bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Transcriptome-Based Mining of Genes Involved in the Export of Polyether Antibiotics for Titer Improvement
Authors: Liu Xian , Wu Yuanting , Zhang Xiaojie , Kang Qianjin , Yan Yusi , Bai Linquan
Published: April 2022

The anti-coccidiosis agent salinomycin is a polyether antibiotic produced by Streptomyces albus BK3-25 with a remarkable titer of 18 g/L at flask scale, suggesting a highly efficient export system. It is worth identifying the involved exporter genes for further titer improvement. In this study, a titer gradient was achieved by varying soybean oil concentrations in a fermentation medium, and the corresponding transcriptomes were studied. Comparative transcriptomic analysis identified eight putative transporter genes, whose transcription increased when the oil content was increased and ranked top among up-regulated genes at higher oil concentrations. All eight genes were proved to be positively involved in salinomycin export through gene deletion and trans-complementation in the mutants, and they showed constitutive expression in the early growth stage, whose overexpression in BK3-25 led to a 7.20–69.75% titer increase in salinomycin. Furthermore, the heterologous expression of SLNHY_0929 or SLNHY_1893 rendered the host Streptomyces lividans with improved resistance to salinomycin. Interestingly, SLNHY_0929 was found to be a polyether-specific transporter because the titers of monensin, lasalocid, and nigericin were also increased by 124.6%, 60.4%, and 77.5%, respectively, through its overexpression in the corresponding producing strains. In conclusion, a transcriptome-based strategy was developed to mine genes involved in salinomycin export, which may pave the way for further salinomycin titer improvement and the identification of transporter genes involved in the biosynthesis of other antibiotics.
Dynamic Evolution Characteristics of Oil–Gas Coupling Fractures and Dynamic Disaster of Coal Mass in Coal and Oil Resources Co-Storage Areas
Authors: Shao Yawu , Suo Yonglu , Xiao Jiang , Bai Yuan , Yang Tao , Fan Siwei
Published: April 2022

The dynamic evolution characteristics of fracture are crucial to analyzing the development of coal and rock mass instability, gas diffusion law, and dynamic disaster prediction. These characteristics affect coal rock fractures and gas-induced disaster channels. Based on the experimental results, we found the following: In areas rich in both coal and oil, the coal mass damage due to high-pressure oil diffusion was inversely correlated with the distance of the coal mass from the disaster source. Moreover, as the coal mass became closer to the disaster source in the abandoned oil well, the average CT number reduced, mechanical performance diminished, fracture volume ratio increased, and capacity of the oil and gas storage improved. The four-dimensional analysis of the rock evolution and strength grade showed that coal mass stress, fracture propagation, and AE incidents were characterized by a low-strength compression stage featured by tensile fractures, medium-strength elastic stage with shear fractures replacing tensile fractures, and high-strength rapid fracture stage with rapid growth in shear fracture quantity and intensity. The dynamic conversion between coal mass instability disaster in coal and oil resources co-storage areas and oil and gas disaster was clarified. We propose high strength, high RA, and low AF of AE incidents in the rapid fracturing stage as the qualitative warning factors for the fracture of coal mass and the occurrence of oil and gas disaster.
Effect of Dough-Related Parameters on the Antimold Activity of Wickerhamomyces anomalus Strains and Mold-Free Shelf Life of Bread
Authors: Syrokou Maria K. , Paramithiotis Spiros , Kanakis Charalabos D. , Papadopoulos Georgios K. , Tarantilis Petros A. , Skandamis Panagiotis N. , Bosnea Loulouda , Mataragas Marios , Drosinos Eleftherios H.
Published: April 2022

The aim of the present study was to assess the antimold capacity of three Wickerhamomyces anomalus strains, both in vitro and in situ, and to identify the responsible volatile organic compounds. For that purpose, two substrates were applied; the former included brain heart infusion broth, adjusted to six initial pH values (3.5, 4.0, 4.5, 5.0, 5.5, 6.0) and supplemented with six different NaCl concentrations (0.0%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5%), while the latter was a liquid dough, fortified with the six aforementioned NaCl concentrations. After a 24 h incubation at 30 °C, the maximum antimold activity was quantified for all strains at 5120 AU/mL, obtained under different combinations of initial pH value and NaCl concentration. A total of twelve volatile compounds were detected; ethanol, ethyl acetate, isoamyl alcohol and isoamyl acetate were produced by all strains. On the contrary, butanoic acid-ethyl ester, acetic acid-butyl ester, ethyl caprylate, 3-methyl-butanoic acid, 2,4-di-tert-butyl-phenol, benzaldehyde, nonanal and octanal were occasionally produced. All compounds exhibited antimold activity; the lower MIC was observed for 2,4-di-tert-butyl-phenol and benzaldehyde (0.04 and 0.06 μL/mL of headspace, respectively), while the higher MIC was observed for butanoic acid-ethyl ester and ethyl caprylate (5.14 and 6.24 μL/mL of headspace, respectively). The experimental breads made with W. anomalus strains LQC 10353, 10346 and 10360 gained an additional period of 9, 10 and 30 days of mold-free shelf life, compared to the control made by commercially available baker’s yeast. Co-culture of the W. anomalus strains with baker’s yeast did not alter the shelf-life extension, indicating the suitability of these strains as adjunct cultures.
Electric Field Distribution Induced by TMS: Differences Due to Anatomical Variation
Authors: Tzirini Marietta , Chatzikyriakou Evangelia , Kouskouras Konstantinos , Foroglou Nikolaos , Samaras Theodoros , Kimiskidis Vasilios K.
Published: April 2022

