermal and light conditions. The phenotypic plasticity of A. cervicornis in adapting to a changing environment underscores the importance that in future studies time of the year should be a meaningful consideration when evaluating the responses of A. cervicornis to the environment.
A multicenter comparative study of the performance of four rapid immunochromatographic tests for the detection of anti-Trypanosoma cruzi antibodies in Brazil
Authors: Iturra Jacqueline Araújo Domingos , Leony Leonardo Maia , Medeiros Fernanda Alvarenga Cardoso , Souza Filho Job Alves de , Siriano Liliane da Rocha , Tavares Suelene Brito , Luquetti Alejandro Ostermayer , Belo Vinícius Silva , Sousa Andréa Silvestre de , Santos Fred Luciano Neves
Published: March 2023

Diagnosis of Trypanosoma cruzi (T. cruzi) infection in the chronic phase of Chagas disease (CD) is performed by serologic testing. Conventional tests are currently used with very good results but require time, laboratory infrastructure, and expertise. Rapid diagnostic tests (RDTs) are an alternative as the results are immediate and do not require specialized knowledge, making them suitable for epidemiologic studies and promising as a screening tool. Nevertheless, few studies conducted comparative evaluations of RDTs to validate the results and assess their performance. In this study, we analyzed four trades of rapid tests (OnSite Chagas Ab Combo Rapid Test-United States, SD Bioline Chagas AB-United States, WL Check Chagas-Argentina, and TR Chagas Bio-Manguinhos-Brazil) using a panel of 190 samples, including sera from 111 infected individuals, most of whom had low T. cruzi antibody levels. An additional 59 samples from uninfected individuals and 20 sera from individuals with other diseases, mainly visceral leishmaniasis, were included. All tests were performed by three independent laboratories in a blinded manner. Results showed differences in sensitivity from 92.8 to 100%, specificity from 78.5 to 92.4%, and accuracy from 90.5 to 95.3% among the four assays. The results presented here show that all four RDTs have high overall diagnostic ability. However, WL Check Chagas and TR Chagas Bio-Manguinhos were considered most suitable for use in screening studies due to their high sensitivity combined with good performance. Although these two RDTs have high sensitivity, a positive result should be confirmed with other tests to confirm or rule out reactivity/positivity, especially considering possible cross-reactivity with individuals with leishmaniasis or toxoplasmosis.
Nitric oxide-releasing gel accelerates healing in a diabetic murine splinted excisional wound model
Authors: Sivaraj Dharshan , Noishiki Chikage , Kosaric Nina , Kiwanuka Harriet , Kussie Hudson C. , Henn Dominic , Fischer Katharina S. , Trotsyuk Artem A. , Greco Autumn H. , Kuehlmann Britta A. , Quintero Filiberto , Leeolou Melissa C. , Granoski Maia B. , Hostler Andrew C. , Hahn William W. , Januszyk Michael , Murad Ferid , Chen Kellen , Gurtner Geoffrey C.
Published: March 2023

Introduction

According to the American Diabetes Association (ADA), 9–12 million patients suffer from chronic ulceration each year, costing the healthcare system over USD $25 billion annually. There is a significant unmet need for new and efficacious therapies to accelerate closure of non-healing wounds. Nitric Oxide (NO) levels typically increase rapidly after skin injury in the inflammatory phase and gradually diminish as wound healing progresses. The effect of increased NO concentration on promoting re-epithelization and wound closure has yet to be described in the context of diabetic wound healing.

Methods

In this study, we investigated the effects of local administration of an NO-releasing gel on excisional wound healing in diabetic mice. The excisional wounds of each mouse received either NO-releasing gel or a control phosphate-buffered saline (PBS)-releasing gel treatment twice daily until complete wound closure.

Results

Topical administration of NO-gel significantly accelerated the rate of wound healing as compared with PBS-gel-treated mice during the later stages of healing. The treatment also promoted a more regenerative ECM architecture resulting in shorter, less dense, and more randomly aligned collagen fibers within the healed scars, similar to that of unwounded skin. Wound healing promoting factors fibronectin, TGF-β1, CD31, and VEGF were significantly elevated in NO vs. PBS-gel-treated wounds.

