bluuebunny/crossref_metadata_2025 huggingface dataset:
Biosynthesis Investigations of Terpenoid, Alkaloid, and Flavonoid Antimicrobial Agents Derived from Medicinal Plants
Authors: Huang Wenqian , Wang Yingxia , Tian Weisheng , Cui Xiaoxue , Tu Pengfei , Li Jun , Shi Shepo , Liu Xiao
Published: October 2022

The overuse of antibiotics in the past decades has led to the emergence of a large number of drug-resistant microorganisms. In recent years, the infection rate caused by multidrug-resistant microorganisms has been increasing, which has become one of the most challenging problems in modern medicine. Plant-derived secondary metabolites and their derivatives have been identified to display significant antimicrobial abilities with good tolerance and less adverse side effects, potentially having different action mechanisms with antibiotics of microbial origin. Thus, these phyto-antimicrobials have a good prospect in the treatment of multidrug-resistant microorganisms. Terpenoids, alkaloids, and flavonoids made up the predominant part of the currently reported phytochemicals with antimicrobial activities. Synthetic biology research around these compounds is one of the hotspot fields in recent years, which not only has illuminated the biosynthesis pathways of these phyto-antimicrobials but has also offered new methods for their production. In this review, we discuss the biosynthesis investigations of terpenoid, alkaloid, and flavonoid antimicrobial agents—using artemisinin and oleanolic acid (terpenoids), berberine and colchicine (alkaloids), and baicalin (flavonoids) as examples—around their antimicrobial action mechanisms, biosynthesis pathway elucidation, key enzyme identification, and heterologous production, in order to provide useful hints for plant-derived antimicrobial agent discovery and development.
Individual Pharmacotherapy Management (IPM)—IV: Optimized Usage of Approved Antimicrobials Addressing Under-Recognized Adverse Drug Reactions and Drug-Drug Interactions in Polypharmacy
Authors: Wolf Ursula , Baust Henning , Neef Rüdiger , Steinke Thomas
Published: October 2022

Antimicrobial therapy is often a life-saving medical intervention for inpatients and outpatients. Almost all medical disciplines are involved in this therapeutic procedure. Knowledge of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) is important to avoid drug-related harm. Within the broad spectrum of antibiotic and antifungal therapy, most typical ADRs are known to physicians. The aim of this study was to evaluate relevant pharmacological aspects with which we are not so familiar and to provide further practical guidance. Individual pharmacotherapy management (IPM) as a synopsis of internal medicine and clinical pharmacology based on the entirety of the digital patient information with reference to drug information, guidelines, and literature research has been continuously performed for over 8 years in interdisciplinary intensive care and trauma and transplant patients. Findings from over 52,000 detailed medication analyses highlight critical ADRs and DDIs, especially in these vulnerable patients with polypharmacy. We present the most relevant ADRs and DDIs in antibiotic and antifungal pharmacology, which are less frequently considered in relation to neurologic, hemostaseologic, hematologic, endocrinologic, and cardiac complexities. Constant awareness and preventive strategies help avoid life-threatening manifestations of these inherent risks and ensure patient and drug safety in antimicrobial therapy.
Prior Antibiotic Use Increases Risk of Urinary Tract Infections Caused by Resistant Escherichia coli among Elderly in Primary Care: A Case-Control Study
Authors: Jensen Maria L. V. , Siersma Volkert , Søes Lillian M. , Nicolaisdottir Dagny , Bjerrum Lars , Holzknecht Barbara J.
Published: October 2022

We investigated whether prior use of antibiotics affects the risk of mecillinam/trimethoprim/nitrofurantoin/multi-resistant Escherichia coli urinary tract infection (UTI) among elderly patients in general practice. Data on urine culture came from urine samples performed in general practice and sent to hospitals in the Capital Region of Denmark, and prescription data came from a nationwide prescription database. The study population consisted of patients with UTI episodes (n = 41,027) caused by E. coli that received a concurrent antibiotic prescription against UTI from 2012 to 2017. We used a case-control design. Cases were UTI episodes caused by mecillinam, trimethoprim, nitrofurantoin or multi-resistant E. coli and controls were UTI episodes caused by E. coli not displaying the respective resistance pattern. We analyzed whether exposure to antibiotics in a period of 8–90 days prior to the UTI episode affected the risk of antibiotic resistant uropathogenic E coli. The analyses were adjusted for age, sex, hospital admission and nursing home status. The odds of resistance to all of the four antibiotics increased significantly after exposure to antibiotics within 90 days prior to the UTI episode. In general, mecillinam showed the lowest increase in the odds for selection of resistance. The results indicate that mecillinam is a favorable antibiotic choice in terms of selection of resistance.
Pragmatic Comparison of Piperacillin/Tazobactam versus Carbapenems in Treating Patients with Nosocomial Pneumonia Caused by Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae
Authors: Zha Lei , Li Xiang , Ren Zhichu , Zhang Dayan , Zou Yi , Pan Lingling , Li Shirong , Chen Shanghua , Tefsen Boris
Published: October 2022

