bluuebunny/crossref_metadata_2025_split huggingface dataset:
The non-SaccharomycesyeastPichia kluyverifor the production of aromatic volatile compounds in alcoholic fermentation
Authors: Méndez-Zamora Andrés , Gutiérrez-Avendaño Daniel Oswaldo , Arellano-Plaza Melchor , De la Torre González Francisco Javier , Barrera-Martínez Iliana , Gschaedler Mathis Anne , Casas-Godoy Leticia 
Published: December 2020

ABSTRACTAlcoholic fermentation is influenced by yeast strain, culture media, substrate concentration and fermentation conditions, which contribute to taste and aroma. Some non-Saccharomyces yeasts are recognized as volatile compound producers that enrich aromatic profile of alcoholic beverages. In this work, 21 strains of Pichia kluyveri isolated from different fermentative processes and regions were evaluated. A principal component analysis (PCA) showed statistical differences between strains mainly associated with the variety and concentration of the compounds produced. From the PCA, two strains (PK1 and PK8) with the best volatile compound production were selected to evaluate the impact of culture media (M12 medium and Agave tequilana juice), stirring speeds (100 and 250 rpm) and temperatures (20°C, 25°C and 30°C). Increased ester production was observed at 250 rpm. Greatest effect in alcohols and ester production was found with A. tequilana, identifying PK1 as higher alcohol producer, and PK8 as better ester producer. Regarding temperature, PK1 increased ester production with decreased fermentation temperature. PK8 presented maximum levels of ethyl acetate and ethyl dodecanoate at 20°C, and finally isoamyl acetate increased its production at 30°C. Therefore, P. kluyveri strains are of great interest to produce different aromatic profiles that are affected by factors including medium, agitation and temperature.
Dose–Response Effect of Dietary Nitrate on Muscle Contractility and Blood Pressure in Older Subjects: A Pilot Study
Authors: Gallardo Edgar J , Gray Derrick A , Hoffman Richard L , Yates Brandon A , Moorthi Ranjani N , Coggan Andrew R 
Published: December 2020

Abstract
We have recently demonstrated that dietary nitrate, a source of nitric oxide (NO) via the nitrate → nitrite → NO enterosalivary pathway, can improve muscle contractility in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. A pilot randomized, double-blind, placebo-controlled crossover study was therefore performed to determine the effects of ingesting 3.3 mL/kg of concentrated beetroot juice containing 0, 200, or 400 µmol/kg of nitrate in 9 healthy older subjects (mean age 70 ± 1 years). Maximal knee extensor power (Pmax) and speed (Vmax) were measured ~2.5 hours after nitrate ingestion using isokinetic dynamometry. Blood pressure was monitored periodically throughout each study. Pmax (in W/kg) was higher (p &lt; .05) after the lower dose (3.9 ± 0.4) compared to the placebo (3.7 ± 0.4) or higher dose (3.7 ± 0.4). Vmax (in rad/s) also tended to be higher (p = .08) after the lower dose (11.9 ± 0.7) compared to the placebo (10.8 ± 0.8) or higher dose (11.2 ± 0.8). Eight out of 9 subjects achieved a higher Pmax and Vmax after the lower versus the higher dose. These dose-related changes in muscle contractility generally paralleled changes in breath NO levels. No significant changes were found in systolic, diastolic, or mean arterial blood pressure. A lower dose of nitrate increases muscle speed and power in healthy older individuals, but these improvements are lost at a higher dose. Blood pressure, on the other hand, is not reduced even with a higher dose.
Local Coupling and Conversion of Surface Waves due to Earth’s Rotation. Part 2: Numerical Examples
Authors: Sens-Schönfelder Christoph , Bozdağ Ebru , Snieder Roel 
Published: December 2020