Transcranial magnetic stimulation (TMS) is a well-established technique for the diagnosis and treatment of neuropsychiatric diseases. The numerical calculation of the induced electric field (EF) distribution in the brain increases the efficacy of stimulation and improves clinical outcomes. However, unique anatomical features, which distinguish each subject, suggest that personalized models should be preferentially used. The objective of the present study was to assess how anatomy affects the EF distribution and to determine to what extent personalized models are useful for clinical studies. The head models of nineteen healthy volunteers were automatically segmented. Two versions of each head model, a homogeneous and a five-tissue anatomical, were stimulated by the model of a Hesed coil (H-coil), employing magnetic quasi-static simulations. The H-coil was placed at two standard stimulating positions per model, over the frontal and central areas. The results show small, but indisputable, variations in the EFs for the homogeneous and anatomical models. The interquartile ranges in the anatomical versions were higher compared to the homogeneous ones, indicating that individual anatomical features may affect the prediction of stimulation volumes. It is concluded that personalized models provide complementary information and should be preferably employed in the context of diagnostic and therapeutic TMS studies.
Object Detection-Based Video Compression
Authors: Kim Myung-Jun , Lee Yung-Lyul
Published: April 2022

Video compression is designed to provide good subjective image quality, even at a high-compression ratio. In addition, video quality metrics have been used to show the results can maintain a high Peak Signal-to-Noise Ratio (PSNR), even at high compression. However, there are many difficulties in object recognition on the decoder side due to the low image quality caused by high compression. Accordingly, providing good image quality for the detected objects is necessary for the given total bitrate for utilizing object detection in a video decoder. In this paper, object detection-based video compression by the encoder and decoder is proposed that allocates lower quantization parameters to the detected-object regions and higher quantization parameters to the background. Therefore, better image quality is obtained for the detected objects on the decoder side. Object detection-based video compression consists of two types: Versatile Video Coding (VVC) and object detection. In this paper, the decoder performs the decompression process by receiving the bitstreams in the object-detection decoder and the VVC decoder. In the proposed method, the VVC encoder and decoder are processed based on the information obtained from object detection. In a random access (RA) configuration, the average Bjøntegaard Delta (BD)-rates of Y, Cb, and Cr increased by 2.33%, 2.67%, and 2.78%, respectively. In an All Intra (AI) configuration, the average BD-rates of Y, Cb, and Cr increased by 0.59%, 1.66%, and 1.42%, respectively. In an RA configuration, the averages of ΔY-PSNR, ΔCb-PSNR, and ΔCr-PSNR for the object-detected areas improved to 0.17%, 0.23%, and 0.04%, respectively. In an AI configuration, the averages of ΔY-PSNR, ΔCb-PSNR, and ΔCr-PSNR for the object-detected areas improved to 0.71%, 0.30%, and 0.30%, respectively. Subjective image quality was also improved in the object-detected areas.
Graphene-Based Flexible Electrode for Electrocardiogram Signal Monitoring
Authors: Cui Tian-Rui , Li Ding , Huang Xiao-Rui , Yan An-Zhi , Dong Yu , Xu Jian-Dong , Guo Yi-Zhe , Wang Yu , Chen Zhi-Kang , Shao Wan-Cheng , Tang Ze-Yi , Tian He , Yang Yi , Ren Tian-Ling
Published: April 2022

With the rapidly aging society and increased concern for personal cardiovascular health, novel, flexible electrodes suitable for electrocardiogram (ECG) signal monitoring are in demand. Based on the excellent electrical and mechanical properties of graphene and the rapid development of graphene device fabrication technologies, graphene-based ECG electrodes have recently attracted much attention, and many flexible graphene electrodes with excellent performance have been developed. To understand the current research progress of graphene-based ECG electrodes and help researchers clarify current development conditions and directions, we systematically review the recent advances in graphene-based flexible ECG electrodes. Graphene electrodes are classified as bionic, fabric-based, biodegradable, laser-induced/scribed, modified-graphene, sponge-like, invasive, etc., based on their design concept, structural characteristics, preparation methods, and material properties. Moreover, some categories are further divided into dry or wet electrodes. Then, their performance, including electrode–skin impedance, signal-to-noise ratio, skin compatibility, and stability, is analyzed. Finally, we discuss possible development directions of graphene ECG electrodes and share our views.
A Systematic Literature Review of Learning-Based Traffic Accident Prediction Models Based on Heterogeneous Sources
Authors: Marcillo Pablo , Valdivieso Caraguay Ángel Leonardo , Hernández-Álvarez Myriam
Published: April 2022