The effectiveness of piperacillin/tazobactam for managing nosocomial pneumonia caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is unknown. To answer this question, we conducted a retrospective cohort study in two tertiary teaching hospitals of patients admitted between January 2018 and July 2021 with a diagnosis of nosocomial pneumonia caused by ESBL-producing K. pneumoniae receiving either piperacillin/tazobactam or carbapenems within 24 h from the onset of pneumonia for at least 72 h. Clinical outcomes, including 28-day mortality and 14-day clinical and microbiological cure, were analyzed. Of the 136 total patients, 64 received piperacillin/tazobactam and 72 received carbapenems. The overall 28-day mortality was 19.1% (26/136). In the inverse probability of treatment weighted cohort, piperacillin/tazobactam therapy was not associated with worse clinical outcomes, as the 28-day mortality (OR, 0.82, 95% CI, 0.23–2.87, p = 0.748), clinical cure (OR, 0.94, 95% CI, 0.38–2.35, p = 0.894), and microbiological cure (OR, 1.10, 95% CI, 0.53–2.30, p = 0.798) were comparable to those of carbapenems. Subgroup analyses also did not demonstrate any statistical differences. In conclusion, piperacillin/tazobactam could be an effective alternative to carbapenems for treating nosocomial pneumonia due to ESBL-producing K. pneumoniae when the MICs are ≤8 mg/L.
Solving a Simple Geduldspiele Cube with a Robotic Gripper via Sim-to-Real Transfer
Authors: Yoo Ji-Hyeon , Jung Ho-Jin , Kim Jang-Hyeon , Sim Dae-Han , Yoon Han-Ul
Published: October 2022

Geduldspiele cubes (also known as patience cubes in English) are interesting problems to solve with robotic systems on the basis of machine learning approaches. Generally, highly dexterous hand and finger movement is required to solve them. In this paper, we propose a reinforcement-learning-based approach to solve simple geduldspiele cubes of a flat plane, a convex plane, and a concave plane. The key idea of the proposed approach is that we adopt a sim-to-real framework in which a robotic agent is virtually trained in simulation environment based on reinforcement learning, then the virtually trained robotic agent is deployed into a physical robotic system and evaluated for tasks in the real world. We developed a test bed which consists of a dual-arm robot with a patience cube in a gripper and the virtual avatar system to be trained in the simulation world. The experimental results showed that the virtually trained robotic agent was able to solve simple patience cubes in the real world as well. Based on the results, we could expect to solve the more complex patience cubes by augmenting the proposed approach with versatile reinforcement learning algorithms.
Calibration and Testing of Discrete Element Simulation Parameters for Sandy Soils in Potato Growing Areas
Authors: Li Junru , Xie Shengshi , Liu Fei , Guo Yaping , Liu Chenglong , Shang Zhenyu , Zhao Xuan
Published: October 2022

To improve the accuracy of discrete element simulation in the process of separating potato–soil mixtures, the contact parameters of sandy soil with 3, 6, 9, and 12% water content were calibrated in DEM simulation using EDEM software simulation. The error of the rest angle between them was used as an index, and the approach of performing only one simulation and multiple Box–Behnken response surface analyses was proposed to determine the optimal parameter combinations. Meanwhile, unconfined compression and direct shear tests were conducted to obtain the parameters of polymer bonds for soil with different water content, and a simulation was carried out using EDEM. The test results show that the significant parameters affecting the rest angle are JKR surface energy, soil interparticle recovery coefficient, and rolling friction factor. The numerical simulation of the rest angle was compared with the physical test, and the maximum relative error between them was 4.72%. The bond parameters of soil with different water content and firmness were obtained and compared with the simulation test, the maximum error was 6.53% for the direct shear test and 8.07% for the unconfined compression test, which proved that the bonding parameters are reliable and provide an effective parametric and theoretical basis for the discrete element simulation of soil particles.
Spectroscopic and Molecular Docking Analysis of π-Acceptor Complexes with the Drug Barbital
Authors: Alamri Abdulhakeem S. , Alhomrani Majid , Alsanie Walaa F. , Alyami Hussain , Shakya Sonam , Habeeballah Hamza , Abdulaziz Osama , Alamri Abdulwahab , Alkhatabi Heba A. , Felimban Raed I. , Alhabeeb Abdulhameed Abdullah , Refat Moamen S. , Gaber Ahmed
Published: October 2022

