bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeptical Learning—An Algorithm and a Platform for Dealing with Mislabeling in Personal Context Recognition
Authors: Zhang Wanyi , Zeni Mattia , Passerini Andrea , Giunchiglia Fausto
Published: March 2022

Mobile Crowd Sensing (MCS) is a novel IoT paradigm where sensor data, as collected by the user’s mobile devices, are integrated with user-generated content, e.g., annotations, self-reports, or images. While providing many advantages, the human involvement also brings big challenges, where the most critical is possibly the poor quality of human-provided content, most often due to the inaccurate input from non-expert users. In this paper, we propose Skeptical Learning, an interactive machine learning algorithm where the machine checks the quality of the user feedback and tries to fix it when a problem arises. In this context, the user feedback consists of answers to machine generated questions, at times defined by the machine. The main idea is to integrate three core elements, which are (i) sensor data, (ii) user answers, and (iii) existing prior knowledge of the world, and to enable a second round of validation with the user any time these three types of information jointly generate an inconsistency. The proposed solution is evaluated in a project focusing on a university student life scenario. The main goal of the project is to recognize the locations and transportation modes of the students. The results highlight an unexpectedly high pervasiveness of user mistakes in the university students life project. The results also shows the advantages provided by Skeptical Learning in dealing with the mislabeling issues in an interactive way and improving the prediction performance.
A Variable Step Size Normalized Least-Mean-Square Algorithm Based on Data Reuse
Authors: Rusu Alexandru-George , Paleologu Constantin , Benesty Jacob , Ciochină Silviu
Published: March 2022

The principal issue in acoustic echo cancellation (AEC) is to estimate the impulse response between the loudspeaker and microphone of a hands-free communication device. This application can be addressed as a system identification problem, which can be solved by using an adaptive filter. The most common one for AEC is the normalized least-mean-square (NLMS) algorithm. It is known that the overall performance of this algorithm is controlled by the value of its normalized step size parameter. In order to obtain a proper compromise between the main performance criteria (e.g., convergence rate/tracking versus accuracy/robustness), this specific term of the NLMS algorithm can be further controlled and designed as a variable parameter. This represents the main motivation behind the development of variable step size algorithms. In this paper, we propose a variable step size NLMS (VSS-NLMS) algorithm that exploits the data reuse mechanism, which aims to improve the convergence rate/tracking of the algorithm by reusing the same set of data (i.e., the input and reference signals) several times. Nevertheless, we involved an equivalent version of the data reuse NLMS, which provides the convergence modes of the algorithm. Based on this approach, a sequence of normalized step sizes can be a priori scheduled, which is advantageous in terms of the computational complexity. The simulation results in the context of AEC supported the good performance features of the proposed VSS-NLMS algorithm.
An Investigation into the Flow of Rotating Orifices with Euler Angle and the Calculation Model of Discharge Coefficient Considering the Effect of Comprehensive Incidence Angle
Authors: Wang Jie , Liu Peng , Qiu Tian , Ding Shuiting
Published: March 2022

As a typical flow element in an aero-engines, orifices play a vital role in the distribution and control of the mass flow rate within the secondary air system. In particular, rotating orifices with complex geometry (Euler angles) may significantly vary the discharge coefficients. Understanding the discharge coefficients of these orifices may guarantee a more reasonable distribution of the internal flow within the air system. This contributes to the safety, reliability, and structural integrity of the aero-engine under the all-inclusive line. In this paper, the flow state within the orifice and the discharge coefficient have been studied under the condition of different Euler angles (α0=0–30° and β0=0–30°) and rotational speeds (0–10,000 r/min). The comprehensive incidence angle is proposed to describe the combined effect of Euler angles and rotation. The correlation between the discharge coefficient and the comprehensive incidence angle is also given. At the same time, a general calculation model of the orifices is established considering the effect of the comprehensive incidence angle. The results indicate that the effects of the circumferential inclination angle, radial inclination angle, and rotation may be more clearly expressed by the comprehensive incidence angle. The larger discharge coefficient is obtained when the comprehensive incidence angle is close to 0, and under the fixed rotational speed and flow condition, the maximum discharge coefficient can be obtained by arranging the appropriate Euler angle for the orifice. Compared with the experimental results in the published literature, the calculation results of the model have an overall error of less than 6%. The calculation accuracy is high enough for the one-dimensional simulation of the secondary air system.
Grocery Waste Compost as an Alternative Hydroponic Growing Medium
Authors: Moschou Christina Emmanouela , Papadimitriou Dimitrios M. , Galliou Fenia , Markakis Nikolaos , Papastefanakis Nikolaos , Daskalakis Georgios , Sabathianakis Michael , Stathopoulou Eugenia , Bouki Chryssa , Daliakopoulos Ioannis N. , Manios Thrassyvoulos
Published: March 2022

