bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatty Acid-Binding Protein 5 Modulates Brain Endocannabinoid Tone and Retrograde Signaling in the Striatum
Authors: Fauzan Mohammad , Oubraim Saida , Yu Mei , Glaser Sherrye T. , Kaczocha Martin , Haj-Dahmane Samir
Published: July 2022

The endocannabinoid (eCB) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are endogenous lipid neurotransmitters that regulate an array of physiological functions, including pain, stress homeostasis, and reward. Fatty acid-binding protein 5 (FABP5) is a key modulator of intracellular eCB transport and inactivation. Recent evidence suggests that FABP5 controls synaptic 2-AG signaling at excitatory synapses in the dorsal raphe nucleus. However, it is currently not known whether this function extends to other brain areas. To address this, we first profiled eCB levels across several brain areas in FABP5 knockout mice and wild-type controls and report that FABP5 deletion elevates AEA levels in the striatum, prefrontal cortex, midbrain, and thalamus, as well as midbrain 2-AG levels. The expression of eCB biosynthetic and catabolic enzymes was largely unaltered in these regions, although minor sex and region-specific changes in the expression of 2-AG catabolic enzymes were observed in female FABP5 KO mice. Robust FABP5 expression was observed in the striatum, a region where both AEA and 2-AG control synaptic transmission. Deletion of FABP5 impaired tonic 2-AG and AEA signaling at striatal GABA synapses of medium spiny neurons, and blunted phasic 2-AG mediated short-term synaptic plasticity without altering CB1R expression or function. Collectively, these results support the role of FABP5 as a key regulator of eCB signaling at excitatory and inhibitory synapses in the brain.
Sodium First Approach, to Reset Our Mind for Improving Management of Sodium, Water, Volume and Pressure in Hemodialysis Patients, and to Reduce Cardiovascular Burden and Improve Outcomes
Authors: Canaud Bernard , Kooman Jeroen , Maierhofer Andreas , Raimann Jochen , Titze Jens , Kotanko Peter
Published: July 2022

New physiologic findings related to sodium homeostasis and pathophysiologic associations require a new vision for sodium, fluid and blood pressure management in dialysis-dependent chronic kidney disease patients. The traditional dry weight probing approach that has prevailed for many years must be reviewed in light of these findings and enriched by availability of new tools for monitoring and handling sodium and water imbalances. A comprehensive and integrated approach is needed to improve further cardiac health in hemodialysis (HD) patients. Adequate management of sodium, water, volume and hemodynamic control of HD patients relies on a stepwise approach: the first entails assessment and monitoring of fluid status and relies on clinical judgement supported by specific tools that are online embedded in the HD machine or devices used offline; the second consists of acting on correcting fluid imbalance mainly through dialysis prescription (treatment time, active tools embedded on HD machine) but also on guidance related to diet and thirst management; the third consist of fine tuning treatment prescription to patient responses and tolerance with the support of innovative tools such as artificial intelligence and remote pervasive health trackers. It is time to come back to sodium and water imbalance as the root cause of the problem and not to act primarily on their consequences (fluid overload, hypertension) or organ damage (heart; atherosclerosis, brain). We know the problem and have the tools to assess and manage in a more precise way sodium and fluid in HD patients. We strongly call for a sodium first approach to reduce disease burden and improve cardiac health in dialysis-dependent chronic kidney disease patients.
Concurrent Tuberculous Meningoencephalitis and Anti-NMDAR Encephalitis: A Case Report
Authors: Xiaoli Chen , Qun Wang , Jing Li , Huan Yang , Si Chen
Published: July 2022

Background

Cases of tuberculosis triggering the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are absent.

Case Presentation

Herein, we report, for the first time, the case of a patient who developed anti-NMDAR encephalitis likely due to tuberculosis. The patient, a 33-year-old man, experienced weight loss during the previous 2 years, along with acute headache, fever, cognitive deficits, and right ophthalmoplegia. Based on these findings and on data from magnetic resonance imaging and cerebrospinal fluid antibody analysis, tuberculous meningoencephalitis combined with anti-NMDAR encephalitis was diagnosed. Marked clinical and brain imaging improvement were observed after antituberculosis and high-dose corticosteroid treatment initiation, which persisted during the 3 months of follow-up.

Conclusions

This case suggests that anti-NMDAR encephalitis may arise after tuberculosis infection. Therefore, clinicians must be aware of this possibility, especially when cognitive and new neurological symptoms suddenly occur.
Application of Diffusion Tensor Imaging (DTI) in the Diagnosis of HIV-Associated Neurocognitive Disorder (HAND): A Meta-Analysis and a System Review
Authors: Ma Juming , Yang Xue , Xu Fan , Li Hongjun
Published: July 2022

Background

The patients with HIV-associated neurocognitive disorder (HAND) are often accompanied by white matter structure damage. Diffusion tensor imaging (DTI) is an important tool to detect white matter structural damage. However, the changes in DTI values reported in many studies are diverse in different white matter fiber tracts and brain regions.

Purpose

Our research is dedicated to evaluating the consistency and difference of the correlation between HAND and DTI measures in different studies. Additionally, the value of DTI in HAND evaluation is used to obtain consensus and independent conclusions between studies.

Methods

We searched PubMed and Web of Science to collect relevant studies using DTI for the diagnosis of HAND. After screening and evaluating the search results, meta-analysis is used for quantitative research on data. Articles that cannot collect data but meet the research relevance will be subjected to a system review.

