bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA-Sequencing in Resistant (QL3) and Susceptible (Theis) Sorghum Cultivars Inoculated With Johnsongrass Isolates of Colletotrichum sublineola
Authors: Natarajan Purushothaman , Ahn Ezekiel , Reddy Umesh K. , Perumal Ramasamy , Prom Louis K. , Magill Clint
Published: August 2021

Gene expression was analyzed at 0- and 24-h post-inoculation of two inbred sorghum cultivars known to differ in response to inoculation with Colletotrichum sublineola, the fungal pathogen that causes anthracnose. QL3 is reported to have quantitative resistance, while Theis is susceptible to most pathotypes of the pathogen; RNASeq identified over 3,000 specific genes in both cultivars as showing significant changes in expression following inoculation; in all but one gene, the changes in QL3 and Thies were in the same direction. Many other genes showed significant changes in only one of the two cultivars. Overall, more genes were downregulated than upregulated. Differences in changes in expression levels of a few genes suggested potential roles for the difference in disease response between QL3 and Theis, but did not identify known resistance genes. Gene ontology (GO) and pathway enrichment analysis identified upregulation of 23 transcription factor encoding genes as well as genes involved in the production of secondary metabolites, which are part of a typical host defense reaction.
Clinical Efficacy and Safety of Eculizumab for Treating Myasthenia Gravis
Authors: Xiao Hai , Wu Ka , Liang Xiaoliu , Li Rong , Lai Keng Po
Published: August 2021

Myasthenia gravis (MG) is an autoimmune disease primarily mediated by acetylcholine receptor antibodies (AChR-Ab), cellular immune dependence, and complement system involvement. Since the AChR on the postsynaptic membrane is destroyed by an immune attack, sufficient endplate potential cannot be generated, resulting in the development of a synaptic transmission disorder at the neuromuscular junction and in muscle weakness. The role of the complement system in MG has been demonstrated in animal models and clinical tests, and it has been determined that complement inhibition in patients with MG can prevent disease induction and reverse its progression. Eculizumab is a humanized monoclonal antibody that inhibits the cleavage of complement protein C5 and prevents autoimmune damage; additionally, it has received subsequent approval by the Federal Drug Administration of the United States for MG treatment. However, various concerns regarding the use of eculizumab persist. In this review, we have discussed the treatment time, cost effectiveness, long-term efficacy, and tolerability of eculizumab for MG treatment. We have also summarized historical information and have presented perspectives on this new therapeutic modality.
Hijacking of the Host’s Immune Surveillance Radars by Burkholderia pseudomallei
Authors: Mariappan Vanitha , Vellasamy Kumutha Malar , Barathan Muttiah , Girija A. S. Smiline , Shankar Esaki M. , Vadivelu Jamuna
Published: August 2021

Burkholderia pseudomallei (B. pseudomallei) causes melioidosis, a potentially fatal disease for which no licensed vaccine is available thus far. The host-pathogen interactions in B. pseudomallei infection largely remain the tip of the iceberg. The pathological manifestations are protean ranging from acute to chronic involving one or more visceral organs leading to septic shock, especially in individuals with underlying conditions similar to COVID-19. Pathogenesis is attributed to the intracellular ability of the bacterium to ‘step into’ the host cell’s cytoplasm from the endocytotic vacuole, where it appears to polymerize actin filaments to spread across cells in the closer vicinity. B. pseudomallei effectively evades the host’s surveillance armory to remain latent for prolonged duration also causing relapses despite antimicrobial therapy. Therefore, eradication of intracellular B. pseudomallei is highly dependent on robust cellular immune responses. However, it remains ambiguous why certain individuals in endemic areas experience asymptomatic seroconversion, whereas others succumb to sepsis-associated sequelae. Here, we propose key insights on how the host’s surveillance radars get commandeered by B. pseudomallei.
Hypoxia Promotes a Mixed Inflammatory-Fibrotic Macrophages Phenotype in Active Sarcoidosis
Authors: Jeny Florence , Bernaudin Jean-François , Valeyre Dominique , Kambouchner Marianne , Pretolani Marina , Nunes Hilario , Planès Carole , Besnard Valérie
Published: August 2021

Background

Macrophages are pivotal cells in sarcoidosis. Monocytes-derived (MD) macrophages have recently been demonstrated to play a major role especially in pulmonary sarcoidosis. From inflammatory tissues to granulomas, they may be exposed to low oxygen tension environments. As hypoxia impact on sarcoidosis immune cells has never been addressed, we designed the present study to investigate MD-macrophages from sarcoidosis patients in this context. We hypothesized that hypoxia may induce functional changes on MD-macrophages which could have a potential impact on the course of sarcoidosis.

Methods

We studied MD-macrophages, from high active sarcoidosis (AS) (n=26), low active or inactive sarcoidosis (IS) (n=24) and healthy controls (n=34) exposed 24 hours to normoxia (21% O2) or hypoxia (1.5% O2). Different macrophage functions were explored: hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-kappa B (NF-κB) activation, cytokines secretion, phagocytosis, CD80/CD86/HLA-DR expression, profibrotic response.

