bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacto en la reducción de la morbilidad utilizando la técnica de ganglio centinela en pacientes con cáncer de mama
Authors: Delgado Dávila Tamara , Tortoledo Rodríguez María
Published: July 2021

Introducción: El cáncer de  mama afecta cada vez más a las mujeres a nivel mundial. Los tipos de tratamiento quirúrgico y quimioterápico han evolucionado, consecuentemente es necesaria la correcta  evaluación del tumor primario y los ganglios linfáticos implicados por ser un importante factor  pronóstico y tratamiento. La técnica de ganglio centinela evalúa al primer ganglio en recibir el drenaje linfático del tumor.

Métodos: el objetivo fue determinar el impacto en pacientes con cáncer de mama en un estudio cuantitativo, observacional no experimental, correlacional de recolección retrospectiva, de tipo cohorte histórico. Se recuperó 153 pacientes en dos grupos de estudio, los que se sometieron a la técnica de ganglio centinela y los que se realizaron linfadenectomía axilar.

Resultados: el tipo histológico de cáncer de mama más frecuente fue el ductal infiltrante de grado histológico 2, un 76.4% y 73.6% de pacientes tuvieron receptores de estrógeno y progesterona positivo respectivamente mientras el receptor 2 de factor de crecimiento epidérmico humano fue positivo en 16.9%. La mediana del número de ganglios metastásicos fue semejante en los dos grupos, no así el número de ganglios libres 3 vs. 14 respectivamente (P < 0.001). En el estudio se evidenció morbilidad en 23.1% de pacientes que se biopsiaron el Ganglio Centinela, en contraste con 45.5% de en quienes no se efectuó dicho procedimiento (P = 0.025), la morbilidad más frecuentemente asociada fue el edema de la extremidad (27%).

Conclusiones: se demostró que la linfadenectomía expone tres veces a desarrollar  morbilidades en comparación con la técnica de ganglio centinela.
MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL
Authors: Liang Gehao , Ling Yun , Lin Qun , Shi Yu , Luo Qing , Cen Yinghuan , Mehrpour Maryam , Hamai Ahmed , Li Jun , Gong Chang
Published: July 2021

Objectives

Circular RNA (circRNA) is a novel class of RNA, which exhibits powerful biological function in regulating cellular fate of various tumors. Previously, we had demonstrated that over-expression of circRNA circCDYL promoted progression of HER2-negative (HER2–) breast cancer via miR-1275-ULK1/ATG7-autophagic axis. However, the role of circCDYL in HER2-positive (HER2+) breast cancer, in particular its role in modulating cell proliferation, one of the most important characteristics of cellular fate, is unclear.

Materials and methods

qRT-PCR and in situ hybridization analyses were performed to examine the expression of circCDYL and miR-92b-3p in breast cancer tissues or cell lines. The biological function of circCDYL and miR-92b-3p were assessed by plate colony formation and cell viability assays and orthotopic animal models. In mechanistic study, circRNAs pull-down, RNA immunoprecipitation, dual luciferase report, western blot, immunohistochemical and immunofluorescence staining assays were performed.

Results

CircCDYL was high-expressed in HER2+ breast cancer tissue, similar with that in HER2– breast cancer tissue. Silencing HER2 gene had no effect on expression of circCDYL in HER2+ breast cancer cells. Over-expression of circCDYL promoted proliferation of HER2+ breast cancer cells but not through miR-1275-ULK1/ATG7-autophagic axis. CircRNA pull down and miRNA deep-sequencing demonstrated the binding of miR-92b-3p and circCDYL. Interestingly, circCDYL did not act as miR-92b-3p sponge, but was degraded in miR-92b-3p-dependent silencing manner. Clinically, expression of circCDYL and miR-92b-3p was associated with clinical outcome of HER2+ breast cancer patients.

Conclusion

MiR-92b-3p-dependent cleavage of circCDYL was an essential mechanism in regulating cell proliferation of HER2+ breast cancer cells. CircCDYL was proved to be a potential therapeutic target for HER2+ breast cancer, and both circCDYL and miR-92b-3p might be potential biomarkers in predicting clinical outcome of HER2+ breast cancer patients.
Hotspots, Frontiers, and Emerging Trends of Superabsorbent Polymer Research: A Comprehensive Review
Authors: Yang Minmin , Wu Jihuai , Graham Geoffrey M. , Lin Jianming , Huang Miaoliang
Published: July 2021

Superabsorbent polymer (SAP) is a kind of functional macromolecule with super-high water absorption and retention properties, which attracts extensive research and has wide application, especially in the areas of hygiene and agriculture. With reference to the Web of Science database, the SAP research literature from 2000 to 2019 is reviewed both quantitatively and qualitatively. By examining research hotspots, top research clusters, the most influential works, the representative frontier literature, and key emerging research trends, a visual panorama of the continuously and significantly increasing SAP research over the past 2 decades was presented, and issues behind the sharp increase in the literature were discovered. The findings are as follows. The top ten keywords/hotspots headed by hydrogel highlight the academic attention on SAP properties and composites. The top ten research themes headed by clay-based composites which boast the longest duration and the strongest impact have revealed the academic preference for application rather than theoretical study. Academically influential scholars and research studies have been acknowledged, and the Wu group was at the forefront of the research; however, more statistically significant works have been less detected in the last 10 years despite the sharper increase in publications. Hydrogel, internal curing, and aerogel are both current advances and future directions.
Diabetes and Oral Health: Summary of Current Scientific Evidence for Why Transdisciplinary Collaboration Is Needed
Authors: Borgnakke Wenche Sylling , Poudel Prakash
Published: July 2021