The drug barbital (Bar) has a strong sedative–hypnotic effect. The intermolecular charge transfer compounds associated with the chemical reactions between Bar and some π acceptors, such as 2,6-dibromoquinone-4-chloroimide (DBQ), tetracyanoquinodimethane (TCNQ), chloranil (CHL), and chloranilic acid (CLA), have been synthesized and isolated in solid state. The synthesized products have the molecular formulas (Bar–DBQ), (Bar–TCNQ), (Bar–CHL), and (Bar–CLA) with 1:1 stoichiometry based on Raman, IR, TG, 1H NMR, XRD, SEM, and UV-visible analysis techniques. Additionally, the comparative analysis of molecular docking between the donor reactant moiety, Bar, and its four CT complexes was conducted using two neurotransmitter receptors (dopamine and serotonin). The docking results obtained from AutoDockVina software were investigated by a molecular dynamics simulation technique with 100ns run. The molecular mechanisms behind receptor–ligand interactions were also looked into. The DFT computations were conducted using theory at the B3LYP/6-311G++ level. In addition, the HOMO LUMO electronic energy gap and the CT complex’s optimal geometry and molecule electrostatic potential were examined.
Novel Bathing Assist Device Decreases the Physical Burden on Caregivers and Difficulty of Bathing Activity in Care Recipients: A Pilot Study
Authors: Kato Kenji , Aimoto Keita , Kawamura Koki , Yoshimi Tatsuya , Itoh Naoki , Kondo Izumi
Published: October 2022

The purpose of this study was to investigate whether the use of a bathing assist device, “Bath Assist” (BA), could reduce the physical burden on caregivers providing bathing assistance and also alleviate the difficulty of bathing activities for care recipients. BA is a robotic device that is attached to the bathtub. The seat can be raised and lowered using the water pressure from the shower tap. The four caregivers and four care recipients were paired one-to-one to simulate bathing activity, and the physical burden on each caregiver during bathing assistance was evaluated with and without the use of BA by observation, questionnaire, and wireless surface electromyography. For caregivers, BA transformed the task of assisting care recipients into and out of the bathtub into a monitoring activity. Additionally, the muscle activity of the caregivers’ lumbar region, trunk, and upper limbs, which are used to assist care recipients out of the bathtub, was significantly reduced when using BA. Questionnaires confirmed that the use of BA reduced the physical burden on caregivers. These results indicate that BA has the potential to reduce both the physical burden on caregivers during bathing assistance and the difficulties care recipients experience during bathing.
Analysis of the Behavior of Vehicle Drivers at Signal-Controlled Intersection Approach while Waiting for a Green Signal—A Case Study in Poland
Authors: Sieklicka Agnieszka , Chądzyńska Patrycja , Iwanowicz Damian
Published: October 2022

The article presents the results of research on the behavior of vehicle drivers who, in the congested city road network (during the transport peak period), were unable to pass a traffic light-controlled intersection during one signaling cycle. They were therefore forced to wait in line at least once on the red signal before they could continue their journey. Empirical research was conducted at several intersections with traffic lights in Poland, in the cities of Bydgoszcz and Toruń. In addition, the database was supplemented with the results of surveys, which were decided to be conducted in the form of electronic form during the COVID-19 pandemic through dedicated surveys and social networking sites. The analysis of the results of field studies confirms that most drivers commit traffic offenses in the form of using mobile devices in their hands (over 60%) in the period after the start of transmitting the red signal and after stopping the vehicle. Interestingly, less than 40% of respondents admitted this offense in the survey.
Numerical Investigation on the Principle of Energy Separation in the Vortex Tube
Authors: Park Seol Yeon , Yoon Sang Hee , Yu Sang Seok , Kim Byoung Jae
Published: October 2022

A vortex tube is a simple device that separates incoming gas into cold and hot gases. Several theories have been proposed to explain the principle of energy separation in the vortex tube. Existing theories have advantages and defects. Recently, various studies employed numerical simulations to study the flow in the vortex tube. As a result, flow structures were well clarified. However, in most cases, the temperature separation was partially discussed based on the temperature distribution in the radial direction. This study aimed to explain the principle of energy separation in the vortex tube. To do so, the relative contributions of the radial pressure gradient, axial pressure gradient, and viscous dissipation to the temperature separation were investigated using numerical simulations and energy equation analysis. The results indicated that the axial pressure gradient in the near-axis region was the major contributor to an increase in hot exit temperature. In addition, the reason for the increase in hot exit temperature with an increase in cold mass fraction was explained. The reason for the decrease in cold exit temperature with an increase in cold mass fraction was also explained.
Player Engagement Analysis of a Business Simulation Game from Physiological, Psychological and Behavioral Perspectives: A Case Study
Authors: Ferreira Cleiton Pons , González Carina Soledad González , Adamatti Diana Francisca
Published: October 2022

