bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing
Authors: Hanson Samuel M. , Forsyth Bruce , Wang Chun
Published: May 2021

Irreversible electroporation (IRE) is used clinically as a focal therapy to ablate solid tumors. A critical disadvantage of IRE as a monotherapy for cancer is the inability of ablating large tumors, because the electric field strength required is often too high to be safe. Previous reports indicate that cells exposed to certain cationic small molecules and surfactants are more vulnerable to IRE at lower electric field strengths. However, low-molecular-weight IRE sensitizers may suffer from suboptimal bioavailability due to poor stability and a lack of control over spatiotemporal accumulation in the tumor tissue. Here, we show that a synthetic membranolytic polymer, poly(6-aminohexyl methacrylate) (PAHM), synergizes with IRE to achieve enhanced cancer cell killing. The enhanced efficacy of the combination therapy is attributed to PAHM-mediated sensitization of cancer cells to IRE and to the direct cell killing by PAHM through membrane lysis. We further demonstrate sustained release of PAHM from embolic beads over 1 week in physiological medium. Taken together, combining IRE and a synthetic macromolecular sensitizer with intrinsic membranolytic activity and sustained bioavailability may present new therapeutic opportunities for a wide range of solid tumors.
Estimating the impact of control measures to prevent outbreaks of COVID-19 associated with air travel into a COVID-19-free country
Authors: Wilson Nick , Baker Michael G. , Blakely Tony , Eichner Martin
Published: May 2021

We aimed to estimate the risk of COVID-19 outbreaks associated with air travel to a COVID-19-free country [New Zealand (NZ)]. A stochastic version of the SEIR model CovidSIM v1.1, designed specifically for COVID-19 was utilised. We first considered historical data for Australia before it eliminated COVID-19 (equivalent to an outbreak generating 74 new cases/day) and one flight per day to NZ with no interventions in place. This gave a median time to an outbreak of 0.2 years (95% range of simulation results: 3 days to 1.1 years) or a mean of 110 flights per outbreak. However, the combined use of a pre-flight PCR test of saliva, three subsequent PCR tests (on days 1, 3 and 12 in NZ), and various other interventions (mask use and contact tracing) reduced this risk to one outbreak after a median of 1.5 years (20 days to 8.1 years). A pre-flight test plus 14 days quarantine was an even more effective strategy (4.9 years; 2,594 flights). For a much lower prevalence (representing only two new community cases per week in the whole of Australia), the annual risk of an outbreak with no interventions was 1.2% and had a median time to an outbreak of 56 years. In contrast the risks associated with travellers from Japan and the United States was very much higher and would need quarantine or other restrictions. Collectively, these results suggest that multi-layered interventions can markedly reduce the risk of importing the pandemic virus via air travel into a COVID-19-free nation. For some low-risk source countries, there is the potential to replace 14-day quarantine with alternative interventions. However, all approaches require public and policy deliberation about acceptable risks, and continuous careful management and evaluation.
Impacts of sheep versus cattle livestock systems on birds of Mediterranean grasslands
Authors: Ramos Rita F. , Diogo João A. , Santana Joana , Silva João P. , Reino Luís , Schindler Stefan , Beja Pedro , Lomba Angela , Moreira Francisco
Published: May 2021

Mediterranean pastures are experiencing strong changes in management, involving shifts from sheep to cattle-based livestock systems. The impacts of such shifts on biodiversity are still poorly understood. Here, we sought to contrast the grazing regime, vegetation structure, bird species richness and abundance, between sheep and cattle grazed parcels, to understand the mechanisms through which management decisions impact farmland birds. During spring 2019, we characterized livestock management, bird populations and sward structure in 23 cattle and 27 sheep grazed parcels. We used a Structural Equation Model to infer the direct and indirect effects of sheep and cattle grazing on birds. Although no effects were found on overall species richness, there were species-specific responses to sheep and cattle grazed systems. Grazing pressure (variable integrating stocking rate and the number of days in the parcel) had negative impacts on the prevalence/abundance of Zitting Cisticola, Corn Bunting and Little Bustard, either directly or indirectly, through the effects of grazing pressure on vegetation height. Animal density and vegetation cover had direct positive effects in Galerida spp. and Common Quail, respectively. Zitting Cisticola and Little Bustard also showed a direct response to livestock type. Our study emphasizes the importance of grazing pressure as a driver of negative impacts for bird populations in Mediterranean grasslands. Since the ongoing transition from sheep to cattle-based systems involves increases in stocking rate, and therefore potentially higher grazing pressure, we propose a policy change to cap the maximum allowed grazing pressure. At the landscape scale, a mix of sheep and cattle grazed fields would be beneficial for maintaining bird diversity.
Development of a novel method for the in-situ dechlorination of immovable iron elements: optimization of Cl− extraction yield through experimental design
Authors: Veneranda Marco , Prieto-Taboada Nagore , Carrero Jose Antonio , Costantini Ilaria , Larrañaga Aitor , Castro Kepa , Arana Gorka , Madariaga Juan Manuel
Published: May 2021

