bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-Associated Endothelial Dysfunction in Rat Mesenteric Arteries: Roles of Calcium-Activated K+ Channels (Kca)
Authors: Zhou E , Qing D , Li J
Published: January 2021

Age-associated changes in large blood vessels were characterized
by increased arterial wall thickness, luminal dilation and impaired
endothelial function. But little is known about the effect of age on
structural and functional changes in small resistance arteries. The
mechanisms underlying age-associated endothelial dysfunction in
rat mesenteric resistance arteries were investigated in the
present study. Small rat mesenteric arteries were excised and
cannulated, and vascular endothelial functions were tested by
acetylcholine (ACh). Our experiments showed (1) endotheliumdependent vasorelaxation induced by ACh was reduced in aged
mesenteric arteries; (2) blockade of Kca channels markedly
reduced the vasodilation in young and adult rats, the resultant
reduction in aged rats was much smaller compared with young
and adult rats; (3) inhibition of endothelial nitric oxide synthase
(NOS) resulted in a significant reduction of vasodilation in young
and adult, but there was a smaller reduction in aged rats. The
results suggest that (1) endothelial function was impaired in
mesenteric arteries of aged rats; (2) both Kca channels and nitric
oxide (NO) contribute together to the ACh-induced vasorelaxation
in small mesenteric arteries, and (3) both the impairment of Kca
channel function and decreased NO account for the age-related
endothelial dysfunction.
Some Current Insights into Oxidative Stress
Authors: Ďuračková Z
Published: January 2021

Oxidative stress is a phenomenon associated with pathogenetic
mechanisms of several diseases including atherosclerosis,
neurodegenerative diseases, such as Alzheimer’s and Parkinson’s
disease, cancer, diabetes mellitus, inflammatory diseases, as well
as psychological diseases or aging processes. Oxidative stress is
defined as an imbalance between production of free radicals and
reactive metabolites, so-called oxidants, and their elimination by
protective mechanisms, referred to as antioxidative systems. This
imbalance leads to damage of important biomolecules and
organs with potential impact on the whole organism. Oxidative
and antioxidative processes are associated with electron transfer
influencing the redox state of cells and the organism. The
changed redox state stimulates or inhibits activities of various
signal proteins, resulting in a changed ability of signal pathways
to influence the fate of cells. At present, the opinion that
oxidative stress is not always harmful, has been accepted.
Depending on the type of oxidants, intensity and time of redox
imbalance as well as on the type of cells, oxidative stress can
play a role in the regulation of other important processes through
modulation of signal pathways, influencing synthesis of
antioxidant enzymes, repair processes, inflammation, apoptosis
and cell proliferation, and thus processes of malignity. Imprudent
administration of antioxidants may therefore have a negative
impact on the organism.
Relationship Between Cough Reflex Sensitivity and Body Mass Index in Children With Chronic Cough – a Pilot Study
Authors: PECOVA R , SOJAK J , DURDIK P , ZATKO T , OMAR MOHAMEDOVA E , GRENDAR M , TATAR M
Published: January 2021

Obesity is characterized by chronic, low-grade systemic inflammation. Obesity may also be associated with chronic cough. The aim of this pilot study was to clarify relation of cough reflex sensitivity and body mass index (BMI) in children with chronic cough. Altogether 41 children having symptoms of chronic cough were submitted to cough reflex sensitivity measurement. We assessed the relation of cough reflex sensitivity (CKR) due to BMI. Cough reflex sensitivity was defined as the lowest capsaicin concentration which evoked two (C2) or five (C5) coughs. Capsaicin aerosol in doubling concentrations (from 0.61 to 1250 µmol/l) was inhaled by a single breath method (KoKo DigiDoser; nSpire heath Inc, Louisville, CO, USA), modified by the addition of an inspiratory flow regulator valve (RIFR; nSpire heath Inc, Louisville, CO, USA). BMI was calculated. Pulmonary function was within normal range. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Children (22 boys and 19 girls, mean age 6.8 years) cough reflex sensitivity (median, with the Inter-Quartile Range) for C2 was 19.5 (73.4) µmol/l; for C5 it was 78.1 (605.5) µmol/l. We have noticed statistically significant relation of the cough reflex sensitivity (C5) and body mass index (P<0.0001); however, the effect size was small, R2=0.03. Increase of body mass index in one unit is associated with -34.959 µmol/l decrease of C5. We did not find a statistically significant relation between C2 and BMI (P=0.41). The median value of CKR (C2) in boys is not statistically significantly different than the median value of CKR (C2) in girls (P-value 0.5). The median value of CKR (C5) in boys is not statistically significantly different than the median value of CKR (C5) in girls (P-value 0.5). Increase of body mass index in children suffering from chronic cough relates to decrease of cough reflex sensitivity (C5 value).
Downregulation of miR-30c-5p Expression in Colorectal Cancer Tissue is Sex-Dependent
Authors: HERICHOVA I , REIS R , HASAKOVA K , VICIAN M
Published: January 2021

