bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing Best Practice Guidance for Discharge Planning Using the RAND/UCLA Appropriateness Method
Authors: Tyler Natasha , Planner Claire , Byrne Matthew , Blakeman Thomas , Keers Richard N. , Wright Oliver , Pascall Jones Paul , Giles Sally , Keyworth Chris , Hodkinson Alexander , Taylor Christopher D. J. , Armitage Christopher J. , Campbell Stephen , Panagioti Maria
Published: December 2021

Background: Discharge from acute mental health inpatient units is often a vulnerable period for patients. Multiple professionals and agencies are involved and processes and procedures are not standardized, often resulting in communication delays and co-ordination failures. Early and appropriate discharge planning and standardization of procedures could make inpatient care safer.

Aim: To inform the development of a multi-component best practice guidance for discharge planning (including the 6 component SAFER patient flow bundle) to support safer patient transition from mental health hospitals to the community.

Methods: Using the RAND/UCLA Appropriateness method, a panel of 10 professional stakeholders (psychiatrists, psychiatric nurses, clinical psychologists, pharmacists, academics, and policy makers) rated evidence-based statements. Six hundred and sixty-eight statements corresponding to 10 potential components of discharge planning best practice were rated on a 9-point integer scale for clarity, appropriateness and feasibility (median ≥ 7–9) using an online questionnaire then remote online face-to-face meetings.

Results: Five of the six “SAFER” patient flow bundle components were appropriate and feasible for inpatient mental health. One component, “Early Flow,” was rated inappropriate as mental health settings require more flexibility. Overall, 285 statements were rated as appropriate and feasible. Forty-four statements were considered appropriate but not feasible to implement.

Discussion: This consensus study has identified components of a best practice guidance/intervention for discharge planning for UK mental health settings. Although some components describe processes that already happen in everyday clinical interactions (i.e., review by a senior clinician), standardizing such processes could have important safety benefits alongside a tailored and timely approach to post-discharge care.
What Does a Language-And-Vision Transformer See: The Impact of Semantic Information on Visual Representations
Authors: Ilinykh Nikolai , Dobnik Simon
Published: December 2021

Neural networks have proven to be very successful in automatically capturing the composition of language and different structures across a range of multi-modal tasks. Thus, an important question to investigate is how neural networks learn and organise such structures. Numerous studies have examined the knowledge captured by language models (LSTMs, transformers) and vision architectures (CNNs, vision transformers) for respective uni-modal tasks. However, very few have explored what structures are acquired by multi-modal transformers where linguistic and visual features are combined. It is critical to understand the representations learned by each modality, their respective interplay, and the task’s effect on these representations in large-scale architectures. In this paper, we take a multi-modal transformer trained for image captioning and examine the structure of the self-attention patterns extracted from the visual stream. Our results indicate that the information about different relations between objects in the visual stream is hierarchical and varies from local to a global object-level understanding of the image. In particular, while visual representations in the first layers encode the knowledge of relations between semantically similar object detections, often constituting neighbouring objects, deeper layers expand their attention across more distant objects and learn global relations between them. We also show that globally attended objects in deeper layers can be linked with entities described in image descriptions, indicating a critical finding - the indirect effect of language on visual representations. In addition, we highlight how object-based input representations affect the structure of learned visual knowledge and guide the model towards more accurate image descriptions. A parallel question that we investigate is whether the insights from cognitive science echo the structure of representations that the current neural architecture learns. The proposed analysis of the inner workings of multi-modal transformers can be used to better understand and improve on such problems as pre-training of large-scale multi-modal architectures, multi-modal information fusion and probing of attention weights. In general, we contribute to the explainable multi-modal natural language processing and currently shallow understanding of how the input representations and the structure of the multi-modal transformer affect visual representations.
Androgens, Endometriosis and Pain
Authors: Evans Susan F. , Hull M. Louise , Hutchinson Mark R. , Rolan Paul E.
Published: December 2021

The intriguing relationship between androgens, endometriosis and chronic pain continues to unfold. Determining this relationship is of crucial importance to gynecologists managing people with these conditions, as common treatments dramatically alter her hormonal profiles, with both intended and unintended consequences. Although they may be present in the same individual, there is a recognized disconnect between pain or pain-related symptoms, and the presence or extent of endometriosis lesions. Reduced androgen levels provide a potential mechanism to link the development of endometriosis lesions and the presence of chronic pain. This research paper expands the presentation of our research at the World Endometriosis Congress in 2021, subsequently published in the Journal of Pain Research which demonstrated a strong inverse relationship between androgen levels and days per month of pelvic and period pain. Here we extend and further explore the evidence for a role for androgens in the etiology and management of dysmenorrhea and pelvic pain in women, both with and without endometriosis. We explore the potential for inflammation to induce low androgen levels and consider ways in which clinicians can optimize levels of androgens when treating women with these conditions. This article prompts the question: Is it estrogens that predispose people to a life of pain, or androgens that are protective?
Preliminary Investigation of Microbial Community in Wastewater and Surface Waters in Sri Lanka and the Philippines
Authors: Cruz Andre Freire , Wijesekara R. G. S. , Jinadasa K. B. S. N. , Gonzales Benjamin J. , Ohura Takeshi , Guruge Keerthi S.
Published: December 2021

