bluuebunny/crossref_metadata_2025 huggingface dataset:
Mle046 Is a Marine Mesophilic MHETase-Like Enzyme
Authors: Meyer-Cifuentes Ingrid E. , Öztürk Başak
Published: July 2021

Accumulation of plastics in the oceans presents a major threat to diverse ecosystems. The introduction of biodegradable plastics into the market aims to alleviate the ecological burden caused by recalcitrant plastics. Poly (butylene adipate-co-terephthalate) (PBAT) is a biodegradable commercial plastic that can be biodegraded similarly to polyethylene terephthalate (PET) by PETase-like enzymes and MHETases. The role of MHETases is to hydrolyze the intermediate degradation product of PET, mono-2-hydroxyethyl terephthalate (MHET) to its monomers. We recently identified a homolog of the MHETase of the PET-degrading bacterium Ideonella sakaiensis, Mle046, from a marine microbial consortium. In this consortium, Mle046 was highly expressed when a PBAT-based blend film (PF) was supplied as the sole carbon source. In this study, we recombinantly expressed and biochemically characterized Mle046 under different conditions. Mle046 degrades MHET but also 4-(4-hydroxybutoxycarbonyl) benzoic acid (Bte), the intermediate of PF degradation. Mle046 is a mesophilic enzyme adapted to marine conditions, which rapidly degrades MHET to terephthalate and ethylene glycol at temperatures between 20 and 40°C. Mle046 degradation rates were similar for Bte and MHET. Despite its mesophilic tendency, Mle046 retains a considerable amount of activity at temperatures ranging from 10 to 60°C. In addition, Mle046 is active at a range of pH values from 6.5 to 9. These characteristics make Mle046 a promising candidate for biotechnological applications related to plastic recycling.
The Mechanism Underlying of Long-Term Stable Indigo Reduction State in Indigo Fermentation Using Sukumo (Composted Polygonum tinctorium Leaves)
Authors: Tu Zhihao , Lopes Helena de Fátima Silva , Narihiro Takashi , Yumoto Isao
Published: July 2021

Indigo fermentation fluid maintains its indigo-reducing state for more than 6 months under open-air. To elucidate the mechanism underlying the sustainability of this indigo reduction state, three indigo fermentation batches with different durations for the indigo reduction state were compared. The three examined batches exhibited different microbiota and consisted of two phases. In the initial phase, oxygen-metabolizing-bacteria derived from sukumo established an initial network. With decreasing redox potential (ORP), the initial bacterial community was replaced by obligate anaerobes (mainly Proteinivoraceae; phase 1). Approximately 1 month after the beginning of fermentation, the predominating obligate anaerobes were decreased, and Amphibacillus and Polygonibacillus, which can decompose macromolecules derived from wheat bran, were predominantly observed, and the transition of microbiota became slow (phase 2). Considering the substrate utilization ability of the dominated bacterial taxa, the transitional change from phase 1 to phase 2 suggests that this changed from the bacterial flora that utilizes substrates derived from sukumo, including intrinsic substrates in sukumo and weakened or dead bacterial cells derived from early events (heat and alkaline treatment and reduction of ORP) to that of wheat bran-utilizers. This succession was directly related to the change in the major substrate sustaining the corresponding community and the turning point was approximately 1 month after the start of fermentation. As a result, we understand that the role of sukumo includes changes in the microbial flora immediately after the start of fermentation, which has an important function in the start-up phase of fermentation, whereas the ecosystem comprised of the microbiota utilizing wheat bran underpins the subsequent long-term indigo reduction.
Ferrimicrobium acidiphilum Exchanges Electrons With a Platinum Electrode via a Cytochrome With Reduced Absorbance Maxima at 448 and 605 nm
Authors: Blake Robert C. , Nautiyal Amit , Smith Kayla A. , Walton Noelle N. , Pendleton Brealand , Wang Zhe
Published: July 2021

Ferrimicrobium acidiphilum is a Gram-positive member of the Actinobacteria phylum that can respire aerobically or anaerobically with soluble Fe(II) or Fe(III), respectively, in sulfuric acid at pH 1.5. Cyclic voltammetry measurements using intact F. acidiphilum at pH 1.5 produced fully reversible voltammograms that were highly reproducible. The maximum current observed with the anodic peak was considerably less than was the maximum current observed with the cathodic peak. This difference was attributed to the competition between the platinum electrode and the soluble oxygen for the available electrons that were introduced by the cathodic wave into this facultative aerobic organism. The standard reduction potential of the intact organism was determined to be 786 mV vs. the standard hydrogen electrode, slightly more positive than that of 735 mV that was determined for soluble iron at pH 1.5 using the same apparatus. Chronocoulometry measurements conducted at different cell densities revealed that the intact organism remained in close proximity to the working electrode during the measurement, whereas soluble ionic iron did not. When the cyclic voltammetry of intact F. acidiphilum was monitored using an integrating cavity absorption meter, the only small changes in absorbance that were detected were consistent with the participation of a cellular cytochrome with reduced absorbance peaks at 448 and 605 nm. The cytochrome that participated in the exchange of electrons between the intact organism and extracellular solid electrodes like platinum was the same cytochrome whose oxidation was previously shown to be rate-limiting when the organism respired aerobically on extracellular soluble iron.
Novel Cyclic Lipopeptides Fusaricidin Analogs for Treating Wound Infections
Authors: Gil Joel , Pastar Irena , Houghten Richard A. , Padhee Shruti , Higa Alexander , Solis Michael , Valdez Jose , Head Cheyanne R. , Michaels Heather , Lenhart Brian , Simms Colin , Williams Brandon , Cudic Predrag , Davis Stephen C.
Published: July 2021

