bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Patent Extension and Take-Back Regulation on Green Pharmacy
Authors: Shi Tianqin , Petruzzi Nicholas C. , Chhajed Dilip
Published: August 2021

Problem definition: The eco-toxicity arising from unused pharmaceuticals has regulators advocating the benign design concept of “green pharmacy,” but high research and development expenses can be prohibitive. We therefore examine the impacts of two regulatory mechanisms, patent extension and take-back regulation, on inducing drug manufacturers to go green. Academic/practical relevance: One incentive suggested by the European Environmental Agency is a patent extension for a company that redesigns its already patented pharmaceutical to be more environmentally friendly. This incentive can encourage both the development of degradable drugs and the disclosure of technical information. Yet, it is unclear how effective the extension would be in inducing green pharmacy and in maximizing social welfare. Methodology: We develop a game-theoretic model in which an innovative company collects monopoly profits for a patented pharmaceutical but faces competition from a generic rival after the patent expires. A social-welfare-maximizing regulator is the Stackelberg leader. The regulator leads by offering a patent extension to the innovative company while also imposing take-back regulation on the pharmaceutical industry. Then the two-profit maximizing companies respond by setting drug prices and choosing whether to invest in green pharmacy. Results: The regulator’s optimal patent extension offer can induce green pharmacy but only if the offer exceeds a threshold length that depends on the degree of product differentiation present in the pharmaceutical industry. The regulator’s correspondingly optimal take-back regulation generally prescribes a required collection rate that decreases as its optimal patent extension offer increases, and vice versa. Managerial implications: By isolating green pharmacy as a potential target to address pharmaceutical eco-toxicity at its source, the regulatory policy that we consider, which combines the incentive inherent in earning a patent extension on the one hand with the penalty inherent in complying with take-back regulation on the other hand, serves as a useful starting point for policymakers to optimally balance economic welfare considerations with environmental stewardship considerations.
Optimal Auction Duration: A Price Formation Viewpoint
Authors: Paul Jusselin , Thibaut Mastrolia , Mathieu Rosenbaum
Published: August 2021

Optimal Auction Duration in Financial Markets

In the considered auction market, market makers fill the order book during a given time period while some other investors send market orders. The clearing price is set to maximize the exchanged volume at the clearing time according to the supply and demand of each market participant. The error made between this clearing price and the efficient price is derived as a function of the auction duration. We study the impact of the behavior of market takers on this error to minimize their transaction costs. We compute the optimal duration of the auctions for 77 stocks traded on Euronext and compare the quality of the price formation process under this optimal value to the case of a continuous limit order book. Continuous limit order books are usually found to be suboptimal. Order of magnitude of optimal auction durations is from 2–10 minutes.
Stability of Parallel Server Systems
Authors: Moyal Pascal , Perry Ohad
Published: August 2021

A parallel server system is a queueing system in which jobs are routed upon their arrivals to one of several buffers, each handled by a different server. The main operational and theoretical problem in such systems is to find an efficient routing policy that maximizes their throughput (or minimizes waiting times). The paper “Stability of Parallel Server Systems” considers a large class of routing policies, which includes the most prevalent policies studies in the literature, under the assumption that routing errors may occur because ofincomplete information about the state of the system at decision epochs. The stability region for this class of policies is studied as a function of the error probability, and it is shown that the standard stability condition, namely, that the traffic intensity is smaller than one, does not guarantee that the system is stable.
A Repeated Route-then-Schedule Approach to Coordinated Vehicle Platooning: Algorithms, Valid Inequalities and Computation
Authors: Luo Fengqiao , Larson Jeffrey
Published: August 2021

In “A Repeated Route-then-Schedule Approach to Coordinated Vehicle Platooning: Algorithms, Valid Inequalities and Computation,” Luo and Larson propose a novel repeated route-then-schedule algorithmic framework to efficiently solve a complex vehicle routing and scheduling problem arising in the intelligent transportation system. The goal is to maximize the collective savings of a set of vehicles (especially heavy-duty vehicles) by utilizing the fact that platooning vehicles save energy due to reduced aerodynamic drag. In the algorithm, the original simultaneous route-and-schedule approach is decomposed into the routing stage and scheduling stage with a sophisticated learning-like feedback mechanism to update the presumed fuel cost for each vehicle traversing through each road segment. This leads to an iterative change of objective function in the routing problem and thereby changes the routes that are fed to the scheduling problem. This approach helps identify high-quality solution. The algorithmic framework leads to a very tight formulation of subproblems that can be solved in a timely manner.
Antimicrobial prescribing and stewardship
Authors: Robertson Deborah
Published: August 2021

Deborah Robertson provides an overview of recently published articles that may be of interest to non-medical prescribers. Should you wish to look at any of the papers in more detail, a full reference is provided
Digital ocular swept source optical coherence aberrometry
Authors: Georgiev Stefan , Kumar Abhishek , Findl Oliver , Hirnschall Nino , Niederleithner Michael , Kendrisic Milana , Drexler Wolfgang , Leitgeb Rainer A.
Published: August 2021

