bluuebunny/crossref_metadata_2025 huggingface dataset:
SeV C Protein Plays a Role in Restricting Macrophage Phagocytosis by Limiting the Generation of Intracellular Double-Stranded RNA
Authors: Morita Naoko , Tanaka Yukie , Takeuchi Kenji , Kitagawa Yoshinori , Sakuma Ryusuke , Koide Naoki , Komatsu Takayuki
Published: February 2022

Macrophages play a central role in the innate immune response to respiratory viral infections through pro-inflammatory factor secretion and phagocytosis. However, as a countermeasure, viral pathogens have evolved virulence factors to antagonize macrophage function. In our recent in vitro analyses of murine macrophage cell lines, Sendai virus (SeV) accessory protein C inhibited the secretion of pro-inflammatory factors, and C gene-knockout SeV (SeVΔC) caused drastic morphological changes in RAW264.7 macrophages, similar to those observed after stimulation with Lipid A, a well-known activator of actin-rich membrane ruffle formation and phagocytosis. Hence, we sought to determine whether the C protein limits phagocytosis in SeV-infected macrophages through the suppression of membrane ruffling. Phagocytosis assays indicated an upregulation of phagocytosis in both SeVΔC-infected and Lipid A-stimulated macrophages, but not in SeV WT-infected cells. Further, the observed membrane ruffling was associated with phagocytosis. RIG-I is essential for Lipid A-induced phagocytosis; its deficiency inhibited SeVΔC-stimulated phagocytosis and ruffling, confirming the essential role of RIG-I. Moreover, treatment with interferon (IFN)-β stimulation and neutralizing antibodies against IFN-β suggested that SeVΔC-induced phagocytosis and ruffling occurred in an IFN-β-independent manner. A newly isolated SeVΔC strain that does not generate dsRNA further highlighted the importance of dsRNA in the induction of phagocytosis and ruffling. Taken together, the current results suggest that SeV C protein might limit phagocytosis-associated membrane ruffling in an RIG-I-mediated but IFN-independent manner via limiting the generation of intracellular dsRNA.
Polycationic Glycopolymer Demonstrates Activity Against Persisters and Biofilms of Non-tuberculosis Mycobacteria Cystic Fibrosis Clinical Isolates in vitro
Authors: Narayanaswamy Vidya P. , Townsend Stacy M. , Loughran Allister J. , Wiesmann William , Baker Shenda
Published: February 2022

Non-tuberculosis Mycobacterium (NTM) is a group of opportunistic pathogens associated with pulmonary infections that are difficult to diagnose and treat. Standard treatment typically consists of prolonged combination antibiotic therapy. Antibiotic resistance and the role of biofilms in pathogen communities, such as NTM persister cells, is an important unmet challenge that leads to increased toxicity, frequent relapse, poor clinical management, and an extended treatment period. Infection recurrence and relapse are not uncommon among individuals with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD), where thick mucus supports bacterial biofilm production and impairs mucociliary clearance. The study evaluates a membrane-active cationic glycopolymer [poly (acetyl, arginyl) glucosamine (PAAG)] being developed to support the safe and effective treatment of NTM biofilm infections. PAAG shows antibacterial activity against a wide range of pathogenic bacteria at concentrations non-toxic to human epithelial cells. Time-kill curves demonstrated PAAG’s rapid bactericidal potential at concentrations as low as 1X MIC against all NTM strains tested and compared to the standard of care. PAAG treatment prevents persister formation and eradicates antibiotic-induced persister cells in planktonic NTM cultures below the limit of detection (10 colony-forming unit (CFU)/ml). Further, PAAG showed the ability to penetrate and disperse NTM biofilms formed by both rapidly and slowly growing strains, significantly reducing the biofilm biomass (p < 0.0001) compared to the untreated NTM biofilms. Microscopical examination confirmed PAAG’s ability to disrupt and disperse mycobacterial biofilms. A single PAAG treatment resulted in up to a 25-fold reduction in live-labeled NTM and a 78% reduction in biofilm thickness. Similar to other polycationic molecules, PAAG’s bactericidal and antibiofilm activities employ rapid permeabilization of the outer membrane of the NTM strains, and subsequently, reduce the membrane potential even at concentrations as low as 50 μg/ml (p < 0.001). The outcomes of these in vitro analyses suggest the importance of this polycationic glycopolymer, PAAG, as a potential therapeutic agent for opportunistic NTM infections.
Population Genomics of Microbial Biostalactites: Non-recombinogenic Genome Islands and Microdiversification by Transposons
Authors: Burkartová Kateřina , Dresler Jiří , Rídl Jakub , Falteisek Lukáš
Published: February 2022

