bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Characterization of Extensively Drug-Resistant NDM-Producing Acinetobacter baumannii Clinical Isolates With the Emergence of Novel blaADC-257
Authors: Zafer Mai M. , Hussein Amira F. A. , Al-Agamy Mohamed H. , Radwan Hesham H. , Hamed Samira M.
Published: November 2021

Acinetobacter baumannii has become a major challenge to clinicians worldwide due to its high epidemic potential and acquisition of antimicrobial resistance. This work aimed at investigating antimicrobial resistance determinants and their context in four extensively drug-resistant (XDR) NDM-producing A. baumannii clinical isolates collected between July and October 2020 from Kasr Al-Ainy Hospital, Cairo, Egypt. A total of 20 A. baumannii were collected and screened for acquired carbapenemases (blaNDM, blaVIM and blaIMP) using PCR. Four NDM producer A. baumannii isolates were identified and selected for whole-genome sequencing, in silico multilocus sequence typing, and resistome analysis. Antimicrobial susceptibility profiles were determined using disk diffusion and broth microdilution tests. All blaNDM-positive A. baumannii isolates were XDR. Three isolates belonged to high-risk international clones (IC), namely, IC2 corresponding to ST570Pas/1701Oxf (M20) and IC9 corresponding to ST85Pas/ST1089Oxf (M02 and M11). For the first time, we report blaNDM-1 gene on the chromosome of an A. baumannii strain that belongs to sequence type ST164Pas/ST1418Oxf. Together with AphA6, blaNDM-1 was bracketed by two copies of ISAba14 in ST85Pas isolates possibly facilitating co-transfer of amikacin and carbapenem resistance. A novel blaADC allele (blaADC-257) with an upstream ISAba1 element was identified in M19 (ST/CC164Pas and ST1418Oxf/CC234Oxf). blaADC genes harbored by M02 and M11 were uniquely interrupted by IS1008. Tn2006-associated blaOXA-23 was carried by M20. blaOXA-94 genes were preceded by ISAba1 element in M02 and M11. AbGRI3 was carried by M20 hosting the resistance genes aph(3`)-Ia, aac(6`)-Ib`, catB8, ant(3``)-Ia, sul1, armA, msr(E), and mph(E). Nonsynonymous mutations were identified in the quinolone resistance determining regions (gyrA and parC) of all isolates. Resistance to colistin in M19 was accompanied by missense mutations in lpxACD and pmrABC genes. The current study provided an insight into the genomic background of XDR phenotype in A. baumannii recovered from patients in Egypt. WGS revealed strong association between resistance genes and diverse mobile genetic elements with novel insertion sites and genetic organizations.
Bacillus subtilis RecA, DisA, and RadA/Sms Interplay Prevents Replication Stress by Regulating Fork Remodeling
Authors: Torres Rubén , Alonso Juan C.
Published: November 2021

Reviving Bacillus subtilis spores require the recombinase RecA, the DNA damage checkpoint sensor DisA, and the DNA helicase RadA/Sms to prevent a DNA replication stress. When a replication fork stalls at a template lesion, RecA filaments onto the lesion-containing gap and the fork is remodeled (fork reversal). RecA bound to single-strand DNA (ssDNA) interacts with and recruits DisA and RadA/Sms on the branched DNA intermediates (stalled or reversed forks), but DisA and RadA/Sms limit RecA activities and DisA suppresses its c-di-AMP synthesis. We show that RecA, acting as an accessory protein, activates RadA/Sms to unwind the nascent lagging-strand of the branched intermediates rather than to branch migrate them. DisA limits the ssDNA-dependent ATPase activity of RadA/Sms C13A, and inhibits the helicase activity of RadA/Sms by a protein-protein interaction. Finally, RadA/Sms inhibits DisA-mediated c-di-AMP synthesis and indirectly inhibits cell proliferation, but RecA counters this negative effect. We propose that the interactions among DisA, RecA and RadA/Sms, which are mutually exclusive, contribute to generate the substrate for replication restart, regulate the c-di-AMP pool and limit fork restoration in order to maintain cell survival.
Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse Lineages
Authors: McCutcheon Cole R. , Pell Macy E. , Gaddy Jennifer A. , Aronoff David M. , Petroff Margaret G. , Manning Shannon D.
Published: November 2021

Although the neonatal and fetal pathogen Group B Streptococcus (GBS) asymptomatically colonizes the vaginal tract of ∼30% of pregnant women, only a fraction of their offspring develops invasive disease. We and others have postulated that these dimorphic clinical phenotypes are driven by strain variability; however, the bacterial factors that promote these divergent clinical phenotypes remain unclear. It was previously shown that GBS produces membrane vesicles (MVs) that contain active virulence factors capable of inducing adverse pregnancy outcomes. Because the relationship between strain variation and vesicle composition or production is unknown, we sought to quantify MV production and examine the protein composition, using label-free proteomics on MVs produced by diverse clinical GBS strains representing three phylogenetically distinct lineages. We found that MV production varied across strains, with certain strains displaying nearly twofold increases in production relative to others. Hierarchical clustering and principal component analysis of the proteomes revealed that MV composition is lineage-dependent but independent of clinical phenotype. Multiple proteins that contribute to virulence or immunomodulation, including hyaluronidase, C5a peptidase, and sialidases, were differentially abundant in MVs, and were partially responsible for this divergence. Together, these data indicate that production and composition of GBS MVs vary in a strain-dependent manner, suggesting that MVs have lineage-specific functions relating to virulence. Such differences may contribute to variation in clinical phenotypes observed among individuals infected with GBS strains representing distinct lineages.
N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein
Authors: Wang Chen , Ling Ting , Zhong Ni , Xu Liang-Guo
Published: November 2021

