bluuebunny/crossref_metadata_2025 huggingface dataset:
Inspection Application in an Industrial Environment with Collaborative Robots
Authors: Magalhaes Paulo , Ferreira Nuno
Published: April 2022

In this study, we analyze the potential of collaborative robotics in automated quality inspections in the industry. The development of a solution integrating an industrial vision system allowed evaluating the performance of collaborative robots in a real case. The use of these tools allows reducing quality defects as well as costs in the manufacturing process. In this system, image processing methods use resources based on depth and surface measurements with high precision. The system fully processes a panel, observing the state of the surface to detect any potential defect in the panels produced to increase the quality of production.
Application of Micro-Engineered Kidney, Liver, and Respiratory System Models to Accelerate Preclinical Drug Testing and Development
Authors: Gholizadeh Hanieh , Cheng Shaokoon , Kourmatzis Agisilaos , Xing Hanwen , Traini Daniela , Young Paul M. , Ong Hui Xin
Published: April 2022

Developing novel drug formulations and progressing them to the clinical environment relies on preclinical in vitro studies and animal tests to evaluate efficacy and toxicity. However, these current techniques have failed to accurately predict the clinical success of new therapies with a high degree of certainty. The main reason for this failure is that conventional in vitro tissue models lack numerous physiological characteristics of human organs, such as biomechanical forces and biofluid flow. Moreover, animal models often fail to recapitulate the physiology, anatomy, and mechanisms of disease development in human. These shortfalls often lead to failure in drug development, with substantial time and money spent. To tackle this issue, organ-on-chip technology offers realistic in vitro human organ models that mimic the physiology of tissues, including biomechanical forces, stress, strain, cellular heterogeneity, and the interaction between multiple tissues and their simultaneous responses to a therapy. For the latter, complex networks of multiple-organ models are constructed together, known as multiple-organs-on-chip. Numerous studies have demonstrated successful application of organ-on-chips for drug testing, with results comparable to clinical outcomes. This review will summarize and critically evaluate these studies, with a focus on kidney, liver, and respiratory system-on-chip models, and will discuss their progress in their application as a preclinical drug-testing platform to determine in vitro drug toxicology, metabolism, and transport. Further, the advances in the design of these models for improving preclinical drug testing as well as the opportunities for future work will be discussed.
Performance Characteristics of a Novel 3D-Printed Bubble Intermittent Mandatory Ventilator (B-IMV) for Adult Pulmonary Support
Authors: Poli Jonathan A. , Howard Christopher , Garcia Alfredo J. , Remboski Don , Littlewood Peter B. , Kress John P. , Kasthuri Narayanan , Comai Alia , Soni Kiran , Kennedy Philip , Ogger John , DiBlasi Robert M.
Published: April 2022

The COVID-19 pandemic has brought attention to the need for developing effective respiratory support that can be rapidly implemented during critical surge capacity scenarios in healthcare settings. Lung support with bubble continuous positive airway pressure (B-CPAP) is a well-established therapeutic approach for supporting neonatal patients. However, the effectiveness of B-CPAP in larger pediatric and adult patients has not been addressed. Using similar principles of B-CPAP pressure generation, application of intermittent positive pressure inflations above CPAP could support gas exchange and high work of breathing levels in larger patients experiencing more severe forms of respiratory failure. This report describes the design and performance characteristics of the BubbleVent, a novel 3D-printed valve system that combined with commonly found tubes, hoses, and connectors can provide intermittent mandatory ventilation (IMV) suitable for adult mechanical ventilation without direct electrification. Testing of the BubbleVent was performed on a passive adult test lung model and compared with a critical care ventilator commonly used in tertiary care centers. The BubbleVent was shown to deliver stable PIP and PEEP levels, as well as timing control of breath delivery that was comparable with a critical care ventilator.
A Hybrid Deep Learning Approach for ECG-Based Arrhythmia Classification
Authors: Madan Parul , Singh Vijay , Singh Devesh Pratap , Diwakar Manoj , Pant Bhaskar , Kishor Avadh
Published: April 2022

