bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Short-Term Memory to Predict 3D Amino Acids Positions in GPCR Molecular Dynamics
Authors: López-Correa Juan Manuel , König Caroline , Vellido Alfredo
Published: October 2022

G-Protein Coupled Receptors (GPCRs) are a big family of eukaryotic cell transmembrane proteins, responsible for numerous biological processes. From a practical viewpoint around 34% of the drugs approved by the US Food and Drug Administration target these receptors. They can be analyzed from their simulated molecular dynamics, including the prediction of their behavior in the presence of drugs. In this paper, the capability of Long Short-Term Memory Networks (LSTMs) are evaluated to learn and predict the molecular dynamic trajectories of a receptor. Several models were trained with the 3D position of the amino acids of the receptor considering different transformations on the position of the amino acid, such as their centers of mass, the geometric centers and the position of the α–carbon for each amino acid. The error of the prediction of the position was evaluated by the mean average error (MAE) and root-mean-square deviation (RMSD). The LSTM models show a robust performance, with results comparable to the state-of-the-art in non-dynamic 3D predictions. The best MAE and RMSD values were found for the mass center of the amino acids with 0.078 Å and 0.156 Å respectively. This work shows the potential of LSTM to predict the molecular dynamics of GPRCs.
Mutual Information Weighing for Probabilistic Movement Primitives
Authors: Colomé Adrià , Torras Carme
Published: October 2022

Reinforcement Learning (RL) of trajectory data has been used in several fields, and it is of relevance in robot motion learning, in which sampled trajectories are run and their outcome is evaluated with a reward value. The responsibility on the performance of a task can be associated to the trajectory as a whole, or distributed throughout its points (timesteps). In this work, we present a novel method for attributing the responsibility of the rewards to each timestep separately by using Mutual Information (MI) to bias the model fitting of a trajectory.
Prospects of Single Cell Omics	(SCO) Analysis for Investigating Nervous System Disorders
Authors: Khan Muhammad Qasim , Bakhtiar Syeda Marriam
Published: October 2022

Single Cell Omics (SCO) is an evolving field in biomedical research which offers prime application in neurosciences. The human nervous system is complex and shows variability in cell types. It includes neurons (functional components), glial cells (supporting cells), astrocytes (provide nourishment), oligodendrocytes (synthesize myelin sheath), and microglia (defense mechanism). To understand the functional and disease states of the nervous system, it is essential to investigate them at the single-cell level. It has been estimated that every 1 in 9 people is affected by mental or neurological disorders, including psychological disorders (generally referred to as mental disorders), psychotic disorders (involving psychosis), and neurological disorders (involving neurological factors), globally. These disorders have multifactorial etiology and are caused by genetic and environmental factors. Every disorder has distinct pathophysiology affecting multiple brain regions. SCO has excellent potential to provide insight regarding the diagnosis, pathophysiology, and treatment of neurological disorders. The stringent well directed SCO methods enhance the understanding of complex nervous system disorders, such as meningitis, stroke, schizophrenia, Parkinson’s disease, and Alzheimer’s disease, which paves the way for future research.
Identification of Anti-inflammatory Metabolites from Trigonella foenum-greacum using Computational Approaches
Authors: Dilshad Erum , Maaz Muhammad , Suliman  , Ashraf Naeem Mehmood
Published: October 2022

Human disease prevalence has increased as a result of modern lifestyle, stress, and toxic waste. Worldwide, researchers aim to discover therapeutic compounds which may cure and prevent the onset of diseases. So, this study was planned to discover potential anti-inflammatory metabolites from Trigonella foenum-graecum. It is an annual plant within the family Fabaceae. This plant is used as a spice throughout the world and has many beneficial medicinal effects. It is commonly grown in Pakistan, India, and some Middle Eastern countries. Ten bioactive compounds representative of all classes, namely alkaloid, flavonoid, phytic acid, 4-hydroxy isoleucine, sapogenin, quercetin, trigonelline, tricin, naringenin, and flavonol were selected. Molecular docking of these ligands was carried out against drug targets namely cyclooxygenase-2, Human Neutrophil Elastase (HNE), microsomal PGES-2, and tyrosinase by using CB Dock and AMDock softwares. Further refining by screening filters produced sapogenin as the lead compound. All the visualization analysis and interaction studies were performed using PyMol molecular visualization tool and Ligplot+. Celebrex was used as the standard for comparison. The comparison between sapogenin and celebrex showed that the former is much more active than the standard drug. This is a novel finding. So, it might be explored further as a drug candidate to treat chronic inflammatory diseases in the future.
BIOLOGICAL EFFECTIVENESS OF ONION PLANT PROTECTION SCHEME
Authors: Bondarenko Anastasia , Tyutyuma Natalya
Published: October 2022

