bluuebunny/crossref_metadata_2025 huggingface dataset:
Schrödinger's tree—On syntax and neural language models
Authors: Kulmizev Artur , Nivre Joakim
Published: October 2022

In the last half-decade, the field of natural language processing (NLP) has undergone two major transitions: the switch to neural networks as the primary modeling paradigm and the homogenization of the training regime (pre-train, then fine-tune). Amidst this process, language models have emerged as NLP's workhorse, displaying increasingly fluent generation capabilities and proving to be an indispensable means of knowledge transfer downstream. Due to the otherwise opaque, black-box nature of such models, researchers have employed aspects of linguistic theory in order to characterize their behavior. Questions central to syntax—the study of the hierarchical structure of language—have factored heavily into such work, shedding invaluable insights about models' inherent biases and their ability to make human-like generalizations. In this paper, we attempt to take stock of this growing body of literature. In doing so, we observe a lack of clarity across numerous dimensions, which influences the hypotheses that researchers form, as well as the conclusions they draw from their findings. To remedy this, we urge researchers to make careful considerations when investigating coding properties, selecting representations, and evaluatingviadownstream tasks. Furthermore, we outline the implications of the different types of research questions exhibited in studies on syntax, as well as the inherent pitfalls of aggregate metrics. Ultimately, we hope that our discussion adds nuance to the prospect of studying language models and paves the way for a less monolithic perspective on syntax in this context.
What implementation strategies are relational? Using Relational Theory to explore the ERIC implementation strategies
Authors: Bartley Leah , Metz Allison , Fleming W. Oscar
Published: October 2022

The identification and use of implementation strategies in implementation research and practice have strengthened our understanding of the implementation process as well as the causal pathways between mechanisms, strategies, and implementation outcomes. Although these contributions have advanced the application of strategies, there is still a need to learn more about how strategies might integrate relational exchanges and interactions. The inclusion of critical perspectives has been limited in implementation science, and theories such as Relational Theory can expand our understanding of the relational nature of implementation and enhance rigor through alternative theoretical applications. This study applied Relational Theory through a qualitative directed content analysis of the 73 Expert Recommendations for Implementation Change (ERIC) implementation strategies and examine relational components in strategy descriptions. Three reviewers used the structured approach to review and categorize the implementation strategies based on the Relational and Transactional Strategy Continuum measure, which operationalizes types of interactions, exchanges and alliances. Relational alliance strategies are those in which there is mutual growth and accountability, frequent interaction, shared power, and potential vulnerability. Operational alliances include forms of working exchanges between parties with balanced transactional and relational features. Operational alliances can be somewhat interactive in nature, with minor exchanges and limited accountability. Transactional alliance strategies are mostly uni-directional, influenced by power differentials, and do not require mutual growth, commitment, or exchange; thus, the power of growth is inherently one-sided. Results from the review suggest more implementation strategies with relational alliance features (highly relational, n = 17, semi-relational, n = 19) compared to transactional (highly transactional, n = 9, semi-transactional, n = 10) and 18 strategies coded as operational alliances. The qualitative review revealed opportunities to further expand how relational exchanges are considered within the implementation strategies descriptions, as well as the role of actors and power dynamics within strategy exchanges. The Relational and Transactional Strategy Continuum measure can help practitioners and researchers consider the sequencing, pairing, and impact on outcomes of different types and combinations of strategies in implementation practice and research. Additionally, the measure can support reflection on strategies that promote positive alliances, frequent connections, bi-directional communication, and power sharing.
Understanding implementation research collaborations from a co-creation lens: Recommendations for a path forward
Authors: Pérez Jolles Mónica , Willging Cathleen E. , Stadnick Nicole A. , Crable Erika L. , Lengnick-Hall Rebecca , Hawkins Jemma , Aarons Gregory A.
Published: October 2022

Increasing calls within the field of implementation science (IS) research seek to promote active engagement of diverse and often disenfranchised stakeholder voices to increase buy-in, fidelity, outcome relevance, and sustainment of evidence-based practices (EBPs). Including such voices requires cultural humility and the integration of multiple perspectives and values among organizations, groups, and individuals. However, the IS field lacks guidance for researchers on structuring collaborative approaches to promote a co-created process (i.e., synergistic approach to goal attainment). We contend that improved operationalization of co-created implementation collaborations is critical to sparking synergy and addressing differentials based on power, privilege, knowledge, and access to resources among stakeholders. These differentials can undermine future implementation and sustainment efforts if not addressed early in the research effort. An insufficient understanding of the guiding principles of co-created implementation collaborations may limit the scientific value of evaluation processes, and researchers' ability to replicate outcomes. We propose a perspective foregrounded in the concept of co-creation to guide the structuring of implementation collaboratives through five principles. We offer three case examples informed by the Exploration, Preparation, Implementation, Sustainment (EPIS) Framework to illustrate the application of these co-creation principles. Lastly, we offer recommendations for promoting co-creation in IS research moving forward.
Internet-based survey evaluating the impact of ground substrate on injury and performance in canine agility athletes
Authors: Jimenez Isabel A. , Canapp Sherman O. , Percival Monica L.
Published: October 2022