Mitochondrial antiviral signaling protein (MAVS), an adaptor protein, is activated by RIG-I, which is critical for an effective innate immune response to infection by various RNA viruses. Viral infection causes the RIG-I-like receptor (RLR) to recognize pathogen-derived dsRNA and then becomes activated to promote prion-like aggregation and activation of MAVS. Subsequently, through the recruitment of TRAF proteins, MAVS activates two signaling pathways mediated by TBK1-IRF3 and IKK- NF-κb, respectively, and turns on type I interferon and proinflammatory cytokines. This study discovered that NEDD4 binding protein 3 (N4BP3) is a positive regulator of the RLR signaling pathway by targeting MAVS. Overexpression of N4BP3 promoted virus-induced activation of the interferon-β (IFN-β) promoter and interferon-stimulated response element (ISRE). Further experiments showed that knockdown or knockout N4BP3 impaired RIG-I-like receptor (RLR)-mediated innate immune response, induction of downstream antiviral genes, and cellular antiviral responses. We also detected that N4BP3 could accelerate the interaction between MAVS and TRAF2. Related experiments revealed that N4BP3 could facilitate the ubiquitination modification of MAVS. These findings suggest that N4BP3 is a critical component of the RIG-I-like receptor (RLR)-mediated innate immune response by targeting MAVS, which also provided insight into the mechanisms of innate antiviral responses.
Multiple Roles of Peripheral Immune System in Modulating Ischemia/Hypoxia-Induced Neuroinflammation
Authors: Guo Liang , Zhu Lingling
Published: November 2021

Given combined efforts of neuroscience and immunology, increasing evidence has revealed the critical roles of the immune system in regulating homeostasis and disorders of the central nervous system (CNS). Microglia have long been considered as the only immune cell type in parenchyma, while at the interface between CNS and the peripheral (meninges, choroid plexus, and perivascular space), embryonically originated border-associated macrophages (BAMs) and multiple surveilling leukocytes capable of migrating into and out of the brain have been identified to function in the healthy brain. Hypoxia-induced neuroinflammation is the key pathological procedure that can be detected in healthy people at high altitude or in various neurodegenerative diseases, during which a very thin line between a beneficial response of the peripheral immune system in maintaining brain homeostasis and a pathological role in exacerbating neuroinflammation has been revealed. Here, we are going to focus on the role of the peripheral immune system and its crosstalk with CNS in the healthy brain and especially in hypobaric or ischemic hypoxia-associated neuroinflammation.
Glutathione Transferases as Efficient Ketosteroid Isomerases
Authors: Mannervik Bengt , Ismail Aram , Lindström Helena , Sjödin Birgitta , Ing Nancy H.
Published: November 2021

In addition to their well-established role in detoxication, glutathione transferases (GSTs) have other biological functions. We are focusing on the ketosteroid isomerase activity, which appears to contribute to steroid hormone biosynthesis in mammalian tissues. A highly efficient GST A3-3 is present in some, but not all, mammals. The alpha class enzyme GST A3-3 in humans and the horse shows the highest catalytic efficiency with kcat/Km values of approximately 107 M−1s−1, ranking close to the most active enzymes known. The expression of GST A3-3 in steroidogenic tissues suggests that the enzyme has evolved to support the activity of 3β-hydroxysteroid dehydrogenase, which catalyzes the formation of 5-androsten-3,17-dione and 5-pregnen-3,20-dione that are substrates for the double-bond isomerization catalyzed by GST A3-3. The dehydrogenase also catalyzes the isomerization, but its kcat of approximately 1 s−1 is 200-fold lower than the kcat values of human and equine GST A3-3. Inhibition of GST A3-3 in progesterone-producing human cells suppress the formation of the hormone. Glutathione serves as a coenzyme contributing a thiolate as a base in the isomerase mechanism, which also involves the active-site Tyr9 and Arg15. These conserved residues are necessary but not sufficient for the ketosteroid isomerase activity. A proper assortment of H-site residues is crucial to efficient catalysis by forming the cavity binding the hydrophobic substrate. It remains to elucidate why some mammals, such as rats and mice, lack GSTs with the prominent ketosteroid isomerase activity found in certain other species. Remarkably, the fruit fly Drosophila melanogaster, expresses a GSTE14 with notable steroid isomerase activity, even though Ser14 has evolved as the active-site residue corresponding to Tyr9 in the mammalian alpha class.
Neuroimaging Biomarkers Predicting the Efficacy of Multimodal Rehabilitative Intervention in the Alzheimer’s Dementia Continuum Pathology
Authors: Di Tella Sonia , Cabinio Monia , Isernia Sara , Blasi Valeria , Rossetto Federica , Saibene Francesca Lea , Alberoni Margherita , Silveri Maria Caterina , Sorbi Sandro , Clerici Mario , Baglio Francesca
Published: November 2021