Ocular aberrometry is an essential technique in vision science and ophthalmology. We demonstrate how a phase-sensitive single mode fiber-based swept source optical coherence tomography (SS-OCT) setup can be employed for quantitative ocular aberrometry with digital adaptive optics (DAO). The system records the volumetric point spread function at the retina in a de-scanning geometry using a guide star pencil beam. Succeeding test-retest repeatability assessment with defocus and astigmatism analysis on a model eye within ± 3 D dynamic range, the feasibility of technique is demonstrated in-vivo at a B-scan rate of >1 kHz in comparison with a commercially available aberrometer.
Disassembly of microtubules by intense terahertz pulses
Authors: Hough Cameron M. , Purschke David N. , Bell Clayton , Kalra Aarat P. , Oliva Patricia J. , Huang Chenxi , Tuszynski Jack A. , Warkentin Brad J. , Hegmann Frank A.
Published: August 2021

The biological effects of terahertz (THz) radiation have been observed across multiple levels of biological organization, however the sub-cellular mechanisms underlying the phenotypic changes remain to be elucidated. Filamentous protein complexes such as microtubules are essential cytoskeletal structures that regulate diverse biological functions, and these may be an important target for THz interactions underlying THz-induced effects observed at the cellular or tissue level. Here, we show disassembly of microtubules within minutes of exposure to extended trains of intense, picosecond-duration THz pulses. Further, the rate of disassembly depends on THz intensity and spectral content. As inhibition of microtubule dynamics is a mechanism of clinically-utilized anti-cancer agents, disruption of microtubule networks may indicate a potential therapeutic mechanism of intense THz pulses.
Construction and electrical performance improvement of MoS2 FET with graphene/metal contact
Authors: Han Tao , Liu Hongxia , Chen Shupeng , Wang Shulong , Yang Kun
Published: August 2021

A field effect transistor (FET) device of a MoS2/graphene vertical heterostructure material combined with the high carrier mobility of graphene material with a permanent band gap of monolayer MoS2 material, can realize the application of digital circuit. In this paper, the high-quality MoS2/graphene vertical heterostructure material can be synthesized by chemical vapor deposition (CVD) and wet transfer methods. The electron transfer, photoluminescence (PL) spectrum and carrier transport of MoS2/graphene heterostructure material can be characterized by microscope, Raman spectrometer, SEM, AFM and XPS, which can be used to judge the quality of the material. Besides, monolayer MoS2 and MoS2/graphene FETs can be prepared by lithography and electron beam evaporation, and the electrical performance is also tested and analyzed. The results show that the Schottky barrier height can be adjusted by the gate voltage and doped graphene. The photoexcited electron-hole pairs of monolayer MoS2 material can be separated by MoS2/graphene heterojunction when the gate voltage is zero, which would greatly decrease the PL characteristics. Compared to the MoS2/metal FET, the on-state current, switching ratio ,and drain current of MoS2/graphene FET are increased by an order of magnitude, the mobility and transconductance can also be increased, which can be explained by the smaller Schottky barrier height and the energy band rearrangement. Meanwhile, drain current exceeds 4×10−6A, which can also confirm the enhanced electronic characteristics of MoS2/graphene FET. Therefore, MoS2/graphene vertical heterostructure material can be applied to the ultra-high electronic device fields.
Aligning silver nanowire films with cellulose nanocrystal nematics
Authors: Li Chenxi , Wang Nan , Lei Qiyun , Evans Julian , He Sailing
Published: August 2021

Anisotropic plasmonic films are a desirable material for many optoelectronic applications. Here, we propose a method to align silver nanowires (AgNWs) with the help of uniaxial nematic alignment of cellulose nanocrystal (CNC) liquid crystals (LCs) that can preserve their LC orientation in solid film. AgNWs are doped into uniaxial nematic CNC LCs, where AgNWs are oriented parallel to the director of shear- aligned CNCs without aggregation. The AgNWs orientations are determined by polarized optical and dark field microscopic images. The alignment of AgNWs is characterized by the scalar order parameter S, and the measured S around 0.59 for aligned AgNWs presents an improved anisotropy with the assistance of uniaxial nematic CNC LCs. The electrical property of aligned AgNWs is examined by the four-probe method and exhibits the maximum ratio of anisotropic sheet resistance around 5, consistent with the simulated percolation probability performance using the Monte Carlo computation. Our results show that the uniaxial nematic CNC LCs can act as an effective template in aligning AgNWs, which is compatible with 3D printing and microfluidics, and allows for the preparation of low-cost, innovative optical materials and devices.
Laser-driven resonant magnetic soft-x-ray scattering for probing ultrafast antiferromagnetic and structural dynamics
Authors: Schick Daniel , Borchert Martin , Braenzel Julia , Stiel Holger , Tümmler Johannes , Bürgler Daniel E. , Firsov Alexander , von Korff Schmising Clemens , Pfau Bastian , Eisebitt Stefan
Published: August 2021