The average yield of bulb onions is still quite low. The purpose of this study was to improve the techniques and methods of cultivating onions using new generation preparations against the background of N180P60K60 in a drip irrigation method. To achieve the objective of this study, field surveys, observations and measurements were carried out using generally accepted methods. The experimental data obtained from the studies were processed using analysis of variance in Excel, which is part of the Microsoft Office installation package. Field experience included both background application of mineral fertilizers, as well as integrated nutrition of plants with Aminofol Plus and Novosil bulb onion growth stimulants and its biological protection with drugs Gaitang, KE, Akzifor, KE and with Monarch, VDG preparations. According to the results of tests carried out in the 3rd soil-climatic zone, they positively influenced the growth processes and yield of the cultivated crop. The use of this scheme gave a significant increase in the number of commercial bulbs and the weight of commercial bulbs relative to the control version, which significantly affected the yield, which was 121.8 tons/ha (commercial yield). Based on the results of the obtained experimental data, the following was identified, the difference in yield is due to the effect of drugs that have a positive effect on the variety and hybrid of onions, which are under study.
The Factors that Influence Customer Purchase Intention: The Tale of Zalora Malaysia
Authors: Man Hong Lu , Alisliza Perak Pillo Anak
Published: October 2022

Since Zalora Malaysia was designated as the top fashion specialised online retailer based on iPrice's Map of e-commerce, this study was done to investigate the factors that impact consumer buying intention in Zalora Malaysia. As a result, brand image, site design, and service quality are the independent variables for those elements. The intention to buy among Zalora Malaysia clients is the dependent variable of this study. Furthermore, the goal of this research is to look at the interaction between elements that impact customers' purchasing intentions in Zalora Malaysia. To confirm the research hypothesis, the researcher gathered 237 responses via a google form created by the researcher and distributed them online to any Malaysian citizen who only purchased from Zalora Malaysia and answered the questionnaire in general via Facebook or Instagram to obtain respondents aged 21 to 50 years and above. Only one hypothesis is validated and approved in this research study, according to the findings, and it is connected to the relationship between site design features and purchase consumers in the Zalora Malaysia application. The brand image and service quality elements that impact customers' purchasing intentions in the Zalora Malaysia application are two hypothetical relationship factors that are not approved and have no value. In the Zalora Malaysia application, this reveals simply the site design variables that are important and the link between client purchase intents.
Ketimpangan Penyedian Pelayanan Keimigrasian di Daerah Terpencil: Proses Pengambilan Keputusan Kolaboratif dalam Vertical Collaborative Governance Menuju Peningkatan Kualitas Pelayanan Publik
Authors: Yurizal Ruky , Aripin Sofjan
Published: October 2022

Artikel ini terkait proses pengambilan keputusan kolaboratif dalam vertical collaborative governance dalam rangka meningkatkan kualitas pelayanan publik pada fungsi keimigrasian bagi masyarakat dan pemangku kepentingan lainnya disekitar area Tembagapura, pelayanan ini dalam rangka mempercepat kesejahteraan masyarakat serta kapasitas masyarakat setempat. Fokus didalam pembahasan terkait dengan tuntutan dan tantangan organisasi publik menjadi organisasi birokrasi yang lebih agile, akuntabel serta transparan ditengah era revolusi industri 4.0 dengan kompleksitas dan perubahan yang cepat terhadap tata kelola organisasi publik baru menjadi lebih kuat dengan penekanan pada pengambilan keputusan kolaboratif pada collaborative governance untuk pengguna layanan publik tersebut. Menjawab tuntutan dan tantangan terhadap perkembangan tersebut maka diperlukan suatu keputusan kolaboratif sebagai jawaban atas aspirasi publik terkait dengan kegiatan pelayanan publiknya melalui penerapan praktik vertical collaborative governance dengan kemampuan menciptakan iklim kepercayaan serta fasilitasi hubungan. Sebagai bagian dari pelaksanaan collaborative governance yang tertuang pada protap dan juknis pada Kementerian Hukum dan HAM RI serta perkembangan ditengah masyarakat terhadap keterbatasan pelayanan keimigrasian yang dihadapi maka pengambilan keputusan kolaboratif antara pemerintah dengan pemangku kepentingan didalam vertical collaborative governance untuk mencapai tujuan dari kolaborasi meningkatkan pelayanan keimigrasian di wilayah Tembagapura dan sekitarnya yang efektif, efisien dan akuntabel.Kata kunci: Keputusan Kolaboratif; Vertical Collaborative Governance; Pelayanan Keimigrasian; Fungsi Keimigrasian.
Cañón del Río Blanco National Park: A Forgotten Protected Natural Area
Authors: Rivera-Hernández Jaime Ernesto , Alcántara-Salinas Graciela , Balderas-San Miguel Osvaldo , Cid-Mora Oscar , Real-Luna Natalia , Pérez-Sato Juan Antonio
Published: October 2022

Objective: To submit a report about the current situation of the Cañón del Río Blanco National Park and to gather all the existing information about this Protected Natural Area (PNA) in a single document.
Design/Methodology/Approach: A bibliographic research and field work were carried out to determine the current state of the PNA.
Results: The decree, the geographical location, the history of its protection, the biological, sociocultural and economic characteristics, the environmental services, the CONANP work program, the environmental problems, and the category issues are described.
Study Limitations/Implications: There were no limitations.
Findings/Conclusions: The area still protects an important biodiversity and fulfills vital environmental services; however, assigning an adequate category to the park and appointing a director is an urgent matter.
Characterization of mamey [Pouteria sapota (Jacq.) Moore & Stearn] in the Totonacapan Poblano region of Puebla, Mexico
Authors: Chepe Cruz Gabriel , Fajardo Franco Marja Liza , Molina Mendoza Pedro , Santacruz Varela Amalio , Hernández Rodríguez Martha , Aguilar Martin
Published: October 2022