Agility is a rapidly growing canine performance sport worldwide, yet the literature is sparse regarding the impact of ground substrate on performance and injury. Approximately 1/3 of dogs participating in agility trials will experience a performance-related injury. The impact of ground material has been well-documented in racing greyhounds, equine athletes, and humans, but has been minimally investigated in agility dogs. In this retrospective, cross-sectional study, 300 respondents (handlers, owners, and trainers) of 308 agility dogs completed an online survey regarding their dog's training and competition regimen, history of injury, perceived association between injury and substrate and/or agility obstacle, markers of decreased performance (MDPs) observed on different substrates, and changes to routine following injury. 35.7% of dogs sustained a training injury (TI) and 11.2% sustained a competition injury (CI). The most commonly reported sites of injury were the shoulder (TI: 33.9%, CI: 25.4%), forelimb digits (TI: 14.7%, CI: 11.9%) and iliopsoas muscle (TI: 11.9%, CI: 13.6%). Dogs most commonly trained on natural grass (85.3%), artificial turf (50.8%), and dirt (34.5%). Significantly fewer MDPs were observed on natural grass than any other substrate except dirt. Significantly more MDPs were noted on rubber mat compared to natural grass, artificial turf, dirt, sand, or foam mat. Rubber mat had the highest Incidence Proportion (IP) (32.0%) of TI and was perceived to be related to TI in 87.5% of cases. Obstacles perceived to be associated with injuries included jumps (TI: 37.5%, CI: 27.8%), contacts (TI: 29.7%, CI: 22.2%), weaves (TI: 11.9%, CI: 13.9%), and tunnels (CI: 25.0%). Overall, agility dogs were perceived to perform best on natural grass and dirt, while rubber mat was associated with injury and decreased performance. Respondents were willing to make significant alterations to their dog's routine due to a perceived association between substrate, injury, and performance. Further prospective studies are needed to assess the impact of substrate composition and maintenance, and inform evidence-based recommendations to maximize performance and minimize performance-related injury in agility dogs.
Experimental Study of the Acoustic Cavitation Threshold in Sunflower Oil Depending on Different Impact Regime
Authors: Mikhailova Natalia , Smirnov Ivan , Yakupov Bulat
Published: October 2022

In engineering problems associated with acoustic wave propagation in a liquid, cavitation onset could be an adverse phenomenon, or, conversely, a required process. In both cases, knowledge of the ultrasonic parameters that lead to cavitation onset under given external conditions is relevant and necessary for solving both fundamental and practical problems. The present work proposes experimental results of studying the threshold of acoustic cavitation, which was implemented at different ultrasound frequencies with a change in external pressure, power of transducer and temperature of the liquid. The experiments were carried out for sunflower oil. The test findings demonstrated how the cavitation threshold changes with varying the power of ultrasound exposure in time. In addition, the effect of external pressure fluctuations on cavitation onset was investigated. The obtained results contribute to the understanding of cavitation processes and could be necessary for verification of theoretical models.
B-Mode and Contrast-Enhanced Ultrasonography Aspects of Benign and Malignant Superficial Neoplasms in Dogs: A Preliminary Study
Authors: Hillaert Amber , Stock Emmelie , Duchateau Luc , de Rooster Hilde , Devriendt Nausikaa , Vanderperren Katrien
Published: October 2022

Contrast-enhanced ultrasonography (CEUS) is considered a promising technique for differentiation of benign and malignant tumors in humans. However, few studies have assessed superficial neoplasms in dogs by means of CEUS. The aim of this study was to identify ultrasonographic criteria evaluated by B-mode ultrasound (US) and CEUS that may be used to distinguish benign and malignant superficial neoplasms in dogs. A total of 63 superficial neoplasms from 59 dogs were evaluated using B-mode US and CEUS prior to histopathologic examination. Qualitative and quantitative parameters were compared between benign and malignant neoplasms by Fischer’s exact test or fixed effects model. With B-mode US, a significant difference was found for border definition, echogenicity and echotexture. With CEUS, a significant difference was found for the enhancement pattern at wash-in and the wash-out area under the curve at the center of the neoplasm. Malignant neoplasms had on average a lower regional blood volume during the wash-out phase compared to benign neoplasms. Despite these significant differences, there was a considerable overlap in B-mode and CEUS parameters between benign and malignant neoplasms. In conclusion, B-mode US and CEUS might contribute to malignancy prediction; however, based on individual ultrasonographic parameters, they seem unable to replace cytology or histopathology.
Improved Deep Recurrent Q-Network of POMDPs for Automated Penetration Testing
Authors: Zhang Yue , Liu Jingju , Zhou Shicheng , Hou Dongdong , Zhong Xiaofeng , Lu Canju
Published: October 2022

