bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional response of individual Hawaiian Culex quinquefasciatus mosquitoes to the avian malaria parasite Plasmodium relictum
Authors: Ferreira Francisco C. , Videvall Elin , Seidl Christa M. , Wagner Nicole E. , Kilpatrick A. Marm , Fleischer Robert C. , Fonseca Dina M. 
Published: August 2022

Abstract
Background
Plasmodium parasites that cause bird malaria occur in all continents except Antarctica and are primarily transmitted by mosquitoes in the genus Culex. Culex quinquefasciatus, the mosquito vector of avian malaria in Hawaiʻi, became established in the islands in the 1820s. While the deadly effects of malaria on endemic bird species have been documented for many decades, vector-parasite interactions in avian malaria systems are relatively understudied.

Methods
To evaluate the gene expression response of mosquitoes exposed to a Plasmodium infection intensity known to occur naturally in Hawaiʻi, offspring of wild-collected Hawaiian Cx. quinquefasciatus were fed on a domestic canary infected with a fresh isolate of Plasmodium relictum GRW4 from a wild-caught Hawaiian honeycreeper. Control mosquitoes were fed on an uninfected canary. Transcriptomes of five infected and three uninfected individual mosquitoes were sequenced at each of three stages of the parasite life cycle: 24 h post feeding (hpf) during ookinete invasion; 5 days post feeding (dpf) when oocysts are developing; 10 dpf when sporozoites are released and invade the salivary glands.

Results
Differential gene expression analyses showed that during ookinete invasion (24 hpf), genes related to oxidoreductase activity and galactose catabolism had lower expression levels in infected mosquitoes compared to controls. Oocyst development (5 dpf) was associated with reduced expression of a gene with a predicted innate immune function. At 10 dpf, infected mosquitoes had reduced expression levels of a serine protease inhibitor, and further studies should assess its role as a Plasmodium agonist in C. quinquefasciatus. Overall, the differential gene expression response of Hawaiian Culex exposed to a Plasmodium infection intensity known to occur naturally in Hawaiʻi was low, but more pronounced during ookinete invasion.

Conclusions
This is the first analysis of the transcriptional responses of vectors to malaria parasites in non-mammalian systems. Interestingly, few similarities were found between the response of Culex infected with a bird Plasmodium and those reported in Anopheles infected with human Plasmodium. The relatively small transcriptional changes observed in mosquito genes related to immune response and nutrient metabolism support conclusions of low fitness costs often documented in experimental challenges of Culex with avian Plasmodium.
Predictive ability of viscoelastic testing using ClotPro® for short-term outcome in patients with severe Covid-19 ARDS with or without ECMO therapy: a retrospective study
Authors: Heubner Lars , Greiner Marvin , Vicent Oliver , Beyer-Westendorf Jan , Tiebel Oliver , Scholz Ute , Güldner Andreas , Mirus Martin , Fries Dietmar , Koch Thea , Spieth Peter Markus 
Published: August 2022

Abstract
Background
SARS-CoV-2 infections are suspected to trigger the coagulation system through various pathways leading to a high incidence of thromboembolic complications, hypercoagulation and impaired fibrinolytic capacity were previously identified as potentially mechanisms. A reliable diagnostic tool for detecting both is still under discussion. This retrospective study is aimed to examine the prognostic relevance of early viscoelastic testing compared to conventional laboratory tests in COVID-19 patients with acute respiratory distress syndrome (ARDS).

Methods
All mechanically ventilated patients with COVID-19 related ARDS treated in our intensive care unit (ICU) between January and March 2021 were included in this study. Viscoelastic testing (VET) was performed using the ClotPro® system after admission to our ICU. Prevalence of thromboembolic events was observed by standardized screening for venous and pulmonary thromboembolism using complete compression ultrasound and thoracic computed tomography pulmonary angiography at ICU admission, respectively. We examined associations between the severity of ARDS at admission to our ICU, in-hospital mortality and the incidence of thromboembolic events comparing conventional laboratory analysis and VET. ECMO related coagulopathy was investigated in a subgroup analysis. The data were analyzed using the Mann–Whitney U test.