Both acute and chronic cutaneous wounds are often difficult to treat due to the high-risk for bacterial contamination. Once hospitalized, open wounds are at a high-risk for developing hospital-associated infections caused by multi drug-resistant bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. Treating these infections is challenging, not only because of antibiotic resistance, but also due to the production of biofilms. New treatment strategies are needed that will help in both stimulating the wound healing process, as well as preventing and eliminating bacterial wound infections. Fusaricidins are naturally occurring cyclic lipopeptides with antimicrobial properties that have shown to be effective against a variety of fungi and Gram-positive bacteria, with low toxicity. Continuing with our efforts toward the identification of novel cyclic lipopeptides Fusaricidin analogs, herein we report the synthesis and evaluation of the antimicrobial activity for two novel cyclic lipopeptides (CLP), CLP 2605-4 and CLP 2612-8.1 against methicillin resistant S. aureus and P. aeruginosa, respectively, in in vivo porcine full thickness wound model. Both CLPs were able to reduce bacterial counts by approximately 3 log CFU/g by the last assessment day. Peptide 2612-8.1 slightly enhanced the wound healing, however, wounds treated with peptide 2605-4, have shown higher levels of inflammation and impaired wound healing process. This study highlights the importance of identifying new antimicrobials that can combat bacterial infection while not impeding tissue repair.
A High Epigenetic Risk Score Shapes the Non-Inflamed Tumor Microenvironment in Breast Cancer
Authors: Zhang Dong , Wang Yingnan , Yang Qifeng
Published: July 2021

Background: Epigenetic dysregulation via aberrant DNA methylation has gradually become recognized as an efficacious signature for predicting tumor prognosis and response to therapeutic targets. However, reliable DNA methylation biomarkers describing tumorigenesis remain to be comprehensively explored regarding their prognostic and therapeutic potential in breast cancer (BC).

Methods: Whole-genome methylation datasets integrated from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were profiled (n = 1,268). A three-stage selection procedure (discovery, training, and external validation) was utilized to screen out the prominent biomarkers and establish a robust risk score from more than 300,000 CpG sites after quality control, rigorous filtering, and reducing dimension. Moreover, gene set enrichment analyses guided us to systematically correlate this epigenetic risk score with immunological characteristics, including immunomodulators, anti-cancer immunity cycle, immune checkpoints, tumor-infiltrating immune cells and a series of signatures upon modulating components within BC tumor microenvironment (TME). Multi-omics data analyses were performed to decipher specific genomic alterations in low- and high-risk patients. Additionally, we also analyzed the role of risk score in predicting response to several treatment options.

Results: A 10-CpG-based prognostic signature which could significantly and independently categorize BC patients into distinct prognoses was established and sufficiently validated. And we hypothesize that this signature designs a non-inflamed TME in BC based on the evidence that the derived risk score is negatively correlated with tumor-associated infiltrating immune cells, anti-cancer immunity cycle, immune checkpoints, immune cytolytic activity, T cell inflamed score, immunophenoscore, and the vast majority of immunomodulators. The identified high-risk patients were characterized by upregulation of immune inhibited oncogenic pathways, higher TP53 mutation and copy number burden, but lower response to cancer immunotherapy and chemotherapy.

Conclusion: Our work highlights the complementary roles of 10-CpG-based signature in estimating overall survival in BC patients, shedding new light on investigating failed events concerning immunotherapy at present.
Evaluation and Comparison of Serological Methods for COVID-19 Diagnosis
Authors: Gong Fanwu , Wei Hua-xing , Li Qiangsheng , Liu Liu , Li Bofeng
Published: July 2021

The worldwide pandemic of COVID-19 has become a global public health crisis. Various clinical diagnosis methods have been developed to distinguish COVID-19–infected patients from healthy people. The nucleic acid test is the golden standard for virus detection as it is suitable for early diagnosis. However, due to the low amount of viral nucleic acid in the respiratory tract, the sensitivity of nucleic acid detection is unsatisfactory. As a result, serological screening began to be widely used with the merits of simple procedures, lower cost, and shorter detection time. Serological tests currently include the enzyme-linked immunosorbent assay (ELISA), lateral flow immunoassay (LFIA), and chemiluminescence immunoassay (CLIA). This review describes various serological methods, discusses the performance and diagnostic effects of different methods, and points out the problems and the direction of optimization, to improve the efficiency of clinical diagnosis. These increasingly sophisticated and diverse serological diagnostic technologies will help human beings to control the spread of COVID-19.
Solution Structure of the dATP-Inactivated Class I Ribonucleotide Reductase From Leeuwenhoekiella blandensis by SAXS and Cryo-Electron Microscopy
Authors: Hasan Mahmudul , Banerjee Ipsita , Rozman Grinberg Inna , Sjöberg Britt-Marie , Logan Derek T.
Published: July 2021