Intrapopulation genetic variability in prokaryotes is receiving increasing attention thanks to improving sequencing methods; however, the ability to distinguish intrapopulation variability from species clusters or initial stages of gene flow barrier development remains insufficient. To overcome this limitation, we took advantage of the lifestyle of Ferrovum myxofaciens, a species that may represent 99% of prokaryotic microbiome of biostalactites growing at acid mine drainage springs. We gained four complete and one draft metagenome-assembled F. myxofaciens genomes using Oxford Nanopore and Illumina sequencing and mapped the reads from each sample on the reference genomes to assess the intrapopulation variability. We observed two phenomena associated with intrapopulation variability: hypervariable regions affected by mobilome expansion called “scrapyards,” and variability in gene disruptions caused by transposons within each population. Both phenomena were previously described in prokaryotes. However, we present here for the first time scrapyard regression and the development of a new one. Nearly complete loss of intrapopulation short sequence variability in the old scrapyard and high variability in the new one suggest that localized gene flow suppression is necessary for scrapyard formation. Concerning the variable gene disruptions, up to 9 out of 41 occurrences per sample were located in highly conserved diguanylate cyclases/phosphodiesterases. We propose that microdiversification of life strategies may be an adaptive outcome of random diguanylate cyclase elimination. The mine biostalactites thus proved as a unique model system for describing genomic intrapopulation processes, as they offer easily sampleable units enriched in a single microbial species.
Breast Cancer; Discovery of Novel Diagnostic Biomarkers, Drug Resistance, and Therapeutic Implications
Authors: Afzal Samia , Hassan Muhammad , Ullah Safi , Abbas Hazrat , Tawakkal Farah , Khan Mohsin Ahmad
Published: February 2022

Breast cancer is the second most reported cancer in women with high mortality causing millions of cancer-related deaths annually. Early detection of breast cancer intensifies the struggle towards discovering, developing, and optimizing diagnostic biomarkers that can improve its prognosis and therapeutic outcomes. Breast cancer-associated biomarkers comprise macromolecules, such as nucleic acid (DNA/RNA), proteins, and intact cells. Advancements in molecular technologies have identified all types of biomarkers that are exclusively studied for diagnostic, prognostic, drug resistance, and therapeutic implications. Identifying biomarkers may solve the problem of drug resistance which is a challenging obstacle in breast cancer treatment. Dysregulation of non-coding RNAs including circular RNAs (circRNAs) and microRNAs (miRNAs) initiates and progresses breast cancer. The circulating multiple miRNA profiles promise better diagnostic and prognostic performance and sensitivity than individual miRNAs. The high stability and existence of circRNAs in body fluids make them a promising new diagnostic biomarker. Many therapeutic-based novels targeting agents have been identified, including ESR1 mutation (DNA mutations), Oligonucleotide analogs and antagonists (miRNA), poly (ADP-ribose) polymerase (PARP) in BRCA mutations, CDK4/6 (cell cycle regulating factor initiates tumor progression), Androgen receptor (a steroid hormone receptor), that have entered clinical validation procedure. In this review, we summarize the role of novel breast cancer diagnostic biomarkers, drug resistance, and therapeutic implications for breast cancer.
Detection of CCR5Δ32 Mutant Alleles in Heterogeneous Cell Mixtures Using Droplet Digital PCR
Authors: Sorokina Alyona , Artyuhov Alexander , Goltsova Alexandra , Dashinimaev Erdem
Published: February 2022

The C-C chemokine receptor type 5 (CCR5 or CD195) is one of the co-receptor binding sites of the human immunodeficiency virus (HIV). Transplantations of hematopoietic stem cells with the CCR5Δ32 knockout mutation could represent an effective tool for the complete cure of HIV; these methods having passed the stage of proof-of-principle. At the same time, using the modern CRISPR/Cas9 genome editing method, we can effectively reproduce the CCR5Δ32 mutation in any wild-type cells. Thus, the task of searching for and accurately quantifying the content of mutant CCR5Δ32 alleles in heterogeneous cell mixtures becomes relevant. In this study, we describe the generation of an artificial CCR5Δ32 mutation using CRISPR/Cas9 followed by multiplex droplet digital polymerase chain reaction (ddPCR) to quantify its content in cell mixtures. The system we have developed allows us to quickly and accurately measure the content of cells with the CCR5Δ32 mutation, down to 0.8%.
Mitoprotective Effects of a Synergistic Nutraceutical Combination: Basis for a Prevention Strategy Against Alzheimer’s Disease
Authors: Jayatunga Dona P. W. , Hone Eugene , Fernando W. M. A. D. Binosha , Garg Manohar L. , Verdile Giuseppe , Martins Ralph N.
Published: February 2022

Evidence to date suggests the consumption of food rich in bioactive compounds, such as polyphenols, flavonoids, omega-3 fatty acids may potentially minimize age-related cognitive decline. For neurodegenerative diseases, such as Alzheimer’s disease (AD), which do not yet have definitive treatments, the focus has shifted toward using alternative approaches, including prevention strategies rather than disease reversal. In this aspect, certain nutraceuticals have become promising compounds due to their neuroprotective properties. Moreover, the multifaceted AD pathophysiology encourages the use of multiple bioactive components that may be synergistic in their protective roles when combined. The objective of the present study was to determine mechanisms of action underlying the inhibition of Aβ1–42-induced toxicity by a previously determined, three-compound nutraceutical combination D5L5U5 for AD. In vitro experiments were carried out in human neuroblastoma BE(2)-M17 cells for levels of ROS, ATP mitophagy, and mitobiogenesis. The component compounds luteolin (LUT), DHA, and urolithin A (UA) were independently protective of mitochondria; however, the D5L5U5 preceded its single constituents in all assays used. Overall, it indicated that D5L5U5 had potent inhibitory effects against Aβ1–42-induced toxicity through protecting mitochondria. These mitoprotective activities included minimizing oxidative stress, increasing ATP and inducing mitophagy and mitobiogenesis. However, this synergistic nutraceutical combination warrants further investigations in other in vitro and in vivo AD models to confirm its potential to be used as a preventative therapy for AD.
Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches
Authors: Sabaie Hani , Talebi Mahnaz , Gharesouarn Jalal , Asadi Mohammad Reza , Jalaiei Abbas , Arsang-Jang Shahram , Hussen Bashdar Mahmud , Taheri Mohammad , Jalili Khoshnoud Reza , Rezazadeh Maryam
Published: February 2022