Modern hydroponic substrates have contributed significantly to the popularity and progress of hydroponic cultivations worldwide, nevertheless, their development, transportation, and disposal often come at a significant environmental cost. Here we investigate the feasibility of partial to total replacement of conventional organic growing media constituents, such as cocodust (C), in a 20% perlite (P) and 80% cocodust substrate (hereafter control 8C), with compost from locally sourced grocery waste (W). For this purpose, four treatment mixtures were developed (6C:2W, 4C:4W, 2C:6W, 8W), with the grocery waste-compost fraction ranging from 20 to 80%, respectively (perlite constant at 20%). The new substrates were tested on hydroponic lettuce (Lactuca sativa var. Tanius) cultivation. During the 35-day experiment, lettuce physiology was evaluated using chlorophyll concentration [SPAD], chlorophyll fluorescence [Fv/Fm], number of leaves, and plant growth index. At harvest, the plant yield was evaluated using leaf area [cm2], leaf fresh and dry weight [g], as well as leaf firmness [g]. Results show that substrates with compost led to superior physiology and yield characteristics, with 8W inducing a significant increase in leaf area, chlorophyll concentration, dry weight, and firmness, by 11.6%, 5.4%, 19.8% and 12.8%, respectively, compared to the control treatment 8C. Results indicate that grocery waste-based compost is an excellent sustainable alternative for the soilless cultivation of lettuce. After its use in hydroponic cultivation, substrate material is safe to dispose of or be used as a soil amendment, thus contributing to a circular agro-food economy model.
Analysis of pH and Electrolytes in Blood and Electrolytes in Ruminal Fluid, including Kidney Function Tests, in Sheep Undergoing General Anaesthesia for Laparotomy
Authors: Grimm Lucie Marie , Ganter Martin
Published: March 2022

Background: Performing Sectio Caesarea in sheep under general anaesthesia is a common procedure in veterinary practice. The abdominal cavity can be accessed via linea alba, for which the ewe is positioned in the supine position, whereby rumen and uterus can compromise lung function. Although the rumen represents an important reservoir for fluid and electrolytes, and kidney function during anaesthesia is essential, these parameters have not been focused on in research. Therefore, the objective of this study is to contribute data on blood parameters, ruminal fluid, and kidney function tests during laparotomy. Methods: Laparotomy was performed in 14 ewes, whereof five animals were pregnant ewes (PE) and nine non-pregnant ewes (NPE). A total of seven animals received isoflurane in addition to oxygen (inhalational anaesthesia (InhA)) and seven ewes were anaesthetised with xylazine and ketamine (total intravenous anaesthesia (TIVA)); all ewes received lumbosacral anaesthesia. Blood, urine, and ruminal fluid were sampled every hour over a three-hour period. Results: On comparing InhA to TIVA, higher values were detected for TIVA in haemoglobin, paced cell volume, sodium, phosphate, glucose concentration in the blood, and phosphate in ruminal fluid. Lower values were detected for TIVA in partial pressure of oxygen, oxygen saturation, and creatinine clearance. On comparing PE to NPE, higher values were detected in PE in magnesium and ruminal calcium. Lower values in PE were detected in chloride, base excess in the blood, and ruminal phosphate. Over time, an increase in partial pressure of carbon dioxide, glucose in the blood, glucose in urine, and a decrease in protein and albumin could be observed. Conclusion: Surgery in sheep in the supine position should be performed with additional oxygen to maintain physiological pO2 and sO2 values. Kidney function could be maintained with a minimal electrolyte infusion regime. Additional glucose is not necessary, even in pregnant ewes. Further research should be conducted on parameters in ruminal fluid.
Biosynthesis and Chemical Synthesis of Albomycin Nucleoside Antibiotics
Authors: Wang Meiyan , Zhang Yuxin , Lv Lanxin , Kong Dekun , Niu Guoqing
Published: March 2022

The widespread emergence of antibiotic-resistant bacteria highlights the urgent need for new antimicrobial agents. Albomycins are a group of naturally occurring sideromycins with a thionucleoside antibiotic conjugated to a ferrichrome-type siderophore. The siderophore moiety serves as a vehicle to deliver albomycins into bacterial cells via a “Trojan horse” strategy. Albomycins function as specific inhibitors of seryl-tRNA synthetases and exhibit potent antimicrobial activities against both Gram-negative and Gram-positive bacteria, including many clinical pathogens. These distinctive features make albomycins promising drug candidates for the treatment of various bacterial infections, especially those caused by multidrug-resistant pathogens. We herein summarize findings on the discovery and structure elucidation, mechanism of action, biosynthesis and immunity, and chemical synthesis of albomcyins, with special focus on recent advances in the biosynthesis and chemical synthesis over the past decade (2012–2022). A thorough understanding of the biosynthetic pathway provides the basis for pathway engineering and combinatorial biosynthesis to create new albomycin analogues. Chemical synthesis of natural congeners and their synthetic analogues will be useful for systematic structure–activity relationship (SAR) studies, and thereby assist the design of novel albomycin-derived antimicrobial agents.
Antibiotic Prescribing in Connection to Childbirth: An Observational Study in Two Districts in Lao PDR
Authors: Yan Weirong , Machowska Anna , Sihavong Amphoy , Sychareun Vanphanom , Chaleunvong Kongmany , Keohavong Bounxou , Eriksen Jaran , Hanson Claudia , Vongsouvath Manivanh , Brauner Annelie , Mayxay Mayfong , Kounnavong Sengchanh , Stålsby Lundborg Cecilia
Published: March 2022