Objective: The objective of this study was to morphologically characterize mamey in 10 municipalities of the Sierra Nororiental of Puebla (Totonacapan Poblano), Mexico.
Design/methodology/approach: In the study, 206 accessions obtained from simple random sampling using qualitative and quantitative morphological descriptors were evaluated, using an analysis of variance, principal components and hierarchical cluster analysis with the Gower distance and the Ward grouping method.
Results: Quantitative descriptors had high coefficients of variability (12.66% to 43.40%). The principal components analysis indicated that components 1 (41.66%), 2 (19.97%) and 3 (16.62%) accounted for 78.25% of the variance and the cluster analysis identified eight groups; the tree and leaf variables turned out to be the most important to group the samples.
Limitations on study/implications: For greater accuracy on the morphological diversity of mamey, it is necessary to include more descriptors of the fruit and the flower.
Findings/conclusions: The descriptors that contributed the most to the grouping were those related to the shape, height and size of the tree, and the weight, size and shape of the leaf; in relation to the fruit, the descriptor that contributed the most was the shape. These results could be useful in programs of conservation, improvement, and use of the mamey.
Чувашстан Республикасы татар эпиграфик һәйкәлләре
Authors: Усманов Венер Мударисович
Published: October 2022

Чувашстан Республикасы авылларында һәм шәһәрләрендә XIII-XX гасырларга нисбәтле йөздән артык гарәп язулы ташъязма истәлек сакланып калган. Китапта ташъязма ядкярләрнең текстлары, фото һәм график сурәтләре каталог-җыентык рәвешендә бер китапка тупланып бирелде. Хезмәт Идел төбәге тарихын һәм мәдәниятен өйрәнүче галимнәр, гомумән татар халкының тарихи үткәне белән кызыксынучы укучылар өчен тәкъдим ителә.
“The Other” In Tony Morrison’s The Bluest Eye Concerning the Female Characters
Authors: Brainee Hilda Jeyakumari
Published: October 2022

Beauty is considered a concept that is certainly perceived by each individual differently. The novel, “The Bluest Eye,” provides values of the African Americans who used tools such as storytelling and music consisting of blues and jazz, much more effective than raising slogans like “Black is beautiful,” which could lead an individual to be confused about the perception of beauty. And thus, it won’t help in the process of gaining love and peace. Claudia, one of the main narrators of the story, finds love and peace by getting to know about the survival of her step-sister and by listening to the blues from her mother. This research paper is based on determining an understanding of the different female characters that are represented in the novel. This analysis is further developed to provide clear identification of the intensive nature of racism, incest, and child molestation, along with the existence of the poor living culture that was being followed in the name of religion. Moreover, it is focused on depicting the extended portrayal of the ways in which the presence of internalized beauty standards was being deformed into the lives of black girls and women.
Dyplomacja cyfrowa w czasie pandemii COVID-19. Zmiana kierunków komunikacji i dyplomacja quasi-medialna
Authors: Pagacz Katarzyna
Published: October 2022

Pandemia COVID-19 wpłynęła znacząco i w bardzo krótkim czasie na funkcjonowanie ludzi, państw i instytucji publicznych. E-dyplomacja, funkcjonująca do początku 2020 roku jako jedna z form dyplomacji, w czasie pandemii zyskała na znaczeniu, a co więcej – na krótki czas stała się jej główną (i jedyną) formą. Cel: praca dotyczy głównie obszaru cyfrowej dyplomacji publicznej. Na tle różnych zmian zachodzących w dyplomacji okresu pandemii COVID-19 starano się uwypuklić dwie z nich, wiążące się z kierunkiem komunikacji oraz rolą mediów w cyfrowej dyplomacji publicznej. Metody badań: w tym celu posłużono się obserwacją niestandaryzowaną i opisem wybranych przypadków, przywołując literaturę i badania dotyczące dyplomacji w pandemii. Wnioski: w okresie poddanym obserwacji (rok 2020) można było zauważyć zarówno zintensyfikowanie dotychczasowych działań z wykorzystaniem nowych technologii, w tym nowych mediów i mediów społecznościowych, jak i wykształcenie się zupełnie nowych podejść do dyplomacji cyfrowej. Wartość poznawcza: walorem opracowanej charakterystyki stanu dyplomacji cyfrowej w czasie pandemii COVID-19 w 2020 roku jest opis nowych jej form (w tym w szczególności dyplomacji quasi-medialnej) i kluczowych zmian, jakie nastąpiły w tym obszarze.
Assessing the Influence of Mobility Behavior on the Covid-19 Transmission: A Case in the Most Affected City of Indonesia
Authors: Umar Najirah , Gani Hamdan , Zuhriyah Sitti , Gani Helmy , Zhipeng Feng
Published: October 2022