Results

The meta-analysis shows that the HAND group has lower fractional anisotropy (standardized mean difference = −0.57 p < 0.0001) and higher mean diffusivity (standardized mean difference = 0.04 p < 0.0001) than the healthy control group in corpus callosum. In other white matter fibers, we found similar changes in fractional anisotropy (standardized mean difference = −1.18 p < 0.0001) and mean diffusivity (standardized mean difference = 0.69 p < 0.0001). However, the heterogeneity (represented by I2) between the studies is high (in corpus callosum 94, 88%, in other matter fibers 95, 81%). After subgroup analysis, the heterogeneity is obtained as 19.5, 40.7% (FA, MD in corpus callosum) and 0, 0% (FA, MD among other white matter fibers).

Conclusion

The changes in white matter fibers in patients with HAND are statistically significant at the observation level of DTI compared with healthy people. The differences between the studies are mainly derived from demographics, start and maintenance time of antiretroviral therapy, differences in nadir CD4+T cells, and the use of different neurocognitive function scales. As an effective method to detect the changes in white matter fibers, DTI is of great significance for the diagnosis of HAND, but there are still some shortcomings. In the absence of neurocognitive function scales, independent diagnosis remains difficult.

Systematic Review Registration:https://inplasy.com/inplasy-2021-10-0079/.
TGFβ1 as a Predictive Biomarker for Collateral Formation Within Ischemic Moyamoya Disease
Authors: Chen Yuanbing , Tang Miao , Li Hui , Liu Hongwei , Wang Junyu , Huang Jun
Published: July 2022

Objective

Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive steno-occlusion within the terminal segment of the internal carotid artery. However, good collaterals from an external carotid artery are essential to compensate for the ischemia in moyamoya disease. This study aimed to investigate the transforming growth factor-beta 1 (TGFβ1) in plasma as a potential biomarker for predicting collateral formation in ischemic MMD.

Methods

The transcriptome profile downloaded from Gene Expression Omnibus (GEO) was used to analyze the differential expression of genes between the ischemic MMD and the control groups. We prospectively recruited 23 consecutive patients with ischemic MMD that was diagnosed via digital subtraction angiography (DSA). Nine patients with intracranial aneurysms and four healthy people served as controls. The collaterals from the external carotid artery were examined using DSA. We evaluated whether the collateral formation was associated with TGFβ1 in patients with ischemic MMD. Western blot, RT-qPCR, ELISA, and tube formation assay were used to explore the relationship between TGFβ1 and angiogenesis, as well as the potential mechanisms.

Results

The mRNA levels of TGFβ1 were upregulated in the patients with ischemic MMD. The plasma TGFβ1 levels were higher in the patients with ischemic MMD than in the aneurysm and healthy patients (p < 0.05). The collateral formation group has higher levels of serum TGFβ1 than the non-collateral formation group (p < 0.05). The levels of vascular endothelial growth factor (VEGF) are positively correlated with TGFβ1 levels in the plasma (R2 = 0.6115; p < 0.0001). TGFβ1 regulates VEGF expression via the activation of the TGFβ pathway within HUVEC cells, as well as TGFβ1 stimulating HUVEC cells to secrete VEGF into the cell culture media. An in vitro assay revealed that TGFβ1 promotes angiogenesis within the endothelial cells.

Conclusion

Our findings suggest that TGFβ1 plays a vital role in promoting collateral formation by upregulating VEGF expression in ischemic MMD.
Retained Primitive Reflexes and Potential for Intervention in Autistic Spectrum Disorders
Authors: Melillo Robert , Leisman Gerry , Machado Calixto , Machado-Ferrer Yanin , Chinchilla-Acosta Mauricio , Kamgang Shanine , Melillo Ty , Carmeli Eli
Published: July 2022

We provide evidence to support the contention that many aspects of Autistic Spectrum Disorder (ASD) are related to interregional brain functional disconnectivity associated with maturational delays in the development of brain networks. We think a delay in brain maturation in some networks may result in an increase in cortical maturation and development in other networks, leading to a developmental asynchrony and an unevenness of functional skills and symptoms. The paper supports the close relationship between retained primitive reflexes and cognitive and motor function in general and in ASD in particular provided to indicate that the inhibition of RPRs can effect positive change in ASD.
Through Thick and Thin: Baseline Cortical Volume and Thickness Predict Performance and Response to Transcranial Direct Current Stimulation in Primary Progressive Aphasia
Authors: Nissim Nicole R. , Harvey Denise Y. , Haslam Christopher , Friedman Leah , Bharne Pandurang , Litz Geneva , Phillips Jeffrey S. , Cousins Katheryn A. Q. , Xie Sharon X. , Grossman Murray , Hamilton Roy H.
Published: July 2022

Objectives

We hypothesized that measures of cortical thickness and volume in language areas would correlate with response to treatment with high-definition transcranial direct current stimulation (HD-tDCS) in persons with primary progressive aphasia (PPA).

Materials and Methods

In a blinded, within-group crossover study, PPA patients (N = 12) underwent a 2-week intervention HD-tDCS paired with constraint-induced language therapy (CILT). Multi-level linear regression (backward-fitted models) were performed to assess cortical measures as predictors of tDCS-induced naming improvements, measured by the Western Aphasia Battery-naming subtest, from baseline to immediately after and 6 weeks post-intervention.