Discussion

The results of this work may have important clinical implications for the management of patients with non-healing wounds.
Social determinants of health derived from people with opioid use disorder: Improving data collection, integration and use with cross-domain collaboration and reproducible, data-centric, notebook-style workflows
Authors: Markatou Marianthi , Kennedy Oliver , Brachmann Michael , Mukhopadhyay Raktim , Dharia Arpan , Talal Andrew H.
Published: March 2023

Deriving social determinants of health from underserved populations is an important step in the process of improving the well-being of these populations and in driving policy improvements to facilitate positive change in health outcomes. Collection, integration, and effective use of clinical data for this purpose presents a variety of specific challenges. We assert that combining expertise from three distinct domains, specifically, medical, statistical, and computer and data science can be applied along with provenance-aware, self-documenting workflow tools. This combination permits data integration and facilitates the creation of reproducible workflows and usable (reproducible) results from the sensitive and disparate sources of clinical data that exist for underserved populations.
Tuberculosis remains a major burden in systemic lupus erythematosus patients in Durban, South Africa
Authors: Al-arbi Khaled Mohamed Sefow , Magula Nombulelo P. , Mody Girish M.
Published: March 2023

Objective:

Infections are common in systemic lupus erythematosus (SLE), with tuberculosis (TB) being important in an endemic environment. We studied the prevalence and spectrum of TB in SLE in Durban, South Africa.

Methods:

A medical records review of SLE patients seen over 13-year period, and the demographic data, clinical manifestations, laboratory findings, treatment and outcome were noted.

Results:

There were 512 SLE patients and 72 (14.1%) had TB. Thirty (41.7%) had pulmonary TB (PTB) and 42 (58.3%) had extra-pulmonary TB (EPTB). The prevalence of TB among the different ethnic groups was 36/282 (12.8%) for Indian people, 29/184 (15.8%) Black African people, 7/26 (26.9%) admixed African people and none among the 18 White people. Comparison of the 72 SLE-TB patients with 72 SLE controls showed no difference in gender, age at SLE diagnosis and disease duration. The SLE-TB patients had a significant increase in the clinical and laboratory features of disease activity (arthritis, mucocutaneous lesions, renal involvement, vasculitis, low complement, raised ds-DNA antibodies), and cumulative prednisone use over the preceding 3 months.

Compared to PTB, the EPTB patients were significantly younger, developed TB earlier after SLE diagnosis, and had higher disease activity. The EPTB patients also had increase in features of disease activity (renal, thrombocytopenia, ds–DNA antibodies), and increase in ever use of intravenous methylprednisolone (IV-MP) and mycophenolate mofetil (MMF). On multivariate analysis, the independent risk factors for EPTB were ever use of MMF (p = 0.003) and IV-MP (p = 0.027). Analysis of the cumulative SLE criteria showed renal involvement was an independent risk factor for EPTB. The outcome was similar in both groups.

Conclusion:

We show an increased prevalence of TB (14.1%) and EPTB (58.3%) in SLE in an endemic area and confirm that features of disease activity and use of immunosuppressive therapy are the major risk factors. Renal involvement (as a cumulative criterion) is an independent risk factor for EPTB.
An integrated transcriptome and microbial community analysis reveals potential mechanisms for increased immune responses when replacing silybum marianum meal with soybean meal in growing lambs
Authors: Zhang Tianxi , Ren Yanbo , Yang Chao , Gebeyew Kefyalew , Gao Min , He Zhixiong , Tan Zhiliang
Published: March 2023

Silybum marianum meal is a by-product that remains silymarin complex and is perceived as a potential-protein source. The potential and its mechanism of silybum marianum meal as a protein supplement in ruminants were evaluated by testing the growth performance, biochemical parameters, cytokine levels, gut transcriptome and microbial community profiles. Forty-two male Hulunbeier growing lambs (aged about 3-month-old; averaged body weight of 21.55 kg) were randomly divided into the CON (with 10% soybean meal) and SIL groups (with 10% silybum marianum meal). There was no significant difference in growth performance, feed intakes, or serum biochemical parameters between CON and SIL. The serum levels of IL-1β, TNF-α, TGF-β, HGF, and VEGF were all increased (p < 0.05) in the SIL group as compared with the CON group. Transcriptome gene set enrichment analysis (GSEA) revealed that the core genes in the rumen from SIL group were enriched with fructose and mannose metabolism, while the core genes in the ileum were enriched for three biological process, including digestive tract development, positive regulation of MAPK cascade, and regulation of I-kappaB kinase/NF-kappaB signaling. The 16S rDNA results showed that the relative abundance of Bacteroidetes, Firmicutes, Synergistetes, and Verrucomicrobia in the rumen from SIL group was significantly higher than that in CON group (p < 0.05), whereas Proteobacteria was significantly lower than that in CON group (p < 0.05). The LEfSe analysis showed that the genera Pyramidobacter, Saccharofermentans, Anaerovibrio, Oscillibacter and Barnesiella were enriched in the rumen from SIL group, whereas Sharpea was enriched in the CON group (LDA > 2). In the ileum, there were no significant differences in the phylum-level classification of microbes observed. At the genus level, the relative abundances of Bifidobacterium and Ruminococcus in the ileum from SIL group were significantly higher than that in the CON group (p < 0.05), whereas the relative abundance of Clostridium_XI was lower (p < 0.05). Correlation analysis showed that Clostridium_XI was negatively correlated with VEGF, TGF-β, TNF-α and HGF (p < 0.05). Core genes BMP4 and CD4 were negatively correlated with Clostridium_XI (p < 0.05). Our results indicated that supplementing silybum marianum meal as a replacement for soybean meal resulted in increased cytokines production without affecting growth performance in growing lambs, and the enrichment of immune-related genes and altered microbial community in the ileum were contributed to the increased immune responses.
First report on the enzymatic and immune response of Metarhizium majus bag formulated conidia against Spodoptera frugiperda: An ecofriendly microbial insecticide
Authors: Perumal Vivekanandhan , Kannan Swathy , Alford Lucy , Pittarate Sarayut , Geedi Ruchika , Elangovan Dilipan , Marimuthu Ramachandran , Krutmuang Patcharin
Published: March 2023

