bluuebunny/crossref_metadata_2025 huggingface dataset:
The formin inhibitor SMIFH2 inhibits members of the myosin superfamily
Authors: Nishimura Yukako , Shi Shidong , Zhang Fang , Liu Rong , Takagi Yasuharu , Bershadsky Alexander D. , Viasnoff Virgile , Sellers James R.
Published: February 2021

The small molecular inhibitor of formin FH2 domains, SMIFH2, is widely used in cell biological studies. It inhibits formin-driven actin polymerization in vitro, but not polymerization of pure actin. It is active against several types of formin from different species. Here, we found that SMIFH2 inhibits retrograde flow of myosin 2 filaments and contraction of stress fibers. We further checked the effect of SMIFH2 on non-muscle myosin 2A and skeletal muscle myosin 2 in vitro, and found that SMIFH2 inhibits activity of myosin ATPase and the ability to translocate actin filaments in the gliding actin in vitro motility assay. Inhibition of non-muscle myosin 2A in vitro required a higher concentration of SMIFH2 compared with that needed to inhibit retrograde flow and stress fiber contraction in cells. We also found that SMIFH2 inhibits several other non-muscle myosin types, including bovine myosin 10, Drosophila myosin 7a and Drosophila myosin 5, more efficiently than it inhibits formins. These off-target inhibitions demand additional careful analysis in each case when solely SMIFH2 is used to probe formin functions.

This article has an associated First Person interview with Yukako Nishimura, joint first author of the paper.
The novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in the Drosophila gut
Authors: Izumi Yasushi , Furuse Kyoko , Furuse Mikio
Published: February 2021

Smooth septate junctions (sSJs) regulate the paracellular transport in the intestinal tract in arthropods. In Drosophila, the organization and physiological function of sSJs are regulated by at least three sSJ-specific membrane proteins: Ssk, Mesh and Tsp2A. Here, we report a novel sSJ membrane protein, Hoka, which has a single membrane-spanning segment with a short extracellular region, and a cytoplasmic region with Tyr-Thr-Pro-Ala motifs. The larval midgut in hoka mutants shows a defect in sSJ structure. Hoka forms a complex with Ssk, Mesh and Tsp2A, and is required for the correct localization of these proteins to sSJs. Knockdown of hoka in the adult midgut leads to intestinal barrier dysfunction and stem cell overproliferation. In hoka-knockdown midguts, aPKC is upregulated in the cytoplasm and the apical membrane of epithelial cells. The depletion of aPKC and yki in hoka-knockdown midguts results in reduced stem cell overproliferation. These findings indicate that Hoka cooperates with the sSJ proteins Ssk, Mesh and Tsp2A to organize sSJs, and is required for maintaining intestinal stem cell homeostasis through the regulation of aPKC and Yki activities in the Drosophila midgut.
Effects of early-life exposure to sublethal levels of a common neonicotinoid insecticide on the orientation and migration of monarch butterflies (Danaus plexippus)
Authors: Wilcox Alana A. E. , Newman Amy E. M. , Raine Nigel E. , Mitchell Greg W. , Norris D. Ryan
Published: February 2021

Migratory insects use a variety of innate mechanisms to determine their orientation and maintain correct bearing. For long-distance migrants, like the monarch butterfly (Danaus plexippus), these journeys could be affected by exposure to environmental contaminants. Neonicotinoids are synthetic insecticides that work by affecting the nervous system of insects resulting in impairment of their mobility, cognitive performance and other physiological and behavioural functions. To examine how neonicotinoids might affect the ability of monarch butterflies to maintain a proper directional orientation on their ∼4,000 km migration, we grew swamp milkweed (Asclepias incarnata) in soil that was either untreated (0 ng/g: control) or mixed with low (15 ng/g of soil), or high (25 ng/g of soil) levels of the neonicotinoid clothianidin. Monarch caterpillars were raised on control or clothianidin-treated milkweed and, after pupation, either tested for orientation in a static flight simulator or radio-tracked in the wild during the fall migration period. Despite clothianidin being detectable in milkweed tissue consumed by caterpillars, there was no evidence that clothianidin influenced the orientation, vector strength (i.e., concentration of direction data around the mean), or the rate of travel of adult butterflies and nor was there evidence that morphological traits (i.e., mass and forewing length), testing time, wind speed, or temperature impacted directionality. While samples sizes for both flight simulator and radio-tracking tests were limited, our preliminary results suggest that clothianidin exposure during early caterpillar development does not affect the directed flight of adult migratory monarch butterflies or influence their orientation at the beginning of migration.
Optimising retention success: a research team’s experience of following-up participants recruited to a pilot trial through community pharmacies in England
Authors: Watson Michelle , van Dongen Anne , Hewitt Catherine , Mandefield Laura , Stewart Duncan , Watson Judith , McCambridge Jim
Published: February 2021

Background: The CHAMP-1 (Community pharmacy: Highlighting Alcohol use in Medication aPpointments) pilot trial aimed to explore an intervention discussing alcohol during medication consultations with community pharmacists. It presented various challenges regarding patient retention, as participants were recruited by their pharmacist and followed-up remotely by a trained researcher, who they had not met, two months later.  We discuss our actions and experiences of completing follow-up activities.