Results

Greater baseline thickness of the pars opercularis significantly predicted naming gains (p = 0.03) immediately following intervention, while greater thickness of the middle temporal gyrus (MTG) and lower thickness of the superior temporal gyrus (STG) significantly predicted 6-week naming gains (p’s < 0.02). Thickness did not predict naming gains in sham. Volume did not predict immediate gains for active stimulation. Greater volume of the pars triangularis and MTG, but lower STG volume significantly predicted 6-week naming gains in active stimulation. Greater pars orbitalis and MTG volume, and lower STG volume predicted immediate naming gains in sham (p’s < 0.05). Volume did not predict 6-week naming gains in sham.

Conclusion

Cortical thickness and volume were predictive of tDCS-induced naming improvement in PPA patients. The finding that frontal thickness predicted immediate active tDCS-induced naming gains while temporal areas predicted naming changes at 6-week suggests that a broader network of regions may be important for long-term maintenance of treatment gains. The finding that volume predicted immediate naming performance in the sham condition may reflect the benefits of behavioral speech language therapy and neural correlates of its short-lived treatment gains. Collectively, thickness and volume were predictive of treatment gains in the active condition but not sham, suggesting that pairing HD-tDCS with CILT may be important for maintaining treatment effects.
In vitro Model Systems for Studies Into Retinal Neuroprotection
Authors: Zhu Yu , Cao Bowen , Tolone Arianna , Yan Jie , Christensen Gustav , Arango-Gonzalez Blanca , Ueffing Marius , Paquet-Durand François
Published: July 2022

Therapy development for neurodegenerative diseases of the retina constitutes a major unmet medical need, and this may be particularly relevant for inherited diseases of the retina, which are largely untreatable to this day. Therapy development necessitates appropriate models to improve the understanding of the underlying degenerative mechanisms, as well as for the testing and evaluation of novel treatment approaches. This review provides an overview of various in vitro model systems used to study retinal neuroprotection. The in vitro methods and technologies discussed range from primary retinal cell cultures and cell lines, to retinal organoids and organotypic retinal explants, to the cultivation of whole eyeballs. The advantages and disadvantages of these methods are compared and evaluated, also in view of the 3R principles (i.e., the refinement, reduction, and replacement of live animal testing), to identify suitable in vitro alternatives for in vivo experimentation. The article further expands on the use of in vitro models to test and evaluate neuroprotective treatments and to aid the development of retinal drug delivery systems. Among the pharmacological agents tested and characterized in vitro are such that interfere with aberrant cyclic guanosine monophosphate (cGMP) -signaling or such that inhibit the activities of poly (ADP-ribose) polymerase (PARP), histone deacetylases (HDAC), calpain-type proteases, as well as unfolded protein response-related stress. We then introduce nanoparticle-based drug delivery systems and discuss how different in vitro systems may be used to assess their efficacy in the treatment of retinal diseases. The summary provides a brief comparison of available in vitro models and relates their advantages and limitations to the various experimental requirements, for instance, for studies into disease mechanisms, novel treatments, or retinal toxicity. In many cases, combinations of different in vitro models may be required to obtain a comprehensive view of the efficacy of a given retinal neuroprotection approach.
Sex Differences in the Role of Neurexin 3α in Zoster Associated Pain
Authors: Kramer Phillip R. , Umorin Mikhail , Hornung Rebecca , Benson M. Douglas , Kinchington Paul R.
Published: July 2022

Varicella zoster virus (VZV) induces orofacial pain and female rats show greater pain than male rats. During the proestrus phase of the estrous cycle the VZV induce pain response is attenuated in female rats. A screen of gene expression changes in diestrus and proestrus female rats indicated neurexin 3α (Nrxn3α) was elevated in the central amygdala of proestrus rats vs. diestrus rats. GABAergic neurons descend from the central amygdala to the lateral parabrachial region and Nrxn3α is important for presynaptic γ-Aminobutyric acid (GABA) release. Thus, we hypothesized that the reduced orofacial pain in male rats and proestrus female rats is the result of increased Nrxn3α within the central amygdala that increases GABA release from axon terminals within the parabrachial and inhibits ascending pain signals. To test this hypothesis Nrxn3 α expression was knocked-down by infusing shRNA constructs in the central amygdala. Then GABA release in the parabrachial was quantitated concomitant with measuring the pain response. Results revealed that knockdown of Nrxn3α expression significantly increases the pain response in both male rats and proestrus female rats vs. diestrus rats. GABA release was significantly reduced in the parabrachial of male and proestrus female rats after Nrxn3α knockdown. Neuronal activity of excitatory neurons was significantly inhibited in the parabrachial after Nrxn3α knockdown. These results are consistent with the idea that Nrxn3 within the central amygdala controls VZV associated pain by regulating GABA release in the lateral parabrachial that then modulates ascending orofacial pain signals.
Regenerative Peripheral Nerve Interfaces Effectively Prevent Neuroma Formation After Sciatic Nerve Transection in Rats
Authors: Wu Jiaqing , Zhang Yajun , Zhang Xiaoyuan , Lin Zhiyu , Li Guangxue
Published: July 2022

Objective

The disordered growth of nerve stumps after amputation leading to the formation of neuromas is an important cause of postoperative pain in amputees. This severely affects the patients' quality of life. Regenerative peripheral nerve interfaces (RPNIs) are an emerging method for neuroma prevention, but its postoperative nerve growth and pathological changes are yet to be studied.