This Perspective provides a brief summary of the scientific evidence for the often two-way links between hyperglycemia, including manifest diabetes mellitus (DM), and oral health. It delivers in a nutshell examples of current scientific evidence for the following oral manifestations of hyperglycemia, along with any available evidence for effect in the opposite direction: periodontal diseases, caries/periapical periodontitis, tooth loss, peri-implantitis, dry mouth (xerostomia/hyposalivation), dysbiosis in the oral microbiome, candidiasis, taste disturbances, burning mouth syndrome, cancer, traumatic ulcers, infections of oral wounds, delayed wound healing, melanin pigmentation, fissured tongue, benign migratory glossitis (geographic tongue), temporomandibular disorders, and osteonecrosis of the jaw. Evidence for effects on quality of life will also be reported. This condensed overview delivers the rationale and sets the stage for the urgent need for delivery of oral and general health care in patient-centered transdisciplinary collaboration for early detection and management of both hyperglycemia and oral diseases to improve quality of life.
Submarine Groundwater Discharge From Non-Tidal Coastal Peatlands Along the Baltic Sea
Authors: Racasa Erwin Don , Lennartz Bernd , Toro Miriam , Janssen Manon
Published: July 2021

Submarine groundwater discharge (SGD) is an important pathway for water and materials within the land-ocean transition zone that can impact coastal environments and marine life. Although research from sandy shorelines has rapidly advanced in recent years, there is very little understanding of coastal areas characterized by a low hydraulic conductivity, such as carbon-rich coastal peatlands. The objective of this study was to determine the magnitude and location of terrestrial SGD to be expected from a non-tidal low-lying coastal peatland located along the Baltic Sea and to understand the controlling factors using numerical modeling. We employed the HYDRUS-2D modeling package to simulate water movement under steady-state conditions in a transect that extends from the dune dike-separated rewetted fen to the shallow sea. Soil physical properties, hydraulic gradients, geological stratifications, and topography were varied to depict the range of properties encountered in coastal peatlands. Our results show that terrestrial SGD occurs at the study site at a flux of 0.080 m2 d−1, with seepage rates of 1.05 cm d−1 (upper discharge region) and 0.16 cm d−1 (lower discharge region above submerged peat layer). These calculated seepage rates compare to observations from other wetland environments and SGD sites in the Baltic Sea. The groundwater originates mainly from the dune dike—recharged by precipitation and infiltration from ponded peatland surface water—and to a lesser extent from the sand aquifer. The scenario simulations yielded a range of potential SGD fluxes of 0.008–0.293 m2 d−1. They revealed that the location of terrestrial SGD is determined by the barrier function of the peat layer extending under the sea. However, it has little impact on volume flux as most SGD occurs near the shoreline. Magnitude of SGD is mainly driven by hydraulic gradient and the hydraulic conductivity of peat and beach/dune sands. Anisotropy in the horizontal direction, aquifer and peat thickness, and peatland elevation have little impacts on SGD. We conclude that SGD is most probable from coastal peatlands with high water levels, large Ks and/or a dune dike or belt, which could be an essential source for carbon and other materials via the SGD pathway.
Seminal Plasma Lipidomics Profiling to Identify Signatures of Kallmann Syndrome
Authors: Li Xiaogang , Wang Xi , Li Haolong , Li Yongzhe , Guo Ye
Published: July 2021

Background

Kallmann syndrome (KS) is a rare developmental disorder. Our previous metabolomics work showed substantial changes in linoleic acid and glycerophospholipid metabolism in KS. Here, we performed targeted lipidomics to further identify the differential lipid species in KS.

Methods

Twenty-one patients with KS (treatment group) and twenty-two age-matched healthy controls (HC, control group) were enrolled. Seminal plasma samples and medical records were collected. Targeted lipidomics analysis of these samples was performed using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS).

Results

Lipidomics profiling of patients with KS and the HCs showed clear separation in the orthogonal projections to latent structures-discriminant analysis (OPLS-DA). There were many differential lipids identified, with the main differential lipid species being triacylglycerols (TAGs), phosphatidylcholines (PCs) and phosphatidylethanolamine (PE).

Conclusions

The lipidomics profile of patients with KS changed. It was also determined that TAGs, PCs and PE are promising biomarkers for KS diagnosis. To our knowledge, this is the first report to analyze lipidomics in men with Kallmann syndrome.
DNA Methylation as a Marker of Body Shape in Premenopausal Women
Authors: Divoux Adeline , Eroshkin Alexey , Erdos Edina , Sandor Katalin , Osborne Timothy F. , Smith Steven R.
Published: July 2021