We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was observed only in males. Expression of miR-30c was decreased in CRC tumor tissue in male patients with nodes involvement compared to those without metastases in nodes and this difference was not observe in females. Next dependency of miR-30c expression on oestrogen receptor β (ERβ) mRNA levels in tumor was tested. In males with low expression of ERβ, we observed a significant decrease in miR-30c levels in patients with nodes involvement compared to those without nodes involvement. This difference was not observed in males with high ERβ mRNA levels and in females. Accordingly, males with low expression of ERβ and high expression of miR-30c showed a better survival that those with low expression ERβ and low expression of miR-30c. It is possible to conclude that whole cohort survival dependence on miR-30c is mostly generated by a subcohort of males with low expression of ERβ mRNA in tumor tissue.
A Mixture of Diethylhexyl, Diisononyl and Dibutyl Phthalate Decreased Anogenital Distance, Postnatal Testosterone Levels, and Changed Social Behavior in Wistar Rats
Authors: MOROVÁ M , SENKO T , OLEXOVÁ L , DZIRBÍKOVÁ Z , KRŠKOVÁ L
Published: January 2021

Phthalates are chemicals interfering with the function of testosterone and are suspected to play a role in the emergence of neurodevelopmental diseases. This could be due to interference with brain development for which optimal testosterone levels are essential. We investigated the effect of prenatal and early postnatal exposure to a phthalate mixture on the anogenital distance (AGD), plasma testosterone levels and social behavior in rats. Pregnant rats were exposed to a mixture of diethylhexyl, diisononyl and dibutyl phthalate, each at a dose of 4.5 mg/kg/day, from gestational day 15 to postnatal day 4. A social interaction test was performed to assess sociability in the three ontogenetic stages (weaning, puberty, adulthood). AGD was measured in adulthood to assess changes in prenatal testosterone levels. Plasma testosterone levels were measured in adults by a radioimmunoassay. The total frequency and time of socio-cohesive interactions were decreased in phthalate exposed females in weaning, puberty and adulthood. Phthalate exposed males showed a decrease in the frequency of social interactions in weaning only. Shorter anogenital distance was observed in adult males exposed to phthalates. Decreased testosterone levels were observed in the exposed group in both sexes. Our results suggest that early developmental phthalate exposure may play an important role in the hormonal and behavioral changes associated with several neurodevelopmental diseases.
Cough Reflex Sensitivity and Fractional Exhaled Nitric Oxide in Children With Asthma
Authors: KUNC P , FABRY J , ZATKO T , GRENDAR M , TATAR M , PECOVA R
Published: January 2021

Individual studies have suggested the utility of fractional exhaled nitric oxide (FeNO) measurement in detecting cough-variant asthma and eosinophilic bronchitis in patients with chronic cough. The aim of this study was to clarify a correlation of cough reflex sensitivity and fractional exhaled nitric oxide in asthmatic children. 25 children with asthma and 15 controls were submitted to cough reflex sensitivity measurement – capsaicin aerosol in doubling concentrations (from 0.61 to 1250 µmol/l) was inhaled by a single breath method. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Fractional exhaled nitric oxide (FeNO) measurement was included. Asthmatic children (11 boys and 14 girls, mean age 9±1 years) and control group (unconfirmed diagnosis of asthma) (6 boys and 9 girls, mean age 8±1 years) were included into the study. FeNO vs. C2 in asthma (Spearman´s rank correlation: -0.146, p=0.49); FENO vs. C5 in asthma (Spearman´s rank correlation: -0.777, p=0.71). We found that there is no correlation between cough reflex sensitivity and fractional exhaled nitric oxide either in children with asthma or in the control group.
Acute Lung Injury – From Pathophysiology to Treatment
Authors: Mokra D
Published: January 2021

Acute lung injury is characterized by acute respiratory insufficiency with tachypnea, cyanosis refractory to oxygen, decreased lung compliance, and diffuse alveolar infiltrates on chest X-ray. The 1994 American-European Consensus Conference defined “acute respiratory distress syndrome, ARDS” by acute onset after a known trigger, severe hypoxemia defined by PaO2/FiO2≤200 mm Hg, bilateral infiltrates on chest X-ray, and absence of cardiogenic edema. Milder form of the syndrome with PaO2/FiO2 between 200-300 mm Hg was named „acute lung injury, ALI“. Berlin Classification in 2012 defined three categories of ARDS according to hypoxemia (mild, moderate, and severe), and the term “acute lung injury” was assigned for general description or for animal models. ALI/ARDS can originate from direct lung triggers such as pneumonia or aspiration, or from extrapulmonary reasons such as sepsis or trauma. Despite growing understanding the ARDS pathophysiology, efficacy of standard treatments, such as lung protective ventilation, prone positioning, and neuromuscular blockers, is often limited. However, there is an increasing evidence that direct and indirect forms of ARDS may differ not only in the manifestations of alterations, but also in the response to treatment. Thus, individualized treatment according to ARDS subtypes may enhance the efficacy of given treatment and improve the survival of patients.
MicroRNA-30e-5p Regulates SOCS1 and SOCS3 During Bacterial Infection
Authors: Mishra Richa , Krishnamoorthy Pandikannan , Kumar Himanshu
Published: January 2021