Entomopathogenic fungi from microbial sources are a powerful tool for combating insecticide resistance in insect pests. The purpose of the current study was to isolate, identify, and evaluate bag-formulated entomopathogenic fungal conidial virulence against insect pests. We further investigated the enzymatic responses induced by the entomopathogenic fungi as well as the effect on a non-target species. Entomopathogenic fungi were isolated from the Palamalai Hills, India, using the insect bait method, and the Metarhizium majus (MK418990.1) entomopathogen was identified using biotechnological techniques (genomic DNA isolation and 18S rDNA amplification). Bag-formulated fungal conidial efficacy (2.5 × 103, 2.5 × 104, 2.5 × 105, 2.5 × 106, and 2.5 × 107 conidia/ml) was evaluated against third instar larvae of Spodoptera frugiperda at 3, 6, 9, and 12 days of treatment, and acid and alkaline phosphatases, catalase, and superoxide dismutase enzymatic responses were evaluated at 3 days post-treatment. After 12 days of treatment, non-target assays on the earthworm Eudrilus eugeniae were performed using an artificial soil assay. Results of the bag formulated fungal conidial treatment showed that S. frugiperda had high susceptibility rates at higher concentrations (2.5 × 107 conidia/ml) of M. majus. Lower concentration of 2.5 × 103 conidia/ml caused 68.6% mortality, while 2.5 × 107 conidia/ml caused 100% mortality at 9 days post treatment. Investigation into enzymatic responses revealed that at 3 days post M. majus conidia exposure (2.5 × 103 conidia/ml), insect enzyme levels had significantly changed, with acid and alkaline phosphatases, and catalase enzymes significantly reduced and superoxide dismutase enzymes significantly raised relative to the control. After 12 days of treatment, no sublethal effects of M. majus conidia were observed on E. eugeniae, with no observed damage to gut tissues including lumen and epithelial cells, the nucleus, setae, coelom, mitochondria, and muscles. This study offers support for the use of fungal conidia in the target-specific control of insect pests.
Excessive consumption of mucin by over-colonized Akkermansia muciniphila promotes intestinal barrier damage during malignant intestinal environment
Authors: Qu Shuang , Zheng Yinghui , Huang Yichun , Feng Yicheng , Xu Kunyao , Zhang Wei , Wang Yawen , Nie Kaili , Qin Meng
Published: March 2023

Gut microbiota disorders damage the intestinal barrier, which causes intestinal disease. Thus, we screened the microbiota with significant changes using an in situ malignant colorectal cancer (CRC) model. Among the colonies with increased abundance, Akkermansia muciniphila (A. muciniphila) is known for its characteristic of breaking down mucin, which is an essential component of the intestinal barrier. The role of A. muciniphila remains controversial. To investigate the effect of excess A. muciniphila on the intestinal barrier, we established an over-colonized A. muciniphila mouse model by administering a live bacterial suspension after disrupting the original gut microbiome with antibiotics. The results showed that over-colonization of A. muciniphila decreased intestinal mucin content. The mRNA and protein expression levels of tight junction proteins also decreased significantly in the over-colonized A. muciniphila mouse model. Our findings reveal that excess colonization by A. muciniphila breaks the dynamic balance between mucin secretion and degradation, reduces the thickness of the intestinal mucus layer, and damages the intestinal barrier, which would eventually aggravate the development of colitis and CRC. These results will raise awareness about the safety of A. muciniphila serving as a probiotic.
Dietary grape pomace extract supplementation improved meat quality, antioxidant capacity, and immune performance in finishing pigs
Authors: Tian Xuekai , Li Dong , Zhao Xin , Xiao Zitong , Sun Jingchun , Yuan Tiantian , Wang Yongcheng , Zuo Xinhui , Yang Gongshe , Yu Taiyong
Published: March 2023