The conservation of iron objects exposed to marine aerosol is threatened by the formation of akaganeite, a highly unstable Cl-bearing corrosion phase. As akaganeite formation is responsible of the exfoliation of the rust layer, chlorides trigger a cyclic alteration phenomenon that often ends with the total consumption of the iron core. To prevent this degradation process, movable iron elements (e.g. archaeometallurgical artefacts) are generally immersed in alkaline dechlorination baths. Aiming to transfer this successful method to the treatment of immovable iron objects, we propose the in-situ application of alkaline solutions through the use of highly absorbent wraps. As first step of this novel research line, the present work defines the best desalination solution to be used and optimizes its extraction yield. After literature review, a screening experimental design was performed to understand the single and synergic effects of common additives used for NaOH baths. Once the most effective variables were selected, an optimization design was carried out to determine the optimal conditions to be set during treatment. According to the experimental work here presented, the use of 0.7 M NaOH solutions applied at high temperatures (above 50 °C) is recommended. Indeed, these conditions enhance chloride extraction and iron leaching inhibition, while promoting corrosion stabilization.
hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis
Authors: Lagosz-Cwik Katarzyna B. , Wielento Aleksandra , Lipska Weronika , Kantorowicz Malgorzata , Darczuk Dagmara , Kaczmarzyk Tomasz , Gibbs Susan , Potempa Jan , Grabiec Aleksander M.
Published: May 2021

In periodontitis, gingival fibroblasts (GFs) interact with and respond to oral pathogens, significantly contributing to perpetuation of chronic inflammation and tissue destruction. The aim of this study was to determine the usefulness of the recently released hTERT-immortalized GF (TIGF) cell line for studies of host–pathogen interactions. We show that TIGFs are unable to upregulate expression and production of interleukin (IL)-6, IL-8 and prostaglandin E2 upon infection with Porphyromonas gingivalis despite being susceptible to adhesion and invasion by this oral pathogen. In contrast, induction of inflammatory mediators in TNFα- or IL-1β-stimulated TIGFs is comparable to that observed in primary GFs. The inability of TIGFs to respond directly to P. gingivalis is caused by a specific defect in Toll-like receptor-2 (TLR2) expression, which is likely driven by TLR2 promoter hypermethylation. Consistently, TIGFs fail to upregulate inflammatory genes in response to the TLR2 agonists Pam2CSK4 and Pam3CSK4. These results identify important limitations of using TIGFs to study GF interaction with oral pathogens, though these cells may be useful for studies of TLR2-independent processes. Our observations also emphasize the importance of direct comparisons between immortalized and primary cells prior to using cell lines as models in studies of any biological processes.
Adsorption of bio-organic eco-corona molecules reduces the toxic response to metallic nanoparticles in Daphnia magna
Authors: Ekvall Mikael T. , Hedberg Jonas , Odnevall Wallinder Inger , Malmendal Anders , Hansson Lars-Anders , Cedervall Tommy
Published: May 2021

As the use of engineered nanomaterials increases, so does the risk of them spreading to natural ecosystems. Hitherto, knowledge regarding the toxic properties of nanoparticles (NP’s) and their potential interactions with natural bio-organic molecules adsorbed to them, and thereby forming surface coronas, is limited. However, we show here that the toxic effect of NPs of tungsten carbide cobalt (WC–Co) and cobalt (Co) on the crustacean Daphnia magna is postponed in the presence of natural biological degradation products (eco-corona biomolecules). For Daphnia exposed to WC–Co NPs the survival time increased with 20–25% and for Co NPs with 30–47% after mixing the particles with a solution of eco-corona biomolecules before exposure. This suggests that an eco-corona, composed of biomolecules always present in natural ecosystems, reduces the toxic potency of both studied NPs. Further, the eco-coronas did not affect the particle uptake, suggesting that the reduction in toxicity was related to the particle-organism interaction after eco-corona formation. In a broader context, this implies that although the increasing use and production of NPs may constitute a novel, global environmental threat, the acute toxicity and long-term effects of some NPs will, at least under certain conditions, be reduced as they enter natural ecosystems.
Prematurity alters the progenitor cell program of the upper respiratory tract of neonates
Authors: Shui Jessica E. , Wang Wei , Liu Helu , Stepanova Anna , Liao Grace , Qian Jun , Ai Xingbin , Ten Vadim , Lu Jining , Cardoso Wellington V.
Published: May 2021

The impact of prematurity on human development and neonatal diseases, such as bronchopulmonary dysplasia, has been widely reported. However, little is known about the effects of prematurity on the programs of stem cell self-renewal and differentiation of the upper respiratory epithelium, which is key for adaptation to neonatal life. We developed a minimally invasive methodology for isolation of neonatal basal cells from nasopharyngeal (NP) aspirates and performed functional analysis in organotypic cultures to address this issue. We show that preterm NP progenitors have a markedly distinct molecular signature of abnormal proliferation and mitochondria quality control compared to term progenitors. Preterm progenitors had lower oxygen consumption at baseline and were unable to ramp up consumption to the levels of term cells when challenged. Although they formed a mucociliary epithelium, ciliary function tended to decline in premature cells as they differentiated, compared to term cells. Together, these differences suggested increased sensitivity of preterm progenitors to environmental stressors under non-homeostatic conditions.
Addressing the COVID-19 transmission in inner Brazil by a mathematical model
Authors: Almeida G. B. , Vilches T. N. , Ferreira C. P. , Fortaleza C. M. C. B.
Published: May 2021

In 2020, the world experienced its very first pandemic of the globalized era. A novel coronavirus, SARS-CoV-2, is the causative agent of severe pneumonia and has rapidly spread through many nations, crashing health systems and leading a large number of people to death. In Brazil, the emergence of local epidemics in major metropolitan areas has always been a concern. In a vast and heterogeneous country, with regional disparities and climate diversity, several factors can modulate the dynamics of COVID-19. What should be the scenario for inner Brazil, and what can we do to control infection transmission in each of these locations? Here, a mathematical model is proposed to simulate disease transmission among individuals in several scenarios, differing by abiotic factors, social-economic factors, and effectiveness of mitigation strategies. The disease control relies on keeping all individuals’ social distancing and detecting, followed by isolating, infected ones. The model reinforces social distancing as the most efficient method to control disease transmission. Moreover, it also shows that improving the detection and isolation of infected individuals can loosen this mitigation strategy. Finally, the effectiveness of control may be different across the country, and understanding it can help set up public health strategies.
Direct gas-in-place measurements prove much higher production potential than expected for shale formations
Authors: Mahzari Pedram , Mitchell Thomas M. , Jones Adrian P. , Westacott Donald , Striolo Alberto
Published: May 2021