Results

We observed that hypoxia, with a significantly more pronounced effect in AS compared with controls and IS, increased the HIF-1α trans-activity, promoted a proinflammatory response (TNFα, IL1ß) without activating NF-κB pathway and a profibrotic response (TGFß1, PDGF-BB) with PAI-1 secretion associated with human lung fibroblast migration inhibition. These results were confirmed by immunodetection of HIF-1α and PAI-1 in granulomas observed in pulmonary biopsies from patients with sarcoidosis. Hypoxia also decreased the expression of CD80/CD86 and HLA-DR on MD-macrophages in the three groups while it did not impair phagocytosis and the expression of CD36 expression on cells in AS and IS at variance with controls.

Conclusions

Hypoxia had a significant impact on MD-macrophages from sarcoidosis patients, with the strongest effect seen in patients with high active disease. Therefore, hypoxia could play a significant role in sarcoidosis pathogenesis by increasing the macrophage proinflammatory response, maintaining phagocytosis and reducing antigen presentation, leading to a deficient T cell response. In addition, hypoxia could favor fibrosis by promoting profibrotic cytokines response and by sequestering fibroblasts in the vicinity of granulomas.
Delayed-Mode Quality Control of Oxygen, Nitrate, and pH Data on SOCCOM Biogeochemical Profiling Floats
Authors: Maurer Tanya L. , Plant Joshua N. , Johnson Kenneth S.
Published: August 2021

The Southern Ocean Carbon and Climate Observations and Modeling (SOCCOM) project has deployed 194 profiling floats equipped with biogeochemical (BGC) sensors, making it one of the largest contributors to global BGC-Argo. Post-deployment quality control (QC) of float-based oxygen, nitrate, and pH data is a crucial step in the processing and dissemination of such data, as in situ chemical sensors remain in early stages of development. In situ calibration of chemical sensors on profiling floats using atmospheric reanalysis and empirical algorithms can bring accuracy to within 3 μmol O2 kg–1, 0.5 μmol NO3– kg–1, and 0.007 pH units. Routine QC efforts utilizing these methods can be conducted manually through visual inspection of data to assess sensor drifts and offsets, but more automated processes are preferred to support the growing number of BGC floats and reduce subjectivity among delayed-mode operators. Here we present a methodology and accompanying software designed to easily visualize float data against select reference datasets and assess QC adjustments within a quantitative framework. The software is intended for global use and has been used successfully in the post-deployment calibration and QC of over 250 BGC floats, including all floats within the SOCCOM array. Results from validation of the proposed methodology are also presented which help to verify the quality of the data adjustments through time.
Liquid Inclusion Collision and Agglomeration in Calcium-Treated Aluminum-Killed Steel
Authors: Ferreira Mauro E. , Pistorius Petrus Christiaan , Fruehan Richard J.
Published: August 2021

This work addresses conflicting results in the literature regarding liquid inclusion agglomeration. To assess whether liquid calcium aluminates do agglomerate in liquid steel, laboratory experiments were performed: melting electrolytic iron, deoxidizing the melt with aluminum and subsequently calcium treating the deoxidation products (alumina and magnesia-alumina spinel inclusions). Under laboratory conditions, solid spinels and alumina inclusions were successfully modified, producing a new population of much smaller calcium aluminate inclusions. The new population of inclusions forms because the presence of calcium in the liquid steel destabilizes alumina and MgO-alumina inclusions, which then dissolve into the melt. The liquid inclusions exhibited a weak but statistically significant tendency to agglomerate. Laboratory results were assessed in the light of different collision mechanisms. Agglomeration mainly occurs by Stokes and laminar fluid flow collision when no external stirring is imposed. Monte Carlo simulations of collisions agree reasonably well with experimental results. For industrial conditions, where the liquid steel is agitated by argon bubbling and/or electromagnetic stirring, turbulent collisions dominate.
Digital Approaches for a Reliable Early Diagnosis of Psoriatic Arthritis
Authors: Fagni Filippo , Knitza Johannes , Krusche Martin , Kleyer Arnd , Tascilar Koray , Simon David
Published: August 2021

Psoriatic arthritis (PsA) is a chronic inflammatory disease that develops in up to 30% of patients with psoriasis. In the vast majority of cases, cutaneous symptoms precede musculoskeletal complaints. Progression from psoriasis to PsA is characterized by subclinical synovio-entheseal inflammation and often non-specific musculoskeletal symptoms that are frequently unreported or overlooked. With the development of increasingly effective therapies and a broad drug armamentarium, prevention of arthritis development through careful clinical monitoring has become priority. Identifying high-risk psoriasis patients before PsA onset would ensure early diagnosis, increased treatment efficacy, and ultimately better outcomes; ideally, PsA development could even be averted. However, the current model of care for PsA offers only limited possibilities of early intervention. This is attributable to the large pool of patients to be monitored and the limited resources of the health care system in comparison. The use of digital technologies for health (eHealth) could help close this gap in care by enabling faster, more targeted and more streamlined access to rheumatological care for patients with psoriasis. eHealth solutions particularly include telemedicine, mobile technologies, and symptom checkers. Telemedicine enables rheumatological visits and consultations at a distance while mobile technologies can improve monitoring by allowing patients to self-report symptoms and disease-related parameters continuously. Symptom checkers have the potential to direct patients to medical attention at an earlier point of their disease and therefore minimizing diagnostic delay. Overall, these interventions could lead to earlier diagnoses of arthritis, improved monitoring, and better disease control while simultaneously increasing the capacity of referral centers.
microRNAs, the Link Between Dengue Virus and the Host Genome
Authors: Su Yinghua , Lin Ting , Liu Chun , Cheng Cui , Han Xiao , Jiang Xiwen
Published: August 2021

