bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins
Authors: Zhu Yanlei , Alvarez Flavio , Wolff Nicolas , Mechaly Ariel , Brûlé Sébastien , Neitthoffer Benoit , Etienne-Manneville Sandrine , Haouz Ahmed , Boëda Batiste , Caillet-Saguy Célia
Published: February 2022

The C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein E contains a PBM (PDZ-binding motif) targeting PDZ (PSD-95/Dlg/ZO-1) domains, which is identical to the PBM of SARS-CoV. The latter is involved in the pathogenicity of the virus. Recently, we identified 10 human PDZ-containing proteins showing significant interactions with SARS-CoV-2 protein E PBM. We selected several of them involved in cellular junctions and cell polarity (TJP1, PARD3, MLLT4, and LNX2) and MPP5/PALS1 previously shown to interact with SARS-CoV E PBM. Targeting cellular junctions and polarity components is a common strategy by viruses to hijack cell machinery to their advantage. In this study, we showed that these host PDZ domains TJP1, PARD3, MLLT4, LNX2, and MPP5/PALS1 interact in a PBM-dependent manner in vitro and colocalize with the full-length E protein in cellulo, sequestrating the PDZ domains to the Golgi compartment. We solved three crystal structures of complexes between human LNX2, MLLT4, and MPP5 PDZs and SARS-CoV-2 E PBM highlighting its binding preferences for several cellular targets. Finally, we showed different affinities for the PDZ domains with the original SARS-CoV-2 C-terminal sequence containing the PBM and the one of the beta variant that contains a mutation close to the PBM. The acquired mutations in the E protein localized near the PBM might have important effects both on the structure and the ion-channel activity of the E protein and on the host machinery targeted by the variants during the infection.
Contribution and Future of High-Throughput Transcriptomics in Battling Tuberculosis
Authors: Martínez-Pérez Amparo , Estévez Olivia , González-Fernández África
Published: February 2022

While Tuberculosis (TB) infection remains a serious challenge worldwide, big data and “omic” approaches have greatly contributed to the understanding of the disease. Transcriptomics have been used to tackle a wide variety of queries including diagnosis, treatment evolution, latency and reactivation, novel target discovery, vaccine response or biomarkers of protection. Although a powerful tool, the elevated cost and difficulties in data interpretation may hinder transcriptomics complete potential. Technology evolution and collaborative efforts among multidisciplinary groups might be key in its exploitation. Here, we discuss the main fields explored in TB using transcriptomics, and identify the challenges that need to be addressed for a real implementation in TB diagnosis, prevention and therapy.
Warning Signs of Potential Black Swan Outbreaks in Infectious Disease
Authors: Velappan Nileena , Davis-Anderson Katie , Deshpande Alina
Published: February 2022

Black swan events in infectious disease describe rare but devastatingly large outbreaks. While experts are skeptical that such events are predictable, it might be possible to identify the warning signs of a black swan event. Specifically, following the initiation of an outbreak, key differentiating features could serve as alerts. Such features could be derived from meta-analyses of large outbreaks for multiple infectious diseases. We hypothesized there may be common features among the pathogen, environment, and host epidemiological triad that characterize an infectious disease black swan event. Using Los Alamos National Laboratory’s tool, Analytics for Investigation of Disease Outbreaks, we investigated historical disease outbreak information and anomalous events for several infectious diseases. By studying 32 different infectious diseases and global outbreaks, we observed that in the past 20–30 years, there have been potential black swan events in the majority of infectious diseases analyzed. Importantly, these potential black swan events cannot be attributed to the first introduction of the disease to a susceptible host population. This paper describes our observations and perspectives and illustrates the value of broad analysis of data across the infectious disease realm, providing insights that may not be possible when we focus on singular infectious agents or diseases. Data analytics could be developed to warn health authorities at the beginning of an outbreak of an impending black swan event. Such tools could complement traditional epidemiological modeling to help forecast future large outbreaks and facilitate timely warning and effective, targeted resource allocation for mitigation efforts.
Antigen-Specific vs. Neutralizing Antibodies Against Conditioned Media of Patients With Clostridioides difficile Infection: A Prospective Exploratory Study
Authors: Roth Sophie , Jung Philipp , Boone James , Mellmann Alexander , Nimmesgern Anna , Becker Sören L. , Berger Fabian K. , von Müller Lutz
Published: February 2022