Results
Of 55 patients enrolled in this study, 22 patients required treatment with ECMO. Thromboembolic complications occurred in 51% of all patients. Overall hospital mortality was 55%. In patients with thromboembolic complications, signs of reduced fibrinolytic capacity could be detected in the TPA assay with prolonged lysis time, median 460 s (IQR 350–560) vs 359 s (IQR 287–521, p = 0.073). Patients with moderate to severe ARDS at admission to our ICU showed increased maximum clot firmness as a sign of hypercoagulation in the EX-test (70 vs 67 mm, p < 0.05), FIB-test (35 vs 24 mm, p < 0.05) and TPA-test (52 vs 36 mm, p < 0.05) as well as higher values of inflammatory markers (CRP, PCT and IL6). ECMO patients suffered more frequently from bleeding complications (32% vs 15%).

Conclusion
Although, the predictive value for thromboembolic complications or mortality seems limited, point-of-care viscoelastic coagulation testing might be useful in detecting hypercoagulable states and impaired fibrinolysis in critically ill COVID-19 ARDS patients and could be helpful in identifying patients with a potentially very severe course of the disease.
Soil conditions on bacterial wilt disease affect bacterial and fungal assemblage in the rhizosphere
Authors: Liu Xiaojiao , Liu Liehua , Gong Jie , Zhang Lixin , Jiang Qipeng , Huang Kuo , Ding Wei 
Published: August 2022

AbstractNatural soil has the ability to suppress the soil-borne pathogen to a certain extent, and the assemblage of soil microbiome plays a crucial role in maintaining such ability. Long-term monoculture accelerates the forms of soil microbiome and leads to either disease conducive or suppressive soils. Here, we explored the impact of soil conditions on bacterial wilt disease (healthy or diseased) under long-term tobacco monoculture on the assemblage of bacterial and fungal communities in bulk and rhizosphere soils during the growth periods. With Illumina sequencing, we compared the bacterial and fungal composition of soil samples from tobacco bacterial wilt diseased fields and healthy fields in three growth periods. We found thatProteobacteriaandAscomycotawere the most abundant phylum for bacteria and fungi, respectively. Factors of soil conditions and tobacco growth periods can significantly influence the microbial composition in bulk soil samples, while the factor of soil conditions mainly determined the microbial composition in rhizosphere soil samples. Next, rhizosphere samples were further analyzed with LEfSe to determine the discriminative taxa affected by the factor of soil conditions. For bacteria, the genusRalstoniawas found in the diseased soils, whereas the genusFlavobacteriumwas the only shared taxon in healthy soils; for fungi, the genusChaetomiumwas the most significant taxon in healthy soils. Besides, network analysis confirmed that the topologies of networks of healthy soils were higher than that of diseased soils. Together, our results suggest that microbial assemblage in the rhizosphere will be largely affected by soil conditions especially after long-term monoculture.
What is the impact of SARS-CoV-2 pandemic on antimicrobial stewardship programs (ASPs)? The results of a survey among a regional network of infectious disease centres
Authors: Comelli Agnese , Genovese Camilla , Lombardi Andrea , Bobbio Chiara , Scudeller Luigia , Restelli Umberto , Muscatello Antonio , Antinori Spinello , Bonfanti Paolo , Casari Salvatore , Castagna Antonella , Castelli Francesco , Monforte Antonella d’Arminio , Franzetti Fabio , Grossi Paolo , Lupi Matteo , Morelli Paola , Piconi Stefania , Puoti Massimo , Pusterla Luigi , Regazzetti Angelo , Rizzi Marco , Rusconi Stefano , Zuccaro Valentina , Gori Andrea , Bandera Alessandra ,   the ASP Lomb Study Group, Giacomelli Andrea , Rossi Marianna , Bruno Raffaele , Garilli Silvia , Marco Ripa , Signorini Liana , Bai Francesca , Pan Angelo , Merli Marco , Ricaboni Davide , Molteni Chiara , Benatti Simone Vasilij , Castiglioni Barbara , Rovelli Cristina , Piazza Manuela , Franzetti Marco 
Published: August 2022

AbstractDiscontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.
Clustered and dispersed: exploring the morphological evolution of traditional villages based on cellular automaton
Authors: Yang Xi , Pu Fuan 
Published: August 2022

Abstract
The spatial pattern of traditional villages can be generally divided into two main types: clustered and dispersed. In order to explore and compare the spatial evolutionary characteristics of different village patterns, and provide a reliable basis for spatial planning, a universal Cellular Automaton (CA) model was built and applied in different spatial simulations. Through model comparison, it was established that: (1) both types of villages have developed in the same cyclical changing mode of "outlying + edge-expansion", which was probably rooted in the inherent spatial sense of the ethnic group inhabiting village types; (2) the spatial growth of the clustered village was more relevant to the distribution structure of pre-existing buildings, whereas the spatial sprawl of a dispersed one was more connected to external natural factors; and (3) the development of every economic unit in a dispersed village was strictly restricted to the building area, and to the proportion of population inhabiting farmland area. Although village patterns developed under the same logical framework rooted in ethnic culture, their development tendency varied, with different dynamic mechanisms and constraints.
Novel nannofossils extraction methods from paintings, coupled with GC–MS for provenance determination and binder analysis
Authors: Jaques Victory Armida Janine , Trubač Jakub , Rathouský Jiří , Cajthaml Tomáš , Holcová Katarína 
Published: August 2022

Abstract
The use of calcareous nannofossils for provenance analysis is a new-old topic for cultural heritage. Several studies have already mentioned it for ceramic, but less for paintings. Preparatory layers of the paintings are often made with chalk, which is composed of microfossils. To extract a calcareous nannofossils assemblage from a painting layer, we need to disaggregate it. The method is to plunge the micro-samples into water and heat it if water alone does not work. The disaggregation process takes a long time and is not efficient in terms of quantitative results. In this work, we aimed to develop a disaggregation method that increases the number of determinable nannofossils extracted from a painting micro-sample. As these samples are valuable and unique, we decided that a combination of analyses on the disaggregated micro-sample should be tried to extract the most information from it. We studied the possibility of binder determination by gas chromatography–mass spectrometer after the nannofossils assemblage extraction on the residual liquid from the disaggregation. The method we are presenting is easy to apply, has a high disaggregation rate for most paintings, and a low impact on binders fatty acids for their determination.
Indication-wide drug pricing: Insights from the pharma market
Authors: Siegmeier Florian , Büssgen Melanie 
Published: August 2022

Abstract
Background
Pharmaceutical spending has been increasing rapidly for years and is higher than ever before. To control the rising costs, countries are implementing regulatory frameworks such as (internal) reference pricing, price cuts or generics substitution. Internal reference pricing establishes a reference price within a country which serves as the maximum level of reimbursement for a group of pharmaceuticals. Price setting in the German market is especially relevant for many European countries, which use Germany as a reference country for their own price setting.

Methods
We evaluate pharmaceutical price dynamics for not reference priced pharmaceuticals (NRPs) as well as for reference priced pharmaceuticals (RPs) in Germany—referring to the internal reference price system. 64,862 medication packs have been extracted from the German pharmaceutical pricing register Lauer-Taxe. For each pack, we extracted detailed data on the company, manufacturer rebates, pharmacy retail prices, reference prices, co-payments, import quotas, and discount agreements. We then investigated price setting and dynamics of NRPs vs. RPs for all 14 indication areas by ATC code level 1.

Results
The average manufacturer price per pack was 604.84€ for NRPs and 112.11€ for RPs. Similar differences were found for the wholesale price and the pharmacy retail price. The reference price was—as expected—0.00€ for NRPs, and 154.40€ for RPs. NRP packs were imported in 42.38%, while RP packs were imported only in 24.62%. Highest average pharmacy retail prices could be found in the therapeutic areas ‘antineoplastic and immunomodulating agents’ (1711.47€), ‘systemic hormonal preparations’ (1331.95€), and ‘blood and blood forming organs’ (1260.58€). We detected high fluctuations in pharmacy retail prices per indication, as well as for reference prices per indication. The indications with the highest number of reference price regulated medical packs are ‘cardiovascular system’, ‘musculo-skeletal system’, and ‘nervous system’. Highest co-payments were found in the indications ‘antineoplastic and immunomodulating agents’, ‘blood and blood forming organs’, and ‘antiinfectives for systemic use’.