With the development of technology, people’s daily lives are closely related to networks. The importance of cybersecurity protection draws global attention. Automated penetration testing is the novel method to protect the security of networks, which enhances efficiency and reduces costs compared with traditional manual penetration testing. Previous studies have provided many ways to obtain a better policy for penetration testing paths, but many studies are based on ideal penetration testing scenarios. In order to find potential vulnerabilities from the perspective of hackers in the real world, this paper models the process of black-box penetration testing as a Partially Observed Markov Decision Process (POMDP). In addition, we propose a new algorithm named ND3RQN, which is applied to the automated black-box penetration testing. In the POMDP model, an agent interacts with a network environment to choose a better policy without insider information about the target network, except for the start points. To handle this problem, we utilize a Long Short-Term Memory (LSTM) structure empowering agent to make decisions based on historical memory. In addition, this paper enhances the current algorithm using the structure of the neural network, the calculation method of the Q-value, and adding noise parameters to the neural network to advance the generalization and efficiency of this algorithm. In the last section, we conduct comparison experiments of the ND3RQN algorithm and other recent state-of-the-art (SOTA) algorithms. The experimental results vividly show that this novel algorithm is able to find a greater attack-path strategy for all vulnerable hosts in the automated black-box penetration testing. Additionally, the generalization and robustness of this algorithm are far superior to other SOTA algorithms in different size simulation scenarios based on the CyberBattleSim simulation developed by Microsoft.
Atmospheric Ultrafine Particulate Matter (PM0.1)-Bound Carbon Composition in Bangkok, Thailand
Authors: Phairuang Worradorn , Hongtieab Surapa , Suwattiga Panwadee , Furuuchi Masami , Hata Mitsuhiko
Published: October 2022

Seasonal variations in atmospheric ultrafine particulate matter (PM0.1) were monitored in Bangkok, Thailand, from 2016 to 2017. PM0.1-bound organic carbon (OC) and elemental carbon (EC) were collected by a cascade air sampler that can collect PM0.1 and were analyzed by a Thermal-Optical carbon analyzer following the IMPROVE-TOR protocol. The annual average PM0.1 in Bangkok was 14.5 ± 4.7 µg/m3, which is higher than in large Asian cities such as Shanghai and Hanoi. Biomass burning from neighboring areas was shown to increase the particle concentration. Apparent increases in carbon species such as OC and EC, and the OC/EC ratios in the wet and dry seasons were observed; the Char-EC/Soot-EC ratio revealed that the PM0.1 in the Bangkok atmosphere was influenced mainly by vehicle exhausts, even though the influence of biomass burning was greater during the dry season. The effective carbon ratio (ECR) shows that Bangkok’s carbonaceous aerosol is light-absorbing and -scattering. The higher SOC/OC in the dry season indicates the high level of secondary sources forming smaller particles from the combustion sources in Bangkok, increasing light scattering during these periods, and contributing to climate and air quality. The findings of this work are of great importance to air pollutant control policies in urban areas.
Routes Alternatives with Reduced Emissions: Large-Scale Statistical Analysis of Probe Vehicle Data in Lyon
Authors: Jayol Alexandre , Lejri Delphine , Leclercq Ludovic
Published: October 2022

Vehicle air pollution is a significant problem for health and climate change that can be solved by several approaches. The route is one of the many components to be considered. In this work, we propose a statistical analysis of a large FCD database in November 2017 in Lyon (France) in order to find alternative sustainable trips and evaluate potential emission reductions (CO2, NOx, PM10). To this end, an innovative framework was built. First, we assessed vehicle speeds for each network section and the fifteen-minute period, when this information was reachable. Then, we used a regression random forest (RF) algorithm to fill in the missing data. This dynamical speed map allowed us to search for fewer pollutant trips, for the first ten days of November. By using COPERT emission factors (EFs) and the time-dependent Dijkstra algorithm, we successfully identified between 51% and 72% of alternative sustainable paths, depending on the engine technology and the pollutant. We investigated the influence of vehicle technology. In all cases, the number of alternative trips found tends to be the same as soon as the emission savings exceed 5%. Moreover, about 400 trips out of 11,000 have the potential to mitigate about 20% of emissions.
Evaluation of Advanced Diesel Particulate Filter Concepts for Post Euro VI Heavy-Duty Diesel Applications
Authors: Mamakos Athanasios , Rose Dominik , Besch Marc C. , He Suhao , Gioria Roberto , Melas Anastasios , Suarez-Bertoa Ricardo , Giechaskiel Barouch
Published: October 2022