To obtain an accurate understanding of player experience (PE) in serious games that simulate organizational environments, many factors must be considered and intertwined, psychological, physiological and related to the game performance itself. Such elements can be analyzed using experimental techniques such as recording attentional aspects or monitoring brain waves and subjective methods such as questionnaires. The objective of this work was to analyze the possible benefits of using a business simulation game (BSG) as a resource to stimulate learning based on the measurement of engagement in its different dimensions, using a hemoencephalogram (HEG) device to monitor cortical activation and the eye tracking (ET), for measuring pupillary dilation, both used concomitantly, in addition to pre- and posttest questionnaires, to record participants’ expectations and perceptions of the game experience. Data collection was carried out with 10 students and professors in the computer engineering course at the University of La Laguna, Spain. The results indicate that critical situations and recurring ethical decisions in the game are important elements of the involvement of participants. In addition, the two devices proved to be suitable as a source of important information in determining the flow and attentional level for BSG.
A Modified Gorilla Troops Optimizer for Global Optimization Problem
Authors: Wu Tingyao , Wu Di , Jia Heming , Zhang Nuohan , Almotairi Khaled H. , Liu Qingxin , Abualigah Laith
Published: October 2022

The Gorilla Troops Optimizer (GTO) is a novel Metaheuristic Algorithm that was proposed in 2021. Its design was inspired by the lifestyle characteristics of gorillas, including migration to a known position, migration to an undiscovered position, moving toward the other gorillas, following silverback gorillas and competing with silverback gorillas for females. However, like other Metaheuristic Algorithms, the GTO still suffers from local optimum, low diversity, imbalanced utilization, etc. In order to improve the performance of the GTO, this paper proposes a modified Gorilla Troops Optimizer (MGTO). The improvement strategies include three parts: Beetle-Antennae Search Based on Quadratic Interpolation (QIBAS), Teaching–Learning-Based Optimization (TLBO) and Quasi-Reflection-Based Learning (QRBL). Firstly, QIBAS is utilized to enhance the diversity of the position of the silverback. Secondly, the teacher phase of TLBO is introduced to the update the behavior of following the silverback with 50% probability. Finally, the quasi-reflection position of the silverback is generated by QRBL. The optimal solution can be updated by comparing these fitness values. The performance of the proposed MGTO is comprehensively evaluated by 23 classical benchmark functions, 30 CEC2014 benchmark functions, 10 CEC2020 benchmark functions and 7 engineering problems. The experimental results show that MGTO has competitive performance and promising prospects in real-world optimization tasks.
Deep Reinforcement Learning for Vehicle Platooning at a Signalized Intersection in Mixed Traffic with Partial Detection
Authors: Trinh Hung Tuan , Bae Sang-Hoon , Tran Duy Quang
Published: October 2022

The intersection management system can increase traffic capacity, vehicle safety, and the smoothness of all vehicle movement. Platoons of connected vehicles (CVs) use communication technologies to share information with each other and with infrastructures. In this paper, we proposed a deep reinforcement learning (DRL) model that applies to vehicle platooning at an isolated signalized intersection with partial detection. Moreover, we identified hyperparameters and tested the system with different numbers of vehicles (1, 2, and 3) in the platoon. To compare the effectiveness of the proposed model, we implemented two benchmark options, actuated traffic signal control (ATSC) and max pressure (MP). The experimental results demonstrated that the DRL model has many outstanding advantages compared to other models. Through the learning process, the average waiting time of vehicles in the DRL method was improved by 20% and 28% compared with the ATSC and MP options. The results also suggested that the DRL model is effective when the CV penetration rate is over 20%.
Shape Optimization of the Streamlined Train Head for Reducing Aerodynamic Resistance and Noise
Authors: Yu Mengge , Liu Jiali , Huo Wei , Zhang Jiye
Published: October 2022

Aiming to improve the comprehensive aerodynamic performance of a high-speed train, a multi-objective shape optimization method for a streamlined train head is proposed in this work. The shape of the streamlined train head is parameterized with some spline curves. The optimization design variables are uniformly sampled using the optimal Latin hypercube design method. The aerodynamic resistance and dipole noise sources are chosen as the optimization objectives, which can be obtained through the computational fluid dynamics (CFD) method. An approximate calculation model is established by the radial basis function neural network so as to effectively predict the values of optimization objectives. The error between the predicted values and actual values of the aerodynamic resistance is less than 1%, and that of the dipole noise source is less than 3 dB, which demonstrate the validity of the approximate calculation model. In the optimization process, the algorithm NSGA-II is adopted to update the values of the optimization design variables, and the approximate calculation model is used to calculate the optimization objectives, which greatly reduces the optimization computation time of the streamlined head shape. Through iterative computation of the optimization algorithm in the design space, each optimized design variable shows a trend of convergence, and the aerodynamic resistance and dipole noise source generally show a decreasing trend. The Pareto front is corrected by the CFD method after optimization. The aerodynamic resistance can be reduced by up to 4.5%, and the dipole noise source can be reduced by up to 3.9 dB.
Global–Local Self-Attention Based Transformer for Speaker Verification
Authors: Xie Fei , Zhang Dalong , Liu Chengming
Published: October 2022