The essential enzyme ribonucleotide reductase (RNR) is highly regulated both at the level of overall activity and substrate specificity. Studies of class I, aerobic RNRs have shown that overall activity is downregulated by the binding of dATP to a small domain known as the ATP-cone often found at the N-terminus of RNR subunits, causing oligomerization that prevents formation of a necessary α2β2 complex between the catalytic (α2) and radical generating (β2) subunits. In some relatively rare organisms with RNRs of the subclass NrdAi, the ATP-cone is found at the N-terminus of the β subunit rather than more commonly the α subunit. Binding of dATP to the ATP-cone in β results in formation of an unusual β4 tetramer. However, the structural basis for how the formation of the active complex is hindered by such oligomerization has not been studied. Here we analyse the low-resolution three-dimensional structures of the separate subunits of an RNR from subclass NrdAi, as well as the α4β4 octamer that forms in the presence of dATP. The results reveal a type of oligomer not previously seen for any class of RNR and suggest a mechanism for how binding of dATP to the ATP-cone switches off catalysis by sterically preventing formation of the asymmetrical α2β2 complex.
Current Perspective on the Membrane-Damaging Action of Thermostable Direct Hemolysin, an Atypical Bacterial Pore-forming Toxin
Authors: Verma Pratima , Chattopadhyay Kausik
Published: July 2021

Thermostable direct hemolysin (TDH) is the major virulence determinant of the gastroenteric bacterial pathogen Vibrio parahaemolyticus. TDH is a membrane-damaging pore-forming toxin (PFT). TDH shares remarkable structural similarity with the actinoporin family of eukaryotic PFTs produced by the sea anemones. Unlike most of the PFTs, it exists as tetramer in solution, and such assembly state is crucial for its functionality. Although the structure of the tetrameric assembly of TDH in solution is known, membrane pore structure is not available yet. Also, the specific membrane-interaction mechanisms of TDH, and the exact role of any receptor(s) in such process, still remain unclear. In this mini review, we discuss some of the unique structural and physicochemical properties of TDH, and their implications for the membrane-damaging action of the toxin. We also present our current understanding regarding the membrane pore-formation mechanism of this atypical bacterial PFT.
Serum miR-96-5P and miR-339-5P Are Potential Biomarkers for Multiple System Atrophy and Parkinson's Disease
Authors: Vallelunga Annamaria , Iannitti Tommaso , Capece Sabrina , Somma Gerardina , Russillo Maria Claudia , Foubert-Samier Alexandra , Laurens Brice , Sibon Igor , Meissner Wassilios G. , Barone Paolo , Pellecchia Maria Teresa
Published: July 2021

Parkinson's disease (PD) and Multiple System Atrophy (MSA) are progressive neurodegenerative diseases with overlap of symptoms in early stages of disease. No reliable biomarker exists and the diagnosis is mainly based on clinical features. Several studies suggest that miRNAs are involved in PD and MSA pathogenesis. Our goal was to study two serum circulating microRNAs (miR-96-5p and miR-339-5p) as novel biomarkers for the differential diagnosis between PD and MSA. Serum samples were obtained from 51 PD patients, 52 MSA patients and 56 healthy controls (HC). We measured levels of miRNAs using quantitative PCR and compared the levels of miR-96-5p and miR-339-5p among PD, MSA and HC groups using a one-way analysis of variance. Correlations between miRNA expression and clinical data were calculated using Pearson's rho test. We used the miRTarBase to detect miRNA targets and STRING to evaluate co-expression relationship among target genes. MiR-96-5p was significantly increased in MSA patients compared with HC (Fold change (fc): 3.6; p = 0.0001) while it was decreased in PD patients compared with HC (Fold change: 4; p = 0.0002). Higher miR-96-5P levels were directly related to longer disease duration in MSA patients. We observed a significant increase of miR-339-5p in MSA patients compared with PD patients (fc: 2.5; p = 0.00013). miR-339-5p was increased in MSA patients compared with HC (fc: 2.4; p = 0.002). We identified 32 target genes of miR-96-5p and miR-339-5p, some of which are involved in neurodegenerative diseases. The study of those miRNAs could be useful to identify non-invasive biomarkers for early differential diagnosis between PD and MSA.
Computational and Molecular Properties of Starburst Amacrine Cell Synapses Differ With Postsynaptic Cell Type
Authors: Pottackal Joseph , Singer Joshua H. , Demb Jonathan B.
Published: July 2021

A presynaptic neuron can increase its computational capacity by transmitting functionally distinct signals to each of its postsynaptic cell types. To determine whether such computational specialization occurs over fine spatial scales within a neurite arbor, we investigated computation at output synapses of the starburst amacrine cell (SAC), a critical component of the classical direction-selective (DS) circuit in the retina. The SAC is a non-spiking interneuron that co-releases GABA and acetylcholine and forms closely spaced (<5 μm) inhibitory synapses onto two postsynaptic cell types: DS ganglion cells (DSGCs) and neighboring SACs. During dynamic optogenetic stimulation of SACs in mouse retina, whole-cell recordings of inhibitory postsynaptic currents revealed that GABAergic synapses onto DSGCs exhibit stronger low-pass filtering than those onto neighboring SACs. Computational analyses suggest that this filtering difference can be explained primarily by presynaptic properties, rather than those of the postsynaptic cells per se. Consistent with functionally diverse SAC presynapses, blockade of N-type voltage-gated calcium channels abolished GABAergic currents in SACs but only moderately reduced GABAergic and cholinergic currents in DSGCs. These results jointly demonstrate how specialization of synaptic outputs could enhance parallel processing in a compact interneuron over fine spatial scales. Moreover, the distinct transmission kinetics of GABAergic SAC synapses are poised to support the functional diversity of inhibition within DS circuitry.
Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit
Authors: Bayasgalan T. , Stupniki S. , Kovács A. , Csemer A. , Szentesi P. , Pocsai K. , Dionisio L. , Spitzmaul G. , Pál B.
Published: July 2021