The European Commission (EC) is in the process of finalizing the proposal for the upcoming legislative stage for light- and heavy-duty vehicles. The emission performance over extended operating conditions is under consideration. Furthermore, a tightening of the Solid Particle Number (SPN) limits with a parallel shift of the lowest detectable size from 23 to 10 nm has been suggested. This paper investigates the SPN emission performance of a Euro VI step E HDV and the potential offered by an advanced Diesel Particulate Filter (DPF) to meet the upcoming regulations. Cold start emissions at clean DPF state were found to be as high as 1.3 × 1012 #/kWh, while passive regeneration events could lead to hot start emissions of 3 × 1011 #/kWh. Improvements in the filtration efficiencies at clean state, similar to those offered by the advanced DPF (>99%), will be needed to tackle these operating conditions. The measurements also revealed the formation of 10 nm SPN in the Selective Catalytic Reduction (SCR) system, at a rate of ~1.2 × 1011 #/kWh. These levels lie above the proposed limit of 1011 #/kWh, highlighting the need to also control these non-volatile nanosized particles.
PM2.5 Source Apportionment and Implications for Particle Hygroscopicity at an Urban Background Site in Athens, Greece
Authors: Diapouli Evangelia , Fetfatzis Prodromos , Panteliadis Pavlos , Spitieri Christina , Gini Maria I. , Papagiannis Stefanos , Vasilatou Vasiliki , Eleftheriadis Konstantinos
Published: October 2022

Aerosol hygroscopicity is a key aerosol property, influencing a number of other physical properties, and the impacts of PM pollution on the environment, climate change, and health. The present work aims to provide insight into the contribution of major PM sources to aerosol hygroscopicity, focusing on an urban background site, with a significant impact from both primary and secondary sources. The EPA PMF 5.0 model was applied to PM2.5 chemical composition and hygroscopicity data collected from August 2016 to July 2017 in Athens, Greece. Source apportionment analysis resulted in six major sources, including four anthropogenic sources (vehicular exhaust and non-exhaust, heavy oil combustion, and a mixed source of secondary aerosol formation and biomass burning) and two natural sources (mineral dust and aged sea salt). The mixed source was found to be the main contributor to PM2.5 levels (44%), followed by heavy oil combustion (26%) and vehicular traffic exhaust and non-exhaust emissions (15%). The aerosol hygroscopic growth factor (GF) was found to be mainly associated with the mixed source (by 36%) and heavy oil combustion (by 24%) and, to a lesser extent, with vehicle exhaust (by 19%), aged sea salt (by 14%), and vehicle non-exhaust (by 6%).
Evaluation of the Barrier Effect of Polylactic Acid-Modified Membrane on Odours at the Excavated Soil Interface of a Pesticide-Contaminated Site
Authors: Zheng Hongguang , Ma Yan , Du Xiaoming , Zhang Meng , Shi Yi , Yao Juejun , Zhao Weiguang
Published: October 2022

Polylactic acid (PLA) is a highly promising bio-based polymer that can replace petroleum-based materials. The PLA-modified membrane has been found to effectively block soil odours in laboratory experiments, but its barrier effect at the excavated soil interfaces of actual pesticide sites requires further evaluation. This study investigates the barrier effect of the PLA-modified membrane on odours at the excavated soil interface of a pesticide-contaminated site in Guangdong Province, China. The membrane’s barrier effect on odours was comprehensively evaluated using the static chamber technique with three indicators: diffusion flux, odour concentration, and a health risk index. The results showed that the initial diffusion fluxes of six main odour substances: m- and p-xylene, o-xylene, toluene, ethylbenzene, n-propylbenzene, and cumene were 1.95 × 100, 2.88 × 10−1, 7.27 × 10−3, 1.49 × 100, 2.97 × 10−3, and 3.89 × 10−3 mg/(m2·s) based on the contribution rate. After laying the PLA-modified membrane, the flux reduction rate of all six odour substances was generally >90%. The background odour concentration in the test area was 109.56, and the odour concentration after laying the membrane was <1.12. The initial non-carcinogenic and carcinogenic risk indices of the test area were 3.03 and 1.62 × 10−4, respectively. After laying the membrane, these indices were <0.05 and <3.78 × 10−7, respectively, indicating no health risk. Overall, the PLA-modified membrane had a good barrier effect on odours in the on-site application, effectively reducing the diffusion and nuisances of odours, as well as their health risks.
Global Ionospheric Disturbance Propagation and Vertical Ionospheric Oscillation Triggered by the 2022 Tonga Volcanic Eruption
Authors: Kong Qiaoli , Li Changsong , Shi Kunpeng , Guo Jinyun , Han Jingwei , Wang Tianfa , Bai Qi , Chen Yanfei
Published: October 2022