Alzheimer’s disease (AD) is a heterogeneous degenerative brain disorder with a rising prevalence worldwide. SHISA7 (CKAMP59) has emerged as one of the most intriguing new members of the SHISA family, in that, unlike other CKAMP counterparts, it exhibits a direct function in inhibitory synaptic GABAAR regulation. We used bioinformatics and experimental methods in this research to explore competing endogenous RNA (ceRNA) regulation of BCAS4 and SHISA7 in tau pathogenesis and their capacity as peripheral biomarkers linked to an abnormal inflammatory response in AD. The Gene Expression Omnibus database included two microarray datasets, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD with different degrees of AD-associated neurofibrillary pathology in the temporal cortex (TC) tissue specimens and corresponding controls were downloaded from the Gene Expression Omnibus database. The limma package in the R software was used to identify differently expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) associated with AD-related neurofibrillary pathology. Additionally, we used the quantitative polymerase chain reaction technique to examine the expression of the BCAS4/hsa-miR-185-5p/SHISA7 ceRNA axis in the peripheral blood (PB) of fifty AD patients and fifty control subjects. BCAS4 was shown to act as a ceRNA to control the SHISA7 expression throughout AD-associated neurofibrillary pathology in TC tissue specimens by sponging hsa-miR-185-5p, based on our bioinformatics study. Furthermore, in PB specimens from individuals suffering from AD and normal controls, we found no substantial differences in BCAS4 expression patterns. SHISA7 expression in AD patients’ PB was found to be reduced, as was the case in the TC. On the other hand, we discovered reduced amounts of hsa-miR-185-5p in AD patients’ PB samples compared to control subjects, unlike in TC tissue, where it had been demonstrated to be overexpressed. BCAS4 and SHISA7 expression levels showed a strong positive correlation, suggesting the presence of an interconnected network, most likely as a result of ceRNA regulation among PB specimens. The present study is the first evidence to highlight the expression of the BCAS4/miR-185-5p/SHISA7 ceRNA axis in the brain and PB of AD patients, and offers a new viewpoint on molecular processes underlying AD pathogenic mechanisms.
Low-Intensity Focused Ultrasound Stimulation Ameliorates Working Memory Dysfunctions in Vascular Dementia Rats via Improving Neuronal Environment
Authors: Wang Faqi , Wang Qian , Wang Ling , Ren Jing , Song Xizi , Tian Yutao , Zheng Chenguang , Yang Jiajia , Ming Dong
Published: February 2022

Working memory impairment is one of the remarkable cognitive dysfunctions induced by vascular dementia (VD), and it is necessary to explore an effective treatment. Recently, low-intensity focused ultrasound stimulation (LIFUS) has been found notable neuroprotective effects on some neurological diseases, including VD. However, whether it could ameliorate VD-induced working memory impairment was still not been clarified. The purpose of this study was to address this issue and the underlying mechanism. We established VD rat model using the bilateral common carotid artery occlusion (BCCAO) and applied the LIFUS (center frequency = 0.5 MHz; Ispta = 500 mW/cm2, 10 mins/day) to bilateral medial prefrontal cortex (mPFC) for 2 weeks since 2 weeks after the surgery. The main results showed that the LIFUS could significantly improve the performance of VD rats in the specific working memory tasks (delayed nonmatch-to-sample task and step-down task), which might be associated with the improved synaptic function. We also found the improvement in the cerebral blood flow (CBF) and reduced neuroinflammation in mPFC after LIFUS treatment indicated by the inhibition of Toll-like receptor (TLR4)/nuclear factor kappa B (NF-κB) pathway and the decrease of proinflammatory cytokines. The amelioration of CBF and neuroinflammation may promote the living environment of the neurons in VD which then contribute to the survival of neurons and the improvement in synaptic function. Taken together, our findings indicate that LIFUS targeted mPFC can effectively ameliorate reward-based spatial working memory and fear working memory dysfunctions induced by VD via restoring the living environment, survivability, and synaptic functions of the neurons in mPFC of VD rats. This study adds to the evidence that LIFUS could become a promising and non-invasive treatment strategy for the clinical treatment of central nervous system diseases related to cognitive impairments in the future.
Potential Neuroprotective Role of Sugammadex: A Clinical Study on Cognitive Function Assessment in an Enhanced Recovery After Cardiac Surgery Approach and an Experimental Study
Authors: Muedra Vicente , Rodilla Vicent , Llansola Marta , Agustí Ana , Pla Clara , Canto Antolín , Hernández-Rabaza Vicente
Published: February 2022

Background

Postoperative cognitive dysfunction affects the quality of recovery, particularly affecting the elderly, and poses a burden on the health system. We hypothesize that the use of sugammadex (SG) could optimize the quality of postoperative cognitive function and overall recovery through a neuroprotective effect.

Methods

A pilot observational study on patients undergoing cardiac surgery with enhanced recovery after cardiac surgery (ERACS) approach, was designed to compare SG-treated (n = 14) vs. neostigmine (NG)-treated (n = 7) patients. The Postoperative Quality Recovery Scale (PQRS) was used at different times to evaluate cognitive function and overall recovery of the patients. An online survey among anesthesiologists on SG use was also performed. Additionally, an animal model study was designed to explore the effects of SG on the hippocampus.