Shale gas exploitation has been the game-changer in energy development of the past decade. However, the existing methods of estimating gas in place in deep formations suffer from large uncertainties. Here, we demonstrate, by using novel high-pressure experimental techniques, that the gas in place within deep shale gas reservoirs can be up to five times higher than that estimated by implementing industry standard approaches. We show that the error between our laboratory approach and the standard desorption test is higher for gases with heavier compositions, which are of strongest commercial interests. The proposed instrumentation is reliable for deep formations and, provides quick assessment of the potential for the gas in place, which could be useful for assessing hydrocarbon reservoirs, and the potential for geological carbon sequestration of a given formation.
The early drift of the Indian plate
Authors: Jokat Wilfried , Altenbernd Tabea , Eagles Graeme , Geissler Wolfram H.
Published: May 2021

Plate kinematic models propose that India and Sri Lanka (INDSRI) separated from Antarctica by extremely slow seafloor spreading that started in early Cretaceous times, and that a long-distance ridge jump left a continental fragment stranded off the Antarctic margin under the Southern Kerguelen Plateau 1-3. Here, we present newly acquired magnetic and deep wide-angle seismic data that require a fundamental re-evaluation of these concepts. The new data clearly define the onset of oceanic crust in the Enderby Basin and off southern Sri Lanka, and date its formation with unprecedented confidence. The revised timing indicates that India and Sri Lanka detached from Antarctica earlier in the east than in the west. Furthermore, no compelling evidence for an extinct spreading axis is found in the Enderby Basin. A refined plate motion model indicates that India and Sri Lanka departed from Antarctica without major rift jumps, but by the action of three spreading ridges with different timings and velocities that must have been accommodated by significant intracontinental deformation.
Folliculin haploinsufficiency causes cellular dysfunction of pleural mesothelial cells
Authors: Okamoto Shouichi , Ebana Hiroki , Kurihara Masatoshi , Mitani Keiko , Kobayashi Etsuko , Hayashi Takuo , Sekimoto Yasuhito , Nishino Koichi , Otsuji Mizuto , Kumasaka Toshio , Takahashi Kazuhisa , Seyama Kuniaki
Published: May 2021

Birt–Hogg–Dubé syndrome (BHDS), an autosomal dominant inheritance disease caused by folliculin (FLCN) mutations, is associated with lung cysts and spontaneous pneumothorax. The possibility of FLCN haploinsufficiency in pleural mesothelial cells (PMCs) contributing to development of pneumothorax has not yet been clarified. Electron microscopy revealed exposed intercellular boundaries between PMCs on visceral pleura and decreased electron density around the adherens junctions in BHDS. To characterize cellular function of PMCs in BHDS patients (BHDS-PMCs), during surgery for pneumothorax, we established the flow cytometry-based methods of isolating high-purity PMCs from pleural lavage fluid. BHDS-PMCs showed impaired cell attachment and a significant decrease in proliferation and migration, but a significant increase in apoptosis compared with PMCs from primary spontaneous pneumothorax (PSP) patients (PSP-PMCs). Microarray analysis using isolated PMCs revealed a significant alteration in the expression of genes belonging to Gene Ontology terms “cell–cell adhesion junction” and “cell adhesion molecule binding”. Gene set enrichment analysis demonstrated that CDH1, encoding E-cadherin, was identified in the down-regulated leading edge of a plot in BHDS-PMCs. AMPK and LKB1 activation were significantly impaired in BHDS-PMCs compared with PSP-PMCs. Our findings indicate that FLCN haploinsufficiency may affect the E-cadherin-LKB1-AMPK axis and lead to abnormal cellular function in BHDS-PMCs.
Unravelling the fatty acid profiles of different polychaete species cultured under integrated multi-trophic aquaculture (IMTA)
Authors: Jerónimo Daniel , Lillebø Ana Isabel , Maciel Elisabete , Domingues M. Rosário M. , Cremades Javier , Calado Ricardo
Published: May 2021

Polychaetes can be successfully employed to recover otherwise wasted nutrients present in particulate organic matter (POM) of aquaculture effluents. The present study describes the fatty acid (FA) profile of four different polychaete species cultured in sand filters supplied with effluent water from a marine fish farm. The FA profile of cultured and wild Hediste diversicolor was compared and revealed a ≈ 24.2% dissimilarity, with cultured biomass displaying a higher content in two essential n-3 highly unsaturated FA (HUFA) (EPA [20:5 n-3] and DHA [22:6 n-3]—eicosapentaenoic and docosahexaenoic acid, respectively). The comparison of the FA profile of cultured H. diversicolor with that of other polychaete species whose larvae successfully settled on the sand filters (Diopatra neapolitana, Sabella cf. pavonina and Terebella lapidaria) revealed that their FA profile, which is here described for the first time, displayed high levels of EPA and DHA (≈ 1.5–4.8 and 1.0–1.1 µg mg−1 DW, respectively). The highest concentration of total FA per biomass of polychaete was recorded in H. diversicolor and T. lapidaria, with both species being the ones whose FA profiles revealed a lowest level of dissimilarity and more closely resembled that of the aquafeed used in the fish farm. In the present work it was demonstrated that it is possible to produce polychaetes biomass with high nutritional value through an eco-design concept such as integrated multi-trophic aquaculture (IMTA). Indeed, this framework promotes a cleaner production and, in this specific case, allowed to recover essential fatty acids that are commonly wasted in aquaculture effluents.
Estimates of gene ensemble noise highlight critical pathways and predict disease severity in H1N1, COVID-19 and mortality in sepsis patients
Authors: de Jong Tristan V. , Guryev Victor , Moshkin Yuri M.
Published: May 2021

Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative approach that could be applied to dissect the disease-associated molecular changes. We define gene ensemble noise as a measure that represents a variance for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes and calculated within an individual. The gene ensemble noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. By comparing gene expression data from COVID-19, H1N1, and sepsis patients we identified common disturbances in a number of pathways and protein complexes relevant to the sepsis pathology. Among others, these include the mitochondrial respiratory chain complex I and peroxisomes. This suggests a Warburg effect and oxidative stress as common hallmarks of the immune host–pathogen response. Finally, we showed that gene ensemble noise could successfully be applied for the prediction of clinical outcome namely, the mortality of patients. Thus, we conclude that gene ensemble noise represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of alterations in the coherent expression of gene circuits.
Antibiofilm and antivirulence potential of silver nanoparticles against multidrug-resistant Acinetobacter baumannii
Authors: Hetta Helal F. , Al-Kadmy Israa M. S. , Khazaal Saba Saadoon , Abbas Suhad , Suhail Ahmed , El-Mokhtar Mohamed A. , Ellah Noura H. Abd , Ahmed Esraa A. , Abd-ellatief Rasha B. , El-Masry Eman A. , Batiha Gaber El-Saber , Elkady Azza A. , Mohamed Nahed A. , Algammal Abdelazeem M.
Published: May 2021

We aimed to isolate Acinetobacter baumannii (A. baumannii) from wound infections, determine their resistance and virulence profile, and assess the impact of Silver nanoparticles (AgNPs) on the bacterial growth, virulence and biofilm-related gene expression. AgNPs were synthesized and characterized using TEM, XRD and FTIR spectroscopy. A. baumannii (n = 200) were isolated and identified. Resistance pattern was determined and virulence genes (afa/draBC, cnf1, cnf2, csgA, cvaC, fimH, fyuA, ibeA, iutA, kpsMT II, PAI, papC, PapG II, III, sfa/focDE and traT) were screened using PCR. Biofilm formation was evaluated using Microtiter plate method. Then, the antimicrobial activity of AgNPs was evaluated by the well-diffusion method, growth kinetics and MIC determination. Inhibition of biofilm formation and the ability to disperse biofilms in exposure to AgNPs were evaluated. The effect of AgNPs on the expression of virulence and biofilm-related genes (bap, OmpA, abaI, csuA/B, A1S_2091, A1S_1510, A1S_0690, A1S_0114) were estimated using QRT-PCR. In vitro infection model for analyzing the antibacterial activity of AgNPs was done using a co-culture infection model of A. baumannii with human fibroblast skin cell line HFF-1 or Vero cell lines. A. baumannii had high level of resistance to antibiotics. Most of the isolates harbored the fimH, afa/draBC, cnf1, csgA and cnf2, and the majority of A. baumannii produced strong biofilms. AgNPs inhibited the growth of A. baumannii efficiently with MIC ranging from 4 to 25 µg/ml. A. baumannii showed a reduced growth rate in the presence of AgNPs. The inhibitory activity and the anti-biofilm activity of AgNPs were more pronounced against the weak biofilm producers. Moreover, AgNPs decreased the expression of kpsMII , afa/draBC,bap, OmpA, and csuA/B genes. The in vitro infection model revealed a significant antibacterial activity of AgNPs against extracellular and intracellular A. baumannii. AgNPs highly interrupted bacterial multiplication and biofilm formation. AgNPs downregulated the transcription level of important virulence and biofilm-related genes. Our findings provide an additional step towards understanding the mechanisms by which sliver nanoparticles interfere with the microbial spread and persistence.
A new primate model of hypophyseal dysfunction
Authors: Kawabata Teppei , Suga Hidetaka , Takeuchi Kazuhito , Nagata Yuichi , Sakakibara Mayu , Ushida Kaori , Ozone Chikafumi , Enomoto Atsushi , Kawamoto Ikuo , Itagaki Iori , Tsuchiya Hideaki , Arima Hiroshi , Wakabayashi Toshihiko
Published: May 2021

For pituitary regenerative medicine, the creation of a hypophyseal model in monkeys is necessary to conduct future preclinical studies; however, previous studies reported that hypophysectomy in monkeys is not always safe or satisfactory. This study aimed to create a hypophyseal dysfunction model in a cynomolgus monkey using a safer surgical technique and establish the protocol of pituitary hormone replacement therapy for this model. Surgical resection of the pituitary gland of a 7.8-year-old healthy adult cynomolgus male monkey weighing 5.45 kg was performed to create a hypophyseal dysfunction model for future regenerative studies. Endoscopic transoral transsphenoidal surgery was used to perform hypophysectomy under navigation support. These procedures were useful for confirming total removal of the pituitary gland without additional bone removal and preventing complications such as cerebrospinal fluid leakage. Total removal was confirmed by pathological examination and computed tomography. Hypopituitarism was verified with endocrinological examinations including stimulation tests. Postoperatively, the monkey’s general condition of hypopituitarism was treated with hormone replacement therapy, resulting in long-term survival. The success of a minimally invasive and safe surgical method and long-term survival indicate the creation of a hypophyseal dysfunction model in a cynomolgus monkey; hence, this protocol can be employed in the future.
Entrapment of glucose oxidase within gold converts it to a general monosaccharide-oxidase
Authors: Baruch-Shpigler Yael , Avnir David
Published: May 2021