Methods

The rat sciatic nerve transection model was used to study the effectiveness of RPNI in this experiment. The RPNI (experimental) group (n = 11) underwent RPNI implantation after sciatic nerve transection, while the control group (n = 11) only underwent sciatic nerve transection. Autotomy behavior, ultrasonography, and histopathology were observed for 2 months postoperatively.

Results

Compared to the control group, the incidence and size of the neuromas formed and the incidence and extent of autotomy were significantly reduced in the RPNI group. The axon density in the stump and degree of stump fibrosis were also significantly reduced in the RPNI group.

Conclusion

RPNI effectively prevented the formation of neuromas.
Long-Duration Sound-Induced Facilitation Changes Population Activity in the Inferior Colliculus
Authors: Burghard Alice L. , Lee Christopher M. , Fabrizio-Stover Emily M. , Oliver Douglas L.
Published: July 2022

The inferior colliculus (IC) is at the midpoint of the auditory system and integrates virtually all information ascending from the auditory brainstem, organizes it, and transmits the results to the auditory forebrain. Its abundant, excitatory local connections are crucial for this task. This study describes a long duration sound (LDS)-induced potentiation in the IC that changes both subsequent tone-evoked responses and spontaneous activity. Afterdischarges, changes of spontaneous spiking following an LDS, were seen previously in single neurons. Here, we used multi-channel probes to record activity before and after a single, tetanic sound and describe the changes in a population of IC neurons. Following a 60 s narrowband-noise stimulation, a subset of recording channels (∼16%) showed afterdischarges. A facilitated response spike rate to tone pips following an LDS was also observed in ∼16% of channels. Both channels with an afterdischarge and channels with facilitated tone responses had higher firing rates in response to LDS, and the magnitude of the afterdischarges increased with increased responses to the LDS. This is the first study examining the effect of LDS stimulation on tone-evoked responses. This observed facilitation in vivo has similarities to post-tetanic potentiation in vitro as both manner of induction (strong stimulation for several seconds) as well as time-course of the facilitation (second to minute range) are comparable. Channels with and without facilitation appear to be intermixed and distributed widely in the central nucleus of IC, and this suggests a heretofore unknown property of some IC neurons or their circuits. Consequently, this sound-evoked facilitation may enhance the sound-evoked output of these neurons, while, simultaneously, most other IC neurons have reduced or unchanged output in response to the same stimulus.
Pea Peptide Supplementation in Conjunction With Resistance Exercise Promotes Gains in Muscle Mass and Strength
Authors: Jia Shaohui , Wu Qiming , Wang Shue , Kan Juntao , Zhang Zhao , Zhang Xiping , Zhang Xuejun , Li Jie , Xu Wenhan , Du Jun , Wei Wei
Published: July 2022

It is generally considered that protein supplementation and resistance exercise significantly increase muscle mass and muscle growth. As the hydrolysis products of proteins, peptides may play the crucial role on muscle growth. In this study, male rats were orally administrated 0.4 g/kg body weight of pea peptide combined with 8 weeks of moderate intensity resistance exercise training. After treatment, the body gains, upper limb grip, muscle thickness, and wet weight of biceps brachii were tested, and the cross-sectional area of biceps brachii muscle fiber and the types of muscle fibers were determined by HE staining, immunofluorescence staining, and lactate dehydrogenase activity, respectively. Western blot analysis was used to investigate the level of growth-signaling pathway-related proteins. The results showed that pea peptide supplementation combined with resistance exercise training significantly increased body weight, upper limb grip, muscle thickness, wet weight of biceps brachii, and cross-sectional area of muscle fiber. Meanwhile, pea peptide supplementation obviously elevated the ratio of fast-twitch fiber (type II) and the expression of muscle growth-signaling pathway-related proteins. In addition, the PP2 oligopeptide in pea peptide with the amino acid sequence of LDLPVL induced a more significant promotion on C2C12 cell growth than other oligopeptides.
Antibody Response to SARS-CoV-2 Vaccination in Patients With Lymphoproliferative Disorders and Plasma Cell Dyscrasias: Anti-Lymphoma Therapy as a Predictive Biomarker of Response to Vaccination
Authors: Gung Carol , McGuire Regina , George Mercy , Abdulkareem Abdullateef , Belden Katherine A. , Porcu Pierluigi , Martinez-Outschoorn Ubaldo , Binder Adam F. , Chervenova Inna , Alpdogan Onder
Published: July 2022