In pig production, reducing production costs and improving immunity are important. Grape pomace, a good agricultural by-product, has been thrown away as food waste for a long time. Recently, we found that it could be used as a new source of pig feed. We investigated the effect of grape pomace on inflammation, gut barrier function, meat quality, and growth performance in finishing pigs. Our results indicated that treatment samples showed a significant decrease in water loss, IL-1β, DAO, ROS, and MDA content (p < 0.05). IgA, IgG, IgM, CAT, T-AOC, SOD, and IFN-γ significantly increased compared with those in control samples (p < 0.05). Meanwhile, the relative mRNA expression of the tight junction protein occludin showed a significant difference (p < 0.05). Analysis of metagenomic sequencing indicated that grape pomace significantly decreased the relative abundance of Treponema and Streptococcus (p < 0.05). In summary, our results demonstrated that grape pomace could improve meat quality, alleviate inflammation, and decrease oxidative stress.
Study on the correlation between microbial communities with physicochemical properties and flavor substances in the Xiasha round of cave-brewed sauce-flavor Baijiu
Authors: Ren Tingting , Su Wei , Mu Yingchun , Qi Qi , Zhang Dangwei
Published: March 2023

The Chishui River basin is the main production area of the sauce-flavor Baijiu. Due to the particularity of sauce-flavor Baijiu technology, a large site of workshops needs to be built for brewing and storage. Therefore, used the natural karst caves of Guizhou province to manufacture the sauce-flavor Baijiu, which has enriched the connotation of sauce-flavor Baijiu and saved valuable land resources. In this study, the fermentation grains in the seven stages during the Xiasha round of the cave-brewed sauce-flavor Baijiu (CBSB) were detected using a combination of physicochemical analysis, Headspace solid-phase microextraction gas chromatography-mass detection, and Illumina HiSeq sequencing methods. The results showed Unspecified_Leuconostocaceae, Weissella, Unspecified_Bacillaceae, Saccharomycopsis, Thermomyces, and Unspecified_Phaffomycetaceae were the main bacterial and fungal genera in the stacking fermentation (SF). In the cellar fermentation (CF), the Lactobacillus, Unspecified_Lactobacillaceae, Thermoactinomyces, Saccharomycopsis, Unspecified_Phaffomycetaceae, and Wickerhamomyces were the main bacterial and fungal genera. A total of 72 volatiles were detected in the fermented grains. Linear discriminant analysis Effect Size (LEfSe) identified 23 significantly different volatile metabolites in the fermentation process, including 7 esters, 6 alcohols, 4 acids, 3 phenols, 1 hydrocarbon, and 2 other compounds. Redundancy analysis was used to explore the correlation between dominant microbial genera and physicochemical properties. Starch was the main physicochemical property affecting microbial succession in the SF. Acidity, moisture, and reducing sugar were the main driving factors of microbial succession in the CF. The Pearson correlation coefficient revealed the correlation between dominant microbial genera and significantly different volatile flavor substances. A total of 18 dominant microbial genera were associated with significantly different volatile metabolites, Lactobacillus, Weissella, Wickerhamomyces, and Aspergillus were shown to play crucial roles in metabolite synthesis. On this basis, a metabolic map of the dominant microbial genera was established. This study provides a theoretical basis for the production and quality control of sauce-flavor Baijiu brewed in natural karst caves and lays a foundation for studying the link between flavor formation and microorganisms.
Metabolic network reconstruction of Euglena gracilis: Current state, challenges, and applications
Authors: Inwongwan Sahutchai , Pekkoh Jeeraporn , Pumas Chayakorn , Sattayawat Pachara
Published: March 2023

A metabolic model, representing all biochemical reactions in a cell, is a prerequisite for several approaches in systems biology used to explore the metabolic phenotype of an organism. Despite the use of Euglena in diverse industrial applications and as a biological model, there is limited understanding of its metabolic network capacity. The unavailability of the completed genome data and the highly complex evolution of Euglena are significant obstacles to the reconstruction and analysis of its genome-scale metabolic model. In this mini-review, we discuss the current state and challenges of metabolic network reconstruction in Euglena gracilis. We have collated and present the available relevant data for the metabolic network reconstruction of E. gracilis, which could be used to improve the quality of the metabolic model of E. gracilis. Furthermore, we deliver the potential applications of the model in metabolic engineering. Altogether, it is supposed that this mini-review would facilitate the investigation of metabolic networks in Euglena and further lay out a direction for model-assisted metabolic engineering.
Restricted and repetitive behaviors and their developmental and demographic correlates in 4–8-year-old children: A transdiagnostic approach
Authors: Keating Jennifer , Van Goozen Stephanie , Uljarevic Mirko , Hay Dale , Leekam Susan R.
Published: March 2023