Statistics affirm that almost half of deaths in traffic accidents were vulnerable road users, such as pedestrians, cyclists, and motorcyclists. Despite the efforts in technological infrastructure and traffic policies, the number of victims remains high and beyond expectation. Recent research establishes that determining the causes of traffic accidents is not an easy task because their occurrence depends on one or many factors. Traffic accidents can be caused by, for instance, mechanical problems, adverse weather conditions, mental and physical fatigue, negligence, potholes in the road, among others. At present, the use of learning-based prediction models as mechanisms to reduce the number of traffic accidents is a reality. In that way, the success of prediction models depends mainly on how data from different sources can be integrated and correlated. This study aims to report models, algorithms, data sources, attributes, data collection services, driving simulators, evaluation metrics, percentages of data for training/validation/testing, and others. We found that the performance of a prediction model depends mainly on the quality of its data and a proper data split configuration. The use of real data predominates over data generated by simulators. This work made it possible to determine that future research must point to developing traffic accident prediction models that use deep learning. It must also focus on exploring and using data sources, such as driver data and light conditions, and solve issues related to this type of solution, such as high dimensionality in data and information imbalance.
Numerical Study on the Effect of Large Deep Foundation Excavation on Underlying Complex Intersecting Tunnels
Authors: Zhao Xiang , Li Zhongwei , Dai Guoliang , Wang Hanxuan , Yin Ziwei , Cao Shuning
Published: April 2022

The effect of large deep foundation excavations on the surrounding existing tunnels is a problem that cannot be avoided in the current construction background. This effect is difficult to assess precisely, especially when the geometry of the tunnels and pits is complex. In this paper, a three-dimensional (3D) finite element model has been developed based on a case containing four complex intersecting tunnels and a large deep foundation pit. The model used the hardening soil model with small-strain stiffness (HSS) and the Hoek–Brown (HB) model to describe the mechanical properties of the soil and rock, and various methods including the standard penetration test (SPT) and heavy dynamic penetration test (HDPT) were used to determine the model parameters. The results of the analysis are as follows: the excavation of the foundation pit caused the tunnels to heave and the heave deformation conforms to the normal distribution; the maximum heave of numerical simulation is 3.1 mm which is consistent with the field data; the horizontal displacement, horizontal convergence, and vertical convergence of the tunnels caused by the excavation of the pits are small, and all kinds of deformations meet the control requirements; the intersection of multiple tunnels shows obvious stress concentration when the tunnels were constructed, and the lining stress slightly decreases as excavation progresses.
Online Service-Time Allocation Strategy for Balancing Energy Consumption and Queuing Delay of a MEC Server
Authors: Park Jaesung , Lim Yujin
Published: April 2022

MEC servers (MESs) support multiple queues to accommodate the delay requirements of tasks offloaded from end devices or transferred from other MESs. The service time assigned to each queue trades off the queue backlog and energy consumption. Because multiple queues share the computational resources of a MES, optimally scheduling the service time among them is important, reducing the energy consumption of a MES and ensuring the delay requirement of each queue. To achieve a balance between these metrics, we propose an online service-time allocation method that minimizes the average energy consumption and satisfies the average queue backlog constraint. We employ the Lyapunov optimization framework to transform the time-averaged optimization problem into a per-time-slot optimization problem and devise an online service-time allocation method whose time complexity is linear to the number of queues. This method determines the service time for each queue at the beginning of each time slot using the observed queue length and expected workload. We adopt a long short-term memory (LSTM) deep learning model to predict the workload that will be imposed on each queue during a time slot. Using simulation studies, we verify that the proposed method strikes a better balance between energy consumption and queuing delay than conventional methods.
Current State of Robotics in Hand Rehabilitation after Stroke: A Systematic Review
Authors: Liu Chang , Lu Jingxin , Yang Hongbo , Guo Kai
Published: April 2022

Among the methods of hand function rehabilitation after stroke, robot-assisted rehabilitation is widely used, and the use of hand rehabilitation robots can provide functional training of the hand or assist the paralyzed hand with activities of daily living. However, patients with hand disorders consistently report that the needs of some users are not being met. The purpose of this review is to understand the reasons why these user needs are not being adequately addressed, to explore research on hand rehabilitation robots, to review their current state of research in recent years, and to summarize future trends in the hope that it will be useful to researchers in this research area. This review summarizes the techniques in this paper in a systematic way. We first provide a comprehensive review of research institutions, commercial products, and literature. Thus, the state of the art and deficiencies of functional hand rehabilitation robots are sought and guide the development of subsequent hand rehabilitation robots. This review focuses specifically on the actuation and control of hand functional rehabilitation robots, as user needs are primarily focused on actuation and control strategies. We also review hand detection technologies and compare them with patient needs. The results show that the trends in recent years are more inclined to pursue new lightweight materials to improve hand adaptability, investigating intelligent control methods for human-robot interaction in hand functional rehabilitation robots to improve control robustness and accuracy, and VR virtual task positioning to improve the effectiveness of active rehabilitation training.
On the Redox-Activity and Health-Effects of Atmospheric Primary and Secondary Aerosol: Phenomenology
Authors: Costabile Francesca , Decesari Stefano , Vecchi Roberta , Lucarelli Franco , Curci Gabriele , Massabò Dario , Rinaldi Matteo , Gualtieri Maurizio , Corsini Emanuela , Menegola Elena , Canepari Silvia , Massimi Lorenzo , Argentini Stefania , Busetto Maurizio , Di Iulio Gianluca , Di Liberto Luca , Paglione Marco , Petenko Igor , Russo Mara , Marinoni Angela , Casasanta Gianpietro , Valentini Sara , Bernardoni Vera , Crova Federica , Valli Gianluigi , Forello Alice Corina , Giardi Fabio , Nava Silvia , Pazzi Giulia , Prati Paolo , Vernocchi Virginia , La Torretta Teresa , Petralia Ettore , Stracquadanio Milena , Zanini Gabriele , Melzi Gloria , Nozza Emma , Iulini Martina , Caruso Donatella , Cioffi Lucia , Imperato Gabriele , Giavarini Flavio , Battistoni Maria , Di Renzo Francesca , Frezzini Maria Agostina , Perrino Cinzia , Facchini Maria Cristina
Published: April 2022