Arrhythmias are defined as irregularities in the heartbeat rhythm, which may infrequently occur in a human’s life. These arrhythmias may cause potentially fatal complications, which may lead to an immediate risk of life. Thus, the detection and classification of arrhythmias is a pertinent issue for cardiac diagnosis. (1) Background: To capture these sporadic events, an electrocardiogram (ECG), a register containing the heart’s electrical function, is considered the gold standard. However, since ECG carries a vast amount of information, it becomes very complex and challenging to extract the relevant information from visual analysis. As a result, designing an efficient (automated) system to analyse the enormous quantity of data possessed by ECG is critical. (2) Method: This paper proposes a hybrid deep learning-based approach to automate the detection and classification process. This paper makes two-fold contributions. First, 1D ECG signals are translated into 2D Scalogram images to automate the noise filtering and feature extraction. Then, based on experimental evidence, by combining two learning models, namely 2D convolutional neural network (CNN) and the Long Short-Term Memory (LSTM) network, a hybrid model called 2D-CNN-LSTM is proposed. (3) Result: To evaluate the efficacy of the proposed 2D-CNN-LSTM approach, we conducted a rigorous experimental study using the widely adopted MIT–BIH arrhythmia database. The obtained results show that the proposed approach provides ≈98.7%, 99%, and 99% accuracy for Cardiac Arrhythmias (ARR), Congestive Heart Failure (CHF), and Normal Sinus Rhythm (NSR), respectively. Moreover, it provides an average sensitivity of the proposed model of 98.33% and a specificity value of 98.35%, for all three arrhythmias. (4) Conclusions: For the classification of arrhythmias, a robust approach has been introduced where 2D scalogram images of ECG signals are trained over the CNN-LSTM model. The results obtained are better as compared to the other existing techniques and will greatly reduce the amount of intervention required by doctors. For future work, the proposed method can be applied over some live ECG signals and Bi-LSTM can be applied instead of LSTM.
Maintenance of Genetic Diversity of Black Sea Bream despite Unmonitored and Large-Scale Hatchery Releases
Authors: Hsu Te-Hua , Lee Hung-Tai , Lu Hsueh-Jung , Liao Cheng-Hsin , Gong Hong-Yi , Huang Chang-Wen
Published: April 2022

Stock enhancement, used for replenishing depleted wild finfish populations, is an aggressive approach. Stock enhancement projects in Taiwan involve black sea bream (Acanthopagrus schlegelii), a major commercial species. During 2004–2015, even management agencies conducted stock enhancement projects, leading to numerous private releases that have not been recorded. Stock enhancement by a private hatchery without accurate genetic records may lead to a genetic structure change in wild populations. Using allele frequencies at nine microsatellite loci, we studied the genetic effects of stock enhancement in 19 samples collected from populations in the hatcheries and the wild. In 458 individuals from nine hatchery samples, most populations showed weak but significant genetic differences and complex clusters in structure analysis, indicating dramatic stock change within and among hatcheries. The 10 wild populations (n = 773) also had a complex genetic composition and were genetically different among sampling sites and times. However, a simple and clear cluster in structure analysis was found for only one sampling site, which had no release history. Thus, stock enhancement with complex genetic sources helps maintain genetic diversity but dramatically changes the genetic structure within and among wild populations, especially when stock enhancement is successful.
Ingestion of Diazotrophs Makes Corals More Resistant to Heat Stress
Authors: Meunier Valentine , Bonnet Sophie , Camps Mercedes , Benavides Mar , Dubosc Jeff , Rodolfo-Metalpa Riccardo , Houlbrèque Fanny
Published: April 2022

Over the past decade, coral bleaching events have continued to recur and intensify. During bleaching, corals expel millions of their symbionts, depriving the host from its main food source. One mechanism used by corals to resist bleaching consists in exploiting food sources other than autotrophy. Among the food sources available in the reefs, dinitrogen (N2)-fixing prokaryotes or planktonic diazotrophs (hereafter called ‘PD’) have the particularity to reduce atmospheric dinitrogen (N2) and release part of this nitrogen (diazotroph-derived nitrogen or DDN) in bioavailable form. Here, we submitted coral colonies of Stylophora pistillata, fed or not with planktonic diazotrophs, to a temperature stress of up to 31 ± 0.5 °C and measured their physiological responses (photosynthetic efficiency, symbiont density, and growth rates). Heat-unfed colonies died 8 days after the heat stress while heat-PD-fed corals remained alive after 10 days of heat stress. The supply of PD allowed corals to maintain minimal chlorophyll concentration and symbiont density, sustaining photosynthetic efficiency and stimulating coral growth of up to 48% compared to unfed ones. By providing an alternative source of bioavailable nitrogen and carbon, this specific planktonic diazotroph feeding may have a profound potential for coral bleaching recovery.
The Blood–Brain Barrier—A Key Player in Multiple Sclerosis Disease Mechanisms
Authors: Schreiner Thomas Gabriel , Romanescu Constantin , Popescu Bogdan Ovidiu
Published: April 2022

Over the past decade, multiple sclerosis (MS), a chronic neuroinflammatory disease with severe personal and social consequences, has undergone a steady increase in incidence and prevalence rates worldwide. Despite ongoing research and the development of several novel therapies, MS pathology remains incompletely understood, and the prospect for a curative treatment continues to be unpromising in the near future. A sustained research effort, however, should contribute to a deeper understanding of underlying disease mechanisms, which will undoubtedly yield improved results in drug development. In recent years, the blood–brain barrier (BBB) has increasingly become the focus of many studies as it appears to be involved in both MS disease onset and progression. More specifically, neurovascular unit damage is believed to be involved in the critical process of CNS immune cell penetration, which subsequently favors the development of a CNS-specific immune response, leading to the classical pathological and clinical hallmarks of MS. The aim of the current narrative review is to merge the relevant evidence on the role of the BBB in MS pathology in a comprehensive and succinct manner. Firstly, the physiological structure and functions of the BBB as a component of the more complex neurovascular unit are presented. Subsequently, the authors review the specific alteration of the BBB encountered in different stages of MS, focusing on both the modifications of BBB cells in neuroinflammation and the CNS penetration of immune cells. Finally, the currently accepted theories on neurodegeneration in MS are summarized.
Extraction of Phenolic Compounds from Populus Salicaceae Bark
Authors: Autor Elsa , Cornejo Alfonso , Bimbela Fernando , Maisterra Maitane , Gandía Luis M. , Martínez-Merino Víctor
Published: April 2022