Methods: Community pharmacists recruited patients aged 18 and over, attending a Medicine Use Review (MUR) or New Medicine Service (NMS) consultation, and drinking alcohol at least twice per week. Pharmacies were randomised to conduct their consultations as usual (control), or to incorporate the Medicines and Alcohol Consultation (MAC) intervention. All participants were followed-up by a researcher after two months to complete data collection via telephone or post. We employed standard follow-up strategies, including a plan to text participants with a reminder in advance of their follow-up.

Results: Forty-seven of 51 participants (92%) completed the two month follow-up. Thirty-eight (81%) responses were provided by telephone and nine (19%) by post. Of the 38 follow-up calls completed by telephone, 17 (45%) participants were reached at first attempt; 16 (42%) at second attempt; and five (13%) at the third attempt. We observed a high percentage of data completion across telephone and postal collection methods.  Participants were willing to discuss potentially sensitive issues, such as alcohol consumption, anxiety, and depression, with a researcher who was external to the pharmacy team. 

Conclusions: The results suggest that patients recruited to a trial by community pharmacists are willing to take part in data collection activities, and remote follow-up can be successfully conducted by researchers. The techniques employed to encourage high levels of retention should be investigated further in a larger study, alongside consideration of optimal strategies to collect data within community pharmacies.
Associated predictor covariates of cervical cancer and impact on survival at Khartoum oncology hospital, Sudan
Authors: Elgoraish Amanda , Alnory Ahmed
Published: February 2021

Background: Cervical cancer can be invasive and advanced at diagnosis causing devastating suffering and premature death. Cancer stage at presentation is related to survival evaluation and several factors determine stage. The aim of the study was to examine predictors covariates associated with cervical cancer stage and its impact on patient prognosis and survival.

Methods: This retrospective cross-sectional study was carried out at Khartoum oncology hospital, Sudan. Participants were 239 cervical cancer patients diagnosed and treated between 2011-2015. Patients’ pathological and socio-demographic data were extracted from their medical files and survival times calculated from follow-up. Chi-square, Kaplan-Meier, Log-rank test and Cox regression model were used to examine relationships between demographic and clinical variables and survival outcome.

Results: The mean age of the participants was 56.91 years and the majority were ≥45 years. Cancer survival analysis showed that stage at diagnosis had limited association with socio-demographic factors, with the exception of where patients residing. Multivariate regression using the Cox proportional hazard model confirmed strongly that stage (p=0.035, chemotherapy (p=0.000) and radiotherapy (p=0.001) were the most likely predictor covariates of patient prognosis and survival time.

Conclusions: The results of this study suggest cancer stage at diagnosis and certain treatments are the most important factors impacting prognosis and survival of patients with cervical cancer. Early detection and vaccination of women against HPV infection provide enormous opportunities for early diagnosis, more effective treatment and better chances of survival.
Study protocol for the COvid-19 Toolbox for All IslaNd (CONTAIN) project: A cross-border analysis in Ireland to disentangle psychological, behavioural, media and governmental responses to COVID-19
Authors: Darker Catherine D. , O'Connell Nicola , Dempster Martin , Graham Christopher D. , O'Connor Cliodhna , Zgaga Lina , Nolan Ann , Tobin Katy , Brennan Niamh , Nicolson Gail , Burke Emma , Mather Luke , Crowley Philip , Scally Gabriel , Barry Joseph
Published: February 2021

COVID-19 represents a serious challenge to governments and healthcare systems. In addition to testing/contact tracing, behavioural and social responses such as handwashing and social distancing or cocooning are effective tools for mitigating the spread of the disease. Psychological (e.g., risk perceptions, self-efficacy) and contextual factors (government, public health messaging, etc.) are likely to drive these behaviours. Collated real-time information of these indicators strengthens local, national and international public health advice and messaging. Further, understanding how well public health and government messages and measures are understood, communicated via (social) media and adhered to is vital. There are two governments and public health jurisdictions on the island of Ireland, the Republic of Ireland (ROI) and Northern Ireland (NI). This represents an opportunity to explore implications of differing measures and messaging across these two jurisdictions as they relate to COVID-19 on two similar populations. The expert research team are drawn from a range of disciplines in the two countries.

This project has four nested studies:

Assessment of key behavioural, social and psychological factors through a large, prospective representative telephone survey of individuals aged over-18 on a weekly basis over eight weeks (n=3072); and conduct qualitative focus groups over the same period.

Interrogation of social media messaging and formal media responses in both jurisdictions to investigate the spread of (mis)information.

Modelling data from Studies 1 and 2, plotting the psychosocial/behavioural and media messaging information with international, ROI and NI incidence and mortality data. 

Conducting an assessment of health policy transfer in an attempt to incorporate the most significant public health and political insights from each jurisdiction.