Overuse and misuse of antibiotics has frequently been reported for obstetric conditions and procedures, which may impact both the mother and the unborn baby and increase antibiotic resistance. This study aimed to investigate the antibiotic prescribing pattern in connection to childbirth in two districts in Lao PDR. It is a cross-sectional observational study. Antibiotic prescription data related to childbirth was collected via reviews of medical records in two district hospitals and five health centers in Lao PDR from September 2019 to November 2020. In total, antibiotic prescription data for 1777 women were extracted from their medical records. It was found that all women received antibiotics during in-patient care irrespective of delivery mode. When in hospital, 85.5% of the women who underwent a caesarean section got antibiotic treatment for 5 days and women who had a vaginal delivery usually had antibiotic treatment for one day or less. All the women got oral antibiotics for an additional 4–5 days upon discharge. Antibiotic prescription rate in connection to childbirth was very high in comparison with the WHO guidelines, and antibiotics were used extensively in the participating health facilities. Interventions to guide appropriate prescribing behavior in relation to childbirth are urgently needed in Lao PDR.
Neurodegenerative Disease Treatment Drug PBT2 Breaks Intrinsic Polymyxin Resistance in Gram-Positive Bacteria
Authors: De Oliveira David M. P. , Keller Bernhard , Hayes Andrew J. , Ong Cheryl-Lynn Y. , Harbison-Price Nichaela , El-Deeb Ibrahim M. , Li Gen , Keller Nadia , Bohlmann Lisa , Brouwer Stephan , Turner Andrew G. , Cork Amanda J. , Jones Thomas R. , Paterson David L. , McEwan Alastair G. , Davies Mark R. , McDevitt Christopher A. , Itzstein Mark von , Walker Mark J.
Published: March 2022

Gram-positive bacteria do not produce lipopolysaccharide as a cell wall component. As such, the polymyxin class of antibiotics, which exert bactericidal activity against Gram-negative pathogens, are ineffective against Gram-positive bacteria. The safe-for-human-use hydroxyquinoline analog ionophore PBT2 has been previously shown to break polymyxin resistance in Gram-negative bacteria, independent of the lipopolysaccharide modification pathways that confer polymyxin resistance. Here, in combination with zinc, PBT2 was shown to break intrinsic polymyxin resistance in Streptococcus pyogenes (Group A Streptococcus; GAS), Staphylococcus aureus (including methicillin-resistant S. aureus), and vancomycin-resistant Enterococcus faecium. Using the globally disseminated M1T1 GAS strain 5448 as a proof of principle model, colistin in the presence of PBT2 + zinc was shown to be bactericidal in activity. Any resistance that did arise imposed a substantial fitness cost. PBT2 + zinc dysregulated GAS metal ion homeostasis, notably decreasing the cellular manganese content. Using a murine model of wound infection, PBT2 in combination with zinc and colistin proved an efficacious treatment against streptococcal skin infection. These findings provide a foundation from which to investigate the utility of PBT2 and next-generation polymyxin antibiotics for the treatment of Gram-positive bacterial infections.
Dynamic Properties of Calcareous Sands from Urban Areas of Abu Dhabi
Authors: Khalil Ahmed , Khan Zahid Hamid , Attom Mousa , El Emam Magdi , Fattah Kazi
Published: March 2022

Abu Dhabi (ABD) has recently developed its national building code that mandates dynamic analysis of large structures to seismic loadings. Large strain dynamic properties such as shear modulus (G) and damping ratio (D) of local undisturbed calcareous sands are not available. Designers are compelled to choose degradation models from studies on calcareous sands of other regions that are usually reconstituted. This research presents for the first time large strain dynamic properties of calcareous sands of urban ABD. Undisturbed samples are collected from different areas of urban ABD and are tested in cyclic triaxial (CT) devices fitted with bender elements (BE). The dynamic properties as functions of confinement are curve fitted with power models, whereas their variation with shear strain level is curve fitted with hyperbolic models. The results are compared with findings of previous studies on calcareous and silica sands. The results indicate that dynamic properties of all samples degrade with shear strain at almost the same rate irrespective of their spatial distribution. The proposed degradation models can therefore be used in dynamic analyses. The results from this study show smaller rates of degradation in dynamic properties compared to other studies on similar sands. The change in low-strain shear wave velocity (Vs) with confinement is significant among the tested samples; therefore, a site-specific evaluation of Vs is recommended. The dynamic properties of calcareous sands of ABD and previous studies however exhibit larger degradation with shear strain and a smaller increase in confinement compared to silica sands.
Modulation Format Identification in a Satellite to Ground Optical Wireless Communication Systems Using a Convolution Neural Network
Authors: Gu Yucong , Wu Zhiyong , Li Xueliang , Tian Ruotong , Ma Shuang , Jia Tao
Published: March 2022

The satellite-to-ground communication system is a significant part of future space communication networks. The free-space optical (FSO) communication technique is a prospective solution for satellite-to-ground communication. However, atmospheric optical turbulence is a major impairment in FSO communication systems. In this paper, to improve the performance and flexibility of a satellite-to-ground laser communication system, we put forward a novel modulation format identification (MFI) technique for an FSO communication system based on a convolution neural network (CNN). The results indicate that our CNN model can blindly and accurately identify the modulation format with classification accuracy up to 99.98% for random channel condition, including the strength of turbulence and signal-to-noise ratio (SNR) of additive Gaussian white noise (AWGN) ranging from 10dB to 30dB. Moreover, the CNN demonstrated robustness against atmospheric optical turbulence and suggested immunity to additive noise. Therefore, the proposed methodology proved to be a viable solution in the application of an FSO communication simulation channel, which can easily deal with the scene of fast modulation format switching and accurate identification to satisfy system requirements. Therefore, we hope this scheme can find a practical implementation in satellite-to-ground optical wireless systems.
Effects of New Tunnelling on a Buried Pipeline with Joints and Its Detachment
Authors: Dong Ye , Liu Xiang , Zhang Rui , Yang Chengyong
Published: March 2022