Lignocellulosic residues have the potential for obtaining high value-added products that could be better valorized if biorefinery strategies are adopted. The debarking of short-rotation crops yields important amounts of residues that are currently underexploited as low-grade fuel and could be a renewable source of phenolic compounds and other important phytochemicals. The isolation of these compounds can be carried out by different methods, but for attaining an integral valorization of barks, a preliminary extraction step for phytochemicals should be included. Using optimized extraction methods based on Soxhlet extraction can be effective for the isolation of phenolic compounds with antioxidant properties. In this study, poplar bark (Populus Salicaceae) was used to obtain a series of extracts using five different solvents in a sequential extraction of 24 h each in a Soxhlet extractor. Selected solvents were put in contact with the bark sample raffinate following an increasing order of polarity: n-hexane, dichloromethane, ethyl acetate, methanol, and water. The oily residues of the extracts obtained after each extraction were further subjected to flash chromatography, and the fractions obtained were characterized by gas chromatography coupled with mass spectrometry (GC–MS). The total phenolic content (TPC) was determined using the Folin–Ciocalteu method, and the antioxidant activity (AOA) of the samples was evaluated in their reaction with the free radical 2,2-Diphenyl-picrylhydrazyl (DPPH method). Polar solvents allowed for higher individual extraction yields, with overall extraction yields at around 23% (dry, ash-free basis). Different compounds were identified, including hydrolyzable tannins, phenolic monomers such as catechol and vanillin, pentoses and hexoses, and other organic compounds such as long-chain alkanes, alcohols, and carboxylic acids, among others. An excellent correlation was found between TPC and antioxidant activity for the samples analyzed. The fractions obtained using methanol showed the highest phenolic content (608 μg of gallic acid equivalent (GAE)/mg) and the greatest antioxidant activity.
Dimethyloxalylglycine (DMOG), a Hypoxia Mimetic Agent, Does Not Replicate a Rat Pheochromocytoma (PC12) Cell Biological Response to Reduced Oxygen Culture
Authors: Chen RuoLi , Ahmed Mohammad Alkataan , Forsyth Nicholas Robert
Published: April 2022

Cells respond to reduced oxygen availability predominately by activation of the hypoxia-inducible factor (HIF) pathway. HIF activation upregulates hundreds of genes that help cells survive in the reduced oxygen environment. The aim of this study is to determine whether chemical-induced HIF accumulation mimics all aspects of the hypoxic response of cells. We compared the effects of dimethyloxalylglycine (DMOG) (a HIF stabiliser) on PC12 cells cultured in air oxygen (20.9% O2, AO) with those cultured in either intermittent 20.9% O2 to 2% O2 (IH) or constant 2% O2 (CN). Cell viability, cell cycle, HIF accumulation, reactive oxygen species (ROS) formation, mitochondrial function and differentiation were used to characterise the PC12 cells and evaluate the impact of DMOG. IH and CN culture reduced the increase in cell numbers after 72 and 96 h and MTT activity after 48 h compared to AO culture. Further, DMOG supplementation in AO induced a dose-dependent reduction in the increase in PC12 cell numbers and MTT activity. IH-cultured PC12 cells displayed increased and sustained HIF-1 expression over 96 h. This was accompanied by increased ROS and mitochondrial burden. PC12 cells in CN displayed little changes in HIF-1 expression or ROS levels. DMOG (0.1 mM) supplementation resulted in an IH-like HIF-1 profile. The mitochondrial burden and action potential of DMOG-supplemented PC12 cells did not mirror those seen in other conditions. DMOG significantly increased S phase cell populations after 72 and 96 h. No significant effect on PC12 cell differentiation was noted with IH and CN culture without induction by nerve growth factor (NGF), while DMOG significantly increased PC12 cell differentiation with and without NGF. In conclusion, DMOG and reduced oxygen levels stabilise HIF and affect mitochondrial activity and cell behaviour. However, DMOG does not provide an accurate replication of the reduced oxygen environments.
Targeted Osmotic Lysis: A Novel Approach to Targeted Cancer Therapies
Authors: Gould Harry J. , Paul Dennis
Published: April 2022

The conventional treatment of cancer has been based on the delivery of non-selective toxins and/or ionizing energy that affect both the cancer and normal tissues in the hope of destroying the offending disease before killing the patient. Unfortunately, resistance often develops to these treatments and patients experience severe, dose-limiting adverse effects that reduce treatment efficacy and compromise quality of life. Recent advances in our knowledge of the biology of tumor cells and their microenvironment, the recognition of surface proteins that are unique to specific cancers and essential to cell growth and survival and signaling pathways associate with invasion and metastasis have led to the development of targeted therapies that are able to identify specific cellular markers and more selectively deliver lethal treatment to the invading cancer thus improving efficacy and limiting adverse effects. In the context of targeted approaches to cancer therapy, we present targeted osmotic lysis as a novel and fundamentally different approach for treating advanced-stage carcinoma that exploits the conserved relationship between voltage-gated sodium channels and Na+, K+-ATPase and has the potential to increase survival without compromising quality of life in a broad spectrum of highly malignant forms of cancer.
A New Labdane-Type Diterpene, 6-O-Acetyl-(12R)-epiblumdane, from Stevia rebaudiana Leaves with Insulin Secretion Effect
Authors: Kang Heesun , Lee Dahae , Kang Ki Sung , Kim Ki Hyun
Published: April 2022