The pedunculopontine nucleus (PPN), a structure known as a cholinergic member of the reticular activating system (RAS), is source and target of cholinergic neuromodulation and contributes to the regulation of the sleep–wakefulness cycle. The M-current is a voltage-gated potassium current modulated mainly by cholinergic signaling. KCNQ subunits ensemble into ion channels responsible for the M-current. In the central nervous system, KCNQ4 expression is restricted to certain brainstem structures such as the RAS nuclei. Here, we investigated the presence and functional significance of KCNQ4 in the PPN by behavioral studies and the gene and protein expressions and slice electrophysiology using a mouse model lacking KCNQ4 expression. We found that this mouse has alterations in the adaptation to changes in light–darkness cycles, representing the potential role of KCNQ4 in the regulation of the sleep–wakefulness cycle. As cholinergic neurons from the PPN participate in the regulation of this cycle, we investigated whether the cholinergic PPN might also possess functional KCNQ4 subunits. Although the M-current is an electrophysiological hallmark of cholinergic neurons, only a subpopulation of them had KCNQ4-dependent M-current. Interestingly, the absence of the KCNQ4 subunit altered the expression patterns of the other KCNQ subunits in the PPN. We also determined that, in wild-type animals, the cholinergic inputs of the PPN modulated the M-current, and these in turn can modulate the level of synchronization between neighboring PPN neurons. Taken together, the KCNQ4 subunit is present in a subpopulation of PPN cholinergic neurons, and it may contribute to the regulation of the sleep–wakefulness cycle.
HIV Associated Neurocognitive Disorders Subsidence Through Citalopram Addition in Anti-retroviral Therapy (HANDS-CARE): A Concept Note
Authors: Ojagbemi Akin
Published: July 2021

There is a pressing need to effectively manage HIV Associated Neurocognitive Disorders (HAND) in sub-Saharan Africa (SSA) where the burden is among the highest in the world. Contemporary approaches based on the use of Highly Active Antiretroviral Therapy (HAART) alone are inadequate interventions for HAND, especially in SSA where there is limited availability of the required combinations of HAART for effective central nervous system penetration and where many currently prescribed agents, including efavirenz, have neurotoxicity as a major drawback. This article reviews data supporting the rationale for additive citalopram in antiretroviral therapy as a latent approach to abate HAND. It proposes the conduct of a HIV Associated Neurocognitive Disorders Subsidence through Citalopram addition in Anti-Retroviral therapy (HANDS-CARE) pilot feasibility trial (RCT) to assess whether the adjunctive use of citalopram, a widely prescribed serotonergic antidepressant, will lead to a meaningful improvement in neurocognitive functioning and quality of life in patients with HAND who are receiving HAART. A preliminarily feasible and efficacy-suggesting HANDS-CARE trial could generate statistical, clinical and operational data necessary to design and conduct a future definitive RCT. If successful, this intervention will be applicable to resource-limited settings as well as developed countries. Effective management of HAND will improve the quality of life of HIV patients, and reduce the cost of managing the disease.
From Three-Months to Five-Years: Sustaining Long-Term Benefits of Endovascular Therapy for Ischemic Stroke
Authors: Ganesh Aravind , Ospel Johanna Maria , Marko Martha , van Zwam Wim H. , Roos Yvo B. W. E. M. , Majoie Charles B. L. M. , Goyal Mayank
Published: July 2021

Background and Purpose: During the months and years post-stroke, treatment benefits from endovascular therapy (EVT) may be magnified by disability-related differences in morbidity/mortality or may be eroded by recurrent strokes and non-stroke-related disability/mortality. Understanding the extent to which EVT benefits may be sustained at 5 years, and the factors influencing this outcome, may help us better promote the sustenance of EVT benefits until 5 years post-stroke and beyond.

Methods: In this review, undertaken 5 years after EVT became the standard of care, we searched PubMed and EMBASE to examine the current state of the literature on 5-year post-stroke outcomes, with particular attention to modifiable factors that influence outcomes between 3 months and 5 years post-EVT.

Results: Prospective cohorts and follow-up data from EVT trials indicate that 3-month EVT benefits will likely translate into lower 5-year disability, mortality, institutionalization, and care costs and higher quality of life. However, these group-level data by no means guarantee maintenance of 3-month benefits for individual patients. We identify factors and associated “action items” for stroke teams/systems at three specific levels (medical care, individual psychosocioeconomic, and larger societal/environmental levels) that influence the long-term EVT outcome of a patient. Medical action items include optimizing stroke rehabilitation, clinical follow-up, secondary stroke prevention, infection prevention/control, and post-stroke depression care. Psychosocioeconomic aspects include addressing access to primary care, specialist clinics, and rehabilitation; affordability of healthy lifestyle choices and preventative therapies; and optimization of family/social support and return-to-work options. High-level societal efforts include improving accessibility of public/private spaces and transportation, empowering/engaging persons with disability in society, and investing in treatments/technologies to mitigate consequences of post-stroke disability.

Conclusions: In the longtime horizon from 3 months to 5 years, several factors in the medical and societal spheres could negate EVT benefits. However, many factors can be leveraged to preserve or magnify treatment benefits, with opportunities to share responsibility with widening circles of care around the patient.
Low-Frequency TMS Results in Condition-Related Dynamic Activation Changes of Stimulated and Contralateral Inferior Parietal Lobule
Authors: Jargow Janine , Zwosta Katharina , Korb Franziska M. , Ruge Hannes , Wolfensteller Uta
Published: July 2021