In this study, the composition and richness of bacterial communities in treated and untreated wastewater from hospitals, commercial, and non-commercial fish farming sites, sewage effluents, and surface waters, which included seawater and fresh water in Sri Lanka and the Philippines, were investigated through 16S rRNA gene amplicon sequence analysis. Firmicutes were found predominantly in Sri Lankan hospital wastewaters, while Cyanobacteria and Acidobacteria were typically detected in fish culture sites and the waste canal in Sri Lanka, respectively. The Shannon–Weaver index (SW) and number of Operational Taxonomic Units (OTUs) were higher in the Philippines than in Sri Lanka. The bacterial richness in the university non-commercial fish pond and sewage effluent displayed greater than that in hospital wastewaters. In addition, the bacterial richness was higher in the untreated wastewater compared to that in the treated wastewater in hospitals. These results indicate the differences among water types in terms of bacterial community, especially influenced by their source.
Farmer and Field Survey in Cassava-Growing Districts of Rwanda Reveals Key Factors Associated With Cassava Brown Streak Disease Incidence and Cassava Productivity
Authors: Nyirakanani Chantal , Bizimana Jean Pierre , Kwibuka Yves , Nduwumuremyi Athanase , Bigirimana Vincent de Paul , Bucagu Charles , Lassois Ludivine , Malice Eléonore , Gengler Nicolas , Massart Sébastien , Bragard Claude , Habtu Michael , Brostaux Yves , Thonar Cécile , Vanderschuren Hervé
Published: December 2021

Cassava (Manihot esculenta Crantz) is a vital crop in Rwanda where it ranks as the third most consumed staple. However, cassava productivity remains below its yield potential due to several constraints, including important viral diseases, such as cassava brown streak disease (CBSD). Because various factors can be addressed to mitigate the impact of viral diseases, it is essential to identify routes of virus contamination in the cassava agrosystems from the seed system to farmer's practices and knowledge. The present study aimed at (1) assessing the current cassava seed system and farmers' practices and their knowledge of the biotic constraints to cassava production, (2) determining the status of CBSD as well as critical factors associated with its spread through the seed system channels, and (3) determining factors that influence cassava productivity in Rwanda. A cross-sectional study was carried out from May to September 2019 in 13 districts of Rwanda. A total of 130 farmers and cassava fields were visited, and the incidence and severity of CBSD were evaluated. CBSD was detected in all cassava-producing districts. The highest field incidence of CBSD was recorded in the Nyanza district (62%; 95% CI = 56–67%) followed by the Bugesera district (60%; 95% CI = 54–65%), which recorded the highest severity score of 3.0 ± 0.6. RT-PCR revealed the presence of CBSD at the rate of 35.3%. Ugandan cassava brown streak virus was predominant (21.5%) although cassava brown streak virus was 4% and mixed infection was 10%. An informal cassava seed system was dominant among individual farmers, whereas most cooperatives used quality seeds. Cassava production was found to be significantly influenced by the use of fertilizer, size of the land, farming system, cassava viral disease, and type of cassava varieties grown (p < 0.001). Disease management measures were practiced by a half of participants only. Factors found to be significantly associated with CBSD infection (p < 0.05) were the source of cuttings, proximity to borders, age of cassava, and knowledge of CBSD transmission and management.
Hexadecimal Aggregate Approximation Representation and Classification of Time Series Data
Authors: He Zhenwen , Zhang Chunfeng , Ma Xiaogang , Liu Gang
Published: December 2021

Time series data are widely found in finance, health, environmental, social, mobile and other fields. A large amount of time series data has been produced due to the general use of smartphones, various sensors, RFID and other internet devices. How a time series is represented is key to the efficient and effective storage and management of time series data, as well as being very important to time series classification. Two new time series representation methods, Hexadecimal Aggregate approXimation (HAX) and Point Aggregate approXimation (PAX), are proposed in this paper. The two methods represent each segment of a time series as a transformable interval object (TIO). Then, each TIO is mapped to a spatial point located on a two-dimensional plane. Finally, the HAX maps each point to a hexadecimal digit so that a time series is converted into a hex string. The experimental results show that HAX has higher classification accuracy than Symbolic Aggregate approXimation (SAX) but a lower one than some SAX variants (SAX-TD, SAX-BD). The HAX has the same space cost as SAX but is lower than these variants. The PAX has higher classification accuracy than HAX and is extremely close to the Euclidean distance (ED) measurement; however, the space cost of PAX is generally much lower than the space cost of ED. HAX and PAX are general representation methods that can also support geoscience time series clustering, indexing and query except for classification.
“Mothers Should Have Freedom of Movement”—Citizens’ Attitudes Regarding Farrowing Housing Systems for Sows and Their Piglets
Authors: Vandresen Bianca , Hötzel Maria José
Published: December 2021