Time-resolved resonant magnetic scattering in the soft-x-ray range is a powerful tool for accessing the spatially resolved and element-specific spin dynamics in magnetic materials. So far, the application of this photon-demanding technique was limited to large-scale facilities. However, upgrades to diffraction-limited storage rings supporting only x-ray pulses beyond 100 ps, and the shift of x-ray free-electron lasers toward attosecond pulses aggravate the competition for beamtime in the picosecond time window, which is of utmost relevance for magnetism research. Here we present the development of a lab-based instrument providing sufficient photon flux up to 1.5 keV photon energy covering the soft-x-ray resonances of transition and rare-earth metal atoms. Our setup features the mandatory tunability in energy and reciprocal space in combination with sub-10 ps temporal resolution, exploiting the broadband emission of a laser-driven plasma x-ray source, which is monochromatized to about 1 eV bandwidth by a reflection zone plate. We benchmark our approach against accelerator-based soft-x-ray sources by simultaneously probing the laser-induced magnetic and structural dynamics from an antiferromagnetically coupled Fe/Cr superlattice. Our development lays the foundation for laser-driven resonant scattering experiments to study ultrafast ordering phenomena of charges, spins, and orbitals.
Supersymmetric analysis of stochastic micro-bending in optical waveguides
Authors: Ward Stuart , Allahverdi Rouzbeh , Mafi Arash
Published: August 2021

Micro-bending attenuation in an optical waveguide can be modeled by a Fokker-Planck equation. It is shown that a supersymmetric transformation applied to the Fokker-Planck equation is equivalent to a change in the refractive index profile, resulting in a larger or smaller attenuation. For a broad class of monomial index profiles, it is always possible to obtain an index profile with a larger micro-bending attenuation using a supersymmetric transformation. However, obtaining a smaller attenuation is not always possible and is restricted to a subset of index profiles.
Large-scale simulations of biological cell sorting driven by differential adhesion follow diffusion-limited domain coalescence regime
Authors: Durand Marc
Published: August 2021

Cell sorting, whereby a heterogeneous cell mixture segregates and forms distinct homogeneous tissues, is one of the main collective cell behaviors at work during development. Although differences in interfacial energies are recognized to be a possible driving source for cell sorting, no clear consensus has emerged on the kinetic law of cell sorting driven by differential adhesion. Using a modified Cellular Potts Model algorithm that allows for efficient simulations while preserving the connectivity of cells, we numerically explore cell-sorting dynamics over very large scales in space and time. For a binary mixture of cells surrounded by a medium, increase of domain size follows a power-law with exponent n = 1/4 independently of the mixture ratio, revealing that the kinetics is dominated by the diffusion and coalescence of rounded domains. We compare these results with recent numerical studies on cell sorting, and discuss the importance of algorithmic differences as well as boundary conditions on the observed scaling.
An uncertainty-based model of the effects of fixation on choice
Authors: Li Zhi-Wei , Ma Wei Ji
Published: August 2021

When people view a consumable item for a longer amount of time, they choose it more frequently; this also seems to be the direction of causality. The leading model of this effect is a drift-diffusion model with a fixation-based attentional bias. Here, we propose an explicitly Bayesian account for the same data. This account is based on the notion that the brain builds a posterior belief over the value of an item in the same way it would over a sensory variable. As the agent gathers evidence about the item from sensory observations and from retrieved memories, the posterior distribution narrows. We further postulate that the utility of an item is a weighted sum of the posterior mean and the negative posterior standard deviation, with the latter accounting for risk aversion. Fixating for longer can increase or decrease the posterior mean, but will inevitably lower the posterior standard deviation. This model fits the data better than the original attentional drift-diffusion model but worse than a variant with a collapsing bound. We discuss the often overlooked technical challenges in fitting models simultaneously to choice and response time data in the absence of an analytical expression. Our results hopefully contribute to emerging accounts of valuation as an inference process.
Transmission of ‘Candidatus Anaplasma camelii’ to mice and rabbits by camel-specific keds, Hippobosca camelina
Authors: Bargul Joel L. , Kidambasi Kevin O. , Getahun Merid N. , Villinger Jandouwe , Copeland Robert S. , Muema Jackson M. , Carrington Mark , Masiga Daniel K.
Published: August 2021

Anaplasmosis, caused by infection with bacteria of the genus Anaplasma, is an important veterinary and zoonotic disease. Transmission by ticks has been characterized but little is known about non-tick vectors of livestock anaplasmosis. This study investigated the presence of Anaplasma spp. in camels in northern Kenya and whether the hematophagous camel ked, Hippobosca camelina, acts as a vector. Camels (n = 976) and > 10,000 keds were sampled over a three-year study period and the presence of Anaplasma species was determined by PCR-based assays targeting the Anaplasmataceae 16S rRNA gene. Camels were infected by a single species of Anaplasma, ‘Candidatus Anaplasma camelii’, with infection rates ranging from 63–78% during the dry (September 2017), wet (June-July 2018), and late wet seasons (July-August 2019). 10–29% of camel keds harbored ‘Ca. Anaplasma camelii’ acquired from infected camels during blood feeding. We determined that Anaplasma-positive camel keds could transmit ‘Ca. Anaplasma camelii’ to mice and rabbits via blood-feeding. We show competence in pathogen transmission and subsequent infection in mice and rabbits by microscopic observation in blood smears and by PCR. Transmission of ‘Ca. Anaplasma camelii’ to mice (8–47%) and rabbits (25%) occurred readily after ked bites. Hence, we demonstrate, for the first time, the potential of H. camelina as a vector of anaplasmosis. This key finding provides the rationale for establishing ked control programmes for improvement of livestock and human health.
Availability, affordability and stock-outs of commodities for the treatment of snakebite in Kenya
Authors: Ooms Gaby Isabelle , van Oirschot Janneke , Okemo Dorothy , Waldmann Benjamin , Erulu Eugene , Mantel-Teeuwisse Aukje K , van den Ham Hendrika A , Reed Tim
Published: August 2021