The Tonga volcano erupted on 15 January 2022, at 04:15:45 UTC, which significantly influenced the atmosphere and space environment, at the same time, an unprecedented opportunity to monitor ionospheric anomalies is provided by its powerful eruption. In current studies of traveling ionospheric disturbance (TID) triggered by the 2022 Tonga volcanic eruption, the particular phenomenon of ionospheric disturbances in various parts of the world has not been reasonably explained, and the vertical ionospheric disturbances are still not effectively detected. In this paper, we calculate the high-precision slant total electron content (STEC) from more than 3000 ground-based GPS stations distributed around the world, then we obtain the radio occultation (RO) data from near-field COSMIC-2 profiles and investigate the horizontal TID and the vertical ionospheric disturbances by the singular spectrum analysis (SSA). Horizontal TID propagation captured by GPS STEC results indicates that acoustic-gravity waves dominate the energy input at the beginning of the ionospheric disturbance with an approximate speed of 1050 m/s initially. With the dissipation of the shock energy, lamb waves become a dominant mode of ionospheric disturbances, moving at a more stable speed of about 326 m/s to a range of 16,000 km beyond the far-field. Local characteristics are evident during the disturbance, such as the ionospheric conjugation in Australia and the rapid decay of TID in Europe. The shock-Lamb-tsunami waves’ multi-fluctuation coupling is recorded successively from the COSMIC-2 RO observation data. The shock and Lamb waves can perturb the whole ionospheric altitude. In contrast, the disturbance caused by tsunami waves is much smaller than that of acoustic-gravity waves and Lamb waves. In addition, influenced by the magnetic field, the propagation speed of TID induced by Lamb waves is higher towards the northern hemisphere than towards the southern hemisphere.
Fabrication of TiFe-Based Electrodes Using High-Energy Ball Mill with Mn Additive for NiMH Batteries
Authors: Zali Amir , Kashani-Bozorg Seyed Farshid , Lalegani Zahra , Hamawandi Bejan
Published: October 2022

Binary and ternary (with the addition of Mn) TiFe-based intermetallic compound powders were fabricated by high energy ball milling, and their electrochemical behavior as negative electrodes was investigated in 6M-KOH. X-ray diffraction exhibited the single phase of nanostructured binary and ternary TiFe-based crystallites after 20 h of milling followed the amorphous phase formation. Addition of Mn increased peak broadening and in turn decreased the nanocrystallite size of TiFe. Electrode properties of 20, 40, 60, and 70 h binary milled products showed that the discharge capacity of the 60 h one offered a maximum discharge capacity of ~169 mAhg−1. Although substitution of Mn for Ti (Ti1−xFeMnx, x = 0.1, 0.2) caused a decrease in initial discharge capacity, the periodic stability increased compared to the binary TiFe and ternary TiFe1-xMnx (x = 0.1, 0.2). The ternary Ti0.9FeMn0.1 electrode maintained ~53% of its initial discharge capacity after five cycles of charge–discharge; this was just 28% in the case of binary TiFe electrode.
Enabling Digital Twins to Support the UN SDGs
Authors: Hassani Hossein , Huang Xu , MacFeely Steve
Published: October 2022

Digitalisation has enjoyed rapid acceleration during the COVID-19 pandemic on top of the already fast-paced expansion impacting almost every aspect of daily life. Digital twin technology, which is considered a building block of Metaverse and an important pillar of Industrial revolution 4.0, has also received growing interest. Apart from its significant contribution to intelligent manufacturing, there has been considerable discussion on its implementation and the as yet undiscovered potential. This paper reviews the current trajectory of digital twin applications in supporting general sustainability, in the context of the 17 UN SDGs. Furthermore, it connects researchers and readers from different fields with the aim of achieving a better understanding of emerging digital twin technologies, the current values this technology has brought to support UN SDGs, and identify areas with potential for future research to better contribute to achieving the remaining tasks of Agenda 2030.
Intercellular Communication Reveals Therapeutic Potential of Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer
Authors: Liu Yang , Fang Yu , Bao Lili , Wu Feng , Wang Shilong , Hao Siyu
Published: October 2022

(1) Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high intra-tumoral heterogeneity. The epithelial-mesenchymal transition (EMT) is one of the inducers of cancer metastasis and migration. However, the description of the EMT process in TNBC using single-cell RNA sequencing (scRNA-seq) remains unclear. (2) Methods: In this study, we analyzed 8938 cellular gene expression profiles from five TNBC patients. We first scored each malignant cell based on functional pathways to determine its EMT characteristics. Then, a pseudo-time trajectory analysis was employed to characterize the cell trajectories. Furthermore, CellChat was used to identify the cellular communications. (3) Results: We identified 888 epithelium-like and 846 mesenchyme-like malignant cells, respectively. A further pseudo-time trajectory analysis indicated the transition trends from epithelium-like to mesenchyme-like in malignant cells. To characterize the potential regulators of the EMT process, we identified 10 dysregulated transcription factors (TFs) between epithelium-like and mesenchyme-like malignant cells, in which overexpressed forkhead box protein A1 (FOXA1) was recognized as a poor prognosis marker of TNBC. Furthermore, we dissected the cell-cell communications via ligand-receptor (L-R) interactions. We observed that tumor-associated macrophages (TAMs) may support the invasion of malignant epithelial cells, based on CXCL-CXCR2 signaling. The tumor necrosis factor (TNF) signaling pathway secreted by TAMs was identified as an outgoing communication pattern, mediating the communications between monocytes/TAMs and malignant epithelial cells. Alternatively, the TNF-related ligand-receptor (L-R) pairs showed promising clinical implications. Some immunotherapy and anti-neoplastic drugs could interact with the L-R pairs as a potential strategy for the treatment of TNBC. In summary, this study enhances the understanding of the EMT process in the TNBC microenvironment, and dissections of EMT-related cell communications also provided us with potential treatment targets.
Adherence and Reactogenicity to Vaccines against SARS-COV-2 in 285 Patients with Neuropathy: A Multicentric Study
Authors: Iacono Salvatore , Di Stefano Vincenzo , Alonge Paolo , Vinciguerra Claudia , Milella Giammarco , Caputo Francesca , Lasorella Piergiorgio , Neto Gabriele , Pignolo Antonia , Torrente Angelo , Lupica Antonino , Ajdinaj Paola , Firenze Alberto , Tozza Stefano , Manganelli Fiore , Di Muzio Antonio , Piscosquito Giuseppe , Brighina Filippo
Published: October 2022