The interactions between the buried pipeline and tunnelling-induced ground movement are studied in this paper, in which the jointed pipeline, Pasternak foundation, and the detachment are considered. A mathematical model using the pulse function is provided to simplify the jointed pipeline to a continuous pipeline with additional local rotations. The determination of detachment is used by the usual iteration method. The finite difference method is utilized to obtain the numerical results. The results calculated by our proposed method agree with the experimental data of centrifuge tests and are close to those obtained by the other methods. The deflection and bending moment of the jointed pipeline can be predicted reasonably, as well as its detachment location. Parametric analyses about the main influencing factors are carried out. The stiffness reduction factor is significant to the discontinuous behavior of the jointed pipeline. During the parametric analyses, the detachment beneath the jointed pipeline sometimes happens and sometimes does not. The responses of the jointed pipeline and its detachment require priority attention.
Low-Latitude Ionospheric Responses and Coupling to the February 2014 Multiphase Geomagnetic Storm from GNSS, Magnetometers, and Space Weather Data
Authors: Calabia Andres , Anoruo Chukwuma , Shah Munawar , Amory-Mazaudier Christine , Yasyukevich Yury , Owolabi Charles , Jin Shuanggen
Published: March 2022

The ionospheric response and the associated mechanisms to geomagnetic storms are very complex, particularly during the February 2014 multiphase geomagnetic storm. In this paper, the low-latitude ionosphere responses and their coupling mechanisms, during the February 2014 multiphase geomagnetic storm, are investigated from ground-based magnetometers and global navigation satellite system (GNSS), and space weather data. The residual disturbances between the total electron content (TEC) of the International GNSS Service (IGS) global ionospheric maps (GIMs) and empirical models are used to investigate the storm-time ionospheric responses. Three clear sudden storm commencements (SSCs) on 15, 20, and 23 February are detected, and one high speed solar wind (HSSW) event on 19 February is found with the absence of classical SSC features due to a prevalent magnetospheric convection. The IRI-2012 shows insufficient performance, with no distinction between the events and overestimating approximately 20 TEC units (TECU) with respect to the actual quiet-time TEC. Furthermore, the median average of the IGS GIMs TEC during February 2014 shows enhanced values in the southern hemisphere, whereas the IRI-2012 lacks this asymmetry. Three low-latitude profiles extracted from the IGS GIM data revealed up to 20 TECU enhancements in the differential TEC. From these profiles, longer-lasting TEC enhancements are observed at the dip equator profiles than in the profiles of the equatorial ionospheric anomaly (EIA) crests. Moreover, a gradual increase in the global electron content (GEC) shows approximately 1 GEC unit of differential intensification starting from the HSSW event, while the IGS GIM profiles lack this increasing gradient, probably located at higher latitudes. The prompt penetration electric field (PPEF) and equatorial electrojet (EEJ) indices estimated from magnetometer data show strong variability after all four events, except the EEJ’s Asian sector. The low-latitude ionosphere coupling is mainly driven by the variable PPEF, DDEF (disturbance dynamo electric fields), and Joule heating. The auroral electrojet causing eastward PPEF may control the EIA expansion in the Asian sector through the dynamo mechanism, which is also reflected in the solar-quiet current intensity variability.
Prediction of Pulmonary Function Parameters Based on a Combination Algorithm
Authors: Zhou Ruishi , Wang Peng , Li Yueqi , Mou Xiuying , Zhao Zhan , Chen Xianxiang , Du Lidong , Yang Ting , Zhan Qingyuan , Fang Zhen
Published: March 2022

Objective: Pulmonary function parameters play a pivotal role in the assessment of respiratory diseases. However, the accuracy of the existing methods for the prediction of pulmonary function parameters is low. This study proposes a combination algorithm to improve the accuracy of pulmonary function parameter prediction. Methods: We first established a system to collect volumetric capnography and then processed the data with a combination algorithm to predict pulmonary function parameters. The algorithm consists of three main parts: a medical feature regression structure consisting of support vector machines (SVM) and extreme gradient boosting (XGBoost) algorithms, a sequence feature regression structure consisting of one-dimensional convolutional neural network (1D-CNN), and an error correction structure using improved K-nearest neighbor (KNN) algorithm. Results: The root mean square error (RMSE) of the pulmonary function parameters predicted by the combination algorithm was less than 0.39L and the R2 was found to be greater than 0.85 through a ten-fold cross-validation experiment. Conclusion: Compared with the existing methods for predicting pulmonary function parameters, the present algorithm can achieve a higher accuracy rate. At the same time, this algorithm uses specific processing structures for different features, and the interpretability of the algorithm is ensured while mining the feature depth information.
Enhanced Cytotoxic Effects in Human Oral Squamous Cell Carcinoma Cells Treated with Combined Methyltransferase Inhibitors and Histone Deacetylase Inhibitors
Authors: Ushio Ryosuke , Hiroi Miki , Matsumoto Ari , Mori Kazumasa , Yamamoto Nobuharu , Ohmori Yoshihiro
Published: March 2022