Preferential accumulation of fat in the gluteo-femoral (GF) depot (pear shape) rather than in the abdominal (A) depot (apple shape), protects against the development of metabolic diseases but the underlying molecular mechanism is still unknown. Recent data, including our work, suggest that differential epigenetic marking is associated with regulation of genes attributed to distinct fat distribution. Here, we aimed to compare the genomic DNA methylation signatures between apple and pear-shaped premenopausal women. To investigate the contribution of upper and lower body fat, we used paired samples of A-FAT and GF-FAT, analyzed on the BeadChip Methylation Array and quantified the differentially methylated sites between the 2 groups of women. We found unique DNA methylation patterns within both fat depots that are significantly different depending on the body fat distribution. Around 60% of the body shape specific DNA methylation sites identified in adipose tissue are maintained ex vivo in cultured preadipocytes. As it has been reported before in other cell types, we found only a hand full of genes showing coordinated differential methylation and expression levels. Finally, we determined that more than 50% of the body shape specific DNA methylation sites could also be detected in whole blood derived DNA. These data reveal a strong DNA methylation program associated with adipose tissue distribution with the possibility that a simple blood test could be used as a predictive diagnostic indicator of young women who are at increased risk for progressing to the apple body shape with a higher risk of developing obesity related complications.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02728635 and https://clinicaltrials.gov/ct2/show/NCT02226640, identifiers NCT02728635 and NCT02226640.
A Novel Model for Identifying Essential Proteins Based on Key Target Convergence Sets
Authors: Peng Jiaxin , Kuang Linai , Zhang Zhen , Tan Yihong , Chen Zhiping , Wang Lei
Published: July 2021

In recent years, many computational models have been designed to detect essential proteins based on protein-protein interaction (PPI) networks. However, due to the incompleteness of PPI networks, the prediction accuracy of these models is still not satisfactory. In this manuscript, a novel key target convergence sets based prediction model (KTCSPM) is proposed to identify essential proteins. In KTCSPM, a weighted PPI network and a weighted (Domain-Domain Interaction) network are constructed first based on known PPIs and PDIs downloaded from benchmark databases. And then, by integrating these two kinds of networks, a novel weighted PDI network is built. Next, through assigning a unique key target convergence set (KTCS) for each node in the weighted PDI network, an improved method based on the random walk with restart is designed to identify essential proteins. Finally, in order to evaluate the predictive effects of KTCSPM, it is compared with 12 competitive state-of-the-art models, and experimental results show that KTCSPM can achieve better prediction accuracy. Considering the satisfactory predictive performance achieved by KTCSPM, it indicates that KTCSPM might be a good supplement to the future research on prediction of essential proteins.
Regulation of CEACAM Family Members by IBD-Associated Triggers in Intestinal Epithelial Cells, Their Correlation to Inflammation and Relevance to IBD Pathogenesis
Authors: Saiz-Gonzalo Gonzalo , Hanrahan Naomi , Rossini Valerio , Singh Raminder , Ahern Mary , Kelleher Maebh , Hill Shane , O’Sullivan Ruairi , Fanning Aine , Walsh Patrick T. , Hussey Seamus , Shanahan Fergus , Nally Ken , O’Driscoll Caitriona M. , Melgar Silvia
Published: July 2021

Carcinoembryogenic antigen cellular adhesion molecules (CEACAMs) are intercellular adhesion molecules highly expressed in intestinal epithelial cells. CEACAM1, -3, -5, -6, -7 are altered in patients suffering from colon cancer and inflammatory bowel diseases (IBD), but their role in the onset and pathogenesis of IBD is not well known. Herein, we aim to correlate CEACAM1, -3, -5, -6, -7 expression to the degree of inflammation in pediatric and adult IBD colon biopsies and to examine the regulation of CEACAMs on human intestinal epithelial cell lines (C2BBe1/HT29) by different IBD-associated triggers (cytokines, bacteria/metabolites, emulsifiers) and IBD-drugs (6-Mercaptopurine, Prednisolone, Tofacitinib). Biopsies from patients with pediatric Crohn’s disease (CD) and adult ulcerative colitis (UC, active/inactive disease) showed a significant increase in CEACAM3, -5, -6 expression, while CEACAM5 expression was reduced in adult CD patients (active/inactive disease). Intestinal epithelial cells cultured with a pro-inflammatory cytokine cocktail and Adherent-invasive Escherichia coli (AIEC) showed a rapid induction of CEACAM1, -5, -7 followed by a reduced RNA and protein expression overtime and a constant expression of CEACAM3, correlating with IL-8 expression. Cells cultured with the emulsifier polysorbate-80 resulted in a significant induction of CEACAM3, -5, -6, -7 at a late time point, while SCFA treatment reduced CEACAM1, -5, -7 expression. No major alterations in expression of CEACAMs were noted on cells cultured with the commensal Escherichia coli K12 or the pathogen Salmonella typhimurium. IBD drugs, particularly Tofacitinib, significantly reduced cytokine-induced CEACAM1, -3, -5, -6, -7 expression associated with a reduced IL-8 secretion. In conclusion, we provide new evidence on the regulation of CEACAMs by different IBD-associated triggers, identifying a role of CEACAMs in IBD pathogenesis.
Tofacitinib Ameliorates Lupus Through Suppression of T Cell Activation Mediated by TGF-Beta Type I Receptor
Authors: Yan Qing , Chen Weiwei , Song Hua , Long Xianming , Zhang Zhuoya , Tang Xiaojun , Chen Hongwei , Lin He , Sun Lingyun
Published: July 2021