Background: The safety of the new vaccines against SARS-CoV-2 have already been shown, although data on patients with polyneuropathy are still lacking. The aim of this study is to evaluate the adherence to SARS-CoV-2 vaccination, as well as the reactogenicity to those vaccines in patients affected by neuropathy. Methods: A multicentric and web-based cross-sectional survey was conducted among patients affected by neuropathy from part of South Italy. Results: Out of 285 responders, n = 268 were included in the final analysis and n = 258 of them (96.3%) were fully vaccinated. Adherence to vaccination was higher in patients with hereditary neuropathies compared to others, while it was lower in patients with anti-MAG neuropathy (all p < 0.05). The overall prevalence of adverse events (AEs) was 61.2% and its occurrence was not associated with neuropathy type. Being female and of younger age were factors associated with higher risk of AEs, while having an inflammatory neuropathy and steroids assumption were associated with a lower risk (all p < 0.05). Younger age, having had an AE, and COVID-19 before vaccination were factors associated with symptoms worsening after vaccination (all p < 0.05). (4) Conclusions: Patients with neuropathy showed a high level of adherence to COVID-19 vaccination. Safety of vaccines in patients with neuropathies was comparable to the general population and it was more favorable in those with inflammatory neuropathy.
Label-Free Surface Enhanced Raman Spectroscopy for Cancer Detection
Authors: Avci Ertug , Yilmaz Hulya , Sahiner Nurettin , Tuna Bilge Guvenc , Cicekdal Munevver Burcu , Eser Mehmet , Basak Kayhan , Altıntoprak Fatih , Zengin Ismail , Dogan Soner , Çulha Mustafa
Published: October 2022

Blood is a vital reservoir housing numerous disease-related metabolites and cellular components. Thus, it is also of interest for cancer diagnosis. Surface-enhanced Raman spectroscopy (SERS) is widely used for molecular detection due to its very high sensitivity and multiplexing properties. Its real potential for cancer diagnosis is not yet clear. In this study, using silver nanoparticles (AgNPs) as substrates, a number of experimental parameters and scenarios were tested to disclose the potential for this technique for cancer diagnosis. The discrimination of serum samples from cancer patients, healthy individuals and patients with chronic diseases was successfully demonstrated with over 90% diagnostic accuracies. Moreover, the SERS spectra of the blood serum samples obtained from cancer patients before and after tumor removal were compared. It was found that the spectral pattern for serum from cancer patients evolved into the spectral pattern observed with serum from healthy individuals after the removal of tumors. The data strongly suggests that the technique has a tremendous potential for cancer detection and screening bringing the possibility of early detection onto the table.
m6A Methyltransferase KIAA1429 Regulates the Cisplatin Sensitivity of Gastric Cancer Cells via Stabilizing FOXM1 mRNA
Authors: Zhu Zhongcheng , Zhou Yuan , Chen Yongheng , Zhou Zhongyi , Liu Wenxue , Zheng Linyi , Pei Qian , Tan Fengbo , Pei Haiping , Li Yuqiang
Published: October 2022

Although cisplatin is frequently used to treat gastric cancer, the resistance is the main obstacle for effective treatment. mRNA modification, N6-methyladenosine (m6A), is involved in the tumorigenesis of many types of cancer. As one of the largest m6A methyltransferase complex components, KIAA1429 bridges the catalytic m6A methyltransferase components, such as METTL3. In gastric cancer, KIAA1429 was reported to promote cell proliferation. However, whether KIAA1429 is involved in the resistance of gastric cancer to cisplatin remains unclear. Here, we generated cisplatin resistant gastric cancer cell lines, and compared the m6A content between resistant cells and wild type cells. The m6A content as well as KIAA1429 expression are higher in resistant cells. Interestingly, the expression of KIAA1429 was significantly increased after cisplatin treatment. We then used shRNA to knockdown KIAA1429 and found that resistant cells responded more to cisplatin treatment after KIAA1429 depletion, while overexpression of KIAA1429 decreased the sensitivity. Moreover, we identified a putative p65 binding site on the promoter area of KIAA1429 and ChIP assay confirmed the binding. p65 depletion decreased the expression of KIAA1429. YTHDF1 is the most abundant m6A “reader” that interacts with m6A modified mRNA. Mechanistically, YTHDF1 was recruited to the 3′-untranslated Region (3′-UTR) of transcriptional factor, FOXM1 by KIAA1429 and stabilized FOXM1 mRNA. More importantly, KIAA1429 knockdown increased the sensitivity of resistant cells to cisplatin in vivo. In conclusion, our results demonstrated that KIAA1429 facilitated cisplatin resistance by stabilizing FOXM1 mRNA in gastric cancer cells.
The Role of [68Ga]PSMA PET/CT for Clinical Suspicion of Prostate Cancer in Patients with or without Previous Negative Biopsy: A Systematic Review
Authors: Caracciolo Matteo , Castello Angelo , Urso Luca , Borgia Francesca , Ortolan Naima , Uccelli Licia , Cittanti Corrado , Castellani Massimo , Bartolomei Mirco , Lazzeri Massimo , Lopci Egesta
Published: October 2022

