bluuebunny/crossref_metadata_2025 huggingface dataset:
A Resistome Roadmap: From the Human Body to Pristine Environments
Authors: Maestre-Carballa Lucia , Navarro-López Vicente , Martinez-Garcia Manuel
Published: May 2022

A comprehensive characterization of the human body resistome [sets of antibiotic resistance genes (ARGs)] is yet to be done and paramount for addressing the antibiotic microbial resistance threat. Here, we study the resistome of 771 samples from five major body parts (skin, nares, vagina, gut, and oral cavity) of healthy subjects from the Human Microbiome Project (HMP) and addressed the potential dispersion of ARGs in pristine environments. A total of 28,714 ARGs belonging to 235 different ARG types were found in the HMP proteome dataset (n = 9.1 × 107 proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high interindividual variability. Nares had the highest ARG load (≈5.4 genes/genome) followed by the oral cavity, whereas the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance (≈1.3 genes/genome). The fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide–lincosamide–streptogramin (MLS) or tetracycline. Most ARGs belonged to common bacterial commensals and multidrug resistance trait were predominant in the nares and vagina. Many ARGs detected here were considered as low risk for human health, whereas only a few of them, such as BlaZ, dfrA14, dfrA17, or tetM, were classified as high-risk ARG. Our data also provide hope, since the spread of common ARG from the human body to pristine environments (n = 271 samples; 77 Gb of sequencing data and 2.1 × 108 proteins analyzed) thus far remains very unlikely (only one case found in an autochthonous bacterium from a pristine environment). These findings broaden our understanding of ARG in the context of the human microbiome and the One-Health Initiative of WHO uniting human host–microbes and environments as a whole.
A Role for the Chicken Interferon-Stimulated Gene CMPK2 in the Host Response Against Virus Infection
Authors: Li Xin , Feng Yiyi , Liu Weiwei , Tan Lei , Sun Yingjie , Song Cuiping , Liao Ying , Xu Chenggang , Ren Tao , Ding Chan , Qiu Xusheng
Published: May 2022

Virus infection can lead to the production of interferon, which activates the JAK/STAT pathway and induces the expression of multiple downstream interferon-stimulated genes (ISGs) to achieve their antiviral function. Cytidine/uridine monophosphate kinase 2 (CMPK2) gene has been identified as an ISG in human and fish, and is also known as a rate-limiting enzyme in mitochondria to maintain intracellular UTP/CTP levels, which is necessary for de novo mitochondrial DNA synthesis. By mining previous microarray data, it was found that both Avian Influenza Virus (AIV) and Newcastle Disease Virus (NDV) infection can lead to the significant upregulation of chicken CMPK2 gene. However, little is known about the function of CMPK2 gene in chickens. In the present study, the open reading frame (ORF) of chicken CMPK2 (chCMPK2) was cloned from DF-1, a chicken embryo fibroblasts cell line, and subjected to further analysis. Sequence analysis showed that chCMPK2 shared high similarity in amino acid with CMPK2 sequences from all the other species, especially reptiles. A thymidylate kinase (TMK) domain was identified in the C-terminus of chCMPK2, which is highly conserved among all species. In vitro, AIV infection induced significant increases in chCMPK2 expression in DF-1, HD11, and the chicken embryonic fibroblasts (CEF), while obvious increase only detected in DF-1 cells and CEF cells after NDV infection. In vivo, the expression levels of chCMPK2 were up-regulated in several tissues from AIV infected chickens, especially the brain, spleen, bursa, kidney, intestine, heart and thymus, and notable increase of chCMPK2 was detected in the bursa, kidney, duodenum, lung, heart, and thymus during NDV infection. Here, using MDA5 and IFN-β knockdown cells, we demonstrated that as a novel ISG, chCMPK2 could be regulated by the MDA5/IFN-β pathway. The high expression level of exogenous chCMPK2 displayed inhibitory effects on AIV and NDV as well as reduced viral RNA in infected cells. We further demonstrated that Asp135, a key site on the TMK catalytic domain, was identified as critical for the antiviral activities of chCMPK2. Taken together, these data demonstrated that chCMPK2 is involved in the chicken immune system and may play important roles in host anti-viral responses.
Plasmopara viticola the Causal Agent of Downy Mildew of Grapevine: From Its Taxonomy to Disease Management
Authors: Koledenkova Kseniia , Esmaeel Qassim , Jacquard Cédric , Nowak Jerzy , Clément Christophe , Ait Barka Essaid
Published: May 2022

Plasmopara viticola (P. viticola, Berk. & M. A. Curtis; Berl. & De Toni) causing grapevine downy mildew is one of the most damaging pathogens to viticulture worldwide. Since its recognition in the middle of nineteenth century, this disease has spread from America to Europe and then to all grapevine-growing countries, leading to significant economic losses due to the lack of efficient disease control. In 1885 copper was found to suppress many pathogens, and is still the most effective way to control downy mildews. During the twentieth century, contact and penetrating single-site fungicides have been developed for use against plant pathogens including downy mildews, but wide application has led to the appearance of pathogenic strains resistant to these treatments. Additionally, due to the negative environmental impact of chemical pesticides, the European Union restricted their use, triggering a rush to develop alternative tools such as resistant cultivars breeding, creation of new active ingredients, search for natural products and biocontrol agents that can be applied alone or in combination to kill the pathogen or mitigate its effect. This review summarizes data about the history, distribution, epidemiology, taxonomy, morphology, reproduction and infection mechanisms, symptoms, host-pathogen interactions, host resistance and control of the P. viticola, with a focus on sustainable methods, especially the use of biocontrol agents.
Effective Biotransformation of Variety of Guaiacyl Lignin Monomers Into Vanillin by Bacillus pumilus
Authors: Zuo Kangjia , Li Huanan , Chen Jianhui , Ran Qiuping , Huang Mengtian , Cui Xinxin , He Lili , Liu Jiashu , Jiang Zhengbing
Published: May 2022