An emerging outbreak of Covid-19 has now been detected across the globe. Given this pandemic condition, the robust estimation reports are urgently needed. Therefore, this study aims to analyze the impacts of community mobility (before, during, and after the lockdown period) on the spread of the Covid-19 in Jakarta, Indonesia. The secondary data was derived from surveillance data for Covid-19 daily cases from the Health Office of DKI Jakarta Province and the Ministry of Health. The community mobility indicators were retrieved from the Google website. Our results showed that in the pre-lockdown period, the Covid-19 daily cases rapidly increased, while community mobility significantly dropped. The increasing number of Covid-19 daily cases was significantly affected by the number of Covid-19 tests per day rather than community mobility. During the restriction period, the number of Covid-19 tests per day, and community mobility statistically affected the decreasing number of Covid-19 daily cases. Meanwhile, after the lockdown period, the number of Covid-19 daily cases rapidly increased, which significantly has a direct relationship with the increasing level of community mobility. Overall, community mobility and the number of tests per day are the essential variables that explain the number of Covid-19 daily cases in Jakarta, Indonesia. Additionally, this study did not observe any impact of average air temperature and air pollution on the spread of Covid-19. This study figures out that community mobility could potentially explain the progression of Covid-19.
Efektivitas Cuka Apel (Apple Cider Vinegar) Sebagai Bahan Alami Bleaching Pada Gigi Yang Mengalami Diskolorasi Ekstrinsik
Authors: Mattulada Indrya Kirana , Asmah Nur , Aslan Sarahfin , Arifin Fadil Abdillah , Setiawan Putri Agung
Published: October 2022

Pendahuluan: Gigi yang putih merupakan salah satu hal yang diidamkan masyarakat untuk menunjang penampilan sehingga seseorang dapat memiliki kepercayaan diri yang tinggi ketika berinteraksi. Stain tidak dapat hilang dengan menyikat gigi saja, penggunaan bahan alami dalam memutihkan gigi sangat berkembangi di imasyarakat dan banyak dilakukan penelitian karena bahan alami dianggap lebih aman, murah dan mudah diperoleh bilai dibandingkan dengan bahan kimia. Tujuan Penelitian: Tujuan dilakukan penelitian ini untuk mengetahui apakah cuka apel efektif sebagai bahan alami bleaching pada gigi yang mengalami diskolorasi ekstrinsik. Bahan dan Metode: Bahan pada penelitian adalah cuka apel anna konsentrasi 10%, karbamid peroksida konsentrasi 10% serta 16 buah gigi insisivus rahang atas terdiri dari 2 perlakuan yaitu perendaman larutan cuka apel anna 10% dan pengaplikasian gel karbamid peroksida 10%. Metode penelitian ini adalah kualitatif dengan jenis penelitianTrue Expermintal Laboratorium yang bertujuan untuk mengetahui suatu gejala atau pengaruh yang timbul akibat adanya perlakuan tertentu. Rancangan penelitian ini adalah  pre-testiipost-test with control group design, penelitian diawali dengan perendaman kopi (diskolorasi) selama 5 hari kemudian diberi perlakuan selama 12 hari, pada hari ke 5, hari ke 10 dan hari ke 12 dilakukan pengambilan gambar pada seluruh sampel penelitian. Hasil : Hasil Penelitian ini menunjukkan hasil uji beda didapatkan nilai p-value 0,872 sehingga dapat diasumsikan bahwa cuka apel 10% dan karbamid peroksida 10% tidak memiliki perbedaan yang signifikan dalam mencerahkan gigi yang terdiskolorasi akibat kopi. Pada hasil pengukuran perubahan warna pada kelompok cuka apel 10% dan karbamid peroksida 10% berdasarkan Uji Statistik Independent T-Test diperoleh nilai 0,009 dan 0,006 yaitu signifikan dapat mencerahkan. Namun karbamid peroksida 10% memiliki efektivitas yang lebih baik. Kesimpulan: berdasrkan hasil penelitian ini menunjukkan bahwa larutan cuka apel 10% memiliki efektivitas untuk mencerahkan gigi yang mengalami diskolorasi ekstrinsik akibat kopi.
Korelasi Antara Keadaan Stres Pada Pasien Covid-19 Terhadap Kesehatan Gigi dan Mulut
Authors: Amran Ardian Jayakusuma , Abdi Muhammad Jayadi , Musdalifah Musdalifah , Tulen Sri Fatmawati , Sode Ali Nur Rifa Imtinan
Published: October 2022

Pendahuluan: Pandemi adalah sebagian besar wabah penyakit yang menyebarluas sebagai akibat dari penyebaran penyakit infeksi manusia ke manusia. Covid 19 (Corona virus disease- 2019) adalah virus yang menyerang saluran pernapasan dapat menular melalui percikan batuk atau bersin droplet. Pasien Covid-19 secara langsung dapat mempengaruhi tingkat kecemasan yang dapat menyebabkan gangguan psikogenik. Dan secara tidak langsung berperan sebagai faktor resiko yang dapat mempengaruhi awal terjadinya infeksi mukosa mulut. Tujuan Penelitian: Mengetahui korelasi keadaan stress pasien Covid-19 terhadap kesehatan gigi dan mulut. Bahan dan Metode : Jenis review yang digunakan dalam artikel ini berbentuk literature review, penelusuran melalui kata kunci, covid-19, pandemi, dan stress melalui database pubmed, google scholar, researchgate, BMC oral health. Hasil: Berdasarkan review jurnal terdapat korelasi antara kejadian stres pasien Covid-19 terhadap kesehatan gigi dan mulut. Kejadian Covid-19 mengakibatkan stres pada pasien sehingga menyebabkan gangguan sistem imun dan hormonal yang bermanifestasi langsung pada gangguan kesehatan gigi dan mulut. Kesimpulan: Terdapat korelasi kejadian stres pasien Covid-19 terhadap kesehatan gigi dan mulut. Penatalaksanaan pasien dengan gangguan kesehatan gigi dan mulut akibat stress karena terpapar Covid-19 dilakukan kolaborasi antara penanganan psikologi dan perawatan rongga mulut untuk hasil yang maksimal.
Concept as the Activist of Creativity in Architectural Design: Exploring Factors Affecting Concept Formation Using the Structural Equation Model
Authors: Onur Beyza
Published: October 2022