Host innate immunity is the major player against continuous microbial infection. Various pathogenic bacteria adopt the strategies to evade the immunity and show resistance toward the various established therapies. Despite the advent of many antibiotics for bacterial infections, there is a substantial need for the host-directed therapies (HDTs) to combat the infection. HDTs are recently being adopted to be useful in eradicating intracellular bacterial infection. Changing the innate immune responses of the host cells alters pathogen’s ability to reside inside the cell. MicroRNAs are the small non-coding endogenous molecules and post-transcriptional regulators to target the 3’UTR of the messenger RNA. They are reported to modulate the host’s immune responses during bacterial infections. Exploiting microRNAs as a therapeutic candidate in HDTs upon bacterial infection is still in its infancy. Here, initially, we re-analyzed the publicly available transcriptomic dataset of macrophages, infected with different pathogenic bacteria and identified significant genes and microRNAs common to the differential infections. We thus identified and miR-30e-5p, to be upregulated in different bacterial infections which enhances innate immunity to combat bacterial replication by targeting key negative regulators such as SOCS1 and SOCS3 of innate immune signaling pathways. Therefore, we propose miR-30e-5p as one of the potential candidates to be considered for additional clinical validation toward HDTs.
Tonsil Mycobiome in PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis) Syndrome: A Case-Control Study
Authors: Tejesvi Mysore V. , Tapiainen Terhi , Vänni Petri , Uhari Matti , Suokas Marko , Lantto Ulla , Koivunen Petri , Renko Marjo
Published: January 2021

Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) is the most common periodic fever syndrome in children with unknown etiology, effectively treated with tonsillectomy. Earlier we have shown that tonsil microbiome is different in patients with PFAPA as compared to that in controls. Recently, fungal microbiome, mycobiome, has been linked to the pathogenesis of inflammatory diseases. We now investigated the role of mycobiome of tonsils in PFAPA. Random forest classification, a machine learning approach, was used for the analysis of mycobiome data. We examined tonsils from 30 children with PFAPA and 22 control children undergoing tonsillectomy for non-infectious reasons. We identified 103 amplicon sequence variants, mainly from two fungal phyla, Ascomycota and Basidiomycota. The mean relative abundance of Candida albicans in the tonsil mycobiome was 11% (95% CI: 19 to 27%) in cases and 3.4 % (95% CI: -0.8% to 8%) in controls, p =0.104. Mycobiome data showed no statistical difference in differentiating between PFAPA cases and controls compared to a random chance classifier (area under the curve (AUC) = 0.47, SD = 0.05, p = 0.809). In conclusion, in this controlled study, tonsillar mycobiome in children with PFAPA syndrome did not differ from that of the controls.
Natural Gas vs. Electricity for Solvent-Based Direct Air Capture
Authors: McQueen Noah , Desmond Michael J. , Socolow Robert H. , Psarras Peter , Wilcox Jennifer
Published: January 2021

Removing CO2from the air with chemicals (Direct Air Capture, DAC) requires a significant amount of energy. Here, we evaluate the cost of co-constructing a solvent DAC process with its energy system. We compare eight energy systems paired with two alternative designs for a liquid-solvent DAC system capturing 1 MtCO2/year, which requires roughly 240 to 300 megawatts of steady power equivalent, 80% thermal and 20% electric. Two energy systems burn natural gas onsite for heat and electricity, capturing nearly all the CO2released during combustion, and six are all-electric non-fossil systems. The cost of the DAC facility alone contributes $310/tCO2for a conventional process-based design and $150/tCO2for a more novel design. When the decomposition of calcium carbonate occurs within a natural-gas-heated calciner, the energy system adds only $80/tCO2to these costs, assuming $3.25/GJ ($3.43/MMBtu) gas. However, leakage in the natural gas supply chain increases the cost of net capture dramatically: with 2.3% leakage (U.S. national average) and a 20-year Global Warming Potential of 86, costs are about 50% higher. For the all-electric systems, the total capture cost depends on the electricity cost: for each $/MWh of levelized cost of electricity, the total capture cost increases by roughly $2/tCO2. Continuous power is required, because the high-temperature calciner cannot be cycled on and off, so solar and wind power must be supplemented with storage. Our representative capture costs are $250–$440/tCO2for geothermal energy, $370–$620/tCO2for nuclear energy (two variants–a light water reactor and small modular nuclear), $360–$570/tCO2for wind, $430–$690/tCO2for solar photovoltaics (two variants assuming different daily solar capacities), and $300–$490/tCO2for a hybrid system with a natural-gas-powered electric calciner.
Visualizing Uncertainty for Non-Expert End Users: The Challenge of the Deterministic Construal Error
Authors: Joslyn Susan , Savelli Sonia
Published: January 2021