Results

Sugammadex (SG) was associated with favorable postoperative recovery in cognitive domains particularly 30 days after surgery in patients undergoing aortic valve replacement by cardiopulmonary bypass and the ERACS approach; however, it failed to demonstrate a short-term decrease in length of intensive care unit (ICU) and hospital stay. The survey information indicated a positive appreciation of SG recovery properties. SG reverts postoperative memory deficit and induces the expression of anti-inflammatory microglial markers.

Conclusion

The results show a postoperative cognitive improvement by SG treatment in patients undergoing aortic valve replacement procedure by the ERACS approach. Additionally, experimental data from an animal model of mild surgery confirm the cognitive effect of SG and suggest a potential effect over glia cells as an underlying mechanism.
Roles of the Cannabinoid System in the Basal Ganglia in Parkinson’s Disease
Authors: Wang Mengya , Liu Huayuan , Ma Zegang
Published: February 2022

Parkinson’s disease (PD) is a neurodegenerative disease usually caused by neuroinflammation, oxidative stress and other etiologies. Recent studies have found that the cannabinoid system present in the basal ganglia has a strong influence on the progression of PD. Altering the cannabinoid receptor activation status by modulating endogenous cannabinoid (eCB) levels can exert an anti-movement disorder effect. Therefore, the development of drugs that modulate the endocannabinoid system may be a novel strategy for the treatment of PD. However, eCB regulation is complex, with diverse cannabinoid receptor functions and the presence of dopaminergic, glutamatergic, and γ-aminobutyric signals interacting with cannabinoid signaling in the basal ganglia region. Therefore, the study of eCB is challenging. Here, we have described the function of the cannabinoid system in the basal ganglia and its association with PD in three parts (eCBs, cannabinoid receptors, and factors regulating the cannabinoid metabolism) and summarized the mechanisms of action related to the cannabinoid analogs currently aimed at treating PD. The shortcomings identified from previous studies and the directions that should be explored in the future will provide insights into new approaches and ideas for the future development of cannabinoid-based drugs and the treatment of PD.
A Lifespan Approach to Balance in Static and Dynamic Conditions: The Effect of Age on Balance Abilities
Authors: Marchesi Giorgia , De Luca Alice , Squeri Valentina , De Michieli Lorenzo , Vallone Francesco , Pilotto Alberto , Leo Alessandra , Casadio Maura , Canessa Andrea
Published: February 2022

Postural control is a complex sensorimotor skill that is fundamental to our daily life. The abilities to maintain and recover balance degrade with age. However, the time decay of balance performance with age is not well understood. In this study, we aim at quantifying the age-dependent changes in standing balance under static and dynamic conditions. We tested 272 healthy subjects with ages ranging from 20 to 90. Subjects maintained the upright posture while standing on the robotic platform hunova®. In the evaluation of static balance, subjects stood on the fixed platform both with eyes open (EO) and eyes closed (EC). In the dynamic condition, subjects stood with eyes open on the moving foot platform that provided three different perturbations: (i) an inclination proportional to the center of pressure displacements, (ii) a pre-defined predictable motion, and (iii) an unpredictable and unexpected tilt. During all these tests, hunova® measured the inclination of the platform and the displacement of the center of pressure, while the trunk movements were recorded with an accelerometer placed on the sternum. To quantify balance performance, we computed spatio-temporal parameters typically used in clinical environments from the acceleration measures: mean velocity, variability of trunk motion, and trunk sway area. All subjects successfully completed all the proposed exercises. Their motor performance in the dynamic balance tasks quadratically changed with age. Also, we found that the reliance on visual feedback is not age-dependent in static conditions. All subjects well-tolerated the proposed protocol independently of their age without experiencing fatigue as we chose the timing of the evaluations based on clinical needs and routines. Thus, this study is a starting point for the definition of robot-based assessment protocols aiming at detecting the onset of age-related standing balance deficits and allowing the planning of tailored rehabilitation protocols to prevent falls in older adults.
Case Report: Atonic PNES Capture in fMRI
Authors: Hologne Emmanuelle , Hossu Gabriela , Fantin Luca , Braun Marc , Husson Cyril , Tyvaert Louise , Hingray Coraline
Published: February 2022

Psychogenic Non-Epileptic Seizures (PNES) are a misunderstood and disabling pathology, characterized by a paroxysmal occurrence of clinical signs without the epileptic activity. Resting-state functional MRI (fMRI) studies in patients with PNES have shown abnormal functional connectivity of the resting-state networks, especially in the limbic and motor systems, and in the precuneus. However, the transient nature of PNES episodes prevents us from elucidating the underlying mechanisms of seizures. Here, we report the case of a patient who presented an atonic episode of PNES during a 3T fMRI session. The patient is a 23-year-old woman, suffering from post-traumatic stress disorder, with no neurological comorbidities. The preprocessing of the fMRI images involved realignment, co-registration, segmentation, normalization, denoising (PhysIO toolbox), and smoothing. The time boundary of the seizure was defined according to the patient's reports, and the seizure period was contrasted with the resting state period before the seizure. A whole-brain analysis showed significant activations (left inferior temporal gyrus, left temporo-occipital junction) and deactivations (right precuneus, right superior parietal lobule, right postcentral gyrus, bilateral lingual gyri, inferior occipital gyri, and cerebellar lobules; right insula in a sub-thresholded analysis). Activations and deactivations occurred in four cerebral networks: emotional processing, agency, self-perception, and dissociation. To our knowledge, this report is the first published case of functional MRI during PNES. These results could confirm the emotional and dissociative hypothesis of the physiopathology of PNES and highlight future targets for neuromodulation.
Engineered Biological Neural Networks on High Density CMOS Microelectrode Arrays
Authors: Duru Jens , Küchler Joël , Ihle Stephan J. , Forró Csaba , Bernardi Aeneas , Girardin Sophie , Hengsteler Julian , Wheeler Stephen , Vörös János , Ruff Tobias
Published: February 2022