Dengue virus (DENV) is a small envelope virus of Flaviviridae that is mainly transmitted by Aedes aegypti and Aedes albopictus. It can cause dengue fever with mild clinical symptoms or even life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). At present, there are no specific drugs or mature vaccine products to treat DENV. microRNAs (miRNAs) are a class of important non-coding small molecular RNAs that regulate gene expression at the post-transcriptional level. It is involved in and regulates a series of important life processes, such as growth and development, cell differentiation, cell apoptosis, anti-virus, and anti-tumor. miRNAs also play important roles in interactions between host and viral genome transcriptomes. Host miRNAs can directly target the genome of the virus or regulate host factors to promote or inhibit virus replication. Understanding the expression and function of miRNAs during infection with DENV and the related signal molecules of the miRNA-mediated regulatory network will provide new insights for the development of miRNA-based therapies.
Development, Phenotypic Characterization and Genomic Analysis of a Francisella tularensis Panel for Tularemia Vaccine Testing
Authors: Bachert Beth A. , Richardson Joshua B. , Mlynek Kevin D. , Klimko Christopher P. , Toothman Ronald G. , Fetterer David P. , Luquette Andrea E. , Chase Kitty , Storrs Jessica L. , Rogers Ashley K. , Cote Christopher K. , Rozak David A. , Bozue Joel A.
Published: August 2021

Francisella tularensisis one of several biothreat agents for which a licensed vaccine is needed to protect against this pathogen. To aid in the development of a vaccine protective against pneumonic tularemia, we generated and characterized a panel ofF. tularensisisolates that can be used as challenge strains to assess vaccine efficacy. Our panel consists of both historical and contemporary isolates derived from clinical and environmental sources, including human, tick, and rabbit isolates. Whole genome sequencing was performed to assess the genetic diversity in comparison to the reference genomeF. tularensisSchu S4. Average nucleotide identity analysis showed >99% genomic similarity across the strains in our panel, and pan-genome analysis revealed a core genome of 1,707 genes, and an accessory genome of 233 genes. Three of the strains in our panel, FRAN254 (tick-derived), FRAN255 (a type B strain), and FRAN256 (a human isolate) exhibited variation from the other strains. Moreover, we identified several unique mutations within theFrancisellaPathogenicity Island across multiple strains in our panel, revealing unexpected diversity in this region. Notably, FRAN031 (Scherm) completely lacked the second pathogenicity island but retained virulence in mice. In contrast, FRAN037 (Coll) was attenuated in a murine pneumonic tularemia model and had mutations inpdpBandiglAwhich likely led to attenuation. All of the strains, except FRAN037, retained full virulence, indicating their effectiveness as challenge strains for future vaccine testing. Overall, we provide a well-characterized panel of virulentF. tularensisstrains that can be utilized in ongoing efforts to develop an effective vaccine against pneumonic tularemia to ensure protection is achieved across a rangeF. tularensisstrains.
Characteristics of Resting State EEG Power in 80+-Year-Olds of Different Cognitive Status
Authors: Fröhlich Stephanie , Kutz Dieter F. , Müller Katrin , Voelcker-Rehage Claudia
Published: August 2021

Compared with healthy older adults, patients with Alzheimer's disease show decreased alpha and beta power as well as increased delta and theta power during resting state electroencephalography (rsEEG). Findings for mild cognitive impairment (MCI), a stage of increased risk of conversion to dementia, are less conclusive. Cognitive status of 213 non-demented high-agers (mean age, 82.5 years) was classified according to a neuropsychological screening and a cognitive test battery. RsEEG was measured with eyes closed and open, and absolute power in delta, theta, alpha, and beta bands were calculated for nine regions. Results indicate no rsEEG power differences between healthy individuals and those with MCI. There were also no differences present between groups in EEG reactivity, the change in power from eyes closed to eyes open, or the topographical pattern of each frequency band. Overall, EEG reactivity was preserved in 80+-year-olds without dementia, and topographical patterns were described for each frequency band. The application of rsEEG power as a marker for the early detection of dementia might be less conclusive for high-agers.
Serum Proteomics of Older Patients Undergoing Major Cardiac Surgery: Identification of Biomarkers Associated With Postoperative Delirium
Authors: Rhee James , Kuznetsov Alexandra , McKay Tina , Lyons Margaret , Houstis Nicholas , Mekkonen Jennifer , Ethridge Breanna , Ibala Reine , Hahm Eunice , Gitlin Jacob , Guseh J. Sawalla , Kitchen Robert , Rosenzweig Anthony , Shaefi Shahzad , Flaczyk Adam , Qu Jason , Akeju Oluwaseun
Published: August 2021

Background

Postoperative delirium (POD) is an acute altered mental state commonly encountered after cardiac surgery. The pathophysiological mechanisms underlying POD remain unclear. We aimed to identify circulating proteins significantly altered after major cardiac surgery with cardiopulmonary bypass (CPB). We also aimed to enable inferences on associations with POD.

Methods

Serum and whole blood samples were collected before CPB (n= 16 patients;n= 8 with POD) and again from the same patients on postoperative day 1. All patients were clinically evaluated for POD on postoperative days 1–3. An aptamer-based proteomics platform (SOMAscan) was used to quantify serum protein abundance in patients with POD compared with non-POD controls. We also performed a lipopolysaccharide (LPS)-basedin vitrofunctional analysis (TruCulture) on whole blood samples from patients with POD and non-POD controls to approximate surgical stress. Cytokine levels were determined using a Luminex immunoassay.