We retrospectively analyzed SARS-CoV-2 vaccination antibody responses in a cohort of 273 patients with lymphoproliferative disorders or plasma cell dyscrasias who were seen at a single tertiary cancer center. Semi-quantitative anti-spike protein serologic testing was performed with enzyme immunoassay method. We found that the antibody response rate to SARS-CoV-2 vaccination was 74.7% in our patient cohort with no difference based on gender, age or race. The highest response rate was found in patients with Multiple Myeloma (MM) (95.5%). The response rates found in Diffuse Large B-Cell Lymphoma (DLBCL), Chronic Lymphocytic Leukemia (CLL), and Low-Grade Non-Hodgkin Lymphoma (LG-NHL) were 73.2%, 61.5% and 53% respectively. We also evaluated the effects of receiving active chemo-immunotherapy on SARS-CoV-2 vaccination antibody response. We found that the patients on treatment had lower response than the patients off treatment (62.1% versus 84.4% p<0.001). Thirty-four of 58 LG-NHL patients were receiving anti-lymphoma treatment with a lower SARS-CoV-2 vaccination response as compared to the patients who were not on treatment (29.4% v 87.5% p<0.001). We observed a similar pattern in CLL patients receiving treatment (48.1 v 76.0 p:0.049). We found that only disease type and treatment status (on-treatment vs. off- treatment), but not gender, age or race were significant predictors of non-response in the multivariable logistic regression model. The interaction between disease type and treatment status was not statistically significant by multivariate analysis. In conclusion, receiving anti-cancer treatment was found to play a significant role in decreasing the response to COVID-19 vaccination.
Arecoline Is Associated With Inhibition of Cuproptosis and Proliferation of Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma: A Potential Mechanism for Tumor Metastasis
Authors: Li Jinfei , Chen Shuangyi , Liao Yuxuan , Wang Hongyi , Zhou Dawei , Zhang Bo
Published: July 2022

Background

Metastatic disease remains the primary cause of death in patients with oral squamous cell carcinoma (OSCC), especially those who use betel nut. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the TME of OSCC. However, the precise mechanisms regulating CAFs in OSCC are poorly understood.

Methods

Thirteen genes related to the arecoline were analyzed to explore the significant ones involved in arecoline-related OSCC metastasis. The GSE139869 (n = 10) and The Cancer Genome Atlas (TCGA)-OSCC data (n = 361) were mined for the identification of the differentially expressed genes. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the independent prognostic signatures. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functional enrichment of selected genes, and gene set enrichment analysis of cuproptosis-related genes was completed. Spearman’s analysis and Tumor Immune Estimation Resource (TIMER) were used to visualize the correlation between the infiltration of CAFs and the gene expression. The correlation analysis of the cells and different genes, including CAF infiltration and transcripts per million expression, was assessed. The relationship between arecoline and CAFs was confirmed by cell counting kit-8 assay (CCK-8). CancerSEA was searched to identify the single-cell phenotype.

Result

Arecoline-associated fibrosis-related OSCC differentially expressed genes (AFOC-DEGs), namely, PLAU, IL1A, SPP1, CCL11, TERT, and COL1A2, were screened out and selected from the Gene Expression Omnibus (GEO) database and TCGA database. AFOC-DEGs were highly expressed in OSCC, which led to poor survival of patients. Functional enrichment analysis, protein–protein interaction network construction, and Spearman’s correlation analysis all suggested that AFOC-DEGs were closely associated with cuproptosis. Cellular experiments demonstrated that arecoline stimulation could significantly increase the cell viability of CAFs. Single-sample Gene Set Enrichment Analysis (ssGSEA) results showed that GLS and MTF1 were highly expressed when fibroblasts proliferated at high enrichment levels. In addition, analysis of single-cell sequencing results suggested that OSCC cells with high expression of AFOC-DEGs were associated with OSCC metastasis.

Conclusion

We found a close association between arecoline, cuproptosis, and CAFs, which might play an important role in the metastasis of OSCC.
Advanced Differentiated Thyroid Cancer: A Complex Condition Needing a Tailored Approach
Authors: Bulfamante Antonio Mario , Lori Eleonora , Bellini Maria Irene , Bolis Elisa , Lozza Paolo , Castellani Luca , Saibene Alberto Maria , Pipolo Carlotta , Fuccillo Emanuela , Rosso Cecilia , Felisati Giovanni , De Pasquale Loredana
Published: July 2022

Differentiated thyroid cancers (DTCs) are slow-growing malignant tumours, including papillary and follicular carcinomas. Overall, prognosis is good, although it tends to worsen when local invasion occurs with bulky cervical nodes, or in the case of distant metastases. Surgery represents the main treatment for DTCs. However, radical excision is challenging and significant morbidity and functional loss can follow the treatment of the more advanced forms. Literature on advanced thyroid tumours, both differentiated and undifferentiated, does not provide clear and specific guidelines. This emerges the need for a tailored and multidisciplinary approach. In the present study, we report our single-centre experience of 111 advanced (local, regional, and distant) DTCs, investigating the rate of radical excision, peri-procedural and post-procedural complications, quality of life, persistence, recurrence rates, and survival rates. Results are critically appraised and compared to the existing published evidence review.
Healthcare-Associated Infection Prevention Interventions for Neonates in Resource-Limited Settings
Authors: Dramowski Angela , Aucamp Marina , Beales Emily , Bekker Adrie , Cotton Mark Frederic , Fitzgerald Felicity C. , Labi Appiah-Korang , Russell Neal , Strysko Jonathan , Whitelaw Andrew , Coffin Susan
Published: July 2022

Healthcare-associated infections (HAIs) and antimicrobial-resistant (AMR) infections are leading causes of neonatal morbidity and mortality, contributing to an extended hospital stay and increased healthcare costs. Although the burden and impact of HAI/AMR in resource-limited neonatal units are substantial, there are few HAI/AMR prevention studies in these settings. We reviewed the mechanism of action and evidence supporting HAI/AMR prevention interventions, including care bundles, for hospitalized neonates in low- and middle-income countries (LMIC).
Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion
Authors: Li Na , Sun Jie , Chen Ji-Lin , Bai Xue , Wang Ting-Hua
Published: July 2022

Objective: To investigate the effect of Zhilong Huoxue Tongyu capsule (ZLH) in the treatment of cerebral ischemia–reperfusion injury and determine the underlying molecular network mechanism.