Transformer models are now widely used for speech processing tasks due to their powerful sequence modeling capabilities. Previous work determined an efficient way to model speaker embeddings using the Transformer model by combining transformers with convolutional networks. However, traditional global self-attention mechanisms lack the ability to capture local information. To alleviate these problems, we proposed a novel global–local self-attention mechanism. Instead of using local or global multi-head attention alone, this method performs local and global attention in parallel in two parallel groups to enhance local modeling and reduce computational cost. To better handle local location information, we introduced locally enhanced location encoding in the speaker verification task. The experimental results of the VoxCeleb1 test set and the VoxCeleb2 dev set demonstrated the improved effect of our proposed global–local self-attention mechanism. Compared with the Transformer-based Robust Embedding Extractor Baseline System, the proposed speaker Transformer network exhibited better performance in the speaker verification task.
Contact Tracing Strategies for COVID-19 Prevention and Containment: A Scoping Review
Authors: Ojokoh Bolanle Adefowoke , Aribisala Benjamin , Sarumi Oluwafemi A. , Gabriel Arome Junior , Omisore Olatunji , Taiwo Abiola Ezekiel , Igbe Tobore , Chukwuocha Uchechukwu Madukaku , Yusuf Tunde , Afolayan Abimbola , Babalola Olusola , Adebayo Tolulope , Afolabi Olaitan
Published: October 2022

Coronavirus Disease 2019 (COVID-19) spreads rapidly and is easily contracted by individuals who come near infected persons. With this nature and rapid spread of the contagion, different types of research have been conducted to investigate how non-pharmaceutical interventions can be employed to contain and prevent COVID-19. In this review, we analyzed the key elements of digital contact tracing strategies developed for the prevention and containment of the dreaded epidemic since its outbreak. We carried out a scoping review through relevant studies indexed in three databases, namely Google Scholar, PubMed, and ACM Digital Library. Using some carefully defined search terms, a total of 768 articles were identified. The review shows that 86.32% (n = 101) of the works focusing on contact tracing were published in 2020, suggesting there was an increased awareness that year, increased research efforts, and the fact that the pandemic was given a very high priority by most journals. We observed that many (47.86%, n = 56) of the studies were focused on design and implementation issues in the development of COVID-19 contact tracing systems. In addition, has been established that most of the studies were conducted in 41 countries and that contract tracing app development are characterized by some sensitive issues, including privacy-preserving and case-based referral characteristics.
Architectural and Technological Improvements to Integrated Bioprocess Models towards Real-Time Applications
Authors: Taylor Christopher , Pretzner Barbara , Zahel Thomas , Herwig Christoph
Published: October 2022

Integrated or holistic process models may serve as the engine of a digital asset in a multistep-process digital twin. Concatenated individual-unit operation models are effective at propagating errors over an entire process, but are nonetheless limited in certain aspects of recent applications that prevent their deployment as a plausible digital asset, particularly regarding bioprocess development requirements. Sequential critical quality attribute tests along the process chain that form output–input (i.e., pool-to-load) relationships, are impacted by nonaligned design spaces at different scales and by simulation distribution challenges. Limited development experiments also inhibit the exploration of the overall design space, particularly regarding the propagation of extreme noncontrolled parameter values. In this contribution, bioprocess requirements are used as the framework to improve integrated process models by introducing a simplified data model for multiunit operation processes, increasing statistical robustness, adding a new simulation flow for scale-dependent variables, and describing a novel algorithm for extrapolation in a data-driven environment. Lastly, architectural and procedural requirements for a deployed digital twin are described, and a real-time workflow is proposed, thus providing a final framework for a digital asset in bioprocessing along the full product life cycle.
Current Genetic Structure Analysis of Leopard Cats Reveals a Weak Disparity Trend in Subpopulations in Beijing, China
Authors: Teng Yang , Yang Jing , Ju Long-Fei , Huang Wen-Hua , Zhang Xin , Gao Fu-Li , Bao Wei-Dong
Published: October 2022

In the face of habitat shrinkage and segregation, the survival of wild cats looks bleak. Interpreting their population genetic structure during habitat fragmentation is critical in planning effective management strategies. To reveal the segregation effects of road construction and human settlements on the population genetic structure, we analyzed non-invasive fecal DNA samples from leopard cats (Prionailurus bengalensis) from five nature reserves in mountainous areas around Beijing. We focused on microsatellite markers. A total of 112 individual leopard cats were identified among 601 samples of scat, and moderate population genetic diversity was detected. Microsatellite-marker-based genetic differentiation (Fst) and gene flow (Nm) showed a weak trend toward discrepancies in the Baihuashan and Songshan subpopulations, which indicated habitat fragmentation effects on individual dispersal. Because the segregated subpopulations may suffer a high risk of genetic diversity loss, we suggest that their genetic structure be monitored with more molecular markers to detect any changes, and that female individuals be artificially introduced as needed to maintain the viability of the leopard cat subpopulations in Beijing.
Structure of the Motor Descending Pathways Correlates with the Temporal Kinematics of Hand Movements
Authors: Begliomini Chiara , Ceccarini Francesco , Dell’Acqua Veronica Pinuccia , Budisavljevic Sanja , Castiello Umberto
Published: October 2022