Summary
Rotation of the Earth affects the propagation of seismic waves. The global coupling of spheroidal and toroidal modes by the Coriolis force over time is described by normal-mode theory. The local action of the Coriolis force on the propagation of surface waves can be described by coefficients for the coupling between propagating Rayleigh and Love waves as derived by (Landau & Lifshitz 1959). Using global wavefield simulations we show how the Coriolis force leads to coupling and conversion between both surface wave types depending on latitude, propagation direction, frequency, and local velocity structure. Surface wave coupling is most efficient for periods where the modes have similar phase velocities, a condition that is equivalent to the selection rules of the angular degree in the normal-mode framework, a phenomenon that we refer to as resonant coupling. In the time-domain, resonant coupling gradually converts energy from one wave type–Rayleigh waves or Love wave–into the other, which then propagates independently. Due to the lateral heterogeneity, the condition of equal phase velocity renders the rotational coupling location-dependent. East-west oriented ray path segments and segments at high latitudes (across the Poles) only weakly couple the fundamental mode Rayleigh and Love waves while coupling is strongest for propagation along the meridians across the equator. At 250 s period, where Love and Rayleigh waves have similar phase velocities, the net energy transfer from Rayleigh to Love wave reaches about 10% for one orbit.
Germline EGFR variants are over-represented in adolescents and young adults (AYA) with adrenocortical carcinoma
Authors: Akhavanfard Sara , Yehia Lamis , Padmanabhan Roshan , Reynolds Jordan P , Ni Ying , Eng Charis 
Published: December 2020

Abstract
Adrenocortical Carcinoma (ACC) is a rare endocrine tumor with poor overall prognosis and 1.5-fold overrepresentation in females. In children, ACC is associated with inherited cancer syndromes with 50–80% of childhood-ACC associated with TP53 germline variants. ACC in adolescents and young adults (AYA) is rarely due to germline TP53, IGF2, PRKAR1A and MEN1 variants. We analyzed exome sequencing data from 21 children (&lt;15y), 32 AYA (15-39y), and 60 adults (&gt;39y) with ACC, and retained all pathogenic, likely pathogenic, and highly prioritized variants of uncertain significance. We engineered a stable lentiviral-mutant ACC cell line, harboring an EGFR variant (p.Asp1080Asn) from a 21-year-old female without germline-TP53-variant and with aggressive ACC. We found that 4.8% of the children (P = 0.004) and 6.2% of AYA (P &lt; 0.0001), all-female participants, harbored germline EGFR variants, compared to only 0.3% of the control group. Expanding our analysis to the RTK-RAS-MAPK pathway, we found that the RTK genes have the highest number of highly prioritized germline variants in these individuals amongst all three arms of this pathway. We showed EGFR mutant cells migrate faster and are characterized by a stem-like phenotype compared to wild type cells. While EGFR inhibitors did not affect the stemness of mutant cells, Sunitinib, a multireceptor tyrosine kinase inhibitor, significantly reduced their stem-like behavior. Our data suggest that EGFR could be a novel underlying germline predisposition factor for ACC, especially in the Childhood-AYA (C-AYA) population. Further clinical validation can improve precision oncology management of this disease, which is known to have limited therapeutic options.
Impact of the Trophic Effects of the Secretome From a Multistrain Probiotic Preparation on the Intestinal Epithelia
Authors: Petito Valentina , Greco Viviana , Laterza Lucrezia , Graziani Cristina , Fanali Caterina , Lucchetti Donatella , Barbaro Maria Raffaella , Bugli Francesca , Pieroni Luisa , Lopetuso Loris Riccardo , Sgambato Alessandro , Sanguinetti Maurizio , Scaldaferri Franco , Urbani Andrea , Gasbarrini Antonio 
Published: December 2020

Abstract

Background
Probiotics are defined as live, nonpathogenic bacteria that confer health benefits beyond their nutritional value. In particular, VSL#3 exhibits demonstrated efficacy in the management of diseases characterized by an increased intestinal permeability. Our study aimed to understand how VSL#3 promotes gut health by secreting bioactive factors and identify which human pathways are modulated by secretome derived from the VSL#3 formula.

Methods
Two different lots of VSL#3 were used, and Caco-2 cell line was treated with conditioned media (CM) prepared using 1 g of the probiotic formula. We evaluated the effects of the probiotics on cellular proliferation and apoptosis by cytometry and the expression of tight junction proteins by western blotting. A proteomics analysis of both culture media and the whole proteome of Caco-2 cells treated with VSL#3-CM was performed by nano-ultra performance liquid chromatography - tandem mass (nUPLC MS/MS) spectrometry.