In this work we aimed to identify neural predictors of the efficacy of multimodal rehabilitative interventions in AD-continuum patients in the attempt to identify ideal candidates to improve the treatment outcome. Subjects in the AD continuum who participated in a multimodal rehabilitative treatment were included in the analysis [n = 82, 38 Males, mean age = 76 ± 5.30, mean education years = 9.09 ± 3.81, Mini Mental State Examination (MMSE) mean score = 23.31 ± 3.81]. All subjects underwent an MRI acquisition (1.5T) at baseline (T0) and a neuropsychological evaluation before (T0) and after intervention (T1). All subjects underwent an intensive multimodal cognitive rehabilitation (8–10 weeks). The MMSE and Neuropsychiatric Inventory (NPI) scores were considered as the main cognitive and behavioral outcome measures, and Delta change scores (T1–T0) were categorized in Improved (ΔMMSE > 0; ΔNPI < 0) and Not Improved (ΔMMSE ≤ 0; ΔNPI ≥ 0). Logistic Regression (LR) and Random Forest classification models were performed including neural markers (Medial Temporal Brain; Posterior Brain (PB); Frontal Brain (FB), Subcortical Brain indexes), neuropsychological (MMSE, NPI, verbal fluencies), and demographical variables (sex, age, education) at baseline. More than 50% of patients showed a positive effect of the treatment (ΔMMSE > 0: 51%, ΔNPI < 0: 52%). LR model on ΔMMSE (Improved vs. Not Improved) indicate a predictive role for MMSE score (p = 0.003) and PB index (p = 0.005), especially the right PB (p = 0.002) at baseline. The Random Forest analysis correctly classified 77% of cognitively improved and not improved AD patients. Concerning the NPI, LR model on ΔNPI (Improved vs. Not Improved) showed a predictive role of sex (p = 0.002), NPI (p = 0.005), PB index (p = 0.006), and FB index (p = 0.039) at baseline. The Random Forest reported a classification accuracy of 86%. Our data indicate that cognitive and behavioral status alone are not sufficient to identify best responders to a multidomain rehabilitation treatment. Increased neural reserve, especially in the parietal areas, is also relevant for the compensatory mechanisms activated by rehabilitative treatment. These data are relevant to support clinical decision by identifying target patients with high probability of success after rehabilitative programs on cognitive and behavioral functioning.
Cerebral Hemodynamics and Carotid Atherosclerosis in Patients With Subcortical Ischemic Vascular Dementia
Authors: Liu Xiao-Jiao , Che Ping , Xing Mengya , Tian Xiao-Bing , Gao Chunli , Li Xiuyan , Zhang Nan
Published: November 2021

A growing body of evidence indicates that atherosclerosis is correlated with cerebral small vessel disease and contributes to cognitive decline. This study aimed to explore the characteristics and contributions of intracranial hemodynamics and carotid atherosclerosis to cognitive dysfunction in subjects with subcortical ischemic vascular dementia (SIVD). Notably, 44 patients with SIVD, 30 patients with Alzheimer’s disease (AD), and 30 healthy controls (HCs) were recruited from our longitudinal MRI study for AD and SIVD (ChiCTR1900027943). The cerebral mean flow velocity (MFV) and pulsatility index (PI) of both anterior and posterior circulations, artery plaque, and lumen diameter in carotid arteries were investigated using transcranial Doppler and carotid ultrasound, respectively. Their correlations with cognitive function were analyzed in patients with dementia. Decreased MFV and increased PI were found in patients with SIVD and AD. Patients with SIVD showed lower MFV and higher PI in the bilateral posterior cerebral arteries compared to patients with AD. Increases in lumen diameter, number of arteries with plaque, and total carotid plaque score were found in patients with SIVD. The Mini-Mental State Examination score was positively correlated with the MFV and negatively correlated with the PI of most major cerebral arteries, while it was negatively correlated with the lumen diameter of the common carotid artery, number of arteries with plaque, and total carotid plaque score in patients with dementia. There were also correlations between these parameters of some arteries and memory and executive function. Our results provide additional evidence suggesting that the pathological changes in macrovascular structure and function are correlated with cognitive impairment in dementia patients with SIVD and to a lesser extent AD.
Nanocoating Is a New Way for Biofouling Prevention
Authors: Kumar Santosh , Ye Fei , Dobretsov Sergey , Dutta Joydeep
Published: November 2021

Biofouling is a major concern to the maritime industry. Biofouling increases fuel consumption, accelerates corrosion, clogs membranes and pipes, and reduces the buoyancy of marine installations, such as ships, platforms, and nets. While traditionally marine installations are protected by toxic biocidal coatings, due to recent environmental concerns and legislation, novel nanomaterial-based anti-fouling coatings are being developed. Hybrid nanocomposites of organic-inorganic materials give a possibility to combine the characteristics of both groups of material generating opportunities to prevent biofouling. The development of bio-inspired surface designs, progress in polymer science and advances in nanotechnology is significantly contributing to the development of eco-friendly marine coatings containing photocatalytic nanomaterials. The review mainly discusses photocatalysis, antifouling activity, and formulation of coatings using metal and metal oxide nanomaterials (nanoparticles, nanowires, nanorods). Additionally, applications of nanocomposite coatings for inhibition of micro- and macro-fouling in marine environments are reviewed.
Specific Posture-Stabilising Effects of Vision and Touch Are Revealed by Distinct Changes of Body Oscillation Frequencies
Authors: Sozzi Stefania , Nardone Antonio , Schieppati Marco
Published: November 2021