Conclusion
Price setting and price dynamics vary substantially between NRP and RP medication packs. Further, we saw major differences across all indication areas as well as when comparing medication packs launched by top 20 pharma companies vs. the rest.
Efficient biodegradation of straw and persistent organic pollutants by a novel strategy using recombinant Trichoderma reesei
Authors: Xia Ying , Lin Xinda 
Published: August 2022

AbstractEfficient biodegradation of lignocellulosic biomass needs a battery of enzymes targeting cellulose, hemicellulose, and lignin. In this study, recombinant Trichoderma reesei ZJ-09 with Pycnoporus sanguineus laccase gene was used to degrade rice straw by in situ production of laccase, xylanase, and cellulases under solid-state fermentation (SSF). Effects of parameters on key enzymes (cellulase, xylanase, and laccase) in biodegradation during SSF were investigated. Under the optimized SSF conditions, the FPA, xylanase activity, and laccase activity reached 110.47 FPU/g, 5787.59 IU/g, and 24.45 IU/g, respectively, on day 12. The obtained recombinant T. reesei SSF system achieved efficient degradation of rice straw with the final mass loss up to 51.16% which was 1.4-fold higher than the host strain. Further, bioconversion of rice straw into a novel laccase-enriched koji for persistent organic pollutants bioremediation (LKPB) was conducted by the optimized SSF system. LKPB was found to degrade persistent organic pollutants (POPs) effectively without the addition of mediators. 4-h removal rates of three POPs mediated by LKPB (87.21% for 2,4,5-trichlorophenol, 92.45% for nonylphenol, and 90.73% for oxytetracycline) were comparable to those achieved by laccase-co-mediator system. The newly established recombinant T. reesei SSF system could be potential to effectively degrade lignocellulosic wastes as well as organic pollutants.
Graphical abstract
Development of highly efficient whole-cell catalysts of cis-epoxysuccinic acid hydrolase by surface display
Authors: Zhou Rui , Dong Sheng , Feng Yingang , Cui Qiu , Xuan Jinsong 
Published: August 2022

AbstractBacterial cis-epoxysuccinic acid hydrolases (CESHs) are intracellular enzymes used in the industrial production of enantiomeric tartaric acids. The enzymes are mainly used as whole-cell catalysts because of the low stability of purified CESHs. However, the low cell permeability is the major drawback of the whole-cell catalyst. To overcome this problem, we developed whole-cell catalysts using various surface display systems for CESH[L] which produces L(+)-tartaric acid. Considering that the display efficiency depends on both the carrier and the passenger, we screened five different anchoring motifs in Escherichia coli. Display efficiencies are significantly different among these five systems and the InaPbN-CESH[L] system has the highest whole-cell enzymatic activity. Conditions for InaPbN-CESH[L] production were optimized and a maturation step was discovered which can increase the whole-cell activity several times. After optimization, the total activity of the InaPbN-CESH[L] surface display system is higher than the total lysate activity of an intracellular CESH[L] overexpression system, indicating a very high CESH[L] display level. Furthermore, the whole-cell InaPbN-CESH[L] biocatalyst exhibited good storage stability at 4 °C and considerable reusability. Thereby, an efficient whole-cell CESH[L] biocatalyst was developed in this study, which solves the cell permeability problem and provides a valuable system for industrial L(+)-tartaric acid production.
Graphical Abstract
Effect of bovine milk fat-based infant formulae on microbiota, metabolites and stool parameters in healthy term infants in a randomized, crossover, placebo-controlled trial
Authors: Looijesteijn Ellen , Brouwer Rutger W. W. , Schoemaker Ruud J. W. , Ulfman Laurien H. , Ham Stephanie L. , Jeurink Prescilla , Karaglani Eva , van IJcken Wilfred F. J. , Manios Yannis 
Published: August 2022

Abstract
Background
Natural enrichment of sn-2 palmitate content of infant formulae by using bovine milk fat is known to reduce formation of faecal fatty acid soaps and to improve stool consistency, but effects on gut microbiota composition are unknown. The purpose of this study was to test the influence of milk fat-based formula high in sn-2 palmitate on the infants’ gut microbiota composition and to confirm the beneficial effects of the formula on formation of faecal fatty acid soaps and stool consistency.