There is a growing body of evidence that numerical uncertainty expressions can be used by non-experts to improve decision quality. Moreover, there is some evidence that similar advantages extend to graphic expressions of uncertainty. However, visualizing uncertainty introduces challenges as well. Here, we discuss key misunderstandings that may arise from uncertainty visualizations, in particular the evidence that users sometimes fail to realize that the graphic depicts uncertainty. Instead they have a tendency to interpret the image as representing some deterministic quantity. We refer to this as thedeterministic construal error. Although there is now growing evidence for thedeterministic construal error, few studies are designed to detect it directly because they inform participants upfront that the visualization expresses uncertainty. In a natural setting such cues would be absent, perhaps making the deterministic assumption more likely. Here we discuss the psychological roots of this key but underappreciated misunderstanding as well as possible solutions. This is a critical question because it is now clear that members of the public understand that predictions involve uncertainty and have greater trust when uncertainty is included. Moreover, they can understand and use uncertainty predictions to tailor decisions to their own risk tolerance, as long as they are carefully expressed, taking into account the cognitive processes involved.
A Hiatus Obscures the Early Evolution of Modern Lineages of Bony Fishes
Authors: Romano Carlo
Published: January 2021

About half of all vertebrate species today are ray-finned fishes (Actinopterygii), and nearly all of them belong to the Neopterygii (modern ray-fins). The oldest unequivocal neopterygian fossils are known from the Early Triassic. They appear during a time when global fish faunas consisted of mostly cosmopolitan taxa, and contemporary bony fishes belonged mainly to non-neopterygian (“paleopterygian”) lineages. In the Middle Triassic (Pelsonian substage and later), less than 10 myrs (million years) after the Permian-Triassic boundary mass extinction event (PTBME), neopterygians were already species-rich and trophically diverse, and bony fish faunas were more regionally differentiated compared to the Early Triassic. Still little is known about the early evolution of neopterygians leading up to this first diversity peak. A major factor limiting our understanding of this “Triassic revolution” is an interval marked by a very poor fossil record, overlapping with the Spathian (late Olenekian, Early Triassic), Aegean (Early Anisian, Middle Triassic), and Bithynian (early Middle Anisian) substages. Here, I review the fossil record of Early and Middle Triassic marine bony fishes (Actinistia and Actinopterygii) at the substage-level in order to evaluate the impact of this hiatus–named herein the Spathian–Bithynian gap (SBG)–on our understanding of their diversification after the largest mass extinction event of the past. I propose three hypotheses: 1) the SSBE hypothesis, suggesting that most of the Middle Triassic diversity appeared in the aftermath of the Smithian-Spathian boundary extinction (SSBE; ∼2 myrs after the PTBME), 2) the Pelsonian explosion hypothesis, which states that most of the Middle Triassic ichthyodiversity is the result of a radiation event in the Pelsonian, and 3) the gradual replacement hypothesis, i.e. that the faunal turnover during the SBG was steady and bony fishes were not affected by extinction events subsequent to the PTBME. Based on current knowledge, hypothesis three is favored herein, but further studies are necessary to test alternative hypotheses. In light of the SBG, claims of a protracted diversification of bony fishes after the PTBME should be treated with caution.
Enhancing the Performance of DFIG Wind Turbines Considering Excitation Parameters of the Insulated Gate Bipolar Transistors and a New PLL Scheme
Authors: Okedu Kenneth E. , Barghash Hind F. A.
Published: January 2021

The major aim for achieving the successful synchronization of a wind turbine system to the grid is to mitigate electrical and mechanical stresses on the wind generator. During transient state, the gearbox, shaft, and rotor of the wind generator could be damaged due to mechanical stress. The rotor and stator windings of the wind generator, including its insulation, could be affected. This paper undertakes an extensive analysis of the effects of the excitation parameters of the power converter Insulated Gate Bipolar Transistors (IGBTs), on the transient state performance of the Doubly Fed Induction Generator (DFIG), considering different scenarios. The optimal excitation parameters of IGBTs were used for further analysis of the wind generator, considering a new Phase-Locked-Loop (PLL) scheme. The PLL computes the phase displacement of the grid required to achieve orientation and synchronization control. Consequently, it helps in preventing power system distortion due to stator-grid interphase. This paper proposes a new approach that integrates PLL control strategy and a Series Dynamic Braking Resistor (SDBR) to augment the fault ride through capability of a variable speed wind turbine that is DFIG-based. The SDBR helps the post fault recovery of the wind generator. Simulations were run in Power System Computer Aided Design and Electromagnetic Transient state Including DC (PSCAD/EMTDC) to examine severe fault conditions, and to test the robustness of the controllers employed. The results show that the proposed hybrid control strategy aids the fast recovery of the DFIG wind generator variables during fault conditions.
Construction of an RNA-Binding Protein-Related Prognostic Model for Pancreatic Adenocarcinoma Based on TCGA and GTEx Databases
Authors: Wen Xin , Shao Zhiying , Chen Shuyi , Wang Wei , Wang Yan , Jiang Jinghua , Ma Qinggong , Zhang Longzhen
Published: January 2021

Background: Recently, RNA-binding proteins (RBPs) were reported to interact with target mRNA to regulate gene posttranscriptional expression, and RBP-mediated RNA modification can regulate the expression and function of proto-oncogenes and tumor suppressor genes. We systematically analyzed the expression of RBPs in pancreatic adenocarcinoma (PAAD) and constructed an RBP-associated prognostic risk model.