Farrowing crates are the most common housing for lactating sows throughout the world, despite known public opposition to housing systems that deprive animals’ freedom to move. This study aimed to investigate Brazilian citizens’ attitudes towards three farrowing housing systems (crates, loose pens, and outdoors). Data were obtained via an online questionnaire containing open- and close-ended questions. Participants’ (n = 1171) attitudes were most negative towards the crates and most positive towards outdoor farrowing, and positively correlated with perceived sows’ quality of life. Participants overwhelmingly rejected the use of farrowing crates, and most supported a proposal to move from farrowing crates to loose pens, even when informed that this entailed an increased risk of piglets’ mortality. Participants’ views were underpinned by concerns about sows’ freedom of movement, behavioral freedom and naturalness, and the belief that it is possible to develop and manage housing that prevents piglet crushing that does not involve confining the sow. Furthermore, loose farrowing pens may not fully address all concerns expressed by participants regarding farrowing housing, which included the possibility of allowing sows to socialize and express maternal behaviors. We conclude that maintaining farrowing crates may erode the pig industry’s social license.
Molecular Epidemiology of Theileria annulata in Cattle from Two Districts in Punjab (Pakistan)
Authors: Parveen Asia , Alkhaibari Abeer Mousa , Asif Muhammad , Almohammed Hamdan I. , Naqvi Zahra , Khan Adil , Aktas Munir , Ozubek Sezayi , Farooq Muhammad , Iqbal Furhan
Published: December 2021

The present study was designed to report the molecular prevalence of T. annulata in cattle blood samples collected from Punjab in Pakistan. A total of 428 cattle blood samples were collected from Districts Lodhran (n = 218) and Dera Ghazi Khan (n = 210). The prevalence of T. annulata was determined by the amplification of a fragment from its cytochrome b gene and parasite prevalence was significantly higher (p = 0.03) in the blood samples of cattle collected from Dera Ghazi Khan (70/210; 33%) as compared to Lodhran (52/218; 24%). Presence of T. annulata was also confirmed by the amplification of a fragment from their 30 kDa gene. The amplified PCR products of both genes were confirmed by DNA sequencing and these partial DNA sequences were submitted to GenBank. Phylogenetic analysis revealed that amplified partial gene sequences resembled previously reported T. annulata sequences in cattle from India, China, Iran, Tunisia, Turkey and Egypt. The incidence of T. annulata infection was higher in Sahiwal cattle (p = 0.04) than the other enrolled cattle breed from Dera Ghazi Khan. Female cattle from Lodhran (p = 0.02), while males (p = 0.02), animals housed in close compounds (p = 0.04), animals with a tick burden (p = 0.005) and farms with only cattle (p = 0.01) in Dear Ghazi Khan were found to be more susceptible to T. annulata infection. We recommend that large-scale tick and tick-borne disease control strategies be implemented in both districts under investigation, especially in Dera Ghazi Khan.
Prediction of the Long-Term Performance Based on the Seepage-Stress-Damage Coupling Theory: A Case in South-to-North Water Diversion Project in China
Authors: Xu Xinyong , Xu Wenjie , Xie Chenlong , Khan Mohd Yawar Ali
Published: December 2021

The South-to-North Water Diversion Project has been in operation since 2014, directly benefiting more than 79 million people in China. Thus, its service life and long-term performance have gained much attention from scholars. To predict its life and performance, this study used the seepage/stress-damage coupling method. In addition, a seepage/stress-damage coupling theory was proposed and a finite element model of a deep excavated canal in the Xichuan Section of the South-to-North Water Diversion Project was established. The results showed that this canal subsided greatly in the first two years of operation, which can be confirmed by the monitoring data. It is predicted that, after 50 years of normal operation, the canal damage may start and spread from the water level, and reach 37.6%, but such damage will not affect its normal water delivery function. The purpose of this study is to provide guidance for the safe operation of the project.
Properties and Colorimetric Performance of Screen-Printed Thermochromic/UV-Visible Fluorescent Hybrid Ink Systems
Authors: Tomašegović Tamara , Mahović Poljaček Sanja , Strižić Jakovljević Maja , Marošević Dolovski Ana
Published: December 2021

In the present research, properties and performance of special effect printing inks were observed with the aim of obtaining a printed product with dual functional properties. Thermochromic liquid crystal-based printing ink (TLC) and UV-visible (daylight invisible) fluorescent inks (UVF), pure and as hybrid ink systems, were printed using a screen-printing technique on two types of uncoated paper substrates. Characterization of the paper substrates was performed, as well as detailed analysis of printed layers. Thickness, surface roughness, surface free energy, and adhesion parameters of printed layers were analysed. Spectral reflectance of pure UVF and TLC printing inks, as well as the spectral reflectance of the proposed hybrid ink systems were measured. The thermochromic effect of the TLC ink and hybrid systems was analysed. Microscopy was used to display the visual colour play effect and the effect of the fluorescence. Results of the measurements showed high compatibility of used materials in the proposed hybrid ink systems. Since the effect of luminescence and the colour play effect in the hybrid systems were preserved, it can be concluded that TLC/UVF hybrid ink systems can find their application in the development of functional packaging and in all other applications with special requirements for temperature monitoring and hidden information for different products.
Effect of Amino Acid and Titanium Foliar Application on Smooth-Stalked Meadow Grass (Poa pratensis L.) Macronutrient Content
Authors: Radkowski Adam , Radkowska Iwona , Bocianowski Jan , Wolski Karol , Bujak Henryk
Published: December 2021