Methods: The treatment effect of Zhilong Huoxue Tongyu capsule (ZLH) was evaluated for cerebral ischemia–reperfusion injury in middle cerebral artery occlusion (MACO) rat, and the underlying molecular network mechanism was explored by using molecular network analysis based on network pharmacology, bioinformatics including protein–protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), as well as molecular docking.

Results: The neurological function of rats in the ZLH group was significantly improved compared to those in the NS group (p = 0.000), confirming the positive effect of ZLH for the treatment of brain ischemia. There were 126 intersecting genes screened in ischemia–reperfusion cerebrum that are associated with several important biological processes, such as lipopolysaccharide, and the most important cell component, such as raft, as well as the most important molecular function pointed as cytokine receptor binding. The most important KEGG signaling pathway was the AGE-RAGE signaling pathway in diabetic complications. Moreover, according to the STRING interaction in the PPI network, 10 hub genes including MAPK14, FOS, MAPK1, JUN, MYC, RELA, ESR1, STAT1, AKT1, and IL6 were selected and exhibited in Cytoscape and molecular docking. Lastly, the relation between PPI, GO, and KEGG was analyzed. These findings indicated that multiple hub network genes have been involved in behavior improvement in cerebral ischemia–reperfusion rats subjected to ZLH treatment.

Conclusion: Zhilong Huoxue Tongyu capsule improves cerebral ischemia–reperfusion and is associated with multiple network gene expressions.
Characterization of Lactate Metabolism Score in Breast and Thyroid Cancers to Assist Immunotherapy via Large-Scale Transcriptomic Data Analysis
Authors: Wang Cheng , Qu Zheng , Chen Li , Pan Yunhao , Tang Yiqing , Hu Guangfu , Gao Ran , Niu Ruijie , Liu Qiang , Gao Xingyan , Fang Yi
Published: July 2022

Breast cancer (BC) and thyroid cancer (TC) have the highest rate of incidence, especially in women. Previous studies have revealed that lactate provides energetic and anabolic support to cancer cells, thus serving as an important oncometabolite with both extracellular and intracellular signaling functions. However, the correlation of lactate metabolism scores with thyroid and breast cancer immune characteristics remains to be systematically analyzed. To investigate the role of lactate at the transcriptome level and its correlation with the clinical outcome of BC and TC, transcriptome data of 1,217 patients with breast cancer (BC) and 568 patients with thyroid cancer (TC) were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets with their corresponding clinical and somatic mutation data. The lactate metabolism score was calculated based on a single-sample gene set enrichment analysis (ssGSEA). The results showed that lactate metabolism-related genes and lactate metabolism scores was significantly associated with the survival of patients with BRCA and THCA. Notably, the lactate metabolism scores were strongly correlated with human leukocyte antigen (HLA) expression, tumor-infiltrating lymphocyte (TIL) infiltration, and interferon (IFN) response in BC and TC. Furthermore, the lactate metabolism score was an independent prognostic factor and could serve as a reliable predictor of overall survival, clinical characteristics, and immune cell infiltration, with the potential to be applied in immunotherapy or precise chemotherapy of BC and TC.
Chalcone Derivatives From Abelmoschus manihot Seeds Restrain NLRP3 Inflammasome Assembly by Inhibiting ASC Oligomerization
Authors: Su Jinsong , Yang Fujing , Kang Xuemei , Liu Jia , Tao Yiwen , Diao Qingchun , Meng Xianli , Liu Deming , Zhang Yi
Published: July 2022

Three chalcone derivatives, abelmanihotols A−C (1–3), and nine known compounds were isolated from A. manihot seeds, and their structures were determined using HRESIMS and NMR spectroscopic analysis. Compound 1 exhibited the most potent inhibitory effect (IC50 = 4.79 ± 0.72 μM) against lipopolysaccharide (LPS)-induced NO release in THP-1 cells, and significantly inhibited interleukin 1β (IL-1β) secretion, which is stimulated by LPS plus nigericin (IC50 = 11.86 ± 1.20 μM), ATP or MSU, in THP-1 cells. A preliminary mechanism of action study indicated that compound 1 blocked the formation of nucleotide oligomerization domain-like receptor protein-3 (NLRP3) inflammasome formation by suppressing apoptosis-associated speck-like protein oligomerization, thereby attenuating caspase-1 activation and IL-1β release. These results reveal that compound 1 is not only a potent and efficacious NLRP3 inflammasome inhibitor but also a promising drug for the treatment of NLRP3-related diseases.
Non-Contact Intracardiac Potential Mapping Using Mesh-Based and Meshless Inverse Solvers
Authors: Meng Shu , Chamorro-Servent Judit , Sunderland Nicholas , Zhao Jichao , Bear Laura R. , Lever Nigel A. , Sands Gregory B. , LeGrice Ian J. , Gillis Anne M. , Budgett David M. , Smaill Bruce H.
Published: July 2022