Stevia rebaudiana (Asteraceae), commonly known as candyleaf, sweetleaf, or sugarleaf, is a branched bushy shrub whose leaves are used as a natural sweetener owing to the high content of sweet diterpenes. As part of our ongoing work to identify structurally novel and bioactive natural products, phytochemical investigation of the ethanolic extract of S. rebaudiana leaves led to the isolation of one new labdane-type diterpene, 6-O-acetyl-(12R)-epiblumdane (1), and nine known terpenoids, including six diterpenes (2–6 and 10), two monoterpenes (7 and 8), and one triterpene (9). The structure of the new compound 1 was elucidated via analysis of one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopic data and high-resolution electrospray ionization mass spectrometry data, and its absolute configuration was established using electronic circular dichroism (ECD) calculations and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4 + probability analysis. The isolated compounds 1–10 were evaluated for their effects on glucose-stimulated insulin secretion in the INS-1 rat pancreatic β-cell line. The new compound 1, 6-O-acetyl-(12R)-epiblumdane, stimulated glucose-stimulated insulin secretion in INS-1 pancreatic β-cells without inducing cytotoxicity. Thus, 6-O-acetyl-(12R)-epiblumdane (1), an active compound derived from S. rebaudiana leaves, can be used as a potential therapeutic agent to prevent type 2 diabetes.
The Role of Osteopontin in Microglia Biology: Current Concepts and Future Perspectives
Authors: Rosmus Dennis-Dominik , Lange Clemens , Ludwig Franziska , Ajami Bahareh , Wieghofer Peter
Published: April 2022

The innate immune landscape of the central nervous system (CNS), including the brain and the retina, consists of different myeloid cell populations with distinct tasks to fulfill. Whereas the CNS borders harbor extraparenchymal CNS-associated macrophages whose main duty is to build up a defense against invading pathogens and other damaging factors from the periphery, the resident immune cells of the CNS parenchyma and the retina, microglia, are highly dynamic cells with a plethora of functions during homeostasis and disease. Therefore, microglia are constantly sensing their environment and closely interacting with surrounding cells, which is in part mediated by soluble factors. One of these factors is Osteopontin (OPN), a multifunctional protein that is produced by different cell types in the CNS, including microglia, and is upregulated in neurodegenerative and neuroinflammatory conditions. In this review, we discuss the current literature about the interaction between microglia and OPN in homeostasis and several disease entities, including multiple sclerosis (MS), Alzheimer’s and cerebrovascular diseases (AD, CVD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD) and diabetic retinopathy (DR), in the context of the molecular pathways involved in OPN signaling shaping the function of microglia. As nearly all CNS diseases are characterized by pathological alterations in microglial cells, accompanied by the disturbance of the homeostatic microglia phenotype, the emergence of disease-associated microglia (DAM) states and their interplay with factors shaping the DAM-signature, such as OPN, is of great interest for therapeutical interventions in the future.
Real-Time Detection of LAMP Products of African Swine Fever Virus Using Fluorescence and Surface Plasmon Resonance Method
Authors: Zhang Hao , Yao Yuan , Chen Zhi , Sun Wenbo , Liu Xiang , Chen Lei , Sun Jianhai , Qiu Xianbo , Yu Duli , Zhang Lulu
Published: April 2022

African swine fever (ASF) is a swine disease with a very high fatality rate caused by a complex double-stranded DNA virus. The fluorescence PCR detection method is widely used for virus nucleic acid detection. Surface plasmon resonance (SPR) is a label-free and real-time detection method, unlike the fluorescence PCR detection method. In this research, we detected the loop-mediated isothermal amplification (LAMP) products of the African swine fever virus by using the SPR and fluorescence methods separately and simultaneously. By comparing the positive and negative control results, we found that the SPR response unit is completely different before and after the LAMP process. In addition, the fluorescence results on a chip showed that with an increase in the concentration of the sample, the cycle threshold (CT) value decreased, which is consistent with commercial instruments. Both the decline rate of the SPR response unit and the CT value of the fluorescence realized were used to distinguish the positive control from the negative control and water, which indicates that the SPR method can be combined with fluorescence to detect LAMP products. This research provides a label-free and simple method for detecting LAMP products.
Safety and Efficacy of Hypofractionated Stereotactic Radiotherapy with Anlotinib Targeted Therapy for Glioblastoma at the First Recurrence: A Preliminary Report
Authors: Guan Yun , Li Jing , Gong Xiu , Zhu Huaguang , Li Chao , Mei Guanghai , Liu Xiaoxia , Pan Li , Dai Jiazhong , Wang Yang , Wang Enmin , Liu Ying , Wang Xin
Published: April 2022