The immunological response against Clostridioides difficile (C. difficile) is crucial for an improved understanding of disease mechanisms and the development of novel therapeutic strategies. From April 2014 to February 2015, adult patients with C. difficile infection (CDI) were recruited, and the clinical course and treatment response were carefully monitored. On day 1, 3, and 6 after diagnosis, patient plasma samples were screened for anti-GDH (glutamate dehydrogenase), anti-TcdA, anti-TcdB, and anti-CWP84 (cell-wall protein 84) antibodies by ELISA. Additionally, neutralization assays of toxins from conditioned media of clinical isolates (RT010, RT014, and RT027) were performed. Most patients with CDI (n = 46) had antibodies against GDH (85%) and CWP84 (61%), but only few had antibodies against TcdA (11%) and TcdB (28%). We found patients with neutralizing antibodies against C. difficile toxins (conditioned media) produced by RT027 (26%). A subgroup of these samples could neutralize both toxins from RT027 and RT014 [11%, (5/46)]; however, no single sample neutralized only RT014. Overall, neutralizing antibody titers were low (≤1:16). In a one week follow-up of acute infection, we never observed an early booster effect with seroconversion or antibody increases, irrespective of disease severity. No correlation was found between the presence of antigen-specific (ELISA) or neutralizing antibodies and the clinical course of disease. Anti-TcdB but not anti-TcdA antibodies correlated with the occurrence of neutralizing antibodies. In conclusion, natural antibody titers against C. difficile toxins were absent or low and were not associated with disease severity. The correlation between the anti-TcdB with toxin neutralization confirms the importance of TcdB for virulence of CDI. Alternative sensitization strategies, e.g., through vaccine development, are required to overcome the regular low-titer antibody production following natural intestinal C. difficile exposure.
Profiling Urinary Sulfate Metabolites With Mass Spectrometry
Authors: Fitzgerald Christopher C. J. , Hedman Rikard , Uduwela Dimanthi R. , Paszerbovics Bettina , Carroll Adam J. , Neeman Teresa , Cawley Adam , Brooker Lance , McLeod Malcolm D.
Published: February 2022

The study of urinary phase II sulfate metabolites is central to understanding the role and fate of endogenous and exogenous compounds in biological systems. This study describes a new workflow for the untargeted metabolic profiling of sulfated metabolites in a urine matrix. Analysis was performed using ultra-high-performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS) with data dependent acquisition (DDA) coupled to an automated script-based data processing pipeline and differential metabolite level analysis. Sulfates were identified through k-means clustering analysis of sulfate ester derived MS/MS fragmentation intensities. The utility of the method was highlighted in two applications. Firstly, the urinary metabolome of a thoroughbred horse was examined before and after administration of the anabolic androgenic steroid (AAS) testosterone propionate. The analysis detected elevated levels of ten sulfated steroid metabolites, three of which were identified and confirmed by comparison with synthesised reference materials. This included 5α-androstane-3β,17α-diol 3-sulfate, a previously unreported equine metabolite of testosterone propionate. Secondly, the hydrolytic activity of four sulfatase enzymes on pooled human urine was examined. This revealed that Pseudomonas aeruginosa arylsulfatases (PaS) enzymes possessed higher selectivity for the hydrolysis of sulfated metabolites than the commercially available Helix pomatia arylsulfatase (HpS). This novel method provides a rapid tool for the systematic, untargeted metabolic profiling of sulfated metabolites in a urinary matrix.
Impact of a Single Nucleotide Polymorphism on the 3D Protein Structure and Ubiquitination Activity of E3 Ubiquitin Ligase Arkadia
Authors: Birkou Maria , Raptis Vasilios , Marousis Konstantinos D. , Tsevis Athanasios , Bourikas Kyriakos , Bentrop Detlef , Episkopou Vasso , Spyroulias Georgios A.
Published: February 2022

Single nucleotide polymorphisms (SNPs) are genetic variations which can play a vital role in the study of human health. SNP studies are often used to identify point mutations that are associated with diseases. Arkadia (RNF111) is an E3 ubiquitin ligase that enhances transforming growth factor-beta (TGF-β) signaling by targeting negative regulators for degradation. Dysregulation of the TGF-β pathway is implicated in cancer because it exhibits tumor suppressive activity in normal cells while in tumor cells it promotes invasiveness and metastasis. Τhe SNP CGT > TGT generated an amino-acid (aa) substitution of Arginine 957 to Cysteine on the enzymatic RING domain of Arkadia. This was more prevalent in a tumor than in a normal tissue sample of a patient with colorectal cancer. This prompted us to investigate the effect of this mutation in the structure and activity of Arkadia RING. We used nuclear magnetic resonance (NMR) to analyze at an atomic-level the structural and dynamic properties of the R957C Arkadia RING domain, while ubiquitination and luciferase assays provided information about its enzymatic functionality. Our study showed that the R957C mutation changed the electrostatic properties of the RING domain however, without significant effects on the structure of its core region. However, the functional studies revealed that the R957C Arkadia exhibits significantly increased enzymatic activity supporting literature data that Arkadia within tumor cells promotes aggressive and metastatic behavior.
Endophytic Microorganisms From the Tropics as Biofactories for the Synthesis of Metal-Based Nanoparticles: Healthcare Applications
Authors: Bogas Andréa Cristina , Henrique Rodrigues Saulo , Gonçalves Mariana Ottaiano , De Assis Marcelo , Longo Elson , Paiva De Sousa Cristina
Published: February 2022

Nanoparticles (NPs) have gained great attention in recent years due to their extensive and innovative applications in the field of medicine. However, conventional physicochemical approaches for the synthesis of NPs may be limited and costly, and the reaction by-products are potentially toxic for human health and the environment. Bio-mediated synthesis of NPs exploiting microorganisms as nanofactories has emerged as an alternative to traditional methods, as it provides economic and environmental benefits. Tropical ecosystems harbor a high diversity of endophytes, which have a diverse array of metabolic pathways that confer habitat adaptation and survival and that can be used to produce novel bioactive compounds with a variety of biological properties. Endophytic bacteria and fungi cultivated under optimum conditions have potential for use in biogenic synthesis of NPs with different characteristics and desired activities for medical applications, such as antimicrobial, antitumoral, antioxidant and anti-inflammatory properties. The bio-mediated synthesis of metal-based NPs can be favored because endophytic microorganisms may tolerate and/or adsorb metals and produce enzymes used as reducing agents. To our knowledge, this is the first review that brings together exclusively current research highlighting on the potential of endophytic bacteria and fungi isolated from native plants or adapted to tropical ecosystems and tropical macroalgae as nanofactories for the synthesis of NPs of silver, gold, copper, iron, zinc and other most studied metals, in addition to showing their potential use in human health.
Altered Spontaneous Brain Activity and Network Property in Patients With Congenital Monocular Blindness
Authors: Ding Jingwen , Qu Xiaoxia , Cui Jing , Dong Jie , Guo Jian , Xian Junfang , Li Dongmei
Published: February 2022