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and percutaneous catheter ablation is widely used to treat it. Panoramic mapping with multi-electrode catheters has been used to identify ablation targets in persistent AF but is limited by poor contact and inadequate coverage of the left atrial cavity. In this paper, we investigate the accuracy with which atrial endocardial surface potentials can be reconstructed from electrograms recorded with non-contact catheters. An in-silico approach was employed in which “ground-truth” surface potentials from experimental contact mapping studies and computer models were compared with inverse potential maps constructed by sampling the corresponding intracardiac field using virtual basket catheters. We demonstrate that it is possible to 1) specify the mixed boundary conditions required for mesh-based formulations of the potential inverse problem fully, and 2) reconstruct accurate inverse potential maps from recordings made with appropriately designed catheters. Accuracy improved when catheter dimensions were increased but was relatively stable when the catheter occupied >30% of atrial cavity volume. Independent of this, the capacity of non-contact catheters to resolve the complex atrial potential fields seen in reentrant atrial arrhythmia depended on the spatial distribution of electrodes on the surface bounding the catheter. Finally, we have shown that reliable inverse potential mapping is possible in near real-time with meshless methods that use the Method of Fundamental Solutions.
Integrative Analysis of the Transcriptome and Metabolome Reveals Genes Involved in Phenylpropanoid and Flavonoid Biosynthesis in the Trapa bispinosa Roxb.
Authors: Yin Dong-Jie , Ye Shi-Jie , Sun Xiao-Yan , Chen Qin-Yi , Min Ting , Wang Hong-Xun , Wang Li-Mei
Published: July 2022

Background

Trapa bispinosa Roxb. is grown worldwide as an important aquatic cash crop. Current research on Trapa bispinosa primarily focuses on the separation and identification of active ingredients, as well as the inhibitory effect on tumors; however, research on the molecular mechanism of secondary metabolite accumulation is rather limited. Consequently, an integrative analysis of transcriptome and metabolome is required to identify the key metabolic pathways, and key genes, and to explain the molecular mechanism of Trapa bispinosa.

Results

The biosynthesis pathways of phenolics in Trapa bispinosa were examined through transcriptome and metabolome analyses. Transcriptome analysis yielded 42.76 million clean reads representing 81,417 unigenes with an average length of 1,752 bp. KEGG pathway analysis revealed that 1,623 unigenes, including 88 candidate unigenes related to phenolics biosynthesis, were up-regulated in Trapa bispinosa shell (FR) when compared to leaves (LF), root (RT), and stem (ST). The FR vs. LF group had the highest number of specific genes involved in phenylpropanoid, flavonoid, flavone, and flavonol biosynthesis pathways compared to all other comparison groups. In addition, RNA sequencing revealed 18,709 SSRs spanning 14,820 unigenes and 4,387 unigenes encoding transcription factors. Metabolome analysis identified 793 metabolites, including 136 flavonoids and 31 phenylpropane compounds. In the FR group compared to the LF group, there were 202 differentially accumulated metabolites (DAMs). The combined transcriptome and metabolome analyses indicated a significant correlation between 1,050 differentially expressed genes (DEGs) and 62 DAMs. This view proposes a schematic of flavonoid biosynthesis in the FR vs. LF group, providing evidence for the differences in genes and metabolites between FR and LF.

Conclusion

In this study, through de novo transcriptome assembly and metabolome analysis, several DEGs and DAMs were identified, which were subsequently used to build flavonoid biosynthesis pathways and a correlation network. The findings pave the way for future research into the molecular mechanisms and functional characterization of Trapa bispinosa candidate genes for phenolics biosynthesis.
2D-HSQC-NMR-Based Screening of Feruloylated Side-Chains of Cereal Grain Arabinoxylans
Authors: Schendel Rachel R. , Bunzel Mirko
Published: July 2022

Arabinoxylans of commelinid monocots are characterized by high contents of ferulic acid that is incorporated into arabinose-bearing side-chains of varying complexity. Species-related differences in the feruloylated side-chain profiles of grain arabinoxylans are observed and lead to differences in arabinoxylan functionality. Here, a semi-quantitative assay based on 1H-13C-correlation NMR spectroscopy (HSQC experiment) was developed to profile feruloylated side-chains of cereal grain arabinoxylans. Following acidic liberation of the feruloylated side-chains from the xylan backbone and a clean-up step using C18 solid phase extraction, the feruloylated oligosaccharides FA (5-O-trans-feruloyl-L-arabinofuranose), FAX (β-d-xylopyranosyl-(1 → 2)-5-O-trans-feruloyl-l-arabinofuranose) and FAXG (α-l-galactopyranosyl-(1 → 2)-β-d-xylopyranosyl-(1 → 2)-5-O-trans-feruloyl-l-arabinofuranose) were analyzed by HSQC-NMR. Marker signals were identified for each compound, and experimental conditions such as solvent and internal standard as well as measurement and processing conditions were optimized for a semi-quantitative determination. The approach was validated with respect to accuracy, precision, limit of detection, and limit of quantification. The newly developed approach was applied to several cereal samples including oats, popcorn maize, wheat, and wild rice. Data were compared to an HPLC-DAD/MS approach published earlier by our group, demonstrating that the results of the HSQC approach were comparable to the more time-consuming and technically more challenging HPLC-DAD/MS method.
The Relationship Between Academic Encouragement and Academic Self-Efficacy: A Moderated Mediation Model
Authors: Gong Zhun , Jiao Xinian , Xia Xinlei , Yu Haixin , Lv Cixian
Published: July 2022