As plant growth stimulants, Ti and amino acids affect physiological processes of plants, promoting their vegetative and generative development and improving their yield and its quality. An experiment was carried out at the Experimental Station of the University of Agriculture in Krakow on degraded black earth soil formed from loess. Its aim was to determine the effect of two products, one containing amino acids and the other with Ti, on the Poa pratensis yield and its quality. Foliar application of amino acids and Ti, used on their own and together, constituted the main factor of the experiment. It was found that the treatment with both stimulants applied together significantly affected plant parameters. Compared to control, plants treated with those growth stimulants produced higher dry matter yields and contained significantly more phosphorus, potassium, calcium, magnesium, and sodium in dry matter. The highest effect was recorded on plots where combined application of amino acids and Ti was used. Almost as good results were recorded when amino acids were applied on their own. Regarding the cuts, higher effects were noted in the first and second ones than in the third. The growth stimulants used in the present experiment had a positive effect on the chemical composition of Poa pratensis meadow plants. The results indicated that the treatment significantly increased macronutrient content, compared to control plants. The most favourable effects were recorded for plants on the plot with combined application of amino acids and Ti. Similar results were also obtained on plots where only amino acids were used. Regarding the harvests, better results were noted in the first and second ones than in the third. In view of the potential benefits, it would be advisable to extend and update research on the effects of these stimulants on other common varieties of forage grasses.
Performance Evaluation of Artificial Neural Networks (ANN) Predicting Heat Transfer through Masonry Walls Exposed to Fire
Authors: Bakas Iasonas , Kontoleon Karolos J.
Published: December 2021

The multiple benefits Artificial Neural Networks (ANNs) bring in terms of time expediency and reduction in required resources establish them as an extremely useful tool for engineering researchers and field practitioners. However, the blind acceptance of their predicted results needs to be avoided, and a thorough review and assessment of the output are necessary prior to adopting them in further research or field operations. This study explores the use of ANNs on a heat transfer application. It features masonry wall assemblies exposed to elevated temperatures on one side, as generated by the standard fire curve proposed by Eurocode EN1991-1-2. A juxtaposition with previously published ANN development processes and protocols is attempted, while the end results of the developed algorithms are evaluated in terms of accuracy and reliability. The significance of the careful consideration of the density and quality of input data offered to the model, in conjunction with an appropriate algorithm architecture, is highlighted. The risk of misleading metric results is also brought to attention, while useful steps for mitigating such risks are discussed. Finally, proposals for the further integration of ANNs in heat transfer research and applications are made.
A Method for Gradient Differentiable Network Architecture Search by Selecting and Clustering Candidate Operations
Authors: Song Ha Yoon
Published: December 2021

The current evolution of deep learning requires further optimization in terms of accuracy and time. From the perspective of new requirements, AutoML is an area that could provide possible solutions. AutoML has a neural architecture search (NAS) field. DARTS is a widely used approach in NAS and is based on gradient descent; however, it has some drawbacks. In this study, we attempted to overcome some of the drawbacks of DARTS by improving the accuracy and decreasing the search cost. The DARTS algorithm uses a mixed operation that combines all operations in the search space. The architecture parameter of each operation comprising a mixed operation is trained using gradient descent, and the operation with the largest architecture parameter is selected. The use of a mixed operation causes a problem called vote dispersion: similar operations share architecture parameters during gradient descent; thus, there are cases where the most important operation is disregarded. In this selection process, vote dispersion causes DARTS performance to degrade. To cope with this problem, we propose a new algorithm based on DARTS called DG-DARTS. Two search stages are introduced, and the clustering of operations is applied in DG-DARTS. In summary, DG-DARTS achieves an error rate of 2.51% on the CIFAR10 dataset, and its search cost is 0.2 GPU days because the search space of the second stage is reduced by half. The speed-up factor of DG-DARTS to DARTS is 6.82, which indicates that the search cost of DG-DARTS is only 13% that of DARTS.
Optimization of Clustering in Wireless Sensor Networks: Techniques and Protocols
Authors: Jubair Ahmed Mahdi , Hassan Rosilah , Aman Azana Hafizah Mohd , Sallehudin Hasimi , Al-Mekhlafi Zeyad Ghaleb , Mohammed Badiea Abdulkarem , Alsaffar Mohammad Salih
Published: December 2021

Recently, Wireless Sensor Network (WSN) technology has emerged extensively. This began with the deployment of small-scale WSNs and progressed to that of larger-scale and Internet of Things-based WSNs, focusing more on energy conservation. Network clustering is one of the ways to improve the energy efficiency of WSNs. Network clustering is a process of partitioning nodes into several clusters before selecting some nodes, which are called the Cluster Heads (CHs). The role of the regular nodes in a clustered WSN is to sense the environment and transmit the sensed data to the selected head node; this CH gathers the data for onward forwarding to the Base Station. Advantages of clustering nodes in WSNs include high callability, reduced routing delay, and increased energy efficiency. This article presents a state-of-the-art review of the available optimization techniques, beginning with the fundamentals of clustering and followed by clustering process optimization, to classifying the existing clustering protocols in WSNs. The current clustering approaches are categorized into meta-heuristic, fuzzy logic, and hybrid based on the network organization and adopted clustering management techniques. To determine clustering protocols’ competency, we compared the features and parameters of the clustering and examined the objectives, benefits, and key features of various clustering optimization methods.
Seasonal and Spatial Variations of Atmospheric Ammonia in the Urban and Suburban Environments of Seoul, Korea
Authors: Singh Rahul , Kim Kyunghoon , Park Gyutae , Kang Seokwon , Park Taehyun , Ban Jihee , Choi Siyoung , Song Jeongin , Yu Dong-Gil , Woo Jung-Hun , Choi Yuri , Lee Taehyoung
Published: December 2021