Individuals with congenital monocular blindness may have specific brain changes since the brain is prenatally deprived of half the normal visual input. To explore characteristic brain functional changes of congenital monocular blindness, we analyzed resting-state functional MRI (rs-fMRI) data of 16 patients with unilateral congenital microphthalmia and 16 healthy subjects with normal vision to compare intergroup differences of amplitude of low frequency fluctuations (ALFFs), functional connectivity (FC), and network topolgoical properties. Compared with controls, patients with microphthalmia exhibited significantly lower ALFF values in the left inferior occipital and temporal gyri, superior temporal gyrus, inferior parietal lobe and post-central gyrus, whereas higher ALFF in the right middle and inferior temporal gyri, middle and superior frontal gyri, left superior frontal, and temporal gyri, such as angular gyrus. Meanwhile, FC between left medial superior frontal gyrus and angular gyrus, FC between left superior temporal gyrus and inferior parietal lobe and post-central gyrus decreased in the patients with congenital microphthalmia. In addition, a graph theory-analysis revealed increased regional network metrics (degree centrality and nodal efficiency) in the middle and inferior temporal gyri and middle and superior frontal gyri, while decreased values in the inferior occipital and temporal gyri, inferior parietal lobule, post-central gyrus, and angular gyrus. Taken together, patients with congenital microphthalmia had widespread abnormal activities within neural networks involving the vision and language and language-related regions played dominant roles in their brain networks. These findings may provide clues for functional reorganization of vision and language networks induced by the congenital monocular blindness.
The Application of Consensus Weighted Gene Co-expression Network Analysis to Comparative Transcriptome Meta-Datasets of Multiple Sclerosis in Gray and White Matter
Authors: Chai Keping , Zhang Xiaolin , Tang Huitao , Gu Huaqian , Ye Weiping , Wang Gangqiang , Chen Shufang , Wan Feng , Liang Jiawei , Shen Daojiang
Published: February 2022

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination, which leads to the formation of white matter lesions (WMLs) and gray matter lesions (GMLs). Recently, a large amount of transcriptomics or proteomics research works explored MS, but few studies focused on the differences and similarities between GMLs and WMLs in transcriptomics. Furthermore, there are astonishing pathological differences between WMLs and GMLs, for example, there are differences in the type and abundance of infiltrating immune cells between WMLs and GMLs. Here, we used consensus weighted gene co-expression network analysis (WGCNA), single-sample gene set enrichment analysis (ssGSEA), and machine learning methods to identify the transcriptomic differences and similarities of the MS between GMLs and WMLs, and to find the co-expression modules with significant differences or similarities between them. Through weighted co-expression network analysis and ssGSEA analysis, CD56 bright natural killer cell was identified as the key immune infiltration factor in MS, whether in GM or WM. We also found that the co-expression networks between the two groups are quite similar (density = 0.79), and 28 differentially expressed genes (DEGs) are distributed in the midnightblue module, which is most related to CD56 bright natural killer cell in GM. Simultaneously, we also found that there are huge disparities between the modules, such as divergences between darkred module and lightyellow module, and these divergences may be relevant to the functions of the genes in the modules.
Chlorovirus ATCV-1 Accelerates Motor Deterioration in SOD1-G93A Transgenic Mice and Its SOD1 Augments Induction of Inflammatory Factors From Murine Macrophages
Authors: Petro Thomas M. , Agarkova Irina V. , Esmael Ahmed , Dunigan David D. , Van Etten James L. , Pattee Gary L.
Published: February 2022

Background

Genetically polymorphic Superoxide Dismutase 1 G93A (SOD1-G93A) underlies one form of familial Amyotrophic Lateral Sclerosis (ALS). Exposures from viruses may also contribute to ALS, possibly by stimulating immune factors, such as IL-6, Interferon Stimulated Genes, and Nitric Oxide. Recently, chlorovirus ATCV-1, which encodes a SOD1, was shown to replicate in macrophages and induce inflammatory factors.

Objective

This study aimed to determine if ATCV-1 influences development of motor degeneration in an ALS mouse model and to assess whether SOD1 of ATCV-1 influences production of inflammatory factors from macrophages.

Methods

Sera from sporadic ALS patients were screened for antibody to ATCV-1. Active or inactivated ATCV-1, saline, or a viral mimetic, polyinosinic:polycytidylic acid (poly I:C) were injected intracranially into transgenic mice expressing human SOD1-G93A- or C57Bl/6 mice. RAW264.7 mouse macrophage cells were transfected with a plasmid vector expressing ATCV-1 SOD1 or an empty vector prior to stimulation with poly I:C with or without Interferon-gamma (IFN-γ).

