bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and Phenotypic Characterization of B Cells in the Teleost Adipose Tissue
Authors: Simón Rocío , Martín-Martín Alba , Morel Esther , Díaz-Rosales Patricia , Tafalla Carolina
Published: May 2022

The immune response of the adipose tissue (AT) has been neglected in most animal models until investigations in human and mice linked obesity to chronic inflammation, highlighting the immune nature of this tissue. Despite this, in teleost fish, only a few studies have addressed the immune role of the AT. These studies have mostly focused on reporting transcriptional changes in the AT in response to diverse intraperitoneally delivered stimuli. Although the presence of B cells within the AT was also previously revealed, these cells have never been phenotypically or functionally characterized and this is what we have addressed in the current study. Initially, the B cell populations present in the rainbow trout (Oncorhynchus mykiss) AT were characterized in comparison to B cells from other sources. As occurs in other rainbow trout tissues, IgM+IgD+, IgM+IgD-and IgD+IgM-B cell subsets were identified in the AT. Interestingly, AT IgM+IgD-B cells showed a transcriptional profile that agrees with that of cells that have committed to plasmablasts/plasma cells, being this profile much more pronounced towards a differentiation state than that of blood IgM+IgD-B cells. Accordingly, the IgM-secreting capacity of AT B cells is significantly higher than that of blood B cells. Additionally, AT IgM+IgD+B cells also showed specific phenotypic traits when compared to their counterparts in other tissues. Finally, we established how these B cell subsets responded when rainbow trout were intraperitoneally injected with a model antigen. Our results demonstrate that the AT hosts plasmablasts/plasma cells that secrete specific IgMs, as happens in the peritoneal cavity and systemic immune tissues. Although the presence of these antigen-specific IgM-secreting cells was more abundant in the peritoneal cavity, these specific differentiated B cells were detected in the AT for long time periods at levels similar to those of spleen and head kidney. Our results provide new evidence regarding the immune role of the teleost AT, indicating that it functions as a secondary lymphoid organ that promotes immunity to peritoneal antigens.
Role and Diagnostic Performance of Host Epigenome in Respiratory Morbidity after RSV Infection: The EPIRESVi Study
Authors: Pischedda Sara , Rivero-Calle Irene , Gómez-Carballa Alberto , Cebey-López Miriam , Barral-Arca Ruth , Gómez-Rial Jose , Pardo-Seco Jacobo , Curras-Tuala María-José , Viz-Lasheras Sandra , Bello Xabier , Crujeiras Ana B. , Diaz-Lagares Angel , González-López María Teresa , Martinón-Torres Federico , Salas Antonio ,   GENDRES consortium
Published: May 2022

Background

Respiratory syncytial virus (RSV) infection has been associated with the subsequent development of recurrent wheezing and asthma, although the mechanisms involved are still unknown. We investigate the role of epigenetics in the respiratory morbidity after infection by comparing methylation patterns from children who develop recurrent wheezing (RW-RSV), subsequent asthma (AS-RVS), and those experiencing complete recovery (CR-RSV).

Methods

Prospective, observational study of infants aged < 2 years with RSV respiratory infection admitted to hospital and followed-up after discharge for at least three years. According to their clinical course, patients were categorized into subgroups: RW-RSV (n = 36), AS-RSV (n = 9), and CR-RSV (n = 32). The DNA genome-wide methylation pattern was analyzed in whole blood samples, collected during the acute phase of the infection, using the Illumina Infinium Methylation EPIC BeadChip (850K CpG sites). Differences in methylation were determined through a linear regression model adjusted for age, gender and cell composition.

Results

Patients who developed respiratory sequelae showed a statistically significant higher proportion of NK and CD8T cells (inferred through a deconvolution approach) than those with complete recovery. We identified 5,097 significant differentially methylated positions (DMPs) when comparing RW-RSV and AS-RVS together against CR-RSV. Methylation profiles affect several genes involved in airway inflammation processes. The most significant DMPs were found to be hypomethylated in cases and therefore generally leading to overexpression of affected genes. The lead CpG position (cg24509398) falls at the gene body of EYA3 (P-value = 2.77×10-10), a tyrosine phosphatase connected with pulmonary vascular remodeling, a key process in the asthma pathology. Logistic regression analysis resulted in a diagnostic epigenetic signature of 3-DMPs (involving genes ZNF2698, LOC102723354 and RPL15/NKIRAS1) that allows to efficiently differentiate sequelae cases from CR-RSV patients (AUC = 1.00). Enrichment pathway analysis reveals the role of the cell cycle checkpoint (FDR P-value = 4.71×10-2), DNA damage (FDP-value = 2.53×10-2), and DNA integrity checkpoint (FDR P-value = 2.56×10-2) in differentiating sequelae from CR-RSV patients.