The purpose of the study is to systematically evaluate the evidence regarding the role of [68Ga]PSMA PET/CT for clinical suspicions of prostate cancer in patients with or without previous negative biopsy. We performed a critical review of PubMed and Web of Science according to the PRISMA statement. Eighteen publications were selected for inclusion in this analysis. QUADAS-2 evaluation was adopted for quality analyses. [68Ga]PSMA-11 was the radiotracer of choice in 15 studies, while [68Ga]PSMA-617 was used in another 3. In 8 articles, there was a direct comparison with mpMRI. The total number of patients included was 1379, ranging from 15 to 291, with a median age of 64 years (range: 42–90). The median baseline PSA value was 12.9 ng/mL, ranging from 0.85 to 4156 ng/mL. Some studies evaluated the PSMA uptake comparing the SUVmax of suspicious lesions with the SUVmax of the normal biodistribution to find out optimal cut-off points. In addition, some studies suggested a significant association between PSA levels, PSA density, and [68Ga]PSMA PET/CT finding. [68Ga]PSMA PET/CT seems to be more accurate in identifying primary prostate cancer with PSA values between 4 and 20 ng/mL than mpMRI. Moreover, in some trials, the combination of PSMA PET/CT and MRI improved the NPV in the detection of clinically significant prostate cancer (csPCa) than MRI alone. Our findings are limited by the small numbers of studies and patient heterogeneity. [68Ga]PSMA PET/CT is a promising technique in patients with clinical suspicion of PCa and precedent negative biopsy or contraindications to MRI. Furthermore, its use combined with MRI improves sensitivity for csPCa detection and can avoid unnecessary biopsies.
Fluorescent Lymphography-Guided Lymphadenectomy during Minimally Invasive Completion Total Gastrectomy for Remnant Gastric Cancer Patients
Authors: Alrashidi Nasser , Kim Ki-Yoon , Park Sung Hyun , Lee Sejin , Cho Minah , Kim Yoo Min , Kim Hyoung-Il , Hyung Woo Jin
Published: October 2022

No study has evaluated fluorescent lymphography for lymphadenectomy in remnant gastric cancer (RGC). This study aimed to assess the clinical application of fluorescent lymphography in minimally invasive completion total gastrectomy for RGC. Patients who had undergone minimally invasive completion total gastrectomy for RGC from 2013 to 2020 were retrospectively reviewed. The perioperative outcomes and long-term prognosis were compared between patients who had undergone minimally invasive completion total gastrectomy with fluorescent lymphography (the FL group) and those without fluorescent lymphography (the non-FL group). The FL group comprised 32 patients, and the non-FL group comprised 36 patients. FL visualized lymphatics in all 32 patients without complications related to the fluorescent injection. The median number [the interquartile range] of LN retrieval was significantly higher in the FL group (17 [9.3–23.5]) than in the non-FL group (12.5 [4–17.8]); p = 0.016). The sensitivity of fluorescent lymphography in detecting metastatic LN stations was 75%, and the negative predictive value was 96.9% in the FL group. The overall relapse-free survivals were comparable between the groups (p = 0.833 and p = 0.524, respectively). FL is an effective tool to perform a more thorough lymphadenectomy during minimally invasive completion total gastrectomy for RGC. Using FL in RGC surgery may improve surgical quality and proper staging.
PET-Uptake in Liver Metastases as Method to Predict Tumor Biological Behavior in Patients Transplanted for Colorectal Liver Metastases Developing Lung Recurrence
Authors: Dueland Svein , Smedman Tor Magnus , Grut Harald , Syversveen Trygve , Jørgensen Lars Hilmar , Line Pål-Dag
Published: October 2022