Results

Serum from sporadic ALS patients had significantly more IgG1 antibody directed against ATCV-1 than healthy controls. Infection of SOD1-G93A mice with active ATCV-1 significantly accelerated onset of motor loss, as measured by tail paralysis, hind limb tucking, righting reflex, and latency to fall in a hanging cage-lid test, but did not significantly affect mortality when compared to saline-treated transgenics. By contrast, poly I:C treatment significantly lengthened survival time but only minimally slowed onset of motor loss, while heat-inactivated ATCV-1 did not affect motor loss or survival. ATCV-1 SOD1 significantly increased expression of IL-6, IL-10, ISG promoter activity, and production of Nitric Oxide from RAW264.7 cells.

Conclusion

ATCV-1 chlorovirus encoding an endogenous SOD1 accelerates pathogenesis but not mortality, while poly I:C that stimulates antiviral immune responses delays mortality in an ALS mouse model. ATCV-1 SOD1 enhances induction of inflammatory factors from macrophages.
Use of Stakeholder Feedback to Develop an App for Vestibular Rehabilitation–Input From Clinicians and Healthy Older Adults
Authors: DSilva Linda J. , Skop Karen M. , Pickle Nathan T. , Marschner Katherine , Zehnbauer Timothy P. , Rossi Michael , Roos Paulien E.
Published: February 2022

Close to half people over 60 years of age experience vestibular dysfunction. Although vestibular rehabilitation has been proven effective in reducing dizziness and falls in older adults, adherence to exercise programs is a major issue and reported to be below 50%. Therefore, this research aimed to develop an app with gaming elements to improve adherence to exercises that are part of vestibular rehabilitation, and to provide feedback to increase the accuracy during exercise performance. A clinician-informed design was used where five physical therapists were asked identical questions about the exercises they would like to see in the app, including their duration and frequency. Games were developed to train the vestibulo-ocular (VOR) reflex using VOR and gaze shifting exercises; and to train the vestibulo-spinal system using weight shifting and balance exercises. The games were designed to progress from simple to more complex visuals. The games were controlled by an Inertial Measurement Unit placed on the head or anterior waist. The app was tested on ten healthy females (69.1 ± 5.1 years) with no prior history of vestibular dysfunction or complaints of dizziness. Participants completed gaze stabilization and balance exercises using the app and provided feedback on the user interface, ease of use, usefulness and enjoyment using standardized questionnaires and changes they would like to see in the form of open-ended questions. In general, participants reported that they found the app easy to use, the user interface was friendly, and they enjoyed playing the games due to the graphics and colors. They reported that the feedback provided during the exercise session helped them recognize their mistakes and motivated them to do better. However, some elements of the app were frustrating due to incomplete instructions and inability to distinguish game objects due to insufficient contrast. Feedback received will be implemented in a revised version which will be trialed in older adults with dizziness due to vestibular hypofunction. We have demonstrated that the “Vestibular AppTM” created for rehabilitation with gaming elements was found to be enjoyable, useful, and easy to use by healthy older adults. In the long term, the app may increase adherence to vestibular rehabilitation.
Anodal Transcranial Direct Current Stimulation Over Prefrontal Cortex Slows Sequence Learning in Older Adults
Authors: Greeley Brian , Barnhoorn Jonathan S. , Verwey Willem B. , Seidler Rachael D.
Published: February 2022

Aging is associated with declines in sensorimotor function. Several studies have demonstrated that transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, can be combined with training to mitigate age-related cognitive and motor declines. However, in some cases, the application of tDCS disrupts performance and learning. Here, we applied anodal tDCS either over the left prefrontal cortex (PFC), right PFC, supplementary motor complex (SMC), the left M1, or in a sham condition while older adults (n = 63) practiced a Discrete Sequence Production (DSP), an explicit motor sequence, task across 3 days. We hypothesized that stimulation to either the right or left PFC would enhance motor learning for older adults, based on the extensive literature showing increased prefrontal cortical activity during motor task performance in older adults. Contrary to our predictions, stimulation to the right and left PFC resulted in slowed motor learning, as evidenced by a slower reduction rate of reduction of reaction time and the number of sequence chunks across trials relative to sham in session one and session two, respectively. These findings suggest an integral role of the right PFC early in sequence learning and a role of the left PFC in chunking in older adults, and contribute to mounting evidence of the difficultly of using tDCS in an aging population.
Novel Intronic Mutations of TBK1 Promote Aberrant Splicing Modes in Amyotrophic Lateral Sclerosis
Authors: Lu Ying-Qian , Chen Jian-Min , Lin Han , Feng Shu-Yan , Che Chun-Hui , Liu Chang-Yun , Huang Hua-Pin , Zou Zhang-Yu
Published: February 2022