Biotransformation has gained increasing attention due to its being an eco-friendly way for the production of value-added chemicals. The present study aimed to assess the potential of Bacillus pumilus ZB1 on guaiacyl lignin monomers biotransformation for the production of vanillin. Consequently, isoeugenol, eugenol, and vanillyl alcohol could be transformed into vanillin by B. pumilus ZB1. Based on the structural alteration of masson pine and the increase of total phenol content in the supernatant, B. pumilus ZB1 exhibited potential in lignin depolymerization and valorization using masson pine as the substrate. As the precursors of vanillin, 61.1% of isoeugenol and eugenol in pyrolyzed bio-oil derived from masson pine could be transformed into vanillin by B. pumilus ZB1. Four monooxygenases with high specific activity were identified that were involved in the transformation process. Thus, B. pumilus ZB1 could emerge as a candidate in the biosynthesis of vanillin by using wide guaiacyl precursors as the substrates.
Targeting the Essential Transcription Factor HP1043 of Helicobacter pylori: A Drug Repositioning Study
Authors: Antoniciello Federico , Roncarati Davide , Zannoni Annamaria , Chiti Elena , Scarlato Vincenzo , Chiappori Federica
Published: May 2022

Antibiotic-resistant bacterial pathogens are a very challenging problem nowadays. Helicobacter pylori is one of the most widespread and successful human pathogens since it colonizes half of the world population causing chronic and atrophic gastritis, peptic ulcer, mucosa-associated lymphoid tissue-lymphoma, and even gastric adenocarcinoma. Moreover, it displays resistance to numerous antibiotics. One of the H. pylori pivotal transcription factors, HP1043, plays a fundamental role in regulating essential cellular processes. Like other bacterial transcription factors, HP1043 does not display a eukaryote homolog. These characteristics make HP1043 a promising candidate to develop novel antibacterial strategies. Drug repositioning is a relatively recent strategy employed in drug development; testing approved drugs on new targets considerably reduces the time and cost of this process. The combined computational and in vitro approach further reduces the number of compounds to be tested in vivo. Our aim was to identify a subset of known drugs able to prevent HP1043 binding to DNA promoters. This result was reached through evaluation by molecular docking the binding capacity of about 14,350 molecules on the HP1043 dimer in both conformations, bound and unbound to the DNA. Employing an ad hoc pipeline including MMGBSA molecular dynamics, a selection of seven drugs was obtained. These were tested in vitro by electrophoretic mobility shift assay to evaluate the HP1043–DNA interaction. Among these, three returned promising results showing an appreciable reduction of the DNA-binding activity of HP1043. Overall, we applied a computational methodology coupled with experimental validation of the results to screen a large number of known drugs on one of the H. pylori essential transcription factors. This methodology allowed a rapid reduction of the number of drugs to be tested, and the drug repositioning approach considerably reduced the drug design costs. Identified drugs do not belong to the same pharmaceutical category and, by computational analysis, bound different cavities, but all display a reduction of HP1043 binding activity on the DNA.
Working-Memory, Alpha-Theta Oscillations and Musical Training in Older Age: Research Perspectives for Speech-on-speech Perception
Authors: Gray Ryan , Sarampalis Anastasios , Başkent Deniz , Harding Eleanor E.
Published: May 2022

During the normal course of aging, perception of speech-on-speech or “cocktail party” speech and use of working memory (WM) abilities change. Musical training, which is a complex activity that integrates multiple sensory modalities and higher-order cognitive functions, reportedly benefits both WM performance and speech-on-speech perception in older adults. This mini-review explores the relationship between musical training, WM and speech-on-speech perception in older age (> 65 years) through the lens of the Ease of Language Understanding (ELU) model. Linking neural-oscillation literature associating speech-on-speech perception and WM with alpha-theta oscillatory activity, we propose that two stages of speech-on-speech processing in the ELU are underpinned by WM-related alpha-theta oscillatory activity, and that effects of musical training on speech-on-speech perception may be reflected in these frequency bands among older adults.
The Microbiome and Gut Endocannabinoid System in the Regulation of Stress Responses and Metabolism
Authors: Srivastava Raj Kamal , Lutz Beat , Ruiz de Azua Inigo
Published: May 2022