Background

Annually, about 2.7 million snakebite envenomings occur globally. Alongside antivenom, patients usually require additional care to treat envenoming symptoms and antivenom side effects. Efforts are underway to improve snakebite care, but evidence from the ground to inform this is scarce. This study, therefore, investigated the availability, affordability, and stock-outs of antivenom and commodities for supportive snakebite care in health facilities across Kenya.

Methodology/principal findings

This study used an adaptation of the standardised World Health Organization (WHO)/Health Action International methodology. Data on commodity availability, prices and stock-outs were collected in July-August 2020 from public (n = 85), private (n = 36), and private not-for-profit (n = 12) facilities in Kenya. Stock-outs were measured retrospectively for a twelve-month period, enabling a comparison of a pre-COVID-19 period to stock-outs during COVID-19. Affordability was calculated using the wage of a lowest-paid government worker (LPGW) and the impoverishment approach. Accessibility was assessed combining the WHO availability target (≥80%) and LPGW affordability (<1 day’s wage) measures. Overall availability of snakebite commodities was low (43.0%). Antivenom was available at 44.7% of public- and 19.4% of private facilities. Stock-outs of any snakebite commodity were common in the public- (18.6%) and private (11.7%) sectors, and had worsened during COVID-19 (10.6% versus 17.0% public sector, 8.4% versus 11.7% private sector). Affordability was not an issue in the public sector, while in the private sector the median cost of one vial of antivenom was 14.4 days’ wage for an LPGW. Five commodities in the public sector and two in the private sector were deemed accessible.

Conclusions

Access to snakebite care is problematic in Kenya and seemed to have worsened during COVID-19. To improve access, efforts should focus on ensuring availability at both lower- and higher-level facilities, and improving the supply chain to reduce stock-outs. Including antivenom into Universal Health Coverage benefits packages would further facilitate accessibility.
Active rheumatoid arthritis in a mouse model is not an independent risk factor for periprosthetic joint infection
Authors: Trikha Rishi , Greig Danielle , Sekimura Troy , Cevallos Nicolas , Kelley Benjamin , Mamouei Zeinab , Hart Christopher , Ralston Micah , Turkmani Amr , Sassoon Adam , Stavrakis Alexandra , Bernthal Nicholas M.
Published: August 2021

Introduction

Periprosthetic joint infection (PJI) represents a devastating complication of total joint arthroplasty associated with significant morbidity and mortality. Literature suggests a possible higher incidence of periprosthetic joint infection (PJI) in patients with rheumatoid arthritis (RA). There is, however, no consensus on this purported risk nor a well-defined mechanism. This study investigates how collagen-induced arthritis (CIA), a validated animal model of RA, impacts infectious burden in a well-established model of PJI.

Methods

Control mice were compared against CIA mice. Whole blood samples were collected to quantify systemic IgG levels via ELISA. Ex vivo respiratory burst function was measured via dihydrorhodamine assay. Ex vivo Staphylococcus aureus Xen36 burden was measured directly via colony forming unit (CFU) counts and crystal violet assay to assess biofilm formation. In vivo, surgical placement of a titanium implant through the knee joint and inoculation with S. aureus Xen36 was performed. Bacterial burden was then quantified by longitudinal bioluminescent imaging.

Results

Mice with CIA demonstrated significantly higher levels of systemic IgG compared with control mice (p = 0.003). Ex vivo, there was no significant difference in respiratory burst function (p = 0.89) or S. aureus bacterial burden as measured by CFU counts (p = 0.91) and crystal violet assay (p = 0.96). In vivo, no significant difference in bacterial bioluminescence between groups was found at all postoperative time points. CFU counts of both the implant and the peri-implant tissue were not significantly different between groups (p = 0.82 and 0.80, respectively).

Conclusion

This study demonstrated no significant difference in S. aureus infectious burden between mice with CIA and control mice. These results suggest that untreated, active RA may not represent a significant intrinsic risk factor for PJI, however further mechanistic translational and clinical studies are warranted.
Detecting drought regulators using stochastic inference in Bayesian networks
Authors: Lahiri Aditya , Zhou Lin , He Ping , Datta Aniruddha
Published: August 2021