In bottom-up neuroscience, questions on neural information processing are addressed by engineering small but reproducible biological neural networks of defined network topology in vitro. The network topology can be controlled by culturing neurons within polydimethylsiloxane (PDMS) microstructures that are combined with microelectrode arrays (MEAs) for electric access to the network. However, currently used glass MEAs are limited to 256 electrodes and pose a limitation to the spatial resolution as well as the design of more complex microstructures. The use of high density complementary metal-oxide-semiconductor (CMOS) MEAs greatly increases the spatial resolution, enabling sub-cellular readout and stimulation of neurons in defined neural networks. Unfortunately, the non-planar surface of CMOS MEAs complicates the attachment of PDMS microstructures. To overcome the problem of axons escaping the microstructures through the ridges of the CMOS MEA, we stamp-transferred a thin film of hexane-diluted PDMS onto the array such that the PDMS filled the ridges at the contact surface of the microstructures without clogging the axon guidance channels. This method resulted in 23 % of structurally fully connected but sealed networks on the CMOS MEA of which about 45 % showed spiking activity in all channels. Moreover, we provide an impedance-based method to visualize the exact location of the microstructures on the MEA and show that our method can confine axonal growth within the PDMS microstructures. Finally, the high spatial resolution of the CMOS MEA enabled us to show that action potentials follow the unidirectional topology of our circular multi-node microstructure.
Normal Variants, Pitfalls, and Artifacts in Ga-68 Prostate Specific Membrane Antigen (PSMA) PET/CT Imaging
Authors: Malan Nico , Vangu Mboyo-di-Tamba
Published: February 2022

The advent of gallium 68 prostate specific membrane antigen (PSMA) PET imaging has revolutionized the diagnosis and treatment of prostate cancer. PSMA is a transmembrane glycoprotein that is overexpressed in prostate cancer and yields images with high tumor-to-background contrast. Effective “one-stop-shop” imaging of the prostate, lymph nodes, soft tissue, and bone is achieved with PSMA PET. Compared to conventional imaging, PSMA PET provides superior sensitivity and specificity and plays a pivotal role in staging high-risk prostate cancer as well as in biochemical recurrence by identifying oligometastatic disease. PSMA PET furthermore assists in the selection of patients with metastatic castrate resistant prostate cancer for possible treatment (e.g., labeled with a beta emitter lutetium 177) by using a theranostic approach. The term “prostate specific” is a misnomer as PSMA is also present in other malignant and benign conditions since it acts as a folate hydrolase. To avoid pitfalls and false-positives, a sound knowledge of the normal biodistribution of PSMA as well as other potential causes for false-positive uptake is imperative. This review will describe the expected patterns of distribution of Ga 68 PSMA PET imaging and the common pitfalls noted in published literature since the topic is still evolving.
Acceptance of Insect-Based Food Products in Western Societies: A Systematic Review
Authors: Kröger Tieneke , Dupont Jacqueline , Büsing Lucy , Fiebelkorn Florian
Published: February 2022

Consuming insects is a possible alternative to meat consumption that has few detrimental impacts on the environment and human health. Whether novel foods made from insects will become established in Western societies in the coming years depends largely on their acceptance by the respective populations. Numerous studies on the acceptance of insects as a novel food have already been conducted. In this systematic review, the main findings of quantitative, experimental, and tasting studies on the acceptance of insects as a novel food are summarized. The present paper is designed to serve as an orientation for practitioners in the food industry and provides information useful for the design of marketing strategies and target group-oriented product development. In addition, we highlight in which fields future studies could be conducted to further improve the understanding of the acceptance of insects as food in Western societies.
Association Between Blood Biochemical Factors Contributing to Cognitive Decline and B Vitamins in Patients With Alzheimer's Disease
Authors: Qian Ting , Zhao Lei , Pan Xiaoli , Sang Shaoming , Xu Yangqi , Wang Changpeng , Zhong Chunjiu , Fei Guoqiang , Cheng Xiaoqin
Published: February 2022

Background

Malnutrition, metabolism stress, inflammation, peripheral organs dysfunction, and B vitamins deficiency significantly contribute to the progression and mortality of Alzheimer's disease (AD). However, it is unclear which blood biochemical indicators are most closely related to cognitive decline and B vitamins deficiency (thiamine, folate, vitamin B12) in patients with AD.

Methods

This was a cross-sectional study of 206 AD patients recruited from six hospitals in China. Thiamine diphosphate (TDP), the bioactive form of thiamine, was measured by high-performance liquid chromatography fluoroscopy (HPLC) at a single center. Levels of biochemical indicators (except TDP) were measured by regular and standard laboratory tests in each hospital. Pearson's rank correlation analysis was used to assess relationships between B vitamins and biochemical indicators. T-test was used to compare the difference between ApoE ε4 and non-ApoE ε4 groups. Differences were considered statistically significant as P < 0.05.