The CONTAIN project will develop an evidence-based toolbox for targeting public health messaging and political leadership and will be created for use for the anticipated second wave of COVID-19, and subsequently for future epidemics/pandemics.
Uexküll and Whitehead on meaning, process and life
Authors: Araújo Arthur
Published: February 2021

The paper approximates Jakob von Uexküll’s theory of meaning and the process-thought in Alfred Whitehead’s philosophy. As the main idea, the paper points at the compatibility of meaning and process according to the perspectives of Uexküll and Whitehead. It suggests that Uexküll’s common meaning rule can describe the processes of novelty in the world as does Whitehead’s principle of creativity. It is also suggested that Uexküll and Whitehead abandon a substantialist view of the organism – the organism means much more process, activity and creation than anything thing-like. In approaching Uexküll’s theory of meaning, a semiotic interpretation of Whitehead’s principle of creativity is proposed in which the concept of the threshold is fundamental to defining the boundary between the semiotic and the non-semiotic areas corresponding to the living (animate) and the non-living (inanimate). In conclusion, the paper suggests that the activity of meaning distinguishes animate entities from inanimate ones in the sense that meaning and life overlap – meaning could not have existed prior to life (and to the contrary).
Hollywood y Viena. Funciones y connotaciones del atonalismo en el cine y la ópera.
Authors: Martín Quintanal Ruymán
Published: February 2021

In our investigation we make an approach to the uses of atonal music in the opera of the Vienese School and the cinema that became known in the second half of the 20th century. Likewise, we make a comparative study on the meanings in both media, that are constituted by the needs within this two kinds of drama that have certain similarities and differences.
El tratamiento por la negociación colectiva de la violencia de género.
Authors: Calvo Gallego Francisco Javier
Published: February 2021

Tras analizar brevemente el posible papel de la negociación colectiva en la lucha contra la violencia de género y su reflejo en los sucesivos Acuerdos Interconfederales de Negociación Colectiva, el trabajo aborda un análisis cuantitativo y cualitativo de este tratamiento en los convenios colectivos de estos últimos años, estudiando su frecuencia y las características de los acuerdos que incorporan dicha regulación. Finalmente se analizan los modelos más utilizados y el contenido de dicha regulación convencional, prestando una especial atención a las principales novedades incorporadas sobre la actual regulación legal.
Adaptación de una escala de procrastinación académica para adolescentes de educación secundaria
Authors: Trias Seferian Daniel , Carbajal Arregui Miguel
Published: February 2021

Las dinámicas adolescentes y las exigencias de la educación secundaria vuelven pertinente la investigación sobre procrastinación, tan extendida y estudiada en universitarios. El objetivo del presente estudio es adaptar y validar la Tuckman Procrastination Scale (TPS) en una muestra de 211 estudiantes de educación media superior, integrada por 125 mujeres (59%) y 86 hombres (41 %), entre los 15 (45 %) y 16 (54 %) años. La escala presentó adecuada consistencia interna. Se obtuvo evidencia sobre la validez de constructo a partir del análisis factorial confirmatorio. Su validez predictiva se apoya en las correlaciones significativas y negativas con rendimiento académico, autoeficacia, valor intrínseco, y la positiva, con ansiedad ante las pruebas. Estos resultados avalan la validez de la interpretación de las puntuaciones obtenidas con la escala tps para esta muestra de adolescentes, lo que permitirá avanzar en la descripción y explicación del fenómeno de procrastinación académica en esta población.
A Tríade Sombria da Personalidade: Afetos e Lócus de Controle
Authors: Bonfá-Araujo Bruno , Costa Ariela Raissa Lima , Cremasco Gabriela da Silva , Sette Catarina Possenti , Jesuíno Ana Deyvis Santos Araújo
Published: February 2021

A tríade sombria da personalidade —narcisismo, maquiavelismo e psicopatia— retrata características antagonistas, insensíveis e socialmente aversivas. É sabido que diversos fatores são afetados por traços de personalidade, tanto saudáveis quanto psicopatológicos. Este estudo buscou compreender a capacidade explicativa da tríade sombria nos afetos positivos e negativos e no lócus de controle. Para tanto foram realizados dois estudos. Compuseram o primeiro deles 154 participantes, com média de idade de 27,14 anos (DP = 9,28) que responderam ao Dirty Dozen e a Escala de Afetos Positivos e Negativos. O segundo estudo foi composto por 660 participantes, com média de idade 22,83 anos (DP = 7,21) que foram avaliados pelo Short Dark Triad e a Escala Multidimensional de Lócus de Controle. Os resultados indicaram que a tríade sombria explica positivamente os afetos negativos, enquanto maquiavelismo explica negativamente lócus de controle externo e narcisismo e psicopatia explicam o lócus de controle interno —de maneira negativa e positiva, respectivamente. Tais achados são possíveis explicações para os desfechos aversivos em indivíduos com altos escores na tríade sombria, de modo que estes vivenciam mais desprazer e raiva, como também se eximem de suas responsabilidades emocionais e se satisfazem ao notarem que causam danos em terceiros.
Introducing Autonomous Vehicles: Adoption Patterns and Impacts on Social Welfare
Authors: Baron Opher , Berman Oded , Nourinejad Mehdi
Published: February 2021