Results

Cardiac surgery with CPB resulted in a significant (padj< 0.01) change in 48.8% (637 out of 1,305) of proteins detected by SOMAscan. Gene set enrichment showed that the most impacted biological processes involved myeloid cell activation. Specifically, activation and degranulation of neutrophils were the top five highest-scoring processes. Pathway analyses with the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that metabolic enzymes, particularly those of glycolysis, were elevated in serum concentration after surgery. Several proteins were significantly increased postoperatively in patients diagnosed with POD relative to the non-POD controls, with interleukin-6 (IL-6) showing the greatest fold-change. LPS stimulation of whole blood samples confirmed these findings. Linear regression analysis showed a highly significant correlation between Confusion Assessment Method (CAM) scores and CPB-mediated changes in cGMP-inhibited 3′,5′-cyclic phosphodiesterase A (PDE3A).

Conclusions

Cardiac surgery with CPB resulted in inflammasome changes accompanied by unexpected increases in metabolic pathways. In exploratory analyses, we found that POD was associated with changes in the expression level of various proteins, most notably IL-6 and PDE3A. This study and ongoing protein biomarker studies will likely help quantify risk or confirm the diagnosis for POD and increase understanding of its pathophysiological mechanisms.
Coordinating With a Robot Partner Affects Neural Processing Related to Action Monitoring
Authors: Czeszumski Artur , Gert Anna L. , Keshava Ashima , Ghadirzadeh Ali , Kalthoff Tilman , Ehinger Benedikt V. , Tiessen Max , Björkman Mårten , Kragic Danica , König Peter
Published: August 2021

Robots start to play a role in our social landscape, and they are progressively becoming responsive, both physically and socially. It begs the question of how humans react to and interact with robots in a coordinated manner and what the neural underpinnings of such behavior are. This exploratory study aims to understand the differences in human-human and human-robot interactions at a behavioral level and from a neurophysiological perspective. For this purpose, we adapted a collaborative dynamical paradigm from the literature. We asked 12 participants to hold two corners of a tablet while collaboratively guiding a ball around a circular track either with another participant or a robot. In irregular intervals, the ball was perturbed outward creating an artificial error in the behavior, which required corrective measures to return to the circular track again. Concurrently, we recorded electroencephalography (EEG). In the behavioral data, we found an increased velocity and positional error of the ball from the track in the human-human condition vs. human-robot condition. For the EEG data, we computed event-related potentials. We found a significant difference between human and robot partners driven by significant clusters at fronto-central electrodes. The amplitudes were stronger with a robot partner, suggesting a different neural processing. All in all, our exploratory study suggests that coordinating with robots affects action monitoring related processing. In the investigated paradigm, human participants treat errors during human-robot interaction differently from those made during interactions with other humans. These results can improve communication between humans and robot with the use of neural activity in real-time.
Adenylate Cyclase 1 Links Calcium Signaling to CFTR-Dependent Cytosolic Chloride Elevations in Chick Amacrine Cells
Authors: Zhong Li , Gleason Evanna L.
Published: August 2021

The strength and sign of synapses involving ionotropic GABA and glycine receptors are dependent upon the Cl− gradient. We have shown that nitric oxide (NO) elicits the release of Cl− from internal acidic stores in retinal amacrine cells (ACs); temporarily altering the Cl− gradient and the strength or even sign of incoming GABAergic or glycinergic synapses. The underlying mechanism for this effect of NO requires the cystic fibrosis transmembrane regulator (CFTR) but the link between NO and CFTR activation has not been determined. Here, we test the hypothesis that NO-dependent Ca2+ elevations activate the Ca2+-dependent adenylate cyclase 1 (AdC1) leading to activation of protein kinase A (PKA) whose activity is known to open the CFTR channel. Using the reversal potential of GABA-gated currents to monitor cytosolic Cl−, we established the requirement for Ca2+ elevations. Inhibitors of AdC1 suppressed the NO-dependent increases in cytosolic Cl− whereas inhibitors of other AdC subtypes were ineffective suggesting that AdC1 is involved. Inhibition of PKA also suppressed the action of NO. To address the sufficiency of this pathway in linking NO to elevations in cytosolic Cl−, GABA-gated currents were measured under internal and external zero Cl− conditions to isolate the internal Cl− store. Activators of the cAMP pathway were less effective than NO in producing GABA-gated currents. However, coupling the cAMP pathway activators with the release of Ca2+ from stores produced GABA-gated currents indistinguishable from those stimulated with NO. Together, these results demonstrate that cytosolic Ca2+ links NO to the activation of CFTR and the elevation of cytosolic Cl−.
Hemodynamic Versus Anatomic Assessment of Symptomatic Atherosclerotic Middle Cerebral Artery Stenosis: the Relationship Between Pressure Wire Translesional Gradient and Angiographic Lesion Geometry
Authors: Li Long , Yang Bin , Dmytriw Adam A. , Wang Tao , Luo Jichang , Li Yanling , Ma Yan , Chen Jian , Wang Yabing , Gao Peng , Feng Yao , Bai Xuesong , Zhang Xiao , Dong Jia , Yang Renjie , Jiao Liqun , Ling Feng
Published: August 2021

Background: Intracranial cerebral atherosclerosis (ICAS) is a leading etiology of ischemic stroke. The diagnosis and assessment of intracranial stenosis are shifting from anatomic to hemodynamic for better risk stratification. However, the relationships between lesion geometry and translesional pressure gradient have not been clearly elucidated.