Results

Among the biochemical results, in AD population, malnutrition indicators (erythrocyte, hemoglobin, serum albumin, and total protein) were most significantly associated with cognitive function, as was free triiodothyronine (FT3) levels which had been observed in previous study. Malnutrition and FT3 levels depend on age but not apolipoprotein E (ApoE) genotype. Meanwhile, Among the B vitamins, TDP was the most significantly associated with malnutrition indicators and FT3.

Conclusion

Our results indicated that TDP reduction could be a modifiable risk factor for malnutrition and FT3 that contributed to cognitive decline in AD patients. Correcting thiamine metabolism could serve as an optional therapy target for AD treatment.
An Analysis of Clinicopathological Outcomes and the Utility of Preoperative MRI for Patients Undergoing Resection of Mucinous and Non-Mucinous Colorectal Cancer Liver Metastases
Authors: Reynolds Ian S. , Cromwell Paul M. , Ryan Éanna J. , McGrath Erinn , Kennelly Rory , Ryan Ronan , Swan Niall , Sheahan Kieran , Winter Des C. , Hoti Emir
Published: February 2022

Background and Aims

Mucinous colorectal cancer has traditionally been associated with high rates of recurrence and poor long-term survival. There is limited published data on outcomes for patients undergoing liver resection for metastatic mucinous colorectal cancer. The aim of this study was to compare the clinicopathological outcomes for patients with mucinous colorectal cancer liver metastases (CRCLM) undergoing liver resection to a matched group of patients with adenocarcinoma not otherwise specified (NOS) and to evaluate the accurary of preoperative magnetic resonance imaging (MRI) at detecting the presence of mucin in liver metastases.

Materials and Methods

Patients with mucinous CRCLM undergoing liver resection were matched 1:3 to patients with adenocarcinoma NOS CRCLM. Clinicopathological data from the primary tumour and metastatic lesion were collected and compared between the groups. Hepatic recurrence-free, disease-free and overall survival were compared between the groups. The ability of preoperative MRI to detect mucin in CRCLM was also evaluated.

Results

A total of 25 patients with mucinous CRCLM underwent surgery over the 12-year period and were matched to 75 patients with adenocarcinoma NOS. Clinicopathological findings were similar between the groups. Resection of mucinous CRCLM was feasible and safe with similar levels of morbidity to adenocarcinoma NOS. There were no differences identified in hepatic recurrence-free (p=0.85), disease-free (p=0.25) and overall survival (p=0.98) between the groups. MRI had a sensitivity of 31.3% in detecting the presence of mucin in CRCLM.

Conclusion

Patients with mucinous CRCLM in this study had similar outcomes to patients with adenocarcinoma NOS. Based on our findings, histological subtype should not be taken into account when deciding on resectability of CRCLM.
Prognostic and Predictive Models for Left- and Right- Colorectal Cancer Patients: A Bioinformatics Analysis Based on Ferroptosis-Related Genes
Authors: Chen Yingying , Li Hua
Published: February 2022

Background

Left- and right-sided colorectal cancer (LCRC, RCRC) are significantly different in epidemiology and clinical manifestations and have altered outcomes. However, as a hot tumor prognostic marker, the role of ferroptosis-related genes (FRGs) in LCRC and RCRC is unknown.

Methods

From The Cancer Genome Atlas (TCGA) database, we downloaded the expression profiles of CRC patients. A “DESeq2” package was performed to compare the differentially expressed genes (DEGs) of LCRC and RCRC. FRGs were identified using the FerrDb. The prognostic value of differentially expressed FRG (DE-FRG) in left- and right-CRC was assessed separately by Cox regression analysis. Subsequently, functional enrichment analysis, ESTIMATE, and single sample Gene Set Enrichment Analysis (ssGSEA) were performed based on LCRC and RCRC samples to reveal the potential function of FRGs-related risk signatures. The differential expression of FRGs in tumor tissues and adjacent normal tissues were verified by Western blot. The differential expression and prognosis in LCC and RCC were verified by immunohistochemistry.

Results

Based on the identified 14 DE-FRGs, the LCRC prognostic model consisted of NOS2 and IFNG; NOS2 and ALOXE established the prognostic signature that could distinguish RCRC outcomes. In the functional analysis, the DEGs (high risk vs. low risk) of the LCRC and RCRC were significantly enriched in the immune- and lipid-related terms and pathways. ESTIMATE and ssGSEA suggested that these FRGs-related risk signatures were affiliated with the infiltration of immune cell subtypes. Western blotting results showed that NOS2 and ALOXE3 were significantly highly expressed in cancer, and the difference was statistically significant (P < 0.05). Immunohistochemical results showed that ALOXE3 was highly expressed in RCC, and those with high expression had a worse prognosis, while NOS2 gene had an effect on the prognosis of both LCC and RCC.