Background: Restricted and repetitive behaviors (RRBs) are a broad class of behaviors characterized by frequent action repetition and intense preference for sameness. Research has predominantly focused on RRBs in diagnosed clinical groups, particularly in autism spectrum disorder and genetic disorders. Using a transdiagnostic approach, the current study examined RRBs in a diverse sample of children in relation to developmental and demographic correlates (age, language, non-verbal ability, child anxiety, sex, and socioeconomic status). Separate analyses examined two RRB subtypes; repetitive sensory and motor behaviors (RSMB) and insistence on sameness (IS).

Method: Children (N = 260, age 4–8 years, 174 male, 86 female) in mainstream schools identified by teachers as having behavioral, emotional, and/or cognitive difficulties, were assessed using the Repetitive Behavior Questionnaire-2 (RBQ-2), the British Picture Vocabulary Scale (BPVS), Lucid Ability Scale, the Welsh Index of Multiple Deprivation (WIMD) and the Screen for Child Anxiety Related Emotional Disorders (SCARED). Recruitment excluded diagnosed clinical conditions. The Strengths and Difficulties Questionnaire (SDQ) was used to assess children’s difficulties.

Results: RRB scores were of high frequency and the scores for the IS were higher than for RSMB. The severity of anxiety symptoms and male sex were significantly associated with both RRB subtypes, and younger age and SES scores were associated with IS. Elevated RRB total and subtype scores were significantly related to SDQ scores for emotion, conduct, hyperactivity, and peer-relations.

Discussion: The study provides the first evidence of RRBs in a diverse sample of young children with emerging difficulties in behavior, cognition, and/or emotion. The results contribute to proposals about psychological development in RRB and indicate that RRBs are best represented on a continuum of severity found across children in the early school years. The results support previous findings of a relation between RRB and anxiety reported in clinical samples and importantly, they indicate that it is time to move beyond the study of categorically defined groups and consider correlates of RRBs that include broad indices of mental health and well-being.
Supplementing transcranial direct current stimulation to local infiltration series for refractory neuropathic craniocephalic pain: A randomized controlled pilot trial
Authors: Wandrey Jan D. , Kastelik Joanna , Fritzsche Thomas , Denke Claudia , Schäfer Michael , Tafelski Sascha
Published: March 2023

Background

Some patients with neuralgia of cranial nerves with otherwise therapy-refractory pain respond to invasive therapy with local anesthetics. Unfortunately, pain regularly relapses despite multimodal pain management. Transcranial direct current stimulation (tDCS) may prolong pain response due to neuro-modulatory effects.

Methods

This controlled clinical pilot trial randomized patients to receive anodal, cathodal or sham-tDCS stimulation prior to local anesthetic infiltration. Pain attenuation, quality-of-life and side effects were assessed and compared with historic controls to estimate effects of tDCS stimulation setting.

Results

Altogether, 17 patients were randomized into three groups with different stimulation protocols. Relative reduction of pain intensity in per protocol treated patients were median 73%, 50% and 69% in anodal, cathodal and sham group, respectively (p = 0.726). Compared with a historic control group, a lower rate of responders with 50% reduction of pain intensity indicates probable placebo effects (OR 3.41 stimulation vs. non-stimulation setting, NNT 3.63). 76.9% (n = 10) of tDCS patients reported mild side-effects. Of all initially included 17 patients, 23.5% (n = 4) withdrew their study participation with highest proportion in the cathodal group (n = 3). A sample size calculation for a confirmatory trial revealed 120 patients using conservative estimations.

Discussion

This pilot trial does not support series of anodal tDCS as neuro-modulatory treatment to enhance pain alleviation of local anesthetic infiltration series. Notably, results may indicate placebo effects of tDCS settings. Feasibility of studies in this population was limited due to relevant drop-out rates. Anodal tDCS warrants further confirmation as neuro-modulatory pain treatment option.
Clinicians' preferences for managing aneurysmal subarachnoid hemorrhage using endothelin receptor antagonists
Authors: Heidenreich Sebastian , Trapali Myrto , Krucien Nicolas , Phillips-Beyer Andrea
Published: March 2023

Background

The endothelin receptor antagonist (ERA) clazosentan is being investigated for the medical prevention of cerebral vasospasm and associated complications, such as delayed cerebral ischemia (DCI), after aneurysmal subarachnoid hemorrhage (aSAH). This study quantified how clinicians weigh the benefits and risks of ERAs for DCI prevention to better understand their treatment needs and expectations.