Problem definition: Autonomous vehicles (AVs) are predicted to enter the consumer market in less than a decade. There is currently no consensus on whether their presence will have a positive impact on users and society. The skeptics of automation foresee increased congestion, whereas the advocates envision smoother traffic with shorter travel times. We study the automation controversy and advise policymakers on how and when to promote AVs. Academic/practical relevance: The AV technology is advancing rapidly and there is a need to study its impact on social welfare and the likelihood of its adoption by the public. Methodology: We use supply-demand theory to find the equilibrium number of trips for autonomous and regular households. We develop a simulation model of peer-to-peer AV sharing. We compare the socially optimal level of automation with the selfish adoption patterns where households independently choose their vehicle type. Results: We establish that the optimal social welfare is influenced by: (i) the network connectivity, that is, the ability of the infrastructure to serve AVs, (ii) the additional comfort provided by AVs that allows passengers to engage in other productive activities instead of driving, and (iii) the AV sharing patterns that reduce ownership costs, but create empty vehicle trips that increase congestion. Managerial implications: We investigate the impact of AVs in a case study of Toronto and show that partial automation maximizes social welfare. We show that the comfort of AVs may add traffic that compromises social welfare. Moreover, although traffic increases with automation, travel times may decrease because of significant improvements in traffic flow caused by AV connectivity in the network.
Demand Shaping Through Bundling and Product Configuration: A Dynamic Multiproduct Inventory-Pricing Model
Authors: Song Jing-Sheng , Xue Zhengliang
Published: February 2021

In today’s digital age with advanced information technology and analytic tools, such as the internet and data mining, many companies use dynamic bundling to influence demand to match up with the operational status, especially in industries with short product life cycles. In “Demand Shaping through Bundling and Product Configuration: A Dynamic Multiproduct Inventory-Pricing Model,” Jing-Sheng Song and Zhengliang Xue present a novel dynamic model to analyze how exactly the inventory dynamics impact the bundling strategy and, in turn, how the bundling strategy affects the firm's inventory decisions. They also characterize how the optimal bundling decision depends on item complementarity, cost structure, inventory levels, demand uncertainty, and supply responsiveness.
The Robust Vehicle Routing Problem with Time Window Assignments
Authors: Hoogeboom Maaike , Adulyasak Yossiri , Dullaert Wout , Jaillet Patrick
Published: February 2021

In practice, there are several applications in which logistics service providers determine the service time windows at the customers, for example, in parcel delivery, retail, and repair services. These companies face uncertain travel times and service times that have to be taken into account when determining the time windows and routes prior to departure. The objective of the proposed robust vehicle routing problem with time window assignments (RVRP-TWA) is to simultaneously determine routes and time window assignments such that the expected travel time and the risk of violating the time windows are minimized. We assume that the travel time probability distributions are not completely known but that some statistics, such as the mean, minimum, and maximum, can be estimated. We extend the robust framework based on the requirements’ violation index, which was originally developed for the case where the specific requirements (time windows) are given as inputs, to the case where they are also part of the decisions. The subproblem of finding the optimal time window assignment for the customers in a given route is shown to be convex, and the subgradients can be derived. The RVRP-TWA is solved by iteratively generating subgradient cuts from the subproblem that are added in a branch-and-cut fashion. Experiments address the performance of the proposed solution approach and examine the trade-off between expected travel time and risk of violating the time windows.
Acyclic Mechanism Design for Freight Consolidation
Authors: Zhang Wentao , Uhan Nelson A. , Dessouky Maged , Toriello Alejandro
Published: February 2021

Freight consolidation is a logistics practice that improves the cost-effectiveness and efficiency of transportation operations, and also reduces energy consumption and carbon footprint. A “fair” shipping cost-sharing scheme is indispensable to help establish and sustain the cooperation of a group of suppliers in freight consolidation. In this paper, we design a truthful acyclic mechanism to solve the cost-sharing problem in a freight consolidation system with one consolidation center and one common destination. Applying the acyclic mechanism, the consolidation center decides which suppliers’ demands ship via the consolidation center and their corresponding cost shares based on their willingness to pay for the service. The proposed acyclic mechanism is designed based on bin packing solutions that are also strong Nash equilibria for a related noncooperative game. We study the budget-balance of the mechanism both theoretically and numerically. We prove a 2-budget-balance guarantee for the mechanism in general and better budget-balance guarantees under specific problem settings. Empirical tests on budget-balance show that our mechanism performs much better than the guaranteed budget-balance ratio. We also study the economic efficiency of our mechanism numerically to investigate its impact on social welfare under different conditions.
The mixed cropping of Anthocephalus cadamba and Glycine max for rehabilitating sloping lands
Authors: KARYATI KARYATI , SARMINAH SRI , KARMINI KARMINI , SIMANGUNSONG GUNAWAN , SIMANGUNSONG GUNAWAN , TAMBA JEKSON
Published: February 2021