Methods: Patients with symptomatic unifocal M1 middle cerebral artery (M1-MCA) stenosis were consecutively recruited. The translesional pressure gradient was measured with a pressure wire and was recorded as both mean distal/proximal pressure ratios (Pd/Pa) and translesional pressure difference (Pa–Pd). Lesion geometry measured on angiography was recorded as diameter stenosis, minimal lumen diameter, and lesion length. The correlations between pressure-derived and angiography-derived indices were then analyzed.

Results: Forty-three patients were analyzed. A negative correlation was found between Pd/Pa and diameter stenosis (r = −0.371; p = 0.014) and between Pa – Pd and minimal lumen diameter (r = −0.507; p = 0.001). A positive correlation was found between Pd/Pa and minimal lumen diameter (r = 0.411; p = 0.006) and between Pa – Pd and diameter stenosis (r = 0.466; p = 0.002).

Conclusions: In a highly selected ICAS subgroup, geometric indices derived from angiography correlate significantly with translesional pressure gradient indices. However, the correlation strength is weak-to-moderate, which implies that anatomic assessment could only partly reflect hemodynamic status. Translesional pressure gradient measured by pressure wire may serve as a more predictive marker of ICAS severity. More factors need to be identified in further studies.
Comparative Study of Multi-Delay Pseudo-Continuous Arterial Spin Labeling Perfusion MRI and CT Perfusion in Ischemic Stroke Disease
Authors: Xu Xi , Tan Zefeng , Fan Meng , Ma Mengjie , Fang Weimin , Liang Jianye , Xiao Zeyu , Shi Changzheng , Luo Liangping
Published: August 2021

With the aging population, stroke has gradually become the leading cause of death and disability among adults. It is necessary to verify whether multi-delay pseudo-continuous arterial spin labeling (pCASL) MRI can be used as a standard neuroimaging protocol in the patients with ischemic stroke. We aimed to investigate the clinical utility of multi-delay pCASL for evaluating cerebral perfusion in ischemic stroke disease. Twenty-one ischemic stroke patients [18 men and 3 women; median age, 62 years (age range, 37–84 years)] were enrolled in this study. All patients underwent examinations, including the multi-delay pCASL protocol (using 6 PLDs between 1,000 and 3,500 ms) and computed tomography perfusion (CTP). The cerebral blood flow (CBF) and arterial transit time (ATT) maps were obtained by the multi-delay pCASL protocol, while CBF and mean transit time (MTT) maps were derived by CTP measurements. Based on the voxel level analysis, Pearson correlation coefficients were used to estimate the associations between the two modalities in the gray matter, white matter, and whole brain of each subject. Moderate to high positive associations between ASL-CBF and CTP-CBF were acquired by voxel-level-wise analysis in the gray matter, white matter, and whole brain of the enrolled patients (all P < 0.005), and the average Pearson correlation coefficients were 0.647, 0.585, and 0.646, respectively. Highly significant positive correlations between ASL-ATT and CTP-MTT were obtained by voxel-level-wise associations in the gray matter, white matter, and whole brain (all P < 0.005), and the average Pearson correlation coefficients were 0.787, 0.707, and 0.799, respectively. In addition, significant associations between ASL and CT perfusion were obtained in the gray, white matter and whole brain, according to the subgroup analyses of patient’s age and disease stage. There is a correlation between perfusion parameters from multi-delay pCASL and CT perfusion imaging in patients with ischemic stroke. Multi-delay pCASL is radiation-free and non-invasive, and could be an alternative method to CT scans for assessing perfusion in ischemic stroke disease.
Brain Volumetric Alterations in Preclinical HIV-Associated Neurocognitive Disorder Using Automatic Brain Quantification and Segmentation Tool
Authors: Li Ruili , Qi Yu , Shi Lin , Wang Wei , Zhang Aidong , Luo Yishan , Kung Wing Kit , Jiao Zengxin , Liu Guangxue , Li Hongjun , Zhang Longjiang
Published: August 2021

Purpose

This study aimed to determine if people living with HIV (PLWH) in preclinical human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), with no clinical symptoms and without decreased daily functioning, suffer from brain volumetric alterations and its patterns.

Method

Fifty-nine male PLWH at the HAND preclinical stage were evaluated, including 19 subjects with asymptomatic neurocognitive impairment (ANI), 17 subjects with cognitive abnormality that does not reach ANI (Not reach ANI), and 23 subjects with cognitive integrity. Moreover, 23 healthy volunteers were set as the seronegative normal controls (NCs). These individuals underwent sagittal three-dimensional T1-weighted imaging (3D T1WI). Quantified data and volumetric measures of brain structures were automatically segmented and extracted using AccuBrain®. In addition, the multiple linear regression analysis was performed to analyze the relationship of volumes of brain structures and clinical variables in preclinical HAND, and the correlations of the brain volume parameters with different cognitive function states were assessed by Pearson’s correlation analysis.