Drought is a natural hazard that affects crops by inducing water stress. Water stress, induced by drought accounts for more loss in crop yield than all the other causes combined. With the increasing frequency and intensity of droughts worldwide, it is essential to develop drought-resistant crops to ensure food security. In this paper, we model multiple drought signaling pathways in Arabidopsis using Bayesian networks to identify potential regulators of drought-responsive reporter genes. Genetically intervening at these regulators can help develop drought-resistant crops. We create the Bayesian network model from the biological literature and determine its parameters from publicly available data. We conduct inference on this model using a stochastic simulation technique known as likelihood weighting to determine the best regulators of drought-responsive reporter genes. Our analysis reveals that activating MYC2 or inhibiting ATAF1 are the best single node intervention strategies to regulate the drought-responsive reporter genes. Additionally, we observe simultaneously activating MYC2 and inhibiting ATAF1 is a better strategy. The Bayesian network model indicated that MYC2 and ATAF1 are possible regulators of the drought response. Validation experiments showed that ATAF1 negatively regulated the drought response. Thus intervening at ATAF1 has the potential to create drought-resistant crops.
Expertise based skills management system to support resource allocation
Authors: Bibi Nazia , Anwar Zeeshan , Rana Tauseef
Published: August 2021

Skills Management is an essential concept of human resource management in which a skill inventory may be created for each employee and managers can assign tasks to workers based on worker’s abilities. This concept is not fully practiced for two reasons: i) employee’s skills are not effectively evaluated and documented, ii) tool support is deficient to manage this complex task. Ineffective skill management of an organization fizzle tasks assigned to the incompetent employees and this may lead to project failure. To fill up this gap, a survey is conducted across various software organizations to find out the best practices for the skill management and to gather requirements for skills management framework. Based on survey findings, a mathematical framework is proposed that calculates the soft and hard skills of employees automatically based on time and achievements as skill increases or decreases over time. In this framework, the Skills Calculation Engine (SCE) is developed for the managers to enhance the capacity of appropriate decisions making in assigning tasks to the rightly skilled workers. This framework is also useful for organizations as it can increase profitability as tasks are assigned to the most appropriate employees. The SCE is implemented as a Windows-based application to calculate skills, store skills in skills inventory, and assign tasks based on an employee’s skills. The skills management tool is evaluated in a facilitated workshop; furthermore, a feature-wise comparison of the tool is also made with existing tools.
Increased livestock weight gain from improved water quality in farm dams: A cost-benefit analysis
Authors: Dobes Leo , Crane Mason , Higgins Tim , Van Dijk Albert I. J. M. , Lindenmayer David B.
Published: August 2021

Access to water is a critical aspect of livestock production, although the relationship between livestock weight gain and water quality remains poorly understood. Previous work has shown that water quality of poorly managed farm dams can be improved by fencing and constructing hardened watering points to limit stock access to the dam, and revegetation to filter contaminant inflow. Here we use cattle weight gain data from three North American studies to develop a cost-benefit analysis for the renovation of farm dams to improve water quality and, in turn, promote cattle weight gain on farms in south-eastern Australia. Our analysis indicated a strong likelihood of positive results and suggested there may be substantial net economic benefit from renovating dams in poor condition to improve water quality. The average per-farm Benefit-Cost Ratios based on deterministic assumptions was 1.5 for New South Wales (NSW) and 3.0 for Victoria in areas where rainfall exceeds 600mm annually. Our analyses suggested that cattle on farms in NSW and Victoria would need to experience additional weight gain from switching to clean water of at least 6.5% and 1.8% per annum respectively, to break even in present value terms. Monte Carlo simulation based on conservative assumptions indicated that the probability of per-farm benefits exceeding costs was greater than 70%. We recommend localised experiments to assess the impact of improved water quality on livestock weight gain in Australian conditions to confirm these expectations empirically.
Psychological factors and consumer behavior during the COVID-19 pandemic
Authors: Di Crosta Adolfo , Ceccato Irene , Marchetti Daniela , La Malva Pasquale , Maiella Roberta , Cannito Loreta , Cipi Mario , Mammarella Nicola , Palumbo Riccardo , Verrocchio Maria Cristina , Palumbo Rocco , Di Domenico Alberto
Published: August 2021

The COVID-19 pandemic is far more than a health crisis: it has unpredictably changed our whole way of life. As suggested by the analysis of economic data on sales, this dramatic scenario has also heavily impacted individuals’ spending levels. To better understand these changes, the present study focused on consumer behavior and its psychological antecedents. Previous studies found that crises differently affect people’s willingness to buy necessities products (i.e., utilitarian shopping) and non-necessities products (i.e., hedonic shopping). Therefore, in examining whether changes in spending levels were associated with changes in consumer behavior, we adopted a fine-grained approach disentangling between necessities and non-necessities. We administered an online survey to 3833 participants (age range 18–64) during the first peak period of the contagion in Italy. Consumer behavior toward necessities was predicted by anxiety and COVID-related fear, whereas consumer behavior toward non-necessities was predicted by depression. Furthermore, consumer behavior toward necessities and non-necessities was predicted by personality traits, perceived economic stability, and self-justifications for purchasing. The present study extended our understanding of consumer behavior changes during the COVID-19 pandemic. Results could be helpful to develop marketing strategies that consider psychological factors to meet actual consumers’ needs and feelings.
Quantitative measurement of the histological features of alpha-1 antitrypsin deficiency-associated liver disease in biopsy specimens
Authors: Marek George , Collinsworth Amy , Liu Chen , Brantly Mark , Clark Virginia
Published: August 2021

Background

Pathological mutations in Alpha-1 Antitrypsin (AAT) protein cause retention of toxic polymers in the hepatocyte endoplasmic reticulum. The risk for cirrhosis in AAT deficiency is likely directly related to retention of these polymers within the liver. Polymers are classically identified on liver biopsy as inclusion bodies by periodic acid schiff staining after diastase treatment and immunohistochemistry. However, characterization of the polymer burden within a biopsy sample is limited to a semi-quantitative scale as described by a pathologist. Better methods to quantify polymer are needed to advance our understanding of pathogenesis of disease. Therefore, we developed a method to quantify polymer aggregation from standard histologic specimens. In addition, we sought to understand the relationship of polymer burden and other histologic findings to the presence of liver fibrosis.