Methods

An online choice experiment was conducted to elicit preferences of neurologists, intensivists, and neurosurgeons treating aSAH in the US and UK for the use of ERAs. The design of the choice experiment was informed by a feasibility assessment (N = 100), one-on-one interviews with clinicians (N = 10), a qualitative pilot (N = 13), and a quantitative pilot (N = 50). Selected treatment attributes included in the choice experiment were: one benefit (likelihood of DCI); and three risks (lung complications, hypotension, and anemia). In the choice experiment, clinicians repeatedly chose best and worst treatment options based on a scenario of a patient being treated in the ICU after aneurism repair. A correlated mixed logit model determined the relative attribute importance (RAI) and associated highest density interval (HDI) as well as acceptable benefit-risk trade-offs.

Results

The final choice experiment was completed by 350 clinicians (116 neurologists, 129 intensivists/intensive care clinicians, and 105 neurosurgeons; mean age, 47.4 years). Reducing the likelihood of DCI (RAI = 56.5% [HDI, 53.6–59.5%]) had the largest impact on clinicians' treatment choices, followed by avoiding the risks of lung complications (RAI = 29.6% [HDI, 27.1–32.3%]), hypotension (RAI = 9.2% [HDI, 7.5–10.8%]), and anemia (RAI = 4.7% [HDI, 3.7–5.8%]). Clinicians expected the likelihood of DCI to decrease by ≥8.1% for a 20% increase in the risk of lung complications, ≥2.4% for a 20% increase in the risk of hypotension, and ≥1.2% for a 20% increase in the risk of anemia.

Conclusions

Clinicians were willing to accept certain increased risks of adverse events for a reduced risk of DCI after aSAH. The likelihood of DCI occurring after aSAH can therefore be considered a clinically relevant endpoint in aSAH treatment development. Thus, evaluations of ERAs might focus on whether improvements (i.e., reductions) in the likelihood of DCI justify the risks of adverse events.
Continuous dynamics in behavior reveal interactions between perceptual warping in categorization and speech-in-noise perception
Authors: Bidelman Gavin M. , Carter Jared A.
Published: March 2023

Introduction

Spoken language comprehension requires listeners map continuous features of the speech signal to discrete category labels. Categories are however malleable to surrounding context and stimulus precedence; listeners’ percept can dynamically shift depending on the sequencing of adjacent stimuli resulting in a warping of the heard phonetic category. Here, we investigated whether such perceptual warping—which amplify categorical hearing—might alter speech processing in noise-degraded listening scenarios.

Methods

We measured continuous dynamics in perception and category judgments of an acoustic-phonetic vowel gradient via mouse tracking. Tokens were presented in serial vs. random orders to induce more/less perceptual warping while listeners categorized continua in clean and noise conditions.

Results

Listeners’ responses were faster and their mouse trajectories closer to the ultimate behavioral selection (marked visually on the screen) in serial vs. random order, suggesting increased perceptual attraction to category exemplars. Interestingly, order effects emerged earlier and persisted later in the trial time course when categorizing speech in noise.

Discussion

These data describe interactions between perceptual warping in categorization and speech-in-noise perception: warping strengthens the behavioral attraction to relevant speech categories, making listeners more decisive (though not necessarily more accurate) in their decisions of both clean and noise-degraded speech.
Individual differences in beta-band oscillations predict motor-inhibitory control
Authors: Ding Qian , Lin Tuo , Cai Guiyuan , Ou Zitong , Yao Shantong , Zhu Hongxiang , Lan Yue
Published: March 2023

Objective

The ability of motor-inhibitory control is critical in daily life. The physiological mechanisms underlying motor inhibitory control deficits remain to be elucidated. Beta band oscillations have been suggested to be related to motor performance, but whether they relate to motor-inhibitory control remains unclear. This study is aimed at systematically investigating the relationship between beta band oscillations and motor-inhibitory control to determine whether beta band oscillations were related to the ability of motor-inhibitory control.

Methods

We studied 30 healthy young adults (age: 21.6 ± 1.5 years). Stop-signal reaction time (SSRT) was derived from stop signal task, indicating the ability of motor-inhibitory control. Resting-state electroencephalography (EEG) was recorded for 12 min. Beta band power and functional connectivity (including global efficiency) were calculated. Correlations between beta band oscillations and SSRT were performed.