The RHAPS (Redox-Activity And Health-Effects Of Atmospheric Primary And Secondary Aerosol) project was launched in 2019 with the major objective of identifying specific properties of the fine atmospheric aerosol from combustion sources that are responsible for toxicological effects and can be used as new metrics for health-related outdoor pollution studies. In this paper, we present the overall methodology of RHAPS and introduce the phenomenology and the first data observed. A comprehensive physico-chemical aerosol characterization has been achieved by means of high-time resolution measurements (e.g., number size distributions, refractory chemical components, elemental composition) and low-time resolution analyses (e.g., oxidative potential, toxicological assays, chemical composition). Preliminary results indicate that, at the real atmospheric conditions observed (i.e., daily PM1 from less than 4 to more than 50 μg m−3), high/low mass concentrations of PM1, as well as black carbon (BC) and water soluble Oxidative Potential (WSOP,) do not necessarily translate into high/low toxicity. Notably, these findings were observed during a variety of atmospheric conditions and aerosol properties and with different toxicological assessments. Findings suggest a higher complexity in the relations observed between atmospheric aerosol and toxicological endpoints that go beyond the currently used PM1 metrics. Finally, we provide an outlook to companion papers where data will be analyzed in more detail, with the focus on source apportionment of PM1 and the role of source emissions on aerosol toxicity, the OP as a predictive variable for PM1 toxicity, and the related role of SOA possessing redox-active capacity, exposure-response relationships for PM1, and air quality models to forecast PM1 toxicity.
Predicting Atlantic Hurricanes Using Machine Learning
Authors: Herrera Victor Manuel Velasco , Martell-Dubois Raúl , Soon Willie , Velasco Herrera Graciela , Cerdeira-Estrada Sergio , Zúñiga Emmanuel , Rosique-de la Cruz Laura
Published: April 2022

Every year, tropical hurricanes affect North and Central American wildlife and people. The ability to forecast hurricanes is essential in order to minimize the risks and vulnerabilities in North and Central America. Machine learning is a newly tool that has been applied to make predictions about different phenomena. We present an original framework utilizing Machine Learning with the purpose of developing models that give insights into the complex relationship between the land–atmosphere–ocean system and tropical hurricanes. We study the activity variations in each Atlantic hurricane category as tabulated and classified by NOAA from 1950 to 2021. By applying wavelet analysis, we find that category 2–4 hurricanes formed during the positive phase of the quasi-quinquennial oscillation. In addition, our wavelet analyses show that super Atlantic hurricanes of category 5 strength were formed only during the positive phase of the decadal oscillation. The patterns obtained for each Atlantic hurricane category, clustered historical hurricane records in high and null tropical hurricane activity seasons. Using the observational patterns obtained by wavelet analysis, we created a long-term probabilistic Bayesian Machine Learning forecast for each of the Atlantic hurricane categories. Our results imply that if all such natural activity patterns and the tendencies for Atlantic hurricanes continue and persist, the next groups of hurricanes over the Atlantic basin will begin between 2023 ± 1 and 2025 ± 1, 2023 ± 1 and 2025 ± 1, 2025 ± 1 and 2028 ± 1, 2026 ± 2 and 2031 ± 3, for hurricane strength categories 2 to 5, respectively. Our results further point out that in the case of the super hurricanes of the Atlantic of category 5, they develop in five geographic areas with hot deep waters that are rather very well defined: (I) the east coast of the United States, (II) the Northeast of Mexico, (III) the Caribbean Sea, (IV) the Central American coast, and (V) the north of the Greater Antilles.
Protein Engineering: The Present and the Future
Authors: Sancho Javier
Published: April 2022

Yes, we are made of proteins, and yes, we can profit from them [...]
Pharmacological Treatment of Pain and Agitation in Severe Dementia and Responsiveness to Change of the Italian Mobilization–Observation–Behavior–Intensity–Dementia (I-MOBID2) Pain Scale: Study Protocol
Authors: Scuteri Damiana , Contrada Marianna , Loria Teresa , Tonin Paolo , Sandrini Giorgio , Tamburin Stefano , Nicotera Pierluigi , Bagetta Giacinto , Corasaniti Maria Tiziana
Published: April 2022