The projection system, a complex organization of ascending and descending white matter pathways, is the principal system for conveying sensory and motor information, connecting frontal and sensorimotor regions with ventral regions of the central nervous system. The corticospinal tract (CST), one of the principal projection pathways, carries distal movement-related information from the cortex to the spinal cord, and whether its microstructure is linked to the kinematics of hand movements is still an open question. The aim of the present study was to explore how microstructure of descending branches of the projection system, namely the hand motor tract (HMT), the corticospinal tract (CST) and its sector within the internal capsule (IC), can relate to the temporal profile of reaching and reach-to-grasp movements. Projection pathways of 31 healthy subjects were virtually dissected by means of diffusion tractography and the kinematics of reaching and reach-to-grasp movements were also analyzed. A positive association between Hindrance Modulated Orientation Anisotropy (HMOA) and kinematics was observed, suggesting that anisotropy of the considered tract can influence the temporal unfolding of motor performance. We highlight, for the first time, that hand kinematics and the visuomotor transformation processes underlying reaching and reach-to-grasp movements relate to the microstructure of specific projection fibers subserving these movements.
COVID-GWAB: A Web-Based Prediction of COVID-19 Host Genes via Network Boosting of Genome-Wide Association Data
Authors: Baek Seungbyn , Yang Sunmo , Lee Insuk
Published: October 2022

Host genetics affect both the susceptibility and response to viral infection. Searching for host genes that contribute to COVID-19, the Host Genetics Initiative (HGI) was formed to investigate the genetic factors involved in COVID-19 via genome-wide association studies (GWAS). The GWAS suffer from limited statistical power and in general, only a few genes can pass the conventional significance thresholds. This statistical limitation may be overcome by boosting weak association signals through integrating independent functional information such as molecular interactions. Additionally, the boosted results can be evaluated by various independent data for further connections to COVID-19. We present COVID-GWAB, a web-based tool to boost original GWAS signals from COVID-19 patients by taking the signals of the interactome neighbors. COVID-GWAB takes summary statistics from the COVID-19 HGI or user input data and reprioritizes candidate host genes for COVID-19 using HumanNet, a co-functional human gene network. The current version of COVID-GWAB provides the pre-processed data of releases 5, 6, and 7 of the HGI. Additionally, COVID-GWAB provides web interfaces for a summary of augmented GWAS signals, prediction evaluations by appearance frequency in COVID-19 literature, single-cell transcriptome data, and associated pathways. The web server also enables browsing the candidate gene networks.
STAT3 Inhibitors: A Novel Insight for Anticancer Therapy of Pancreatic Cancer
Authors: Li Xin , Jiang Wenkai , Dong Shi , Li Wancheng , Zhu Weixiong , Zhou Wence
Published: October 2022

The signal transducer and activator of transcription (STAT) is a family of intracellular cytoplasmic transcription factors involved in many biological functions in mammalian signal transduction. Among them, STAT3 is involved in cell proliferation, differentiation, apoptosis, and inflammatory responses. Despite the advances in the treatment of pancreatic cancer in the past decade, the prognosis for patients with pancreatic cancer remains poor. STAT3 has been shown to play a pro-cancer role in a variety of cancers, and inhibitors of STAT3 are used in pre-clinical and clinical studies. We reviewed the relationship between STAT3 and pancreatic cancer and the latest results on the use of STAT3 inhibitors in pancreatic cancer, with the aim of providing insights and ideas around STAT3 inhibitors for a new generation of chemotherapeutic modalities for pancreatic cancer.
Involuntary Breathing Movement Pattern Recognition and Classification via Force-Based Sensors
Authors: Singh Rajat , Fleury Jordan , Gupta Sonu , Bachman Nate , Alumbaugh Brent , White Gannon
Published: October 2022

The study presents a novel scheme that recognizes and classifies different sub-phases within the involuntary breathing movement (IBM) phase during breath-holding (BH). We collected force data from eight recreational divers until the conventional breakpoint (CB). They were in supine positions on force plates. We segmented their data into no-movement (NM) phases, i.e., the easy phase (EP) and IBM phase (comprising several events or sub-phases of IBM). Acceleration and jerk were estimated from the data to quantify the IBMs, and phase portraits were developed to select and extract specific features. K means clustering was performed on these features to recognize different sub-phases within the IBM phase. We found five–six optimal clusters separating different sub-phases within the IBM phase. These clusters separating different sub-phases have physiological relevance to internal struggles and were labeled as classes for classification using support vector machine (SVM), naive Bayes (NB), decision tree (DT), and K-nearest neighbor (K-NN). In comparison with no feature selection and extraction, we found that our phase portrait method of feature selection and extraction had low computational costs and high robustness of 96–99% accuracy.
Analysis of the Results of Severe Intraepithelial Squamous Cell Lesions and Preinvasive Cervical Cancer Phototheranostics in Women of Reproductive Age
Authors: Gilyadova Aida , Ishchenko Anton , Ishenko Anatoly , Samoilova Svetlana , Shiryaev Artem , Kiseleva Alevtina , Petukhova Natalya , Efendiev Kanamat , Alekseeva Polina , Stranadko Evgeny , Loschenov Victor , Reshetov Igor
Published: October 2022