Conclusion

This study constructed a potential prognostic model of LCRC and RCRC, respectively. We also identified the crucial pathways that contribute to elucidating the pathogenesis of CRC.
Whole-Exome Sequencing Reveals a Missense Variant c.1612C>T (p.Arg538Cys) in the BTD Gene Leading to Neuromyelitis Optica Spectrum Disorder in Saudi Families
Authors: Naseer Muhammad Imran , Pushparaj Peter Natesan , Abdulkareem Angham Abdulrahman , Muthaffar Osama Y.
Published: February 2022

Biotinidase deficiency is an autosomal recessive, multiple carboxylase deficiency usually associated with seizures, eczema, hypotonia, visual disturbances, hearing loss, and developmental delays. Only a handful of cases of biotinidase deficiency that had clinical features of neuromyelitis optica spectrum disorder have been reported in the literature. The case report study is about the clinical and genetic features of two pediatric patients from different families with biotinidase deficiency whose brain and spine MRI scans were suggestive of neuromyelitis optica. Neither child improved with immunotherapy. They come from a first-degree blood-related family. In both cases, a deficiency of the enzyme biotinidase was detected. The missense variant NM_001370658.1 (BTD):c.1612C>T (p.Arg538Cys) NM_000060.4 in exon 4 was identified by whole-exome sequencing. The identified sequence variation was validated using Sanger sequencing analysis. The intake of biotin resulted in clinical improvement. After a follow-up period of 12 months, the patient was gradually weaned from tracheostomy. His vision had improved significantly. He was able to walk and run independently. In conclusion, biotinidase deficiency is a rare and treatable cause of neuromyelitis optica. Early diagnosis can prevent poor clinical outcomes. Biotinidase enzyme levels should be considered as part of the examination algorithm for neuromyelitis optica spectrum disorder.
Influence of Maternal Fish Oil Supplementation on the Risk of Asthma or Wheeze in Children: A Meta-Analysis of Randomized Controlled Trials
Authors: Wu Shaojing , Li Changhong
Published: February 2022

Background

Previous studies evaluating the influences of maternal fish oil supplementation on the risk of asthma or wheeze in children showed inconsistent results. We performed a meta-analysis or randomized controlled trials (RCTs) to systematically evaluate the efficacy of maternal fish oil supplementation for asthma or wheeze.

Methods

Relevant RCTs were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effects model incorporating the potential publication bias was used to pool the results.

Results

Ten RCTs with 3,676 infants were included. Compared to control, maternal supplementation with fish oil was not associated with a reduced risk of asthma or wheeze [odds ratio (OR): 0.91, 95% confidence interval (CI): 0.72–1.14, P = 0.40] with mild heterogeneity (I2 = 28%). Subgroup analyses showed that maternal fish oil supplementation significantly reduced the risk of asthma (OR: 0.56, 95% CI: 0.35–0.91, P = 0.02; I2 = 0%), but not the risk of wheeze (OR: 1.12, 95% CI: 0.90–1.41, P = 0.32; I2 = 0%). In addition, maternal fish oil supplementation was associated with reduced risk of asthma or wheeze in high-dose studies (≥1,200 mg/d, OR: 0.65, 95% CI: 0.48–0.87, P = 0.003; I2 = 0%), but not in low-dose studies (<1,200 mg/d, OR: 1.10, 95% CI: 0.88–1.38, P = 0.39; I2 = 0%, P for subgroup difference = 0.005). Study characteristics such as the risk of the infants, timing of supplementation, and follow-up duration did not significantly affect the results.

Conclusions

Maternal fish oil supplementation may reduce the risk of clinically diagnosed asthma in children, particularly with high-dose fish oil.
Teamwork and Adherence to Guideline on Newborn Resuscitation—Video Review of Neonatal Interdisciplinary Teams
Authors: Brogaard Lise , Hvidman Lone , Esberg Gitte , Finer Neil , Hjorth-Hansen Kristiane R. , Manser Tanja , Kierkegaard Ole , Uldbjerg Niels , Henriksen Tine B.
Published: February 2022

Background

Little is known about the importance of non-technical skills for the adherence to guidelines, when teams of midwives, obstetricians, anesthesiologists, and pediatricians resuscitate and support the transition of newborns. Non-technical skills are competences underpinning successful teamwork in healthcare. These are usually referred to as leadership, situational awareness, communication, teamwork, decision making, and coping with stress and fatigue.

Objective

By review of videos of teams managing newborns with difficult transition, we aimed to investigate whether the level of the teams' non-technical skills was associated with the degree of adherence to guidelines for newborn resuscitation and transitional support at birth.

Methods

Four expert raters independently assessed 43 real-life videos of teams managing newborns with transitional difficulties, two assessed the non-technical score and two assessed the clinical performance. Exposure was the non-technical score, obtained by the Global Assessment Of Team Performance checklist (GAOTP). GAOTP was rated on a Likert Scale 1–5 (1 = poor, 3 = average and 5 = excellent). The outcome was the clinical performance score of the team assessed according to adherence of the European Resuscitation Counsel (ERC) guideline for neonatal resuscitation and transitional support. The ERC guideline was adapted into the checklist TeamOBS-Newborn to facilitate a structured and simple performance assessment (low score 0–60, average 60–84, high 85–100). Interrater agreement was analyzed by intraclass correlation (ICC), Bland-Altman analysis, and Cohen's kappa weighted. The risk of high and low clinical performance was analyzed on the logit scale to meet the assumptions of normality and constant standard deviation.

Results

Teams with an excellent non-technical score had a relative risk 5.5 [95% confidence interval (CI) 2.4–22.5] of high clinical performance score compared to teams with average non-technical score. In addition, we found a dose response like association. The specific non-technical skills associated with the highest degree of adherence to guidelines were leadership and teamwork, coping with stress and fatigue, and communication with parents. Inter-rater agreement was high; raters assessing non-technical skills had an interclass coefficient (ICC) 0.88 (95% CI 0.79–0.94); the neonatologists assessing clinical performance had an ICC of 0.81 (95% CI 0.66–0.89).

