bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in the development and financing of investment and innovation activities in the agricultural sector of the economy
Authors: Gurnovich T G , Piterskaya L Yu , Agarkova L V , Buraeva E V , Chistyakova M K
Published: April 2021

The purpose of the study is to develop and improve the tools for enhancing investment and innovation processes in the regional agrarian industrial complex under the influence of modern economic threats. Confirmation of the hypothesis about the interdependence of innovation processes in the agricultural economy and changes in the external environment of the industry’s functioning is reflected in the generated provisions of the theory and practice of investment and innovative development of the agro-industrial complex sectors, the use of instruments of state regulation of financing of investment, and innovation flows. Using the methodology of systems analysis, a study of innovation and investment processes in the agricultural economy was carried out, considering the manifestation of trends in the digitalization of the industry. Structural deformations and imbalances in investment and innovation processes in the agricultural sector of the economy are revealed. With the use of statistical and economic-mathematical methods, a forecast for the development of agricultural production is proposed, the factors for enhancing the development of the agricultural industry, and the levers of state regulation of innovative processes are substantiated.
Analysis of the effectiveness of ways to improve the performance in underground gas storage wells
Authors: Verzhbitsky V V , Gunkina T A , Vasilyev VA , Poltavskaya M D , Verzhbitskaya V V
Published: April 2021

The article provides an assessment of the effectiveness of various ways to improve the productivity of wells in underground gas storage facilities. We conducted comparisons of the performance of wells of increased diameter in the interval of the productive reservoir with wells in which hydraulic fracturing or horizontal ending was carried out.
Agricultural cooperation as a factor in sustainable rural development
Authors: Lipatova N N , Mamai O V , Mamai I N , Gazizyanova Yu Yu , Galenko N N
Published: April 2021

The efficiency of production in the agriculture domain directly affects the socio-economic development of the country, the rural areas. Recently, agricultural cooperation has been held high regard among all the factors of sustainable development of the agricultural production. That allows achieving financial stability of an agricultural enterprise, increasing the labor productivity in it, and reducing production costs. On the other hand, it promotes the development of rural settlements and employment there; therefore, conducting research in the agricultural cooperation field is so relevant. The purpose of the research is to study the development of agricultural cooperation in Russia and identify the problems that hinder the cooperative movement development; and suggest the main directions for further development in the field of cooperation over the country. A variety of methods have been used to study the processes and phenomena in the field of organizational and economic relations, such as analysis and synthesis, reliance on systemic and logical approaches to study the trends in the development of agricultural cooperation, besides using the graphic interpretation of theoretical information and the empirical data. This work takes into consideration the granting support for cooperatives. In addition, it defines the main problems and conditions of the cooperatives’ effective performance and suggests directions for further development of cooperation.
Study of dispersed-reinforced expanding plugging materials to improve the quality of well cementing
Authors: Egorova E V , Minchenko Yu S , Dolgova U V , Selivanov S V , Salavatov T Sh
Published: April 2021

The most common complications during the construction and operation of wells, such as gas and water showings and interstratal crossflows, in most cases result from seal failure of the annular space caused by cracking and destruction of the cement ring. The main way to improve the stability and tightness of well support is a rational cementing technology using high-quality plugging materials. Recently, due to the toughening of environmental requirements for a number of chemical reagents used for the treatment of plugging solutions, the most expedient in terms of increasing the fracture strength of a stone has become a method for developing plugging materials from several components with different physicochemical and physicomechanical properties. These are dispersed-reinforced materials, which are a mixture of backfill cement and mineral or artificial fibers, as well as organic fibrous additives from cellulose, jute, cotton, etc. The article discusses the results of studies of expanding reinforced plugging solutions in order to study their main technological and strength characteristics.
State and prospects of providing Russian rural areas with engineering life support systems
Authors: Levushkina S V , Lisova O M , Svistunova I G , Shutova O A
Published: April 2021

The article establishes the relationship between the favorable living environment in rural areas and the level of housing equipment with engineering systems. The analysis of the condition of residential premises in rural areas in terms of the level of their provision with life support systems is carried out. The problems of low level and quality of rural housing improvement are identified. The reasons that prevent the formation of comfortable conditions for providing housing with life support systems, namely centralized engineering networks, are identified. Using statistical forecasting methods, an inertial variant of changing the target indicators of residential improvement in rural areas of Russia by types of life support systems, taking into account the existing level, is created.
Investigation of methods for setting packers used for hydraulic fracturing
Authors: Verisokin A E , Kutovoy A S , Handzel A V , Datsyuk I O , Markov A V
Published: April 2021

Hydraulic fracturing is one of the effective methods of increasing the oil recovery of reservoirs. An important factor in hydraulic fracturing is the reliability of the packers, which are used to ensure the integrity of the production column. To prevent complications associated with tightness of casing pipes during hydraulic fracturing, studies were conducted to evaluate the methods of setting packers. After analyzing the practice of the application of packers, it was realized that five methods of setting them are used. The paper discusses the advantages and disadvantages of packer setting techniques. It is revealed, that the most reliable method is the combined version of setting of packers. The use of the combined setting method significantly increases the success of sealing the annular space of the well.
An Algorithm for Processing Data Received from a Distributed Monitoring Network Consisting of Several Sensors
Authors: Chernetsova E , Shishkin A
Published: April 2021