Up to 80% of Alzheimer’s disease (AD) patients in nursing homes experiences chronic pain and 97% develops fluctuant neuropsychiatric symptoms (NPS). Agitation, associated with unrelieved pain, is managed through antipsychotics and may increase the risk of death. Evidence is accumulating in favor of analgesia for a safer, effective therapy of agitation. The Italian version of Mobilization–Observation–Behavior–Intensity–Dementia, I-MOBID2, recently validated in the Italian setting, shows: good scale content validity index (0.89), high construct validity (Spearman rank-order correlation Rho = 0.748), reliable internal consistency (Cronbach’s α coefficient = 0.751), good-excellent inter-rater (intraclass correlation coefficient, ICC = 0.778) and test-retest (ICC = 0.902) reliability, and good inter-rater and test-retest agreement (Cohen’s K = 0.744) with 5.8 min completion time. This study intends to identify the responsiveness of the I-MOBID2 based on COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) recommendations, assessing the a priori hypotheses of (1) the efficacy of painkillers administered to severe AD patients after proper pain assessment and (2) the effect of reduction of the Cohen-Mansfield Agitation Inventory (CMAI) score and of agitation rescue medications. This protocol is approved by Calabria Region Ethics Committee protocol No. 31/2017 and follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.
Weak Hand Grip Strength Is Associated with Alexithymia in Outpatients in a Mexican Population
Authors: Genis-Mendoza Alma Delia , Fresán Ana , González-Castro Thelma Beatriz , Pool-García Sherezada , Tovilla-Zárate Carlos Alfonso , Castillo-Avila Rosa Giannina , Arias-Vázquez Pedro Iván , López-Narváez María Lilia , Nicolini Humberto
Published: April 2022

Hand grip strength has been considered as a possible marker for metabolic and psychiatric disease. To date, however, no research has focused on the association between alexithymia and hand grip strength. The objective of the present study was to investigate the correct association between hand grip strength and alexithymia. A cross-sectional study was carried out in Comalcalco, Tabasco, México. A total of 246 individuals were included. Hand grip strength was evaluated in the dominant hand using a Takei® portable digital dynamometer. Alexithymia was measured using the Toronto Alexithymia Scale (TAS-20). Two linear regression models adjusted by confounders were used to determine the association between alexithymia and hand grip strength. The rate for positive alexithymia was 39.0% (n = 94). Individuals with alexithymia showed a weaker hand grip strength than the comparison group (t = 2.4, 244 df, p = 0.01). Individuals with alexithymia had significantly reduced levels of hand grip strength (β = −0.39 ± 0.14; p = 0.006); after additional adjustment for clinical variables, decreased hand grip strength remained (β = 8.00 ± 1.86; p ≤ 0.001). Our results suggest that a decrease in hand grip strength could be associated with alexithymia. This measurement could be useful as a predictive marker for the identification of alexithymia in Mexican individuals who attend outpatient clinics.
The Role of Music Therapy with Infants with Perinatal Brain Injury
Authors: Ormston Kirsty , Howard Rachel , Gallagher Katie , Mitra Subhabrata , Jaschke Arthur
Published: April 2022

Perinatal brain injury occurs in 5.14/1000 live births in England. A significant proportion of these injuries result from hypoxic ischaemic encephalopathy (HIE) in term infants and intracranial haemorrhage (IVH) or periventricular leukomalacia (PVL) in preterm infants. Standardised care necessitates minimal handling from parents and professionals to reduce the progression of injury. This can potentially increase parental stress through the physical inability to bond with their baby. Recent research highlights the ability of music therapy (MT) to empower parental bonding without handling, through sharing culturally informed personal music with their infant. This review therefore aimed to systematically evaluate the use of MT with infants diagnosed with perinatal brain injury in a neonatal intensive care unit (NICU). Search terms were combined into three categories (audio stimulation (MT), population (neonates) and condition (brain injury), and eight electronic databases were used to identify relevant studies following PRISMA guidelines. Eleven studies using music or vocal stimulation with infants diagnosed with perinatal brain injury were identified and quality assessed using Cochrane ROB2, the ROBINSI Tool and the Newcastle Ottawa Scale. Studies used either voice as live (n = 6) or pre-recorded (n = 3) interventions or pre-recorded instrumental music (n = 2). Studies had two primary areas of focus: developmental outcomes and physiological effects. Results suggested the use of music interventions led to a reduction of infants’ pain scores during procedures and cardiorespiratory events, improved feeding ability (increase oral feeding rate, volume intake and feeds per day) and resulted in larger amygdala volumes than control groups. Additionally, MT intervention on the unit supported long-term hospitalised infants in the acquisition of developmental milestones. Vocal soothing was perceived to be an accessible intervention for parents. However, infants with PVL showed signs of stress in complex interventions, which also potentially resulted in an increase in maternal anxiety in one study. MT with infants diagnosed with perinatal brain injury can have positive effects on infants’ behavioural and neurological parameters and support parental involvement in their infants’ developmental care. Further feasibility studies are required using MT to determine appropriate outcome measures for infants and the support required for parents to allow future comparison in large-scale randomised control trials.
Algorithm-Based Hearing and Speech Therapy Rehabilitation after Cochlear Implantation
Authors: Eichler Theda , Rötz Wiebke , Kayser Christoph , Bröhl Felix , Römer Michael , Witteborg Arne Henning , Kummert Franz , Sandmeier Tobias , Schulte Christoph , Stolz Patricia , Meyer Katharina , Sudhoff Holger , Todt Ingo
Published: April 2022