Conclusions

Epigenetic mechanisms might play a fundamental role in the long-term sequelae after RSV infection, contributing to explain the different phenotypes observed.
Advances in Immune Monitoring Approaches for Sepsis-Induced Immunosuppression
Authors: Yao Ren-Qi , Ren Chao , Zheng Li-Yu , Xia Zhao-Fan , Yao Yong-Ming
Published: May 2022

Sepsis represents a life-threatening organ dysfunction due to an aberrant host response. Of note is that majority of patients have experienced a severe immune depression during and after sepsis, which is significantly correlated with the occurrence of nosocomial infection and higher risk of in-hospital death. Nevertheless, the clinical sign of sepsis-induced immune paralysis remains highly indetectable and ambiguous. Given that, specific yet robust biomarkers for monitoring the immune functional status of septic patients are of prominent significance in clinical practice. In turn, the stratification of a subgroup of septic patients with an immunosuppressive state will greatly contribute to the implementation of personalized adjuvant immunotherapy. In this review, we comprehensively summarize the mechanism of sepsis-associated immunosuppression at the cellular level and highlight the recent advances in immune monitoring approaches targeting the functional status of both innate and adaptive immune responses.
Antiviral Activities of Interleukin-27: A Partner for Interferons?
Authors: Amsden Heather , Kourko Olena , Roth Madison , Gee Katrina
Published: May 2022

Emergence of new, pandemic-level viral threats has brought to the forefront the importance of viral immunology and continued improvement of antiviral therapies. Interleukin-27 (IL-27) is a pleiotropic cytokine that regulates both innate and adaptive immune responses. Accumulating evidence has revealed potent antiviral activities of IL-27 against numerous viruses, including HIV, influenza, HBV and more. IL-27 contributes to the immune response against viruses indirectly by increasing production of interferons (IFNs) which have various antiviral effects. Additionally, IL-27 can directly interfere with viral infection both by acting similarly to an IFN itself and by modulating the differentiation and function of various immune cells. This review discusses the IFN-dependent and IFN-independent antiviral mechanisms of IL-27 and highlights the potential of IL-27 as a therapeutic cytokine for viral infection.
Linkage of Macro- and Microscale Modeling Tools for Additive Manufacturing of Steels
Authors: Sjöström Julia , Durga A. , Lindwall Greta
Published: May 2022

Additive manufacturing (AM) offers several benefits including the capability to produce unique microstructures, geometrical freedom allowing for material and energy savings, and easy production lines with fewer post-processing steps. However, AM processes are complex and phenomena occurring at different length and time scales need to be understood and controlled to avoid challenges with, for example, defects, residual stresses, distortions, and alloy restrictions. To overcome some of these challenges and to have more control over the final product, computational tools for different length scales need to be combined. In this work, an 18Ni300 maraging steel part is studied to understand the link between the process parameters and the as-built microstructure. The temperature evolution during laser powder bed fusion is simulated using the MSC simulation software Simufact Additive. This result is then linked to microscale models within the Thermo-Calc software package to predict the elemental micro-segregation, martensite start (Ms) temperature, and martensite fraction. The different values of the key process parameters such as laser speed, laser power, heating efficiency, and baseplate temperature are considered, leading to different thermal histories. The thermal histories affect the elemental segregation across the solidification structure, which in turn results in different Ms temperatures at different locations of the built part. It is found that higher laser energy generally causes higher temperatures and higher cooling rates, which results in a larger degree of elemental segregation and lower Ms temperatures in segregated regions. Furthermore, the segregated regions are predicted to have Ms temperatures below 200°C, which would result in retained austenite when using a baseplate temperature of 200°C. On the other hand, by using a baseplate temperature of 100°C, all regions would reach temperatures below the Ms temperature, and an almost fully martensitic structure would be possible. In summary, it is demonstrated how the linkage of macro- and microscale modeling tools for AM can be used to optimize the process and produce the desired microstructure, thereby achieving the desired mechanical properties.
Processing Method for Metallic Substrate Using the Liquid Metal Lapping-Polishing Plate
Authors: Ji Renquan , Zhang Liyang , Zhang Li , Li Yanbiao , Lu Shasha , Fu Yufei
Published: May 2022

Metal is the primary substrate for fabricating flexible sensors, and its surface quality has a significant effect on the performance of these sensors. The traditional lapping-polishing technology has the disadvantages of being time-consuming and presenting difficulty in controlling the uniformity. In this paper, a liquid metal lapping-polishing plate with a self-shaping function is proposed and developed, which can realize high quality and low surface damage in the processing of the metallic substrate. It is found from the fundaments of the liquid metal lapping-polishing plate that the temperature generated by the friction between the workpiece and plate plays an important role in affecting the processing performance, and then a numerical study of the temperature field on the liquid metal lapping-polishing plate surface has been carried out, and it is found that the temperature increase with the increment of the pressure and rotation speed of the lapping-polishing plate on the target surface. Finally, it is found from experiments that the experimental results have shown to be in good agreement with the corresponding experimental data for the highest temperature under specific conditions and the processing performance has been significantly improved as well.
Nonlinear Viscoelastic Properties of 3D-Printed Tissue Mimicking Materials and Metrics to Determine the Best Printed Material Match to Tissue Mechanical Behavior
Authors: Verga Adam S. , Tucker Sarah Jo , Gao Yuming , Plaskett Alena M. , Hollister Scott J.
Published: May 2022

3D-printed biomaterials have become ubiquitous for clinical applications including tissue-mimicking surgical/procedure planning models and implantable tissue engineering scaffolds. In each case, a fundamental hypothesis is that printed material mechanical properties should match those of the tissue being replaced or modeled as closely as possible. Evaluating these hypotheses requires 1) consistent nonlinear elastic/viscoelastic constitutive model fits of 3D-printed biomaterials and tissues and 2) metrics to determine how well 3D-printed biomaterial mechanical properties match a corresponding tissue. Here we utilize inverse finite element modeling to fit nonlinear viscoelastic models with Neo-Hookean kernels to 29 Polyjet 3D-printed tissue-mimicking materials. We demonstrate that the viscoelastic models fit well with R2 > 0.95. We also introduce three metrics ( least-squares difference, Kolmogorov–Smirnov statistics, and the area under stress/strain or load/displacement curve) to compare printed material properties to tissue properties. All metrics showed lower values for better matches between 3D-printed materials and tissues. These results provide a template for comparing 3D-printed material mechanical properties to tissue mechanical properties, and therefore, a basis for testing the fundamental hypotheses of 3D-printed tissue-mimicking materials.
A Brain Tumor Image Segmentation Method Based on Quantum Entanglement and Wormhole Behaved Particle Swarm Optimization
Authors: Zhang Tianchi , Zhang Jing , Xue Teng , Rashid Mohammad Hasanur
Published: May 2022