Karyati, Sarminah S, Karmini, Simangunsong G, Tamba J. 2018. The mixed cropping of Anthocephalus cadamba and Glycine max for rehabilitating sloping lands. Biodiversitas 19: 2088-2095. Agroforestry system is one of the many alternatives to overcome problems concerning sloping lands. The objectives of this current study were to analyze the effect of agroforestry system in the form of mixed cropping of jabon tree (Anthocephalus cadamba Mig) and soybean (Glycine max Merr) on growth and hydro-orological aspects on sloping lands with different steepness (a slightly steep and a steep slope gradient). The growth parameters (survival rate, ground coverage, diameter increment, and height increment) and hydro-orological parameters (surface runoff, potential erosion, erosion hazard index, and erosion hazard level) were observed in this study. The findings showed that on the slightly steep slope (>15-25%) land, the survival rate of A. cadamba was 90%, the ground coverage of the G. max was 70-79%, the diameter and the height increments of A. cadamba trees were 1.8 cm year-1 and 13.8 cm year-1 respectively. Meanwhile, the potential erosion rate and the erosion hazard index were 32.13 ton ha-1 year-1 and 1.29, respectively. In the steeper slope (>25-45%), the survival rate of A. cadamba reached 90%, the G. max ground cover reached 60-69%, the diameter and height increments of the A. cadamba reached 1.5 cm year-1 and 12.0 cm year-1 respectively. Furthermore, in the steep slope, the potential erosion rate was 52.51 ton ha-1 year-1 and the erosion hazard index was 2.10. In addition, the potential erosion rate and the erosion hazard index in the control plot were higher than those in slightly steep slope. Therefore, it could be implied that the application of A. cadamba and G. max mixed cropping system could rehabilitate sloping lands.
A checklist of Bombyliidae (Diptera) from Mordovia, Russia and variation of wing shape in Bombylius species
Authors: CHURSINA MARIYA ALEXANDROVNA , RUCHIN ALEXANDER BORISOVICH
Published: February 2021

Chursina MA, Ruchin AB. 2018. A checklist of Bombyliidae (Diptera) from Mordovia, Russia and variation of wing shape in Bombylius species. Biodiversitas 19: 2147-2156. A checklist of Bombyliidae (Diptera) of Republic of Mordovia (Russia) is provided, based on material collected from 2008 to 2017. One hundred ninety specimens from 75 localities were collected. Fourteen of the twenty species are listed as belonging to the fauna for the first time. Intraspecific variation and sexual dimorphism in the wing shape of three species of the genus Bombylius Linnaeus, 1758 were investigated using geometric morphometric techniques. The analysis revealed that wing shape is a good discriminator of the species. In addition, significant sexual dimorphism were found: females of two of the three species had larger wings than males. The sex shape differences consisted mainly of сhanges in the placement of the CuA and A1, while interspecific wing shape variation distributed in more dimensions. There was no evidence for allometric relationships relating to sexual dimorphism and interspecific variation. Potential adaptive significance of interspecific and intersex variation in wing size and shape is discussed.
Figures of merit for mid-IR evanescent-wave absorption sensors and their simulation by FEM methods
Authors: Consani Cristina , Dubois Florian , Auböck Gerald
Published: February 2021

Proper optimization of a photonic structure for sensing applications is of extreme importance for integrated sensor design. Here we discuss on the definition of suitable parameters to determine the impact of photonic structure designs for evanescent-wave absorption sensors on the achievable resolution and sensitivity. In particular, we analyze the most widespread quantities used to classify photonic structures in the context of sensing, namely the evanescent-field ratio (or evanescent power factor) and the confinement factor Γ. We show that, somewhat counterintuitively, the confinement factor is the only parameter that can reliably describe the absorption of the evanescent-field in the surrounding medium, and, by quantifying the discrepancy between the two parameters for a set of realistic photonic structures, we demonstrate that using the evanescent-field ratio can lead to a wrong classification of the performance of different structures for absorption sensing. We finally discuss the most convenient simulation strategies to retrieve the confinement factor by FEM simulations.
Geometric representation and the adiabatic geometric phase in four-wave mixing processes
Authors: Li Yongyao , Lü Jiantao , Fu Shenhe , Arie Ady
Published: February 2021

The application of the adiabatic geometric phase (AGP) to nonlinear frequency conversion may help to develop new types of all-optical devices, which leads to all-optical modulation of the phase front of one wave by the intensity of other waves. In this paper, we develop the canonical Hamilton equation and a corresponding geometric representation for two schemes of four-wave mixing (FWM) processes (ω1 + ω2 = ω3 + ω4 and ω1 + ω2 + ω3 = ω4), which can precisely describe and calculate the AGP controlled by the quasi-phase matching technique. The AGPs of the idler (ω1) and signal (ω4) waves for these two schemes of FWM are studied systematically when the two pump waves (ω2 and ω3) are in either the undepleted or in the depleted pump cases, respectively. The analysis reveals that the proposed methods for calculating the AGP are universal in both cases. We expect that the analysis of AGP in FWM processes can be applied to all-optically shaping or encoding of ultrafast light pulse.
Real-time all-optical random numbers based on optical Boolean chaos
Authors: Sang Luxiao , Guo Yuanyuan , Liu Haifang , Zhang Jianguo , Wang Yuncai
Published: February 2021