Methods: Gene expression data of normal pancreatic samples as well as PAAD samples were downloaded from TCGA-PAAD and GTEx databases. Wilcoxon test and univariate Cox analysis were, respectively, applied to screen differential expression RBPs (DE-RBPs) and prognostic-associated RBPs (pRBPs). Functional enrichment was analyzed by GO, KEGG, and GSEA. Protein–protein interaction (PPI) network was constructed by STRING online database. Modeling RBPs were selected by multivariate Cox analysis. Kaplan–Meier survival and Cox analysis were applied to evaluate the effects of risk score on the overall survival of PAAD patients. ROC curves and validation cohort were applied to verify the accuracy of the model. Nomogram was applied for predicting 1-, 3-, and 5-year overall survival (OS) of PAAD patients. At last, modeling RBPs were further analyzed to explore their differential expression, prognostic value, as well as enrichment pathways in PAAD.

Results: RBPs (453) were differentially expressed in normal and tumor samples, besides, 28 of which were prognostic associated. DE-RBPs (453) are functionally associated with ribosome, ribonuclease, spliceosome, etc. Eight RBPs (PABPC1, PRPF6, OAS1, RBM5, LSM12, IPO7, FXR1, and RBM6) were identified to construct a prognostic risk model. Higher risk score not only predicted poor prognosis but also was an independent poor prognostic indicator, which was verified by ROC curves and validation cohort. Eight modeling RBPs were confirmed to be significantly differentially expressed between normal and tumor samples from RNA and protein level. Besides, all of eight RBPs were related with overall survival of PAAD patients.

Conclusions: We successfully constructed an RBP-associated prognostic risk model in PAAD, which has a potential clinical application prospect.
Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis
Authors: Yu Mullin Ho Chung , Chau Jeffrey Fong Ting , Au Sandy Leung Kuen , Lo Hei Man , Yeung Kit San , Fung Jasmine Lee Fong , Mak Christopher Chun Yu , Chung Claudia Ching Yan , Chan Kelvin Yuen Kwong , Chung Brian Hon Yin , Kan Anita Sik Yau
Published: January 2021

Balanced chromosomal abnormalities (BCAs) are changes in the localization or orientation of a chromosomal segment without visible gain or loss of genetic material. BCAs occur at a frequency of 1 in 500 newborns and are associated with an increased risk of multiple congenital anomalies and/or neurodevelopmental disorders, especially if it is a de novo mutation. In this pilot project, we used short read genome sequencing (GS) to retrospectively re-sequence ten prenatal subjects with de novo BCAs and compared the performance of GS with the original karyotyping. GS characterized all BCAs found by conventional karyotyping with the added benefit of precise sub-band delineation. By identifying BCA breakpoints at the nucleotide level using GS, we found disruption of OMIM genes in three cases and identified cryptic gain/loss at the breakpoints in two cases. Of these five cases, four cases reached a definitive genetic diagnosis while the other one case had a BCA interpreted as unknown clinical significance. The additional information gained from GS can change the interpretation of the BCAs and has the potential to improve the genetic counseling and perinatal management by providing a more specific genetic diagnosis. This demonstrates the added clinical utility of using GS for the diagnosis of BCAs.
Developmental Dysfunction of the Central Nervous System Lymphatics Modulates the Adaptive Neuro-Immune Response in the Perilesional Cortex in a Mouse Model of Traumatic Brain Injury
Authors: Wojciechowski Sara , Virenque Anaïs , Vihma Maria , Galbardi Barbara , Rooney Erin Jane , Keuters Meike Hedwig , Antila Salli , Koistinaho Jari , Noe Francesco M.
Published: January 2021

Rationale

The recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous system. The role of mLVs in modulating the neuro-immune response following a traumatic brain injury (TBI), however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after TBI, suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of T cell response in the brain after TBI.

Methods

TBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI.

Results

In both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44hiCD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, suggesting that mLVs could be involved in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate to alterations in peripheral circulating T cells, as assessed one month after injury.

Conclusions

Our results are consistent with the hypothesis that mLVs are involved in the neuro-immune response after TBI. We also defined the resident memory CD8+ T cells as one of the main population activated within the brain after a traumatic injury.
Systemic Inflammation in Pregnant Women With Latent Tuberculosis Infection
Authors: Naik Shilpa , Alexander Mallika , Kumar Pavan , Kulkarni Vandana , Deshpande Prasad , Yadana Su , Leu Cheng-Shiun , Araújo-Pereira Mariana , Andrade Bruno B. , Bhosale Ramesh , Babu Subash , Gupta Amita , Mathad Jyoti S. , Shivakoti Rupak
Published: January 2021

Background

Recent studies in adults have characterized differences in systemic inflammation between adults with and without latent tuberculosis infection (LTBI+ vs. LTBI−). Potential differences in systemic inflammation by LTBI status has not been assess in pregnant women.