The endocannabinoid system, with its receptors and ligands, is present in the gut epithelium and enteroendocrine cells, and is able to modulate brain functions, both indirectly through circulating gut-derived factors and directly through the vagus nerve, finally acting on the brain’s mechanisms regarding metabolism and behavior. The gut endocannabinoid system also regulates gut motility, permeability, and inflammatory responses. Furthermore, microbiota composition has been shown to influence the activity of the endocannabinoid system. This review examines the interaction between microbiota, intestinal endocannabinoid system, metabolism, and stress responses. We hypothesize that the crosstalk between microbiota and intestinal endocannabinoid system has a prominent role in stress-induced changes in the gut-brain axis affecting metabolic and mental health. Inter-individual differences are commonly observed in stress responses, but mechanisms underlying resilience and vulnerability to stress are far from understood. Both gut microbiota and the endocannabinoid system have been implicated in stress resilience. We also discuss interventions targeting the microbiota and the endocannabinoid system to mitigate metabolic and stress-related disorders.
Association Between Rheumatoid Arthritis and Risk of Parkinson's Disease: A Meta-Analysis and Systematic Review
Authors: Li Dongxiu , Hong Xia , Chen Tingyu
Published: May 2022

Background

Rheumatoid arthritis (RA) and Parkinson's disease (PD) are two common chronic diseases worldwide, and any potential link between the two would significantly impact public health practice. Considering the current inconsistent evidence, we conducted a meta-analysis and systematic review to examine the risk of PD in patients with RA.

Methods

Two investigators (DL and XH) conducted a comprehensive search of PubMed, Embase, and Web of Science using medical subject headings terms combined with free words to identify relevant papers published from inception through December 31, 2021. All studies that explored the relationship between RA and PD were included for quantitative analysis and qualitative review. Random- and fixed-effects models were used to pool the risk ratios (RRs) of PD in patients with RA. The Newcastle-Ottawa scale was used to assess the quality of included studies. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guideline.

Results

Four population-based studies involving 353,246 patients and one Mendelian randomized study were included in our study. The pooled result showed a significantly reduced risk of PD in patients with RA than in the general population (RR = 0.74, 95% CI: 0.56-0.98, P = 0.034). No apparent effects of gender, age, region, follow-up time, or study design on PD risk were observed. Sensitivity analysis showed that pooled results were relatively stable, and no publication bias was detected. The Mendelian randomization study indicated a significant inverse association between RA and PD (genetic correlation: −0.10, P = 0.0033) and that each one standard deviation increase in the risk of RA was significantly associated with a lower risk of PD. Of note, the current study is limited by the relatively small number of included studies and unmeasured confounding factors, especially for RA-related anti-inflammatory agents.

Conclusions

This study supports that people with RA had a lower PD risk than those without RA. Further studies are needed to explore the underlying molecular mechanisms of the interaction between the two diseases.
Demyelinating Syndromes in Systemic Lupus Erythematosus: Data From the “Attikon” Lupus Cohort
Authors: Nikolopoulos Dionysis , Kitsos Dimitrios , Papathanasiou Matilda , Kapsala Noemin , Garantziotis Panagiotis , Pieta Antigone , Gioti Ourania , Grivas Alexandros , Voumvourakis Konstantinos , Boumpas Dimitrios , Fanouriakis Antonis
Published: May 2022

Background

The demyelinating syndromes of the central nervous system (CNS) that occur in the context of systemic lupus erythematosus (SLE) may represent a manifestation of neuropsychiatric lupus (NPSLE) or an overlap of SLE and multiple sclerosis (MS). The differential diagnosis between the two entities has important clinical implications because the therapeutic management differs.

Objectives

To characterize CNS demyelinating syndromes in a large SLE cohort as neuropsychiatric SLE (NPSLE) or SLE-MS overlap using a multidisciplinary approach and existing diagnostic (for MS) and classification criteria (for SLE).

Methods

Patients from the “Attikon” lupus cohort (n = 707) were evaluated for demyelinating syndromes. Clinical, laboratory, and neuroimaging data were recorded for each patient. Following multidisciplinary evaluation and application of criteria, the demyelinating syndrome was attributed to either SLE or MS. Patients with transverse myelitis were not included in this study.

Results

We identified 26 patients with demyelinating syndromes (3.7%). Of them, 12 were diagnosed as primary SLE-demyelination (46.2%) and 14 as overlap SLE-MS (53.8%). The two groups did not differ with respect to rheumatologic and neurologic manifestations or autoantibodies. SLE patients with demyelination manifested mild extra-CNS disease mainly involving joints and skin, while severe non-CNS manifestations were rare. However, these patients were less likely to have elevated IgG index (OR 0.055 95% CI: 0.008–0.40) and positive oligoclonal bands (OR 0.09 95% CI: 0.014–0.56), as well as brain lesions in the spinal cord, infratentorial, periventricular, and juxtacortical regions. A single brain region was affected in 9 patients with SLE-demyelination (75%), while all patients with MS-SLE had multiple affected brain regions. MS-SLE overlap was associated with an increased likelihood of neurologic relapses (OR 18.2, 95% CI: 1.76–188), while SLE-demyelination patients were less likely to exhibit neurological deficits (EDSS >0) at the last follow-up visit (50 vs. 78.6% in SLE-MS, respectively).