Results

The significant difference was shown in the relative volumes of the ventricular system, bilateral lateral ventricle, thalamus, caudate, and left parietal lobe gray matter between the preclinical HAND and NCs. Furthermore, the relative volumes of the bilateral thalamus in preclinical HAND were negatively correlated with attention/working memory (left: r = −0.271, p = 0.042; right: r = −0.273, p = 0.040). Higher age was associated with increased relative volumes of the bilateral lateral ventricle and ventricular system and reduced relative volumes of the left thalamus and parietal lobe gray matter. The lower CD4+/CD8+ ratio was associated with increased relative volumes of the left lateral ventricle and ventricular system. Longer disease course was associated with increased relative volumes of the bilateral thalamus. No significant difference was found among preclinical HAND subgroups in all indices, and the difference between the individual groups (Not reach ANI and Cognitive integrity groups) and NCs was also insignificant. However, there was a significant difference between ANI and NCs in the relative volumes of the bilateral caudate and lateral ventricle.

Conclusion

Male PLWH at the HAND preclinical stage suffer from brain volumetric alterations. AccuBrain® provides potential value in evaluating HIV-related neurocognitive dysfunction.
Screening of MicroRNA Related to Irradiation Response and the Regulation Mechanism of miRNA-96-5p in Rectal Cancer Cells
Authors: Wu Fengpeng , Wu Bingyue , Zhang Xiaoxiao , Yang Congrong , Zhou Chaoxi , Ren Shuguang , Wang Jun , Yang Yafan , Wang Guiying
Published: August 2021

Neoadjuvant chemoradiotherapy has been widely used in the treatment of locally advanced rectal cancer due to the excellent advantages of irradiation in cancer therapy. Unfortunately, not every patient can benefit from this treatment, therefore, it is of great significance to explore biomarkers that can predict irradiation sensitivity. In this study, we screened microRNAs (miRNAs) which were positively correlated with irradiation resistance and found that miRNA-552 and miRNA-183 families were positively correlated with the irradiation resistance of rectal cancer, and found that high expression of miRNA-96-5p enhanced the irradiation resistance of rectal cancer cells through direct regulation of the GPC3 gene and abnormal activation of the canonical Wnt signal transduction pathway. Based on the radioreactivity results of patient-derived xenograft models, this is the first screening report for radio-resistant biomarkers in rectal cancer. Our results suggest that miRNA-96-5p expression is an important factor affecting the radiation response of colorectal cancer cells.
Antimetastatic Effects of Curcumin in Oral and Gastrointestinal Cancers
Authors: Davoodvandi Amirhossein , Farshadi Marjan , Zare Noushid , Akhlagh Seyed Amirreza , Alipour Nosrani Esmail , Mahjoubin-Tehran Maryam , Kangari Parisa , Sharafi Seyedeh Maryam , Khan Haroon , Aschner Michael , Baniebrahimi Ghazaleh , Mirzaei Hamed
Published: August 2021

Gastrointestinal (GI) cancers are known as frequently occurred solid malignant tumors that can cause the high rate mortality in the world. Metastasis is a significant destructive feature of tumoral cells, which directly correlates with decreased prognosis and survival. Curcumin, which is found in turmeric, has been identified as a potent therapeutic natural bioactive compound (Curcuma longa). It has been traditionally applied for centuries to treat different diseases, and it has shown efficacy for its anticancer properties. Numerous studies have revealed that curcumin inhibits migration and metastasis of GI cancer cells by modulating various genes and proteins, i.e., growth factors, inflammatory cytokines and their receptors, different types of enzymes, caspases, cell adhesion molecules, and cell cycle proteins. Herein, we summarized the antimetastatic effects of curcumin in GI cancers, including pancreatic cancer, gastric cancer, colorectal cancer, oral cancer, and esophageal cancer.
Retinal Inflammation, Oxidative Stress, and Vascular Impairment Is Ablated in Diabetic Mice Receiving XMD8-92 Treatment
Authors: Howell Scott J. , Lee Chieh A. , Batoki Julia C. , Zapadka Thomas E. , Lindstrom Sarah I. , Taylor Brooklyn E. , Taylor Patricia R.
Published: August 2021

The global number of diabetics continues to rise annually. As diabetes progresses, almost all of Type I and more than half of Type II diabetics develop diabetic retinopathy. Diabetic retinopathy is a microvascular disease of the retina, and is the leading cause of blindness in the working-age population worldwide. With such a significant health impact, new drugs are required to halt the blinding threat posed by this visual disorder. The cause of diabetic retinopathy is multifactorial, and an optimal therapeutic would halt inflammation, cease photoreceptor cell dysfunction, and ablate vascular impairment. XMD8-92 is a small molecule inhibitor that blocks inflammatory activity downstream of ERK5 (extracellular signal-related kinase 5) and BRD4 (bromodomain 4). ERK5 elicits inflammation, is increased in Type II diabetics, and plays a pathologic role in diabetic nephropathy, while BRD4 induces retinal inflammation and plays a role in retinal degeneration. Further, we provide evidence that suggests both pERK5 and BRD4 expression are increased in the retinas of our STZ (streptozotocin)-induced diabetic mice. Taken together, we hypothesized that XMD8-92 would be a good therapeutic candidate for diabetic retinopathy, and tested XMD8-92 in a murine model of diabetic retinopathy. In the current study, we developed an in vivo treatment regimen by administering one 100 μL subcutaneous injection of saline containing 20 μM of XMD8-92 weekly, to STZ-induced diabetic mice. XMD8-92 treatments significantly decreased diabetes-mediated retinal inflammation, VEGF production, and oxidative stress. Further, XMD8-92 halted the degradation of ZO-1 (zonula occludens-1), which is a tight junction protein associated with vascular permeability in the retina. Finally, XMD8-92 treatment ablated diabetes-mediated vascular leakage and capillary degeneration, which are the clinical hallmarks of non-proliferative diabetic retinopathy. Taken together, this study provides strong evidence that XMD8-92 could be a potentially novel therapeutic for diabetic retinopathy.
Transcriptome Alterations of an in vitro-Selected, Moderately Resistant, Two-Row Malting Barley in Response to 3ADON, 15ADON, and NIV Chemotypes of Fusarium graminearum
Authors: Tucker James R. , Legge William G. , Maiti Sujit , Hiebert Colin W. , Simsek Senay , Yao Zhen , Xu Wayne , Badea Ana , Fernando W. G. Dilantha
Published: August 2021