Methods

Liver samples from a well-categorized AATD cohort were used to develop histo-morphometric tools to measure protein aggregation.

Results

Whole-slide morphometry reliably quantifies aggregates in AATD individuals. Despite very low levels of inclusions present (0–0.41%), accumulation of globules is not linear and is associated with higher fibrosis stages. Immunohistochemistry demonstrates that fibrosis is associated with polymer accumulation and not total AAT. A proportion of patients were found to be “heavy accumulators” with a polymer burden above the upper 25% of normal distribution. Males had significantly more liver inclusions and polymer than females. These measurements also highlight interrelated phenotypes of hepatocellular degeneration and autophagy in AATD liver disease.

Conclusion

Quantitative inclusion analysis measures AAT accumulation in liver biopsy specimens. Quantification of polymer may identify individuals at risk for progressive disease and candidates for therapeutic interventions. Furthermore, these methods may be useful for evaluating efficacy of drugs targeting accumulation of AAT.
Impact of heavy precipitation events on pathogen occurrence in estuarine areas of the Puzi River in Taiwan
Authors: Shih Yi-Jia , Chen Jung-Sheng , Chen Yi-Jen , Yang Pei-Yu , Kuo Yi-Jie , Chen Tsung-Hsien , Hsu Bing-Mu
Published: August 2021

Pathogen populations in estuarine areas are dynamic, as they are subject to multiple natural and anthropogenic challenges. Heavy rainfall events bring instability to the aquatic environment in estuaries, causing changes in pathogen populations and increased environmental sanitation and public health concerns. In this study, we investigated the effects of heavy precipitation on the occurrence of pathogens in the Puzi River estuary, which is adjacent to the largest inshore oyster farming area in Taiwan. Our results indicated that Vibrio parahaemolyticus and adenovirus were the most frequently detected pathogens in the area. There was a significant difference (Mann-Whitney U test, p < 0.01) in water quality parameters, including total coliform, Escherichia coli, water temperature, turbidity, salinity, and dissolved oxygen, between groups with and without V. parahaemolyticus. In addition, the detection rate was negatively correlated with the average daily rainfall (r2 > 0.8). There was no significant difference between water quality parameters and the presence/absence of adenovirus, but a positive correlation was observed between the average daily rainfall and the detection rate of adenovirus (r2 ≥ 0.75). We conclude that heavy precipitation changes estuarine water quality, causing variations in microbial composition, including pathogens. As extreme weather events become more frequent due to climate change, the potential impacts of severe weather events on estuarine environments require further investigation.
An improved NFC device authentication protocol
Authors: Lu He-Jun , Liu Dui
Published: August 2021

Aimed at the security authentication problem between Near Field Communication (NFC) devices, this paper uses the technology of asymmetric encryption algorithm, symmetric encryption algorithm, hash function, timestamp and survival period to improve the confidentiality, performance and security of the protocol. The symmetric encryption algorithm encrypts the transmission content, while the asymmetric encryption algorithm encrypts the shared key. The whole authentication process is secure, and the key distribution is secure. The improved NFC device authentication protocol can effectively resist the brute force attack, man-in-the-middle attack and replay attack in the authentication process, it can reduce the number of message transmission in the authentication process, improve the transmission efficiency, enhance the confidentiality, integrity, non-repudiation and improve the security of NFC device authentication.
Assessment of the activity and organ damage in antiphospholipid syndrome
Authors: Cheldieva F. A. , Reshetnyak T. M. , Lila A. M.
Published: August 2021

The review provides a brief description of the clinical and serological markers of antiphospholipid syndrome (APS), risk factors for the development and recurrence of thrombosis in APS. A complete description of the GAPSS and its simplified (corrected) version, adjusted GAPSS (aGAPSS), as well as the DIAPS, is presented. These scales allow one to determine the activity of APS and reflect the range of cumulative and/or irreversible damage due to the disease.
Pharmacotherapy of gout – modern approaches and prospects
Authors: Lebedev P. A. , Garanin A. A. , Novichkova N. L.
Published: August 2021

The article discusses modern approaches to the gout treatment, presented in foreign and domestic clinical guidelines. While the use of urate-lowering therapy for gout is a necessary and highly effective strategy, in the case of asymptomatic hyperuricemia, the benefits of this approach are not clear. The safety and efficacy of colchicine, as well as its cardioprotective properties, were noted in comorbid patients suffering from gout and cardiovascular diseases. Comparative data on safety and efficacy of the main urate-lowering drugs, allopurinol and febuxostat, are presented. It has been shown that, according to recent studies, febuxostat is more effective than allopurinol in normalizing serum uric acid levels, is not inferior in its cardio safety and is characterized by a lower incidence of other adverse reactions.
A case of effective use of interleukin 6 inhibitors in patients with ankylosing spondylitis with secondary amyloidosis
Authors: Erdes Sh. F. , Rumyantseva D. G. , Agafonova E. M. , Urumova M. M. , Starkova A. S. , Krasnenko S. O.
Published: August 2021