In the contemporary understanding of architectural design, the concept is essential in that it drives the creative aspect of a designer, provides design a wealth of meaning, and initiates and shapes the design process. Based on the importance of the concept in architectural design, this study aimed to examine the factors affecting the concept formation of architect candidates/architects in design education and practice. For this purpose, a pilot study in the first phase of the study tested a survey distributed to two groups of participants, namely architecture undergraduate students and practising architects in Ankara, the capital of Turkey. The data obtained from the survey were analyzed with the SPSS software and measurement tools were identified and then, weights of the factors were determined using the Structural Equation Model (SEM). According to the analysis results, the factors affecting concept formation in architectural design are the design problem, context, designer-induced values, and user-induced values according to their weighted importance. One of the main reasons the design problem and context are pioneers in determining concept is that these factors hold a strong place in the traditions and teachings of design education. In addition, depending on the way architecture students and practicing architects experience the profession, their attitudes towards creating concepts in their designs may vary.
A new system of socio-humanitarian education as a response to the challenges of modernity
Authors: Kirvel Cheslav S. , Semernik Snezhana Z.
Published: October 2022

The object of research in this article is the system of socio-humanitarian training of students. The article reveals the idea of the influence of the education system on the most important spheres of public life. The authors show that with the help of changes in the education system, it is possible to change not only the individual consciousness of the subjects of social development, but also to change the way of social life in general. Socio-humanitarian knowledge is of particular importance in the preparation of students. It forms the value-worldview attitudes of students, influences their behavioural models and civic position. Optimisation of the content and form of socio-humanitarian education is a strategically important task for society, a necessary condition for the implementation of national security imperatives. The authors argue that society today needs to update the system of socio-humanitarian training of students, especially at the higher school level. They point out the need to carry out this training throughout the entire period of training of students, paying special attention to the direct interaction of teachers and students. At the same time, the theoretical and ideological training of teachers themselves, whose thinking should correspond to state strategic objectives, is of no small importance. The authors convincingly prove that the axiological component should also be given great importance in the preparation of students, since in modern society there is a rapid deethisation and dehumanisation of socialisation, attempts are being made to break traditional values. The practical significance of the research results lies in the possibility of applying the data obtained in determining strategies and priorities for the development of the modern education system, the organisation of educational and educational processes in institutions of secondary and higher education.
The Basic Laws of Trade
Authors: Rahman Abdurrahman Arum
Published: October 2022

We develop hypothetical basic laws of trade to improve the theory of comparative advantage and the theory of international trade. According to the theory of comparative advantage of David Ricardo and Ohlin-Heckscher, countries with different resources and technology will benefit from trading, regardless of competitiveness. This is the core theory in international trade. However, in the real world, this theory does not always work well. Some countries may gain from trading, some may not, and some may even lose. The total gain for all parties is also not optimal. The basic laws of trade could fix this problem. They restore the trade balance at the very heart of international trade. In that way, the basic laws make all countries benefit from trading, regardless of competitiveness and cost. Gains from trade are also optimal for all parties. To demonstrate the workability of this hypothesis, we make trade simulations 2x2 and 5x20.
Deep learning with an attention mechanism for continuous biomechanical motion estimation across varied activities
Authors: Ding Guanlin , Plummer Andrew , Georgilas Ioannis
Published: October 2022

Reliable estimation of desired motion trajectories plays a crucial part in the continuous control of lower extremity assistance devices such as prostheses and orthoses. Moreover, reliable estimation methods are also required to predict hard-to-measure biomechanical quantities (e.g., joint contact moment/force) for use in sports injury science. Recognising that human locomotion is an inherently time-sequential and limb-synergetic behaviour, this study investigates models and learning algorithms for predicting the motion of a subject’s leg from the motion of complementary limbs. The novel deep learning model architectures proposed are based on the Long Short-Term Memory approach with the addition of an attention mechanism. A dataset comprising Inertial Measurement Unit signals from 21 subjects traversing varied terrains was used, including stair ascent/descent, ramp ascent/descent, stopped, level-ground walking and the transitions between these conditions. Fourier Analysis is deployed to evaluate the model robustness, in addition to assessing time-based prediction errors. The experiment on three unseen test participants suggests that the branched neural network structure is preferred to tackle the multioutput problem, and the inclusion of an attention mechanism demonstrates improved performance in terms of accuracy, robustness and network size. An experimental comparison found that 57% of the model parameters were not needed after adding attention layers meanwhile the prediction error is lower than the LSTM model without attention mechanism. The attention model has errors of 9.06% and 7.64% (normalised root mean square error) for ankle and hip acceleration prediction respectively. Also, less high-frequency noise is present in the attention model predictions. We conclude that the internal structure of the proposed deep learning model is justified, principally the benefit of using an attention mechanism. Experimental results for biomechanical motion estimation are obtained, showing greater accuracy than only with LSTM. The trained attention model can be used throughout despite transitioning between terrain types. Such a model will be useful in, for example, the control of lower-limb prostheses, instead of the need to identify and switch between different trajectory generators for different walking modes.
Cortical bone continuum damage mechanics constitutive model with stress triaxiality criterion to predict fracture initiation and pattern
Authors: Cronin D. S , Watson B , Khor F , Gierczycka D , Malcolm S
Published: October 2022