Conclusions

Demyelination in the context of SLE follows a more benign course compared to a frank SLE-MS overlap. Extension of follow-up will ascertain whether patients with SLE-demyelination evolve to MS, or this is a bona fide NPSLE syndrome.
An Action-Independent Role for Midfrontal Theta Activity Prior to Error Commission
Authors: Estiveira João , Dias Camila , Costa Diana , Castelhano João , Castelo-Branco Miguel , Sousa Teresa
Published: May 2022

Error-related electroencephalographic (EEG) signals have been widely studied concerning the human cognitive capability of differentiating between erroneous and correct actions. Midfrontal error-related negativity (ERN) and theta band oscillations are believed to underlie post-action error monitoring. However, it remains elusive how early monitoring activity is trackable and what are the pre-response brain mechanisms related to performance monitoring. Moreover, it is still unclear how task-specific parameters, such as cognitive demand or motor control, influence these processes. Here, we aimed to test pre- and post-error EEG patterns for different types of motor responses and investigate the neuronal mechanisms leading to erroneous actions. We implemented a go/no-go paradigm based on keypresses and saccades. Participants received an initial instruction about the direction of response to be given based on a facial cue and a subsequent one about the type of action to be performed based on an object cue. The paradigm was tested in 20 healthy volunteers combining EEG and eye tracking. We found significant differences in reaction time, number, and type of errors between the two actions. Saccadic responses reflected a higher number of premature responses and errors compared to the keypress ones. Nevertheless, both led to similar EEG patterns, supporting previous evidence for increased ERN amplitude and midfrontal theta power during error commission. Moreover, we found pre-error decreased theta activity independent of the type of action. Source analysis suggested different origin for such pre- and post-error neuronal patterns, matching the anterior insular cortex and the anterior cingulate cortex, respectively. This opposite pattern supports previous evidence of midfrontal theta not only as a neuronal marker of error commission but also as a predictor of action performance. Midfrontal theta, mostly associated with alert mechanisms triggering behavioral adjustments, also seems to reflect pre-response attentional mechanisms independently of the action to be performed. Our findings also add to the discussion regarding how salience network nodes interact during performance monitoring by suggesting that pre- and post-error patterns have different neuronal sources within this network.
The Relationship Between Pre-existing Coronary Heart Disease and Cognitive Impairment Is Partly Explained by Reduced Left Ventricular Ejection Fraction in the Subjects Without Clinical Heart Failure: A Cross-Sectional Study
Authors: Shang Suhang , Liu Ziyu , Gao Jinying , Wang Jin , Lu Wenhui , Fei Yulang , Zhang Binyan , Mi Baibing , Li Pei , Ma Louyan , Jiang Yu , Chen Chen , Dang Liangjun , Liu Jie , Qu Qiumin
Published: May 2022

Background

Coronary heart disease (CHD) is closely associated with cognitive impairment, especially in severe cases of heart failure. However, it is unclear whether cardiac systolic function plays a role in the relationship between pre-existing CHD and cognitive impairment in subjects without clinical heart failure.

Methods

In total, 208 subjects from the First Affiliated Hospital of Xi’an Jiaotong University were recruited from June 2014 to January 2015, and were divided into CHD (n = 118) and non-CHD (n = 90) groups according to the inclusion and exclusion criteria. The global cognitive function of all subjects was assessed by the Mini-Mental State Examination (MMSE) and cognitive impairment was defined as the score lower than the cutoff value. Left ventricular ejection fraction (LVEF) was measured using transthoracic echocardiograms. The relationship among pre-existing CHD, LVEF, and cognitive impairment was analyzed by multivariate logistic regression.

Results

In total, 34 subjects met the criteria of cognitive impairment. Univariate analysis showed that the cognitive impairment prevalence in the CHD group was significantly higher than that in the non-CHD group (22.0 vs. 8.9%, p = 0.011). Multivariate logistic analysis revealed that CHD was significantly associated with a higher risk of cognitive impairment (odds ratio [OR] = 3.284 [95% CI, 1.032–10.450], p = 0.044) after adjusting for confounds except for LVEF. However, the OR of CHD decreased (OR = 2.127 [95% CI, 0.624–7.254], p = 0.228) when LVEF was further corrected as a continuous variable, and LVEF was negatively associated with the risk of cognitive impairment (OR = 0.928 [95% CI, 0.882–0.976], p = 0.004).

Conclusion

Pre-existing CHD is associated with a higher risk of cognitive impairment, and such an association can be considerably explained by reduced LVEF. An impaired cardiac systolic function may play a key role in the relationship between CHD and cognitive impairment among patients with pre-heart failure conditions.
Walking and Balance Outcomes Are Improved Following Brief Intensive Locomotor Skill Training but Are Not Augmented by Transcranial Direct Current Stimulation in Persons With Chronic Spinal Cord Injury
Authors: Evans Nicholas H. , Suri Cazmon , Field-Fote Edelle C.
Published: May 2022