Autoreactive T cells play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). TGF-β type I receptor (TGFβRI) is pivotal in determining T cell activation. Here, we showed that TGFβRI expression in naïve CD4+ T cells was decreased in SLE patients, especially in those with high disease activity. Moreover, IL-6 was found to downregulate TGFβRI expression through JAK/STAT3 pathway in SLE patients. In vitro, the JAK inhibitor tofacitinib inhibited SLE T cell activating by upregulating TGFβRI expression in a dose-dependent manner. In MRL/lpr mice, tofacitinib treatment ameliorated the clinical indicators and lupus nephritis, as evidenced by reduced plasma anti-dsDNA antibody levels, decreased proteinuria, and lower renal histopathological score. Consistently, tofacitinib enhanced TGFβRI expression and inhibited T cell activation in vivo. TGFβRI inhibitor SB431542 reversed the effects of tofacitinib on T cell activation. Thus, our results have indicated that tofacitinib can suppress T cell activation by upregulating TGFβRI expression, which provides a possible molecular mechanism underlying clinical efficacy of tofacitinib in treating SLE patients.
Zap70 Regulates TCR-Mediated Zip6 Activation at the Immunological Synapse
Authors: Kim Bonah , Kim Hee Young , Lee Won-Woo
Published: July 2021

The essential microelement zinc plays immunoregulatory roles via its ability to influence signaling pathways. Zinc deficiency impairs overall immune function and resultantly increases susceptibility to infection. Thus, zinc is considered as an immune-boosting supplement for populations with hypozincemia at high-risk for infection. Besides its role as a structural cofactor of many proteins, zinc also acts as an intracellular messenger in immune cell signaling. T-cell activation instructs zinc influx from extracellular and subcellular sources through the Zip6 and Zip8 zinc transporters, respectively. Increased cytoplasmic zinc participates in the regulation of T-cell responses by modifying activation signaling. However, the mechanism underlying the activation-dependent movement of zinc ions by Zip transporters in T cells remains elusive. Here, we demonstrate that Zip6, one of the most abundantly expressed Zip transporters in T cells, is mainly localized to lipid rafts in human T cells and is recruited into the immunological synapse in response to TCR stimulation. This was demonstrated through confocal imaging of the interaction between CD4+ T cells and antigen-presenting cells. Further, immunoprecipitation assays show that TCR triggering induces tyrosine phosphorylation of Zip6, which has at least three putative tyrosine motifs in its long cytoplasmic region, and this phosphorylation is coupled with its physical interaction with Zap70. Silencing Zip6 reduces zinc influx from extracellular sources and suppresses T-cell responses, suggesting an interaction between Zip6-mediated zinc influx and TCR activation. These results provide new insights into the mechanism through which Zip6-mediated zinc influx occurs in a TCR activation-dependent manner in human CD4+ T cells.
Apolipoprotein A4 Defines the Villus-Crypt Border in Duodenal Specimens for Celiac Disease Morphometry
Authors: Taavela Juha , Viiri Keijo , Välimäki Anna , Sarin Jani , Salonoja Kristiina , Mäki Markku , Isola Jorma
Published: July 2021

Histological evaluation of the small intestinal mucosa is the cornerstone of celiac disease diagnostics and an important outcome in scientific studies. Gluten-dependent injury can be evaluated either with quantitative morphometry or grouped classifications. A drawback of mucosal readings is the subjective assessment of the border where the crypt epithelium changes to the differentiated villus epithelium. We studied potential immunohistochemical markers for the detection of the villus-crypt border: apolipoprotein A4 (APOA4), Ki-67, glucose transporter 2, keratin 20, cytochrome P450 3A4 and intestinal fatty-acid binding protein. Among these, villus-specific APOA4 was chosen as the best candidate for further studies. Hematoxylin-eosin (H&E)- and APOA4 stained duodenal biopsy specimens from 74 adult patients were evaluated by five observers to determine the villus-to-crypt ratio (VH : CrD). APOA4 delineated the villus to crypt epithelium transition clearly, and the correlation coefficient of VH : CrD values between APOA4 and H&E was excellent (r=0.962). The VH : CrD values were lower in APOA4 staining (p<0.001) and a conversion factor of 0.2 in VH : CrD measurements was observed to make the two methods comparable to each other. In the intraobserver analysis, the doubled standard deviations, representing the error ranges, were 0.528 for H&E and 0.388 for APOA4 staining, and the ICCs were 0.980 and 0.971, respectively. In the interobserver analysis, the average error ranges were 1.017 for H&E and 0.847 for APOA4 staining, and the ICCs were better for APOA4 than for H&E staining in all analyses. In conclusion, the reliability and reproducibility of morphometrical VH : CrD readings are improved with the use of APOA4 staining.
Association Between Insulin Resistance and Remote Diffusion-Weighted Imaging Lesions in Primary Intracerebral Hemorrhage
Authors: Ye Xiang-hua , Zhang Jian-li , Jin Yu-jia , Shen Dan , Hao Xiao-di , Li Jia-wen , Zhong Jia-wei , Jin Lu-hang , Tong Lu-sha , Gao Feng
Published: July 2021

Background

Abnormal glucose metabolism was shown to be associated with the occurrence of remote diffusion-weighted imaging lesions (R-DWILs) after primary intracerebral hemorrhage (ICH) onset. Insulin resistance is a metabolic disorder that was regarded as an indicator of chronic systemic inflammation. In this study, we aimed to determine the effect of insulin resistance on the occurrence of R-DWILs in ICH.