Ineffectiveness of interleukin 6 inhibitors (iIL6), tocilizumab (TCZ) and sarilimumab in ankylosing spondylitis (AS) was shown in randomized clinical trials. However, there is ample evidence that IL6 is actively involved in the pathogenesis of this disease. In addition, the efficacy of iIL6 in patients with secondary AA-amyloidosis was established.Objective: to analyze the results of TCZ administration in AS, complicated by secondary AA-amyloidosis.Patients and methods. The analysis included 6 patients with AS with secondary AA-amyloidosis. All patients were HLA-B27 positive male. The average age of patients was 44±9.2 years, the average age of the disease onset was 16.3±7.9 years, the average duration of AS was 26.0±7.5 years. All 6 patients had pathomorphologic confirmed secondary AA-amyloidosis: all had kidney affection, 5 patients also had gastrointestinal tract affection and 2 had heart affection. As a first biological drug TCZ was prescribed in 2 patients, and 4 patients had previously received one or more inhibitors of tumor necrosis factor α. The average duration of TCZ treatment was 27.6 [3.0; 36.0] months.Results and discussion. During TCZ therapy, the level of CRP (M±σ) significantly decreased: from 81.1±74.5 to 1.2±0.8 mg/L (p<0.05), as well as daily proteinuria (Me [25th ; 75th percentile]): from 1.8 [1.0; 2.1] to 0.2 [0.1; 0.3] g/day (p<0.05) and AS activity indices – BASDAI (M±σ): from 6.2±1.6 to 3.3±0.9 (p<0.05 ); ASDAS-CRP (M±σ) from 4.6±1.1 to 2.04±0.7 (p<0.05). Positive dynamics was also noted in relation to a decrease in the number of patients with inflammatory back pain, arthritis and coxitis. A case of clinical and laboratory remission of AS on TCZ treatment is described. Conclusion. The presented data show that in certain clinical situations iIL6 can be highly effective in AS.
Response to Rituximab after Failure of Cyclophosphamide in the Induction Treatment in a Patient with cANCA-associated Vasculitis and Pachymeningitis: a Case Report
Authors: Psenak O. , Greil R.
Published: August 2021

A 36-year-old male patient who originally presented with recurrent inflammations in the mastoid, otitis media and peripheral facial paralysis was diagnosed with sterile pachymeningitis, associated with high titres of antineutrophil cytoplasmic antibodies (cANCA) directed against proteinase 3 (PR3). Induction therapy with oral prednisolone 1 mg/kg body weight and cyclophosphamide (CYC) 750 mg/m 2 i.v. every 4 weeks was initiated. Due to side effects, increasing arthralgias and progressive meningitis after 5 doses of CYC, treatment was changed to rituximab (RTX), one cycle comprising two administrations of 1000 mg RTX i.v. two weeks apart, repeated every 6 months. After the very first cycle of RTX, we confirmed subjective improvement of the patient’s fitness as well as radiologic response. Methotrexate (MTX) was added to ease arthralgias. Painful bleeding ulcerations on finger tips were successfully treated with 22 iloprost infusions. Up to date, we have administered 7 cycles of RTX and achieved complete remission of the cANCA-associated vasculitis. After the induction therapy, maintenance treatment with MTX or rituximab will be performed for at least 18–24 months.We can demonstrate a complete remission with the use of RTX in a patient with cANCA-associated vasculitis and sterile pachymeningitis who failed to respond to the induction treatment with CYC. RTX has been well tolerated.
Molecular basis for new approaches to therapy of osteoarthritis (part I)
Authors: Chetina E. V. , Markova G. A. , Lila A. M.
Published: August 2021

Osteoarthritis (OA) is the most common disease of the elderly, which is accompanied by pain and damages all tissues of the joint. OA is associated with progressive loss of articular cartilage, sclerotic changes in the subchondral bone and the formation of osteophytes. Cartilage destruction is caused by resorption of the extracellular matrix, which consists mainly of type II collagen and aggrecan proteoglycan. Excessive cleavage of type II collagen in OA is associated with increased synthesis and activity of metalloproteinases and the expression of pro-inflammatory cytokines of interleukin 1β and tumor necrosis factor α. Currently, OA therapy is symptomatic, often ineffective, and in some cases is accompanied by adverse side effects. Therefore, the search for new therapeutic approaches to the treatment of the disease, using modern technological capabilities and knowledge of the metabolic disorders that cause the disease. The review presents new promising methods in the treatment of OA using stem cells and subcellular structures, based on modern knowledge of molecular and cellular mechanisms that are disrupted during development and disease progression.
Combination of ankylosing spondylitis and rheumatoid arthritis: clinical observations and literature review
Authors: Godzenko A. A. , Cheremushkina E. V. , Dimitreva A. E. , Urumova M. M.
Published: August 2021