Motor training to improve walking and balance function is a common aspect of rehabilitation following motor-incomplete spinal cord injury (MISCI). Evidence suggests that moderate- to high-intensity exercise facilitates neuroplastic mechanisms that support motor skill acquisition and learning. Furthermore, enhancing corticospinal drive via transcranial direct current stimulation (tDCS) may augment the effects of motor training. In this pilot study, we investigated whether a brief moderate-intensity locomotor-related motor skill training (MST) circuit, with and without tDCS, improved walking and balance outcomes in persons with MISCI. In addition, we examined potential differences between within-day (online) and between-day (offline) effects of MST. Twenty-six adults with chronic MISCI, who had some walking ability, were enrolled in a 5-day double-blind, randomized study with a 3-day intervention period. Participants were assigned to an intensive locomotor MST circuit and concurrent application of either sham tDCS (MST+tDCSsham) or active tDCS (MST+tDCS). The primary outcome was overground walking speed measured during the 10-meter walk test. Secondary outcomes included spatiotemporal gait characteristics (cadence and stride length), peak trailing limb angle (TLA), intralimb coordination (ACC), the Berg Balance Scale (BBS), and the Falls Efficacy Scale-International (FES-I) questionnaire. Analyses revealed a significant effect of the MST circuit, with improvements in walking speed, cadence, bilateral stride length, stronger limb TLA, weaker limb ACC, BBS, and FES-I observed in both the MST+tDCSsham and MST+tDCS groups. No differences in outcomes were observed between groups. Between-day change accounted for a greater percentage of the overall change in walking outcomes. In persons with MISCI, brief intensive MST involving a circuit of ballistic, cyclic locomotor-related skill activities improved walking outcomes, and selected strength and balance outcomes; however, concurrent application of tDCS did not further enhance the effects of MST.

Clinical Trial Registration

[ClinicalTrials.gov], identifier [NCT03237234].
The No-Report Paradigm: A Revolution in Consciousness Research?
Authors: Duman Irem , Ehmann Isabell Sophia , Gonsalves Alicia Ronnie , Gültekin Zeynep , Van den Berckt Jonathan , van Leeuwen Cees
Published: May 2022

In the cognitive neuroscience of consciousness, participants have commonly been instructed to report their conscious content. This, it was claimed, risks confounding the neural correlates of consciousness (NCC) with their preconditions, i.e., allocation of attention, and consequences, i.e., metacognitive reflection. Recently, the field has therefore been shifting towards no-report paradigms. No-report paradigms draw their validity from a direct comparison with no-report conditions. We analyze several examples of such comparisons and identify alternative interpretations of their results and/or methodological issues in all cases. These go beyond the previous criticism that just removing the report is insufficient, because it does not prevent metacognitive reflection. The conscious mind is fickle. Without having much to do, it will turn inward and switch, or timeshare, between the stimuli on display and daydreaming or mind-wandering. Thus, rather than the NCC, no-report paradigms might be addressing the neural correlates of conscious disengagement. This observation reaffirms the conclusion that no-report paradigms are no less problematic than report paradigms.
Unilateral GPi-DBS Improves Ipsilateral and Axial Motor Symptoms in Parkinson’s Disease as Evidenced by a Brain Perfusion Single Photon Emission Computed Tomography Study
Authors: Hayashi Yuka , Mishima Takayasu , Fujioka Shinsuke , Morishita Takashi , Inoue Tooru , Nagamachi Shigeki , Tsuboi Yoshio
Published: May 2022

Introduction

Deep brain stimulation (DBS) is an effective treatment for advanced Parkinson’s disease (PD) with the targeting bilateral subthalamic nucleus or globus pallidus internus (STN or GPi-DBS). So far, detailed studies on the efficacy of unilateral STN-DBS for motor symptoms have been reported, but few studies have been conducted on unilateral GPi-DBS.

Materials and Methods

Seventeen patients with Parkinson’s disease (PwPD) who underwent unilateral GPi-DBS were selected. We conducted comparison analyses between scores obtained 6–42 months pre- and postoperatively using the following measurement tools: the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III, the Hoehn and Yahr stage, the presence/absence of dyskinesia, Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS), levodopa equivalent dose (LED), and cerebral blood flow by single photon emission computed tomography (SPECT). Patient backgrounds were compared between four cohorts with favorable (good responders, ≥50% improvement) and unfavorable (poor responders, <50% improvement) postoperative outcome.

Results

Significant improvement was observed postoperatively in the following: total MDS-UPDRS Part III scores during the off period, contralateral scores, ipsilateral scores, and axial scores. Similarly, the Hoehn and Yahr stages during the off period, and GDS also showed significant decrease. In contrast, LED, MMSE, and FAB remained unchanged while the number of patients who scored positive for dyskinesia decreased by 40%. Abnormal cerebral blood flow preoperatively seen in the cerebral cortex had normalized in the total score-based good responder cohort. In the ipsilateral score-based good responder cohort, cerebral blood flow increased in the contralateral frontal lobe including in the premotor cortex, contralateral to the DBS. Compared to the poor responders, postoperative good responders demonstrated significantly higher preoperative MMSE scores.

Discussion

Unilateral GPi-DBS therapy was effective in improving contralateral, ipsilateral, and axial motor symptoms of patients with advanced PD; in particular, it was found to be especially beneficial in PwPD whose cognitive function was unimpaired; the treatment efficacy rivaled that of bilateral counterparts up till at least 6 months postoperatively. Finally, normalization of preoperative abnormalities in cerebral blood flow and increased cerebral blood flow in the contralateral frontal lobe indicated the beneficial potential of this therapy on ipsilateral motor symptoms.
Resilient Hippocampal Gamma Rhythmogenesis and Parvalbumin-Expressing Interneuron Function Before and After Plaque Burden in 5xFAD Alzheimer’s Disease Model
Authors: Mackenzie-Gray Scott Connie A. , Pelkey Kenneth A. , Caccavano Adam P. , Abebe Daniel , Lai Mandy , Black Khayla N. , Brown Nicolette D. , Trevelyan Andrew J. , McBain Chris J.
Published: May 2022