We addressed postural instability during stance with eyes closed (EC) on a compliant surface in healthy young people. Spectral analysis of the centre of foot pressure oscillations was used to identify the effects of haptic information (light-touch, EC-LT), or vision (eyes open, EO), or both (EO-LT). Spectral median frequency was strongly reduced by EO and EO-LT, while spectral amplitude was reduced by all “stabilising” sensory conditions. Reduction in spectrum level by EO mainly appeared in the high-frequency range. Reduction by LT was much larger than that induced by the vision in the low-frequency range, less so in the high-frequency range. Touch and vision together produced a fall in spectral amplitude across all windows, more so in anteroposterior (AP) direction. Lowermost frequencies contributed poorly to geometric measures (sway path and area) for all sensory conditions. The same subjects participated in control experiments on a solid base of support. Median frequency and amplitude of the spectrum and geometric measures were largely smaller when standing on solid than on foam base but poorly affected by the sensory conditions. Frequency analysis but not geometric measures allowed to disclose unique tuning of the postural control mode by haptic and visual information. During standing on foam, the vision did not reduce low-frequency oscillations, while touch diminished the entire spectrum, except for the medium-high frequencies, as if sway reduction by touch would rely on rapid balance corrections. The combination of frequency analysis with sensory conditions is a promising approach to explore altered postural mechanisms and prospective interventions in subjects with central or peripheral nervous system disorders.
Case Report: Take a Second Look: Covid-19 Vaccination-Related Cerebral Venous Thrombosis and Thrombotic Thrombocytopenia Syndrome
Authors: Braun Tobias , Viard Maxime , Juenemann Martin , Struffert Tobias , Schwarm Frank , Huttner Hagen B. , Roessler Florian C.
Published: November 2021

We present two cases of ChAdOx1 nCov-19 (AstraZeneca)-associated thrombotic thrombocytopenia syndrome (TTS) and cerebral venous sinus thrombosis (CVST). At the time of emergency room presentation due to persistent headache, blood serum levels revealed reduced platelet counts. Yet, 1 or 4 days after the onset of the symptom, the first MR-angiography provided no evidence of CVST. Follow-up imaging, performed upon headache refractory to nonsteroidal pain medication verified CVST 2–10 days after initial negative MRI. Both the patients received combined treatment with intravenous immunoglobulins and parenteral anticoagulation leading to an increase of platelet concentration in both the individuals and resolution of the occluded cerebral sinus in one patient.
The Association of Olfactory Dysfunction With Depression, Cognition, and Disease Severity in Parkinson's Disease
Authors: Fang Ting-Chun , Chang Ming-Hong , Yang Chun-Pai , Chen Yi-Huei , Lin Ching-Heng
Published: November 2021

Background: Non-motor subtypes of Parkinson's disease (PD) include the limbic, cognitive, and brainstem phenotype, which may have different pathological pathways with olfaction. In this work, we aim to clarify the association between olfactory dysfunction, depression, cognition, and disease severity in PD.

Methods: A total of 105 PD subjects were included and divided into anosmia and non-anosmic groups, using the University of Pennsylvania Smell Identification Test (UPSIT). All patients were evaluated with the movement disorder society unified Parkinson's disease rating scale (MDS-UPDRS), the Beck depression inventory (BDI)-II, and the Montreal cognitive assessment (MoCA).

Results: The BDI-II and UPSIT scores had a trend of reverse correlation without statistical significance (β-coefficient −0.12, p = 0.232). However, the odds ratio (OR) in anosmia was 2.74 (95% CI 1.01–7.46) for depression and 2.58 (95% CI 1.06–6.29) for cognitive impairment. For the MDS-UPDRS total and Part 3 score, the anosmia had a β-coefficient of 12.26 (95% CI 5.69–18.82) and 8.07 (95% CI 3.46–12.67), respectively. Neither depression nor cognitive impairment is associated with motor symptoms.

Conclusion: More severe olfactory dysfunction in PD is associated with cognitive impairment and greater disease severity. Depression in PD may involve complex pathways, causing relatively weak association with olfactory dysfunction.
Distribution of Immune Cells Including Macrophages in the Human Cochlea
Authors: Liu Wei , Danckwardt-Lillieström Niklas , Schrott-Fischer Anneliese , Glueckert Rudolf , Rask-Andersen Helge
Published: November 2021

Background: The human cochlea was earlier believed to lack capacity to mount specific immune responses. Recent studies established that the human cochlea holds macrophages. The cells appear to surveil, dispose of, and restore wasted cells to maintain tissue integrity. Macrophage activities are believed to be the central elements in immune responses and could swiftly defuse invading microbes that enter via adjacent infection-prone areas. This review updates recent human studies in light of the current literature and adds information about chemokine gene expression.

Materials and Methods: We analyzed surgically obtained human tissue using immunohistochemistry, confocal microscopy, and multichannel super-resolution structured illumination microscopy. The samples were considered representative of steady-state conditions. Antibodies against the ionized calcium-binding adaptor molecule 1 were used to identify the macrophages. CD68 and CD11b, and the major histocompatibility complex type II (MHCII) and CD4 and CD8 were analyzed. The RNAscope technique was used for fractalkine gene localization.

Results: Many macrophages were found around blood vessels in the stria vascularis but not CD4 and CD8 lymphocytes. Amoeboid macrophages were identified in the spiral ganglion with surveilling “antennae” projecting against targeted cells. Synapse-like contacts were seen on spiral ganglion cell bodies richly expressing single CXC3CL gene transcripts. Branching neurite-like processes extended along central and peripheral axons. Active macrophages were occasionally found near degenerating hair cells. Some macrophage-interacting T lymphocytes were observed between the scala tympani wall and Rosenthal's canal. CD4 and CD8 cells were not found in the organ of Corti.