The article discusses one of the variants of overlap syndrome – a combination of symptoms of ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Three clinical cases are described, in these cases characteristic signs of both diseases were noted and the criteria of both diseases were met. The genetic factors and immunopathogenetic mechanisms underlying AS and RA are analyzed. A review of the literature on the combination of AS and RA is presented.
Difficulties in management of patients with systemic lupus erythematosus and antiphospholipid syndrome in combination with melanoma and infiltrative tuberculosis (clinical observations)
Authors: Shumilova A. A. , Reshetnyak T. M. , Cheldieva F. A. , Lila A. M.
Published: August 2021

We present two clinical cases: the first patient had combination of antiphospholipid syndrome (APS) and melanoma, and the second – systemic lupus erythematosus (SLE) and APS, melanoma, infiltrative tuberculosis and Herpes zoster. Managing patients with SLE combined with APS is really challenging. Infections and malignant neoplasms, along with kidney damage and cardiovascular diseases, are a significant cause of death in this cohort of patients. The role of antibodies to phospholipids in the onset of malignancy is still under discussion. The combination of rheumatic diseases with oncological or infectious pathology complicates therapy, limiting the use of drugs, recommended by clinical guidelines.
APPLICATION OF COMPUTER VISION TECHNOLOGIES FOR THE DEVELOPMENT OF A MODEL FOR THE RECOGNITION OF LESIONS OF CULTIVATED PLANTS
Authors:   Orenburg State University, Orenburg, Russian Federation, Yanishevskaya N.A. , Bolodurina I.P. ,   Orenburg State University, Orenburg, Russian Federation
Published: August 2021

In the Russian Federation, the agro-industrial complex is one of the leading sectors of the eco-nomy with a volume of domestic product of 4.5%. Russia owns 10 % of all arable land in the world. According to the data on the sown areas by crops in 2020, most of the agricultural area of Russia is occupied by wheat. The Russian Federation ranks third in the ranking of leading countries in the production of this type of grain crops, as well as leading positions in its export. Brown (leaf) and linear (stem) rust is the most harmful disease of grain crops. It is the reason for the sparseness of wheat crops and leads to a sharp decrease in yield. Therefore, one of the main tasks of farmers is to preserve the crop from diseases. The application of such areas of artificial intelligence as computer vision, machine learning and deep learning is able to cope with this task. These artificial intelligence technologies allow us to successfully solve applied problems of the agro-industrial complex using automated analysis of photographic materials. Aim. To consider the application of computer vision methods for the problem of classification of lesions of cultivated plants on the example of wheat. Materials and methods. The CGIAR Computer Vision for Crop Disease dataset for the crop disease recognition task is taken from the open source Kaggle. It is proposed to use an approach to the re-cognition of lesions of cultivated plants using the well-known neural network models ResNet50, DenseNet169, VGG16 and EfficientNet-B0. Neural network models receive images of wheat as in-put. The output of neural networks is the class of plant damage. To overcome the effect of overfit-ting neural networks, various regularization techniques are investigated. Results. The results of the classification quality, estimated by the software using the F1-score metric, which is the average harmonic between the Precision and Recall measures, are presented. Conclusion. As a result of the conducted research, it was found that the DenseNet model showed the best recognition accuracy us-ing a combination of transfer learning technology and DropOut and L2 regulation technologies to overcome the effect of retraining. The use of this approach allowed us to achieve a recognition ac-curacy of 91%.
Development of Algorithms for Choosing the Best Time Series Models and Neural Networks to Predict COVID-19 Cases
Authors:   South Ural State University, Chelyabinsk, Russian Federation, Abotaleb M.S.A. , Makarovskikh T.A.
Published: August 2021

Time series analysis became one of the most investigated fields of knowledge during spreading of the COVID-19 around the world. The problem of modeling and forecasting infection cases of COVID-19, deaths, recoveries and other parameters is still urgent. Purpose of the study. Our article is devoted to investigation of classical statistical and neural network models that can be used for forecasting COVID-19 cases. Materials and methods. We discuss neural network model NNAR, compare it with linear and nonlinear models (BATS, TBATS, Holt's linear trend, ARIMA, classical epidemiological SIR model). In our article we discuss the Epemedic.Network algorithm using the R programming language. This algorithm takes the time series as input data and chooses the best model from SIR, statistical models and neural network model. The model selection criterion is the MAPE error. We consider the implementation of our algorithm for analysis of time series for COVID -19 spreading in Chelyabinsk region, and predicting the possible peak of the third wave using three possible scenarios. We mention that the considered algorithm can work for any time se-ries, not only for epidemiological ones. Results. The developed algorithm helped to identify the pat-tern of COVID -19 infection for Chelyabinsk region using the models realized as parts of the consi-dered algorithm. It should be noted that the considered models make it possible to form short-term forecasts with sufficient accuracy. We show that the increase in the number of neurons led to in-creasing accuracy, as there are other cases where the error is reduced in case of reducing the number of neurons, and this depends on COVID -19 infection spreading pattern. Conclusion. Hence, to get a very accurate forecast, we recommend re-running the algorithm weekly. For medium-range fore-casting, only the NNAR model can be used from among those considered but it also allows to get good forecasts only with horizon 1–2 weeks.