Non-invasive brain stimulation is a promising approach to study the causal relationship between brain function and behavior. However, it is difficult to interpret behavioral null results as dynamic brain network changes have the potential to prevent stimulation from affecting behavior, ultimately compensating for the stimulation. The present study investigated local and remote changes in brain activity via functional magnetic resonance imaging (fMRI) after offline disruption of the inferior parietal lobule (IPL) or the vertex in human participants via 1 Hz repetitive transcranial magnetic stimulation (rTMS). Since the IPL acts as a multimodal hub of several networks, we implemented two experimental conditions in order to robustly engage task-positive networks, such as the fronto-parietal control network (on-task condition) and the default mode network (off-task condition). The condition-dependent neural after-effects following rTMS applied to the IPL were dynamic in affecting post-rTMS BOLD activity depending on the exact time-window. More specifically, we found that 1 Hz rTMS applied to the right IPL led to a delayed activity increase in both, the stimulated and the contralateral IPL, as well as in other brain regions of a task-positive network. This was markedly more pronounced in the on-task condition suggesting a condition-related delayed upregulation. Thus together, our results revealed a dynamic compensatory reorganization including upregulation and intra-network compensation which may explain mixed findings after low-frequency offline TMS.
The Effects of Group Therapeutic Singing on Cortisol and Motor Symptoms in Persons With Parkinson's Disease
Authors: Stegemöller Elizabeth L. , Zaman Andrew , Shelley Mack , Patel Bhavana , Kouzi Ahmad El , Shirtcliff Elizabeth A.
Published: July 2021

The inclusion of music into the treatment plan for persons with Parkinson's disease (PD) may be a viable strategy to target multiple motor symptoms. However, potential mechanisms to explain why music has an impact on multiple motor symptoms in persons with PD remain understudied. The purpose of this study was to examine the acute effects of 1 h of group therapeutic singing (GTS) on physiological measures of stress and clinical motor symptoms in persons with PD. We posit that improvement in motor symptoms after GTS may be related to stress reduction. Seventeen participants with PD completed 1 h of GTS and eight participants completed 1 h of a quiet reading (control session). Cortisol was collected via passive drool immediately before and after the singing and control session. The Unified Parkinson's Disease Rating Scale (UPDRS) Part-III (motor examination) was also video-recorded immediately before and after the singing and control session and scored by two raters masked to time and condition. Secondary outcome measures for quality of life, depression, and mood were collected. Results revealed no significant change in cortisol or motor UPDRS scores, as well as no significant relationship between cortisol and motor UPDRS scores. There was a trend for the singing group to report feeling less sad compared to the control group after the 1-h session (effect size = 0.86), and heart rate increased in the singing group while heart rate decreased in the control group after the 1-h session. These results suggest that an acute session of GTS is not unduly stressful and promotes the use of GTS for persons with PD. Multiple mechanisms may underlie the benefits of GTS for persons with PD. Further exploring potential mechanisms by which singing improves motor symptoms in persons with PD will provide greater insight on the therapeutic use of music for persons with PD.
Analysis and Synthesis of Natural Texture Perception From Visual Evoked Potentials
Authors: Orima Taiki , Motoyoshi Isamu
Published: July 2021

The primate visual system analyzes statistical information in natural images and uses it for the immediate perception of scenes, objects, and surface materials. To investigate the dynamical encoding of image statistics in the human brain, we measured visual evoked potentials (VEPs) for 166 natural textures and their synthetic versions, and performed a reverse-correlation analysis of the VEPs and representative texture statistics of the image. The analysis revealed occipital VEP components strongly correlated with particular texture statistics. VEPs correlated with low-level statistics, such as subband SDs, emerged rapidly from 100 to 250 ms in a spatial frequency dependent manner. VEPs correlated with higher-order statistics, such as subband kurtosis and cross-band correlations, were observed at slightly later times. Moreover, these robust correlations enabled us to inversely estimate texture statistics from VEP signals via linear regression and to reconstruct texture images that appear similar to those synthesized with the original statistics. Additionally, we found significant differences in VEPs at 200–300 ms between some natural textures and their Portilla–Simoncelli (PS) synthesized versions, even though they shared almost identical texture statistics. This differential VEP was related to the perceptual “unnaturalness” of PS-synthesized textures. These results suggest that the visual cortex rapidly encodes image statistics hidden in natural textures specifically enough to predict the visual appearance of a texture, while it also represents high-level information beyond image statistics, and that electroencephalography can be used to decode these cortical signals.
Effects of Selenomethionine on Cell Viability, Selenoprotein Expression and Antioxidant Function in Porcine Mammary Epithelial Cells
Authors: Chen Jun , Zhang Yinzhi , Lv Yantao , Tian Min , You Jinming , Chen Fang , Zhang Shihai , Guan Wutai
Published: July 2021

This study investigated the effects of selenomethionine (Se-Met) on the cell viability, selenoprotein expression, and antioxidant function of porcine mammary epithelial cells (pMECs) to reveal the underlying molecular mechanism of Se-Met on the lactation performance and antioxidant capacity of sowsin vitro. The pMECs were used as anin vitromodel and were treated with various concentrations of Se-Met (0, 0.5, 1, 2, and 4 μM). Cells were analyzed for cell viability, selenoprotein transcriptome, selenoprotein expression, and antioxidant enzyme activities. The results showed that, with increasing Se-Met concentrations, cell viability first increased and then decreased at 24, 48, or 72 h posttreatment with maximum values at 0.5-μM Se-Met. As the Se-Met concentrations increased, the mRNA expression of 17 selenoproteins first upregulated and then downregulated, with maximum values at 0.5-μM Se-Met. The 17 selenoproteins includedSEPHS2, SELENOP, GPX1, GPX2, GPX3, GPX6, TXNRD1, SELENOK, SELENOW, DIO1, DIO2, DIO3, SELENOF, SELENOS, SELENOH, SELENOI, andSELENOT. Additionally, the protein expression levels of SEPHS2, SELENOP, GPX1, and TXNRD1 and the activities of glutathione peroxidase and thioredoxin were highest at 0.5-μM Se-Met. In conclusion, 0.5-μM Se-Met promotes cell viability partially by improving selenoprotein expression and antioxidant function in pMECs, which provides evidence for the potential ability of Se-Met to improve mammary gland health in sows.
Quarantine During COVID-19 Outbreak: Eating Behavior, Perceived Stress, and Their Independently Associated Factors in a Brazilian Sample
Authors: Liboredo Juliana Costa , Anastácio Lucilene Rezende , Ferreira Lívia Garcia , Oliveira Lívya Alves , Della Lucia Ceres Mattos
Published: July 2021