In this work, a method of generating all-optical random numbers based on optical Boolean chaotic entropy source is proposed. This all-optical random number generation system consists of a Boolean chaotic entropy source and an optical D flip-flop. The Boolean chaotic entropy source is composed of an optical XOR gate and two self-delayed feedback; meanwhile, the optical D flip-flop is composed of two optical AND gates and one SR latch. The optical Boolean chaotic signal possesses the dynamic characteristics of complexity and binarization, so random numbers would be generated only by extracted from chaotic signals with the optical D flip-flop. This all-optical random number generation system achieves the result of 5 Gb/s random numbers that is testable. The whole process of random number generation could be completed in the optical domain without photoelectric conversion, more importantly, the device could be integrated.
The influence of low-fidelity simulator training on canine peripheral venous puncture procedure
Authors: da Silva Dayane Aparecida Francisco , Fernandes Aline Angela , Ventrone Ana Evellyn , Dias Ariane , Silveira Ana Maria Siqueira , Santarém Cecilia Laposy , Ribeiro Gabrielle Gomes dos Santos , Nogueira Rosa Maria Barilli
Published: February 2021

Background and Aim: Blood collection from dogs is the most commonly performed procedure in the medical clinic. However, different factors can interfere with the quality of the material collected, potentially causing complications for patients. Simulated skill training is a teaching strategy designed to provide early training to students, develop their skills and self-confidence, and increase the procedure's success while reducing complications. Therefore, the aim of this study was to evaluate skill training using a low-fidelity simulator in the peripheral venipuncture procedure and examine the training's influence on the in vivo procedure.

Materials and Methods: To assess skill training, this study used a low-fidelity simulator in the peripheral venipuncture procedure and examines the training's effect on the in vivo procedure. In total, 100 dogs, 65 undergraduate students, 3 veterinarians, and 4 previously trained evaluators participated. The canine in vivo venipuncture procedure was evaluated both before and after the simulated skill training and the low-fidelity simulator training. Data were collected on participants' self-confidence levels.

Results: Local complications occurred during in vivo practice; however, after training, they decreased. Gloves were more frequently used during the procedure, resulting in a reduction of both harvest attempts and complications, as well as increased levels of self-confidence in post-training participants. The simulator developed had low fidelity, low cost, and was easy to create.

Conclusion: Skill training in peripheral venipuncture using a low-fidelity simulator positively influences student learning, increases their self-confidence during in vivo harvesting, and reduces the complications of the procedure, improving patient well-being.
Impairment of microvascular blood flow in patients with type 2 diabetes and cardiovascular autonomic neuropathy
Authors: Zelenina T. A. , Salukhov V. V. , Zemlianoi A. B. , Zheleznjak S. G. , Klitsenko O. A.
Published: February 2021

BACKGROUND: Diabetic autonomic neuropathy is the reason for early morbidity and mortality on diabetic patients. The pathology not only cardiac innervation but microvascular is presented.

AIMS: We estimated the parameters of skin microvascular blood flow in accordance with cardiovascular autonomic neuropathy (CAN) staging in diabetic patients. We also assessed other risk factors of CAN in patients with diabetes.

MATERIALS AND METHODS: We included 76 patients with type 2 diabetes in the study (24 patients with resent-onset diabetes and/or diabetes without microvascular complications, 26 with diabetic sensorimotor neuropathy (SMN) and 26 with SMN and previous history of diabetic foot amputation). The SMN was diagnosed on the basis of patients complaints, anamnesis and data of clinical neurological examinations. CAN was detected using several cardiovascular autonomic reflex tests (CART) as a gold standard of diagnosis: the tilt-table test, a deepbreathing and Valsalva Maneuver, handgrip test, cold-stress vasoconstriction. According to the Toronto Diabetic Neuropathy Expert Group Recommendation all patients was separated on the groups: CAN 0 (all CARTs were normal), CAN 1 (possible/early CAN — one abnormal CART was presented), CAN 2 (definite/confirmed CAN –at least two abnormal CARTs were found), CAN 3 (severe/advanced CAN — in the cases of orthostatic hypotension in addition to CARTs abnormalities). Microvascular blood flow of skin at the nail roller of fingers skin was valuated at rest as well as in functional cold test by the method of High-frequency Ultrasonic Dopplerography using the “Minimax Doppler K” device (LLC JV “Minimax”, St. Petersburg, Russia).

RESULTS: CAN 1 was found in 8% diabetic patients without microvascular complications, 42 and 21% patients with SMN and diabetic foot amputations respectively. CAN 2 was diagnosed in 27% patients with SMN and 58% patients history of diabetic foot amputations. CAN 3 in 8% and 19% cases in patients with SMN and history of diabetic foot amputations respectively. The parameters of microvascular blood flow at rest were significantly decreased in patients with confirmed/severe CAN in comparison with early staging of CAN and patients without CAN (Vm=2.5±0.66 sm/sec vs. 4.4±0.54 sm/sec and 5.1±1.01 sm/sec respectively; p=0.0033). The abnormal result of cold test was detected in 94% patients with confirmed/ severe CAN and 26% patients with CAN 1.