Results

Beta band EEG power in left and right motor cortex (MC), right somatosensory cortex (SC), and right inferior frontal cortex (IFC) was positively correlated with SSRT (P’s = 0.031, 0.021, 0.045, and 0.015, respectively). Beta band coherence between bilateral MC, SC, and IFC was also positively correlated with SSRT (P’s < 0.05). Beta band global efficiency was positively correlated with SSRT (P = 0.01).

Conclusion

This is the first study to investigate the relationship between resting-state cortical beta oscillations and response inhibition. Our findings revealed that individuals with better ability of motor inhibitory control tend to have less cortical beta band power and functional connectivity. This study has clinical significance on the underlying mechanisms of motor inhibitory control deficits.
Acid-sensing ion channel 3 is required for agmatine-induced histamine-independent itch in mice
Authors: Zhou Guo-Kun , Xu Wen-Jing , Lu Yi , Zhou Yan , Feng Chen-Zhang , Zhang Jiang-Tao , Sun Shi-Yu , Wang Ruo-Meng , Liu Tong , Wu Bin
Published: March 2023

Introduction

Itch is a common symptom of many skin and systemic diseases. Identifying novel endogenous itch mediators and the downstream signaling pathways involved will contribute to the development of new strategies for the treatment of chronic itch. In the present study, we adopted behavioral testing, patch clamp recording and metabonomics analysis to investigate the role of agmatine in itch and the underlying mechanism.

Methods

Behavioral analysis was used to evaluate the establishing of acute and chronic itch mice model, and to test the effects of different drugs or agents on mice itch behavior. Western blotting analysis was used to test the effect of agmatine on phosphorylation of ERK (p-ERK) expression in the spinal cord. Patch clamp recording was used to determine the effect agmatine on the excitability of DRG neurons and the role of ASIC3. Finally, the metabonomics analysis was performed to detect the concentration of agmatine in the affected skin under atopic dermatitis or psoriasis conditions.

Results

We fused a mouse model and found that an intradermal injection of agmatine (an endogenous polyamine) into the nape of the neck or cheek induced histamine-independent scratching behavior in a dose-dependent manner. In addition, the ablation of nociceptive C-fibers by resiniferatoxin (RTX) abolished agmatine-induced scratching behavior. However, agmatine-induced itch was not affected by the pharmacological inhibition of either transient receptor potential vanilloid 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1); similar results were obtained from TRPV1−/− or TRPA1−/− mice. Furthermore, agmatine-induced itch was significantly suppressed by the administration of acid-sensing ion channel 3 (ASIC3) inhibitors, APETx2 or amiloride. Agmatine also induced the upregulation of p-ERK in the spinal cord; this effect was inhibited by amiloride. Current clamp recording showed that the acute perfusion of agmatine reduced the rheobase and increased the number of evoked action potentials in acute dissociated dorsal root ganglion (DRG) neurons while amiloride reversed agmatine-induced neuronal hyperexcitability. Finally, we identified significantly higher levels of agmatine in the affected skin of a mouse model of atopic dermatitis (AD) when compared to controls, and the scratching behavior of AD mice was significantly attenuated by blocking ASIC3.

Discussion

Collectively, these results provide evidence that agmatine is a novel mediator of itch and induces itch via the activation of ASIC3. Targeting neuronal ASIC3 signaling may represent a novel strategy for the treatment of itch.
Central obesity as assessed by conicity index and a-body shape index associates with cardiovascular risk factors and mortality in kidney failure patients
Authors: Ryu Kakei , Suliman Mohamed E. , Qureshi Abdul Rashid , Chen Zhimin , Avesani Carla Maria , Brismar Torkel B. , Ripsweden Jonaz , Barany Peter , Heimbürger Olof , Stenvinkel Peter , Lindholm Bengt
Published: March 2023

Background

Anthropometric indices of central obesity, waist circumference (WC), conicity index (CI), and a-body shape index (ABSI), are prognostic indicators of cardiovascular (CV) risk. The association of CI and ABSI with other CV risk indices, markers of nutritional status and inflammation, and clinical outcomes in chronic kidney disease (CKD) stage 5 (CKD5) patients was investigated.

Methods

In a cross-sectional study with longitudinal follow up of 203 clinically stable patients with CKD5 (median age 56 years; 68% males, 17% diabetics, 22% with CV disease, and 39% malnourished), we investigated CI and ABSI and their associations with atherogenic index of plasma (AIP), Framingham CV risk score (FRS), Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC), handgrip strength (HGS), high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). CV events (CVE) and all-cause mortality during up to 10-years follow up were analyzed by multivariate survival analysis of restricted mean survival time (RMST).