The paper presents an algorithm for detecting an object during the coherent reception of signals coming from an environmental monitoring network consisting of several sensors. The sensors of the monitoring network can change their location in space, for example, as it happens in a freely drifting system of sensors for detecting oil pollution on the water surface. The proposed algorithm uses statistics that take into account the most stable features of the distribution of the source data. It provides a constant probability of false alarm at any noise level. This algorithm can be implemented in software in an automated decision support system for the presence or absence of environmental pollution. At the same time, decisions on the detection of a monitoring object made by an automated system will be more reliable.
Geodynamic Setting on the Paleo-Asia Continent Eastern Margin in the Paleocene
Authors: Kemkin I V , Grebennikov A V , Ma X H
Published: April 2021

The isotopic-geochemical and geochronological data obtained allow us to justify the middle Paleocene - early Eocene stage of magmatism within the Sikhote-Alin. The volcano-plutonic complexes of this stage are characterized by distinctive mineralogical and geochemical features of the A-type igneous rocks that differ greatly from the Late Cretaceous I-type igneous rocks, which imply a geodynamic regime other than subduction at the paleo-Asian eastern margin during this period. According to the geological-structural data of the Cretaceous and Paleogene parts of the Shimanto accretionary complex, this magmatic stage coincides with changing of the geodynamic mode of subduction of an oceanic plate by geodynamic mode of transform sliding of the latter along the paleo-Asian continent eastern margin and, again, by geodynamic mode of subduction of an oceanic plate.
On the Geological and Environmental Problems of Aging Mining Enterprises
Authors: Yadransky D N , Latypov R T , Chumak E V
Published: April 2021

The article considers the totality of environmental and geological problems of the Kryvyi Rih iron ore basin. The aim of the article is to analyze the mountain-ecological consequences of increasing (expanding) the pace of mining in densely populated regions with a well-developed infrastructure. Based on the analysis of the current situation in the city Kryvyi Rih (Ukraine), it was proposed to transfer the established trends to the potential future consequences of increasing mining in the Urals. The research methods are the method of logical and structural analysis, logical modeling, analysis of literary sources.

The main hypothesis of the study is a mining enterprise, which, regardless of current economic indicators, cannot be liquidated (reorganized) in a short time, since it requires preliminary systematic preparation. According to the results of the analysis, it was established that the main problems of mining enterprises are that they cannot be quickly eliminated, since this will negatively affect the natural environment, giving rise to numerous mining and geological problems, primarily related to hydrogeology and filling the voids. In case of refusal to solve these problems, serious consequences arise related to public health.

The solution of large and global environmental investment projects is complicated by the fact that competing enterprises often operate within the same basin, which objectively cannot independently combine investment efforts to solve environmental and geological problems. Based on the results of the article, the main conclusion is formulated that it is advisable to develop an appropriate methodology for controlled attenuation of mining operations.
Can plastome data resolve recent radiations?Rhodiola(Crassulaceae) as a case study
Authors: Zhao Dan-Ni , Ren Chun-Qian , Zhang Jian-Qiang
Published: April 2021

Recent radiations provide excellent models to gain more insights into evolution, speciation and adaptation. To this end, a well-resolved phylogenetic tree is needed. However, resolving phylogenetic relationships within recent radiations has been difficult as traditional phylogenetic markers failed to provide enough information. We here use plastome data to test their capacity in resolving phylogenetic relationships among a recent rapidly diverging group, Rhodiola, on the Qinghai-Tibetan Plateau. We reconstructed a robust phylogenetic backbone of Rhodiola using 23 plastomes representing all subgenera and sections in previous taxonomic treatments. Based on the backbone, we inferred the spatio-temporal pattern of diversification of the genus. We also traced evolution of five important morphological characters of Rhodiola, including sexual system, inflorescence type and flowering stem, based on the maximum likelihood and the threshold models. Two well-supported clades were revealed in Rhodiola, and the two clades were distinguished by sexual system: species in clade I are mostly hermaphrodite (except R. stapfii and R. integrifolia), and those in clade II are all dioecious. Biogeographic analysis showed that Rhodiola probably originated in the Qinghai-Tibetan Plateau and the Hengduan Mountains. The two major clades diverged c. 6.34 Mya, corresponding to a period of rapid uplift of the Hengduan Mountains and intensification of the Asian monsoon. Character evolution analysis confirmed parallel evolution of dioecy and other adaptive traits, such as marcescent flowering stems, in the genus. We demonstrate that plastome data could significantly improve phylogenetic resolution in plant groups resulting from recent radiations. Our results not only shed new light on the evolutionary history of Rhodiola, but also indicate that more plastome data should be used in resolving phylogenetic relationship in plant groups that have undergone recent radiations.
Massive pulmonary embolism and thrombus-in-transit via a patent foramen ovale: a case report of successful use of extracorporeal membrane oxygenation to manage post-embolectomy severe right ventricular dysfunction
Authors: Saunders Helen , Al Khalifa Abdulwahab , Espinosa Angel , Jain Manish
Published: April 2021

Background

Pulmonary embolism with thrombus-in-transit through a patent foramen ovale is rare. It may present with neurological sequalae and rapid diagnosis is needed to prevent mortality and morbidity. The European Society of Cardiology (ESC) published guidelines in 2019 for diagnosis and management of acute pulmonary embolism which were useful in this case.

