bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of the life cycle of the innovation apiproduct from drone larvae and its introduction in the food industry
Authors: Prokhoda I A , Eliseeva E V , Polesskaya O P , Potseluev E I , Zabenko D V 
Published: June 2019

Abstract
The articles summarizes the experience the small innovative enterprise “Apiproduct” (Open Company SIP “Apiproduct”) - the first Russian enterprise that manages a life cycle of the innovation apiproduct from drone larvae, and its introduction in the food industry for the enrichment of mass consumption products with high-grade protein, biologically active high-functional substances and complexes. The authors analyzed the key stages of the life cycle of the apiproduct that consist of the justification of the idea of utilization of products of the larval origin in the food industry, experimental scientific and practical research, technology of the apiproduct manufacturing in a powder form with the author’s name “Bilar”, and production of its pilot batch in the Open Company SIP “Apiproducts”. The authors’ technology of production of the apiproduct “Bilar” includes the following stages: cultivation, reception and grinding of larvae to biomass, sublimation vacuum drying of biomass and production of powder with a mass fraction of 2% moisture. To date, the Russian apiproduct “Bilar” passed the sanitary-hygienic examination and can be used in its pure form as a food processor, containing in addition to protein, vitamins b, β-carotene, α-tocopherol, additionally biotin, vitamins PP, 28 macro-and microelements, unsaturated fatty acids (linoleic and arachidonic), phenolic compounds with p-vitamin activity, 80 enzymes, biopolymers, growth factor, etc., that has a long shelf life due to removal of water from the structure. The practice of the SIP “Apiproduct” work demonstrates that manufacturing and introduction of this innovation product - apiproduct “Bilar” - to the market significantly increases the assortment and competitiveness of the enterprise.
Analytical solution for the vertical structure eigenfunction in diagnosis of the low frequency wave-type perturbations in primitive dynamics equation
Authors: Rainchik S E 
Published: June 2019

Abstract
This study presents an analytical solution to the problem of determining the vertical modal structure of low-frequency atmospheric oscillations. This analytical solution is critically compared with the numerical solution of this problem known in the literature, and good agreement for vertical normal modes with the wave number less than 9 is found. Applicability of the analytical solution for diagnosing the atmospheric climate variability and the quality of its simulation by contemporary GCM is briefly discussed.
Numerical modeling of the influence of different options for feeding fuel on the combustion process for turbine profiles
Authors: Dostiyarov A M , Umyshev D R , Katranova G S 
Published: June 2019

Abstract
The article presents the results of numerical modeling of the effect of various fuel supply options on the combustion processes behind the turbine profiles. The article considered three options for fuel supply. In the first option, (a) the fuel is supplied to the wide side of the profile; in the second option, (b) the fuel is sprayed directly into the recirculation zone formed between the plate and the profiles; in the third option, (c) the fuel is sprayed from the convex (back) part of the profile. On the basis of the analysis performed, it can be concluded that the profiles of the blades have rather high stabilization parameters. The best performance has the option of supplying fuel from the back of the turbine profile. This option provides the minimum concentration of nitrogen oxides, with all other factors being equal.
Blood Pressure, Chronic Kidney Disease Progression, and Kidney Allograft Failure in Kidney Transplant Recipients: A Secondary Analysis of the FAVORIT Trial
Authors: Malhotra Rakesh , Katz Ronit , Weiner Daniel E , Levey Andrew S , Cheung Alfred K , Bostom Andrew G , Ix Joachim H 
Published: June 2019

Abstract

BACKGROUND
In chronic kidney disease, intensive systolic blood pressure (SBP) control reduces mortality at a cost of greater acute kidney injury risk. Kidney transplantation involves implantation of denervated kidneys and immunosuppressive medications that increase acute kidney injury risk. The optimal blood pressure (BP) target in kidney transplant recipients (KTRs) is uncertain. Prior observational studies from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial demonstrate associations of lower SBP levels and reduced mortality risk, but the relationship of BP with kidney allograft function remains unknown. Thus, in FAVORIT, we investigated the relationship of SBP and diastolic blood pressure (DBP) with risk of kidney allograft failure and estimated glomerular filtration rate (eGFR) slope among stable KTRs.

METHODS
Cox proportional hazards and multivariable linear regression models adjusted for demographics, transplant characteristics, comorbidities, baseline eGFR, and urine albumin-to-creatinine ratio were used to determine associations of SBP and DBP with time to a composite kidney outcome of ≥50% eGFR decline or dialysis dependence, and with annualized eGFR change, respectively. Multivariable restricted cubic spline plots were developed to evaluate the functional form of the relationships.