A primary objective of finite element human body models (HBMs) is to predict response and injury risk in impact scenarios, including cortical bone fracture initiation, fracture pattern, and the potential to simulate post-fracture injury to underlying soft tissues. Current HBMs have been challenged to predict the onset of failure and bone fracture patterns owing to the use of simplified failure criteria. In the present study, a continuum damage mechanics (CDM) model, incorporating observed mechanical response (orthotropy, asymmetry, damage), was coupled to a novel phenomenological effective strain fracture criterion based on stress triaxiality and investigated to predict cortical bone response under different modes of loading. Three loading cases were assessed: a coupon level notched shear test, whole bone femur three-point bending, and whole bone femur axial torsion. The proposed material model and fracture criterion were able to predict both the fracture initiation and location, and the fracture pattern for whole bone and specimen level tests, within the variability of the reported experiments. There was a dependence of fracture threshold on finite element mesh size, where higher mesh density produced similar but more refined fracture patterns compared to coarser meshes. Importantly, the model was functional, accurate, and numerically stable even for relatively coarse mesh sizes used in contemporary HBMs. The proposed model and novel fracture criterion enable prediction of fracture initiation and resulting fracture pattern in cortical bone such that post-fracture response can be investigated in HBMs.
Improvement in osteogenesis, vascularization, and corrosion resistance of titanium with silicon-nitride doped micro-arc oxidation coatings
Authors: Shen Yiding , Fang Kai , Xiang Yun , Xu Keyuan , Yu Liang , Chen Jiaquan , Ma Pingping , Cai Kaiyong , Shen Xinkun , Liu Jinsong
Published: October 2022

Titanium (Ti) implants have been widely used for the treatment of tooth loss due to their excellent biocompatibility and mechanical properties. However, modifying the biological properties of these implants to increase osteointegration remains a research challenge. Additionally, the continuous release of various metal ions in the oral microenvironment due to fluid corrosion can also lead to implant failure. Therefore, simultaneously improving the bioactivity and corrosion resistance of Ti-based materials is an urgent need. In recent decades, micro-arc oxidation (MAO) has been proposed as a surface modification technology to form a surface protective oxide layer and improve the comprehensive properties of Ti. The present study doped nano silicon nitride (Si3N4) particles into the Ti surface by MAO treatment to improve its corrosion resistance and provide excellent osteoinduction by enhancing alkaline phosphatase activity and osteogenic-related gene expression. In addition, due to the presence of silicon, the Si3N4-doped materials showed excellent angiogenesis properties, including the promotion of cell migration and tubule formation, which play essential roles in early recovery after implantation.
Microneedle-mediated drug delivery for cutaneous diseases
Authors: Chen Jian , Ren Hui , Zhou Pan , Zheng Shuai , Du Bin , Liu Xiaowen , Xiao Fei
Published: October 2022

Microneedles have garnered significant interest as transdermal drug delivery route owing to the advantages of nonselective loading capacity, minimal invasiveness, simple operation, and good biocompatibility. A number of therapeutics can be loaded into microneedles, including hydrophilic and hydrophobic small molecular drugs, and macromolecular drugs (proteins, mRNA, peptides, vaccines) for treatment of miscellaneous diseases. Microneedles feature with special benefits for cutaneous diseases owing to the direct transdermal delivery of therapeutics to the skin. This review mainly introduces microneedles fabricated with different technologies and transdermal delivery of various therapeutics for cutaneous diseases, such as psoriasis, atopic dermatitis, skin and soft tissue infection, superficial tumors, axillary hyperhidrosis, and plantar warts.
Comparison of the biomechanical differences in the occlusal movement of wild-type and BMP9 knockout mice with apical periodontitis
Authors: Peng Mengtian , Ma Xiaofei , Cao Yuying , Wang Chunjuan , Tan Qin , Chu Xinyue , Zhou Pengfei , Fu Tiwei , Liang Panpan , Ran Shidian , He Tong-Chuan , Wang Jinhua , Huang Enyi
Published: October 2022