Case summary

A 32-year-old sedentary male presented with sudden onset shortness of breath, syncope, a probable seizure, and chest pain. Investigations showed an acute pulmonary embolism with mobile thrombus in the right atrium and right ventricle and also thrombus-in-transit passing through a patent foramen ovale into the left atrium. He was resuscitated and rapidly transferred to theatre where he underwent surgical thromboembolectomy. There was difficulty in separating him from cardiopulmonary bypass due to right ventricular failure and he was initiated on extracorporeal membrane oxygenator support. He recovered fully and was discharged home after 43 days.

Discussion

This case report highlights the presentation of this rare diagnosis and discusses the management of acute pulmonary embolism according to recent ESC guidelines.
What are the differences in protective characteristics of orthodontic mouthguards? An in vitro study
Authors: Harrington Claire , Minhas Gursharan , Papageorgiou Spyridon N , Cobourne Martyn T
Published: April 2021

Background

Orthodontic patients wearing fixed appliances are susceptible to traumatic dental injuries during contact-sport. This laboratory study investigated the protective qualities of orthodontic mouthguards using impact-testing to a typodont fitted with a fixed appliance through peak load transfer and retention of the mouthguard.

Methods

Seven orthodontic mouthguards [three custom-made (Medium-CM, Heavy-CM, Heavy-pro-CM); three commercially-available mouth-formed (Shock-Doctor® Ultra Braces, Opro® Ortho-Gold Braces, Opro® Ortho-Bronze Braces) and a Shock-Doctor® Instant-Fit] were fitted to a maxillary arch typodont bonded with a fixed appliance and impact-tested using 0.5 or 1 Joule (J) energy via hockey-ball, cricket-ball or steel-ball projectile. A load-cell recorded peak load transfer through mouthguard to typodont with retention scored in a binary manner dependent upon any displacement following impact. Differences across mouthguards were calculated with ANOVA or Kruskal–Wallis test for normal and non-normal data, respectively. Post hoc comparisons across mouthguards were conducted via Dunnett's test with Sidak correction.

Results

Only the three custom-made and Opro® Ortho-Gold Braces were not displaced by impact-testing. For these, Opro® Ortho-Gold Braces transferred the smallest load for 3/6 impact-tests, followed by Medium-CM. Heavy-pro-CM performed poorly, ranking penultimate or worst for all impact-tests. Significant differences were found between mouthguards for cricket-ball and steel-ball set-ups. The Opro® Ortho-Gold Braces performed better than the Heavy and Heavy-pro-CM for 0.5 J cricket-ball impact-test (P < 0.05), whilst Medium-CM performed better than Heavy-pro-CM. For 1 J cricket-ball, there were significant differences between Medium-CM and Heavy-pro-CM (P < 0.05). For 0.5 J steel-ball, the Medium-CM performed significantly better than both Heavy-pro-CM and Opro® Ortho-Gold Braces (P < 0.05), whilst Heavy-CM performed better than the Heavy-pro-CM (P < 0.05). For the 1 J steel-ball, Medium and Heavy-CM performed better than Opro® Ortho-Gold Braces (P < 0.05).

Conclusions

Opro® Ortho-Gold and Medium-CM mouthguards offer the best protection for low-impact sports, whilst Medium or Heavy-CM mouthguards are recommended for high-impact sport.
Differential regulation of undecylprodigiosin biosynthesis in the yeast-scavenging Streptomyces strain MBK6
Authors: Bikash Baral , Vilja Siitonen , Mitchell Laughlin , Keith Yamada , Mikael Ilomäki , Mikko Metsä-Ketelä , Jarmo Niemi
Published: April 2021

Streptomyces are efficient chemists with a capacity to generate diverse and potent chemical scaffolds. The secondary metabolism of these soil-dwelling prokaryotes is stimulated upon interaction with other microbes in their complex ecosystem. We observed such an interaction when a Streptomyces isolate was cultivated in a media supplemented with dead yeast cells. Whole-genome analysis revealed that Streptomyces sp. MBK6 harbors the red cluster that is cryptic under normal environmental conditions. An interactive culture of MBK6 with dead yeast triggered the production of the red pigments metacycloprodigiosin and undecylprodigiosin. Streptomyces sp. MBK6 scavenges dead-yeast cells and preferentially grows in aggregates of sequestered yeasts within its mycelial network. We identified that the activation depends on the cluster-situated regulator, mbkZ, which may act as a cross-regulator. Cloning of this master regulator mbkZ in S. coelicolor with a constitutive promoter and promoter-deprived conditions generated different production levels of the red pigments. These surprising results were further validated by DNA–protein binding assays. The presence of the red cluster in Streptomyces sp. MBK6 provides a vivid example of horizontal gene transfer of an entire metabolic pathway followed by differential adaptation to a new environment through mutations in the receiver domain of the key regulatory protein MbkZ.
Selection Maintains Protein Interactome Resilience in the Long-Term Evolution Experiment with Escherichia coli
Authors: Maddamsetti Rohan
Published: April 2021