(1) Background: Hypofractionated stereotactic radiotherapy (HSRT) and anti-vascular endothelial growth factor (VEGF) antibodies have been reported to have a promising survival benefit in recent studies. Anlotinib is a new oral VEGF receptor inhibitor. This report describes our experience using HSRT and anlotinib for recurrent glioblastoma (rGBM). (2) Methods: Between December 2019 and June 2020, rGBM patients were retrospectively analysed. Anlotinib was prescribed at 12 mg daily during HSRT. Adjuvant anlotinib was administered d1-14 every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS) after salvage treatment, and toxicity. (3) Results: Five patients were enrolled. The prescribed dose was 25.0 Gy in 5 fractions. The median number of cycles of anlotinib was 21 (14–33). The ORR was 100%. Three (60%) patients had the best outcome of a partial response (PR), and 2 (40%) achieved a complete response (CR). One patient died of tumour progression at the last follow-up. Two patients had grade 2 hand-foot syndrome. (4) Conclusions: Salvage HSRT combined with anlotinib showed a favourable outcome and acceptable toxicity for rGBM. A prospective phase II study (NCT04197492) is ongoing to further investigate the regimen.
Personalized Frequency Modulated Transcranial Electrical Stimulation for Associative Memory Enhancement
Authors: Bjekić Jovana , Živanović Marko , Paunović Dunja , Vulić Katarina , Konstantinović Uroš , Filipović Saša R.
Published: April 2022

Associative memory (AM) is the ability to remember the relationship between previously unrelated items. AM is significantly affected by normal aging and neurodegenerative conditions, thus there is a growing interest in applying non-invasive brain stimulation (NIBS) techniques for AM enhancement. A growing body of studies identifies posterior parietal cortex (PPC) as the most promising cortical target for both transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES) to modulate a cortico-hippocampal network that underlines AM. In that sense, theta frequency oscillatory tES protocols, targeted towards the hallmark oscillatory activity within the cortico-hippocampal network, are increasingly coming to prominence. To increase precision and effectiveness, the need for EEG guided individualization of the tES protocols is proposed. Here, we present the study protocol in which two types of personalized oscillatory tES–transcranial alternating current stimulation (tACS) and oscillatory transcranial direct current stimulation (otDCS), both frequency-modulated to the individual theta-band frequency (ITF), are compared to the non-oscillatory transcranial direct current stimulation (tDCS) and to the sham stimulation. The study has cross-over design with four tES conditions (tACS, otDCS, tDCS, sham), and the comprehensive set of neurophysiological (resting state EEG and AM-evoked EEG) and behavioral outcomes, including AM tasks (short-term associative memory, face–word, face–object, object-location), as well as measures of other cognitive functions (cognitive control, verbal fluency, and working memory).
A Tumor Suppressor Gene, N-myc Downstream-Regulated Gene 1 (NDRG1), in Gliomas and Glioblastomas
Authors: Nakahara Yukiko , Ito Hiroshi , Namikawa Hiroki , Furukawa Takashi , Yoshioka Fumitaka , Ogata Atsushi , Masuoka Jun , Abe Tatsuya
Published: April 2022

The development of potent and selective therapeutic approaches to glioblastoma (GBM) requires the identification of molecular pathways that critically regulate the survival and proliferation of GBM. Glioblastoma stem-like cells (GSCs) possess stem-cell-like properties, self-renewal, and differentiation into multiple neural cell lineages. From a clinical point of view, GSCs have been reported to resist radiation and chemotherapy. GSCs are influenced by the microenvironment, especially the hypoxic condition. N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress the proliferation, invasion, and migration of cancer cells. Previous studies have reported that deregulated expression of NDRG1 affects tumor growth and clinical outcomes of patients with GBM. This literature review aimed to clarify the critical role of NDRG1 in tumorigenesis and acquirement of resistance for anti-GBM therapies, further to discussing the possibility and efficacy of NDRG1 as a novel target of treatment for GBM. The present review was conducted by searching the PubMed and Scopus databases. The search was conducted in February 2022. We review current knowledge on the regulation and signaling of NDRG1 in neuro-oncology. Finally, the role of NDRG1 in GBM and potential clinical applications are discussed.
Understanding Temporal Relations in Mandarin Chinese: An ERP Investigation
Authors: Chen Lijuan , Lu Yiyi , Xu Xiaodong
Published: April 2022

Temporal connectives play a crucial role in marking the sequence of events during language comprehension. Although existing studies have shown that sentence comprehension can be modulated by temporal connectives, they have mainly focused on languages with grammatical tense such as English. It thus remains unclear how temporal information is processed in tenseless languages. The present study used event-related potentials (ERPs) to examine how world knowledge is retrieved and integrated in sentences linked by zhiqian (before) and zhihou (after) in Mandarin Chinese (e.g., After/Before going to the countryside, Grandpa went to the city because the air there was fresh and pure). The critical words (e.g., fresh) were either congruent or incongruent with world knowledge. Relative to the after-congruent sentences, the after-incongruent sentences evoked a P600 on critical words and a negativity on sentence-final words, whereas relative to before-congruent sentences, before-incongruent sentences showed no significant difference on critical words but a sustained negativity on sentence-final words. Additionally, before-congruent sentences elicited a larger sustained positivity (P600) than after-congruent sentences. The results suggest that before is more difficult to process than after in Mandarin Chinese, supporting the iconicity account of temporal relations.
Effective Use of Tower Cranes over Time in the Selected Construction Process
Authors: Motyčka Vít , Gašparík Jozef , Přibyl Oto , Štěrba Martin , Hořínková Dita , Kantová Radka
Published: April 2022