Apical periodontitis is a common clinical disease caused by bacteria; bacterial metabolites can cause an imbalance in bone homeostasis, bone mass reduction, and tooth loss. Bone resorption in apical periodontitis causes a concentration of stress in the tooth and periodontal tissues during occlusion, which aggravates the disease. Emerging evidence indicates that bone morphogenetic protein 9 (BMP9), also known as growth differentiation factor 2(Gdf2), may play an important role in tooth and dentoalveolar development. Herein, we investigated the role of BMP9 in the development of apical periodontitis and its effects on the biomechanics of dentoalveolar bone. Apical periodontitis models were established in five BMP9 knockout (KO) mice and five C57BL/6 WT (wild-type) mice. At baseline and 14, 28, and 42 days after modeling, in vivo micro-computed tomography analysis and three-dimensional (3D) reconstruction were performed to evaluate the apical lesion in each mouse, and confirm that the animal models were successfully established. Finite element analysis (FEA) was performed to study the stress and strain at the alveolar fossa of each mouse under the same vertical and lateral stress. FEA revealed that the stress and strain at the alveolar fossa of each mouse gradually concentrated on the tooth cervix. The stress and strain at the tooth cervix gradually increased with time but were decreased at day 42. Under the same lingual loading, the maximum differences of the stress and strain at the tooth root in KO mice were greater than those in WT mice. Thus, these findings demonstrate that BMP9 could affect the biomechanical response of the alveolar fossa at the tooth root in mice with apical periodontitis. Moreover, the effects of BMP9 on the biomechanical response of the alveolar bone may be site-dependent. Overall, this work contributes to an improved understanding of the pathogenesis of apical periodontitis and may inform the development of new treatment strategies for apical periodontitis.
Enhanced small green fluorescent proteins as a multisensing platform for biosensor development
Authors: Liang Guo-Teng , Lai Cuixin , Yue Zejun , Zhang Hanbin , Li Danyang , Chen Zhong , Lu Xingyu , Tao Liang , Subach Fedor V. , Piatkevich Kiryl D.
Published: October 2022

Engineered light, oxygen, and voltage (LOV)-based proteins are able to fluoresce without oxygen requirement due to the autocatalytic incorporation of exogenous flavin as a chromophore thus allowing for live cell imaging under hypoxic and anaerobic conditions. They were also discovered to have high sensitivity to transition metal ions and physiological flavin derivatives. These properties make flavin-binding fluorescent proteins (FPs) a perspective platform for biosensor development. However, brightness of currently available flavin-binding FPs is limited compared to GFP-like FPs creating a need for their further enhancement and optimization. In this study, we applied a directed molecular evolution approach to develop a pair of flavin-binding FPs, named miniGFP1 and miniGFP2. The miniGFP proteins are characterized by cyan-green fluorescence with excitation/emission maxima at 450/499 nm and a molecular size of ∼13 kDa. We carried out systematic benchmarking of miniGFPs in Escherichia coli and cultured mammalian cells against spectrally similar FPs including GFP-like FP, bilirubin-binding FP, and bright flavin-binding FPs. The miniGFPs proteins exhibited improved photochemical properties compared to other flavin-binding FPs enabling long-term live cell imaging. We demonstrated the utility of miniGFPs for live cell imaging in bacterial culture under anaerobic conditions and in CHO cells under hypoxia. The miniGFPs’ fluorescence was highly sensitive to Cu(II) ions in solution with Kd values of 67 and 68 nM for miniGFP1 and miniGFP2, respectively. We also observed fluorescence quenching of miniGFPs by the reduced form of Cu(I) suggesting its potential application as an optical indicator for Cu(I) and Cu(II). In addition, miniGFPs showed the ability to selectively bind exogenous flavin mononucleotide demonstrating a potential for utilization as a selective fluorescent flavin indicator. Altogether, miniGFPs can serve as a multisensing platform for fluorescence biosensor development for in vitro and in-cell applications.
MicroRNAs in extracellular vesicles: Sorting mechanisms, diagnostic value, isolation, and detection technology
Authors: Xu Dongjie , Di Kaili , Fan Boyue , Wu Jie , Gu Xinrui , Sun Yifan , Khan Adeel , Li Peng , Li Zhiyang
Published: October 2022

MicroRNAs (miRNAs) are a class of short, single-stranded, noncoding RNAs, with a length of about 18–22 nucleotides. Extracellular vesicles (EVs) are derived from cells and play a vital role in the development of diseases and can be used as biomarkers for liquid biopsy, as they are the carriers of miRNA. Existing studies have found that most of the functions of miRNA are mainly realized through intercellular transmission of EVs, which can protect and sort miRNAs. Meanwhile, detection sensitivity and specificity of EV-derived miRNA are higher than those of conventional serum biomarkers. In recent years, EVs have been expected to become a new marker for liquid biopsy. This review summarizes recent progress in several aspects of EVs, including sorting mechanisms, diagnostic value, and technology for isolation of EVs and detection of EV-derived miRNAs. In addition, the study reviews challenges and future research avenues in the field of EVs, providing a basis for the application of EV-derived miRNAs as a disease marker to be used in clinical diagnosis and even for the development of point-of-care testing (POCT) platforms.
Advances in biomaterials as a retinal patch for the repair of rhegmatogenous retinal detachment
Authors: Zheng Chuanzhen , Wen Dejia , Xu Kejia , Zhang Xiaomin , Ren Xinjun , Li Xiaorong
Published: October 2022