RESULTS
Among 3,598 KTRs, mean age was 52 ± 9 years, SBP was 136 ± 20 mm Hg, DBP was 79 ± 12 mm Hg, and eGFR was 49 ± 18 ml/minute/1.73 m2. There were 369 events of ≥50% eGFR decline or dialysis dependence during a mean follow-up of 4.0 ± 1.5 years. There was no association of either SBP (compared with SBP 120 to &lt;130 mm Hg, hazard ratio (HR) for the SBP &lt; 110 was 1.01 (95% confidence interval (CI) 0.60 to 1.70) and 130 to &lt;140 was 0.89 (0.64 to 1.24)) or DBP (compared with DBP 70 to &lt;80 mm Hg, HR for the DBP 60 to &lt;70 was 1.00 (95% CI 0.74 to 1.34) and 80 to &lt;90 was 0.90 (0.68 to 1.18)) with the kidney failure outcome or annualized eGFR slope, and, when examined using restricted cubic splines, there was no evidence of “J”- or “U”-shaped relationships.

CONCLUSIONS
In a large sample of stable KTRs, we found no evidence of thresholds at which lower BPs were related to higher risk of allograft failure or eGFR decline. In light of prior findings of mortality benefit at low SBP, these observational findings suggest lower BP may be beneficial in KTRs. This important question requires confirmation in future randomized trials in KTRs.
What have we recently learned about song learning and social interactions?
Authors: García Natalia C 
Published: June 2019

Abstract
Vocal learning in birds is a complex animal behavior with several parallels to vocal learning in humans. Early experiments in the 70s showing that juvenile birds could learn their species’ normal song presented only through loudspeakers led to the general notion that social interactions are unnecessary for song learning. These views were soon challenged, and after decades of research we know that different social factors influence song learning. Here, I discuss recent research that is getting us closer to understanding how. Juvenile birds in the wild are exposed to both direct and indirect interactions with singing adults, which can be relevant to different aspects of the learning process. The exposure to a potential living tutor may trigger or enhance the learning process, but direct interaction with a tutor producing the song type that is finally learned or incorporated to the repertoire is not required. Social interactions that the learner witnesses may be more important in determining which songs are included in the final repertoire of an adult bird. Further research is also required to better understand the role of interactions with females, not by providing a model song to imitate but by exhibiting responses contingent to juveniles practicing their songs.
Smooth muscle cell-specific TMEM16A deletion does not alter Ca2+ signaling, uterine contraction, gestation length, or litter size in mice†
Authors: Qu Mingzi , Lu Ping , Bellve Karl , Fogarty Kevin , Lifshitz Lawrence , Shi Fangxiong , Zhuge Ronghua 
Published: June 2019

Abstract
Ion channels in myometrial cells play critical roles in spontaneous and agonist-induced uterine contraction during the menstrual cycle, pregnancy maintenance, and parturition; thus, identifying the genes of ion channels in these cells and determining their roles are essential to understanding the biology of reproduction. Previous studies with in vitro functional and pharmacological approaches have produced controversial results regarding the presence and role of TMEM16A Ca2+-activated Cl− channels in myometrial cells. To unambiguously determine the function of this channel in these cells, we employed a genetic approach by using smooth muscle cell-specific TMEM16A deletion (i.e. TMEM16ASMKO) mice. We found that myometrial cells from TMEM16ASMKO mice generated the same pattern and magnitude in Ca2+ signals upon stimulation with KCl, oxytocin, and PGF2α compared to the isogenic control myometrial cells. At the uterine tissue level, TMEM16A deletion also did not cause detectable changes in either spontaneous or agonist (i.e. KCl, oxytocin, and PGF2α)-induced contractions. Moreover, in vivo the TMEM16ASMKO mice gave birth at full term with the same litter size as genetically identical control mice. Finally, TMEM16A immunostaining in both control and TMEM16ASMKO mice revealed that this protein was highly expressed in the endometrial stroma, but did not co-localize with a smooth muscle specific marker MYH11. Collectively, these results unequivocally demonstrate that TMEM16A does not serve as a pacemaking channel for spontaneous uterine contraction, neither does it function as a depolarizing channel for agonist-evoked uterine contraction. Yet these two functions could underlie the normal gestation length and litter size in the TMEM16ASMKO mice.
Statistical inference of genetic pathway analysis in high dimensions
Authors: Liu Yang , Sun Wei , Reiner Alexander P , Kooperberg Charles , He Qianchuan 
Published: June 2019