Fusarium head blight caused by Fusarium graminearum is a devastating disease of malting barley. Mycotoxins associated with contaminated grain can be transferred from malt to beer and pose a health risk to consumers. In western Canada, F. graminearum has undergone an adaptive shift from 15ADON constituency to dominance by virulent 3ADON-producers; likewise, NIV-producers have established in regions of southern United States. Lack of adapted resistance sources with adequate malting quality has promoted the use of alternative breeding methodologies, such as in vitro selection. We studied the low-deoxynivalenol characteristic of in vitro selected, two-row malting barley variety “Norman” by RNAseq in contrast to its parental line “CDC Kendall,” when infected by 15ADON-, 3ADON-, and NIV-producing isolates of F. graminearum. The current study documents higher mycotoxin accumulation by 3ADON isolates, thereby representing increased threat to barley production. At 72–96-h post infection, significant alterations in transcription patterns were observed in both varieties with pronounced upregulation of the phenylpropanoid pathway and detoxification gene categories (UGT, GST, CyP450, and ABC), particularly in 3ADON treatment. Defense response was multitiered, where differential expression in “Norman” associated with antimicrobial peptides (thionin 2.1, defensing, non-specific lipid-transfer protein) and stress-related proteins, such as late embryogenesis abundant proteins, heat-shock, desiccation related, and a peroxidase (HvPrx5). Several gene targets identified in “Norman” would be useful for application of breeding varieties with reduced deoxynivalenol content.
Identifying Methamphetamine Abstainers With Convolutional Neural Networks and Short-Time Fourier Transform
Authors: Lai Xin , Huang Qiuping , Xin Jiang , Yu Hufei , Wen Jingxi , Huang Shucai , Zhang Hao , Shen Hongxian , Tang Yan
Published: August 2021

Few studies have investigated the functional patterns of methamphetamine abstainers. A better understanding of the underlying neurobiological mechanism in the brains of methamphetamine abstainers will help to explain their abnormal behaviors. Forty-two male methamphetamine abstainers, currently in a long-term abstinence status (for at least 14 months), and 32 male healthy controls were recruited. All subjects underwent functional MRI while responding to drug-associated cues. This study proposes to combine a convolutional neural network with a short-time Fourier transform to identify different brain patterns between methamphetamine abstainers and controls. The short-time Fourier transformation provides time-localized frequency information, while the convolutional neural network extracts the structural features of the time–frequency spectrograms. The results showed that the classifier achieved a satisfactory performance (98.9% accuracy) and could extract robust brain voxel information. The highly discriminative power voxels were mainly concentrated in the left inferior orbital frontal gyrus, the bilateral postcentral gyri, and the bilateral paracentral lobules. This study provides a novel insight into the different functional patterns between methamphetamine abstainers and healthy controls. It also elucidates the pathological mechanism of methamphetamine abstainers from the view of time–frequency spectrograms.
Neuroscience Concepts Changed Teachers’ Views of Pedagogy and Students
Authors: Chang Zhengsi , Schwartz Marc S. , Hinesley Vicki , Dubinsky Janet M.
Published: August 2021

Advances in neuroscience reveal how individual brains change as learning occurs. Translating this neuroscience into practice has largely been unidirectional, from researchers to teachers. However, how teachers view and incorporate neuroscience ideas in their classroom practices remains relatively unexplored. Previously fourteen non-science teachers participated in a 3-week three credit graduate course focusing on foundational ideas in neuroscience. The current work was undertaken to gain insight into if and how individual teachers choose to later apply the proposed set of educational neuroscience concepts (ENCs) in their classrooms. This qualitative follow-up study examined commonalities in how teachers of diverse ages and subjects utilized their new neuroscience understandings. To this end, a year after the course, all participants assessed their perceived usefulness of the ENCs in a survey. Six of those teachers permitted classroom observations and participated in interviews that focused on how the ENCs may have influenced their lesson planning and teaching. The survey revealed that irrespective of subject areas or grade levels taught, teachers found the ENCs useful as organizing principles for their pedagogy now and in the future. Overall teachers estimated that the ENCs’ influence on lesson design had increased from 51% prior to the course to an estimated 90% for future lessons. A cross-case analysis of classroom observations and interviews revealed how teachers used ENCs to inform their pedagogical decisions, organize actions in their classroom, influence their understanding of students, and respond to individual contexts. Teachers recognized the importance of student agency for engaging them in the learning process. The ENCs also offered teachers explanations that affirmed known practices or helped justify exploring untried techniques. The foundational neuroscience concepts offered a small group of teachers a lens to reconsider, re-envision and re-design their lessons. Some teachers applied these ideas more broadly or frequently than others. This case study provided insights into how teachers can directly apply neuroscience knowledge to their practice and views of students.
Neuropsychological Development of Cool and Hot Executive Functions Between 6 and 12 Years of Age: A Systematic Review
Authors: Fernández García Laura , Merchán Ana , Phillips-Silver Jessica , Daza González María Teresa
Published: August 2021