TANK-binding kinase 1 (TBK1) has been identified as a causative gene of amyotrophic lateral sclerosis (ALS) in the Caucasian population in 2015. Here, we sequenced for TBK1 variants in a cohort of 15 familial ALS (fALS) and 275 sporadic ALS (sALS) of Chinese origin by targeted next-generation sequencing. We identified one likely benign missense variant (p. Ser398Pro), two missense variants of uncertain significance (p. Ile37Leu and p. Tyr677Asn), and two novel heterozygous variants in introns of TBK1, c.1522-3T > G and c.2066 + 4A > G. We performed splicing assays through minigene plasmids and RNA pull-down assay to determine that the two substitutions of nucleotides disrupted the binding of the important splicing regulator hnRNPA1 and promoted aberrant pre-mRNA splicing modes. The c.1522-3T > G variant promoted nearly 50.0% of abnormal transcripts (3 different types of insertions and deletions (indels) in junction of intron 13-exon 14) and the c.2066 + 4A > G variant inhibited about 75.0% inclusion of exon 19, both causing premature stop codon and producing TBK1 protein without CCD2. Immunofluorescence analysis showed that the expression of TBK1 with intronic variants was lower since less TBK1 distribution was observed in HEK293T cells. Both patients carrying TBK1 c.1522-3T > G and c.2066 + 4A > G variants developed a rapidly progressive ALS, with a survival of 31 and 10 months, respectively. The frequency of loss of function (LoF) variants in TBK1 was 0.73% in sALS in our cohort. We emphasize that intronic sequencing and pre-mRNA splicing analysis cannot be ignored to demonstrate the complex mutational spectrum and pathogenesis of ALS.
Investigating Differences in Behavior and Brain in Human-Human and Human-Autonomous Vehicle Interactions in Time-Critical Situations
Authors: Unni Anirudh , Trende Alexander , Pauley Claire , Weber Lars , Biebl Bianca , Kacianka Severin , Lüdtke Andreas , Bengler Klaus , Pretschner Alexander , Fränzle Martin , Rieger Jochem W.
Published: February 2022

Some studies provide evidence that humans could actively exploit the alleged technological advantages of autonomous vehicles (AVs). This implies that humans may tend to interact differently with AVs as compared to human driven vehicles (HVs) with the knowledge that AVs are programmed to be risk-averse. Hence, it is important to investigate how humans interact with AVs in complex traffic situations. Here, we investigated whether participants would value interactions with AVs differently compared to HVs, and if these differences can be characterized on the behavioral and brain-level. We presented participants with a cover story while recording whole-head brain activity using fNIRS that they were driving under time pressure through urban traffic in the presence of other HVs and AVs. Moreover, the AVs were programmed defensively to avoid collisions and had faster braking reaction times than HVs. Participants would receive a monetary reward if they managed to finish the driving block within a given time-limit without risky driving maneuvers. During the drive, participants were repeatedly confronted with left-lane turning situations at unsignalized intersections. They had to stop and find a gap to turn in front of an oncoming stream of vehicles consisting of HVs and AVs. While the behavioral results did not show any significant difference between the safety margin used during the turning maneuvers with respect to AVs or HVs, participants tended to be more certain in their decision-making process while turning in front of AVs as reflected by the smaller variance in the gap size acceptance as compared to HVs. Importantly, using a multivariate logistic regression approach, we were able to predict whether the participants decided to turn in front of HVs or AVs from whole-head fNIRS in the decision-making phase for every participant (mean accuracy = 67.2%, SD = 5%). Channel-wise univariate fNIRS analysis revealed increased brain activation differences for turning in front of AVs compared to HVs in brain areas that represent the valuation of actions taken during decision-making. The insights provided here may be useful for the development of control systems to assess interactions in future mixed traffic environments involving AVs and HVs.
Entrainment and Spike-Timing Dependent Plasticity – A Review of Proposed Mechanisms of Transcranial Alternating Current Stimulation
Authors: Vogeti Sreekari , Boetzel Cindy , Herrmann Christoph S.
Published: February 2022

Specific frequency bands of neural oscillations have been correlated with a range of cognitive and behavioral effects (e.g., memory and attention). The causal role of specific frequencies may be investigated using transcranial alternating current stimulation (tACS), a non-invasive brain stimulation method. TACS involves applying a sinusoidal current between two or more electrodes attached on the scalp, above neural regions that are implicated in cognitive processes of interest. The theorized mechanisms by which tACS affects neural oscillations have implications for the exact stimulation frequency used, as well as its anticipated effects. This review outlines two main mechanisms that are thought to underlie tACS effects – entrainment, and spike-timing dependent plasticity (STDP). Entrainment suggests that the stimulated frequency synchronizes the ongoing neural oscillations, and is thought to be most effective when the stimulated frequency is at or close to the endogenous frequency of the targeted neural network. STDP suggests that stimulation leads to synaptic changes based on the timing of neuronal firing in the target neural network. According to the principles of STDP, synaptic strength is thought to increase when pre-synaptic events occur prior to post-synaptic events (referred to as long-term potentiation, LTP). Conversely, when post-synaptic events occur prior to pre-synaptic events, synapses are thought to be weakened (referred to as long-term depression, LTD). In this review, we summarize the theoretical frameworks and critically review the tACS evidence for each hypothesis. We also discuss whether each mechanism alone can account for tACS effects or whether a combined account is necessary.
Underlying Causes and Co-existence of Malnutrition and Infections: An Exceedingly Common Death Risk in Cancer
Authors: Fan Yuanyuan , Yao Qianqian , Liu Yufeng , Jia Tiantian , Zhang Junjuan , Jiang Enshe
Published: February 2022