Introduction: Due to the changes in the indication range for cochlear implants and the demographic development towards an aging society, more and more people are in receipt of cochlear implants. An implantation requires a close-meshed audiological and logopedic aftercare. Hearing therapy rehabilitation currently requires great personnel effort and is time consuming. Hearing and speech therapy rehabilitation can be supported by digital hearing training programs. However, the apps currently on the market are to a limited degree personalized and structured. Increasing digitalization makes it possible, especially in times of pandemics, to decouple hearing therapy treatment from everyday clinical practice. Material and Methods: For this purpose, an app is in development that provides hearing therapy tailored to the patient. The individual factors that influence hearing outcome are considered. Using intelligent algorithms, the app determines the selection of exercises, the level of difficulty and the speed at which the difficulty is increased. Results: The app works autonomously without being connected to local speech therapists. In addition, the app is able to analyze patient difficulties within the exercises and provides conclusions about the need for technical adjustments. Conclusions: The presented newly developed app represents a possibility to support, replace, expand and improve the classic outpatient hearing and speech therapy after CI implantation. The way the application works allows it to reach more people and provide a time- and cost-saving alternative to traditional therapy.
The Clinical Spectrum of Autoimmune-Mediated Neurological Diseases in Paediatric Population
Authors: Lubarski Karol , Mania Anna , Michalak Sławomir , Osztynowicz Krystyna , Mazur-Melewska Katarzyna , Figlerowicz Magdalena
Published: April 2022

Neurological autoimmune diseases have various origins and pathogeneses. Specific antibodies are associated with paraneoplastic syndromes, other infectious agents, or inherited disorders. We aim to evaluate the relation between the autoantibodies, the chosen symptoms, demographic characteristics, and infection history. We retrospectively analysed 508 children during neurological diagnostics. We investigated serum antineuronal, IgG, IgM anti-ganglioside, and anti-aquaporin-4 in both the serum and cerebrospinal fluid (CSF) anti-cell surface and anti-synaptic protein antibodies in 463, 99, 44, 343, and 119 patients, respectively. The CSF polymerase chain reaction detection of Herpesviridae, enterovirus, B19 parvovirus, adenovirus, and parechovirus involved 261 patients. We included available clinical information and electroencephalographic, radiologic, and microbiological results. The IgM anti-ganglioside antibodies increased the risk of tics and positive symptoms (p = 0.0345, p = 0.0263, respectively), the anti-glutamic acid decarboxylase particle of paresis (p = 0.0074), and anti-neuroendothelium of mutism (p = 0.0361). Anti-neuroendothelium, IgM anti-ganglioside, and CSF anti-N-methyl-D-aspartate antibodies were more often associated with consciousness loss (p = 0.0496, p = 0.0044, p = 0.0463, respectively). Anti-myelin antibodies co-occured with Herpes simplex virus (HSV)-2 IgG (p = 0.0415), anti-CV2 with HSV-1 IgM (p = 0.0394), whereas anti-glial fibrillary acidic protein was linked with past Epstein-Barr virus infection. The anti-ganglioside IgM and anti-myelin particles were bilaterally correlated (p = 0.0472). The clinical pictures may overlap, requiring specialistic diagnostics. We noticed the links between the infection aetiology and the specific autoantibody’s positivity.
Probabilistic Moment Bearing Capacity Model and Fragility of Beam-Column Joints with Cast Steel Stiffeners
Authors: Li Xinxia , Xu Hao
Published: April 2022

Beam-column joint with cast steel stiffeners (CSS) is a new type of joint with a large degree of design freedom. The joint stress distribution can be improved by designing a reasonable cross-sectional shape of the CSS with high rigidity, high integrity, and good seismic performance. Due to the construction specificity, the exact theoretical formula for the moment bearing capacity of the CSS joint is hard to deduce. Some researchers have proposed empirical or simplified theoretical formulas for the prediction of moment bearing capacity. However, the formulas are biased and cannot capture uncertainties in the data measurement and modeling process. In addition, current formulas cannot be updated efficiently over time, and no work has been conducted regarding the reliability of the CSS joints subject to different loading conditions. In this paper, a new approach to address the above issues is proposed. A probabilistic model for the joint capacity is established to capture the uncertainties and correct the bias. A Bayesian method is proposed for model training, which allows the model to be updated efficiently whenever new experiment or simulation data are available. A fragility analysis is conducted using the proposed capacity model to quantify the failure probability of joints under different loading conditions. The advantages of the proposed approach are validated by analyzing joints in a database obtained from experiments and numerical simulations. Results show that the proposed capacity model provides unbiased and more accurate estimates of the bending moment than the currently available ones. New factors such as column thickness and concrete filling are found to significantly impact the moment capacity. The bending fragility of CSS joints can be lowered at different degrees by increasing concrete strength, steel strength, column thickness, etc. Guidance on CSS joint design and retrofitting based on the capacity model and fragility analysis is also presented at the end of this paper.
Nutritional Interventions in Pancreatic Cancer: A Systematic Review
Authors: Emanuel Aline , Krampitz Julia , Rosenberger Friederike , Kind Sabine , Rötzer Ingeborg
Published: April 2022