(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22–49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients.
Intensive Periodontal Treatment Does Not Affect the Lipid Profile and Endothelial Function of Patients with Type 2 Diabetes: A Randomized Clinical Trial
Authors: Rapone Biagio , Ferrara Elisabetta , Qorri Erda , Quadri Mir Faeq Ali , Dipalma Gianna , Mancini Antonio , Del Fabbro Massimo , Scarano Antonio , Tartaglia Gianluca , Inchingolo Francesco
Published: October 2022

Background: Local eradication of periodontal infection could potentially have a much broader impact on the diabetic condition by also contributing to the modification of the lipid profile, which is directly compromised in the alteration of endothelium-dependent vasodilation. The aim of this trial was to assess the benefits of intensive periodontal treatment (IPT) on the lipid profile and endothelial function of diabetic patients. Methods: This was a 6-month, randomized controlled trial involving diabetic patients with generalized periodontitis. The study group comprised 290 individuals who were randomly assigned to receive Intensive Periodontal Treatment (IPT, Intervention Group) or conventional adult prophylaxis (Control Periodontal Treatment, CPT, Control Group). Outcomes encompassed lipid profile involving serum total cholesterol, serum triglyceride, low-density lipoprotein cholesterol, high-density lipo-protein cholesterol, and flow-mediated vasodilation (FMD) as an index of endothelium-dependent vasodilation (primary outcomes); periodontal indices and high-sensitive C-reactive protein were evaluated at baseline, 3 and 6 months after periodontal treatment. Results: An increase in endothelium-dependent flow-mediated dilatation (FMD) was observed in the Intensive Periodontal Treatment group in comparison with Control (p < 0.001), but results are not statistically different. There were no differences in lipid profile in individuals of both groups. Conclusions: An intensive periodontal treatment might improve endothelial function, suggesting a direct beneficial effect on the vasculature, possibly mediated by systemic inflammatory reduction. However, no statistically significant differences between groups were observed, and no benefits were proved on lipid profile.
Early Effects of Nivolumab and Ipilimumab Combined Immunotherapy in the Treatment of Metastatic Melanoma in Poland: A Multicenter Experience
Authors: Pacholczak-Madej Renata , Grela-Wojewoda Aleksandra , Puskulluoglu Mirosława , Lompart Joanna , Las-Jankowska Manuela , Krawczak Katarzyna , Wrona Ewa , Zaręba Lech , Żubrowska Justyna , Walocha Jerzy , Bazan-Socha Stanisława , Ziobro Marek
Published: October 2022

Nivolumab and ipilimumab combination became the first-line standard in advanced melanoma. We assessed its efficacy in a real-life study in Poland. In a one-year follow-up, we evaluated the medical records of 50 melanoma patients treated with that modality in five oncology centers. We recorded therapy outcomes and adverse events (AEs) after 3 and 12 months of therapy. At the first checkpoint, the disease control rate (DCR) was recorded in 58% (n = 29) of patients, but the same number of patients (n = 29, 58%) stopped immunotherapy due to disease progression (PD, n = 14, 48.3%), toxicity (n = 11, 37.9%) or death (n = 4, 13.8%). Among patients with DCR after the induction phase, 8 (27.6%) terminated due to toxicity, and 21 (72.4%) continued. However, at the 12-month checkpoint, only 14 patients (27% of all) were still receiving immunotherapy. In 7 (33.3%) it was discontinued due to PD (n = 2), toxicity (n = 2, 28.6% each), or death (n = 3, 42.9%). AEs occurred in 66.7% (n = 34) of patients; severe (grade 3 or 4) in half of them. Interestingly, those with AEs had an 80% lower risk of death (hazard ratio [HR] 0.2, 95% confidence interval [CI] 0.07–0.57, p = 0.001) and PD (HR 0.2, 95%CI 0.09–0.47, p < 0.0001). In the entire group of patients, after a 12-month follow-up, the median overall survival was not reached (NR, range: 6.8 months-NR) and progression-free survival was 6.3 (range: 3-NR) months. Our results demonstrate that combined immunotherapy is less effective in real-life than in pivotal trials. However, early responders will likely continue the therapy after a one-year follow-up. AEs occurrence might be a predictor of clinical effectiveness.
Design and Fabrication of α-MnO2-Nanorods-Modified Glassy-Carbon-Electrode-Based Serotonin Sensor
Authors: Khan Mohd Quasim , Khan Rais Ahmad , Alsalme Ali , Ahmad Khursheed , Kim Haekyoung
Published: October 2022