In nutrition science, malnutrition is a state of imbalance between intake and the needs of the organism, leading to metabolic changes, impaired physiological functions, and weight loss. Regardless of the countless efforts being taken and researched for years, the burden of malnutrition is still alarming and considered a significant agent of mortality across the globe. Around 45% of 12 million children deaths (0–5 years old) annually are due to malnutrition, mostly from developing countries. Malnutrition develops associations with other infections and leads to substantial clinical outcomes, such as mortality, more visits to hospitals, poor quality of life and physical frailty, and socioeconomic issues. Here, in this review, we intend to provide an overview of the current burden, underlying risk factors, and co-existence of malnutrition and other infections, such as cancer. Following the rising concern of the vicious interplay of malnutrition and other medical illnesses, we believed that this narrative review would highlight the need to re-make and re-define the future strategies by giving comprehensive and sustainable programs to alleviate poverty and combat the rampant infectious diseases and those nutrition-related health problems. Furthermore, the study also raises the concern for hospitalized malnourished cancer patients as it is crucially important to knowledge the caregiver healthcare staff for early interventions of providing nutritional support to delay or prevent the onset of malnutrition.
Dietary Magnesium Intake Modifies the Association Between Vitamin D and Systolic Blood Pressure: Results From NHANES 2007–2014
Authors: Huang Weichao , Ma Xiaoman , Chen Yue , Zheng Jiayi , Li Haojia , Nizhamu Ayinigaer , Hong Qingting , Guo Xuguang
Published: February 2022

Introduction

Although the association between blood pressure and vitamin D has been well studied, the effects of dietary magnesium intake on this relationship are still unclear. Thus, this study aimed to determine the effects of dietary magnesium intake on the association between vitamin D and blood pressure.

Methods

The present study analyzed data from the continuous the National Health and Nutrition Examination Survey (NHANES) 2007–2014. We included 8,799 participants aged 20 years or older. Multivariable linear regression was performed to assess the association between vitamin D and systolic blood pressure (SBP) and diastolic blood pressure (DBP). Dietary magnesium intake was stratified by low magnesium intake (<299 mg/d) and high magnesium intake (≥299 mg/d). Effect modification by dietary magnesium intake was assessed through interaction tests between vitamin D and SBP in the multivariable linear regression.

Results

In this cross-sectional study, we found that vitamin D was negatively related to SBP, but not to DBP. The relationship between vitamin D and SBP was different in the low and high magnesium intake group (β: −0.25 95%Cl: −0.4~0.07 vs β: −0.32 95%Cl: −0.52~-0.12). Furthermore, magnesium intake significantly modified the negative relationship between vitamin D and SBP in most of the models.

Conclusion

Our research showed that magnesium and vitamin D have an interactive effect in reducing SBP, which may have great importance for clinical medication.
Effect of Different Extraction Methods and Geographical Origins on the Total Phenolic Yield, Composition, and Antimicrobial Activity of Sugarcane Bagasse Extracts
Authors: Velázquez-Martínez Victor , Valles-Rosales Delia , Rodríguez-Uribe Laura , Laguna-Camacho Juan Rodrigo , López-Calderón Hector Daniel , Delgado Efren
Published: February 2022

Several parameters, including particle size, solvent, temperature, and extraction method, affect phenolic compounds' extraction yield from a plant matrix. Considering the wide availability of sugarcane bagasse (SCB), this study analyzed the effect of different extraction methods and geographical origins on the yield, quality, and antimicrobial activity of phenolic compounds from SCB extracts. Samples from three geographical locations (Veracruz, Mexico; Santa Rosa, Texas, USA; and St. Mary, Louisiana, USA) were analyzed. Extraction was performed using an orbital shaker or ultrasonic bath at various times at a fixed temperature of 50°C, with 90% ethanol or methanol. The highest yield (5.91 mg GAE) was obtained using an orbital shaker for 24 h with 90% methanol as the solvent. HPLC-MS identified desferrioxamine b, baicalein, madecassic acid, and podototarin at different concentrations in all three SCB samples. The antimicrobial activity of these compounds was tested against Escherichia coli K12, Bacillus cereus, Enterobacter aerogenes, Streptococcus aureus, and Enterobacter cloacae. The antimicrobial activity was also tested against modifications of the Saccharomyces cerevisiae: the MutL Homolog 1 (MLH1), Slow Growth Suppressor (SGS1), O-6-MethylGuanine-DNA methyltransferase (MGT1), and RADiation sensitive (RAD14), carrying mutations related to different cancer types. In addition, the results were compared with the effect of ampicillin and kanamycin. The SCB extracts showed up to 90% growth inhibition against B. cereus at 200–800 μg/mL and 50% growth inhibition against S. aureus at 800 μg/mL. The inhibitory effect against modified yeast SGS1, RAD14, and MLH1 was 50–80% at 800 μg/mL. The percentage of inhibition and the phenolic compound contents differed depending on the origin of the SCB sample. These findings are promising for using this industrial byproduct to obtain compounds for nutraceutical, food additive, or medical uses.
RETRACTED: ZNF655 Promotes the Progression of Glioma Through Transcriptional Regulation of AURKA
Authors: Chen Xu , Liu Chao , Zhang Zhenyu , Wang Meng , Guo Shewei , Li Tianhao , Sun Hongwei , Zhang Peng
Published: February 2022

Objectives

Glioma has a high degree of malignancy, strong invasiveness, and poor prognosis, which is always a serious threat to human health. Previous studies have reported that C2H2 zinc finger (ZNF) protein is involved in the progression of various cancers. In this study, the clinical significance, biological behavior, and molecule mechanism of ZNF655 in glioma were explored.