Results

Chronic kidney disease patients with middle and highest CI and ABSI tertiles (indicating greater abdominal fat deposition), compared to those with the lowest CI and ABSI tertiles, tended to be older, more often men and diabetic, had significantly higher levels of hsCRP, IL-6, AIP, FRS, CAC and AVC scores. CI and ABSI were positively correlated with CAC, FRS, AIP, hsCRP and IL-6. Both CI and ABSI were negatively correlated with HGS. In age-weighted survival analysis, higher CI and ABSI were associated with higher risk of CVE (Wald test = 4.92, p = 0.027; Wald test = 4.95, p = 0.026, respectively) and all-cause mortality (Wald test = 5.24, p = 0.022; Wald test = 5.19, p = 0.023, respectively). In RMST analysis, low vs. high and middle tertiles of CI and ABSI associated with prolonged CVE-free time and death-free time, and these differences between groups increased over time.

Conclusion

Abdominal fat deposit indices, CI and ABSI, predicted CV outcomes and all-cause mortality, and were significantly associated with the inflammatory status in CKD patients.
Functional roles of FAP-α in metabolism, migration and invasion of human cancer cells
Authors: Mori Noriko , Jin Jiefu , Krishnamachary Balaji , Mironchik Yelena , Wildes Flonné , Vesuna Farhad , Barnett James D. , Bhujwalla Zaver M.
Published: March 2023

Fibroblast activation protein-α (FAP-α) is a transmembrane serine protease that is attracting significant interest as it is expressed by a subgroup of cancer-associated fibroblasts that play a role in immune suppression and cancer metastasis. FAP-α is also expressed by some cancer cells, such as melanoma, colorectal and breast cancer cells. Triple negative breast cancer (TNBC) is an aggressive cancer that urgently requires identification of novel targets for therapy. To expand our understanding of the functional roles of FAP-α in TNBC we engineered a human TNBC cell line, MDA-MB-231, to stably overexpress FAP-α and characterized changes in metabolism by 1H magnetic resonance spectroscopy, cell proliferation, migration characterized by wound healing, and invasion. FAP-α overexpression resulted in significant alterations in myoinositol, choline metabolites, creatine, and taurine, as well as a significant increase of migration and invasion, although proliferation remained unaltered. The increase of migration and invasion are consistent with the known activities of FAP-α as an exopeptidase and endopeptidase/gelatinase/collagenase in tissue remodeling and repair, and in cell migration. We additionally determined the effects of FAP-α overexpression on the human fibrosarcoma HT1080 cell line that showed increased migration, accompanied by limited changes in metabolism that identified the dependency of the metabolic changes on cell type. These metabolic data identify a previously unknown role of FAP-α in modifying cancer cell metabolism in the TNBC cell line studied here that may provide new insights into its functional roles in cancer progression.
Investigation of trends in gut microbiome associated with colorectal cancer using machine learning
Authors: Yu Chaoran , Zhou Zhiyuan , Liu Bin , Yao Danhua , Huang Yuhua , Wang Pengfei , Li Yousheng
Published: March 2023

Background

The rapid growth of publications on the gut microbiome and colorectal cancer (CRC) makes it feasible for text mining and bibliometric analysis.

Methods

Publications were retrieved from the Web of Science. Bioinformatics analysis was performed, and a machine learning-based Latent Dirichlet Allocation (LDA) model was used to identify the subfield research topics.

Results

A total of 5,696 publications related to the gut microbiome and CRC were retrieved from the Web of Science Core Collection from 2000 to 2022. China and the USA were the most productive countries. The top 25 references, institutions, and authors with the strongest citation bursts were identified. Abstracts from all 5,696 publications were extracted for a text mining analysis that identified the top 50 topics in this field with increasing interest. The colitis animal model, expression of cytokines, microbiome sequencing and 16s, microbiome composition and dysbiosis, and cell growth inhibition were increasingly noticed during the last two years. The 50 most intensively investigated topics were identified and further categorized into four clusters, including “microbiome sequencing and tumor,” “microbiome compositions, interactions, and treatment,” “microbiome molecular features and mechanisms,” and “microbiome and metabolism.”

Conclusion

This bibliometric analysis explores the historical research tendencies in the gut microbiome and CRC and identifies specific topics of increasing interest. The developmental trajectory, along with the noticeable research topics characterized by this analysis, will contribute to the future direction of research in CRC and its clinical translation.