Most cellular functions are carried out by a dynamic network of interacting proteins. An open question is whether the network properties of protein interactomes represent phenotypes under natural selection. One proposal is that protein interactomes have evolved to be resilient, such that they tend to maintain connectivity when proteins are removed from the network. This hypothesis predicts that interactome resilience should be maintained by natural selection during long-term experimental evolution. I tested this prediction by modeling the evolution of protein–protein interaction (PPI) networks in Lenski’s long-term evolution experiment with Escherichia coli (LTEE). In this test, I removed proteins affected by nonsense, insertion, deletion, and transposon mutations in evolved LTEE strains, and measured the resilience of the resulting networks. I compared the rate of change of network resilience in each LTEE population to the rate of change of network resilience for corresponding randomized networks. The evolved PPI networks are significantly more resilient than networks in which random proteins have been deleted. Moreover, the evolved networks are generally more resilient than networks in which the random deletion of proteins was restricted to those disrupted in LTEE. These results suggest that evolution in the LTEE has favored PPI networks that are, on average, more resilient than expected from the genetic variation across the evolved strains. My findings therefore support the hypothesis that selection maintains protein interactome resilience over evolutionary time.
Balancing biological and economic goals in commercial and recreational fisheries: systems modelling of sea bass fisheries
Authors: Tidbury Hannah J , Muench Angela , Lamb Philip D , Hyder Kieran
Published: April 2021

The importance of social and economic factors, in addition to biological factors, in fisheries management is being increasingly recognised. However, exploration of trade-offs between biological, social, and economic factors under different sustainable catch limits for recreational and commercial fisheries is limited, especially in Europe. The European sea bass (Dicentrarchus labrax) is valuable and important for both commercial and recreational fisheries. Stocks have rapidly declined and management measures have been implemented, but trade-offs between social, biological, and economic factors have not been explicitly considered. In this study, a system dynamics model framework capturing biological and economic elements of the European sea bass fishery was developed and refined to incorporate a catch limit reflecting sustainable fishing with adjustable partition between recreational and commercial sectors, under low, medium, or high recruitment. Model outputs were used to explore the relative impact of different catch allocations on trade-offs between biological sustainability and economic impact when recruitment was limiting or not. Recruitment had a large impact on the fish population dynamics and the viability of the sectors. At high and moderate recruitment, management contributed to stock sustainability and sector economic impact, but recruitment is important in determining the balance between sectors.
Does microbiological contamination of homografts prior to decontamination affect the outcome after right ventricular outflow tract reconstruction?
Authors: Axelsson Ida , Malm Torsten , Nilsson Johan
Published: April 2021

OBJECTIVES

Homografts are often in short supply. Today, European guidelines recommend that all tissues contaminated by any of 18 different bacteria and fungi be discarded before antibiotic decontamination has been conducted. The tissue bank in Lund uses more liberal protocols: It accepts all microbes prior to decontamination except multiresistant microbes and Pseudomonas species. The aim of this study was to analyse the effect of contamination on the long-term outcome and occurrence of endocarditis in recipients.

METHODS

Data were collected on homografts and on recipients of homografts in the right ventricular (RV) outflow tract who were operated on between 1995 and 2018 in Lund. The long-term outcome of recipients was analysed in relation to different types of contamination using Cox proportional hazard regression. The proportion of patients with endocarditis was analysed with the χ2 test.

RESULTS

The study included 509 implanted homografts. Follow-up was a maximum of 24 years and 99% complete. A total of 156 (31%) homografts were contaminated prior to antibiotic decontamination. Homografts contaminated with low-risk microbes had the lowest reintervention rate, but there was no significant difference compared to no contamination [hazard ratio (HR) 1.1, 95% confidence interval (CI) 0.73–1.7] or contamination with high-risk microbes (HR 1.6, 95% CI 0.87–2.8) in the multivariable analysis. There was no significant difference in the proportion of cases of endocarditis during the follow-up period between recipients of homografts contaminated prior to decontamination and recipients of homografts with no contamination (P = 0.83).

CONCLUSIONS

Contamination of homograft tissue prior to decontamination did not show any significant effect on the long-term outcome or the occurrence of endocarditis after implantation in the RV outflow tract. Most contaminated homografts can be used safely after approved decontamination.
Starr–Edwards mitral valve—48 years till redo surgery, with over 54 years of patient survival after primary mitral valve replacement
Authors: Dimitrakakis Georgios , Wheeler Richard , von Oppell Ulrich
Published: April 2021

We report a male patient who underwent successful redo cardiac surgery in 2014; tricuspid valve repair and redo mitral valve replacement of a Starr–Edwards mitral valve implanted 48 years previously. Six years after the redo operation, the patient remains well and therefore has an impressive over 54 years of survival following mitral valve replacement surgery.
On the Action of Multiplicative Cascades on Measures
Authors: Barral Julien , Jin Xiong
Published: April 2021

We consider the action of Mandelbrot multiplicative cascades on probability measures supported on a symbolic space. For general probability measures, we obtain almost a sharp criterion of non-degeneracy of the limiting measure; it relies on the lower and upper Hausdorff dimensions of the measure and the entropy of the random weights. We also obtain sharp bounds for the lower Hausdorff and upper packing dimensions of the limiting measure. When the original measure is a Gibbs measure associated with a potential of certain modulus of continuity (weaker than Hölder), all our results are sharp. This improves results previously obtained by Kahane and Peyrière, Ben Nasr, and Fan. We exploit our results to derive dimension estimates and absolute continuity for some random fractal measures.
Free Flags Over Local Rings and Powering of High-dimensional Expanders
Authors: Kaufman Tali , Parzanchevski Ori
Published: April 2021