Methods

The expression of ZNF655 in glioma and its correlation with prognosis were analyzed through public datasets and immunohistochemical (IHC) staining. The shRNA-mediated ZNF655 knockdown was used to explore the effects of ZNF655 alteration on the phenotypes and tumorigenesis of human glioma cell lines. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were performed to determine the potential mechanism of ZNF655 regulating Aurora kinase A (AURKA).

Results

ZNF655 was abundantly expressed in glioma tissue and cell lines SHG-44 and U251. Knockdown of suppressed the progression of glioma cells, which was characterized by reduced proliferation, enhanced apoptosis, cycle repression in G2, inhibition of migration, and weakened tumorigenesis. Mechanistically, transcription factor ZNF655 activated the expression of AURKA by directly binding to the promoter of AURKA. In addition, downregulation of AURKA partially reversed the promoting effects of overexpression of ZNF655 on glioma cells.

Conclusions

ZNF655 promoted the progression of glioma by binding to the promoter of AURKA, which may be a promising target for molecular therapy.
COL5A2 Inhibits the TGF-β and Wnt/β-Catenin Signaling Pathways to Inhibit the Invasion and Metastasis of Osteosarcoma
Authors: Han Yan-Long , Luo Dan , Habaxi Kakeng , Tayierjiang Julaiti , Zhao Wei , Wang Wei , Aikebaier Wumaierjiang , Wang Li
Published: February 2022

Osteosarcoma is the most common skeletal malignancy and is the second leading cause of cancer death in adolescents. Its highly aggressive nature and high propensity to metastasize lead to an extremely poor prognosis for patients with osteosarcoma. Therefore, finding a suitable treatment has become a matter of urgency. In this study, we first divided the samples into metastatic and non-metastatic groups using the Target database and obtained 1136 differentially expressed genes (DEGs) using differential analysis. A PPI network was constructed to analyze the network of action relationships among DEGs, and the top 10 genes were derived using the MCC algorithm in Cytoscape software. A risk scoring system for 10 key genes was constructed using the LASSO-COX prognostic risk model, and genes associated with osteosarcoma prognosis were screened based on multifactorial COX. COL5A2 gene was highly expressed in metastatic osteosarcoma and led to a poor prognosis. Furthermore, qRT-PCR and immunofluorescence assays confirmed the high expression of COL5A2 in human osteosarcoma cells. CCK-8 assay and scratch WB was used to determine whether the downregulation of COL5A2 expression inhibits the TGF-β signaling and Wnt/β-Catenin signaling pathways. In this study, we screened COL5A2 for prognostic relevance to osteosarcoma through bioinformatics analysis and demonstrated that COL5A2 inhibited osteosarcoma invasion and metastasis by suppressing the TGF-β signaling and Wnt/β-Catenin signaling pathways.
A Predictive Model of 2yDFS During MR-Guided RT Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients
Authors: Chiloiro Giuditta , Boldrini Luca , Preziosi Francesco , Cusumano Davide , Yadav Poonam , Romano Angela , Placidi Lorenzo , Lenkowicz Jacopo , Dinapoli Nicola , Bassetti Michael F. , Gambacorta Maria Antonietta , Valentini Vincenzo
Published: February 2022

Purpose

Distant metastasis is the main cause of treatment failure in locally advanced rectal cancer (LARC) patients, despite the recent improvement in treatment strategies. This study aims to evaluate the “delta radiomics” approach in patients undergoing neoadjuvant chemoradiotherapy (nCRT) treated with 0.35-T magnetic resonance-guided radiotherapy (MRgRT), developing a logistic regression model able to predict 2-year disease-free-survival (2yDFS).

Methods

Patients affected by LARC were enrolled in this multi-institutional study. A predictive model of 2yDFS was developed taking into account both clinical and radiomics variables. Gross tumour volume (GTV) was delineated on the magnetic resonance (MR) images acquired during MRgRT, and 1,067 radiomic features (RF) were extracted using the MODDICOM platform. The performance of RF in predicting 2yDFS was investigated in terms of the Wilcoxon–Mann–Whitney test and area under receiver operating characteristic (ROC) curve (AUC).

Results

48 patients have been retrospectively enrolled, with 8 patients (16.7%) developing distant metastases at the 2-year follow-up. A total of 1,099 variables (1,067 RF and 32 clinical variables) were evaluated in two different models: radiomics and radiomics/clinical. The best-performing 2yDFS predictive model was a delta radiomics one, based on the variation in terms of area/surface ratio between biologically effective doses (BED) at 54 Gy and simulation (AUC of 0.92).

Conclusions

The results of this study suggest a promising role of delta radiomics analysis on 0.35-T MR images in predicting 2yDFS for LARC patients. Further analyses including larger cohorts of patients and an external validation are needed to confirm these preliminary results.
Linear Skeletal Muscle Index and Muscle Attenuation May Be New Prognostic Factors in Colorectal Carcinoma Treated by Radical Resection
Authors: Wang Yang , Wang Yuliuming , Ai Lianjie , Zhang Hao , Li Guodong , Wang Zitong , Jiang Xia , Yan Guoqing , Liu Yunxiao , Wang Chunlin , Xiong Huan , Wang Guiyu , Liu Ming
Published: February 2022

Objective

This study evaluated the association between body composition and clinical parameters and prognosis in patients with colorectal cancer (CRC) treated by radical resection.