Purpose

Although classical techniques for image segmentation may work well for some images, they may perform poorly or not work at all for others. It often depends on the properties of the particular image segmentation task under study. The reliable segmentation of brain tumors in medical images represents a particularly challenging and essential task. For example, some brain tumors may exhibit complex so-called “bottle-neck” shapes which are essentially circles with long indistinct tapering tails, known as a “dual tail.” Such challenging conditions may not be readily segmented, particularly in the extended tail region or around the so-called “bottle-neck” area. In those cases, existing image segmentation techniques often fail to work well.

Methods

Existing research on image segmentation using wormhole and entangle theory is first analyzed. Next, a random positioning search method that uses a quantum-behaved particle swarm optimization (QPSO) approach is improved by using a hyperbolic wormhole path measure for seeding and linking particles. Finally, our novel quantum and wormhole-behaved particle swarm optimization (QWPSO) is proposed.

Results

Experimental results show that our QWPSO algorithm can better cluster complex “dual tail” regions into groupings with greater adaptability than conventional QPSO. Experimental work also improves operational efficiency and segmentation accuracy compared with current competing reference methods.

Conclusion

Our QWPSO method appears extremely promising for isolating smeared/indistinct regions of complex shape typical of medical image segmentation tasks. The technique is especially advantageous for segmentation in the so-called “bottle-neck” and “dual tail”-shaped regions appearing in brain tumor images.
Impact of High-Altitude Hypoxia on Bone Defect Repair: A Review of Molecular Mechanisms and Therapeutic Implications
Authors: Chen Pei , Liu Yushan , Liu Wenjing , Wang Yarong , Liu Ziyi , Rong Mingdeng
Published: May 2022

Reaching areas at altitudes over 2,500–3,000 m above sea level has become increasingly common due to commerce, military deployment, tourism, and entertainment. The high-altitude environment exerts systemic effects on humans that represent a series of compensatory reactions and affects the activity of bone cells. Cellular structures closely related to oxygen-sensing produce corresponding functional changes, resulting in decreased tissue vascularization, declined repair ability of bone defects, and longer healing time. This review focuses on the impact of high-altitude hypoxia on bone defect repair and discusses the possible mechanisms related to ion channels, reactive oxygen species production, mitochondrial function, autophagy, and epigenetics. Based on the key pathogenic mechanisms, potential therapeutic strategies have also been suggested. This review contributes novel insights into the mechanisms of abnormal bone defect repair in hypoxic environments, along with therapeutic applications. We aim to provide a foundation for future targeted, personalized, and precise bone regeneration therapies according to the adaptation of patients to high altitudes.
20 Years of Legislation - How Australia Has Responded to the Challenge of Regulating Genetically Modified Organisms in the Clinic
Authors: O’Sullivan Gabrielle M. , Philips Joshua G. , Mitchell Heidi J. , Dornbusch Michael , Rasko John E. J.
Published: May 2022

•

In contrast to the prior voluntary system, since 2001, gene technology in Australia has been regulated under a legislated national Gene Technology Regulatory Scheme which is administered by the Gene Technology Regulator.

•

The Scheme provides science-based assessment of the potential risks of gene technology to the health and safety of people and the environment.

•

It complements the role of the Australian Therapeutic Goods Administration which regulates all therapeutic products in Australia to ensure they are safe and effective.

•

Recent reforms to the Scheme contribute to, and anticipate, the continued safe development and delivery of gene-based human therapeutics in Australia as a successful model for other jurisdictions.
Glucose-6-phosphate Reduces Fosfomycin Activity Against Stenotrophomonas maltophilia
Authors: Gil-Gil Teresa , Martínez José Luis
Published: May 2022

It is generally accepted that fosfomycin activity is higher in the presence of glucose-6-phosphate, since its inducible transporter UhpT is one of the gates for fosfomycin entry. Accordingly, fosfomycin susceptibility tests are performed in the presence of this sugar; however, since Stenotrophomonas maltophilia lacks UhpT, it is doubtful that glucose-6-phosphate might be a fosfomycin adjuvant in this microorganism. The aim of the work was to determine whether glucose-6-phosphate or other metabolites may alter the activity of fosfomycin against S. maltophilia. To that goal, checkerboard assays were performed to analyze the synergy and antagonism of compounds, such as glucose-6-phosphate, fructose, phosphoenolpyruvate, and glyceraldehyde-3-phosphate, among others, with fosfomycin. Besides, minimal inhibitory concentrations of fosfomycin against a set of clinical S. maltophilia isolates presenting different levels of expression of the SmeDEF efflux pump were determined in the presence and absence of said compounds. Finally, intracellular fosfomycin concentrations were determined using a bioassay. Our results show that, opposite to what has been described for other bacteria, glucose-6-phosphate does not increase fosfomycin activity against S. maltophilia; it is a fosfomycin antagonist. However, other metabolites such as fructose, phosphoenolpyruvate and glyceraldehyde-3-phosphate, increase fosfomycin activity. Consistent with these results, glucose-6-phosphate decreases fosfomycin internalization (a feature against current ideas in the field), while the other three compounds increase the intracellular concentration of this antibiotic. These results support that current standard fosfomycin susceptibility tests made in the presence of glucose-6-phosphate do not account for the actual susceptibility to this antibiotic of some bacteria, such as S. maltophilia. Finally, the innocuous metabolites that increase S. maltophilia susceptibility to fosfomycin found in this work are potential adjuvants, which might be included in fosfomycin formulations used for treating infections by this resistant pathogen.
Chromatin Regulators Ahc1p and Eaf3p Positively Influence Nitrogen Metabolism in Saccharomyces cerevisiae
Authors: Chen Yu , Zeng Weizhu , Ma Wenjian , Ma Wei , Zhou Jingwen
Published: May 2022