We report that entrapping glucose oxidase (GOx) within metallic gold, expands its activity to become an oxidase for monosaccharides that do not have a natural enzyme with that activity—fructose and xylose—and that this entrapment also removes the enantioselectivity, rendering this enzyme capable of oxidizing the “wrong” l-enantiomer of glucose. These observations suggest that in this biomaterial adsorptive interactions of the outer regions of the protein with the gold cage, pull apart and widen the tunnel between the two monomeric units of GOx, to a degree that its stereoselectivity is compromised; then, the active sites which are more versatile than currently attributed to, are free and capable of acting on the foreign sugars. To test this proposition, we entrapped in gold l-asparaginase, which is also a dimeric enzyme (a dimer of tight dimers), and found, again, that this metallic biomaterial widens the activity of that enzyme, to include the D-amino acid counter enantiomer as well. Detailed kinetic analyses for all substrates are provided for the gold bio-composites, including determination of the difference between the activation energies towards two opposite enantiomers.
A validated model for predicting live birth after embryo transfer
Authors: Awadalla Michael S. , Bendikson Kristin A. , Ho Jacqueline R. , McGinnis Lynda K. , Ahmady Ali
Published: May 2021

Accurately predicting the probability of live birth and multiple gestations is important for determining a safe number of embryos to transfer after in vitro fertilization. We developed a model that can be fit to individual clinic data for predicting singleton, twin, and total live birth rates after human embryo transfer. The predicted and observed rates of singleton and twin deliveries were compared in a tenfold cross-validation study using data from a single clinic. The model presented accounts for patient age, embryo stage (cleavage or blastocyst), type of transfer cycle (fresh or frozen) and uterine/universal factors. The standardized errors for rates of singleton and twin deliveries were normally distributed and the mean errors were not significantly different from zero (all p > 0.05). The live birth rates per embryo varied from as high as 43% for fresh blastocysts in the 35-year-old age group to as low as 1% for frozen cleavage stage embryos in the 43-year-old age group. This quantitative model or a simplified version can be used for clinics to generate and analyze their own data to guide the number of embryos to transfer to limit the risk of multiple gestations.
A radiomics-based model to classify the etiology of liver cirrhosis using gadoxetic acid-enhanced MRI
Authors: Elkilany Aboelyazid , Fehrenbach Uli , Auer Timo Alexander , Müller Tobias , Schöning Wenzel , Hamm Bernd , Geisel Dominik
Published: May 2021

The implementation of radiomics in radiology is gaining interest due to its wide range of applications. To develop a radiomics-based model for classifying the etiology of liver cirrhosis using gadoxetic acid-enhanced MRI, 248 patients with a known etiology of liver cirrhosis who underwent 306 gadoxetic acid-enhanced MRI examinations were included in the analysis. MRI examinations were classified into 6 groups according to the etiology of liver cirrhosis: alcoholic cirrhosis, viral hepatitis, cholestatic liver disease, nonalcoholic steatohepatitis (NASH), autoimmune hepatitis, and other. MRI examinations were randomized into training and testing subsets. Radiomics features were extracted from regions of interest segmented in the hepatobiliary phase images. The fivefold cross-validated models (2-dimensional—(2D) and 3-dimensional—(3D) based) differentiating cholestatic cirrhosis from noncholestatic etiologies had the best accuracy (87.5%, 85.6%), sensitivity (97.6%, 95.6%), predictive value (0.883, 0.877), and area under curve (AUC) (0.960, 0.910). The AUC was larger in the 2D-model for viral hepatitis, cholestatic cirrhosis, and NASH-associated cirrhosis (P-value of 0.05, 0.05, 0.87, respectively). In alcoholic cirrhosis, the AUC for the 3D model was larger (P = 0.01). The overall intra-class correlation coefficient (ICC) estimates and their 95% confident intervals (CI) for all features combined was 0.68 (CI 0.56–0.87) for 2D and 0.71 (CI 0.61–0.93) for 3D measurements suggesting moderate reliability. Radiomics-based analysis of hepatobiliary phase images of gadoxetic acid-enhanced MRI may be a promising noninvasive method for identifying the etiology of liver cirrhosis with better performance of the 2D- compared with the 3D-generated models.
Electrical behaviour and evolutionary computation in thin films of bovine brain microtubules
Authors: Vissol-Gaudin Eléonore , Pearson Chris , Groves Chris , Zeze Dagou A. , Cantiello Horacio F. , Cantero María del Rocio , Petty Michael C.
Published: May 2021

We report on the electrical behaviour of thin films of bovine brain microtubules (MTs). For samples in both their dried and hydrated states, the measured currents reveal a power law dependence on the applied DC voltage. We attribute this to the injection of space-charge from the metallic electrode(s). The MTs are thought to form a complex electrical network, which can be manipulated with an applied voltage. This feature has been exploited to undertake some experiments on the use of the MT mesh as a medium for computation. We show that it is possible to evolve MT films into binary classifiers following an evolution in materio approach. The accuracy of the system is, on average, similar to that of early carbon nanotube classifiers developed using the same methodology.
IGF1R and Src inhibition induce synergistic cytotoxicity in HNSCC through inhibition of FAK
Authors: Lehman Christine E. , Spencer Adam , Hall Sarah , Shaw Jeremy J. P. , Wulfkuhle Julia , Petricoin Emanuel F. , Bekiranov Stefan , Jameson Mark J. , Gioeli Daniel
Published: May 2021