Recent studies have implicated impaired Parvalbumin Fast-Spiking Interneuron (PVIN) function as a precipitating factor underlying abnormalities in network synchrony, oscillatory rhythms, and cognition associated with Alzheimer’s disease (AD). However, a complete developmental investigation of potential gamma deficits, induced by commonly used carbachol or kainate in ex vivo slice preparations, within AD model mice is lacking. We examined gamma oscillations using field recordings in acute hippocampal slices from 5xFAD and control mice, through the period of developing pathology, starting at 3 months of age, when there is minimal plaque presence in the hippocampus, through to 12+ months of age, when plaque burden is high. In addition, we examined PVIN participation in gamma rhythms using targeted cell-attached recordings of genetically-reported PVINs, in both wild type and mutant mice. In parallel, a developmental immunohistochemical characterisation probing the PVIN-associated expression of PV and perineuronal nets (PNNs) was compared between control and 5xFAD mice. Remarkably, this comprehensive longitudinal evaluation failed to reveal any obvious correlations between PVIN deficits (electrical and molecular), circuit rhythmogenesis (gamma frequency and power), and Aβ deposits/plaque formation. By 6–12 months, 5xFAD animals have extensive plaque formation throughout the hippocampus. However, a deficit in gamma oscillatory power was only evident in the oldest 5xFAD animals (12+ months), and only when using kainate, and not carbachol, to induce the oscillations. We found no difference in PV firing or phase preference during kainate-induced oscillations in younger or older 5xFAD mice compared to control, and a reduction of PV and PNNs only in the oldest 5xFAD mice. The lack of a clear relationship between PVIN function, network rhythmicity, and plaque formation in our study highlights an unexpected resilience in PVIN function in the face of extensive plaque pathology associated with this model, calling into question the presumptive link between PVIN pathology and Alzheimer’s progression.
Dietary Inflammatory Potential Is Associated With Sarcopenia Among Chronic Kidney Disease Population
Authors: Huang Ying , Zeng Mengru , Zhang Lei , Shi Jingzheng , Yang Yuan , Liu Fuyou , Sun Lin , Xiao Li
Published: May 2022

Background

Sarcopenia, characterized by impaired muscle mass and function, is a common complication and the main reason for bad life quality and high mortality in chronic kidney disease (CKD). Limiting systemic inflammation is a potable intervention for sarcopenia. Dietary inflammatory potential can influence systemic inflammation. However, research about the association between dietary inflammatory potential and sarcopenia in CKD is limited.

Aim

To investigate the association between dietary inflammatory potential and sarcopenia in the CKD population.

Methods

We conducted a cross-section study based on the public database of the National Health and Nutrition Examination Survey (NHANES). In total, 2,569 adult CKD participants who had complete data for dietary inflammatory potential and sarcopenia were included. The dietary inflammatory potential was calculated by the dietary inflammation index (DII) score based on dietary recall interviews. We assessed sarcopenia via low skeletal muscle mass measured by dual-energy X-ray absorptiometry. Smooth curve fitting and a generalized linear mixed model were used to evaluate the relationship between DII and sarcopenia. Moreover, subgroup and sensitivity analyses were performed.

Results

The overall prevalence of sarcopenia among patients with CKD is 19.11%. Smooth curve fitting results displayed that the DII score is near-linear positively associated with sarcopenia. Logistic regression confirmed sarcopenia is independently related to DII scores (odds ratio [OR], 1.17; 95% CI, 1.06–1.29). Subgroup analyses revealed relatively stronger associations between DII and sarcopenia among patients with CKD with other sarcopenia risk factors, such as hypoalbuminemia, low energy intake, low protein intake, and comorbidities.

Conclusion

The dietary inflammatory potential is independently related to sarcopenia among patients with CKD. Anti-inflammatory diet patterns may be a protective intervention for CKD-associated sarcopenia.
High Hydrostatic Pressure-Based Combination Strategies for Microbial Inactivation of Food Products: The Cases of Emerging Combination Patterns
Authors: Xia Qiang , Liu Qianqian , Denoya Gabriela I. , Yang Caijiao , Barba Francisco J. , Yu Huaning , Chen Xiaojia
Published: May 2022

The high demand for fresh-like characteristics of vegetables and fruits (V&F) boosts the industrial implementation of high hydrostatic pressure (HHP), due to its capability to simultaneously maintain original organoleptic characteristics and to achieve preservative effect of the food. However, there remains great challenges for assuring complete microbial inactivation only relying on individual HHP treatments, including pressure-resistant strains and regrowth of injured microbes during the storage process. Traditional HHP-assisted thermal processing may compromise the nutrition and functionalities due to accelerated chemical kinetics under high pressure conditions. This work summarizes the recent advances in HHP-based combination strategies for microbial safety, as exemplified by several emerging non-thermally combined patterns with high inactivation efficiencies. Considerations and requirements about future process design and development of HHP-based combination technologies are also given.
Antimicrobial Activity, Microstructure, Mechanical, and Barrier Properties of Cassava Starch Composite Films Supplemented With Geranium Essential Oil
Authors: Wang Bin , Yan Shouxin , Qiu Lizhong , Gao Wei , Kang Xuemin , Yu Bin , Liu Pengfei , Cui Bo , Abd El-Aty A. M.
Published: May 2022