Methods

Baseline data on patient age, body mass index (BMI), bowel obstruction and tumor-related factors were collected retrospectively. Body composition parameters such as visceral fat area (VFA), total abdominal muscle area (TAMA), muscle attenuation (MA), posterior renal fat thickness (PPNF) and intermuscular fat area (IMF) are measured using Computed tomography (CT) scans. We also propose a new predictor of linear skeletal muscle index (LSMI) that can be easily measured clinically at CT. Follow-up endpoints were disease-free survival and all-cause death. We follow up with patients in hospital or by telephone. Univariate and multifactorial Cox proportional hazards analyses were performed to identify risk factors associated with prognosis. Survival analysis was performed using the Kaplan-Meier method and a nomogram was established to predict survival.

Results

A total of 1761 patients (median age 62 years) with CRC were enrolled in our study, of whom 201 had intestinal obstruction and 673 had a BMI > 24.0. Among all patients, the 3- and 5-year disease-free survival rates were 84.55% and 68.60% respectively, and the overall survival rates were 88.87% and 76.38%. Overall survival was significantly correlated with MA, LSMI, SMI, Tumor size, N stage, metastasis and adjuvant therapy by Cox regression analysis (p < 0.05). The risk of tumor progression was significantly associated with MA, VFA, LSMI, SMI, Male, N stage, metastasis and adjuvant therapy (p < 0.05). In addition, based on the Chinese population, we found that female patients with MA < 30.0 HU, LSMI < 18.2, and SMI < 38.0 had a worse prognosis, male patients with MA < 37.6 HU, LSMI < 21.9, and SMI < 40.3 had a poorer prognosis.

Conclusion

Our findings suggest that linear skeletal muscle index and MA can be used as new independent predictors for colorectal cancer patients treated with radical surgery, and that baseline data such as body composition parameters, LSMI and tumor-related factors can collectively predict patient prognosis. These results could help us to optimize the management and treatment of patients after surgery.
Flap Reconstruction of the Oropharyngeal Defect After Tumor Resection via Combined Transcervical and Transoral Approach in Patients With HPV-Positive and -Negative Oropharyngeal Squamous Cell Carcinoma
Authors: Chen Jiaming , Fang Jugao , Zhong Qi , Feng Ling , He Shizhi , Ma Hongzhi , Hou Lizhen , Lian Meng , Wang Ru , Shen Xixi , Yang Yifan
Published: February 2022

Objective

To investigate a novel surgical approach of combined transcervical parapharyngeal space (PPS) with the transoral approach to dissect oropharyngeal cancer.

Methods

31 patients who were pathologically diagnosed with oropharyngeal cancer and had undergone surgical treatment in Beijing Tongren Hospital during June 2018 and December 2020 were enrolled. All patients were squamous cell carcinoma patients. There were 25 males and 6 females, and the age ranged between 44 and 70 years old. The number of patients with T1, T2, T3, and T4 stage disease was 8, 15, 8, and 0, respectively, according to the American Joint Committee on Cancer staging method, 8th edition. After the dissection of the submandibular and cervical lymph nodes, the parapharyngeal space was exposed, and the parapharyngeal space lymph node and the outer borderline of the tumor were dissected, and then the inner borderline of the tumor was dissected via a transoral approach; the tumor was dissected en bloc, and the defects were reconstructed with the flap from the neck through the parapharyngeal space.

Results

Among the patients enrolled, 21 were HPV positive and 10 were HPV negative. 8 patients were free of lymph node metastasis. The tumor resection margins were negative in all 31 patients. Safe and sufficient excision of tumors was feasible by this new surgical approach, avoiding complications associated with mandibulotomy or lip-splitting. All patients had no obvious dysfunctions of swallowing and voice. By the time of this follow-up, none died caused by OPSCC, and only two patients suffered from local recurrence. The 3-year survival rate is 100%, and the 3-year recurrence-free survival rate is 84.58%.

Conclusion

The surgical approach of combined transcervical parapharyngeal space with the transoral approach was effective and safe. On this basis, this approach has the advantage of fewer postoperative complications and better functional results.
Case Report: DRESS Syndrome Induced by Two Antituberculosis Drugs in an 8-Year-Old Girl
Authors: Urbonas Vaidotas , Varnas Dominykas , Mociskiene Kristina , Kvedariene Violeta , Rudzeviciene Odilija
Published: February 2022

DRESS syndrome is defined as drug-induced hypersensitivity syndrome with rash, eosinophilia, and systemic symptoms. This syndrome is mostly associated with anticonvulsants, antibacterial and anti-inflammatory drugs. DRESS syndrome is a rare disease and is more frequently seen in adults. We present the first case report of DRESS syndrome in an 8-year-old girl, after 3 months of treatment with isoniazid and rifampicin. After discontinuation of drugs and a short course of prednisolone the girl recovered. After 5 years of follow-up, she is healthy and has no complaints but patch tests with isoniazid and rifampicin remain positive. The reported case emphasizes the importance of thorough medical history and including drug reactions in differential diagnosis.