Atmospheric ammonia is a significant pollutant throughout the year, necessitating standardized measurement and identification of emission factors. We performed a quantized evaluation of ammonia concentrations at various locations in and around Seoul, South Korea. The established testing methods of the Radiello Passive Sampler were used for ammonia sampling, and the method was validated using annular denuder sampling. Urban and suburban areas were studied to gain a deeper understanding of the factors responsible for ammonia pollution. This study aimed to establish the fluctuations in concentration over one year, by analyzing the seasonal and regional variation in ammonia concentration. Livestock and agricultural areas recorded the highest concentration of ammonia among all sites, with the highest concentration recorded in autumn. However, at most of the other studied sites, the highest and lowest ammonia concentrations were recorded during summer and winter, respectively. This study attempted to establish a correlation between ammonia concentration and temperature, as well as ammonia concentration and altitude.
Comparison of Inland Ship Emission Results from a Real-World Test and an AIS-Based Model
Authors: Jiang Han , Peng Di , Wang Yunjing , Fu Mingliang
Published: December 2021

Inland shipping is pivotal to the comprehensive transport system of China. However, ship emission has become a major air polluter in inland river regions, and relevant emission inventories are urgently needed. Currently, the Automatic identification System based (AIS-based)emission model is widely used in calculating the ocean-going ship emission inventory. However, due to the lack of AIS data in the river area, the inland ship emission inventory mainly uses the fuel consumption method. With the continuous improvement of AIS data quality in the river area, the AIS-based emission model can be adopted in the development of inland ship emission inventory. However, there are few studies on the evaluation of the accuracy of the inland ship emissions using the AIS-based emission model. This study makes a comparison between test data and model-calculated data to evaluate the accuracy of the AIS-based emission models. Inland ship activities are divided into being at berth, maneuvering (port departure and port arrival), and on cruise modes in an AIS-based emission model. The model-calculated CO2, HC, and NOx emission rates can cover those onboard emission test data, but the values from the model are much lower. The total average ratios of test data to model-calculated data for CO2, CO, HC, and NOx are 2.66, 19.12, 2.46, and 3.16 when engine loads are below 60%. In upstream cruise mode, average emission rates of CO2, CO, HC, and NOx from the real-world test are 1.91–6.48, 8.78–27.83, 3.05–8.96, and 4.06–5.96 times higher than those from the AIS-based model, respectively. However, those are only 1.08–1.51, 6.74–9.67, 2.03–3.75, and 1.65–2.75 times higher than those from the AIS-based model in downstream cruise mode.
Plant Organic Matter in Palsa and Khasyrei Type Mires: Direct Observations in West Siberian Sub-Arctic
Authors: Kosykh Natalia P. , Mironycheva-Tokareva Nina P. , Vishnyakova Evgeniya K. , Koronatova Natalia G. , Stepanova Vera A. , Kolesnychenko Larisa G. , Khovalyg Aldynai O. , Peregon Anna M.
Published: December 2021

This article presents the first results of long-term direct measurements of a few major components of carbon cycle in permafrost mire landforms in the sub-Arctic region of Western Siberia, Russia. It reveals the main features of geographical distribution of plant organic matter, including both the above-ground and below-ground fractions of live biomass, the biomass of dead roots (mortmass), and net primary production (NPP) in peat-accumulating flat palsa mires and in “khasyrei”—ecosystems of drained lakes in thermokarst depression on epigenetic permafrost. The study based on original methods of direct field measurements elaborated by authors for northern peatlands. In northern taiga, the NPP of palsa mires was found in the range of 300–580 g m−2 yr−1 and an average biomass of 1800 g m−2; in khasyrei, it accounts for 1100 g m−2 yr−1 and 2000 g m−2 of NPP and live biomass, respectively. In forest tundra, the live biomass of palsa mires was found in the range of 1000–1800 g m−2, and in khasyrei it was 2300 g m−2. The NPP of palsa mires were in the range of 400–560 g m−2 yr−1, and in khasyrei it was 800 g m−2 yr−1. Overall, we conclude that the south–north climatic gradient in Western Siberia is the main driver of plant organic matter accumulation. It was found different across mire ecosystems of the same types but located in different bioclimatic regions.
L-Type Ca2+ Channel Regulation by Calmodulin and CaBP1
Authors: Ames James B.
Published: December 2021