The quality of preparations carried out before building work commences has a significant impact on the smooth running and overall financial costs of a construction project. The use of construction machinery, which is crucial with regard to the efficiency of the construction process, plays an important role. In building construction, the machines in question are mainly tower cranes. The paper presents a new method for assessing the utilisation of tower cranes over time during the construction of reinforced concrete monolithic structures. The method, which contributes to the efficient utilisation of such cranes, is based on a mathematical simulation model that predicts the work cycles of a tower crane during a work shift when work is being performed on individual construction sub-processes. Construction sub-processes are analysed in detail with regard to the service provided to them by a tower crane. Data can also be obtained from binding construction schedules and boundary conditions, which in every case are for a specific executed construction project. The simulation model of the work of tower cranes has been developed for use in software applications. The created application expands the possibilities of smart construction site design in a digital environment and can also be used directly from an internet browser.
Prediction of Concrete Compressive Strength Using a Back-Propagation Neural Network Optimized by a Genetic Algorithm and Response Surface Analysis Considering the Appearance of Aggregates and Curing Conditions
Authors: Reza Kashyzadeh Kazem , Amiri Nima , Ghorbani Siamak , Souri Kambiz
Published: April 2022

In the present research, the authors have attempted to examine the compressive strength of conventional concrete, which is made using different aggregate sizes and geometries considering various curing temperatures. To this end, different aggregate geometries (rounded and angular) were utilized in various aggregate sizes (10, 20, and 30 mm) to prepare 108 rectangular cubic specimens. Then, the curing process was carried out in the vicinity of wind at different temperatures (5 °C < T < 30 °C). Next, the static compression experiments were performed on 28-day concrete specimens. Additionally, each test was repeated three times to check the repeatability of the results. Finally, the mean results were reported as the strength of concrete specimens. Response Surface Analysis (RSA) was utilized to determine the interaction effects of different parameters including the appearance of aggregates (shape and size) and curing temperature on the concrete strength. Afterwards, the optimum values of parameters were reported based on the RSA results to achieve maximum compressive strength. Moreover, to estimate concrete strength, a back-propagation neural network (OBPNN) optimized by a genetic algorithm (GA) was used. The findings of this study indicated that the developed neural network approach is greatly consistent with the experimental ones. Additionally, the compressive strength of concrete can be significantly increased (about 30%) by controlling the curing temperature in the range of 5–15 °C.
Higher Incidence of Diabetes in Cancer Patients Compared to Cancer-Free Population Controls: A Systematic Review and Meta-Analysis
Authors: Yang Keyi , Liu Zhunzhun , Thong Melissa S. Y. , Doege Daniela , Arndt Volker
Published: April 2022

Background: Diabetes increases the risk of certain types of cancer. However, the literature regarding the incidence of diabetes after cancer diagnosis is inconsistent. We aimed to assess whether there was a higher incidence of diabetes among cancer patients by performing a systematic review and meta-analysis of results from cohort studies. Methods: A systematic electronic literature search was carried out from cohort studies regarding the incidence of diabetes in cancer patients, using the databases PubMed (MEDLINE), Embase, Web of Science, and the Cochrane Library. Random-effects meta-analyses were conducted to pool the estimates. Results: A total of 34 articles involving 360,971 cancer patients and 1,819,451 cancer-free controls were included in the meta-analysis. An increased pooled relative risk (RR) of 1.42 (95% confidence interval (CI): 1.30–1.54, I2 = 95, τ2 = 0.0551, p < 0.01) for diabetes in cancer patients was found compared with the cancer-free population. The highest relative risk was observed in the first year after cancer diagnosis (RR = 2.06; 95% CI 1.63–2.60). Conclusions: New-onset diabetes is positively associated with cancer, but this association varies according to cancer type. More prospective studies with large sample sizes and longer follow-up times are advocated to further examine the association and the underlying mechanisms.
Fundus Autofluorescence Imaging in Patients with Choroidal Melanoma
Authors: Bindewald-Wittich Almut , Holz Frank G. , Ach Thomas , Fiorentzis Miltiadis , Bechrakis Nikolaos E. , Willerding Gregor D.
Published: April 2022