Methods
Twenty-two healthy term, formula-fed infants were enrolled in a single-blinded randomized, crossover, placebo-controlled trial. After a 2-week run-in period, infants received either a 50% milk fat-based formula containing 39% sn-2 palmitate (MF) or a vegetable fat-based formula (VF) containing 10% sn-2 palmitate in a 2 × 2-week crossover design. Faecal microbiota composition was the primary outcome of the study. Other outcomes included faecal fatty acid soap excretion, calcium excretion, gut comfort parameters and faecal metabolites.

Results
Microbiota analysis showed that bifidobacteria dominated the gut microbiota of most infants. Neither alpha- nor beta-diversity was significantly influenced by the intervention. Also, abundance of metabolic pathways was independent of the intervention. The MF formula resulted in significantly lower faecal levels of palmitic acid soap (p = 0.0002) and total fatty acid soaps (p = 0.0001) than the VF formula. Additionally, calcium excretion and palmitic acid concentration were significantly (p = 0.0335) lower in stool samples after MF intervention. Furthermore, a significant physiological effect on softer stools was observed in the MF intervention compared to the VF intervention (p = 0.02).
Of the 870 measured faecal metabolites, 190 were significantly different after MF and VF intervention (FDR corrected p < 0.05). Most of these were found at higher levels after MF intervention, potentially indicative of the complex structure of milk fat. Metabolites with more than twofold change between interventions were mostly lipid-derived and included several milk fat-specific fatty acids.

Conclusions
Replacing part of the vegetable fat in infant formula with bovine milk fat with high sn-2 palmitate levels did not change the microbiota composition, although a reduction in faecal palmitate soaps, total fatty acid soaps and calcium excretion while improving stool consistency in the MF intervention was confirmed. In addition, 190 faecal metabolites were significantly different, many related to the fat source.

Trial registration
Netherlands Trial Registry Identifier: NL7815 19/06/2019.
Computation of contrast-enhanced perfusion using only two CT scan phases: a proof-of-concept study on abdominal organs
Authors: Cressoni Massimo , Cozzi Andrea , Schiaffino Simone , Cadringher Paolo , Vitali Paolo , Basso Gianpaolo , Ippolito Davide , Sardanelli Francesco 
Published: August 2022

Abstract
Background
Computed tomography perfusion imaging (CTPI) by repeated scanning has clinical relevance but implies relatively high radiation exposure. We present a method to measure perfusion from two CT scan phases only, considering tissue enhancement, feeding vessel (aortic) peak enhancement, and bolus shape.

Methods
CTPI scans (each with 40 frames acquired every 1.5 s) of 11 patients with advanced hepatocellular carcinoma (HCC) enrolled between 2012 and 2016 were retrospectively analysed (aged 69 ± 9 years, 8/11 males). Perfusion was defined as the maximal slope of the time-enhancement curve divided by the peak enhancement of the feeding vessel (aorta). Perfusion was computed two times, first using the maximum slope derived from all data points and then using the peak tissue enhancement and the bolus shape obtained from the aortic curve.

Results
Perfusion values from the two methods were linearly related (r2 = 0.92, p < 0.001; Bland–Altman analysis bias -0.12). The mathematical model showed that the perfusion ratio of two ROIs with the same feeding vessel (aorta) corresponds to their peak enhancement ratio (r2 = 0.55, p < 0.001; Bland–Altman analysis bias -0.68). The relationship between perfusion and tissue enhancement is predicted to be linear in the clinical range of interest, being only function of perfusion, peak feeding vessel enhancement, and bolus shape.

Conclusions
This proof-of-concept study showed that perfusion values of HCC, kidney, and pancreas could be computed using enhancement measured only with two CT scan phases, if aortic peak enhancement and bolus shape are known.