Serotonin is a very important monoamine neurotransmitter, which takes part in biological and psychological processes. In the present scenario, design and fabrication of a serotonin electrochemical sensor is of great significance. In this study, we have synthesized α-MnO2 via a hydrothermal synthesis method using potassium permanganate as a precursor. The physiochemical properties, such as structural and phase-purity of the prepared α-MnO2, were investigated by various characterization techniques and methods (powder X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy). Furthermore, the serotonin sensor was fabricated using α-MnO2 as an electrode modifier or electro-catalyst. The bare glassy carbon electrode (GCE) was adopted as a working substrate, and its active carbon surface was modified with the synthesized α-MnO2. This modified GCE (α-MnO2/GCE = MGCE) was explored as a serotonin sensor. The electrochemical investigations showed that the MGCE has excellent electro-catalytic properties towards determination of serotonin. The MGCE exhibits an excellent detection limit (DL) of 0.14 µM, along with good sensitivity of 2.41 µAµM−1 cm−2. The MGCE also demonstrated excellent selectivity for determination of serotonin in the presence of various electro-active/interfering molecules. The MGCE also exhibits good cyclic repeatability, stability, and storage stability.
An Exploratory Study about the Characterization of Caffeine Consumption in a Portuguese Sample
Authors: Batista Patrícia , Peixoto João , Oliveira-Silva Patrícia
Published: October 2022

Caffeine is one of the most used psychoactive substances worldwide, with an impact in multiple spheres (individual, social, and economic). In addition, there is evidence of the physiological, cognitive, and emotional effects after consumption. This study aimed to examine caffeine consumption in a Portuguese sample by characterizing and understanding the pattern of consumption and the reasons for it. The sample was composed of 208 subjects recruited through the university’s social media channels to answer an online questionnaire between April and June 2020. The results showed a higher consumption in males and the group of subjects aged between 31 and 35 years. The coffee “express” is the most consumed source of caffeine in this Portuguese sample (70.2%). The data showed that improvement in alertness and the taste of products with caffeine were the main reasons for consuming caffeinated products. In conclusion, this study calls attention to the characterization of caffeine consumption to understand the need for such consumption and its effects on body functions and health. It is important to highlight the potential benefit of caffeine consumption due to its impact on the quality of life and health since this substance has effects not only on physical and mental health but also on social well-being.
Barriers to Adopting Lean Construction in Small and Medium-Sized Enterprises—The Case of Peru
Authors: Huaman-Orosco Cristian , Erazo-Rondinel Andrews A. , Herrera Rodrigo F.
Published: October 2022

The competitiveness in the construction industry is leading companies to implement the Lean philosophy to improve project management and prepare to begin the adoption of Construction 4.0. However, this implementation generates several barriers, depending on the type of company and the country where it is implemented. For this reason, the following research aims to identify the barriers generated in implementing the Lean philosophy in Peru and SMEs. The following study began with a literature review, followed by a questionnaire, which six Lean experts evaluated. Then, 127 Peruvian professionals answered the survey, and the data were analyzed with RII and Exploratory Factor Analysis. As a result, the barriers to Lean Construction were grouped into four groups to analyze their impact on the industry: collaboration, education and implementation, organizational vision and system; Lean theory and philosophy; and Lean tools, coordination, and information flow. Barriers were also analyzed by project type, stage, and organization size to conclude that implementation barriers are directly related to company size. Finally, the obtained barriers are discussed, and Construction 4.0 is proposed to reduce their impact on construction projects. These results can be helpful for implementers to plan strategies, improve knowledge about Lean Construction implementation, and adopt new techniques that could help improve the construction industry’s productivity.
Novel Therapies for Unmet Clinical Needs in Myelodysplastic Syndromes
Authors: Cassanello Giulio , Pasquale Raffaella , Barcellini Wilma , Fattizzo Bruno
Published: October 2022

Myelodysplastic syndromes (MDS) are a very heterogeneous disease, with extremely variable clinical features and outcomes. Current management relies on risk stratification based on IPSS and IPSS-R, which categorizes patients into low (LR-) and high-risk (HR-) MDS. Therapeutic strategies in LR-MDS patients mainly consist of erythropoiesis stimulating agents (ESAs), transfusion support, and luspatercept or lenalidomide for selected patients. Current unmet needs include the limited options available after treatment failure, and the consequent transfusion burden with several hospital admissions and poor quality of life. Therapeutic approaches in HR-MDS patients are aimed at changing the natural course of the disease and hypometylating agents (HMA) are the first choice. The only potentially curative treatment is allogeneic stem cell transplant (allo-HCT), restricted to a minority of young and fit candidates. Patients unfit for or those that relapse after the abovementioned options harbor an adverse prognosis, with limited overall survival and frequent leukemic evolution. Recent advances in genetic mutations and intracellular pathways that are relevant for MDS pathogenesis are improving disease risk stratification and highlighting therapeutic targets addressed by novel agents. Several drugs are under evaluation for LR and HR patients, which differ by their mechanism of action, reported efficacy, and phase of development. This review analyzes the current unmet clinical needs for MDS patients and provides a critical overview of the novel agents under development in this setting.