The study aimed to assess the eating behavior [uncontrolled eating (UE), emotional eating (EE), and cognitive restraint (CR)], the perceived stress, and independently associated factors among Brazilians during the COVID-19 pandemic. An online survey was conducted and data about 1,368 participants were evaluated. Multivariate logistic regression models were performed to identify factors independently associated (socioeconomic, lifestyle, and eating habits data) with eating behaviors and perceived stress. Working in the COVID-19 frontline (OR = 2.19), increased food delivery (OR = 1.49), increased food intake (OR = 1.48), increased number of meals (OR = 1.13), and EE (OR = 1.05) were factors independently associated with UE. Variables that were independently associated with EE were: increased food intake (OR = 2.57), graduation in a non-health-related course (OR = 1.78), perceived stress (OR = 1.08), UE (OR = 1.07), and CR (OR = 1.02). Reduced snacking (OR = 2.08), female gender (OR = 1.47), having a higher degree (OR = 1.44), increased homemade meals (OR = 1.31), the higher difference in the frequency of instant meals and snacks intake (OR = 0.91), EE (OR = 1.01), not increased alcohol dose intake (OR = 0.57), and increased physical activity (OR = 0.54) were independently associated with CR. Perceived stress was independently associated with changes in the way of working or studying (OR = 2.48), worse sleep quality (OR = 2.22), younger age (OR = 1.06), and EE (OR = 1.02). This study indicates that socioeconomic variables, lifestyle, and eating habits were independently associated with the eating behaviors of Brazilians and perceived stress during the quarantine.
Bioaccessibility and Gut Metabolism of Free and Melanoidin-Bound Phenolic Compounds From Coffee and Bread
Authors: Alves Genilton , Lobo Leandro Araújo , Domingues Regina Maria Cavalcanti Pilotto , Monteiro Mariana , Perrone Daniel
Published: July 2021

The aim of this study is to investigate the bioaccessibility and gut metabolism of free and melanoidin-bound phenolic compounds from coffee and bread. Phenolics from coffee were predominantly found in free forms (68%, mainly chlorogenic acids), whereas those from bread were mostly bound to melanoidins (61%, mainly ferulic acid). Bioacessibility of coffee total free phenolics slightly decreased during simulated digestion (87, 86, and 82% after the oral, gastric, and intestinal steps, respectively), with caffeoylquinic acids being isomerized and chlorogenic acids being partially hydrolyzed to the corresponding hydroxycinnamic acids. Bioacessibility of bread total free phenolics decreased during simulated digestion (91, 85, and 67% after the oral, gastric, and intestinal steps, respectively), probably related to complexation with the proteins in simulated gastric and intestinal fluids. Upon gut fermentation, the bioaccessibility of total free phenolics from both coffee and bread decreased, mainly after the first 4 h (56 and 50%, respectively). Caffeic and ferulic acids were the predominant metabolites found during coffee and bread gut fermentation, respectively. Melanoidin-bound phenolics from coffee and bread were progressively released after the gastric and intestinal steps, probably due to hydrolysis caused by the acidic conditions of the stomach and the action of pancreatin from the intestinal fluid. The bioaccessibilities of all phenolics from coffee and bread melanoidins after the gastric and intestinal steps were, on average, 11 and 26%, respectively. During gut fermentation, phenolics bound to both coffee and bread melanoidins were further released by the gut microbiota, whereas those from coffee were also metabolized. This difference could be related to the action of proteases on melanoproteins during gastrointestinal digestion, probably anticipating phenolics release. Nevertheless, bioaccessibilities of melanoidin-bound phenolics reached maximum values after gut fermentation for 24 h (50% for coffee and 51% for bread). In conclusion, the bioaccessibilities of coffee and bread free phenolics during simulated digestion and gut fermentation were remarkably similar, and so were the bioaccessibilities of coffee and bread melanoidin-bound phenolics.
Predictors for Fear of Cancer Recurrence in Breast Cancer Patients Referred to Radiation Therapy During the COVID-19 Pandemic: A Multi-Center Cross-Section Survey
Authors: Xie Jinrong , Qi Weixiang , Cao Lu , Tan Yuting , Huang Jin , Gu Xiaodong , Chen Bingguang , Shen Peipei , Zhao Yutian , Zhang Ying , Zhao Qingwen , Huang Hecheng , Wang Yubin , Fang Haicheng , Jin Zhenjun , Li Hui , Zhao Xuehong , Qian Xiaofang , Xu Feifei , Ou Dan , Wang Shubei , Xu Cheng , Li Min , Jiang Zefei , Wang Yu , Huang Xiaobo , Chen Jiayi
Published: July 2021

Objective

The outbreak of COVID-19 pandemic has greatly impacted on radiotherapy (RT) strategy for breast cancer patients, which might lead to increased distressing psychological symptoms. We performed a multi-center cross-section survey to investigate prevalence of fear of cancer recurrence (FCR) and predictors for FCR in patients referred to RT during pandemic.