Methods

We conducted a cohort study of 155 LTBI+ and 65 LTBI− pregnant women, stratified by HIV status, attending an antenatal clinic in Pune, India. LTBI status was assessed by interferon gamma release assay. Plasma was used to measure systemic inflammation markers using immunoassays: IFNβ, CRP, AGP, I-FABP, IFNγ, IL-1β, soluble CD14 (sCD14), sCD163, TNF, IL-6, IL-17a and IL-13. Linear regression models were fit to test the association of LTBI status with each inflammation marker. We also conducted an exploratory analysis using logistic regression to test the association of inflammatory markers with TB progression.

Results

Study population was a median age of 23 (Interquartile range: 21–27), 28% undernourished (mid-upper arm circumference (MUAC) <23 cm), 12% were vegetarian, 10% with gestational diabetes and 32% with HIV. In multivariable models, LTBI+ women had significantly lower levels of third trimester AGP, IL1β, sCD163, IL-6 and IL-17a. Interestingly, in exploratory analysis, LTBI+ TB progressors had significantly higher levels of IL1β, IL-6 and IL-13 in multivariable models compared to LTBI+ non-progressors.

Conclusions

Our data shows a distinct systemic immune profile in LTBI+ pregnant women compared to LTBI− women. Data from our exploratory analysis suggest that LTBI+ TB progressors do not have this immune profile, suggesting negative association of this profile with TB progression. If other studies confirm these differences by LTBI status and show a causal relationship with TB progression, this immune profile could identify subsets of LTBI+ pregnant women at high risk for TB progression and who can be targeted for preventative therapy.
Next Generation Imaging Techniques to Define Immune Topographies in Solid Tumors
Authors: Pietrobon Violena , Cesano Alessandra , Marincola Francesco , Kather Jakob Nikolas
Published: January 2021

In recent years, cancer immunotherapy experienced remarkable developments and it is nowadays considered a promising therapeutic frontier against many types of cancer, especially hematological malignancies. However, in most types of solid tumors, immunotherapy efficacy is modest, partly because of the limited accessibility of lymphocytes to the tumor core. This immune exclusion is mediated by a variety of physical, functional and dynamic barriers, which play a role in shaping the immune infiltrate in the tumor microenvironment. At present there is no unified and integrated understanding about the role played by different postulated models of immune exclusion in human solid tumors. Systematically mapping immune landscapes or “topographies” in cancers of different histology is of pivotal importance to characterize spatial and temporal distribution of lymphocytes in the tumor microenvironment, providing insights into mechanisms of immune exclusion. Spatially mapping immune cells also provides quantitative information, which could be informative in clinical settings, for example for the discovery of new biomarkers that could guide the design of patient-specific immunotherapies. In this review, we aim to summarize current standard and next generation approaches to define Cancer Immune Topographies based on published studies and propose future perspectives.
The Sp1-Responsive microRNA-15b Negatively Regulates Rhabdovirus-Triggered Innate Immune Responses in Lower Vertebrates by Targeting TBK1
Authors: Chang Renjie , Chu Qing , Zheng Weiwei , Zhang Lei , Xu Tianjun
Published: January 2021

As is known to all, the production of type I interferon (IFN) plays pivotal roles in host innate antiviral immunity, and its moderate production play a positive role in promoting the activation of host innate antiviral immune response. However, the virus will establish a persistent infection model by interfering with the production of IFN, thereby evading the organism inherent antiviral immune response. Therefore, it is of great necessity to research the underlying regulatory mechanisms of type I IFN appropriate production under viral invasion. In this study, we report that a Sp1–responsive miR-15b plays a negative role in siniperca chuatsi rhabdovirus (SCRV)-triggered antiviral response in teleost fish. We found that SCRV could dramatically upregulate miiuy croaker miR-15b expression. Enhanced miR-15b could negatively regulate SCRV-triggered antiviral genes and inflammatory cytokines production by targeting TANK-binding kinase 1 (TBK1), thereby accelerating viral replication. Importantly, we found that miR-15b feedback regulates antiviral innate immune response through NF-κB and IRF3 signaling pathways. These findings highlight that miR-15b plays a crucial role in regulating virus–host interactions, which outlines a new regulation mechanism of fish’s innate immune responses.
Taxonomy of Three Oxytrichids (Protozoa, Ciliophora, Hypotrichia), With Establishment of the New Species Rubrioxytricha guangzhouensis spec. nov.
Authors: Luo Xiaotian , Huang Jie , Bourland William A. , El-Serehy Hamed A. , Al-Farraj Saleh A. , Chen Xumiao , Song Weibo
Published: January 2021

Two oxytrichid ciliates collected from China, Oxytricha lithofera Foissner, 2016 and Rubrioxytricha haematoplasma (Blatterer and Foissner, 1990) Berger, 1999 were investigated based on living observations, protargol preparations, and molecular analyses. The Chinese population of O. lithofera shares highly distinctive features with the type population, e.g., lithosomes, abutting macronuclear nodules, straight undulating membranes, and long dorsal bristles. The morphology and morphogenesis of our new isolate of R. haematoplasma corresponds well with the type population. The 18S rRNA gene sequences of both species were obtained, and the molecular phylogeny of the genera Oxytricha Bory de Saint-Vincent in Lamouroux et al., 1824 and Rubrioxytricha Berger, 1999 was analyzed. In addition, we found that the Guangzhou population of R. haematoplasma described by Chen et al. (2015) can be distinguished from the type population and our isolate by the reddish-brown cortical granules (vs. lemon yellowish to greenish) and mitochondria-like granules present (vs. absent), as well as the slightly red cytoplasm (vs. slightly orange) and the marine or brackish water habitat (vs. freshwater). In addition, a 20-bp divergence in their 18S rRNA gene sequences indicates that they are not conspecific. Thus, we establish a new species, Rubrioxytricha guangzhouensis, for R. haematoplasma sensu Chen et al. (2015).
Variability of Lipids and Fatty Acids in Pacific Walrus Blubber
Authors: Jay Chadwick V. , Iverson Sara J. , Fischbach Anthony S.
Published: January 2021