Methods

Patients with primary ICH within 14 days after onset were prospectively enrolled from November 2017 to October 2019. R-DWILs was defined as remote focal hyperintensity from the hematoma in DWI, with corresponding hypointensity in apparent diffusion coefficient. The homeostasis model assessment of insulin resistance (HOMA-IR) was used for insulin resistance estimation and calculated as fasting insulin (μU/ml) × fasting glucose (mmol/L)/22.5. Patients in our cohort were divided into four groups according to HOMA-IR index quartiles. Logistic regression analysis and smoothing plots were used to evaluate the association of HOMA-IR with R-DWIL occurrence. Sensitivity analysis was performed in non-diabetic patients, non-obese patients, hypertensive ICH patients, and patients 60 years and older separately. The association between HOMA-IR and systemic inflammatory immune indices neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) was examined with multiple linear regression analysis.

Results

Among the 345 patients, 54 (15.7%) had R-DWILs. Both the third and fourth quartiles of HOMA-IR index were robustly associated with an increased risk of R-DWIL occurrence (adjusted OR 3.58, 95% CI 1.33-9.65; adjusted OR 3.91, 95%CI 1.47-10.41) when compared with the first quartile. The association was consistent in non-diabetic, non-obese, hypertensive ICH patients, as well as in patients 60 years and older. Furthermore, both NLR and MLR were independently associated with HOMA-IR.

Conclusions

Our study suggested that insulin resistance evaluated with HOMA-IR index was independently associated with the presence of R-DWILs in patients with acute and subacute primary ICH. It may provide new insights into the metabolism-related brain injury after ICH ictus.
Science Alone Won’t Do It! South Africa’s Endangered Humpback Dolphins Sousa plumbea Face Complex Conservation Challenges
Authors: Plön Stephanie , Atkins Shanan , Cockcroft Vic , Conry Danielle , Dines Sasha , Elwen Simon , Gennari Enrico , Gopal Keshni , Gridley Tess , Hörbst Sandra , James Bridget S. , Penry Gwenith , Thornton Meredith , Vargas-Fonseca O. Alejandra , Vermeulen Els
Published: July 2021

The Indian Ocean humpback dolphin (Sousa plumbea) is “endangered” with likely less than 500 animals remaining in South African waters. Established in 2016, the SouSA Consortium is a formalised network of scientists and conservationists to combine knowledge and research efforts, and make coordinated decisions with the aim of conserving the species. The first collaborative project collated available photo-identification data in an attempt to refine a national population estimate and investigate movements between research sites. This work was able to identify 250 uniquely marked individuals, with the population divided into the south-coast (Agulhas bioregion) and east-coast (Natal bioregion) populations. Environmental factors almost certainly play a role in the declining numbers of the species in South African waters. However, individual threats and solutions are challenging to identify as the South African marine environment is undergoing significant natural and anthropogenic changes with major shifts in the distribution and numbers of some prey, competitor and predator species. Therefore, we believe that a continued investigation of potential contributing factors and their interaction will take too long, inevitably resulting in another case of documenting extinction. With this in mind, we present the results of a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis in an effort to help us identify the next steps to take toward the conservation of humpback dolphins in South African waters. We unanimously conclude that no single cause for the rapid decline of humpback dolphins in South African waters can be identified, and that the cumulative effects of multiple stressors, which are difficult to pinpoint and mitigate, are impacting population numbers. While highlighting the need for continued research, we suggest a shift toward more action-focused conservation efforts, the first concrete steps being the development of a Conservation Management Plan with input from other stakeholders.
Characterization of Spacesuit Associated Microbial Communities and Their Implications for NASA Missions
Authors: Danko David , Malli Mohan Ganesh Babu , Sierra Maria A. , Rucker Michelle , Singh Nitin K. , Regberg Aaron B. , Bell Mary S. , O’Hara Niamh B. , Ounit Rachid , Mason Christopher E. , Venkateswaran Kasthuri
Published: July 2021

Background

Crewed National Aeronautics and Space Administration (NASA) missions to other solar system bodies are currently being planned. One high-profile scientific focus during such expeditions would be life detection, specifically the discovery of past or present microbial life, if they exist. However, both humans and associated objects typically carry a high microbial burden. Thus, it is essential to distinguish between microbes brought with the expedition and those present on the exploring planets. Modern spacesuits are unique, customized spacecraft which provide protection, mobility and life support to crew during spacewalks, yet they vent, and the mobility of microbes through spacesuits has not been studied.

Results

To evaluate the microbial colonization of spacesuits, NASA used an Extravehicular Activity swab kit to examine viable microbial populations of 48 samples from spacesuits using both traditional microbiological methods and molecular sequencing methods. The cultivable microbial population ranged from below the detection limit to 9 × 102 colony forming units per 25 cm2 of sample and also significantly varied by the location. The cultivable microbial diversity was dominated by members of Bacillus, Arthrobacter, and Ascomycota. However, 16S rRNA-based viable bacterial burden ranged from 105 to 106 copies per 25 cm2 of sample. Shotgun metagenome sequencing revealed the presence of a diverse microbial population on the spacesuit surfaces, including Curtobacterium and Methylobacterium from across all sets of spacesuits in high abundance. Among bacterial species identified, higher abundance of Cutibacterium acnes, Methylobacterium oryzae, and M. phyllosphaerae reads were documented.