Combined treatment of human oral squamous cell carcinoma (OSCCs) with DNA methyltransferase inhibitors (DNMTis), histone methyltransferase inhibitors (HMTis), and histone deacetylase inhibitors (HDACis), and the molecular mechanisms underlying their anticancer effects, have not been fully elucidated. Herein, we investigated the cytotoxic effects of combined DNMTis (5-Aza-deoxycytidine: 5-Aza-dC, RG108), HMTis (3-deazaneplanocin A: DZNep), and HDACis (trichostatin A: TSA) treatment on human OSCC cells and explored their molecular mechanisms. Combined 5-Aza-dC, or RG108, and TSA treatment significantly decreased HSC-2 and Ca9-22 cell viability. Combinatorial DZNep and TSA treatment also decreased Ca9-22 cell viability. Although caspase 3/7 activation was not observed in HSC-2 cells following combined treatment, caspase activity was significantly increased in Ca9-22 cells treated with DZNep and TSA. Moreover, combined treatment with 5-Aza-dC, RG108, and TSA increased the proportion of HSC-2 and Ca9-22 cells in the S and G2/M phases. Meanwhile, increased phosphorylation of the histone variant H2A.X, a marker of double-stranded DNA breaks, was observed in both cells after combination treatment. Hence, the decreased viability induced by combined treatment with epigenomic inhibitors results from apoptosis and cell cycle arrest in S and G2/M phases. Thus, epigenomic therapy comprising combined low concentrations of DNMTi, HMTi, and HDACi is effective against OSCC.
Role of Serotonin in the Maintenance of Inflammatory State in Crohn’s Disease
Authors: Pergolizzi Simona , Alesci Alessio , Centofanti Antonio , Aragona Marialuisa , Pallio Socrate , Magaudda Ludovico , Cutroneo Giuseppina , Lauriano Eugenia Rita
Published: March 2022

Crohn’s disease (CD) is a chronic intestinal inflammation considered to be a major entity of inflammatory bowel diseases (IBDs), affecting different segments of the whole gastrointestinal tract. Peripheral serotonin (5-HT), a bioactive amine predominantly produced by gut enterochromaffin cells (ECs), is crucial in gastrointestinal functions, including motility, sensitivity, secretion, and the inflammatory response. These actions are mediated by a large family of serotonin receptors and specialized serotonin transporter (SERT) located on a variety of cell types in the gut. Several studies indicate that intestinal 5-HT signaling is altered in patients with inflammatory bowel disease. Paraformaldehyde-fixed intestinal tissues, obtained from fifteen patients with Crohn’s disease were analyzed by immunostaining for serotonin, Langerin/CD207, and alpha-Smooth Muscle Actin (α-SMA). As controls, unaffected (normal) intestinal specimens of seven individuals were investigated. This study aimed to show the expression of serotonin in dendritic cells (DCs) and myofibroblast which have been characterized with Langerin/CD207 and α-SMA, respectively; furthermore, for the first time, we have found the presence of serotonin in goblet cells. Our results show the correlation between different types of intestinal cells in the maintenance of the inflammatory state in CD linked to the recall of myofibroblasts.
Bone Cell Exosomes and Emerging Strategies in Bone Engineering
Authors: Vig Sanjana , Fernandes Maria Helena
Published: March 2022

Bone tissue remodeling is a highly regulated process balancing bone formation and resorption through complex cellular crosstalk between resident bone and microenvironment cells. This cellular communication is mediated by direct cell and cell–matrix contact, autocrine, endocrine, and paracrine receptor mediated mechanisms such as local soluble signaling molecules and extracellular vesicles including nanometer sized exosomes. An impairment in this balanced process leads to development of pathological conditions. Bone tissue engineering is an emerging interdisciplinary field with potential to address bone defects and disorders by synthesizing three-dimensional bone substitutes embedded with cells for clinical implantation. However, current cell-based therapeutic approaches have faced hurdles due to safety and ethical concerns, challenging their clinical translation. Recent studies on exosome-regulated bone homeostasis and regeneration have gained interest as prospective cell free therapy in conjugation with tissue engineered bone grafts. However, exosome research is still in its nascent stages of bone tissue engineering. In this review, we specifically describe the role of exosomes secreted by cells within bone microenvironment such as osteoblasts, osteocytes, osteoclasts, mesenchymal stem cell cells, immune cells, endothelial cells, and even tumor cells during bone homeostasis and crosstalk. We also review exosome-based osteoinductive functionalization strategies for various bone-based biomaterials such as ceramics, polymers, and metals in bone tissue engineering. We further highlight biomaterials as carrier agents for exosome delivery to bone defect sites and, finally, the influence of various biomaterials in modulation of cell exosome secretome.
Molecular Basis for Paradoxical Activities of Polymorphonuclear Neutrophils in Inflammation/Anti-Inflammation, Bactericide/Autoimmunity, Pro-Cancer/Anticancer, and Antiviral Infection/SARS-CoV-II-Induced Immunothrombotic Dysregulation
Authors: Wu Tsai-Hung , Hsieh Song-Chou , Li Tsu-Hao , Lu Cheng-Hsun , Liao Hsien-Tzung , Shen Chieh-Yu , Li Ko-Jen , Wu Cheng-Han , Kuo Yu-Min , Tsai Chang-Youh , Yu Chia-Li
Published: March 2022