Head and neck cancer is the sixth most common cancer worldwide with a 5-year survival of only 65%. Targeting compensatory signaling pathways may improve therapeutic responses and combat resistance. Utilizing reverse phase protein arrays (RPPA) to assess the proteome and explore mechanisms of synergistic growth inhibition in HNSCC cell lines treated with IGF1R and Src inhibitors, BMS754807 and dasatinib, respectively, we identified focal adhesion signaling as a critical node. Focal Adhesion Kinase (FAK) and Paxillin phosphorylation were decreased as early as 15 min after treatment, and treatment with a FAK inhibitor, PF-562,271, was sufficient to decrease viability in vitro. Treatment of 3D spheroids demonstrated robust cytotoxicity suggesting that the combination of BMS754807 and dasatinib is effective in multiple experimental models. Furthermore, treatment with BMS754807 and dasatinib significantly decreased cell motility, migration, and invasion in multiple HNSCC cell lines. Most strikingly, treatment with BMS754807 and dasatinib, or a FAK inhibitor alone, significantly increased cleaved-PARP in human ex-vivo HNSCC patient tissues demonstrating a potential clinical utility for targeting FAK or the combined targeting of the IGF1R with Src. This ex-vivo result further confirms FAK as a vital signaling node of this combinatorial treatment and demonstrates therapeutic potential for targeting FAK in HNSCC patients.
A systematic review and meta-analysis on correlation of weather with COVID-19
Authors: Majumder Poulami , Ray Partha Pratim
Published: May 2021

This study presents a systematic review and meta-analysis over the findings of significance of correlations between weather parameters (temperature, humidity, rainfall, ultra violet radiation, wind speed) and COVID-19. The meta-analysis was performed by using ‘meta’ package in R studio. We found significant correlation between temperature (0.11 [95% CI 0.01–0.22], 0.22 [95% CI, 0.16–0.28] for fixed effect death rate and incidence, respectively), humidity (0.14 [95% CI 0.07–0.20] for fixed effect incidence) and wind speed (0.58 [95% CI 0.49–0.66] for fixed effect incidence) with the death rate and incidence of COVID-19 (p < 0.01). The study included 11 articles that carried extensive research work on more than 110 country-wise data set. Thus, we can show that weather can be considered as an important element regarding the correlation with COVID-19.
Decline in influenza cases in Mexico after the implementation of public health measures for COVID-19
Authors: Arellanos-Soto Daniel , Padilla-Rivas Gerardo , Ramos-Jimenez Javier , Galan-Huerta Kame , Lozano-Sepulveda Sonia , Martinez-Acuña Natalia , Treviño-Garza Consuelo , Montes-de-Oca-Luna Roberto , de-la-O-Cavazos Manuel , Rivas-Estilla Ana Maria
Published: May 2021

Mexico took swift action and has strictly followed mitigation measures to prevent the spread of coronavirus disease, COVID-19. In this study we compared influenza activity indicators in our country after the implementation of public health measures for COVID-19. We compared indicators of influenza activity in 2020 before and after public health measures were taken to reduce COVID-19 with the corresponding indicators from three preceding years and the immediate one, and the potential decrease in seasonal influenza cases/deaths. Nationwide surveillance data revealed a drastic decline in influenza diagnosis in outpatient clinics and public hospitals, influenza positivity rates of clinical specimens, and confirmed severe cases during the following 10 weeks of 2020 as lockdown activities and control measures were established compared with the same period of 2019. Our results suggest that the measures taken for COVID-19 were effective in reducing the spread of other viral respiratory diseases as influenza in our country.
Dissection of the anti-Candida albicans mannan immune response using synthetic oligomannosides reveals unique properties of β-1,2 mannotriose protective epitopes
Authors: Sendid Boualem , Lecointe Karine , Collot Mayeul , Danzé Pierre-Marie , Damiens Sébastien , Drucbert Anne-Sophie , Fradin Chantal , Vilcot Jean-Pierre , Grenouillet Frédéric , Dubar Faustine , de Ruyck Jérôme , Jawhara Samir , Mallet Jean-Maurice , Poulain Daniel
Published: May 2021

Candida albicans mannan consists of a large repertoire of oligomannosides with different types of mannose linkages and chain lengths, which act as individual epitopes with more or less overlapping antibody specificities. Although anti-C. albicans mannan antibody levels are monitored for diagnostic purposes nothing is known about the qualitative distribution of these antibodies in terms of epitope specificity. We addressed this question using a bank of previously synthesized biotin sulfone tagged oligomannosides (BSTOs) of α and β anomery complemented with a synthetic β-mannotriose described as a protective epitope. The reactivity of these BSTOs was analyzed with IgM isotype monoclonal antibodies (MAbs) of known specificity, polyclonal sera from patients colonized or infected with C. albicans, and mannose binding lectin (MBL). Surface plasmon resonance (SPR) and multiple analyte profiling (MAP) were used. Both methods confirmed the usual reactivity of MAbs against either α or β linkages, excepted for MAb B6.1 (protective epitope) reacting with β-Man whereas the corresponding BSTO reacted with anti-α-Man. These results were confirmed in western blots with native C. albicans antigens. Using patients’ sera in MAP, a significant correlation was observed between the detection of anti-mannan antibodies recognizing β- and α-Man epitopes and detection of antibodies against β-linked mannotriose suggesting that this epitope also reacts with human polyclonal antibodies of both specificities. By contrast, the reactivity of human sera with other α- and β-linked BSTOs clearly differed according to their colonized or infected status. In these cases, the establishment of an α/β ratio was extremely discriminant. Finally SPR with MBL, an important lectin of innate immunity to C. albicans, classically known to interact with α-mannose, also interacted in an unexpected way with the protective epitope. These cumulative data suggest that structure/activity investigations of the finely tuned C. albicans anti-mannose immune response are worthwhile to increase our basic knowledge and for translation in medicine.
Derivation of stationary distributions of biochemical reaction networks via structure transformation
Authors: Hong Hyukpyo , Kim Jinsu , Ali Al-Radhawi M. , Sontag Eduardo D. , Kim Jae Kyoung
Published: May 2021