Conclusions: The results indicate that the human cochlea is equipped with macrophages and potentially lymphocytes, suggesting both an innate and adaptive immune capacity. A rich expression of fractalkine gene transcripts in spiral ganglion neurons suggest an essential role for auditory nerve protection, as has been demonstrated experimentally. The findings provide further information on the important role of the immune machinery present in the human inner ear and its potential to carry adverse immune reactions, including cytotoxic and foreign body responses. The results can be used to form a rationale for therapies aiming to modulate these immune activities.
Food Habit Associated Mycobiota Composition and Their Impact on Human Health
Authors: Shankar Jata
Published: November 2021

Mycobiota is not only associated with healthy homeostasis in the human gut but also helps to adapt to the environment. Food habits, alcohol consumption, intake of probiotics, and contaminated food with a mycotoxin, often lead to the alteration in the mycobiota composition. Impaired immunity of the host may affect fungal symbiosis leading to mycosis. The human gut adapts to the commensalism fungi belonging to the phylum Ascomycota and Basidiomycota. Diet habits such as plant-or animal-based, phytoestrogens enriched plant products, fat-rich diets also influence the colonization of certain fungal species in the mammalian gut. Food habits or mycotoxin-contaminated food or fungal peptides have an impact on bacterial-fungal interaction and human health. The mycobiota population such as Fusarium, Humicola, Aspergillus, and Candida are altered due to alcohol intake in alcoholic liver disease. The role of associated gut mycobiota due to irregular bowel habits or lifestyle change has been observed in inflammatory bowel disease. In this review, it has been observed that Saccharomyces, Aspergillus, Fusarium, Cladosporium, Candida, and Malassezia were the common genus in the human mycobiota. Therefore, this study focused on how diet habits and alcohol intake, among others., influence mycobiota composition that may affect the human immune system or overall health.
Radiomics for the Prediction of Epilepsy in Patients With Frontal Glioma
Authors: Gao Ankang , Yang Hongxi , Wang Yida , Zhao Guohua , Wang Chenglong , Wang Haijie , Zhang Xiaonan , Zhang Yong , Cheng Jingliang , Yang Guang , Bai Jie
Published: November 2021

Objective

This study was conducted in order to investigate the association between radiomics features and frontal glioma-associated epilepsy (GAE) and propose a reliable radiomics-based model to predict frontal GAE.

Methods

This retrospective study consecutively enrolled 166 adult patients with frontal glioma (111 in the training cohort and 55 in the testing cohort). A total 1,130 features were extracted from T2 fluid-attenuated inversion recovery images, including first-order statistics, 3D shape, texture, and wavelet features. Regions of interest, including the entire tumor and peritumoral edema, were drawn manually. Pearson correlation coefficient, 10-fold cross-validation, area under curve (AUC) analysis, and support vector machine were adopted to select the most relevant features to build a clinical model, a radiomics model, and a clinical–radiomics model for GAE. The receiver operating characteristic curve (ROC) and AUC were used to evaluate the classification performance of the models in each cohort, and DeLong’s test was used to compare the performance of the models. A two-sided t-test and Fisher’s exact test were used to compare the clinical variables. Statistical analysis was performed using SPSS software (version 22.0; IBM, Armonk, New York), and p <0.05 was set as the threshold for significance.

Results

The classification accuracy of seven scout models, except the wavelet first-order model (0.793) and the wavelet texture model (0.784), was <0.75 in cross-validation. The clinical–radiomics model, including 17 magnetic resonance imaging-based features selected among the 1,130 radiomics features and two clinical features (patient age and tumor grade), achieved better discriminative performance for GAE prediction in both the training [AUC = 0.886, 95% confidence interval (CI) = 0.819–0.940] and testing cohorts (AUC = 0.836, 95% CI = 0.707–0.937) than the radiomics model (p = 0.008) with 82.0% and 78.2% accuracy, respectively.

Conclusion

Radiomics analysis can non-invasively predict GAE, thus allowing adequate treatment of frontal glioma. The clinical–radiomics model may enable a more precise prediction of frontal GAE. Furthermore, age and pathology grade are important risk factors for GAE.
Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells
Authors: He Yanyan , Duan Lin , Wu Haigang , Chen Song , Lu Taoyuan , Li Tianxiao , He Yingkun
Published: November 2021

Blood vessels in the brain tissue form a compact vessel structure and play an essential role in maintaining the homeostasis of the neurovascular system. The low dosage of photodynamic intervention (PDT) significantly affects the expression of cellular biomarkers. To understand the impact of photodynamic interventions on cerebrovascular endothelial cells, we evaluated the dosage-dependent impact of porfimer sodium-mediated PDT on B.END3 cells using flow cytometer, comet assay, RNA sequencing, and bioinformatics analysis. To examine whether PDT can induce disorder of intracellular organelles, we did not observe any significance damage of DNA and cellular skeleton. Moreover, expression levels of cellular transporters-related genes were significantly altered, implying the drawbacks of PDT on cerebrovascular functions. To address the potential molecular mechanisms of these phenotypes, RNA sequencing and bioinformatics analysis were employed to identify critical genes and pathways among these processes. The gene ontology (GO) analysis and protein-protein interaction (PPI) identified 15 hub genes, highly associated with cellular mitosis process (CDK1, CDC20, MCM5, MCM7, MCM4, CCNA2, AURKB, KIF2C, ESPL1, BUB1B) and DNA replication (POLE2, PLOE, CDC45, CDC6). Gene set enrichment analysis (GSEA) reveals that TNF-α/NF-κB and KRAS pathways may play a critical role in regulating expression levels of transporter-related genes. To further perform qRT-PCR assays, we find that TNF-α/NF-κB and KRAS pathways were substantially up-regulated, consistent with GSEA analysis. The current findings suggested that a low dosage of PDT intervention may be detrimental to the homeostasis of blood-brain barrier (BBB) by inducing the inflammatory response and affecting the expression of surface biomarkers.
Surgical Treatment and Clinical Outcomes of Petroclival Meningiomas: A Single-Center Experience of 107 Patients
Authors: Gao Baocheng , Zhang Yongfa , Tan Jiang , Ouyang Jinsong , Tai Bai , Cao Xianbao , Li Tao , Hu Shuang
Published: November 2021

Objective

This study aimed to establish optimal surgical strategies via reviewing the clinical outcomes of various surgical approaches for the pertroclival meningiomas (PCMs).