Conclusion

The results of this study provide evidence that identical microbial strains may live on the wrist joint, inner gauntlet, and outer gauntlet of spacesuits. This raises the possibility, but does not confirm that microbial contaminants on the outside of the suits could contaminate planetary science operations unless additional measures are taken. Overall, these data provide the first estimate of microbial distribution associated with spacesuit surfaces, which will help future mission planners develop effective planetary protection strategies.
Modulation of Quorum Sensing and Biofilms in Less Investigated Gram-Negative ESKAPE Pathogens
Authors: Lazar Veronica , Holban Alina Maria , Curutiu Carmen , Chifiriuc Mariana Carmen
Published: July 2021

Pathogenic bacteria have the ability to sense their versatile environment and adapt by behavioral changes both to the external reservoirs and the infected host, which, in response to microbial colonization, mobilizes equally sophisticated anti-infectious strategies. One of the most important adaptive processes is the ability of pathogenic bacteria to turn from the free, floating, or planktonic state to the adherent one and to develop biofilms on alive and inert substrata; this social lifestyle, based on very complex communication networks, namely, the quorum sensing (QS) and response system, confers them an increased phenotypic or behavioral resistance to different stress factors, including host defense mechanisms and antibiotics. As a consequence, biofilm infections can be difficult to diagnose and treat, requiring complex multidrug therapeutic regimens, which often fail to resolve the infection. One of the most promising avenues for discovering novel and efficient antibiofilm strategies is targeting individual cells and their QS mechanisms. A huge amount of data related to the inhibition of QS and biofilm formation in pathogenic bacteria have been obtained using the well-established gram-positive Staphylococcus aureus and gram-negative Pseudomonas aeruginosa models. The purpose of this paper was to revise the progress on the development of antibiofilm and anti-QS strategies in the less investigated gram-negative ESKAPE pathogens Klebsiella pneumoniae, Acinetobacter baumannii, and Enterobacter sp. and identify promising leads for the therapeutic management of these clinically significant and highly resistant opportunistic pathogens.
Channeling of Carbon Flux Towards Carotenogenesis in Botryococcus braunii: A Media Engineering Perspective
Authors: Mariam Iqra , Kareya Mukul Suresh , Rehmanji Mohammed , Nesamma Asha Arumugam , Jutur Pannaga Pavan
Published: July 2021

Microalgae, due to their unique properties, gained attention for producing promising feedstocks having high contents of proteins, antioxidants, carotenoids, and terpenoids for applications in nutraceutical and pharmaceutical industries. Optimizing production of the high-value renewables (HVRs) in microalgae requires an in-depth understanding of their functional relationship of the genes involved in these metabolic pathways. In the present study, bioinformatic tools were employed for characterization of the protein-encoding genes of methyl erythritol phosphate (MEP) pathway involved in carotenoid and squalene biosynthesis based upon their conserved motif/domain organization. Our analysis demonstrates nearly 200 putative genes showing a conservation pattern within divergent microalgal lineages. Furthermore, phylogenomic studies confirm the close evolutionary proximity among these microalgal strains in the carotenoid and squalene biosynthetic pathways. Further analysis employing STRING predicts interactions among two rate-limiting genes, i.e., phytoene synthase (PSY) and farnesyl diphosphate farnesyl synthase (FPPS), which are specifically involved in the synthesis of carotenoids and squalene. Experimentally, to understand the carbon flux of these rate-limiting genes involved in carotenogenesis, an industrial potential strain, namely, Botryococcus braunii, was selected in this study for improved biomass productivity (i.e., 100 mg L–1 D–1) along with enhanced carotenoid content [0.18% dry cell weight (DCW)] when subjected to carbon supplementation. In conclusion, our approach of media engineering demonstrates that the channeling of carbon flux favors carotenogenesis rather than squalene synthesis. Henceforth, employing omics perspectives will further provide us with new insights for engineering regulatory networks for enhanced production of high-value carbon biorenewables without compromising growth.
Genomic Surveillance and Phylodynamic Analyses Reveal the Emergence of Novel Mutations and Co-mutation Patterns Within SARS-CoV-2 Variants Prevalent in India
Authors: Biswas Nupur , Mallick Priyanka , Maity Sujay Krishna , Bhowmik Debaleena , Mitra Arpita Ghosh , Saha Soumen , Roy Aviral , Chakrabarti Partha , Paul Sandip , Chakrabarti Saikat
Published: July 2021

Identification of the genomic diversity and the phylodynamic profiles of prevalent variants is critical to understand the evolution and spread of SARS-CoV-2 variants. We performed whole-genome sequencing of 54 SARS-CoV-2 variants collected from COVID-19 patients in Kolkata, West Bengal during August–October 2020. Phylogeographic and phylodynamic analyses were performed using these 54 and other sequences from India and abroad that are available in the GISAID database. We estimated the clade dynamics of the Indian variants and compared the clade-specific mutations and the co-mutation patterns across states and union territories of India over the time course. Frequent mutations and co-mutations observed within the major clades across time periods do not show much overlap, indicating the emergence of newer mutations in the viral population prevailing in the country. Furthermore, we explored the possible association of specific mutations and co-mutations with the infection outcomes manifested in Indian patients.
How Do We Motorically Resonate in Aging? A Compensatory Role of Prefrontal Cortex
Authors: Di Tella Sonia , Blasi Valeria , Cabinio Monia , Bergsland Niels , Buccino Giovanni , Baglio Francesca
Published: July 2021