Choroidal melanocytic lesions require reliable and precise clinical examination and diagnosis to differentiate benign choroidal nevi from choroidal melanoma, as the latter may become life-threatening through metastatic disease. To come to an accurate diagnosis, as well as for monitoring, and to assess the efficacy of therapy, various imaging modalities may be used, one of which is non-invasive fundus autofluorescence (FAF) imaging using novel high-resolution digital imaging technology. FAF imaging is based on the visualization of intrinsic fluorophores in the ocular fundus. Lipofuscin and melanolipofuscin within the postmitotic retinal pigment epithelium (RPE) cells represent the major fluorophores that contribute to the FAF signal. In addition, the presence or loss of absorbing molecular constituents may have an impact on the FAF signal. A choroidal melanoma can cause secondary retinal and RPE alterations that affect the FAF signal (e.g., occurrence of orange pigment). Therefore, FAF imaging supports multimodal imaging and gives additional information over and above conventional imaging modalities regarding retinal metabolism and RPE health status. This article summarises the features of FAF imaging and the role of FAF imaging in the context of choroidal melanoma, both before and following therapeutic intervention.
Colorectal Cancer: The Contribution of CXCL12 and Its Receptors CXCR4 and CXCR7
Authors: Goïta Aïssata Aimée , Guenot Dominique
Published: April 2022

Colorectal cancer is one of the most common cancers, and diagnosis at late metastatic stages is the main cause of death related to this cancer. This progression to metastasis is complex and involves different molecules such as the chemokine CXCL12 and its two receptors CXCR4 and CXCR7. The high expression of receptors in CRC is often associated with a poor prognosis and aggressiveness of the tumor. The interaction of CXCL12 and its receptors activates signaling pathways that induce chemotaxis, proliferation, migration, and cell invasion. To this end, receptor inhibitors were developed, and their use in preclinical and clinical studies is ongoing. This review provides an overview of studies involving CXCR4 and CXCR7 in CRC with an update on their targeting in anti-cancer therapies.
Utility of Continuous Disease Subtyping Systems for Improved Evaluation of Etiologic Heterogeneity
Authors: Li Ruitong , Ugai Tomotaka , Xu Lantian , Zucker David , Ogino Shuji , Wang Molin
Published: April 2022

Molecular pathologic diagnosis is important in clinical (oncology) practice. Integration of molecular pathology into epidemiological methods (i.e., molecular pathological epidemiology) allows for investigating the distinct etiology of disease subtypes based on biomarker analyses, thereby contributing to precision medicine and prevention. However, existing approaches for investigating etiological heterogeneity deal with categorical subtypes. We aimed to fully leverage continuous measures available in most biomarker readouts (gene/protein expression levels, signaling pathway activation, immune cell counts, microbiome/microbial abundance in tumor microenvironment, etc.). We present a cause-specific Cox proportional hazards regression model for evaluating how the exposure–disease subtype association changes across continuous subtyping biomarker levels. Utilizing two longitudinal observational prospective cohort studies, we investigated how the association of alcohol intake (a risk factor) with colorectal cancer incidence differed across the continuous values of tumor epigenetic DNA methylation at long interspersed nucleotide element-1 (LINE-1). The heterogeneous alcohol effect was modeled using different functions of the LINE-1 marker to demonstrate the method’s flexibility. This real-world proof-of-principle computational application demonstrates how the new method enables visualizing the trend of the exposure effect over continuous marker levels. The utilization of continuous biomarker data without categorization for investigating etiological heterogeneity can advance our understanding of biological and pathogenic mechanisms.
Beyond PD-L1—Identification of Further Potential Therapeutic Targets in Oral Cancer
Authors: Weber Manuel , Lutz Rainer , Olmos Manuel , Glajzer Jacek , Baran Christoph , Nobis Christopher-Philipp , Möst Tobias , Eckstein Markus , Kesting Marco , Ries Jutta
Published: April 2022

Background: The involvement of immune cell infiltration and immune regulation in the progression of oral squamous cell carcinoma (OSCC) is shown. Anti-PD-1 therapy is approved for the treatment of advanced OSCC cases, but not all patients respond to immune checkpoint inhibitors. Hence, further targets for therapeutic approaches are needed. The number of identified cellular receptors with immune checkpoint function is constantly increasing. This study aimed to perform a comparative analysis of a large number of immune checkpoints in OSCC in order to identify possible targets for therapeutic application. Materials and Methods: A NanoString mRNA analysis was performed to assess the expression levels of 21 immune regulatory checkpoint molecules in OSCC tissue (n = 98) and healthy oral mucosa (NOM; n = 41). The expression rates were compared between the two groups, and their association with prognostic parameters was determined. Additionally, relevant correlations between the expression levels of different checkpoints were examined. Results: In OSCC tissue, significantly increased expression of CD115, CD163, CD68, CD86, CD96, GITRL, CD28 and PD-L1 was detected. Additionally, a marginally significant increase in CD8 expression was observed. BTLA and PD-1 levels were substantially increased, but the differential expression was not statistically significant. The expression of CD137L was significantly downregulated in OSCC compared to NOM. Correlations between immune checkpoint expression levels were demonstrated, and some occurred specifically in OSCC tissue. Conclusions: The upregulation of inhibitory receptors and ligands and the downregulation of activators could contribute to reduced effector T-cell function and could induce local immunosuppression in OSCC. Increased expression of activating actors of the immune system could be explained by the increased infiltration of myeloid cells and T-cells in OSCC tissue. The analysis contributes to the understanding of immune escape in OSCC and reveals potential targets for oral cancer immunotherapy.
Genetic Clonality as the Hallmark Driving Evolution of Non-Small Cell Lung Cancer
Authors: Nicoś Marcin , Krawczyk Paweł
Published: April 2022