There is a complex regulatory network of nitrogen metabolism in Saccharomyces cerevisiae, and many details of this regulatory network have not been revealed. This study explored the global regulation of nitrogen metabolism in S. cerevisiae from an epigenetic perspective. Comparative transcriptome analysis of S. cerevisiae S288C treated with 30 nitrogen sources identified nine chromatin regulators (CRs) that responded significantly to different nitrogen sources. Functional analysis showed that among the CRs identified, Ahc1p and Eaf3p promoted the utilization of non-preferred nitrogen sources through global regulation of nitrogen metabolism. Ahc1p regulated nitrogen metabolism through amino acid transport, nitrogen catabolism repression (NCR), and the Ssy1p-Ptr3p-Ssy5p signaling sensor system. Eaf3p regulated nitrogen metabolism via amino acid transport and NCR. The regulatory mechanisms of the effects of Ahc1p and Eaf3p on nitrogen metabolism depended on the function of their histone acetyltransferase complex ADA and NuA4. These epigenetic findings provided new insights for a deeper understanding of the nitrogen metabolism regulatory network in S. cerevisiae.
The Role of Gut Microbiota in Mice With Bile Duct Ligation-Evoked Cholestatic Liver Disease-Related Cognitive Dysfunction
Authors: Yang Bowen , Sun Tianning , Chen Yingle , Xiang Hongbing , Xiong Jun , Bao Shiting
Published: May 2022

The pathogenesis of Hepatic Encephalopathy (HE) is complex and multifactorial. The development of metagenomics sequencing technology led to show the significant role of gut microbiota in the pathogenesis of cognitive dysfunction, which paved the way for further research in this field. However, it is unknown whether gut microbiota plays a role in bile duct ligation (BDL)-evoked cholestatic liver disease-related cognitive dysfunction. The aim of this investigation is to assess BDL mice induced cognitive dysfunction and meanwhile to delineate the alteration of gut microbiota in cognitive dysfunction mice, which may underline the role of gut microbiota in BDL mice induced cognitive dysfunction. Our study was carried out in male C57BL/6 J mice with bile duct ligation. The liver functions were assessed via different biochemical markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and total bile acid (TBA)] and a histopathological examination of the liver tissue. We used the novel object recognition test (NORT) to assess cognitive dysfunction. And BDL mice were divided into BDL with cognitive dysfunction (BDL-CD) or BDL without cognitive dysfunction (BDL-NCD groups) by the result of hierarchical cluster analysis of NORT. Then, 16S ribosomal RNA (rRNA) gene sequencing was used to compare the gut bacterial composition between BDL-CD and BDL-NCD groups. According to our results, we concluded that bile duct ligation can significantly change the gut microbiota composition, and Bacteroides fragilis, Bacteroides ovatus V975, and Bacteroides thetaiotaomicron play a vital role in BDL-evoked cholestatic liver disease-related cognitive dysfunction.
Identification of TRP-Related Subtypes, Development of a Prognostic Model, and Characterization of Tumor Microenvironment Infiltration in Lung Adenocarcinoma
Authors: Sun Sibo , Wang Yu , Li Min , Wu Jianqing
Published: May 2022

The TRP (transient receptor potential) superfamily, as cation channels, is a critical chemosensor for potentially harmful irritants. Their activation is closely related not only to tumor progression and prognosis but also to tumor therapy response. Nevertheless, the TRP-related immune gene (TRIG) expression of the tumor microenvironment (TME) and the associations with prognosis remain unclear. First, we represented the transcriptional and genetic variations in TRIGs in 535 lung adenocarcinoma (LUAD) samples as well as their expression patterns. LUAD samples were divided into two distinct subtypes based on the TRIG variations. Significant differences had been found in prognosis, clinical features, and TME cell-infiltration features between the two subtypes of patients. Second, we framed a TRIG score for predicting overall survival (OS) and validated the predictive capability of the TRIG score in LUAD patients. Accordingly, to enhance the clinical applicability of TRIG score, we developed a considerable nomogram. A low TRIG score, characterized by increased immunity activation, indicated favorable advantages of OS compared with a high TRIG score. Furthermore, the TRIG score was found to have a significant connection with the TME cell-infiltration and immune checkpoint expressions. Our analysis of TRIGs in LUAD showed their potential roles in prognosis, clinical features, and tumor-immune microenvironments. These results may advance our knowledge of TRP genes in LUAD and show a new light on prognosis estimation and the improvement of immunotherapy strategies.
Molecular Mechanisms of HIV Protease Inhibitors Against HPV-Associated Cervical Cancer: Restoration of TP53 Tumour Suppressor Activities
Authors: Makgoo Lilian , Mosebi Salerwe , Mbita Zukile
Published: May 2022