Rhegmatogenous retinal detachment (RRD) is the most common retinological emergency that can cause blindness without surgical treatment. RRD occurs when liquefied vitreous accumulates between the neurosensory retina and the retinal pigment epithelium via retinal breaks, which are caused by the separation of the vitreous from the retina with aging. Currently, the main treatment option is pars plana vitrectomy, which involves surgical removal of the vitreous and laser photocoagulation around retinal breaks to generate firm chorioretinal adhesion, as well as subsequent filling of the vitreous cavity with long-lasting substitutes (expansile gas or silocone oil) to prevent the connection between the subretinal space and the vitreous cavity via the breaks before the chorioretinal adhesion firm enough. However, the postoperative face-down position and the not very satisfactory first retinal reattachment rate place a heavy burden on patients. With the development of technology and materials engineering, researchers have developed biomaterials that can be used as a retinal patch to seal retinal breaks and prevent the connection of subretinal space and vitreous cavity via breaks, thus replacing the long-lasting vitreous substitutes and eliminating the postoperative face-down position. Preclinical studies have demonstrated that biomaterial sealants have enough biocompatibility and efficacy in the in vitro and in vivo experiments. Some sealants have been used in clinical trials on a small scale, and the results indicate promising application prospects of the biomaterial sealants as retinal patches in the repair of RRD. Herein, we review the recent advances in biomaterials as retinal patches for the repair of RRD, focusing on the biomaterial categories, methods, and procedures for sealing retinal breaks, as well as their biocompatibility and efficacy, current limitations, and development perspectives.
Recent developments in evaluation methods and characteristics of comfort environment in underground subway
Authors: Yan Weichao , Meng Xiangzhao , Zhou Haiyun , Yang Chuanjun , Chen Qian , Oh Seung Jin , Cui Xin
Published: October 2022

In recent years, due to the rapid progress of urbanization, the subway system with the advantages of large transport capacity, punctuality, efficiency, convenience and safety has become one of the main transportation modes in metropolitan areas. With the increase in passenger flow, the comfort of subway passengers has attracted extensive attention from the academic community. In this paper, we begin by analyzing the characteristics of the subway environment and sort out six environmental elements that affect passengers’ comfort, including thermal environment, vibration, noise, lighting, air quality, and air pressure. In addition, the measurement scheme, calculation model, and evaluation method of each element are outlined based on relevant norms and literature. Through reviewing the studies in the past 2 decades, it is found that the in-depth research is still in demand for a comprehensive comfort evaluation model with multi-element coupling. A deep understanding of the subway passengers’ comfort is the basis for the design, development, and operation regulation of the subway environmental control system. Measures to improve comfort, especially the exploitation of energy-saving air conditioning systems, will provide strong support for the sustainable and sound growth of the rail transit industry.
Metabolic fingerprinting of chemotherapy-resistant prostate cancer stem cells. An untargeted metabolomic approach by liquid chromatography-mass spectrometry
Authors: Bort Alicia , G. Sánchez Belén , León Carlos , Nozal Leonor , Mora-Rodríguez José M. , Castro Florentina , Crego Antonio L. , Díaz-Laviada Inés
Published: October 2022

Chemoresistance is one of the most important challenges in cancer therapy. The presence of cancer stem cells within the tumor may contribute to chemotherapy resistance since these cells express high levels of extrusion pumps and xenobiotic metabolizing enzymes that inactivate the therapeutic drug. Despite the recent advances in cancer cell metabolism adaptations, little is known about the metabolic adaptations of the cancer stem cells resistant to chemotherapy. In this study, we have undertaken an untargeted metabolomic analysis by liquid chromatography–high-resolution spectrometry combined with cytotoxicity assay, western blot, quantitative real-time polymerase chain reaction (qPCR), and fatty acid oxidation in a prostate cancer cell line resistant to the antiandrogen 2-hydroxiflutamide with features of cancer stem cells, compared to its parental androgen-sensitive cell line. Metabolic fingerprinting revealed 106 out of the 850 metabolites in ESI+ and 67 out of 446 in ESI- with significant differences between the sensitive and the resistant cell lines. Pathway analysis performed with the unequivocally identified metabolites, revealed changes in pathways involved in energy metabolism as well as posttranscriptional regulation. Validation by enzyme expression analysis indicated that the chemotherapy-resistant prostate cancer stem cells were metabolically dormant with decreased fatty acid oxidation, methionine metabolism and ADP-ribosylation. Our results shed light on the pathways underlying the entry of cancer cells into dormancy that might contribute to the mechanisms of drug resistance.
Principles of glycocalyx engineering with hydrophobic-anchored synthetic mucins
Authors: Wardzala Casia L. , Clauss Zachary S. , Kramer Jessica R.
Published: October 2022

The cellular glycocalyx is involved in diverse biological phenomena in health and disease. Yet, molecular level studies have been challenged by a lack of tools to precisely manipulate this heterogeneous structure. Engineering of the cell surface using insertion of hydrophobic-terminal materials has emerged as a simple and efficient method with great promise for glycocalyx studies. However, there is a dearth of information about how the structure of the material affects membrane insertion efficiency and resulting density, the residence time of the material, or what types of cells can be utilized. Here, we examine a panel of synthetic mucin structures terminated in highly efficient cholesterylamide membrane anchors for their ability to engineer the glycocalyx of five different cell lines. We examined surface density, residence time and half-life, cytotoxicity, and the ability be passed to daughter cells. We report that this method is robust for a variety of polymeric structures, long-lasting, and well-tolerated by a variety of cell lines.