Long-term behaviors of biochemical reaction networks (BRNs) are described by steady states in deterministic models and stationary distributions in stochastic models. Unlike deterministic steady states, stationary distributions capturing inherent fluctuations of reactions are extremely difficult to derive analytically due to the curse of dimensionality. Here, we develop a method to derive analytic stationary distributions from deterministic steady states by transforming BRNs to have a special dynamic property, called complex balancing. Specifically, we merge nodes and edges of BRNs to match in- and out-flows of each node. This allows us to derive the stationary distributions of a large class of BRNs, including autophosphorylation networks of EGFR, PAK1, and Aurora B kinase and a genetic toggle switch. This reveals the unique properties of their stochastic dynamics such as robustness, sensitivity, and multi-modality. Importantly, we provide a user-friendly computational package, CASTANET, that automatically derives symbolic expressions of the stationary distributions of BRNs to understand their long-term stochasticity.
Integrated genomics and comprehensive validation reveal drivers of genomic evolution in esophageal adenocarcinoma
Authors: Kumar Subodh , Buon Leutz , Talluri Srikanth , Roncador Marco , Liao Chengcheng , Zhao Jiangning , Shi Jialan , Chakraborty Chandraditya , Gonzalez Gabriel , Tai Yu-Tzu , Prabhala Rao , Samur Mehmet K. , Munshi Nikhil C. , Shammas Masood A.
Published: May 2021

Esophageal adenocarcinoma (EAC) is associated with a marked genomic instability, which underlies disease progression and development of resistance to treatment. In this study, we used an integrated genomics approach to identify a genomic instability signature. Here we show that elevated expression of this signature correlates with poor survival in EAC as well as three other cancers. Knockout and overexpression screens establish the relevance of these genes to genomic instability. Indepth evaluation of three genes (TTK, TPX2 and RAD54B) confirms their role in genomic instability and tumor growth. Mutational signatures identified by whole genome sequencing and functional studies demonstrate that DNA damage and homologous recombination are common mechanisms of genomic instability induced by these genes. Our data suggest that the inhibitors of TTK and possibly other genes identified in this study have potential to inhibit/reduce growth and spontaneous as well as chemotherapy-induced genomic instability in EAC and possibly other cancers.
Seismic evidence for a thermochemical mantle plume underplating the lithosphere of the Ontong Java Plateau
Authors: Isse Takehi , Suetsugu Daisuke , Ishikawa Akira , Shiobara Hajime , Sugioka Hiroko , Ito Aki , Kawano Yuki , Yoshizawa Kazunori , Ishihara Yasushi , Tanaka Satoru , Obayashi Masayuki , Tonegawa Takashi , Yoshimitsu Junko
Published: May 2021

The Ontong Java Plateau in the western Pacific Ocean is the world’s largest oceanic plateau. It was formed 122 million years ago by a massive volcanic event that significantly affected Earth’s environment. The cause of the magmatic event remains controversial because the upper mantle structure beneath the plateau is poorly known. Here we use passive seismic data obtained through seafloor observations, alongside existing seismic data, to determine the three-dimensional radially anisotropic shear wave velocity to depths of up to 300 km. We find that the lithosphere–asthenosphere boundary is approximately 40 km deeper beneath the centre of the Ontong Java Plateau than beneath the surrounding seafloor. Based on our results and petrological and rheological constraints, we propose that the lithosphere–asthenosphere boundary has deepened as a result of underplating of dehydrated residual material beneath the pre-existing lithosphere during formation of the Ontong Java Plateau by a thermochemical mantle plume.
Dual sensitive and rapid detection of glycated human serum albumin using a versatile lead/graphene nanocomposite probe as a fluorescence–electrochemical aptasensor
Authors: Putnin Thitirat , Waiwinya Wassa , Pimalai Dechnarong , Chawjiraphan Wireeya , Sathirapongsasuti Nuankanya , Japrung Deanpen
Published: May 2021

Monitoring of glycated human serum albumin (GHSA) as a glycemic marker for screening and monitoring of diabetes mellitus is widely practiced for patients with conditions that affect red blood cells.
Rapid and sensitive detection ofStaphylococcus aureusandKlebsiella pneumoniabased on bacitracin-modified Fe3O4@PDA magnetic beads combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry
Authors: Qin Feng , Wang Shujuan , Gao Mingxia , Zhang Xiangmin
Published: May 2021

Bacitracin was immobilized on the surface of Fe3O4@PDA magnetic nanoparticles for the rapid enrichment and sensitive detection ofStaphylococcus aureus(G+) andKlebsiella pneumoniae(G−) in biological samples combined with MALDI-TOF MS.
In-site synthesis of an inorganic-framework molecular imprinted TiO2/CdS heterostructure for the photoelectrochemical sensing of bisphenol A
Authors: Wang Lan , Zhang Huan , Shi Hang , Jin Baodan , Qin Xiaoyun , Wang Geng , Li Kucong , Zhang Tingting , Zhang Hongzhong
Published: May 2021