CONCLUSIONS: This investigation has demonstrated in a cohort with type 2 diabetes patients with/without SMN and with/ without history of previously foot amputations that decrease the Vm (the variable of microvascular blood flow assessed by High-frequency Ultrasonic Dopplerography) lower than 2.4 sm/sec is associated with 6.4 times increased likelihood of confirmed/severe CAN as well as positive cold test result. That the patients with positive cold test results were 28.6 times more likely have confirmed/severe CAN.
Structural and functional indicators of the heart of patients with ischemic heart disease and type 2 diabetes mellitus. Rhythmoinotropic response isolated myocardium at different levels of glycated hemoglobin
Authors: Kondratieva D. S. , Afanasiev S. A. , Budnikova O. V. , Vorozhtsova I. N. , Akhmedov S. D. , Kozlov B. N.
Published: February 2021

BACKGROUND: Adequate glycemic control can significantly reduce the risk of developing cardiovascular events. However, until now, glycaemic targets in aged patients remain a subject of discussion, especially in the conditions of the combined development of Type 2 Diabetes Mellitus (T2DM) and ischemic heart disease (IHD).

AIMS: To examine the structural and functional heart parameters in patients with IHD associated with T2DM and the rhythmoinotropic responses of their isolated myocardium depending on glycated hemoglobin level.

MATERIALS AND METHODS: The study included 44 patients with a diagnosis of "chronic IHD associated with T2DM", of which 2 groups were formed. Patients with glycated hemoglobin level (HbA1c) <8% were included in the 1st group, and patients with HbA1c ≥8% were included in the 2nd group. The structural and functional heart parameters obtained with ultrasonography, and the rhythmoinotropic responses of myocardium in patients ex vivo were analyzed using the right atrial appendage fragments obtained during elective coronary artery bypass graft. The inotropic response of muscle strips at a basic stimulation frequency of 0,5 Hz to testing influences was assessed. An extrasystolic test and post-rest test were performed.

RESULTS: It was found that extrasystolic contractions of isolated myocardial strips in patients of the 2nd group appeared at shorter extrasystolic intervals, which indicates a greater excitability of the myocardium in patients of this group. Postextrasystolic muscle contractions in patients of the 2nd group had significant potentiation. The amplitude of the muscle strips contractions in patients of both groups was potentiative after short rest periods. However, with an increase in the rest duration, potentiation of contractions was observed only in the group with a higher HbA1c level. According to the ultrasonography data, it was found that the values of the endsystolic and diastolic volumes, the interventricular septum thickness and the left ventricular (LV) myocardium mass were significantly lower in the patients of the 1st group compared with the corresponding indicators in the patients of the 2nd group. The early LV filling velocity (peak E) was significantly lower in the patients of the 1st group, which indicates a slower LV relaxation. At the same time, the rapid LV filling velocity did not have a significant intergroup difference, but this indicator exceeded the reference values in both groups.

CONCLUSIONS: With a moderately increased glycemic level (9,2 [8,0; 10,3]%), the structural and functional heart parameters are preserved both at the level of the isolated myocardial tissue and at the level of the whole heart.
Results of a clinical trial of the efficacy and safety of vildagliptin and metformin fixed combination in real clinical practice in Russia (MASTER study)
Authors: Demidov N. A. , Antsiferov M. B. , Zilov A. V.
Published: February 2021

BACKGRAUND: The widespread prevalence of type 2 diabetes mellitus (T2DM), high mortality and disability of such patients are the reason for the constant active search for effective approaches to hypoglycemic therapy. Recent years have been marked by a change in the strategy for treatment initiation of T2DM. In clinical studies, evidence has been obtained about the benefits of prescribing combination therapy from the time of diagnosis. It seems important to study this treatment option also in real clinical practice.

AIMS: To evaluate the effectiveness and safety of the initiation with Galvus Met® as compared with any other combination therapy approaches used in everyday clinical practice.

MATERIALS AND METHODS: multicenter prospective observational study in 15 regions of Russia lasting 6 months. Patients were included in the study after the endocrinologist made a decision on the appointment of therapy. Of the men and women over 18 years of age with first diagnosed or previously untreated type 2 diabetes and a level of glycated hemoglobin >7.5%, two groups were formed. The first group included patients who received vildagliptin + metformin (Galvus Met®) in a fixed dose of 50/1000 mg, n=729, the second — another double combination (with the exception of insulin and GLP-1), n=669. The primary endpoint was defined as the proportion of patients (%) who achieved the level of HbA1c <7.0% without proven hypoglycemia at the end of the observation. The NHPQ questionnaire was used to assess the frequency of hypoglycemia.

RESULTS: 1385 patients completed the study. For the other combination therapy group, metformin and sulfonylurea derivatives were most often selected (66.5%). In the Galvus Met® group, 68.7% of patients achieved an HbA1c level of <7.0% without proven hypoglycemia, which is significantly better compared to the group of other combinations (40.7%, p <0.001). Galvus Met® therapy contributed to a significantly greater decrease in HbA1c levels by the end of the study compared to other combinations (delta HbA1c -1.6 ± 0.8% versus -1.4 ± 0.9%, p <0.001). In the same group, the average level of HbA1c reached 6.7 ± 0.6% by the end of the study versus 7.1 ± 0.8% in the comparison group, p <0.001. In the Galvus Met® group, body weight decreased by 3.2 ± 3.9 kg, and in the comparison group by 1.3 ± 4.8 kg, p <0.001. The frequency of hypoglycemia episodes in the Galvus Met® group by the end of the study was significantly lower than in the comparison group: 0.8 ± 0.7 episodes per person, versus 1.4 ± 0.8, p = 0.037. In the Galvus Met® group, there were significantly fewer adverse events (4.9% versus 17.7%, p <0.001).