Powering the adjacency matrix of an expander graph results in a better expander of higher degree. In this paper we seek an analogue operation for high-dimensional (HD) expanders. We show that the naive approach to powering does not preserve HD expansion and define a new power operation, using geodesic walks on quotients of Bruhat–Tits buildings. Applying this operation results in HD expanders of higher degrees. The crux of the proof is a combinatorial study of flags of free modules over finite local rings. Their geometry describes links in the power complex, and showing that they are excellent expanders implies HD expansion for the power complex by Garland’s local-to-global technique. As an application, we use our power operation to obtain new efficient double samplers.
Information needs and perceptions of chatbots for hypertension medication self-management: a mixed methods study
Authors: Griffin Ashley C , Xing Zhaopeng , Mikles Sean P , Bailey Stacy , Khairat Saif , Arguello Jaime , Wang Yue , Chung Arlene E
Published: April 2021

Objective

Chatbots have potential to deliver interactive self-management interventions but have rarely been studied in the context of hypertension or medication adherence. The objective of this study was to better understand patient information needs and perceptions of chatbots to support hypertension medication self-management.

Materials and Methods

Mixed methods were used to assess self-management needs and preferences for using chatbots. We purposively sampled adults with hypertension who were prescribed at least one medication. Participants completed questionnaires on sociodemographics, health literacy, self-efficacy, and technology use. Semi-structured interviews were conducted, audio-recorded, and transcribed verbatim. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed using applied thematic analysis.

Results

Thematic saturation was met after interviewing 15 participants. Analysis revealed curiosity toward chatbots, and most perceived them as humanlike. The majority were interested in using a chatbot to help manage medications, refills, communicate with care teams, and for accountability toward self-care tasks. Despite general enthusiasm, there were concerns with chatbots providing too much information, making demands for lifestyle changes, invading privacy, and usability issues with deployment on smartphones. Those with overall positive perceptions toward chatbots were younger and taking fewer medications.

Discussion

Chatbot-related informational needs were consistent with existing self-management research, and many felt chatbots would be valuable if customizable and compatible with patient portals, pharmacies, or health apps.

Conclusion

Although most were not familiar with chatbots, patients were interested in interacting with them, but this varied. This research informs future design and functionalities of conversational interfaces to support hypertension self-management.
Neuroprotection of Heme Oxygenase-2 in Mice AfterIntracerebral Hemorrhage
Authors: Zhang Ze , Pang Yuxin , Wang Wei , Zhu Hong , Jin Sinan , Yu Zihan , Gu Yunhe , Wu He
Published: April 2021

There are few effective preventive or therapeutic strategies to mitigate the effects of catastrophic intracerebral hemorrhage (ICH) in humans. Heme oxygenase is the rate-limiting enzyme in heme metabolism; heme oxygenase-2 (HO-2) is a constitutively expressed heme oxygenase. We explored the involvement of HO-2 in a collagenase-induced mouse model of ICH in C57BL/6 wild-type and HO-2 knockout mice. We assessed oxidative stress injury, blood-brain barrier permeability, neuronal damage, late-stage angiogenesis, and hematoma clearance using immunofluorescence, Western blot, MRI, and special staining methods. Our results show that HO-2 reduces brain injury volume and brain edema, alleviates cytotoxic injury, affects vascular function in the early stage of ICH, and improves hematoma absorbance and angiogenesis in the late stage of ICH in this model. Thus, we found that HO-2 has a protective effect on brain injury after ICH.
Reducing Variance with Sample Allocation Based on Expected Response Rates in Stratified Sample Designs
Authors: Szeitl Blanka , Rudas TamÁs
Published: April 2021

This paper demonstrates that the sample allocation that takes the expected response rates (ERRs) into account has certain advantages over other approaches in terms of reducing the variances of the estimates. The performance of the ERR allocation is assessed within the framework of stratified sampling by comparing the resulting variances with those obtained using the classical procedure of proportional-to-stratum size (PS) allocation and then applying poststratification. The main theoretical tool is asymptotic calculations using the δ-method, which are complemented with extensive finite sample evaluations using various combinations of specific population parameters. The main finding was that within a stratified sample design, ERR allocation leads to lower variances than PS allocation, not only when the response rates are correctly specified but also under a wide range of conditions where the response rates can only be approximately specified in advance.
Power spectrum of density fluctuations, halo abundances, and clustering with primordial black holes
Authors: Padilla Nelson D , Magaña Juan , Sureda Joaquín , Araya Ignacio J
Published: April 2021