L-type voltage-gated Ca2+ channels (CaV1.2 and CaV1.3, called CaV) interact with the Ca2+ sensor proteins, calmodulin (CaM) and Ca2+ binding Protein 1 (CaBP1), that oppositely control Ca2+-dependent channel activity. CaM and CaBP1 can each bind to the IQ-motif within the C-terminal cytosolic domain of CaV, which promotes increased channel open probability under basal conditions. At elevated cytosolic Ca2+ levels (caused by CaV channel opening), Ca2+-bound CaM binding to CaV is essential for promoting rapid Ca2+-dependent channel inactivation (CDI). By contrast, CaV binding to CaBP1 prevents CDI and promotes Ca2+-induced channel opening (called CDF). In this review, I provide an overview of the known structures of CaM and CaBP1 and their structural interactions with the IQ-motif to help understand how CaM promotes CDI, whereas CaBP1 prevents CDI and instead promotes CDF. Previous electrophysiology studies suggest that Ca2+-free forms of CaM and CaBP1 may pre-associate with CaV under basal conditions. However, previous Ca2+ binding data suggest that CaM and CaBP1 are both calculated to bind to Ca2+ with an apparent dissociation constant of ~100 nM when CaM or CaBP1 is bound to the IQ-motif. Since the neuronal basal cytosolic Ca2+ concentration is ~100 nM, nearly half of the neuronal CaV channels are suggested to be bound to Ca2+-bound forms of either CaM or CaBP1 under basal conditions. The pre-association of CaV with calcified forms of CaM or CaBP1 are predicted here to have functional implications. The Ca2+-bound form of CaBP1 is proposed to bind to CaV under basal conditions to block CaV binding to CaM, which could explain how CaBP1 might prevent CDI.
RalA, PLD and mTORC1 Are Required for Kinase-Independent Pathways in DGKβ-Induced Neurite Outgrowth
Authors: Kano Takuya , Tsumagari Ryosuke , Nakashima Akio , Kikkawa Ushio , Ueda Shuji , Yamanoue Minoru , Takei Nobuyuki , Shirai Yasuhito
Published: December 2021

Diacylglycerol kinase β (DGKβ) is an enzyme that converts diacylglycerol to phosphatidic acid and is mainly expressed in the cerebral cortex, hippocampus and striatum. We previously reported that DGKβ induces neurite outgrowth and spinogenesis, contributing to higher brain functions, including emotion and memory. To elucidate the mechanisms involved in neuronal development by DGKβ, we investigated the importance of DGKβ activity in the induction of neurite outgrowth using human neuroblastoma SH-SY5Y cells. Interestingly, both wild-type DGKβ and the kinase-negative (KN) mutant partially induced neurite outgrowth, and these functions shared a common pathway via the activation of mammalian target of rapamycin complex 1 (mTORC1). In addition, we found that DGKβ interacted with the small GTPase RalA and that siRNA against RalA and phospholipase D (PLD) inhibitor treatments abolished DGKβKN-induced neurite outgrowth. These results indicate that binding of RalA and activation of PLD and mTORC1 are involved in DGKβKN-induced neurite outgrowth. Taken together with our previous reports, mTORC1 is a key molecule in both kinase-dependent and kinase-independent pathways of DGKβ-mediated neurite outgrowth, which is important for higher brain functions.
On the Evaluation of a Novel Hypoxic 3D Pancreatic Cancer Model as a Tool for Radiotherapy Treatment Screening
Authors: Wishart Gabrielle , Gupta Priyanka , Nisbet Andrew , Schettino Giuseppe , Velliou Eirini
Published: December 2021

Tissue engineering is evolving to mimic intricate ecosystems of tumour microenvironments (TME) to more readily map realistic in vivo niches of cancerous tissues. Such advanced cancer tissue models enable more accurate preclinical assessment of treatment strategies. Pancreatic cancer is a dangerous disease with high treatment resistance that is directly associated with a highly complex TME. More specifically, the pancreatic cancer TME includes (i) complex structure and complex extracellular matrix (ECM) protein composition; (ii) diverse cell populations (e.g., stellate cells), cancer associated fibroblasts, endothelial cells, which interact with the cancer cells and promote resistance to treatment and metastasis; (iii) accumulation of high amounts of (ECM), which leads to the creation of a fibrotic/desmoplastic reaction around the tumour; and (iv) heterogeneous environmental gradients such as hypoxia, which result from vessel collapse and stiffness increase in the fibrotic/desmoplastic area of the TME. These unique hallmarks are not effectively recapitulated in traditional preclinical research despite radiotherapeutic resistance being largely connected to them. Herein, we investigate, for the first time, the impact of in vitro hypoxia (5% O2) on the radiotherapy treatment response of pancreatic cancer cells (PANC-1) in a novel polymer (polyurethane) based highly macroporous scaffold that was surface modified with proteins (fibronectin) for ECM mimicry. More specifically, PANC-1 cells were seeded in fibronectin coated macroporous scaffolds and were cultured for four weeks in in vitro normoxia (21% O2), followed by a two day exposure to either in vitro hypoxia (5% O2) or maintenance in in vitro normoxia. Thereafter, in situ post-radiation monitoring (one day, three days, seven days post-irradiation) of the 3D cell cultures took place via quantification of (i) live/dead and apoptotic profiles and (ii) ECM (collagen-I) and HIF-1a secretion by the cancer cells. Our results showed increased post-radiation viability, reduced apoptosis, and increased collagen-I and HIF-1a secretion in in vitro hypoxia compared to normoxic cultures, revealing hypoxia-induced radioprotection. Overall, this study employed a low cost, animal free model enabling (i) the possibility of long-term in vitro hypoxic 3D cell culture for pancreatic cancer, and (ii) in vitro hypoxia associated PDAC radio-protection development. Our novel platform for radiation treatment screening can be used for long-term in vitro post-treatment observations as well as for fractionated radiotherapy treatment.
Measurement of the Drug Sensitivity of Single Prostate Cancer Cells
Authors: Abali Fikri , Baghi Narges , Mout Lisanne , Broekmaat Joska J. , Tibbe Arjan G. J. , Terstappen Leon W. M. M.
Published: December 2021