Results
The probiotic formula increased cell proliferation, decreased cellular apoptosis cells, and increased re-epithelialization in the scratch assay. Several peptides specifically synthetized by all the species within the probiotic preparation were recognized in the proteomics analysis. Human proteins synthesized by CaCo-2 cells were also identified.

Conclusions
To our knowledge, this manuscript describes the first evaluation of the probiotic secretome, and the results showed that the improvement in intestinal barrier functions induced by probiotics seems to be accompanied by the modulation of some human cellular pathways.
Assessing Patient Decision-Making on Biologic and Small-Molecule Therapies in Inflammatory Bowel Diseases: Insights From a Conjoint Analysis in the United States, Canada, and the United Kingdom
Authors: Patel Devin B , van Deen Welmoed K , Almario Christopher V , Khalil Carine , Warui Esther , Bonthala Nirupama , Melmed Gil Y , Spiegel Brennan M R 
Published: December 2020

Abstract

Background
Recent drug approvals have increased the number of therapies available for inflammatory bowel disease (IBD), making it difficult for patients to navigate available treatment options. We examined patient decision-making surrounding biologic and small-molecule therapies in an international cohort of patients from the United States, Canada, and the United Kingdom using conjoint analysis (CA), a form of tradeoff analysis examining how respondents make complex decisions.

Methods
We performed a CA survey that quantified the relative importance of therapy attributes (eg, efficacy, adverse effects) in decision-making. Patients with IBD were recruited from the general population and through specialty IBD clinics. We used a hierarchical Bayes analysis to model individual patients’ preferences and compared the relative importance of medication attributes between countries and practice settings. Using a series of multivariable linear regression models, we assessed whether demographic and clinical characteristics (eg, IBD subtype, severity) predicted how patients made decisions.

Results
Overall, 1077 patients in 3 countries completed the survey. No differences in the relative importance of medication attributes were observed between the 3 countries’ general IBD populations. However, efficacy was more important for patients in the US-based IBD specialty care cohort than for the general IBD population (29% and 23% importance, respectively; P &lt; 0.0001). A few demographic and clinical characteristics were associated with small changes in individual preferences.

Conclusions
In this large international CA study, patients prioritized efficacy as the most important therapeutic attribute. Decision-making seemed to be highly personalized in that therapeutic preferences were hard to predict based on patient characteristics.
Serrated Epithelial Change Is Associated With High Rates of Neoplasia in Ulcerative Colitis Patients: A Case-controlled Study and Systematic Review With Meta-analysis
Authors: Parian Alyssa M , Limketkai Berkeley N , Chowdhury Reezwana , Brewer Gala Godoy , Salem George , Falloon Katie , Selaru Florin , Melia Joanna , Lazarev Mark G 
Published: December 2020

Abstract

Background
Patients with long-standing ulcerative colitis (UC) are at an increased risk of colorectal cancer. Risk stratification is important to identify patients who require more frequent endoscopic surveillance. Serrated epithelial change (SEC) found in patients with long-standing colitis may be associated with neoplasia and serve as a marker to stratify patients at higher risk of colorectal cancer (CRC).

Methods
A case-control study was performed to compare the rates of neoplasia between UC patients with SEC and UC patients without SEC who were matched for age, disease duration, and disease extent. Paired tests, conditional logistic regression, and Kaplan-Meier analyses were used to compare groups. A systematic review with meta-analysis was performed, combining our local data with previously published data.

Results
This study included 196 UC patients without prior neoplasia, 98 with SEC and 98 without SEC. Ulcerative colitis patients with SEC had a significantly higher rate of synchronous or metachronous neoplasia than UC patients without SEC (26.5% vs 3.1%; P &lt; 0.001). Synchronous or metachronous high-grade dysplasia and CRC were found more frequently in UC patients with SEC than UC patients without SEC (11.2% vs 2.0%; P = 0.02). A meta-analysis was consistent with these findings, showing a higher rate of neoplasia in patients with SEC compared with those without SEC (16.4% vs 3.9%; P &lt; 0.001).