A novel inorganic framework molecular imprinting TiO2/CdS heterostructure based photoelectrochemical sensor was achieved for the specific determination of bisphenol A (BPA).
Positively charged collective oscillations induce efficient Aβ1–42 fibril degradation in the presence of novel Au@Cu2−xS core/shell nanorods
Authors: Wan Xiaodong , Xu Meng , Huang Liu , Tu Guopeng , Ji Muwei , Su Mengyao , Li Yuemei , Li Xinyuan , Wang Hongzhi , Zhang Jiatao
Published: May 2021

We synthesized Au@Cu2−xS core/shell nanorods that have synergistic surface plasmon resonance effects using a new cation exchange process in ethylene glycol.
Investigating the iodide and bromide ion exchange in metal halide perovskite single crystals and thin films
Authors: Huang Qingyi , Li Zhe , Chen Xiayan , Xia Yongkang , Zheng Ziwei , Mei Anyi , Zhu Kai , Hu Yue , Wang Ti , Rong Yaoguang , Han Hongwei
Published: May 2021

Anion exchange can occur between MAPbX3 (X = I− or Br−) and MAX salts in a solution environment. Due to the lattice variation, I− and Br− show different intrusion behaviors, making the reaction partially reversible.
Synergistic Cu/Pd-catalyzed asymmetric allylation: a facile access to α-quaternary cysteine derivatives
Authors: Wu Hui-Min , Zhang Zongpeng , Wei Liang , Dong Xiu-Qin , Wang Chun-Jiang
Published: May 2021

Highly efficient synergistic Cu/Pd catalyzed asymmetric α-allylation of 2-thiazoline-4-carboxylate was successfully achieved to access various α-allylated cysteine derivatives in moderate to high yields with excellent enantioselectivities (45–98% yields and 69–>99% ee).
Valence tautomerism in a [2 × 2] Co4 grid complex containing a ditopic arylazo ligand
Authors: Bonanno Nico M. , Watts Zackery , Mauws Cole , Patrick Brian O. , Wiebe Christopher R. , Shibano Yuki , Sugisaki Kenji , Matsuoka Hideto , Shiomi Daisuke , Sato Kazunobu , Takui Takeji , Lemaire Martin T.
Published: May 2021

A [2 × 2] cobalt grid complex containing a ditopic arylazo trianion-radical ligand is shown to exhibit valence tautomerism in the solid state.
Electronic properties of N-rich graphene nano-chevrons
Authors: da Costa Azevêdo Anderson Soares , Saraiva-Souza Aldilene , Meunier Vincent , Girão Eduardo Costa
Published: May 2021

Theoretical analysis based on density functional theory describes the microscopic origins of emerging electronic and magnetic properties in quasi-1D nitrogen-rich graphene nanoribbon structures with chevron-like (or wiggle-edged) configurations.
Interfacial photoinduced carrier dynamics tuned by polymerization of coronene molecules encapsulated in carbon nanotubes: bridging type-I and type-II heterojunctions
Authors: Xie Xiao-Ying , Yang Jia-Jia , Liu Xiang-Yang , Fang Qiu , Fang Wei-Hai , Cui Ganglong
Published: May 2021

Theoretical studies demonstrate that the polymerization degree of molecules encapsulated in carbon nanotubes can be used to tune their interfacial and optoelectrical properties.
Structure-based redesign of the bacterial prolidase active-site pocket for efficient enhancement of methyl-parathion hydrolysis
Authors: Yang Jian , Xiao Yunzhu , Liu Yu , Li Ru , Long Lijuan
Published: May 2021

Mutagenesis at four residues surrounding the active-site pocket of an old bacterial prolidase scaffold led to a 10 000-fold increase in methyl-parathion hydrolysis and broadening substrate specificity against organophosphorus compounds.
Tunable linear donor–π–acceptor conjugated polymers with a vinylene linkage for visible-light driven hydrogen evolution
Authors: Han Shitong , Huang Tao , Pan Yi , Zhao Jiwu , Lin Huan , Lin Huaxiang , Ding Zhengxin , Xi Hailing , Long Jinlin
Published: May 2021

Extending the in-plane conjugation or/and increasing the electron push–pull interaction of linear D–π–A polymers with a vinylene linkage could broaden the visible-light absorption band, promote the charge separation and transfer and the photocatalytic hydrogen production.
Unveiling the catalytic potential of the Fe(iv)oxo species for the oxidation of hydrocarbons in the solid state
Authors: Saiz Fernan , Bernasconi Leonardo
Published: May 2021

We have investigated the three steps in the conversion of methane into methanol by Fe(iv)Ooxo species supported in MOF-74. We use ab initio MD and static approximations to predict the reaction barriers using enthalpy ΔH and free energy ΔG.
Polyimide with enhanced π stacking for efficient visible-light-driven photocatalysis
Authors: Zhang Kelian , Li Hanmei , Shi Haixian , Hong Wei
Published: May 2021

Polyimide photocatalysts with enhanced π stacking are prepared through the solvothermal condensation of pyromellitic dianhydride and N,N-dialkylmelamine, exhibiting extended light absorption ranges and efficient visible-light-driven photocatalysis.
Critical practices in conducting electrochemical conversion of 5-hydroxymethylfurfural
Authors: Zhou Yongfang , Shen Yi , Luo Xuanli
Published: May 2021

This work systematically studied the effects of various experimental parameters on the catalytic activity and product yield of HMF conversion and affords a rigorous assessment protocol for conducting electrochemical conversion of HMF.