In this study, we prepared cassava starch-based films by the casting method. Afterwards, the effects of geranium essential oil (GEO) on the prepared films' physicochemical, morphology, and antibacterial properties were revealed. We found that the thickness and elongation at the break of cassava starch films increased with increasing GEO concentration (from 0.5, 1, and 2%). However, increasing GEO concentration decreased the water content, water vapor permeability, and tensile strength of the prepared films'. Further, the addition of GEO increased the surface roughness, opacity, and antibacterial properties of the prepared films. With the increase of GEO concentration, L* and a* of cassava starch film decreased, while b* and Δ E increased. This study provides a theory for cassava starch-based films as a biological packaging material.
Application of Machine Vision System in Food Detection
Authors: Xiao Zhifei , Wang Jilai , Han Lu , Guo Shubiao , Cui Qinghao
Published: May 2022

Food processing technology is an important part of modern life globally and will undoubtedly play an increasingly significant role in future development of industry. Food quality and safety are societal concerns, and food health is one of the most important aspects of food processing. However, ensuring food quality and safety is a complex process that necessitates huge investments in labor. Currently, machine vision system based image analysis is widely used in the food industry to monitor food quality, greatly assisting researchers and industry in improving food inspection efficiency. Meanwhile, the use of deep learning in machine vision has significantly improved food identification intelligence. This paper reviews the application of machine vision in food detection from the hardware and software of machine vision systems, introduces the current state of research on various forms of machine vision, and provides an outlook on the challenges that machine vision system faces.
A Combination of Cytokine-Induced Killer Cells With PD-1 Blockade and ALK Inhibitor Showed Substantial Intrinsic Variability Across Non-Small Cell Lung Cancer Cell Lines
Authors: Li Yutao , Sharma Amit , Wu Xiaolong , Weiher Hans , Skowasch Dirk , Essler Markus , Schmidt-Wolf Ingo G. H.
Published: May 2022

Background

Cancer heterogeneity poses a serious challenge concerning the toxicity and adverse effects of therapeutic inhibitors, especially when it comes to combinatorial therapies that involve multiple targeted inhibitors. In particular, in non-small cell lung cancer (NSCLC), a number of studies have reported synergistic effects of drug combinations in the preclinical models, while they were only partially successful in the clinical setup, suggesting those alternative clinical strategies (with genetic background and immune response) should be considered. Herein, we investigated the antitumor effect of cytokine-induced killer (CIK) cells in combination with ALK and PD-1 inhibitors in vitro on genetically variable NSCLC cell lines.

Methods

We co-cultured the three genetically different NSCLC cell lines NCI-H2228 (EML4-ALK), A549 (KRAS mutation), and HCC-78 (ROS1 rearrangement) with and without nivolumab (PD-1 inhibitor) and crizotinib (ALK inhibitor). Additionally, we profiled the variability of surface expression multiple immune checkpoints, the concentration of absolute dead cells, intracellular granzyme B on CIK cells using flow cytometry as well as RT-qPCR. ELISA and Western blot were performed to verify the activation of CIK cells.

Results

Our analysis showed that (a) nivolumab significantly weakened PD-1 surface expression on CIK cells without impacting other immune checkpoints or PD-1 mRNA expression, (b) this combination strategy showed an effective response on cell viability, IFN-γ production, and intracellular release of granzyme B in CD3+ CD56+ CIK cells, but solely in NCI-H2228, (c) the intrinsic expression of Fas ligand (FasL) as a T-cell activation marker in CIK cells was upregulated by this additive effect, and (d) nivolumab induced Foxp3 expression in CD4+CD25+ subpopulation of CIK cells significantly increased. Taken together, we could show that CIK cells in combination with crizotinib and nivolumab can enhance the anti-tumor immune response through FasL activation, leading to increased IFN-γ and granzyme B, but only in NCI-H2228 cells with EML4-ALK rearrangement. Therefore, we hypothesize that CIK therapy may be a potential alternative in NSCLC patients harboring EML4-ALK rearrangement, in addition, we support the idea that combination therapies offer significant potential when they are optimized on a patient-by-patient basis.
Selected Patients With Peritoneal Metastases From Breast Cancer May Benefit From Cytoreductive Surgery: The Results of a Multicenter Survey
Authors: Cardi Maurizio , Pocard Marc , Dico Rea Lo , Fiorentini Gianmaria , Valle Mario , Gelmini Roberta , Vaira Marco , Pasqual Enrico Maria , Asero Salvatore , Baiocchi Gianluca , Di Giorgio Andrea , Spagnoli Alessandra , Di Marzo Francesco , Sollazzo Bianca , D’Ermo Giuseppe , Biacchi Daniele , Iafrate Franco , Sammartino Paolo
Published: May 2022

Background

Even though breast cancer is the most frequent extra-abdominal tumor causing peritoneal metastases, clear clinical guidelines are lacking. Our aim is to establish whether cytoreductive surgery (CRS) could be considered in selected patients with peritoneal metastases from breast cancer (PMBC) to manage abdominal spread and allow patients to resume or complete other medical treatments.