Data indicate that many driver alterations from the primary tumor of non-small cell lung cancer (NSCLC) are predominantly shared across all metastases; however, disseminating cells may also acquire a new genetic landscape across their journey. By comparing the constituent subclonal mutations between pairs of primary and metastatic samples, it is possible to derive the ancestral relationships between tumor clones, rather than between tumor samples. Current treatment strategies mostly rely on the theory that metastases are genetically similar to the primary lesions from which they arise. However, intratumor heterogeneity (ITH) affects accurate diagnosis and treatment decisions and it is considered the main hallmark of anticancer therapy failure. Understanding the genetic changes that drive the metastatic process is critical for improving the treatment strategies of this deadly condition. Application of next generation sequencing (NGS) techniques has already created knowledge about tumorigenesis and cancer evolution; however, further NGS implementation may also allow to reconstruct phylogenetic clonal lineages and clonal expansion. In this review, we discuss how the clonality of genetic alterations influence the seeding of primary and metastatic lesions of NSCLC. We highlight that wide genetic analyses may reveal the phylogenetic trajectories of NSCLC evolution, and may pave the way to better management of follow-up and treatment.
Unmet Needs and Perspectives in Oral Cancer Prevention
Authors: Bouaoud Jebrane , Bossi Paolo , Elkabets Moshe , Schmitz Sandra , van Kempen Léon C. , Martinez Pierre , Jagadeeshan Sankar , Breuskin Ingrid , Puppels Gerwin J. , Hoffmann Caroline , Hunter Keith D. , Simon Christian , Machiels Jean-Pascal , Grégoire Vincent , Bertolus Chloé , Brakenhoff Ruud H. , Koljenović Senada , Saintigny Pierre
Published: April 2022

Oral potentially malignant disorders (OPMD) may precede oral squamous cell carcinoma (OSCC). Reported rates of malignant transformation of OPMD range from 3 to 50%. While some clinical, histological, and molecular factors have been associated with a high-risk OPMD, they are, to date, insufficiently accurate for treatment decision-making. Moreover, this range highlights differences in the clinical definition of OPMD, variation in follow-up periods, and molecular and biological heterogeneity of OPMD. Finally, while treatment of OPMD may improve outcome, standard therapy has been shown to be ineffective to prevent OSCC development in patients with OPMD. In this perspective paper, several experts discuss the main challenges in oral cancer prevention, in particular the need to (i) to define an OPMD classification system by integrating new pathological and molecular characteristics, aiming (ii) to better identify OPMD at high risk of malignant transformation, and (iii) to develop treatment strategies to eradicate OPMD or prevent malignant transformation.
Methylene Blue Near-Infrared Fluorescence Imaging in Breast Cancer Sentinel Node Biopsy
Authors: Budner Oliver , Cwalinski Tomasz , Skokowski Jarosław , Marano Luigi , Resca Luca , Cwalina Natalia , Kalinowski Leszek , Hoveling Richelle , Roviello Franco , Polom Karol
Published: April 2022

Introduction: Fluorescence-based navigation for breast cancer sentinel node biopsy is a novel method that uses indocyanine green as a fluorophore. However, methylene blue (MB) also has some fluorescent properties. This study is the first in a clinical series presenting the possible use of MB as a fluorescent dye for the identification of sentinel nodes in breast sentinel node biopsy. Material and methods: Forty-nine patients with breast cancer who underwent sentinel node biopsy procedures were enrolled in the study. All patients underwent standard simultaneous injection of nanocolloid and MB. We visualized and assessed the sentinel nodes and the lymphatic channels transcutaneously, with and without fluorescence, and calculated the signal-to-background ratio (SBR). We also analyzed the corresponding fluorescence intensity of various dilutions of MB. Results: In twenty-three patients (46.9%), the location of the sentinel node, or the end of the lymphatic path, was visible transcutaneously. The median SBR for transcutaneous sentinel node location was 1.69 (range 1.66–4.35). Lymphatic channels were visible under fluorescence in 14 patients (28.6%) prior to visualization by the naked eye, with an average SBR of 2.01 (range 1.14–5.6). The sentinel node was visible under fluorescence in 25 patients (51%). The median SBR for sentinel node visualization with MB fluorescence was 2.54 (range 1.34–6.86). Sentinel nodes were visualized faster under fluorescence during sentinel node preparation. Factors associated with the rate of visualization included diabetes (p = 0.001), neoadjuvant chemotherapy (p = 0.003), and multifocality (p = 0.004). The best fluorescence was obtained using 40 μM (0.0128 mg/mL) MB, but we also observed a clinically relevant dilution range between 20 μM (0.0064 mg/mL) and 100 μM (0.032 mg/mL). Conclusions: For the first time, we propose the clinical usage of MB as a fluorophore for fluorescence-guided sentinel node biopsy in breast cancer patients. The quenching effect of the dye may be the reason for its poor detection rate. Our analysis of different concentrations of MB suggests a need for a detailed clinical analysis to highlight the practical usefulness of the dye.