Conclusion
Serrated epithelial change is associated with a significantly increased risk of synchronous and metachronous neoplasia including high-grade dysplasia and CRC in patients with UC. Histopathological findings of SEC should warrant closer endoscopic surveillance for CRC.
The Role of Dipeptidyl Peptidase 4 as a Therapeutic Target and Serum Biomarker in Inflammatory Bowel Disease: A Systematic Review
Authors: Melo Francisco Jorge , Pinto-Lopes Pedro , Estevinho Maria Manuela , Magro Fernando 
Published: December 2020

AbstractBackgroundThe roles dipeptidyl peptidase 4 (DPP4), aminopeptidase N (APN), and their substrates in autoimmune diseases are being increasingly recognized. However, their significance in inflammatory bowel diseases (IBD) is not entirely understood. This systematic review aims to discuss the pathophysiological processes related to these ectopeptidases while comparing findings from preclinical and clinical settings.MethodsThis review was conducted according to the PRISMA guidelines. We performed a literature search in PubMed, SCOPUS, and Web of Science to identify all reports from inception until February 2020. The search included validated animal models of intestinal inflammation and studies in IBD patients. Quality assessment was performed using SYRCLE’s risk of bias tool and CASP qualitative and cohort checklists.ResultsFrom the 45 included studies, 36 were performed in animal models and 12 in humans (3 reports included both). Overall, the methodological quality of preclinical studies was acceptable. In animal models, DPP4 and APN inhibition significantly improved intestinal inflammation.Glucagon-like peptide (GLP)-1 and GLP-2 analogs and GLP-2-relase-inducing drugs also showed significant benefits in recovery from inflammatory damage. A nonsignificant trend toward disease remission with the GLP-2 analog teduglutide was observed in the sole interventional human study. All human studies reported an inverse correlation between soluble DPP4/CD26 levels and disease severity, in accordance with the proposal of DPP4 as a biomarker for IBD.ConclusionsThe use of DPP4 inhibitors and analogs of its substrates has clear benefits in the treatment of experimentally induced intestinal inflammation. Further research is warranted to validate their potential diagnostic and therapeutic applications in IBD patients.
Domain decomposition preconditioners for high-order discretizations of the heterogeneous Helmholtz equation
Authors: Gong Shihua , Graham Ivan G , Spence Euan A 
Published: December 2020

Abstract
We consider one-level additive Schwarz domain decomposition preconditioners for the Helmholtz equation with variable coefficients (modelling wave propagation in heterogeneous media), subject to boundary conditions that include wave scattering problems. Absorption is included as a parameter in the problem. This problem is discretized using $H^1$-conforming nodal finite elements of fixed local degree $p$ on meshes with diameter $h = h(k)$, chosen so that the error remains bounded with increasing $k$. The action of the one-level preconditioner consists of the parallel solution of problems on subdomains (which can be of general geometry), each equipped with an impedance boundary condition. We prove rigorous estimates on the norm and field of values of the left- or right-preconditioned matrix that show explicitly how the absorption, the heterogeneity in the coefficients and the dependence on the degree enter the estimates. These estimates prove rigorously that, with enough absorption and for $k$ large enough, GMRES is guaranteed to converge in a number of iterations that is independent of $k,p$ and the coefficients. The theoretical threshold for $k$ to be large enough depends on $p$ and on the local variation of coefficients in subdomains (and not globally). Extensive numerical experiments are given for both the absorptive and the propagative cases; in the latter case, we investigate examples both when the coefficients are nontrapping and when they are trapping. These experiments support (i) our theory in terms of dependence on polynomial degree and the coefficients; and (ii) the sharpness of our field of values estimates in terms of the level of absorption required.
Efficacy of a Dengue Vaccine Candidate (TAK-003) in Healthy Children and Adolescents 2 Years after Vaccination
Authors: López-Medina Eduardo , Biswal Shibadas , Saez-Llorens Xavier , Borja-Tabora Charissa , Bravo Lulu , Sirivichayakul Chukiat , Vargas Luis Martinez , Alera Maria Theresa , Velásquez Hector , Reynales Humberto , Rivera Luis , Watanaveeradej Veerachai , Rodriguez-Arenales Edith Johana , Yu Delia , Espinoza Felix , Dietze Reynaldo , Fernando Lak Kumar , Wickramasinghe Pujitha , Duarte Moreira Edson , Fernando Asvini D , Gunasekera Dulanie , Luz Kleber , da Cunha Rivaldo Venâncio , Tricou Vianney , Rauscher Martina , Liu Mengya , LeFevre Inge , Wallace Derek , Kosalaraksa Pope , Borkowski Astrid 
Published: December 2020

Abstract

Background
Takeda’s dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update.