Polymorphonuclear neutrophils (PMNs) are the most abundant white blood cells in the circulation. These cells act as the fast and powerful defenders against environmental pathogenic microbes to protect the body. In addition, these innate inflammatory cells can produce a number of cytokines/chemokines/growth factors for actively participating in the immune network and immune homeostasis. Many novel biological functions including mitogen-induced cell-mediated cytotoxicity (MICC) and antibody-dependent cell-mediated cytotoxicity (ADCC), exocytosis of microvesicles (ectosomes and exosomes), trogocytosis (plasma membrane exchange) and release of neutrophil extracellular traps (NETs) have been successively discovered. Furthermore, recent investigations unveiled that PMNs act as a double-edged sword to exhibit paradoxical activities on pro-inflammation/anti-inflammation, antibacteria/autoimmunity, pro-cancer/anticancer, antiviral infection/COVID-19-induced immunothrombotic dysregulation. The NETs released from PMNs are believed to play a pivotal role in these paradoxical activities, especially in the cytokine storm and immunothrombotic dysregulation in the recent SARS-CoV-2 pandemic. In this review, we would like to discuss in detail the molecular basis for these strange activities of PMNs.
Isolating Action Prediction from Action Integration in the Perception of Social Interactions
Authors: Pesquita Ana , Bernardet Ulysses , Richards Bethany E. , Jensen Ole , Shapiro Kimron
Published: March 2022

Previous research suggests that predictive mechanisms are essential in perceiving social interactions. However, these studies did not isolate action prediction (a priori expectations about how partners in an interaction react to one another) from action integration (a posteriori processing of both partner’s actions). This study investigated action prediction during social interactions while controlling for integration confounds. Twenty participants viewed 3D animations depicting an action–reaction interaction between two actors. At the start of each action–reaction interaction, one actor performs a social action. Immediately after, instead of presenting the other actor’s reaction, a black screen covers the animation for a short time (occlusion duration) until a still frame depicting a precise moment of the reaction is shown (reaction frame). The moment shown in the reaction frame is either temporally aligned with the occlusion duration or deviates by 150 ms or 300 ms. Fifty percent of the action–reaction trials were semantically congruent, and the remaining were incongruent, e.g., one actor offers to shake hands, and the other reciprocally shakes their hand (congruent action–reaction) versus one actor offers to shake hands, and the other leans down (incongruent action–reaction). Participants made fast congruency judgments. We hypothesized that judging the congruency of action–reaction sequences is aided by temporal predictions. The findings supported this hypothesis; linear speed-accuracy scores showed that congruency judgments were facilitated by a temporally aligned occlusion duration, and reaction frames compared to 300 ms deviations, thus suggesting that observers internally simulate the temporal unfolding of an observed social interction. Furthermore, we explored the link between participants with higher autistic traits and their sensitivity to temporal deviations. Overall, the study offers new evidence of prediction mechanisms underpinning the perception of social interactions in isolation from action integration confounds.
The Impact of PD Check-In, a Model for Supported Self-Managed Maintenance of Speech on the Quality of Life of People with Parkinson’s Disease: A Phase 1 Study
Authors: Finnimore Ann , Theodoros Deborah , Rumbach Anna
Published: March 2022

Quality of life (QoL) for people with Parkinson’s Disease (PD) is diminished by speech and communication changes. The impact of PD Check-In, an intervention for supported self-managed maintenance of speech following LSVT LOUD®, on QoL of people with PD was investigated. Sixteen people with PD and dysarthria completed LSVT LOUD followed by PD Check-Ins up until 24 months post-treatment. Self-rated QoL and voice handicap scales were used to determine the psychosocial and perceived impact of PD Check-In on the speech and voice of people with PD. The perceived impact of PD Check-In on speech and voice was also sought from 15 communication partners (CPs). A significant treatment effect for time was identified for the Dysarthria Impact Profile (DIP), Voice Handicap Index (VHI), and Voice Handicap Index-Partner (VHI-P) (p < 0.05). There was no significant effect for time for the Parkinson’s Disease Questionnaire (PDQ-39). Planned comparisons of timepoints for DIP, VHI, and VHI-P showed no significant differences (p > 0.01). Comparison of perceived voice handicap by people with PD and CPs revealed no significant differences (p > 0.01). The impact of PD Check-In on QoL of people with PD and CPs for 24 months post-LSVT-LOUD is unclear. Self-reported outcome measures alone do not fully capture changes in QoL in PD.
Autocrine Neuromodulation and Network Activity Patterns in the Locus Coeruleus of Newborn Rat Slices
Authors: Waselenchuk Quinn , Ballanyi Klaus
Published: March 2022