We study the effect of dark matter (DM) being encapsulated in primordial black holes (PBHs) on the power spectrum of density fluctuations P(k); we also look at its effect on the abundance of haloes and their clustering. We allow the growth of Poisson fluctuations since matter and radiation equality and study both monochromatic and extended PBH mass distributions. We present updated monochromatic black hole mass constraints by demanding $\lt 10{{\ \rm per\ cent}}$ deviations from the Λ cold dark matter (CDM) power spectrum at a scale of k = 1 h Mpc−1. Our results show that PBHs with masses $\gt 10^4\, h^{-1}\, \mathrm{M}_\odot$ are excluded from conforming all of the DM in the Universe. We also apply this condition to our extended Press–Schechter (PS) mass functions, and find that the Poisson power is scale dependent even before applying evolution. We find that characteristic masses $M^*\le 10^2 \, \mathrm{ h}^{-1}\, \mathrm{M}_\odot$ are allowed, leaving only two characteristic PBH mass windows of PS mass functions when combining with previous constraints, at $M^*\sim 10^2\, h^{-1}\, \mathrm{M}_\odot$ and $\sim \!10^{-8}\, h^{-1}\, \mathrm{M}_\odot$ where all of the DM can be in PBHs. The resulting DM halo mass functions within these windows are similar to those resulting from CDM made of fundamental particles. However, as soon as the parameters produce unrealistic P(k), the resulting halo mass functions and their bias as a function of halo mass deviate strongly from the behaviour measured in the real Universe.
Mycobacterium tuberculosis Phe-tRNA synthetase: structural insights into tRNA recognition and aminoacylation
Authors: Michalska Karolina , Jedrzejczak Robert , Wower Jacek , Chang Changsoo , Baragaña Beatriz , Gilbert Ian H , Forte Barbara , Joachimiak Andrzej
Published: April 2021

Tuberculosis, caused by Mycobacterium tuberculosis, responsible for ∼1.5 million fatalities in 2018, is the deadliest infectious disease. Global spread of multidrug resistant strains is a public health threat, requiring new treatments. Aminoacyl-tRNA synthetases are plausible candidates as potential drug targets, because they play an essential role in translating the DNA code into protein sequence by attaching a specific amino acid to their cognate tRNAs. We report structures of M. tuberculosis Phe-tRNA synthetase complexed with an unmodified tRNAPhe transcript and either L-Phe or a nonhydrolyzable phenylalanine adenylate analog. High-resolution models reveal details of two modes of tRNA interaction with the enzyme: an initial recognition via indirect readout of anticodon stem-loop and aminoacylation ready state involving interactions of the 3′ end of tRNAPhe with the adenylate site. For the first time, we observe the protein gate controlling access to the active site and detailed geometry of the acyl donor and tRNA acceptor consistent with accepted mechanism. We biochemically validated the inhibitory potency of the adenylate analog and provide the most complete view of the Phe-tRNA synthetase/tRNAPhe system to date. The presented topography of amino adenylate-binding and editing sites at different stages of tRNA binding to the enzyme provide insights for the rational design of anti-tuberculosis drugs.
What is the Best Latent Structure of Negative Symptoms in Schizophrenia? A Systematic Review
Authors: Haguiara Bernardo , Koga Gabriela , Diniz Elton , Fonseca Lais , Higuchi Cinthia H , Kagan Simão , Lacerda Acioly , Correll Christoph U , Gadelha Ary
Published: April 2021

Background

Determining the best latent structure of negative symptoms in schizophrenia could benefit assessment tools, neurobiological research, and targeted interventions. However, no review systematically evaluated studies that assessed and validated latent models of negative symptoms.

Objective

To identify and evaluate existing latent structure models in the literature of negative symptoms and to determine the best model.

Method

Systematic search of MEDLINE, EMBASE, and Scopus on July 19, 2020, for confirmatory factor analysis models of negative symptoms in patients with schizophrenia. The available evidence was assessed through 2 sets of criteria: (1) study design quality—based on negative symptoms assessment and modeling strategy and (2) psychometric quality and model fit—based on fit indices and factor definition quality.

Results

In total, 22 studies (n = 17 086) from 9 countries were included. Studies differed greatly regarding symptom scales, setting, and sample size (range = 86–6889). Dimensional models included 2–6 factors (median = 4). Twelve studies evaluated competing models and adopted appropriate instruments to assess the latent structure of negative symptoms. The 5-factor and hierarchical models outperformed unitary, 2-factor, and 3-factor models on all direct comparisons, and most of the analyses derived from the Brief Negative Symptom Scale. Considering the quality criteria proposed, 5-factor and hierarchical models achieved excellent fit in just one study.

Conclusions

Our review points out that the 5-factor and hierarchical models represent the best latent structure of negative symptoms, but the immaturity of the relevant current literature may affect the robustness of this conclusion. Future studies should address current limitations regarding psychometric properties and also address biological and clinical validity to refine available models.
Carbon Nanotube Exposure Triggers a Cerebral Peptidomic Response: Barrier Compromise, Neuroinflammation, and a Hyperexcited State
Authors: Mostovenko Ekaterina , Saunders Samantha , Muldoon Pretal P , Bishop Lindsey , Campen Matthew J , Erdely Aaron , Ottens Andrew K
Published: April 2021