The variability of lipid content and fatty acid (FA) composition across blubber depth and body sites are important considerations for condition and diet studies of marine mammals. We investigated lipid and FA variability among inner and outer blubber layers, three body sites, four study years, and lactation status of adult female Pacific walruses (Odobenus rosmarus divergens) using blubber samples collected from subsistence-harvested walruses in spring 2007–2010. Percent lipid content did not differ between the inner and outer blubber layers at the rump, flank, or sternum of walruses. Although FA composition differed between the inner and outer blubber layers, the difference was consistent across body sites, and differences between layers within individual FAs were small (<2%). Lipid content at the sternum of lactating females was 6% higher than non-lactating females, consistent with known variation in body condition among these reproductive classes. Across study years, lipid content varied 18% and individual FAs varied 6%, likely reflecting population-level interannual variability in energy budgets and small differences in diet among years. Consistency in blubber lipid content across blubber depth and body sites and detectable variation in blubber lipid content among reproductive classes and years suggests the potential for lipid content to be a useful indicator of walrus body condition. In addition to information on condition, FA composition of blubber samples could potentially provide insights into changes in walrus diet that may be expected to occur from changes in their access to prey resources resulting from continued sea ice loss.
Thromboembolism in Older Adults
Authors: Gross Peter L. , Chan Noel C.
Published: January 2021

Arterial and venous thromboembolism are both more common in older adults. The use of anticoagulants, the mainstay to prevent thromboembolism, requires consideration of the balance between risk and benefit. Such consideration is even more important in the very elderly in whom the risk of anticoagulant-related bleeding and thrombosis are higher. This review will focus on the challenges of implementing and managing anticoagulant therapy in older patients in an era when the options for anticoagulants include not only vitamin K antagonists (VKAs), but also direct-acting oral anticoagulants (DOACs).
Diagnosis of COVID-19 Pneumonia Based on Graph Convolutional Network
Authors: Liang Xiaoling , Zhang Yuexin , Wang Jiahong , Ye Qing , Liu Yanhong , Tong Jinwu
Published: January 2021

A three-dimensional (3D) deep learning method is proposed, which enables the rapid diagnosis of coronavirus disease 2019 (COVID-19) and thus significantly reduces the burden on radiologists and physicians. Inspired by the fact that the current chest computed tomography (CT) datasets are diversified in equipment types, we propose a COVID-19 graph in a graph convolutional network (GCN) to incorporate multiple datasets that differentiate the COVID-19 infected cases from normal controls. Specifically, we first apply a 3D convolutional neural network (3D-CNN) to extract image features from the initial 3D-CT images. In this part, a transfer learning method is proposed to improve the performance, which uses the task of predicting equipment type to initialize the parameters of the 3D-CNN structure. Second, we design a COVID-19 graph in GCN based on the extracted features. The graph divides all samples into several clusters, and samples with the same equipment type compose a cluster. Then we establish edge connections between samples in the same cluster. To compute accurate edge weights, we propose to combine the correlation distance of the extracted features and the score differences of subjects from the 3D-CNN structure. Lastly, by inputting the COVID-19 graph into GCN, we obtain the final diagnosis results. In experiments, the dataset contains 399 COVID-19 infected cases, and 400 normal controls from six equipment types. Experimental results show that the accuracy, sensitivity, and specificity of our method reach 98.5%, 99.9%, and 97%, respectively.
United by Hope, Divided by Access: Country Mapping of COVID-19 Information Accessibility and Its Consequences on Pandemic Eradication
Authors: Dror Amiel A. , Morozov Nicole G. , Layous Eli , Mizrachi Matti , Daoud Amani , Eisenbach Netanel , Rayan Doaa , Kaykov Edward , Marei Hesham , Barhum Masad , Srouji Samer , Avraham Karen B. , Sela Eyal
Published: January 2021

Many government websites and mobile content are inaccessible for people with vision, hearing, cognitive, and motor impairments. The COVID-19 pandemic highlighted these disparities when health authority website information, critical in providing resources for curbing the spread of the virus, remained inaccessible for numerous disabled populations. The Web Content Accessibility Guidelines provide comparatively universally accepted guidelines for website accessibility. We utilized these parameters to examine the number of countries with or without accessible health authority websites. The resulting data indicate a dearth of countries with websites accessible for persons with disabilities. Methods of information dissemination must take into consideration individuals with disabilities, particularly in times of global health crises.
Size Matters: Biological and Food Safety Relevance of Leaf Damage for Colonization of Escherichia coli O157:H7 gfp+
Authors: Mulaosmanovic Emina , Windstam Sofia T. , Vågsholm Ivar , Alsanius Beatrix W.
Published: January 2021