Cervical cancer is a Human Papilloma virus-related disease, which is on the rise in a number of countries, globally. Two essential oncogenes,E6andE7, drive cell transformation and cancer development. These two oncoproteins target two of the most important tumour suppressors, p53 and pRB, for degradation through the ubiquitin ligase pathway, thus, blocking apoptosis activation and deregulation of cell cycle. This pathway can be exploited for anticancer therapeutic interventions, and Human Immunodeficiency Virus Protease Inhibitors (HIV-PIs) have attracted a lot of attention for this anticancer drug development. HIV-PIs have proven effective in treating HPV-positive cervical cancers and shown to restore impaired or deregulated p53 in HPV-associated cervical cancers by inhibiting the 26S proteasome. This review will evaluate the role players, such as HPV oncoproteins involved cervical cancer development and how they are targeted in HIV protease inhibitors-induced p53 restoration in cervical cancer. This review also covers the therapeutic potential of HIV protease inhibitors and molecular mechanisms behind the HIV protease inhibitors-induced p53-dependent anticancer activities against cervical cancer.
The Correlation Between Falls and Cognitive Frailty in Elderly Individuals With Hypertension in a Chinese Community
Authors: Wang Can , Chong Yue , Wang Ling , Wang Yanbo
Published: May 2022

Background

Cognitive frailty refers to the presence of both physical frailty and mild cognitive impairment without simultaneous diagnosis of Alzheimer's disease or other dementia. Epidemiological studies have confirmed the correlation between falls and cognitive frailty, but no study has investigated the relationship between fall risk and cognitive frailty in hypertensive elderly Chinese individuals.

Methods

From December 2020 to March 2021, during face-to-face interviews, community-dwelling elderly individuals with hypertension aged 60~89 in Pudong New Area, Shanghai, were evaluated for cognitive frailty, fall history, and depression, and sociodemographic characteristics were collected. Logistic regression was used to analyze the correlation between falls and cognitive frailty.

Results

A total of 305 elderly people were investigated in this study, and 173 (56.7%, 95% CI =51.2%~62.2%) reported falling once or more in the previous year. Cognitive frailty is closely related to falls and was an independent risk factor for falls (OR = 2.661, 95% CI = 1.063~6.659). Other risk factors included old age (OR = 4.306, 95% CI = 1.852~10.013), female sex (OR = 1.988, 95% CI = 1.185~3.335) and depression (OR = 2.936, 95% CI = 1.069~8.060).

Conclusion

Cognitive frailty is an important risk factor for falls in elderly individuals with hypertension in Chinese communities.
Implicit Counterfactual Effect in Partial Feedback Reinforcement Learning: Behavioral and Modeling Approach
Authors: Barakchian Zahra , Vahabie Abdol-Hossein , Nili Ahmadabadi Majid
Published: May 2022

Context remarkably affects learning behavior by adjusting option values according to the distribution of available options. Displaying counterfactual outcomes, the outcomes of the unchosen option alongside the chosen one (i.e., providing complete feedback), would increase the contextual effect by inducing participants to compare the two outcomes during learning. However, when the context only consists of the juxtaposition of several options and there is no such explicit counterfactual factor (i.e., only partial feedback is provided), it is not clear whether and how the contextual effect emerges. In this research, we employ Partial and Complete feedback paradigms in which options are associated with different reward distributions. Our modeling analysis shows that the model that uses the outcome of the chosen option for updating the values of both chosen and unchosen options in opposing directions can better account for the behavioral data. This is also in line with the diffusive effect of dopamine on the striatum. Furthermore, our data show that the contextual effect is not limited to probabilistic rewards, but also extends to magnitude rewards. These results suggest that by extending the counterfactual concept to include the effect of the chosen outcome on the unchosen option, we can better explain why there is a contextual effect in situations in which there is no extra information about the unchosen outcome.
Biological and Molecular Docking Evaluation of a Benzylisothiocyanate Semisynthetic Derivative From Moringa oleifera in a Pre-clinical Study of Temporomandibular Joint Pain
Authors: Silveira Felipe Dantas , Gomes Francisco Isaac Fernandes , do Val Danielle Rocha , Freitas Hermany Capistrano , de Assis Ellen Lima , de Almeida Diana Kelly Castro , Braz Helyson Lucas Bezerra , Barbosa Francisco Geraldo , Mafezoli Jair , da Silva Marcos Reinaldo , Jorge Roberta Jeane Bezerra , Clemente-Napimoga Juliana Trindade , Costa Deiziane Viana da Silva , Brito Gerly Anne de Castro , Pinto Vicente de Paulo Teixeira , Cristino-Filho Gerardo , Bezerra Mirna Marques , Chaves Hellíada Vasconcelos
Published: May 2022

Graphical Abstract

Semisynthetic derivative from Moringa oleifera on temporomandibular joint pain.
PtNPs/PEDOT:PSS-Modified Microelectrode Arrays Reveal Electrophysiological Activities of Different Neurons in Medial Amygdala of Mice Under Innate Fear
Authors: Fan Penghui , Song Yilin , Lu Botao , Wang Yiding , Dai Yuchuan , Xie Jingyu , He Enhui , Xu Zhaojie , Yang Gucheng , Mo Fan , Liu Juntao , Wang Mixia , Cai Xinxia
Published: May 2022