To explore the influence mechanism and boundary conditions of academic encouragement on college students’ academic self-efficacy, this study did a questionnaire survey and used the four scales, namely, Academic Encouragement Scale (AES), Course Subscale of the College Self-Efficacy Inventory (CCSI), Adult Hope Scale (AHS), and Campus Connectedness Scale (CCS). The questionnaires were distributed both online and offline. A total of 355 questionnaires were distributed, with 267 valid returns. Among them, 139 were women (52.1%) and 128 were men (47.9%), and the age range is 18–24 years old. As for the grade level, 123 were first-year college students (46.1%), 58 were second-year college students (21.7%), and 86 were third-year college students (32.2%). The results of this study showed the following. (1) Campus connectedness or hope mediated the relations between (challenge-focused or potential-focused) encouragement and academic self-efficacy. (2) Academic engagement could not moderate the above mediation models.
Similarities and Differences in the Outsiders and Insiders' Visual Preferences on Sacred Landscape
Authors: Li Chang , Ge Shanwei , Wang Ruiying
Published: July 2022

Previous studies have reported religious and non-religious people as having different psychological experiences when visiting sacred landscapes; however, the visual consensus and differences between diverse groups visiting them have rarely been considered. This study used subjective preference evaluation and experimental eye tracking to assess the visual preferences of different groups regarding sacred landscapes. Overall, 48 photos of the Han Chinese Buddhist temples were selected as stimulus materials, including the categories of squares, architecture, waterscapes, and plants. In all, 90 participants were classified into two groups of outsiders and insiders to view the photos. The consensus and differences in their visual preferences and eye movement metrics were evaluated. The results showed that the two groups were more inclined toward the visual preference of religious architectures than the natural landscape that people usually prefer. Another noteworthy discovery revealed the significant differences between the outsiders and the insiders in viewing and evaluating sacred landscapes; the immersion effect explains this result. Specifically, the group with a higher interaction with the environment had greater visual experiences, easier visual information coding, and larger visual exploration range. In addition, this study revealed familiarity with the religious background facilitated achieving a higher consistency between the landscape preference scores and the eye movement metrics. These findings expand the theory of religious environment perception and provided important insights for subsequent research on sacred landscape planning and management.
Effects of Human-Social Capital Congruence and Environmental Dynamism on Dynamic of Encouragement and Organizational Innovation in New Ventures
Authors: Lu Yurong , Cai Wendi , Bi Xiaoliang
Published: July 2022

Although human capital and social capital can provide knowledge and social network for organizations, existing studies are inadequate to explore how the interaction between the two types of capital shapes organizational behaviors or organizational outcomes. The present study investigates whether the linkage of human capital to social capital was compensatory or complementary, and how they impact organizational innovation in consideration of the dynamic of encouragement. Using data from more than 200 technological new ventures in China, we analyze the associations among all the parameters through bootstrapping and response surface methods. The findings suggest that organizational innovation is stronger when human and social capital are congruent and that the dynamic of encouragement fully mediates the relationship between capital congruence and organizational innovation performance. Furthermore, environmental dynamism positively moderates the relationship between capital congruence and the dynamic of the environment, that is, the relationship is stronger for new ventures in high rather than low dynamic environments. Finally, the theoretical and managerial implications of this study are discussed.
Online Mindfulness Intervention, Mental Health and Attentional Abilities: A Randomized Controlled Trial in University Students During COVID-19 Lockdown
Authors: Devillers-Réolon Louise , Mascret Nicolas , Sleimen-Malkoun Rita
Published: July 2022

The COVID-19 pandemic has led to worldwide restrictive measures, raising concerns about mental health in young adults who were not particularly vulnerable to the virus itself. This study investigated the impact of these restrictions on mental and cognitive health of university students, and tested the efficacy of a brief online mindfulness meditation intervention in countering psychological distress and improving attentional abilities. Ninety-six university students forced into remote learning due to COVID-19 pandemic restrictions and with no experience in meditation were randomly assigned to either a passive control group (n = 48) or to an experimental group (n = 48) following daily, for 17 days, an online mindfulness intervention (10–20 min per day). Due to drop-out, 38 participants in each group were finally analyzed. Pre- and post-tests assessed participants’ mental health (psychological well-being, depression, anxiety, stress) and attentional abilities. The analysis of baseline data in comparison with normative scores and pre-pandemic statistics confirmed the expected psychological distress, but it did not reveal any attentional deficits in our participants. Pre-post change scores analyses showed a reduction in stress (p = 0.006, ηp2 = 0.10), anxiety (p = 0.002, ηp2 = 0.13), and depression (p = 0.025, ηp2 = 0.07), and an improvement in well-being (p = 0.013, ηp2 = 0.12) in the experimental group, but not in the control group. In both groups, no significant effect was found on attentional abilities. Our results confirmed the psychological vulnerability of higher education students in the midst of the remote learning period during the second COVID-19 lockdown in France, while suggesting preservation of attentional functioning. Although the tested mindfulness intervention did not enhance the attentional abilities in already good performing students, it did promote their mental health. This study offers additional evidence on the feasibility and efficacy of mindfulness-based interventions in students during psychologically straining periods, like the COVID-19 pandemic.