Conclusion

Teams with an excellent non-technical score had five times the chance of high clinical performance compared to teams with average non-technical skills. High performance teams were characterized by good leadership and teamwork, coping with stress, and fatigue and communication with parents.
Case Report: Superior Mesenteric Artery Syndrome in an Adolescent With Cannabinoid Hyperemesis
Authors: Berken Jonathan A. , Saul Samantha , Osgood Peter T.
Published: February 2022

Background

Superior mesenteric artery syndrome (SMAS) occurs when the third portion of the duodenum is compressed between the superior mesenteric artery (SMA) and the aorta, causing duodenal obstruction. This condition most commonly arises from marked weight loss that reduces the size of the fat pad between these vessels, causing greater acuity of angulation. We present an unusual case of SMAS occurring in an adolescent due to precipitous weight loss resulting from cannabinoid hyperemesis syndrome (CHS).

Case Presentation

A 17-year-old adolescent presented emergently with voluminous bilious emesis. She endorsed a history of recent weight loss and a longstanding history of chronic heavy cannabis use associated with recurrent nausea and vomiting. Her chronic symptoms satisfied the Rome IV criteria for cannabinoid hyperemesis syndrome, but her acute vomiting symptoms were more extreme. Evaluation was significant for mild abdominal tenderness and fullness of the epigastrium. Contrast abdominal CT demonstrated moderate gastric and proximal duodenal distention with tapering of the lumen between the SMA and the aorta, consistent with SMAS.

Conclusions

To our knowledge, this is the first reported case of SMAS occurring as the result of CHS. Clinicians should be aware of this possible juxtaposition, when a patient with a history of chronic excessive cannabis use, stereotypical vomiting resembling cyclic vomiting syndrome, and considerable rapid weight loss presents with a sudden exacerbation of symptoms, even when a normal BMI is maintained.
Molecular Docking as a Therapeutic Approach for Targeting Cancer Stem Cell Metabolic Processes
Authors: Arjmand Babak , Hamidpour Shayesteh Kokabi , Alavi-Moghadam Sepideh , Yavari Hanieh , Shahbazbadr Ainaz , Tavirani Mostafa Rezaei , Gilany Kambiz , Larijani Bagher
Published: February 2022

Cancer stem cells (CSCs) are subpopulation of cells which have been demonstrated in a variety of cancer models and involved in cancer initiation, progression, and development. Indeed, CSCs which seem to form a small percentage of tumor cells, display resembling characteristics to natural stem cells such as self-renewal, survival, differentiation, proliferation, and quiescence. Moreover, they have some characteristics that eventually can demonstrate the heterogeneity of cancer cells and tumor progression. On the other hand, another aspect of CSCs that has been recognized as a central concern facing cancer patients is resistance to mainstays of cancer treatment such as chemotherapy and radiation. Owing to these details and the stated stemness capabilities, these immature progenitors of cancerous cells can constantly persist after different therapies and cause tumor regrowth or metastasis. Further, in both normal development and malignancy, cellular metabolism and stemness are intricately linked and CSCs dominant metabolic phenotype changes across tumor entities, patients, and tumor subclones. Hence, CSCs can be determined as one of the factors that correlate to the failure of common therapeutic approaches in cancer treatment. In this context, researchers are searching out new alternative or complementary therapies such as targeted methods to fight against cancer. Molecular docking is one of the computational modeling methods that has a new promise in cancer cell targeting through drug designing and discovering programs. In a simple definition, molecular docking methods are used to determine the metabolic interaction between two molecules and find the best orientation of a ligand to its molecular target with minimal free energy in the formation of a stable complex. As a comprehensive approach, this computational drug design method can be thought more cost-effective and time-saving compare to other conventional methods in cancer treatment. In addition, increasing productivity and quality in pharmaceutical research can be another advantage of this molecular modeling method. Therefore, in recent years, it can be concluded that molecular docking can be considered as one of the novel strategies at the forefront of the cancer battle via targeting cancer stem cell metabolic processes.
Natural Kinase Inhibitors for the Treatment and Management of Endometrial/Uterine Cancer: Preclinical to Clinical Studies
Authors: Singla Rajeev K. , Behzad Sahar , Khan Johra , Tsagkaris Christos , Gautam Rupesh K. , Goyal Rajat , Chopra Hitesh , Shen Bairong
Published: February 2022

Endometrial cancer (EC) is the sixth most prevalent type of cancer among women. Kinases, enzymes mediating the transfer of adenosine triphosphate (ATP) in several signaling pathways, play a significant role in carcinogenesis and cancer cells’ survival and proliferation. Cyclin-dependent kinases (CDKs) are involved in EC pathogenesis; therefore, CDK inhibitors (CDKin) have a noteworthy therapeutic potential in this type of cancer, particularly in EC type 1. Natural compounds have been used for decades in the treatment of cancer serving as a source of anticancer bioactive molecules. Many phenolic and non-phenolic natural compounds covering flavonoids, stilbenoids, coumarins, biphenyl compounds, alkaloids, glycosides, terpenes, and terpenoids have shown moderate to high effectiveness against CDKin-mediated carcinogenic signaling pathways (PI3K, ERK1/2, Akt, ATM, mTOR, TP53). Pharmaceutical regimens based on two natural compounds, trabectedin and ixabepilone, have been investigated in humans showing short and midterm efficacy as second-line treatments in phase II clinical trials. The purpose of this review is twofold: the authors first provide an overview of the involvement of kinases and kinase inhibitors in the pathogenesis and treatment of EC and then discuss the existing evidence about natural products’ derived kinase inhibitors in the management of the disease and outline relevant future research.