The medial amygdala (MA) plays an important role in the innate fear circuit. However, the electrophysiological mechanism of MA for processing innate fear needs to be further explored. In this study, we fabricated microelectrode arrays (MEAs) with detecting sites arranged to match the location and shape of MA in mice and detected the electrophysiology in freely behaving mice under 2-methyl-2-thiazoline (2MT)-induced fear. The detection performance of MEA is improved by modifying metal nanoparticles and conductive polymers (PtNPs/PEDOT:PSS). After modification, the impedance magnitude and phase of electrodes were decreased to 27.0 ± 2.3 kΩ and −12.30 ± 0.52°, respectively, leading to a signal-to-noise ratio of 10. Its electrochemical stability and mechanical stability were also verified by cyclic voltammetry (CV) sweeping and ultrasonic vibration. MEAs were then implanted into the MA of mice, and the electrophysiology and behavioral characteristics were synchronously recorded and analyzed. The results showed that 2MT induced strong defensive behaviors in mice, accompanied by increases in the average spike firing rate and local field potential (LFP) power of MA neurons. According to principles commonly applied to cortical extracellular recordings, the recorded neurons are divided into two classes based on waveforms. Statistics showed that about 37% of type 1 neurons (putative GABAergic neurons) and 87% of type 2 neurons (putative glutamatergic neurons) were significantly activated under innate fear. At the same time, the firing rate of some activated neurons had a good linear correlation with the freezing rate.
Potential Anti-aging Components From Moringa oleifera Leaves Explored by Affinity Ultrafiltration With Multiple Drug Targets
Authors: Xu Yongbing , Chen Guilin , Guo Mingquan
Published: May 2022

Moringa oleifera (M. oleifera), widely used in tropical and subtropical regions, has been reported to possess good anti-aging benefits on skincare. However, the potential bioactive components responsible for its anti-aging effects, including anti-collagenase, anti-elastase, and anti-hyaluronidase activities, have not been clarified so far. In this study, M. oleifera leaf extracts were first conducted for anti-elastase and anti-collagenase activities in vitro by spectrophotometric and fluorometric assays, and the results revealed that they possessed good activities against skin aging-related enzymes. Then, multi-target bio-affinity ultrafiltration coupled to high-performance liquid chromatography-mass spectrometry (AUF-HPLC-MS) was applied to quickly screen anti-elastase, anti-collagenase, and anti-hyaluronidase ligands in M. oleifera leaf extracts. Meanwhile, 10, 8, and 14 phytochemicals were screened out as the potential anti-elastase, anti-collagenase, and anti-hyaluronidase ligands, respectively. Further confirmation of these potential bioactive components with anti-aging target enzymes was also implemented by molecule docking analysis. In conclusion, these results suggest that the M. oleifera leaves might be a very promising natural source of anti-aging agent for skincare, which can be further explored in the cosmetics and cosmeceutical industries combating aging and skin wrinkling.
Prognostic Roles of Glucose to Lymphocyte Ratio and Modified Glasgow Prognosis Score in Patients With Non-small Cell Lung Cancer
Authors: Yang Ming , Zhang Qi , Ge Yi-Zhong , Tang Meng , Hu Chun-Lei , Wang Zi-Wen , Zhang Xi , Song Meng-Meng , Ruan Guo-Tian , Zhang Xiao-Wei , Liu Tong , Xie Hai-Lun , Zhang He-Yang , Zhang Kang-Ping , Li Qin-Qin , Li Xiang-Rui , Liu Xiao-Yue , Lin Shi-Qi , Shi Han-Ping
Published: May 2022

Background

Non-small cell lung cancer (NSCLC) is among the most prevalent malignancies worldwide. Previous studies have shown that the status of inflammation, nutrition and immune are closely related to overall survival (OS) of patients with NSCLC, but little is known about their interactive and combined roles. Hence, we chose glucose to lymphocyte ratio (GLR) and modified Glasgow Prognosis Score (mGPS) as prognostic factors and assessed the prognostic values of them for patients with NSCLC.

Methods

Baseline clinicopathologic and laboratory characteristics of 862 patients with NSCLC were obtained from a multicenter prospective cohort. The Cox proportional hazard regression models were used to determine prognostic values of the clinical factors. A nomogram was also constructed integrating the clinical factors with clinical significance or independent prognostic values. Concordance index (C-index) was utilized to evaluate the prediction accuracy of the TNM stage and the nomogram.

Results

Multivariate analyses demonstrated that GLR [Hazard ratio (HR) = 1.029, 95% confidence interval (CI) = 1.004–1.056, P = 0.023] and mGPS (score of 1: HR = 1.404, 95% CI = 1.143–1.726, P = 0.001; score of 2: HR = 1.515, 95% CI = 1.159–1.980, P = 0.002) were independent prognostic factors for patients with NSCLC. The C-indexes of the TNM stage and the nomogram were 0.642 (95% CI = 0.620–0.663) and 0.694 (95% CI = 0.671–0.717), respectively.

Conclusion

GLR and mGPS were independent prognostic factors for patients with NSCLC. Moreover, our constructed nomogram might be superior in predicting prognosis of patients with NSCLC compared with the TNM stage.
Prognostic Significance of Preoperative Sarcopenia in Patients With Gastric Cancer Liver Metastases Receiving Hepatectomy
Authors: Xiong Jianping , Wu Yunzi , Hu Haitao , Kang Wenzhe , Li Yang , Jin Peng , Shao Xinxin , Li Weikun , Tian Yantao
Published: May 2022

Background

The present work focused on assessing the role of computed tomography (CT)-determined sarcopenia in the prognosis of patients with gastric cancer liver metastases (GCLM) receiving hepatectomy.