Methods

542 patients were consecutively enrolled from three regions in China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients’ characteristics were collected using an information sheet, Fear of progression questionnaire-short form, Hospital Anxiety/Depression Scale and EORTC QLQ-C30. The hierarchical multiple regression models were performed.

Results

488 patients with complete data were eligible. The RT strategy was affected in 265 (54.3%) patients, including 143 with delayed RT initiation, 66 believing to have delayed RT initiation but actually not, 24 with RT interruptions, 19 shifting to local hospitals for RT and the remaining 13 influenced on both RT schedule and hospital level. The model explained 59.7% of observed variances in FCR (p<0.001) and showed that influence of RT strategy had significantly impacted on FCR (△R2 = 0.01, △F=2.966, p=0.019). Hospitals in Shanxi province (β=-0.117, p=0.001), emotional function (β=-0.19, p<0.001), social function (β=-0.111, p=0.006), anxiety (β=0.434, p<0.001) and RT interruption (β=0.071, p=0.035) were independent predictors.

Conclusions

RT strategy for breast cancer patients was greatly influenced during pandemic. RT interruption is an independent predictor for high FCR. Our findings emphasize the necessity to ensure continuum of RT, and efforts should be taken to alleviate FCR through psychological interventions.
Case Report: Circulating Tumor DNA Fraction Analysis Using Ultra-Low-Pass Whole-Genome Sequencing Correlates Response to Chemoradiation and Recurrence in Stage IV Small-Cell Carcinoma of the Cervix - A Longitudinal Study
Authors: Abbas Ata , Gruner Morgan , Karohl Jennifer , Rose Peter G. , Joehlin-Price Amy , Stover Daniel , Mahdi Haider
Published: July 2021

Neuroendocrine carcinoma of the cervix is a rare and aggressive form of cervical cancer that presents with frequent metastasis at diagnosis and high recurrence rates. Primary treatment is multimodal, which often includes chemotherapy with or without radiation therapy. There are no data available to guide treatment for recurrence, and second-line therapies are extrapolated from small-cell lung carcinoma data. Close monitoring of these patients for recurrence is paramount. Evaluation of circulating tumor DNA (ctDNA) in the peripheral blood is an attractive approach due to its non-invasive nature. Ultra-low-pass whole-genome sequencing (ULP-WGS) can assess tumor burden and response to therapy and predict recurrence; however, data are lacking regarding the role of ULP-WGS in small-cell carcinoma of the cervix. This study demonstrates a patient whose response to chemotherapy and cancer recurrence was accurately monitored by ctDNA analysis using ULP-WGS and confirmed with radiologic imaging findings.
Disease-Specific Survival of AJCC 8th Stage II Gastric Cancer Patients After D2 Gastrectomy
Authors: Zheng Xiaohao , Wu Yunzi , Zheng Li , Xue Liyan , Jiang Zhichao , Wang Chenfeng , Xie Yibin
Published: July 2021

The association between the risk factors and long-term prognosis in patients with stage II gastric cancer after radical gastrectomy has been fully revealed. The purpose of this study was to investigate the independent risk factors for treatment failure in stage II gastric cancer. Demographic, clinical, and pathological information of 247 stage II gastric cancer patients who underwent radical D2 gastrectomy in our department between January 2011 and December 2014 were collected and retrospectively analyzed. The relationship between and long-term clinical outcomes of stage II gastric cancer was analyzed using t-tests, chi-square tests, receiver operating characteristic (ROC) analysis, time-dependent ROC analysis, K–M curves, and a Cox regression model. The median follow-up of 247 stage II gastric cancer patients was 5.49 years (range: 0.12–8.62 years). The Kaplan–Meier estimated 3-year and 5-year DSS rates of the study group were 92.7% (95% CI 89.4–95.9) and 88.7% (95% CI 84.7–92.7), respectively. Higher age (>70 vs. ≤70, log-rank p = 0.0406), nerve invasion (positive vs. negative, log-rank p = 0.0133), and non-distal gastrectomy (distal partial gastrectomy vs. other surgical methods, log-rank p = 0.00235) had worse prognoses compared to controls. Univariate and multivariate analyses of disease-specific survival showed that these three factors were independent prognostic factors for patients with stage II disease. The area under time-dependent ROC curve (AUC) is 0.748 of 5-year survival and c-index is 0.696 based on the three-marker model drawn for stage II patients. Subgroup analyses showed an interaction between tumor location and nerve invasion. The age, perineural invasion, and surgical approach are independent prognostic factors for disease-specific survival after radical gastrectomy. Tumor location may be an important confounding factor for outcomes by affecting surgical methods and the hazards of nerve invasion.
m6A Modification: A Double-Edged Sword in Tumor Development
Authors: Gao Runnan , Ye Mujie , Liu Baihui , Wei Meng , Ma Duan , Dong Kuiran
Published: July 2021