Methods

This retrospective study enrolled 107 patients with PCMs at the authors’ institution from year 2010 to 2020. Patient demographics, the clinical characteristics, various operative approaches, major morbidity, post-operative cranial nerve deficits and tumor progression or recurrence were analyzed.

Results

The subtemporal transtentorial approach (STA), the Kawase approach (KA), the retrosigmoid approach (RSA) and the anterior sigmoid approach (ASA), namely the posterior petrosal approach (PPA) were adopted for 17 cases, 22 cases, 31 cases and 34 cases respectively. Total or subtotal resection was achieved in 96 cases (89.7%). The incidence of new-onset and aggravated cranial nerve dysfunction were 13.1% (14/107) and 10.4% (15/144), respectively. Furthermore, 14 cases suffered from intracranial infection, 9 cases had cerebrospinal fluid leakage, and 3 cases sustained intracranial hematoma (1 case underwent second operation). The mean preoperative and postoperative Karnofsky Performance Status (KPS) score was 80 (range 60-100) and 78.6 (range 0-100), but this was not statistically significant (P>0.05). After a mean follow-up of 5.1 years (range 0.3- 10.6 years), tumor progression or recurrence was confirmed in 23 cases. Two cases died from postoperative complications.

Conclusions

For the treatment of PCMs, it is still a challenge to achieve total resection. With elaborate surgical plans and advanced microsurgical skills, most patients with PCMs can be rendered tumor resection with satisfactory extent and functional preservation, despite transient neurological deterioration during early postoperative periods.
Positive Reciprocal Feedback of lncRNA ZEB1-AS1 and HIF-1α Contributes to Hypoxia-Promoted Tumorigenesis and Metastasis of Pancreatic Cancer
Authors: Jin Yan , Zhang Zhengming , Yu Qiao , Zeng Zhu , Song Hong , Huang Xiaoxu , Kong Qi , Hu Hao , Xia Yabin
Published: November 2021

Background

Many studies have reported the roles of the extracellular hypoxia microenvironment in the tumorigenesis and metastasis of multiple cancers. However, long noncoding RNAs (lncRNAs) that induce cancer oncogenicity and metastasis of pancreatic cancer (PC) under hypoxia conditions remain unclear.

Methods

In PC cells, the expression levels of lncRNAs in different conditions (normoxia or hypoxia) were compared through RNA sequencing (RNA-seq). The effects of the zinc finger E-box-binding homeobox 1 (ZEB1-AS1) antisense lncRNA on PC cells cultured in normoxia/hypoxia medium were measured through gain and loss-of-function experiments. Fluorescence in situ hybridization and luciferase reporter assays in addition to in vivo studies were utilized to explore the adaptive mechanisms of ZEB1-AS1 in the hypoxia-promoted proliferation, migration, and invasion ability of PC cells. Moreover, the level of ZEB1-AS1 and its associated targets or pathways were investigated in both PC and pancreatic normal tissues.

Results

RNA-seq revealed that ZEB1-AS1 was significantly upregulated in PC cells under hypoxia conditions. The ZEB1-AS1 expression level was closely associated with poor prognosis of PC patients. Knockdown of ZEB1-AS1 suppressed the proliferation, migration, and invasion of PC cells in vitro as well as PC xenograft tumor growth in vivo. In PC cells, RNAi-mediated reduction of ZEB1-AS1 inhibited zinc finger E-box-binding homeobox 1 (ZEB1), while ZEB1-AS1 overexpression rescued ZEB1 expression, indicating that ZEB1-AS1 promotes ZEB1 expression. Moreover, hypoxia-inducible factor-1α (HIF-1α)induced the expression of ZEB1-AS1 by binding to the ZEB1-AS1 promoter, which contains a putative hypoxia response element (HRE). Mechanistically, ZEB1-AS1 scaffolded the interaction among HIF-1α, ZEB1, and histone deacetylase 1 (HDAC1), leading to deacetylation-mediated stabilization of HIF-1α. We further revealed that ZEB1 induced the deacetylase capacity of HDAC1 to suppress the acetylation or degradation of HIF-1α, improving HIF-1α assembly. Thus, hypoxia-induced ZEB1-AS1 facilitated ZEB1 transcription and the stability of HIF-1α, which promoted the metastasis of PC cells. Clinically, dysregulated ZEB1 and HIF-1α expression was significantly correlated with histological grade, lymphatic metastasis, and distant metastasis in PC patients.

Conclusions

Our results emphasized that the positive reciprocal loop of HIF-1α/ZEB1-AS1/ZEB1/HDAC1 contributes to hypoxia-promoted oncogenicity and PC metastasis, indicating that it might be a novel therapeutic target for PC.
Managing Severe Dysgeusia and Dysosmia in Lung Cancer Patients: A Systematic Scoping Review
Authors: Spencer Ana Sofia , da Silva Dias David , Capelas Manuel Luís , Pimentel Francisco , Santos Teresa , Neves Pedro Miguel , Mäkitie Antti , Ravasco Paula
Published: November 2021

Introduction

Lung cancer (LC) is highly prevalent worldwide, with elevated mortality. In this population, taste and smell alterations (TSAs) are frequent but overlooked symptoms. The absence of effective therapeutic strategies and evidence-based guidelines constrain TSAs’ early recognition, prevention and treatment (Tx), promoting cancer-related malnutrition and jeopardizing survival outcomes and quality of life.