Aging is the major risk factor for chronic age-related neurological diseases such as neurodegenerative disorders and neurovascular injuries. Exploiting the multimodal nature of the Mirror Neuron System (MNS), rehabilitative interventions have been proposed based on motor-resonance mechanisms in recent years. Despite the considerable evidence of the MNS’ functionality in young adults, further investigation of the action-observation matching system is required in aging, where well-known structural and functional brain changes occur. Twenty-one healthy young adults (mean age 26.66y) and 19 healthy elderly participants (mean age 71.47y) underwent a single MRI evaluation including a T1-3D high-resolution and functional MRI (fMRI) with mirror task. Morphological and functional BOLD data were derived from MRI images to highlight cortical activations associated with the task; to detect differences between the two groups (Young, Elderly) in the two MRI indexes (BOLD and thickness z-scores) using mixed factorial ANOVA (Group∗Index analyses); and to investigate the presence of different cortical lateralization of the BOLD signal in the two groups. In the entire sample, the activation of a bilateral MNS fronto-parietal network was highlighted. The mixed ANOVA (pFDR-corr < 0.05) revealed significant interactions between BOLD signal and cortical thickness in left dorsal premotor cortex, right ventral premotor and prefrontal cortices. A different cortical lateralization of the BOLD signal in frontal lobe activity between groups was also found. Data herein reported suggest that age-related cortical thinning of the MNS is coupled with increased interhemispheric symmetry along with premotor and prefrontal cortex recruitment. These physiological changes of MNS resemble the aging of the motor and cognitive neural systems, suggesting specific but also common aging and compensatory mechanisms.
Comparison of Thalamus and Basal Ganglia Signs Between Multiple Sclerosis and Primary Angiitis of the Central Nervous System: An Exploratory Study
Authors: Chen Ying , Li Rui , Wu Aimin , Qiu Wei , Hu Xueqiang , Hu Zhaoqi , Yang Qian , Zhou Zhiming
Published: July 2021

Based on the symptoms, especially those affecting small vessels, it is difficult to distinguish multiple sclerosis (MS) from primary angiitis of the central nervous system (PACNS). Magnetic resonance imaging (MRI) helps understand the characteristics of deep gray matter lesions (DGML) in MS and PACNS. We aimed to compare the MRI characteristics of thalamus and basal ganglia lesions between relapsing-remitting MS and PACNS. In our study, 49 relapsing-remitting MS patients and 16 PACNS with MRI-confirmed thalamus or basal ganglia lesions were enrolled. Among the DGMLs in basal ganglia, putamen had significantly higher (P = 0.037) involvement in PACNS than in MS. More importantly, larger lesion sizes in thalamus helps to distinguish PACNS (12.4 ± 4.3 mm) from MS (7.9 ± 3.7 mm) (P = 0.006). But using lesions in basal ganglia, researchers were unable to differentiate the two disorders. Presently, our study shows that MRI performances of deep gray matter differ between MS and PACNS.
Peer Support to Enhance Social and Emotional Self-Management Following Acquired Brain Injury Rehabilitation: Design of a Pre–post Study With Process Evaluation
Authors: Baumgartner-Dupuits Milou , Sep Simone J. S. , Verbunt Jeanine , Bosma Hans , van Eijk Jacques
Published: July 2021

Background: Specialized rehabilitation following acquired brain injury provides intensive multidisciplinary treatment to individuals with complex disabilities for optimizing recovery and supporting a safe transition to the community. Post-specialist rehabilitation, patients and caregivers have reported a need for support. We present the design of an implementation study to evaluate a new self-management support service for individuals with acquired brain injury and their caregivers.

Methods: This is a pre–post intervention study with a mixed-method design. The study population comprises individuals aged ≥18 years with acquired brain injury living independently following specialized rehabilitation in the Southern part of the Netherlands. All participants receive a post-rehabilitation support service. The support service consists of several house visits by a peer support volunteer in the first weeks after specialized rehabilitation treatment. The peer support volunteers are trained according to an adapted version of the previously developed Self-Management Support (SMS) program. The SMS program is directed at improving social and emotional self-management. Patient outcomes are assessed by questionnaire pre-, directly post-, and 6 months post-intervention. The primary patient outcome measure is self-efficacy. Secondary outcomes are perceived autonomy, quality of life, and psychological well-being. A process evaluation will be performed to gain insight into barriers and facilitators for the implementation of peer-led SMS by combining both quantitative, questionnaire data and qualitative data derived from focus groups with peer supporters and patients. In a workshop with relevant stakeholders, possibilities for dissemination and sustainability will be explored.