Methods

We analyzed data collected from GCLM cases that underwent hepatectomy between March 2011 and July 2017. The third lumbar vertebra (L3) level skeletal muscle index (SMI) was analyzed by abdominal CT to determine the sarcopenia before surgery. The thresholds for CT-based sarcopenia of sex-specific L3 SMI were ≤ 34.9 cm2/m2 and ≤ 40.8 cm2/m2 for female and male, separately We determined overall survival (OS) and recurrence-free survival (RFS)by univariate and multivariate analyses.

Results

The cohort enrolled altogether 114 patients with GCLM receiving hepatectomy (average age: 62.6 years, male: 79.8%), and 58 (50.8%) patients had sarcopenia. The mean SMI was 34.2 in patients with sarcopenia compared to 42.7 in patients without sarcopenia (p < 0.001). The 1-, 3-, and 5-year OS rates in patients with GCLM after hepatectomy were 78.1, 43.7, and 34.3%, respectively. The 1-, 3-, and 5-year RFS rates in patients were 49.8, 33.6, and 29.3%, respectively. Sarcopenia was related to an advanced age (≥65.0 years) (p = 0.009), reduced BMI (<18.5 kg/m2) (p < 0.001) and number of liver metastases (>1) (p = 0.025). Sarcopenia had a significant associated with the patterns of recurrence (p < 0.001). In addition, patients with sarcopenia had a significant difference in number of liver metastases in comparison with those without sarcopenia (p = 0.025). We discovered from multivariate analysis that sarcopenia independently predicted RFS [hazard ratio (HR) = 1.76; 95% confidence interval (CI)= 1.18–2.35, p = 0.007]. Nevertheless, sarcopenia was not the prognostic factors that independently predicted OS (HR = 1.62; 95% CI = 0.57–2.73; p = 0.330).

Conclusions

In conclusion, we showed that CT-determined sarcopenia was the facile and effective prognostic factor for RFS inpatients with GCLM after hepatectomy. Patients with sarcopenia are associated with an increased tumor recurrence risk, and thereby customized treatment should be applied.
Validation Study of the Estimated Glycemic Load Model Using Commercially Available Fast Foods
Authors: Lee Miran , Kang Haejin , Chung Sang-Jin , Nam Kisun , Park Yoo Kyoung
Published: May 2022

The recent popularization of low-glycemic foods has expanded interest in glycemic index (GI) not only among diabetic patients but also healthy people. The purpose of this study is to validate the estimated glycemic load model (eGL) developed in 2018. This study measured the glycemic load (GL) of 24 fast foods in the market in 20 subjects. Then, the transportability of the model was assessed, followed by an assessment of model calibration and discrimination based on model performance. The transportability assessment showed that the subjects at the time of model development are different from the subjects of this validation study. Therefore, the model can be described as transportable. As for the model's performance, the calibration assessment found an x2 value of 11.607 and a p-value of 0.160, which indicates that the prediction model fits the observations. The discrimination assessment found a discrimination accuracy exceeding 0.5 (57.1%), which confirms that the performance and stability of the prediction model can be discriminated across all classifications. The correlation coefficient between GLs and eGLs measured from the 24 fast foods was statistically significant at 0.712 (p < 0.01), indicating a strong positive linear relationship. The explanatory powers of GL and eGL was high at 50.7%. The findings of this study suggest that this prediction model will greatly contribute to healthy food choices because it allows for predicting blood glucose responses solely based on the nutrient content labeled on the fast foods.
LGBTQI Inclusive Cancer Care: A Discourse Analytic Study of Health Care Professional, Patient and Carer Perspectives
Authors: Ussher Jane M. , Power Rosalie , Perz Janette , Hawkey Alexandra J. , Allison Kimberley
Published: May 2022

Background

Awareness of the specific needs of LGBTQI cancer patients has led to calls for inclusivity, cultural competence, cultural safety and cultural humility in cancer care. Examination of oncology healthcare professionals’ (HCP) perspectives is central to identifying barriers and facilitators to inclusive LGBTQI cancer care.

Study Aim

This study examined oncology HCPs perspectives in relation to LGBTQI cancer care, and the implications of HCP perspectives and practices for LGBTQI patients and their caregivers.

Method

357 oncology HCPs in nursing (40%), medical (24%), allied health (19%) and leadership (11%) positions took part in a survey; 48 HCPs completed an interview. 430 LGBTQI patients, representing a range of tumor types, sexual and gender identities, age and intersex status, and 132 carers completed a survey, and 104 LGBTQI patients and 31 carers undertook an interview. Data were analysed using thematic discourse analysis.

Results

Three HCP subject positions – ways of thinking and behaving in relation to the self and LGBTQI patients – were identified:’Inclusive and reflective’ practitioners characterized LGBTQI patients as potentially vulnerable and offered inclusive care, drawing on an affirmative construction of LGBTQI health. This resulted in LGBTQI patients and their carers feeling safe and respected, willing to disclose sexual orientation and gender identity (SOGI) status, and satisfied with cancer care. ‘Egalitarian practitioners’ drew on discourses of ethical responsibility, positioning themselves as treating all patients the same, not seeing the relevance of SOGI information. This was associated with absence of LGBTQI-specific information, patient and carer anxiety about disclosure of SOGI, feelings of invisibility, and dissatisfaction with healthcare. ‘Anti-inclusive’ practitioners’ expressed open hostility and prejudice towards LGBTQI patients, reflecting a cultural discourse of homophobia and transphobia. This was associated with patient and carer distress, feelings of negative judgement, and exclusion of same-gender partners.