Objectives

To systematically review the literature on TSAs in LC patients, understand the physiopathology, identify potential preventive and Tx strategies and to further encourage research in this area.

Methods

Literature search on English language articles indexed to PubMed, CINALH, SCOPUS and Web of Science using MeSH terms “Lung neoplasms”,”Dysgeusia”, “Olfaction Disorders”, “Carcinoma, Small Cell”,”Carcinoma, Non- Small-Cell Lung “Adenocarcinoma of Lung”,”Carcinoma, Large Cell”, and non-MeSH terms “Parageusia”, “Altered Taste”, “Smell Disorder”, “Paraosmia”, “Dysosmia”,”Lung Cancer” and “Oat Cell Carcinoma”.

Results

Thirty-four articles were reviewed. TSAs may follow the diagnosis of LC or develop during cancer Tx. The estimated prevalence of self-reported dysgeusia is 35-38% in treatment-naïve LC patients, and 35-69% in those undergoing Tx, based on studies involving LC patients only.

One prospective pilot trial and 1 RCT demonstrated a clinically significant benefit in combining flavor enhancement, smell and taste training and individualized nutritional counselling; a systematic review, 1 RCT and 1 retrospective study favored using intravenous or oral zinc-based solutions (150mg 2-3 times a day) for the prevention and Tx of chemotherapy (CT) and radiotherapy (RT) -induced mucositis and subsequent dysgeusia.

Conclusions

This is the first review on dysgeusia and dysosmia in LC patients to our knowledge. We propose combining taste and smell training, personalized dietary counselling and flavor enhancement with oral zinc-based solutions (150mg, 2-3 times a day) during CT and/or RT in this population, in order to prevent and help ameliorate Tx-induced dysgeusia and mucositis. However due to study heterogeneity, the results should be interpreted with caution. Developing standardized TSA measurement tools and performing prospective randomized controlled trials to evaluate their effect are warranted.
Prognostic Value of Preoperative Peak Expiratory Flow to Predict Postoperative Pulmonary Complications in Surgical Lung Cancer Patients
Authors: Chang Shuai , Zhou Kun , Wang Yan , Lai Yutian , Che Guowei
Published: November 2021

Objectives

Cough impairment may lead to excessive accumulation of pulmonary secretions and increase the risk of postoperative pulmonary complications (PPCs). Peak expiratory flow (PEF) is a sensitive indicator of cough ability. We aimed to investigate the correlation between PEF and PPCs for lung cancer patients undergoing lobectomy or segmental resection for improved risk assessment.

Methods

This retrospective study assessed 560 patients with non-small cell lung cancer admitted for surgery between January 2014 to June 2016. The measurements of PEF were performed before surgery and the clinical outcomes were recorded, including PPCs, postoperative hospital stay, hospitalization costs, and other variables.

Results

Preoperative PEF was significantly lower in PPCs group compared to non-PPCs group (294.2 ± 95.7 vs. 363.0 ± 105.6 L/min, P < 0.001). Multivariable regression analysis showed that high PEF (OR=0.991, 95%CI: 0.988-0.993, P < 0.001) was an independent protective factor for PPCs. According to the receiver operating characteristic (ROC) curve, a PEF value of 250 L/min was selected as the optimal cutoff value in female patients, and 320 L/min in male patients. Patients with PEF under cutoff value of either sex had higher PPCs rate and unfavorable clinical outcomes.

Conclusions

Preoperative PEF was found to be a significant predictor of PPCs for surgical lung cancer patients. It may be beneficial to consider the cutoff value of PEF in perioperative risk assessment.
Acetylation in Tumor Immune Evasion Regulation
Authors: Lu Jun , He Xiang , Zhang Lijuan , Zhang Ran , Li Wenzheng
Published: November 2021

Acetylation is considered as one of the most common types of epigenetic modifications, and aberrant histone acetylation modifications are associated with the pathological process of cancer through the regulation of oncogenes and tumor suppressors. Recent studies have shown that immune system function and tumor immunity can also be affected by acetylation modifications. A comprehensive understanding of the role of acetylation function in cancer is essential, which may help to develop new therapies to improve the prognosis of cancer patients. In this review, we mainly discussed the functions of acetylase and deacetylase in tumor, immune system and tumor immunity, and listed the information of drugs targeting these enzymes in tumor immunotherapy.
Multi-Omics Comparison of the Spontaneous Diabetes Mellitus and Diet-Induced Prediabetic Macaque Models
Authors: Yang Zhu , Yang Dianqiang , Tan Fancheng , Wong Chi Wai , Yang James Y. , Zhou Da , Cai Zongwei , Lin Shu-Hai
Published: November 2021