Already in newborns, the locus coeruleus (LC) controls multiple brain functions and may have a complex organization as in adults. Our findings in newborn rat brain slices indicate that LC neurons (i) generate at ~1 Hz a ~0.3 s-lasting local field potential (LFP) comprising summated phase-locked single spike discharge, (ii) express intrinsic ‘pacemaker’ or ‘burster’ properties and (iii) receive solely excitatory or initially excitatory–secondary inhibitory inputs. μ-opioid or ɑ2 noradrenaline receptor agonists block LFP rhythm at 100–250 nM whereas slightly lower doses transform its bell-shaped pattern into slower crescendo-shaped multipeak bursts. GABAA and glycine receptors hyperpolarize LC neurons to abolish rhythm which remains though unaffected by blocking them. Rhythm persists also during ionotropic glutamate receptor (iGluR) inhibition whereas <10 mV depolarization during iGluR agonists accelerates spiking to cause subtype-specific fast (spindle-shaped) LFP oscillations. Similar modest neuronal depolarization causing a cytosolic Ca2+ rise occurs (without effect on neighboring astrocytes) during LFP acceleration by CNQX activating a TARP-AMPA-type iGluR complex. In contrast, noradrenaline lowers neuronal Ca2+ baseline via ɑ2 receptors, but evokes an ɑ1 receptor-mediated ‘concentric’ astrocytic Ca2+ wave. In summary, the neonatal LC has a complex (possibly modular) organization to enable discharge pattern transformations that might facilitate discrete actions on target circuits.
Decision-Making under Uncertainty: How Easterners and Westerners Think Differently
Authors: Guo Wei , Chen Xin-Rong , Liu Hu-Chen
Published: March 2022

It has long been known that Easterners exhibit more conservative attitudes, cautiousness behaviors, and self-control ability than Westerners; people in Eastern countries show stronger defensive reactions to societal threats than Western people. Are East Asians really risk averters or do some richer underlying preferences drive their behaviors in their decision-making under uncertainty? To answer this question, we examined the risk and ambiguity attitudes of East Asian populations in both gain and loss domains using classical behavioral economic experimental methods. Based on our sample of university students, we found that Easterners are more risk intolerant but more willing to accept ambiguous conditions than their Westerner counterparts in the gain domain. Perhaps surprisingly, Eastern people and Western people have a similar attitude toward risk and ambiguity in the loss domain. The higher level of risk aversion observed among East Asians may be due to the cultural difference between Western countries and Eastern countries. Historically, such risk aversion may make sense, because it would minimize the influence of numerous ecological and historical threats and socio-political practices. Our findings suggest that models that were designed to analyze and predict aggregate behaviors and markets may be ineffective for Eastern populations, and, in the future, it is of significance to develop appropriate representative agent models from the eastern perspective.
Advanced Timber Construction Industry: A Review of 350 Multi-Storey Timber Projects from 2000–2021
Authors: Svatoš-Ražnjević Hana , Orozco Luis , Menges Achim
Published: March 2022

Throughout the last two decades the timber building sector has experienced a steady growth in multi-storey construction. Although there has been a growing number of research focused on trends, benefits, and disadvantages in timber construction from various technical perspectives, so far there is no extensive literature on the trajectory of emerging architectural typologies. This paper presents an examination of architectural variety and spatial possibilities in current serial and modular multi-storey timber construction. It aims to draw a parallel between architectural characteristics and their relation to structural systems in timber. The research draws from a collection of 350 contemporary multi-storey timber building projects between 2000 and 2021. It consists of 300 built projects, 12 projects currently in construction, and 38 design proposals. The survey consists of quantitative and qualitative project data, as well as classification of the structural system, material, program, massing, and spatial organization of the projects. It then compares the different structural and design aspects to achieve a comprehensive overview of possibilities in timber construction. The outcome is an identification of the range of morphologies and a better understanding of the design space in current serial and modular multi-storey mass timber construction.
Inside the Black Box: A Narrative Review on Comprehensive Geriatric Assessment-Driven Interventions in Older Adults with Cancer
Authors: Thibaud Vincent , Billy Claire , Prud’homm Joaquim , Garin Jeanne , Hue Benoit , Cattenoz Catherine , Somme Dominique , Corvol Aline
Published: March 2022

There is a consensus that the use of comprehensive geriatric assessment (CGA) is good clinical practice for older patients with solid tumors or hematological malignancies. To be complete, a CGA must include a geriatric assessment and an intervention plan. According to the SIOG consensus, a CGA should assess several domains: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and the presence of geriatric syndromes. Progress has been made in the definition of the best way to detect problems, but the benefits are mostly based on prognosis stratification and on the adaptation of cancer treatment. The present review aims to evaluate the level of evidence regarding geriatric interventions proposed following the detection of a problem in cancer patients in each domain mentioned in the SIOG consensus. An online search of the PubMed database was performed using predefined search algorithms specific for each domain of the CGA. Eligible articles had to have well-defined interventions targeting specific domains of the CGA. We screened 1864 articles, but only a few trials on single-domain interventions were found, and often, these studies involved small groups of patients. This review highlights the scarcity of published studies on this topic. The specific impacts of CGA-based interventions have not yet been demonstrated. Multi-domain interventions seem promising, especially when they are based on global assessments. However, standardization seems difficult considering the lack of evidence for each domain. New studies are necessary in multiple care contexts, and innovative designs must be used to balance internal and external validity. An accurate description of the intervention and what “usual care” means will improve the external validity of such studies.
The Role of Simultaneous Integrated Boost in Locally Advanced Rectal Cancer Patients with Positive Lateral Pelvic Lymph Nodes
Authors: Meldolesi Elisa , Chiloiro Giuditta , Giannini Roberta , Menghi Roberta , Persiani Roberto , Corvari Barbara , Coco Claudio , Manfrida Stefania , Ratto Carlo , De Luca Viola , Sofo Luigi , Reina Sara , Crucitti Antonio , Masiello Valeria , Dinapoli Nicola , Valentini Vincenzo , Gambacorta Maria Antonietta
Published: March 2022