Discussion: This paper describes the design of a practice-based study on feasibility, barriers, and facilitators to the implementation of a home-based, peer-led self-management support intervention for patients with acquired brain injury. We will quantitatively and qualitatively evaluate the change in relevant patient outcomes pre- and post-intervention and the barriers and facilitators related to the implementation of the intervention. Following a positive evaluation, the final stage of the study aims to facilitate deployment and utilization of the intervention.
Assessment of the Effect of Erenumab on Efficacy and Quality-of-Life Parameters in a Cohort of Migraine Patients With Treatment Failure in Cyprus
Authors: Tziakouri Andria , Tsangari Haritini , Michaelides Costas
Published: July 2021

Erenumab is the first human monoclonal antibody to be approved as a selective therapy for migraine prophylaxis in adults. This study assessed, in a real-world setting, the efficacy of erenumab and its impact on the quality of life (QoL) of Cypriot migraine patients who had failed several treatments in the past. Erenumab was prescribed as a stand-alone or as an add-on therapy to 16 patients with chronic migraine. The first component of the study examined migraine parameters before and after erenumab therapy and included an interim 3-month subjective assessment. In the second component, the patients were asked to complete the validated Migraine-Specific Quality-of-Life Questionnaire—Version 2.1 (MSQ V2.1) during the last month of their individual treatment as a measure of the QoL. The results showed a statistically significant improvement in almost all migraine parameters following erenumab treatment. In the 3-month-interval assessment, 81.3% of the patients reported an improvement in their mental well-being, anxiety, and depression levels, with more than 80% of the patients reporting an improvement in almost all assessed migraine parameters. MSQ V2.1 indicated a good health status in all three domains (mean values > 60 on a scale 0–100), with the “role function preventative” domain having the highest health scores (85). Over a period of 6 months, erenumab was safe, well-tolerated, and effective in preventing migraine symptoms and improving HR-QoL. We conclude that this novel medication, which is not yet part of the national formulary in Cyprus, may be a cost-effective solution in reducing the disease burden of chronic migraine.
Cognitive Impairment After COVID-19—A Review on Objective Test Data
Authors: Daroische Rania , Hemminghyth Mathilde S. , Eilertsen Thomas H. , Breitve Monica H. , Chwiszczuk Luiza J.
Published: July 2021

Objective: The aim was to conduct a review on the literature on objective cognitive impairment in patients after COVID-19.

Methods: We performed a literature review and searched Ovid Medline in February 2021 based on a PECO scheme.

Results: Twelve articles met all inclusion criteria. Total patient sample was <1,000. All studies on global cognitive function found impairment, ranging from 15 to 80% of the sampled patients. Seven studies on attention and executive functions reported impairment, with varying results depending on sub-domain and different tests. Three out of four studies reported memory difficulties, with two studies reporting short-term memory deficits. Although results indicate possible language impairment, only one study used domain-specific language tasks. Two out of four studies on visuospatial function did not report any impairment.

Conclusion: Patients with recent SARS-CoV-2 infection appear to experience global cognitive impairment, impairment in memory, attention and executive function, and in particular verbal fluency. Based on the current results, we recommend clinicians to evaluate the need for cognitive assessment of patients with a recent COVID-19 infection, regardless of the severity of the disease, treatment methods and length of ICU stay. We need studies with larger sample and control group.
Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Stroke Severity and Short-Term Prognosis in Acute Ischemic Stroke With Intracranial Atherosclerotic Stenosis
Authors: Ying Yuanlin , Yu Fang , Luo Yunfang , Feng Xianjing , Liao Di , Wei Minping , Li Xi , Huang Qin , Liu Zeyu , Zhang Lin , Zhao Tingting , Tu Ruxin , Xia Jian
Published: July 2021

Background: Neutrophil-to-lymphocyte ratio (NLR) is an indicator of poor prognosis in acute ischemic stroke (AIS), but associations between NLR with stroke severity and prognosis of intracranial atherosclerotic stenosis (ICAS)-related ischemic events have not been well-elucidated; therefore, we aimed to evaluate whether admission NLR levels correlate with the early stroke severity and short-term functional prognosis in patients with symptomatic intracranial atherosclerotic stenosis (sICAS).

Methods: This retrospective study enrolled 899 consecutive patients with AIS attributed to ICAS at Xiangya Hospital stroke center between May 2016 and September 2020. The initial stroke severity was rated by the admission National Institutes of Health Stroke Scale (NIHSS) scores, and the short-term prognosis was evaluated using the 14-day modified Rankin Scale (mRS) scores after stroke onset. A severe stroke was defined as NIHSS >8; an unfavorable functional outcome was defined as mRS scores of 3–6. Admission NLR was determined based on circulating neutrophil and lymphocyte counts.

Results: The median admission NLR of all patients was 2.80 [interquartile range (IQR), 2.00–4.00]. In univariate analysis, admission NLR was significantly elevated in patients with severe stroke and poor short-term prognosis. After multivariate adjustment, admission NLR levels were significantly correlated with severe stroke [odds ratio (OR), 1.132; 95% confidence interval (95% CI), 1.038–1.234; P = 0.005] and unfavorable short-term prognosis (OR, 1.102; 95% CI, 1.017–1.195; P = 0.018) in Model 1. In Model 2, the highest NLR tertile (≥3.533) remained an independent predictor of severe stroke (OR, 2.736; 95% CI, 1.590–4.708; P < 0.001) and unfavorable functional outcome (OR, 2.165; 95% CI, 1.416–3.311; P < 0.001) compared with the lowest NLR tertile (<2.231). The receiver operating characteristic (ROC) curves showed the predictability of NLR regarding the stroke severity [area under the curve (AUC), 0.659; 95% CI, 0.615–0.703; P < 0.001] and short-term prognosis (AUC, 0.613; 95% CI, 0.575–0.650; P < 0.001). The nomograms were constructed to create the predictive models of the severity and short-term outcome of sICAS.

Conclusions: Elevated admission NLR levels were independently associated with the initial stroke severity and could be an early predictor of severity and poor short-term prognosis in AIS patients with ICAS, which might help us identify a target group timely for preventive therapies.