Summary
Genetic pathway analysis has become an important tool for investigating the association between a group of genetic variants and traits. With dense genotyping and extensive imputation, the number of genetic variants in biological pathways has increased considerably and sometimes exceeds the sample size $n$. Conducting genetic pathway analysis and statistical inference in such settings is challenging. We introduce an approach that can handle pathways whose dimension $p$ could be greater than $n$. Our method can be used to detect pathways that have nonsparse weak signals, as well as pathways that have sparse but stronger signals. We establish the asymptotic distribution for the proposed statistic and conduct theoretical analysis on its power. Simulation studies show that our test has correct Type I error control and is more powerful than existing approaches. An application to a genome-wide association study of high-density lipoproteins demonstrates the proposed approach.
A Mortality Analysis of Letermovir Prophylaxis for Cytomegalovirus (CMV) in CMV-seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation
Authors: Ljungman Per , Schmitt Michael , Marty Francisco M , Maertens Johan , Chemaly Roy F , Kartsonis Nicholas A , Butterton Joan R , Wan Hong , Teal Valerie L , Sarratt Kendra , Murata Yoshihiko , Leavitt Randi Y , Badshah Cyrus 
Published: June 2019

Abstract

Background
In a phase 3 trial, letermovir reduced clinically significant cytomegalovirus infections (CS-CMVi) and all-cause mortality at week 24 versus placebo in CMV-seropositive allogeneic hematopoietic cell transplantation (HCT) recipients. This post hoc analysis of phase 3 data further investigated the effects of letermovir on all-cause mortality.

Methods
Kaplan-Meier survival curves were generated by treatment group for all-cause mortality. Observations were censored at trial discontinuation for reasons other than death or at trial completion. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox modeling, adjusting for risk factors associated with mortality.

Results
Of 495 patients with no detectable CMV DNA at randomization, 437 had vital-status data available through week 48 post-HCT at trial completion (101 deaths, 20.4%). Following letermovir prophylaxis, the HR for all-cause mortality was 0.58 (95% CI, 0.35–0.98; P = .04) at week 24 and 0.74 (95% CI, 0.49–1.11; P = .14) at week 48 post-HCT versus placebo. Incidence of all-cause mortality through week 48 post-HCT in the letermovir group was similar in patients with or without CS-CMVi (15.8 vs 19.4%; P = .71). However, in the placebo group, all-cause mortality at week 48 post-HCT was higher in patients with versus those without CS-CMVi (31.0% vs 18.2%; P = .02). The HR for all-cause mortality in patients with CS-CMVi was 0.45 (95% CI, 0.21–1.00; P = .05) at week 48 for letermovir versus placebo.

Conclusions
Letermovir may reduce mortality by preventing or delaying CS-CMVi in HCT recipients.

Clinical Trials Registration
clinicaltrials.gov, NCT02137772.
Mantle-induced temperature anomalies do not reach the inner core boundary
Authors: Davies Christopher J , Mound Jon E 
Published: June 2019

SUMMARY
Temperature anomalies in Earth’s liquid core reflect the vigour of convection and the nature and extent of thermal core–mantle coupling. Numerical simulations suggest that longitudinal temperature anomalies forced by lateral heat flow variations at the core–mantle boundary (CMB) can greatly exceed the anomalies that arise in homogeneous convection (i.e. with no boundary forcing) and may even penetrate all the way to the inner core boundary. However, it is not clear whether these simulations access the relevant regime for convection in Earth’s core, which is characterized by rapid rotation (low Ekman number E) and strong driving (high Rayleigh number Ra). We access this regime using numerical simulations of non-magnetic rotating convection with imposed heat flow variations at the outer boundary (OB) and investigate the amplitude and spatial pattern of thermal anomalies, focusing on the inner and outer boundaries. The 108 simulations cover the parameter range 10−4 ≤ E ≤ 10−6 and Ra = 1−800 times the critical value. At each Ra and E we consider two heat flow patterns—one derived from seismic tomography and the hemispheric $Y_1^1$ spherical harmonic pattern—with amplitudes measured by the parameter q⋆ = 2.3, 5 as well as the case of homogeneous convection. At the OB the forcing produces strong longitudinal temperature variations that peak in the equatorial region. Scaling relations suggest that the longitudinal variations are weakly dependent on E and Ra and are much stronger than in homogeneous convection, reaching O(1) K at core conditions if q⋆ ≈ 35. At the inner boundary, latitudinal and longitudinal temperature variations depend weakly on Ra and q⋆ and decrease strongly with E, becoming practically indistinguishable between homogeneous and heterogeneous cases at E = 10−6. Interpreted at core conditions our results suggest that heat flow variations on the CMB are unlikely to explain the large-scale variations observed by seismology at the top of the inner core.
Key aspects for the sustainable coordination of a process to facilitate holistic well-being in South African schools
Authors: Kitching Ansie Elizabeth , van Rooyen Bianke 
Published: June 2019