The unique physicochemical properties of carbon nanomaterials and their ever-growing utilization generate a serious concern for occupational risk. Pulmonary exposure to these nanoparticles induces local and systemic inflammation, cardiovascular dysfunction, and even cognitive deficits. Although multiple routes of extrapulmonary toxicity have been proposed, the mechanism for and manner of neurologic effects remain minimally understood. Here, we examine the cerebral spinal fluid (CSF)-derived peptidomic fraction as a reflection of neuropathological alterations induced by pulmonary carbon nanomaterial exposure. Male C57BL/6 mice were exposed to 10 or 40 µg of multiwalled carbon nanotubes (MWCNT) by oropharyngeal aspiration. Serum and CSFs were collected 4 h post exposure. An enriched peptide fraction of both biofluids was analyzed using ion mobility-enabled data-independent mass spectrometry for label-free quantification. MWCNT exposure induced a prominent peptidomic response in the blood and CSF; however, correlation between fluids was limited. Instead, we determined that a MWCNT-induced peptidomic shift occurred specific to the CSF with 292 significant responses found that were not in serum. Identified MWCNT-responsive peptides depicted a mechanism involving aberrant fibrinolysis (fibrinopeptide A), blood-brain barrier permeation (homeobox protein A4), neuroinflammation (transmembrane protein 131L) with reactivity by astrocytes and microglia, and a pro-degradative (signal transducing adapter molecule, phosphoglycerate kinase), antiplastic (AF4/FMR2 family member 1, vacuolar protein sorting-associated protein 18) state with the excitation-inhibition balance shifted to a hyperexcited (microtubule-associated protein 1B) phenotype. Overall, the significant pathologic changes observed were consistent with early neurodegenerative disease and were diagnostically reflected in the CSF peptidome.
Principal Component Analysis of Striatal and Extrastriatal D2 Dopamine Receptor Positron Emission Tomography in Manganese-Exposed Workers
Authors: Criswell Susan R , Searles Nielsen Susan , Dlamini Wendy W , Warden Mark N , Perlmutter Joel S , Sheppard Lianne , Moerlein Stephen M , Lenox-Krug Jason , Checkoway Harvey , Racette Brad A
Published: April 2021

The relationships between the neurotoxicant manganese (Mn), dopaminergic pathology, and parkinsonism remain unclear. Therefore, we used [11C](N-methyl)benperidol (NMB) positron emission tomography to investigate the associations between Mn exposure, striatal and extrastriatal D2 dopamine receptors (D2R), and motor function in 54 workers with a range of Mn exposure. Cumulative Mn exposure was estimated from work histories, and all workers were examined by a movement specialist and completed a Grooved Pegboard test (GPT). NMB D2R nondisplaceable binding potentials (BPND) were calculated for brain regions of interest. We identified 2 principal components (PCs) in a PC analysis which explained 66.8% of the regional NMB BPND variance (PC1 = 55.4%; PC2 = 11.4%). PC1 was positively correlated with NMB binding in all regions and inversely correlated with age. PC2 was driven by NMB binding in 7 brain regions (all p < .05), positively in the substantia nigra, thalamus, amygdala, and medial orbital frontal gyrus and negatively in the nucleus accumbens, anterior putamen, and caudate. PC2 was associated with both Mn exposure status and exposure duration (years). In addition, PC2 was associated with higher Unified Parkinson’s Disease Rating Scale motor subsection 3 (UPDRS3) scores and slower GPT performance. We conclude Mn exposure is associated with both striatal and extrastriatal D2R binding. Multifocal alterations in D2R expression are also associated with motor dysfunction as measured by both the GPT and UPDRS3, demonstrating a link between Mn exposure, striatal and extrastriatal D2R expression, and clinical neurotoxicity.
Grape Transcriptome Response to Powdery Mildew Infection: Comparative Transcriptome Profiling of Chinese Wild Grapes Provides Insights Into Powdery Mildew Resistance
Authors: Jiao Chen , Sun Xuepeng , Yan Xiaoxiao , Xu Xiaozhao , Yan Qin , Gao Min , Fei Zhangjun , Wang Xiping
Published: April 2021

Erysiphe necator, the fungal pathogen of grape powdery mildew disease, poses a great threat to the grape market and the wine industry. To better understand the molecular basis of grape responses to E. necator, we performed comparative transcriptome profiling on two Chinese wild grape accessions with varying degrees of resistance to E. necator. At 6-, 24-, and 96-h postinoculation of E. necator, 2,856, 2,678, and 1,542 differentially expressed genes (DEGs) were identified in the susceptible accession Vitis pseudoreticulata ‘Hunan-1’, and at those same time points, 1,921, 2,498, and 3,249 DEGs, respectively, were identified in the resistant accession V. quinquangularis ‘Shang-24’. ‘Hunan-1’ had a substantially larger fraction of down-regulated genes than ‘Shang-24’ at every infection stage. Analysis of DEGs revealed that up-regulated genes were mostly associated with defense response and disease resistance-related metabolite biosynthesis, and such signaling genes were significantly suppressed in ‘Hunan-1’. Interestingly, fatty acid biosynthesis- and elongation-related genes were suppressed by the fungus in the ‘Shang-24’ accession but somehow induced in the ‘Hunan-1’ accession, consistent with the concept that E. necator is likely to be a fatty acid auxotroph that requires lipids from the host. Moreover, genes involved in biosynthesis and signaling of phytohormones, such as jasmonic acid and cytokinin, as well as genes encoding protein kinases and nucleotide-binding domain leucine-rich repeat proteins, differentially responded to E. necator in the two wild grapes. The variation of gene regulation associated with nutrient uptake by the fungus and with signaling transduction and pathogen recognition suggests a multilayered regulatory network that works in concert to assist in the establishment of fungal pathogen infections.
Phase I Study of Muscadine Grape Extract for Patients With Advanced Cancer
Authors: Bitting Rhonda L. , Tooze Janet A. , Isom Scott , Petty W. Jeffrey , Grant Stefan C. , Desnoyers Rodwige J. , Thomas Alexandra , Thomas Christopher Y. , Alistar Angela T. , Golden Shannon L. , Pleasant Katherine , Chappell Mark C. , Tallant E. Ann , Gallagher Patricia E. , Klepin Heidi D.
Published: April 2021