Aims: Between 11 to 14% of patients with locally advanced rectal cancer (LARC) have positive lateral pelvic lymph nodes (LPLN) at diagnosis, related to a worse prognosis with a 5-year survival rate between 30 to 40%. The best treatment choice for this group of patients is still a challenge. The optimal radiotherapy (RT) dose for LPLN patients has been investigated. Methods: We retrospectively collected data from LARC patients with LPLN at the primary staging MRI, treated in our center from March 2003 to December 2020. Patients underwent a neoadjuvant concomitant chemo-radiotherapy (CRT) treatment on the primary tumor (T), mesorectum, and pelvic nodes, associated with a fluoride-based chemotherapy. The total reached dose was 45 Gy at 1.8 Gy/fr on the elective sites and 55 Gy at 2.2 Gy/fr on the disease and mesorectum. Patients were divided in two groups based on whether they received a simultaneous integrated RT boost on the LPLN or not. Overall Survival (OS), Disease Free Survival (DFS), Metastasis Free Survival (MFS), and Local Control (LC) were evaluated in the whole group and then compared between the two groups. Results: A total of 176 patients were evaluated: 82 were included in the RT boost group and 94 in the non-RT boost group. The median follow-up period was 57.8 months. All the clinical endpoint (OS, DFS, MFS, LC), resulted were affected by the simultaneous integrated boost on LPLN with a survival rate of 84.7%, 79.5%, 84.1%, and 92%, respectively, in the entire population. From the comparison of the two groups, there was a statistical significance towards the RT boost group with a p < 0.006, 0.030, 0.042, 0.026, respectively. Conclusions: Concomitant radiotherapy boost on positive LPLN has shown to be beneficial on the survival outcomes (OS, DFS, MFR, and LC) in patients with LARC and LPLN. This analysis demonstrates that a higher dose of radiotherapy on positive pelvic lymph nodes led not only to a higher local control but also to a better survival rate. These results, if validated by future prospective studies, can bring a valid alternative to the surgery dissection without the important side effects and permanent disabilities observed during the years.
The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development
Authors: Fasoulakis Zacharias , Koutras Antonios , Ntounis Thomas , Pergialiotis Vasilios , Chionis Athanasios , Katrachouras Alexandros , Palios Vasileios-Chrysovalantis , Symeonidis Panagiotis , Valsamaki Asimina , Syllaios Athanasios , Diakosavvas Michail , Angelou Kyveli , Samara Athina A. , Pagkalos Athanasios , Theodora Marianna , Schizas Dimitrios , Kontomanolis Emmanuel N.
Published: March 2022

The Notch signaling pathway regulates the development of embryonic and tissue homeostasis of various types of cells. It also controls cell proliferation, variation, fate and cell death because it emits short-range messages to nearby cells. The pathway plays an important role in the pathophysiology of various malignancies, controlling cancer creation. It also limits cancer development by adjusting preserved angiogenesis and cellular programs. One of the Notch signaling ligands (in mammals) is Delta-like ligand 4 (Dll4), which plays a significant role in the overall malignancies’ advancement. Particularly, sequencing Notch gene mutations, including those of Dll4, have been detected in many types of cancers portraying information on the growth of particular gynecological types of tumors. The current research article examines the background theory that implies the ability of Dll4 in the development of endometrial and other cancer types, and the probable therapeutic results of Dll4 inhibition.
Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study
Authors: Jouandet Marie , Nakouri Inès , Nadin Lawrence , Kieny Alice , Samimi Mahtab , Adamski Henri , Quéreux Gaëlle , Chaby Guillaume , Dompmartin Anne , L’Orphelin Jean-Matthieu
Published: March 2022

Background: Advanced mycosis fungoides (MF) and Sézary syndrome (SS) are rare, aggressive cutaneous T-cell lymphomas that may be difficult to treat. Mogamulizumab is a recent monoclonal antibody targeting the CCR4 receptor expressed on the surface of Sézary cells. It can be prescribed in MF/SS stages III to IV in the second line after systemic therapy or in stages IB-II after two unsuccessful systemic therapies. We lack data on long-term efficiency and potential side effects in real-life conditions. Our study aims to determine efficacy considering the median PFS of advanced CTCL with mogamulizumab. Secondary objectives were to consider tolerance and estimate delay until side effects appeared. Methods: Data on patients with advanced cutaneous T-cell lymphomas were collected since French Authorization, in six French university hospitals. Patients were followed until they stopped mogamulizumab because of relapse or toxicity. For those still treated by mogamulizumab, the end point was 1 September 2021. We excluded 3 patients as they had already been included in the MAVORIC study and data was not available. Results: The median time of follow-up was 11.6 months. Of the 21 patients included, we reported four full-response patients, eight in partial response, one in stability, three in progression, and five were deceased. One patient had visceral progression, and seven had new lymphadenopathy. Progression-free survival was estimated at 22 months. Twenty patients presented adverse events, of which 10 were severe, i.e., grade III-IV. The median time between the introduction of mogamulizumab and the first adverse event was 21 days. Conclusions: Our study suggests that mogamulizumab can give patients with advanced refractory CTCL a consequent PFS, estimated at 22 months. The long-term safety of mogamulizumab was determined to be acceptable since we reported few grade III–IV AEs, comparable with other studies. No other study using real-life data has been performed to investigate the AEs of mogamulizumab.