Methods

We considered patients with PMBC treated in 10 referral centers from January 2002 to May 2019. Clinical data included primary cancer characteristics (age, histology, and TNM) and data on metastatic disease (interval between primary BC and PM, molecular subtype, other metastases, and peritoneal spread). Overall survival (OS) was estimated using the Kaplan–Meier method. Univariate and multivariable data for OS were analyzed using the Cox proportional hazards model.

Results

Of the 49 women with PMBC, 20 were treated with curative aim (CRS with or without HIPEC) and 29 were treated with non-curative procedures. The 10-year OS rate was 27%. Patients treated with curative intent had a better OS than patients treated with non-curative procedures (89.2% vs. 6% at 36 months, p < 0.001). Risk factors significantly influencing survival were age at primary BC, interval between BC and PM diagnosis, extra-peritoneal metastases, and molecular subtype.

Conclusions

The improved outcome in selected cases after a multidisciplinary approach including surgery should lead researchers to regard PMBC patients with greater attention despite their scarce epidemiological impact. Our collective efforts give new information, suggest room for improvement, and point to further research for a hitherto poorly studied aspect of metastatic BC.
Automatic Tumor Grading on Colorectal Cancer Whole-Slide Images: Semi-Quantitative Gland Formation Percentage and New Indicator Exploration
Authors: Chen Shenlun , Zhang Meng , Wang Jiazhou , Xu Midie , Hu Weigang , Wee Leonard , Dekker Andre , Sheng Weiqi , Zhang Zhen
Published: May 2022

Tumor grading is an essential factor for cancer staging and survival prognostication. The widely used the WHO grading system defines the histological grade of CRC adenocarcinoma based on the density of glandular formation on whole-slide images (WSIs). We developed a fully automated approach for stratifying colorectal cancer (CRC) patients’ risk of mortality directly from histology WSI relating to gland formation. A tissue classifier was trained to categorize regions on WSI as glands, stroma, immune cells, background, and other tissues. A gland formation classifier was trained on expert annotations to categorize regions as different degrees of tumor gland formation versus normal tissues. The glandular formation density can thus be estimated using the aforementioned tissue categorization and gland formation information. This estimation was called a semi-quantitative gland formation ratio (SGFR), which was used as a prognostic factor in survival analysis. We evaluated gland formation percentage and validated it by comparing it against the WHO cutoff point. Survival data and gland formation maps were then used to train a spatial pyramid pooling survival network (SPPSN) as a deep survival model. We compared the survival prediction performance of estimated gland formation percentage and the SPPSN deep survival grade and found that the deep survival grade had improved discrimination. A univariable Cox model for survival yielded moderate discrimination with SGFR (c-index 0.62) and deep survival grade (c-index 0.64) in an independent institutional test set. Deep survival grade also showed better discrimination performance in multivariable Cox regression. The deep survival grade significantly increased the c-index of the baseline Cox model in both validation set and external test set, but the inclusion of SGFR can only improve the Cox model less in external test and is unable to improve the Cox model in the validation set.
Study on the Mechanism of Sancao Tiaowei Decoction in the Treatment of MNNG-Induced Precancerous Lesions of Gastric Carcinoma Through Hedgehog Signaling Pathway
Authors: Cai Yan , Cao Ying , Cheng Shuang , Zou Lijun , Yang Ting , Zhang Yuxin , Shou Qiyang , Chen Binhai , Chen Weijian
Published: May 2022

Sancao Tiaowei Decoction (SCTWD), a traditional Chinese medicine created by Professor Chen Weijian, has been used in the prevention and treatment of precancerous lesions of gastric carcinoma (PLGC). However, its mechanism has not been made clear. This study aimed to evaluate the therapeutic effect of SCTWD on 1-methyl-3-nitro-1-nitrosoguanidine-induced PLGC in rats and the mechanism of this effect. We found that SCTWD effectively repaired gastric mucosal injury, reversed the process of PLGC, and inhibited the occurrence of gastric cancer to some extent. In the results of hematoxylin-eosin (HE) staining, the number and arrangement of mucosal glands and the number of mononuclear cells in the lamina propria were improved in varying degrees; the enzyme-linked immunosorbent assay (ELISA) showed that the PG I and PGR of the medication treatment group were significantly higher; a Reverse Transcription-Polymerase Chain Reaction (RT-PCR) test showed that SCTWD could significantly upregulate the expression levels of Shh, Ptch, and Gli-1 in the gastric tissue of rats. The immunohistochemical method showed that SCTWD could significantly upregulate the protein expressions of Shh, Gli-1, Smo, cyclin D1, CDKN2A/p16INK4a, and NF-κBP65 and could reduce the expression of Ptch at the same time. Through the preliminary analysis of 75 compounds screened by UPLC-Q-TOF-MS, the main components, such as organic acids, esters and anhydrides, flavonoids, phenols, tanshinones, and so on, have anti-inflammatory and anti-tumor pharmacological effects. The results of KEGG enrichment analysis showed that 5 signaling pathways related to this project were found, and 33 differential genes were presented to construct the interaction network. These results suggested that SCTWD had a good regulatory effect on PLGC and thus may have a multi-targeted effect; SCTWD can not only significantly improve the pathological changes of gastric mucosa in rats with PLGC but also exert a strong effect of the regulation of the hedgehog signaling pathway.