Modification of m6A, as the most abundant mRNA modification, plays diverse roles in various biological processes in eukaryotes. Emerging evidence has revealed that m6A modification is closely associated with the activation and inhibition of tumor pathways, and it is significantly linked to the prognosis of cancer patients. Aberrant reduction or elevated expression of m6A regulators and of m6A itself have been identified in numerous tumors. In this review, we give a description of the dynamic properties of m6A modification regulators, such as methyltransferases, demethylases, and m6A binding proteins, and indicate the value of the balance between these proteins in regulating the expression of diverse genes and the underlying effects on cancer development. Furthermore, we summarize the “dual-edged weapon” role of RNA methylation in tumor progression and discuss that RNA methylation can not only result in tumorigenesis but also lead to suppression of tumor formation. In addition, we summarize the latest research progress on small-molecule targeting of m6A regulators to inhibit or activate m6A. These studies indicate that restoring the balance of m6A modification via targeting specific imbalanced regulators may be a novel anti-cancer strategy.
Adjuvant Radiotherapy After Minimally Invasive Surgery in Patients With Stage IA1-IIA1 Cervical Cancer
Authors: Gan Yi-xiu , Du Qing-hua , Li Jian , Wei Ye-ping , Jiang Xu-wei , Xu Xue-mei , Yue Hai-ying , Li Xiang-de , Zhu Hui-jun , Ou Xue , Zhong Qiu-lu , Luo Dan-jing , Liang Qian-fu , Xie Yi-ting , Zhang Qiang-qiang , Li Ge-li , Shang Yuan-ting , Liu Wen-qi
Published: July 2021

To estimate whether adjuvant radiotherapy is necessary for patients with stage IA1-IIA1 cervical cancer after laparoscopic hysterectomy, 221 patients were retrospectively analyzed. Sixty-two of them were treated with laparoscopic hysterectomy and adjuvant radiotherapy (group A), 115 underwent open surgery (group B) and 44 received laparoscopic hysterectomy alone (group C). Results showed that the 3-year local recurrence-free survival (LRFS) rates of group A, B and C were 98.4%, 97.4% and 86.4%, respectively. The LRFS rates of group A and B surpassed C (A vs. B, p=0.634; A vs. C, p=0.011; B vs. C, p=0.006). The inter-group differences of 3-year overall survival (OS) and distant metastasis free survival (DMFS) were not statistically significant. In subgroup analysis of stage IB disease, the 3-year LRFS rates of group A, B and C were 100%, 98.8% and 83.1%, the 3-year OS rates of group A, B and C were 100%, 98.9% and 91.5%, respectively. The 3-year LRFS and OS rates of group A and B were significantly superior to group C (p<0.05). Our findings suggest that adjuvant radiotherapy can reduce the risk of recurrence for women with early-stage cervical cancer after laparoscopic hysterectomy and bring survival benefits for patients with stage IB disease.
Comparing the Effectiveness of Endoscopic Surgeries With Intensity-Modulated Radiotherapy for Recurrent rT3 and rT4 Nasopharyngeal Carcinoma: A Meta-Analysis
Authors: Peng Zhouying , Wang Yumin , Wang Yaxuan , Fan Ruohao , Gao Kelei , Zhang Hua , Jiang Weihong
Published: July 2021

Background

This meta-analysis aimed to compare the efficacy of intensity-modulated radiotherapy (IMRT) and endoscopic surgery (ES) for high T-stage recurrent nasopharyngeal carcinoma (NPC).

Methods

Relevant studies were retrieved in six databases from 02/28,2011 to 02/28,2021. The 2-year, 3-year, 5-year overall survival (OS) rates and 2-year disease-free survival (DFS) rates were calculated to compare the survival outcomes of the two treatments of IMRT and ES. Combined odds ratios (ORs) and 95% confidence interval (C Is) were measured as effect size on the association between high T-stage and 5-year OS rates.

Results

A total of 23 publications involving 2,578 patients with recurrent NPC were included in this study. Of these, 1611 patients with recurrent rT3-4 NPC were treated with ES and IMRT in 358 and 1,253 patients, respectively. The combined 2-year OS and 5-year OS rates for the two treatments were summarized separately, and the 2-year OS and 5-year OS rate for ES were 64% and 52%, respectively. The 2-year OS and 5-year OS rate for IMRT were 65% and 31%, respectively. The combined 2-year DFS rates of IMRT and ES were 60% and 50%, respectively. Combined ORs and 95% confidence intervals for 5-year survival suggest that ES may improve survival in recurrent NPC with rT3-4. In terms of complications, ES in the treatment of high T-stage recurrent NPC is potentially associated with fewer complications.

Conclusions

The results of our study suggest that ES for rT3-4 may be a better treatment than IMRT, but the conclusion still needs to be sought by designing more studies.
Prognostic and Immunological Role of Gasdermin E in Pan-Cancer Analysis
Authors: Zhang Zheng , Zhao Shuangshuang , Yang Haizhen , Chen Yanwei , Feng Huahui , An Maohui , Chen Baoding
Published: July 2021

Despite accumulating cell- or animal-based experiments providing the relationship between Gasdermin E (GSDME) and human diseases, especially in malignant cancers, no pan-cancer analysis about the function of GSMDE in cancer management can be available up to date. Our research, for the first time, explored the potential carcinogenic role of GSDME across 33 tumors from the public platform of TCGA (The cancer genome atlas) database. GSDME is highly expressed in most malignant cancers, and obvious relationship exists between GSDME level and survival prognosis of cancer patients. The expression of GSDME was statically associated with the cancer-associated fibroblast infiltration in diverse cancer types, such as BLCA, CHOL, GBM, KIRC, LIHC, MESO, STAD, and UCEC. Furthermore, pyroptosis, sensory perception of sound, and defense response to bacterium were involved in the functional mechanisms of GSDME expression from GO analysis. Last but not the least, in vitro experiments were also performed to identify GSDME-induced pyroptosis. Our first pan-cancer analysis of GSDME not only broadens the understanding of the carcinogenic roles of GSDME but also provides a promising therapeutic strategy for benefiting an increasing number of cancerous patients based on GSDME-induced pyroptosis.