This study examined the biological and food safety relevance of leaf lesions for potential invasion of food pathogens into the plant tissue (internalization). This was done by determining the role of artificial leaf damage in terms of damaged leaf area on proliferation of E. coli O157:H7 gfp+. In a two-factorial experiment, unwashed fresh baby leaf spinach (Spinacia oleracea L.) was subjected to four damage levels (undamaged, low, moderate, high damage; factor 1) and three incubation intervals (0, 1, 2 days post-inoculation; factor 2). Individual leaves were immersed for 15 s in a suspension loaded with E. coli O157:H7 gfp+ (106 CFU × mL–1). The leaves were analyzed individually using image analysis tools to quantify leaf area and number and size of lesions, and using confocal laser scanning and scanning electron microscopy to visualize leaf lesions and presence of the introduced E. coli strain on and within the leaf tissue. Prevalence of E. coli O157:H7 gfp+ was assessed using a culture-dependent technique. The results showed that size of individual lesions and damaged leaf area affected depth of invasion into plant tissue, dispersal to adjacent areas, and number of culturable E. coli O157:H7 gfp+ directly after inoculation. Differences in numbers of the inoculant retrieved from leaf macerate evened out from 2 days post-inoculation, indicating rapid proliferation during the first day post-inoculation. Leaf weight was a crucial factor, as lighter spinach leaves (most likely younger leaves) were more prone to harbor E. coli O157:H7 gfp+, irrespective of damage level. At the high inoculum density used, the risk of consumers’ infection was almost 100%, irrespective of incubation duration or damage level. Even macroscopically intact leaves showed a high risk for infection. These results suggest that the risk to consumers is correlated with how early in the food chain the leaves are contaminated, and the degree of leaf damage. These findings should be taken into account in different steps of leafy green processing. Further attention should be paid to the fate of viable, but non-culturable, shiga-toxigenic E. coli on and in ready-to-eat leafy vegetables.
Application of CRISPR/Cas for Diagnosis and Management of Viral Diseases of Banana
Authors: Tripathi Leena , Ntui Valentine Otang , Tripathi Jaindra Nath , Kumar P. Lava
Published: January 2021

Viral diseases are significant biotic constraints for banana (Musa spp.) production as they affect the yield and limit the international movement of germplasm. Among all the viruses known to infect banana, the banana bunchy top virus and banana streak viruses are widespread and economically damaging. The use of virus-resistant bananas is the most cost-effective option to minimize the negative impacts of viral-diseases on banana production. CRISPR/Cas-based genome editing is emerging as the most powerful tool for developing virus-resistant crop varieties in several crops, including the banana. The availability of a vigorous genetic transformation and regeneration system and a well-annotated whole-genome sequence of banana makes it a compelling candidate for genome editing. A robust CRISPR/Cas9-based genome editing of the banana has recently been established, which can be applied in developing disease-resistant varieties. Recently, the CRISPR system was exploited to detect target gene sequences using Cas9, Cas12, Cas13, and Cas14 enzymes, thereby unveiling the use of this technology for virus diagnosis. This article presents a synopsis of recent advancements and perspectives on the application of CRISPR/Cas-based genome editing for diagnosing and developing resistance against banana viruses and challenges in genome-editing of banana.
Comparison of Alginate Utilization Pathways in Culturable Bacteria Isolated From Arctic and Antarctic Marine Environments
Authors: Cha Qian-Qian , Wang Xiu-Juan , Ren Xue-Bing , Li Dong , Wang Peng , Li Ping-Yi , Fu Hui-Hui , Zhang Xi-Ying , Chen Xiu-Lan , Zhang Yu-Zhong , Xu Fei , Qin Qi-Long
Published: January 2021

Alginate, mainly derived from brown algae, is an important carbon source that can support the growth of marine microorganisms in the Arctic and Antarctic regions. However, there is a lack of systematic investigation and comparison of alginate utilization pathways in culturable bacteria from both polar regions. In this study, 88 strains were isolated from the Arctic and Antarctic regions, of which 60 strains could grow in the medium with alginate as the sole carbon source. These alginate-utilizing strains belong to 9 genera of the phyla Proteobacteria and Bacteroidetes. The genomes of 26 alginate-utilizing strains were sequenced and genomic analyses showed that they all contain the gene clusters related to alginate utilization. The alginate transport systems of Proteobacteria differ from those of Bacteroidetes and there may be unique transport systems among different genera of Proteobacteria. The biogeographic distribution pattern of alginate utilization genes was further investigated. The alginate utilization genes are found to cluster according to bacterial taxonomy rather than geographic location, indicating that the alginate utilization genes do not evolve independently in both polar regions. This study systematically illustrates the alginate utilization pathways in culturable bacteria from the Arctic and Antarctic regions, shedding light into the distribution and evolution of alginate utilization pathways in polar bacteria.