(1) Background: Pancreatic cancer (PaCa) is directly related to malnutrition, cachexia and weight loss. Nutritional interventions (NI) are used in addition to standard therapy. The aim of this systematic review is to provide an overview of the types of NI and their effects. (2) Methods: We included RCTs with at least one intervention group receiving an NI and compared them with a control group with no NI, placebo or alternative treatment on cachexia, malnutrition or weight loss in patients with PaCa. Any available literature until 12 August 2021 was searched in the Pubmed and Cochrane databases. RCTs were sorted according to NI (parenteral nutrition, enteral nutrition, dietary supplements and mixed or special forms). (3) Results: Finally, 26 studies with a total of 2720 patients were included. The potential for bias was mostly moderate to high. Parenteral nutrition is associated with a higher incidence of complications. Enteral nutrition is associated with shorter length of stay in hospital, lower rate and development of complications, positive effects on cytokine rates and lower weight loss. Dietary supplements enriched with omega-3 fatty acids lead to higher body weight and lean body mass. (4) Conclusions: Enteral nutrition and dietary supplements with omega-3 fatty acids should be preferred in nutritional therapy of PaCa patients.
Preoperative Osteopenia Is Associated with Significantly Shorter Survival in Patients with Perihilar Cholangiocarcinoma
Authors: Watanabe Jun , Miki Atsushi , Sakuma Yasunaru , Shimodaira Kentaro , Aoki Yuichi , Meguro Yoshiyuki , Morishima Kazue , Endo Kazuhiro , Sasanuma Hideki , Lefor Alan Kawarai , Teratani Takumi , Fukushima Noriyoshi , Kitayama Joji , Sata Naohiro
Published: April 2022

Background: Osteopenia is defined as low bone mineral density (BMD) and has been shown to be associated with outcomes of patients with various cancers. The association between osteopenia and perihilar cholangiocarcinoma is unknown. The aim of this study was to evaluate osteopenia as a prognostic factor in patients with perihilar cholangiocarcinoma. Methods: A total of 58 patients who underwent surgery for perihilar cholangiocarcinoma were retrospectively analyzed. The BMD at the 11th thoracic vertebra was measured using computed tomography scan within one month of surgery. Patients with a BMD < 160 HU were considered to have osteopenia and b BMD ≥ 160 did not have osteopenia. The log-rank test was performed for survival using the Kaplan–Meier method. After adjusting for confounding factors, overall survival was assessed by Cox′s proportional-hazards model. Results: The osteopenia group had 27 (47%) more females than the non-osteopenia group (p = 0.036). Median survival in the osteopenia group was 37 months and in the non-osteopenia group was 61 months (p = 0.034). In multivariable analysis, osteopenia was a significant independent risk factor associated with overall survival in patients with perihilar cholangiocarcinoma (hazard ratio 3.54, 95% confidence interval 1.09–11.54, p = 0.036), along with primary tumor stage. Conclusions: Osteopenia is associated with significantly shorter survival in patients with perihilar cholangiocarcinoma.
Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice
Authors: Bruss Christina , Kellner Kerstin , Ortmann Olaf , Seitz Stephan , Brockhoff Gero , Hutchinson James A. , Wege Anja Kathrin
Published: April 2022

“Humanized” mice have been widely used for the characterization of human cancer progression and as a powerful preclinical model. Standardization of multicolor phenotyping could help to identify immune cell patterns involved in checkpoint-related complications. Therefore, we applied established protocols for immune cell profiling to our humanized Patient-Derived Xenograft (hPDX) model. hPDX are characterized by the co-existence of a human immune system and a patient-derived tumor transplant. These mice possess a human-like immune system after CD34+ stem cell transplantation while the reconstitution level of the immune system was not related to the quantity of transplanted CD34+ cells. Contamination ≤ 1.2% by CD3+ cells in the hematopoietic stem cell (HSC) transplant did not trigger abnormal T cell maturation. Different B and T cell differentiation stages were identified, as well as regulatory T cells (Tregs) and exhausted T cells that expressed TIGIT, PD-1, or KLRG1. Overall, the application of standardized protocols for the characterization of immune cells using flow cytometry will contribute to a better understanding of immune-oncologic processes.
An Invasive Disease Event-Free Survival Analysis to Investigate Ki67 Role with Respect to Breast Cancer Patients’ Age: A Retrospective Cohort Study
Authors: Massafra Raffaella , Bove Samantha , La Forgia Daniele , Comes Maria Colomba , Didonna Vittorio , Gatta Gianluca , Giotta Francesco , Latorre Agnese , Nardone Annalisa , Palmiotti Gennaro , Quaresmini Davide , Rinaldi Lucia , Tamborra Pasquale , Zito Alfredo , Rizzo Alessandro , Fanizzi Annarita , Lorusso Vito
Published: April 2022

Characterization of breast cancer into intrinsic molecular profiles has allowed women to live longer, undergoing personalized treatments. With the aim of investigating the relation between different values of ki67 and the predisposition to develop a breast cancer-related IDE at different ages, we enrolled 900 patients with a first diagnosis of invasive breast cancer, and we partitioned the dataset into two sub-samples with respect to an age value equal to 50 years. For each sample, we performed a Kaplan–Meier analysis to compare the IDE-free survival curves obtained with reference to different ki67 values. The analysis on patients under 50 years old resulted in a p-value < 0.001, highlighting how the behaviors of patients characterized by a ki67 ranging from 10% to 20% and greater than 20% were statistically significantly similar. Conversely, patients over 50 years old characterized by a ki67 ranging from 10% to 20% showed an IDE-free survival probability significantly greater than patients with a ki67 greater than 20%, with a p-value of 0.01. Our work shows that the adoption of two different ki67 values, namely, 10% and 20%, might be discriminant in designing personalized treatments for patients under 50 years old and over 50 years old, respectively.
Nucleolin Overexpression Predicts Patient Prognosis While Providing a Framework for Targeted Therapeutic Intervention in Lung Cancer
Authors: Valério-Fernandes Ângela , Fonseca Nuno A. , Gonçalves Nélio , Cruz Ana F. , Pereira Marta I. , Gregório Ana C. , Moura Vera , Ladeirinha Ana F. , Alarcão Ana , Gonçalves Joana , Abrunhosa Antero , Melo Joana B. , Carvalho Lina , Simões Sérgio , Moreira João N.
Published: April 2022