Previous studies on the development of executive functions (EFs) in middle childhood have traditionally focused on cognitive, or “cool,” EFs: working memory, inhibitory control and cognitive flexibility. However, knowledge of the development of socio-emotional, or “hot,” EFs, such as delay of gratification, decision-making and theory of mind, is more limited. The main aims of this systematic review were to characterize the typical development of both the primary cool and hot EFs in middle childhood, and to identify the main tools for evaluating EFs as a whole. We conducted a systematic search on studies of cognitive and socio-emotional EFs published in the last 5 years in Pubmed, PsycInfo, and WoS databases. Of 44 studies selected, we found a variety of tasks measuring cool EFs, while measures of hot EFs were limited. Nevertheless, the available data suggest that cool and hot components follow distinct, but related, developmental trajectories during middle childhood.
Adaptive Behavior as an Alternative Outcome to Intelligence Quotient in Studies of Children at Risk: A Study of Preschool-Aged Children in Flint, MI, USA
Authors: Zheng Shuting , LeWinn Kaja , Ceja Tiffany , Hanna-Attisha Mona , O'Connell Lauren , Bishop Somer
Published: August 2021

Intelligence quotient (IQ) is commonly measured in child development studies, while adaptive behavior is less frequently considered. Given its associations with functional outcomes in children with neurodevelopmental disabilities, adaptive behavior may be a useful outcome in general population samples, as well. This study aimed to compare social and environmental correlates of adaptive behavior vs. IQ in a sample of preschoolers exposed to the Flint water crisis (N= 184). Mother–child dyads were recruited from the community and administered a comprehensive battery to obtain information about child neurodevelopmental functioning, including direct assessment of IQviathe Wechsler Preschool and Primary Scale of Intelligence and assessment of parent-reported adaptive functioningviathe Vineland Adaptive Behavior Scales. Multiple social environmental factors were explored as potential correlates of child outcomes (i.e., IQ and adaptive behavior), and robust correlates were identified using a data-driven approach [i.e., least absolute shrinkage and selection operator (LASSO) regression]. We then examined associations between the LASSO-selected predictors and IQ and adaptive behavior while controlling for child age, child sex, and maternal age. Children in this sample showed relative strength in adaptive behaviors, with scores in the adequate range, while average IQs fell in the low-average range. Adaptive behavior was significantly associated with maternal nurturance practices, while IQ was associated with the maternal education level. Implications for the use of adaptive behavior as an outcome measure in studies of children at an increased risk for neurodevelopmental problems are discussed.
Segmentation of Older Adults in the Acceptance of Social Networking Sites Using Machine Learning
Authors: Ramírez-Correa Patricio E. , Rondán-Cataluña F. Javier , Arenas-Gaitán Jorge , Grandón Elizabeth E. , Alfaro-Pérez Jorge L. , Ramírez-Santana Muriel
Published: August 2021

This study analyzes the most important predictors of acceptance of social network sites in a sample of Chilean elder people (over 60). We employ a novelty procedure to explore this phenomenon. This procedure performs apriori segmentation based on gender and generation. It then applies the deep learning technique to identify the predictors (performance expectancy, effort expectancy, altruism, telepresence, social identity, facilitating conditions, hedonic motivation, perceived physical condition, social norms, habit, and trust) by segments. The predictor variables were taken from the literature on the use of social network sites, and an empirical study was carried out by quota sampling with a sample size of 395 older people. The results show different predictors of social network sites considering all the samples, baby boomer (born between 1947 and 1966) males and females, silent (born between 1927 and 1946) males and females. The high heterogeneity among older people is confirmed; this means that dealing with older adults as a uniform set of users of social network sites is a mistake. This study demonstrates that the four segments behave differently, and many diverse variables influence the acceptance of social network sites.
Possible Association of Polymorphisms in Ubiquitin Specific Peptidase 46 Gene With Post-traumatic Stress Disorder
Authors: Seo Jun Ho , Kim Tae Yong , Kim Se Joo , Choi Jin Hee , So Hyung Seok , Kang Jee In
Published: August 2021

Introduction: Dynamic proteolysis, through the ubiquitin-proteasome system, has an important role in DNA transcription and cell cycle, and is considered to modulate cell stress response and synaptic plasticity. We investigated whether genetic variants in the ubiquitin carboxyl-terminal hydrolase 46 (USP46) would be associated with post-traumatic stress disorder (PTSD) in people with exposure to combat trauma using a case-control candidate gene association design.

Methods: Korean male veterans exposed to the Vietnam War were grouped into those with (n = 128) and without (n = 128) PTSD. Seven tagging SNPs of USP46 were selected, and single-marker and haplotype-based association analyses were performed. All analyses were adjusted for sociodemographic factors and levels of combat exposure severity and alcohol problem.

Results: One single-marker (rs2244291) showed nominal evidence of association with PTSD status and with the “re-experiencing” cluster, although the association was not significant after Bonferroni correction. No significant association with the other SNPs or the haplotypes was detected.

Conclusion: The present finding suggests preliminarily that genetic vulnerability regarding the ubiquitin-proteasome system may be related to fear memory processes and the development of PTSD symptoms after trauma exposure. Further studies with a larger sample size will be needed to examine the role of the ubiquitin-proteasome system including USP46 in PTSD.