AbstractA holistic well-being approach, understood as an approach that pays attention to the promotion of individual, relational and collective well-being in a particular context, is proposed as a way to address the fragmented nature in which mental health and well-being programmes are implemented in school communities in South Africa. The goal of this paper is to indicate key aspects for sustainable coordination of a process to facilitate holistic well-being in South African schools. Research was conducted in six South African schools with the aim of developing an integrated, multilevel process to facilitate holistic well-being in these contexts. A participatory action learning and action research approach was applied. As part of this research, key aspects that could contribute to the sustainable coordination of holistic well-being were identified. The research comprised a cross-case analysis of the data gathered, as well as a focus group that was held with the coordinators who facilitated the development of the process in each school. In addition, the school principals completed a semi-structured questionnaire, and Skype interviews were conducted with four international experts. The five aspects identified as key to the sustainable coordination of well-being are: that ownership and responsibility should reside in the school context; that there should be a clear vision for the promotion of holistic well-being; that the connections between all involved should be deepened; that all efforts to promote holistic well-being should be integrated, and that the complexity of the process should be acknowledged.
Gene therapy for hearing loss
Authors: Omichi Ryotaro , Shibata Seiji B , Morton Cynthia C , Smith Richard J H 
Published: June 2019

Abstract
Sensorineural hearing loss (SNHL) is the most common sensory disorder. Its underlying etiologies include a broad spectrum of genetic and environmental factors that can lead to hearing loss that is congenital or late onset, stable or progressive, drug related, noise induced, age related, traumatic or post-infectious. Habilitation options typically focus on amplification using wearable or implantable devices; however exciting new gene-therapy-based strategies to restore and prevent SNHL are actively under investigation. Recent proof-of-principle studies demonstrate the potential therapeutic potential of molecular agents delivered to the inner ear to ameliorate different types of SNHL. Correcting or preventing underlying genetic forms of hearing loss is poised to become a reality. Herein, we review molecular therapies for hearing loss such as gene replacement, antisense oligonucleotides, RNA interference and CRISPR-based gene editing. We discuss delivery methods, techniques and viral vectors employed for inner ear gene therapy and the advancements in this field that are paving the way for basic science research discoveries to transition to clinical trials.
Long-term fluorescence hyperspectral imaging of on-chip treated co-culture tumour spheroids to follow clonal evolution
Authors: St-Georges-Robillard Amélie , Cahuzac Maxime , Péant Benjamin , Fleury Hubert , Lateef Muhammad Abdul , Ricard Alexis , Sauriol Skye Alexandre , Leblond Frédéric , Mes-Masson Anne-Marie , Gervais Thomas 
Published: June 2019

Abstract
Multicellular tumour spheroids are an ideal in vitro tumour model to study clonal heterogeneity and drug resistance in cancer research because different cell types can be mixed at will. However, measuring the individual response of each cell population over time is challenging: current methods are either destructive, such as flow cytometry, or cannot image throughout a spheroid, such as confocal microscopy. Our group previously developed a wide-field fluorescence hyperspectral imaging system to study spheroids formed and cultured in microfluidic chips. In the present study, two subclones of a single parental ovarian cancer cell line transfected to express different fluorophores were produced and co-culture spheroids were formed on-chip using ratios forming highly asymmetric subpopulations. We performed a 3D proliferation assay on each cell population forming the spheroids that matched the 2D growth behaviour. Response assays to PARP inhibitors and platinum-based drugs were also performed to follow the clonal evolution of mixed populations. Our experiments show that hyperspectral imaging can detect spheroid response before observing a decrease in spheroid diameter. Hyperspectral imaging and microfluidic-based spheroid assays provide a versatile solution to study clonal heterogeneity, able to measure response in subpopulations presenting as little as 10% of the initial spheroid.
MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis
Authors: Spec Andrej , Pullman John , Thompson George R , Powderly William G , Tobin Ellis H , Vazquez Jose , Wring Stephen A , Angulo David , Helou Silvia , Pappas Peter G ,   Mycoses Study Group, Vasquez Jose , Ostrosky-Zeichner Luis , Patterson Thomas , Alexander Barbara , Boucher Helen , Pappas Peter , Betts Robert , Schuster Mindy , Shoham Shmuel , Revankar Sanjay , Mushatt David , Bedimo Roger , Freifeld Alison , Nguyen Minh Hong , Mylonakis Eleftherios , Kett Daniel , Reboli Annette , Walsh Thomas , Pouch Stephanie , Almyroudis Nikolaos , Andes David , Hadley Susan , Barron Michelle , Mullane Katheen , Miller Loren 
Published: June 2019

Abstract

Objectives
To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable β-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 μM·h) in >80% of the intended population.

Methods
In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment.

Results
Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response.

Conclusions
The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.