Notwithstanding the advances in the treatment of lung cancer with immune checkpoint inhibitors, the high percentage of non-responders supports the development of novel anticancer treatments. Herein, the expression of the onco-target nucleolin in patient-derived pulmonary carcinomas was characterized, along with the assessment of its potential as a therapeutic target. The clinical prognostic value of nucleolin for human pulmonary carcinomas was evaluated through data mining from the Cancer Genome Atlas project and immunohistochemical detection in human samples. Cell surface expression of nucleolin was evaluated by flow cytometry and subcellular fraction Western blotting in lung cancer cell lines. Nucleolin mRNA overexpression correlated with poor overall survival of lung adenocarcinoma cancer patients and further predicted the disease progression of both lung adenocarcinoma and squamous carcinoma. Furthermore, a third of the cases presented extra-nuclear expression, contrasting with the nucleolar pattern in non-malignant tissues. A two- to twelve-fold improvement in cytotoxicity, subsequent to internalization into the lung cancer cell lines of doxorubicin-loaded liposomes functionalized by the nucleolin-binding F3 peptide, was correlated with the nucleolin cell surface levels and the corresponding extent of cell binding. Overall, the results suggested nucleolin overexpression as a poor prognosis predictor and thus a target for therapeutic intervention in lung cancer.
Cell-Free Circulating (Tumor) DNA before Surgery as a Prognostic Factor in Non-Metastatic Colorectal Cancer: A Systematic Review
Authors: Schraa Suzanna J. , van Rooijen Karlijn L. , Koopman Miriam , Vink Geraldine R. , Fijneman Remond J. A.
Published: April 2022

Identification of non-metastatic colorectal cancer (CRC) patients with a high risk of recurrence after tumor resection is important to select patients who might benefit from adjuvant treatment. Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) analyses after surgery are promising biomarkers to predict recurrence in these patients. However, these analyses face several challenges and do not allow guidance of neoadjuvant treatment, which might become a novel standard option in colon cancer treatment. The prognostic value of cfDNA/ctDNA before surgery is unclear. This systematic review aims to provide an overview of publications in which the prognostic value of presurgery cfDNA/ctDNA in non-metastatic CRC patients was studied and is performed according to PRISMA guidelines. A total of 29 out of 1233 articles were included and categorized into three groups that reflect the type of approach: measurement of cfDNA, ctDNA somatic alterations, and ctDNA methylation. Overall, a clear association between presurgery cfDNA/ctDNA and the outcome was not observed, but large studies that primarily focus on the prognostic value of presurgery cfDNA/ctDNA are lacking. Designing and performing studies that focus on the value of presurgery cfDNA/ctDNA is needed, in addition to standardization in the reporting of cfDNA/ctDNA results according to existing guidelines to improve comparability and interpretation among studies.
Tumor-Associated Macrophages and Ovarian Cancer: Implications for Therapy
Authors: Schweer David , McAtee Annabel , Neupane Khaga , Richards Christopher , Ueland Frederick , Kolesar Jill
Published: April 2022

The tumor microenvironment (TME) has been implicated to play an important role in the progression of ovarian cancer. One of the most important components of the TME is tumor associated macrophages (TAMs). Phenotypically, macrophages are broadly categorized as M1 pro-inflammatory or M2 anti-inflammatory, based on the cytokines and chemokines that they secrete. The tumor microenvironment is associated with macrophages of an M2 phenotype which suppress the surrounding immune environment, assist tumor cells in evading immune targeting, and support tumor growth and metastasis. Contrarily, M1 macrophages help mount an immune response against tumors, and are associated with a more favorable prognosis in solid tumors. One of the characteristic indicators of a poor prognosis in ovarian cancer is the overrepresentation of M2-type TAMs. As such, therapeutic modalities targeting TME and TAMs are of increasing interest. Pharmacological approaches to eliminate TAMs, include decreasing macrophage survival and recruitment and increasing phagocytosis, have been underwhelming. Clinical strategies targeting these macrophage subtypes via repolarization to an M1 antitumoral state deserve increasing attention, and may serve as a new modality for immunotherapy.
Copy Number Alterations as Novel Biomarkers and Therapeutic Targets in Colorectal Cancer
Authors: Tan Elaine S. , Knepper Todd C. , Wang Xuefeng , Permuth Jennifer B. , Wang Liang , Fleming Jason B. , Xie Hao
Published: April 2022

In colorectal cancer, somatic mutations have played an important role as prognostic and predictive biomarkers, with some also functioning as therapeutic targets. Another genetic aberration that has shown significance in colorectal cancer is copy number alterations (CNAs). CNAs occur when a change to the DNA structure propagates gain/amplification or loss/deletion in sections of DNA, which can often lead to changes in protein expression. Multiple techniques have been developed to detect CNAs, including comparative genomic hybridization with microarray, low pass whole genome sequencing, and digital droplet PCR. In this review, we summarize key findings in the literature regarding the role of CNAs in the pathogenesis of colorectal cancer, from adenoma to carcinoma to distant metastasis, and discuss the roles of CNAs as prognostic and predictive biomarkers in colorectal cancer.