The treatment of cancer faces a serious challenge as cancer cells within patients are heterogeneous and frequently resistant to therapeutic drugs. Here, we introduce a technology enabling the assessment of single cancer cells exposed to different drugs. PCa cells were individually sorted in self-seeding microwells, cultured for 24 h, and then exposed to several drugs to induce (R1881) or inhibit (Enzalutamide/Abiraterone) the secretion of a protein (PSA). Cell viability and PSA secretion of each individual prostate cell were monitored over a 3-day period. The PSA protein secreted by each cell was captured on a PVDF membrane through a pore in the bottom of each well. The basal PSA secretion was found to be 6.1 ± 4.5 and 3.7 ± 1.9 pg/cell/day for LNCaP and VCaP, respectively. After exposure to R1881, the PSA secretion increased by ~90% on average and was not altered for ~10% of the cells. PSA production decreased in the majority of cells after exposure to enzalutamide and abiraterone.
T Lymphocyte Maturation Profile in the EBUS-TBNA Lymph Node Depending on the DLCO Parameter in Patients with Pulmonary Sarcoidosis
Authors: Rutkowska Elżbieta , Kwiecień Iwona , Bednarek Joanna , Sokołowski Rafał , Raniszewska Agata , Jahnz- Różyk Karina , Rzepecki Piotr
Published: December 2021

Sarcoidosis (SA) is a systemic granulomatous disorder of unknown etiology with lung and mediastinal lymph nodes (LNs) as the main location. T lymphocytes play important role in the formation of granulomas in SA, but still little is known about the role of maturation profile in the development of inflammatory changes. The aim of this study was to determine the CD4+ and CD8+ T cells maturation profile in LNs and in peripheral blood (PB) and its relation to disease severity expressed by diffusing capacity of the lung for carbon monoxide (DLCO). 29 patients with newly pulmonary SA were studied. Flow cytometry was used for cells evaluation in EBUS-TBNA samples. We observed lower median proportion of T lymphocytes, CD4+ T and CD8+ T cells in patients with DLCO< 80% than in patients with normal diffusion (DLCO > 80%). Patients with DLCO < 80% had lower median proportion of effector and higher median proportion of central memory CD4+ and CD8+ T cells than patients with DLCO > 80%. We reported for the first time that LNs CD4+ and CD8+ T cells maturation differs depending on the DLCO value in sarcoidosis. Lymphocytes profiles in LNs may reflect the immune status of patients with SA and can be analysed by flow cytometry of EBUS-TBNA samples.
Life Cycle Assessment of Coated and Thermally Modified Wood Façades
Authors: Búryová Dominika , Sedlák Pavol
Published: December 2021

Façades—their design, aesthetics, performance, type of cladding material, and understructure—determine architectural expression and form unique appearances of individual buildings. In connection to the sustainable development idea, wood façades provide one of the alternatives of a contemporary building exterior look. Façade cladding made of coated and thermally modified wood can be successfully used for these buildings. In addition, thermally modified wood allows the use of local European wood species, while keeping cladding elements relatively thin. On the other hand, wood has certain structural limitations and disadvantages due to the properties of wood. The main weakness is caused by the surface durability of wood and its related need for maintenance over time. The scope of the study was a comprehensive assessment of coated non-heat-treated and thermally modified wood façades, performed in terms of life cycle assessment. The aim was to identify which type of wooden façade had the lowest environmental impact. According to the EN 15804 + A2 standard, the principle of evaluation of environmental parameters “cradle-to-gate-with options” was used to evaluate wooden façades and coatings and surface preservation methods. Simulations with the SimaPro program showed that the thermal modification of wood has a significant impact on the environment at the product stage. Nonetheless the thermally modified façade without any surface coating showed the lowest environmental impact in a 30 year time-horizon of the “use stage”. It was showed that surface maintenance methods applied, the coatings used, and the frequency of their application play an important role in the environmental impact of the investigated wooden façades.
Measurement of Blood Pressure by Ultrasound—The Applicability of Devices, Algorithms and a View in Local Hemodynamics
Authors: Meusel Moritz , Wegerich Philipp , Bode Berit , Stawschenko Elena , Kusche-Vihrog Kristina , Hellbrück Horst , Gehring Hartmut
Published: December 2021

Objective: Due to ongoing technical progress, the ultrasonic measurement of blood pressure (BP) as an alternative to oscillometric measurement (NIBP) or the continuous non-invasive arterial pressure method (CNAP) moves further into focus. The US method offers several advantages over NIBP and CNAP, such as deep tissue penetration and the utilization of different arterial locations. Approach: Ten healthy subjects (six female, aged 30.9 ± 4.6 years) volunteered in our investigation. In the ultrasonic BP measurement, we differentiated between the directly measured (pulsatile diastolic and systolic vessel diameter) and indirectly calculated variables at three different artery locations on both arms, with two different ultrasound devices in the transversal and longitudinal directions of the transducer. Simultaneously, NIBP monitoring served as reference BP, while CNAP monitored the steady state condition of the arm under investigation. The Moens–Korteweg algorithm (MKE) and the algorithm of the working group of San Diego (SanD) were selected for the indirectly calculated ultrasonic BP data. Main results: With US, we were able to measure the BP at each selected arterial position. Due to the investigation setup, we found small but significant interactions of the main effects. Bland and Altman analysis revealed that US-BP measurement was similar to NIBP, with superior accuracy when compared to the established CNAP method. In addition, US-BP measurement showed that the measurement accuracy of both arms can be regarded as identical. In a detailed comparison of the selected arterial vascular sections, systematic discrepancies between the right and left arm could be observed. Conclusion: In our pilot study, we measured BP effectively and accurately by US using two different devices. Our findings suggest that ultrasonic BP measurement is an adequate alternative for live and continuous hemodynamic monitoring.
Unseen Artificial Intelligence—Deep Learning Paradigm for Segmentation of Low Atherosclerotic Plaque in Carotid Ultrasound: A Multicenter Cardiovascular Study
Authors: Jain Pankaj K. , Sharma Neeraj , Saba Luca , Paraskevas Kosmas I. , Kalra Mandeep K. , Johri Amer , Laird John R. , Nicolaides Andrew N. , Suri Jasjit S.
Published: December 2021