Conclusion

Derogatory views and descriptions of LGBTQI patients, and cis-normative practices need to be challenged, to ensure that HCPs offer inclusive and affirmative care. Building HCP’s communicative competence to work with LGBTQI patients needs to become an essential part of basic training and ongoing professional development. Visible indicators of LGBTQI inclusivity are essential, alongside targeted resources and information for LGBTQI people.
Advances in Renal Cell Carcinoma Drug Resistance Models
Authors: Xiang Yien , Zheng Ge , Zhong Jianfeng , Sheng Jiyao , Qin Hanjiao
Published: May 2022

Renal cell carcinoma (RCC) is the most common form of kidney cancer. Systemic therapy is the preferred method to eliminate residual cancer cells after surgery and prolong the survival of patients with inoperable RCC. A variety of molecular targeted and immunological therapies have been developed to improve the survival rate and prognosis of RCC patients based on their chemotherapy-resistant properties. However, owing to tumor heterogeneity and drug resistance, targeted and immunological therapies lack complete and durable anti-tumor responses; therefore, understanding the mechanisms of systemic therapy resistance and improving clinical curative effects in the treatment of RCC remain challenging. In vitro models with traditional RCC cell lines or primary cell culture, as well as in vivo models with cell or patient-derived xenografts, are used to explore the drug resistance mechanisms of RCC and screen new targeted therapeutic drugs. Here, we review the established methods and applications of in vivo and in vitro RCC drug resistance models, with the aim of improving our understanding of its resistance mechanisms, increasing the efficacy of combination medications, and providing a theoretical foundation for the development and application of new drugs, drug screening, and treatment guidelines for RCC patients.
Development and Validation of a Risk Prediction Model for Breast Cancer Prognosis Based on Depression-Related Genes
Authors: Wang Xuan , Wang Neng , Zhong Linda L. D. , Su Kexin , Wang Shengqi , Zheng Yifeng , Yang Bowen , Zhang Juping , Pan Bo , Yang Wei , Wang Zhiyu
Published: May 2022

Background

Depression plays a significant role in mediating breast cancer recurrence and metastasis. However, a precise risk model is lacking to evaluate the potential impact of depression on breast cancer prognosis. In this study, we established a depression-related gene (DRG) signature that can predict overall survival (OS) and elucidate its correlation with pathological parameters and sensitivity to therapy in breast cancer.

Methods

The model training and validation assays were based on the analyses of 1,096 patients from The Cancer Genome Atlas (TCGA) database and 2,969 patients from GSE96058. A risk signature was established through univariate and multivariate Cox regression analyses.

Results

Ten DRGs were determined to construct the risk signature. Multivariate analysis revealed that the signature was an independent prognostic factor for OS. Receiver operating characteristic (ROC) curves indicated good performance of the model in predicting 1-, 3-, and 5-year OS, particularly for patients with triple-negative breast cancer (TNBC). In the high-risk group, the proportion of immunosuppressive cells, including M0 macrophages, M2 macrophages, and neutrophils, was higher than that in the low-risk group. Furthermore, low-risk patients responded better to chemotherapy and endocrine therapy. Finally, a nomogram integrating risk score, age, tumor-node-metastasis (TNM) stage, and molecular subtypes were established, and it showed good agreement between the predicted and observed OS.

Conclusion

The 10-gene risk model not only highlights the significance of depression in breast cancer prognosis but also provides a novel gene-testing tool to better prevent the potential adverse impact of depression on breast cancer prognosis.
lncRNA-LET Regulates Glycolysis and Glutamine Decomposition of Esophageal Squamous Cell Carcinoma Through miR-93-5p/miR-106b-5p/SOCS4
Authors: Su Xincheng , Xue Cong , Xie Chengke , Si Xianzhe , Xu Jie , Huang Wenbo , Huang Zhijun , Lin Jianqing , Chen Zhiyao
Published: May 2022

Background

Dysregulated non-coding RNAs exhibit critical functions in various cancers. Nonetheless, the levels and corresponding functions of cirCSNX14 in esophageal squamous cell carcinoma (ESCC) yet remain to be elucidated.

Methods

Initially, the aberrant low levels of lncRNA-LET within ESCC tissues are validated via qRT-PCR observations. Moreover, the effects of lncRNA-LET upregulation on cell proliferation in vitro are determined. In addition, a series of assays determining the mechanistic views related to metabolism is conducted. Furthermore, the effects of lncRNA-LET in affecting tumor growth are investigated in vivo in a mouse model. Moreover, the interactions between lncRNA-LET and its networks are predicted and determined by RNA immunoprecipitation-assisted qRT-PCR as well as luciferase reporter assays.

Results

The downregulation of lncRNA-LET is correlated to the poor prognosis of ESCC patients. Moreover, the upregulated expression of lncRNA-LET could have reduced the cell viability. In vivo tumor inhibition efficacy assays showed that an increase of lncRNA-LET presented excellent inhibitory effects on cancer proliferation as reflected by tumor weight and volume in mice. Finally, the mechanistic views regarding the effects of miR-106b-5p or miR-93-5p and SOCS4 on ESCC are related to the feedback of lncRNA-LET.

Conclusion

Collectively, this study suggested that lncRNA-LET miR-93-5p or the miR-106b-5p–SOCS4 axis may provide great potential in establishing ESCC therapy.