The prevalence of diabetes mellitus has been increasing for decades worldwide. To develop safe and potent therapeutics, animal models contribute a lot to the studies of the mechanisms underlying its pathogenesis. Dietary induction using is a well-accepted protocol in generating insulin resistance and diabetes models. In the present study, we reported the multi-omics profiling of the liver and sera from both peripheral blood and hepatic portal vein blood from Macaca fascicularis that spontaneously developed Type-2 diabetes mellitus with a chow diet (sDM). The other two groups of the monkeys fed with chow diet and high-fat high-sugar (HFHS) diet, respectively, were included for comparison. Analyses of various omics datasets revealed the alterations of high consistency. Between the sDM and HFHS monkeys, both the similar and unique alterations in the lipid metabolism have been demonstrated from metabolomic, transcriptomic, and proteomic data repeatedly. The comparison of the proteome and transcriptome confirmed the involvement of fatty acid binding protein 4 (FABP4) in the diet-induced pathogenesis of diabetes in macaques. Furthermore, the commonly changed genes between spontaneous diabetes and HFHS diet-induced prediabetes suggested that the alterations in the intra- and extracellular structural proteins and cell migration in the liver might mediate the HFHS diet induction of diabetes mellitus.
Reduced Regional Cerebral Blood Flow Measured by 99mTc-Hexamethyl Propylene Amine Oxime Single-Photon Emission Computed Tomography in Microgravity Simulated by 5-Day Dry Immersion
Authors: Guillon Laurent , Kermorgant Marc , Charvolin Thomas , Bonneville Fabrice , Bareille Marie-Pierre , Cassol Emmanuelle , Beck Arnaud , Beaurain Marie , Péran Patrice , Lotterie Jean-Albert , Traon Anne Pavy-Le , Payoux Pierre
Published: November 2021

Microgravity induces a cephalad fluid shift that is responsible for cephalic venous stasis that may increase intracranial pressure (ICP) in astronauts. However, the effects of microgravity on regional cerebral blood flow (rCBF) are not known. We therefore investigated changes in rCBF in a 5-day dry immersion (DI) model. Moreover, we tested thigh cuffs as a countermeasure to prevent potential microgravity-induced modifications in rCBF. Around 18 healthy male participants underwent 5-day DI with or without a thigh cuffs countermeasure. They were randomly allocated to a control (n=9) or cuffs (n=9) group. rCBF was measured 4days before DI and at the end of the fifth day of DI (DI5), using single-photon emission computed tomography (SPECT) with radiopharmaceutical 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO). SPECT images were processed using statistical parametric mapping (SPM12) software. At DI5, we observed a significant decrease in rCBF in 32 cortical and subcortical regions, with greater hypoperfusion in basal ganglia (right putamen peak level: z=4.71, puncorr<0.001), bilateral occipital regions (left superior occipital peak level: z=4.51, puncorr<0.001), bilateral insula (right insula peak level: 4.10, puncorr<0.001), and bilateral inferior temporal (right inferior temporal peak level: 4.07, puncorr<0.001). No significant difference was found between the control and cuffs groups on change in rCBF after 5days of DI. After a 5-day DI, we found a decrease in rCBF in cortical and subcortical regions. However, thigh cuffs countermeasure failed to prevent hypoperfusion. To date, this is the first study measuring rCBF in DI. Further investigations are needed in order to better understand the underlying mechanisms in cerebral blood flow (CBF) changes after exposure to microgravity.
Study on Flow Velocity Distribution in Open Channel With Flexible Vegetation
Authors: Wang Shiyu , Zhou Yi , Li Tongshu , Li Song , Zhang Mingwu , Han Yu
Published: November 2021

Ecological management of river channels is a hot topic for current sustainable development and flow measurement of ecological river is an important part. In this article, a flow velocity distribution model of the channel containing flexible vegetation is constructed from the vegetation riverbed theory and the bursting phenomenon to reveal the microscopic mechanism of the flow velocity distribution in the upper layer of vegetation. In the vegetation riverbed law, the effect of flexible vegetation is evaluated by the mixed length formula. The bursting phenomenon law considers the influence of the channel sidewalls on the flow and a two-dimensional velocity model is established by introducing the concept of average turbulence structure. The mechanism of the downward shift of the maximum flow velocity point on the channel sidewall is explained. The verification of the calculated velocity profiles is carried out based on data obtained in laboratory experiments. The results show that the combination of the two models can well describe the velocity distribution of the whole channel. At the end, the phenomenon of flow velocity zoning in open channel is discussed, which provides a solution for flow measurement in ecological channel.
From Self-Esteem to Selflessness: An Evidence (Gap) Map of Self-Related Processes as Mechanisms of Mindfulness-Based Interventions
Authors: Britton Willoughby B. , Desbordes Gaëlle , Acabchuk Rebecca , Peters Sarah , Lindahl Jared R. , Canby Nicholas K. , Vago David R. , Dumais Travis , Lipsky Jonah , Kimmel Hannah , Sager Lauren , Rahrig Hadley , Cheaito Aya , Acero Pamela , Scharf Jodi , Lazar Sara W. , Schuman-Olivier Zev , Ferrer Rebecca , Moitra Ethan
Published: November 2021

Self-related processes (SRPs) have been theorized as key mechanisms of mindfulness-based interventions (MBIs), but the evidence supporting these theories is currently unclear. This evidence map introduces a comprehensive framework for different types of SRPs, and how they are theorized to function as mechanisms of MBIs (target identification). The evidence map then assesses SRP target engagement by mindfulness training and the relationship between target engagement and outcomes (target validation). Discussion of the measurement of SRPs is also included. The most common SRPs measured and engaged by standard MBIs represented valenced evaluations of self-concept, including rumination, self-compassion, self-efficacy, and self-esteem. Rumination showed the strongest evidence as a mechanism for depression, with other physical and mental health outcomes also supported. Self-compassion showed consistent target engagement but was inconsistently related to improved outcomes. Decentering and interoception are emerging potential mechanisms, but their construct validity and different subcomponents are still in development. While some embodied self-specifying processes are being measured in cross-sectional and meditation induction studies, very few have been assessed in MBIs. The SRPs with the strongest mechanistic support represent positive and negative evaluations of self-concept. In sum, few SRPs have been measured in MBIs, and additional research using well-validated measures is needed to clarify their role as mechanisms.