Objective:

Preclinical studies with muscadine grape extract (MGE) show antitumor activity and decreased systemic inflammation. This phase I study (NCT02583269) assessed safety and tolerability of a proprietary MGE preparation in patients with advanced solid tumors.

Methods:

Patients with metastatic or unresectable cancers who were progressing on standard therapies were assigned to MGE in a standard 3+3 design. Five dose levels were tested (320 to 1600 mg total phenolics/d). Safety and maximum-tolerated dose were assessed after 4 weeks. Patients were evaluated for response at 8 weeks and continued on MGE if clinically stable. Secondary outcomes were response, survival, adherence, fatigue, and quality of life (QOL).

Results:

In total, 23 patients (lung, n=7; gastrointestinal, n=7; genitourinary, n=6; other, n=3) received MGE capsules by mouth twice daily. The cohort [median age 72 years, 48% Eastern Cooperative Oncology Group (ECOG) 2] was heavily pretreated. After 4 weeks on MGE, possibly attributable adverse events grade 2 or higher were fatigue (n=1), decreased lymphocyte count (n=1), and constipation (n=2), including 1 dose-limiting toxicity for grade 3 constipation. Maximum-tolerated dose was not reached. No partial responses were observed. Median time on therapy was 8 weeks, with 29% of patients treated beyond 16 weeks and a median overall survival of 7.2 months. QOL and fatigue levels were stable from baseline to 8 weeks. Higher MGE dose was correlated with improvement in self-reported physical well-being QOL at 8 weeks (r=0.6; P=0.04).

Conclusions:

MGE is safe and well-tolerated in heavily pretreated and older cancer patients. The potential anticancer properties and the effects of MGE on physical well-being and QOL metrics will be evaluated in future studies.
Review of the Current Medical and Surgical Treatment Options for Microstomia in Patients With Scleroderma
Authors: Gonzalez Cristian D. , Pamatmat Jarod John , Hutto Jake C. , Goff Heather W.
Published: April 2021

BACKGROUND

Most patients with scleroderma suffer from microstomia, which can have debilitating consequences on their quality of life. Unfortunately, treatment options remain limited. No specific guidelines exist; hence, microstomia remains a challenge to treat in this patient population.

OBJECTIVE

This review aims to evaluate the different medical and surgical treatment modalities currently available for microstomia in patients with scleroderma and make recommendations for future research.

MATERIALS AND METHODS

A search of PubMed, Ovid MEDLINE, and Ovid Embase was conducted to identify articles discussing the treatment of microstomia in scleroderma. Twenty articles discussing surgical therapy and one article discussing medical therapy were reviewed.

RESULTS

Mostly because of a scarcity of high-level evidence, no individual therapy has documented long-term efficacy. Some treatments demonstrate positive results and warrant further research.

CONCLUSION

Given the variability of results, specific recommendations for the treatment of microstomia in patients with scleroderma are difficult to establish. A multifaceted approach that includes surgical and medical therapy is likely the best option to improve oral aperture in this patient population. Surgical treatments such as neurotoxins, autologous fat grafting, and ultraviolet A1 phototherapy may hold the most potential for improvement.
Nonsurgical Postpartum Abdominal Rejuvenation: A Review and Our Experience
Authors: Kream Elizabeth , Boen Monica , Fabi Sabrina G. , Goldman Mitchel P.
Published: April 2021

BACKGROUND

A significant population of aesthetic patients are postpartum women motivated to achieve a more youthful abdomen. Although traditionally, abdominoplasty was the treatment of choice, minimally invasive procedures have grown in popularity because of minimal downtime and the favorable side effect profile. so many women share concerns regarding their postpartum abdominal appearance, a limited number of studies focus specifically on postpartum abdominal rejuvenation.

OBJECTIVE

To review pertinent aspects of abdominal anatomy, associated changes with pregnancy, available nonsurgical cosmetic procedures, and to provide our experience to help guide treatment combinations which comprehensively address the concerns of the postpartum patient.

MATERIALS AND METHODS

A review of the literature surrounding nonsurgical treatment options for postpartum abdominal lipohypertrophy, muscle changes, tissue laxity, and striae gravidarum, along with the authors' experience in this area are provided.

CONCLUSION

This review summarizes available nonsurgical modalities to address postpartum abdominal defects, including procedures that tone muscles, reduce fat, tighten skin, and improve the appearance of striae. Both the published literature and the authors' experience favor a combination of treatments to address the various lamellae affected by pregnancy. Further clinical trials focusing on the postpartum patient would further help create a standardized approach for postpartum abdominal rejuvenation.