Methods
Children (20 099, 4–16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR.

Results
Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%–77.3%), including 67.0% (95% CI, 53.6%–76.5%) in dengue-naive and 89.2% (95% CI, 82.4%–93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%–66.8%) with the largest decline in 4–5 year olds (24.5%; 95% CI, −34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%–72.4%) in 6–11 year and 71.2% (95% CI, 41.0%–85.9%) in 12–16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adverse events occurred during the second year.

Conclusions
TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further.
Clinical Trials Registration. NCT02747927.
Takeda’s tetravalent dengue vaccine (TAK-003) continued to demonstrate benefit in reducing dengue independent of baseline serostatus up to 2 years after completing vaccination with some decline in efficacy during the second year in 4–16 year olds in dengue-endemic countries.
Systematic Position of the Enigmatic Psocid Family Lesneiidae (Insecta: Psocodea: Psocomorpha), With Description of Two New Species
Authors: Yoshizawa Kazunori , Marusik Yuri M , Yao Izumi , Lienhard Charles 
Published: December 2020

Abstract
The systematic placement of an enigmatic psocid family restricted to Africa, Lesneiidae, was estimated by using a multiple gene data set. The candidates for its close relatives are now classified under two different infraorders, the family Archipsocidae of the infraorder Archipsocetae or the families Elipsocidae/Mesopsocidae of the infraorder Homilopsocidea. The maximum likelihood and Bayesian analyses of the molecular data set strongly suggested that the Lesneiidae belongs to Homilopsocidea and forms a clade with Elipsocidae/Mesopsocidae/Eolachesillinae (Lachesillidae). However, the relationships among these (sub)families and Lesneiidae, including the monophyly of Elipsocidae and Mesopsocidae, were ambiguous or questionable, showing the necessity of further investigations for elucidating their relationships and validating the status of these families. Two species, L. johnsoni Yoshizawa & Lienhard, n. sp. and L. testudinata Yoshizawa & Lienhard, n. sp. (Psocodea: Lesneiidae), were described from South Africa. There appears to be a tight association between the reproductive biology and morphological specialization of this group.
Inter-prescriber variability in the decision to prescribe antibiotics to febrile patients attending primary care in Myanmar
Authors: Swe Myo Maung Maung , Ashley Elizabeth A , Althaus Thomas , Lubell Yoel , Smithuis Frank , Mclean Alistair R D 
Published: December 2020

Abstract

Background
Most antibiotic prescribing occurs in primary care. Even within the same health facility, there may be differences between prescribers in their tendency to prescribe antibiotics, which may be masked by summary data. We aimed to quantify prescriber variability in antibiotic prescription to patients with acute fever in primary care clinics in Myanmar.

Methods
We conducted a secondary analysis of prescribing data from 1090 patient consultations with 40 prescribing doctors from a trial investigating the effect of point-of-care C-reactive protein (CRP) tests on antibiotic prescription for acute fever. We used multilevel logistic regression models to assess inter-prescriber variability in the decision to prescribe antibiotics.

Results
The median odds ratio (MOR) in the unadjusted model was 1.82 (95% CI: 1.47–2.56) indicating that when two prescribers from this population are randomly selected then in half of these pairs the odds of prescription will be greater than 1.82-fold higher in one prescriber than the other. The estimated variability from this sample of prescribers corresponds to a population of prescribers where the top 25% of prescribers will prescribe antibiotics to over 41% of patients while the bottom 25% will prescribe antibiotics to less than 23% of patients. Inter-prescriber variation in antibiotic prescribing remained after adjustment for patient characteristics and CRP information (P &lt; 0.001).

Conclusions
Despite sharing the same management guidelines, there was substantial inter-prescriber variation in antibiotic prescription to patients with acute fever. This variation should be considered when designing trials and stewardship programmes aiming to reduce inappropriate antibiotic prescribing.