CONCLUSIONS: In real clinical practice, Galvus Met® starting therapy has shown better efficacy and safety in terms of achieving glycemic control, HbA1c dynamics, effects on body weight, the frequency of hypoglycemic conditions compared with other combined oral hypoglycemic therapy.
Prospects for the use of fecal microbiota transplantation in obese patients with Type 2 Diabetes Mellitus for weight loss and improvement of insulin sensitivity
Authors: Pokrovskaya E. V. , Sklyanik I. A. , Shestakova E. A. , Shestakova M. V.
Published: February 2021

Concerning the uncontrolled growth in the incidence of obesity and Type 2 Diabetes Mellitus (T2DM), numerous research have been carried out to study the pathogenetic mechanisms of progress of these diseases and development of new methods for their prevention and treatment in recent years. T2DM is known to be a multifactorial disease, in the development of which both lifestyle and various environmental factors, and genetic predisposition are involved. At the same time, in recent years, a theory has been discussed that intestinal dysbiosis, which is caused with quantitative and qualitative changes in the gut microbiota (GM) is one of the mechanisms of obesity and T2DM development. At the moment, various methods have been proposed for restoring the normal composition of GM, including the administration of prebiotics and metabiotics that stimulate the growth of gut flora, as well as probiotics, which directly include the necessary beneficial bacteria (mainly Bifidobacterium and Lactobacillus). Fecal microflora transplantation (FMT), which allows transferring an entire microbial community into the recipient's body, rather than individual bacteria is the newest and least studied method of GM normalization. In this connection, this method of GM influencing is of great interest for the prevention and treatment of metabolic diseases.
On the centenary of the insulin discovery
Authors: Dedov I. I. , Shestakova M. V.
Published: February 2021

The discovery of insulin and the beginning of its use in 1921–1922 made a revolution in endocrinology and in medicine in general. This significant event gave millions of patients with diabetes not only the opportunity to live, but also the hope that their life with this disease would be full.

The article examines the history of insulin discovery, as well as the evolution of several generations of insulin preparations and the advantages of each of the generations that have radically changed not only life expectancy, but also its quality.

The first generation — insulins of animal origin and the solution of the first tasks of their sufficient production and purification. The next generation is human insulins, the purification of which was also a problem. The third generation is insulin analogues, the action of which became closer to the action profile of natural insulin. And the last generation — insulin analogues, most closely mimicking the action of endogenous insulin.

Along with the development of insulin preparations, the article traces the evolution of the devices of its administration.
Jubilee Greetings from Endocrinologists
Authors: Editorial Article
Published: February 2021

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The prospects for the creation of the National Center for Personalized Medicine of Endocrine Diseases
Authors: Dedov I. I. , Mokrysheva N. G. , Shestakova M. V. , Volchkov P. Y. , Mayorov A. Y. , Rebrova O. Yu. , Barysheva V. O. , Krupinova Ju. A. , Troshina E. A. , Dzeranova L. K. , Melnichenko G. A.
Published: February 2021

The National Medical Research Center for Endocrinology (NMRCE) received the right to implement the development program of the World-class Research Centre “The National Center for personalized medicine of endocrine diseases” (NMCPMED). The objective of the NMCPMED will be not only the creation of a system of personalized treatment, but also the training of new specialists for medicine.  Fundamental researches, carried out on the basis of the already existing institutes and laboratories of the NMRCE will be expanded by creating new laboratories of the NCPMED created de novo in accordance with the approved project. This article introduces the reader to the most important laboratories that would be created in NCPMED. These are laboratories of general, molecular and population genetics, bioinformatics, pharmacogenomics, microbiota, genome editing, mathematical and digital technologies, non-invasive technologies for the diagnosis of endocrinopathies, cellular technologies, artificial intelligence and a fundamentally new laboratory of metabolic visualization and radioteranostics. The authors hope that readers of one of the main journals for endocrinologists in our country will actively participate in the  implementation of NMRCE, as both young and experienced talented researchers will have a chance to be a part of the Centre. To realize the ambitious implementation plans for the achievements of the Centre, it is necessary to radically change the worldview of the doctors in our country, to train them in a new way, and to expand the structure of the Center’s team by increasing the number of specialists in medical genetics, transcriptomics, biostatistics and bioinformatics, working at the intersection of experimental and clinical endocrinology, and ensuring the transit of innovative technologies into clinical practice. New laboratories of the World-Class Research Center, will become the place of routine work of a new generation of doctors, who possess not only the basics of clinical work, but also the skills of fundamental researches that will allow them to significantly improve the methods of diagnosis and treatment.