Background: The early detection of carotid wall plaque is recommended in the prevention of cardiovascular disease (CVD) in moderate-risk patients. Previous techniques for B-mode carotid atherosclerotic wall plaque segmentation used artificial intelligence (AI) methods on monoethnic databases, where training and testing are from the “same” ethnic group (“Seen AI”). Therefore, the versatility of the system is questionable. This is the first study of its kind that uses the “Unseen AI” paradigm where training and testing are from “different” ethnic groups. We hypothesized that deep learning (DL) models should perform in 10% proximity between “Unseen AI” and “Seen AI”. Methodology: Two cohorts from multi-ethnic groups (330 Japanese and 300 Hong Kong (HK)) were used for the validation of our hypothesis. We used a four-layered UNet architecture for the segmentation of the atherosclerotic wall with low plaque. “Unseen AI” (training: Japanese, testing: HK or vice versa) and “Seen AI” experiments (single ethnicity or mixed ethnicity) were performed. Evaluation was conducted by measuring the wall plaque area. Statistical tests were conducted for its stability and reliability. Results: When using the UNet DL architecture, the “Unseen AI” pair one (Training: 330 Japanese and Testing: 300 HK), the mean accuracy, dice-similarity, and correlation-coefficient were 98.55, 78.38, and 0.80 (p < 0.0001), respectively, while for “Unseen AI” pair two (Training: 300 HK and Testing: 330 Japanese), these were 98.67, 82.49, and 0.87 (p < 0.0001), respectively. Using “Seen AI”, the same parameters were 99.01, 86.89 and 0.92 (p < 0.0001), respectively. Conclusion: We demonstrated that “Unseen AI” was in close proximity (<10%) to “Seen AI”, validating our DL model for low atherosclerotic wall plaque segmentation. The online system runs < 1 s.
Dental Trauma at a University Dental Clinic in Milan including the SARS-CoV-2 Period
Authors: Pederielli Sara , Mirelli Cristina , Pozzi Federico , Giannì Aldo Bruno , Biagi Roberto
Published: December 2021

The aim of this study i.e., is to present the distribution of traumatic dental injuries (TDI) in 306 patients registered at the Unit of Dental Emergencies at a University Dental Clinic in Milan, Italy, between June 2019 and May 2021. This time frame includes the beginning of the SARS-CoV-2 pandemic. Information regarding age, gender, number and type of injured teeth, type of traumatic injury, and data on where or how the injury happened were recorded. Seventy-nine percent of patients can be classified as pediatric (under 14 years old), and in all age groups, male patients were found to be more susceptible (1.6:1). A total of 480 teeth were involved, 59% of which were deciduous, and 41% permanent. The most affected teeth in both dentitions were upper central incisors. In deciduous teeth, periodontal lesions were more common, whereas in permanent dentitions, dental fractures were diagnosed more often. Most data found in this study confirms the results found in the literature. The biggest difference, due to changes in daily routine during the SARS-CoV-2 pandemic, can be found by analyzing the incidence and etiology. As a matter of fact, there was a decrease in school accidents, whereas domestic falls remained constant.
Analysis of Intrinsic Mechanistic of Stability-Tracking Control for Distributed Drive Autonomous Electric Vehicle
Authors: Tang Xuequan , Yan Yunbing , Wang Baohua , Xu Xiaowei , Zhang Lin
Published: December 2021

For distributed drive autonomous vehicles, adding lateral stability control (LSC) to the trajectory tracking control (TTC) can optimize the distribution of the driving torque of each wheel, so that the vehicle can track the planned trajectory while maintaining stable lateral motion. However, the influence of adding LSC on the TTC system is still unclear. Firstly, a stability-track hierarchical control structure composed of LSC and TTC was established, and the interaction between the two layers was identified as the key of this paper. Then, the Intrinsic Mechanistic framework of the stability-tracking control (STC) was proposed by establishing and analyzing the vehicle dynamic model and control process of two layers. Finally, through simulation experiments, it was found that the change in the curvature of the target trajectory will make the tracking target trajectory and maintaining the lateral stability of the vehicle appear to conflict; in addition, in the LSC layer, the steering characteristics and delay characteristics of different reference models have a greater impact on the lateral stability and trajectory tracking performance; moreover, adjusting the preview time has a more obvious effect on trajectory tracking and lateral stability than the stability correction intensity coefficient.