The objective of the study was to determine the impact of PET uptake on liver metastases on overall survival (OS) after resection of pulmonary metastases in patients who had received liver transplantation (LT) due to unresectable colorectal liver-only metastases. Resection of pulmonary colorectal metastases is controversial. Some hospitals offer this treatment to selected patients, whereas other hospitals do not perform the procedure in colorectal cancer patients who develop pulmonary metastases. All patients included in the LT studies who developed pulmonary metastases as first site of relapse, and had resection of these as first treatment, were included in this report. Metabolic tumor volume (MTV) in liver was derived from the pre-transplant PET examinations. OS from time of resection was calculated by the Kaplan–Meier method. Patients with low MTV (<70 cm3) had significantly longer OS from time of resection of pulmonary metastases compared to patients with high MTV (>70 cm3). Patients with low MTV in the liver had 10-year OS from time of pulmonary resections of 86%. Liver MTV values from pre-transplant PET examinations may predict long OS in colorectal cancer patients with a resection of pulmonary metastases developing after LT. Thus, in selected colorectal cancer patients developing pulmonary metastases resection of these metastases should be the treatment of choice.
Virtual Screening and Quantitative Structure–Activity Relationship of Moringa oleifera with Melanoma Antigen A (MAGE-A) Genes against the Therapeutics of Non-Small Cell Lung Cancers (NSCLCs)
Authors: Bhat Smitha S. , Mahapatra Shreya Das , R Sindhu , Sommano Sarana Rose , Prasad Shashanka K.
Published: October 2022

In the last decade, there have been significant advancements in the treatment of non-small cell lung cancer, including remarkable gains in detection, diagnosis, and therapy. The emergence of molecular targeted therapies, immunotherapeutic inhibitors, and antiangiogenesis medicines has largely fueled improvements in combination therapy and systemic treatments, all of which have dramatically ameliorated patient outcomes. The Moringa oleifera bioactive compounds have been effective in the suppression of cancers, making them the therapeutic agents of choice for the current investigation to treat MAGE-A presented in NSCLC. The ligand entrants were screened for their pharmacological properties, and 2,2-diphenyl-1,3-benzodioxole was stipulated as the lead candidate. 2,2-Diphenyl-1,3-benzodioxole exhibited better pharmacological properties and superior binding with branched-chain amino acids, making it an ideal candidate to address MAGE-A. The study concluded that addressing MAGE-A to impede their activity and antigenicity can be exploited as immunotarget(s).
Mechanical Properties of Colorectal Cancer Cells Determined by Dynamic Atomic Force Microscopy: A Novel Biomarker
Authors: Brás M. Manuela , Cruz Tânia B. , Maia André F. , Oliveira Maria José , Sousa Susana R. , Granja Pedro L. , Radmacher Manfred
Published: October 2022

Colorectal cancer (CRC) has been addressed in the framework of molecular, cellular biology, and biochemical traits. A new approach to studying CRC is focused on the relationship between biochemical pathways and biophysical cues, which may contribute to disease understanding and therapy development. Herein, we investigated the mechanical properties of CRC cells, namely, HCT116, HCT15, and SW620, using static and dynamic methodologies by atomic force microscopy (AFM). The static method quantifies Young’s modulus; the dynamic method allows the determination of elasticity, viscosity, and fluidity. AFM results were correlated with confocal laser scanning microscopy and cell migration assay data. The SW620 metastatic cells presented the highest Young’s and storage moduli, with a defined cortical actin ring with distributed F-actin filaments, scarce vinculin expression, abundant total focal adhesions (FAK), and no filopodia formation, which could explain the lessened migratory behavior. In contrast, HCT15 cells presented lower Young’s and storage moduli, high cortical tubulin, less cortical F-actin and less FAK, and more filopodia formation, probably explaining the higher migratory behavior. HCT116 cells presented Young’s and storage moduli values in between the other cell lines, high cortical F-actin expression, intermediate levels of total FAK, and abundant filopodia formation, possibly explaining the highest migratory behavior.
Fabrication of Basalt Matrix Composite Material by Pressureless Aluminum Melt Infiltration in Air Atmosphere
Authors: Shishkin Roman A. , Yuferov Yuliy V. , Polyvoda Dmitriy O.
Published: October 2022

The microstructure of Basalt matrix composite materials produced by pressureless aluminum melt infiltration at 950 °C was investigated. It is established that uniform elements distribution is observed within the whole sample depth. Interestingly, aluminum content variation considerably matches the hardness of the sample profile that is connected with alumina phase presence. Sample color changes during temperature treatment due to phase transitions were observed. The appearance of the hematite (Fe2O3) phase makes the initial preform red. After infiltration by molten aluminum, oxygen-deficient alumosilicate phases turn the color black. The infiltration process decreases the porosity insufficiently due to a partial reduction of alumosilicates by molten Al and the hardness of infiltrated samples was only 2.2 GPa. Nevertheless, a huge thermal conductivity rise from 1.45 to 4.53 W/(m·K), along with a fracture toughness increase, makes the produced composite a prospective wear-resistant material. Moreover, the developed low-temperature production technology allows for obtaining a very cost-effective material.
Therapeutic Use and Chronic Abuse of CNS Stimulants and Anabolic Drugs
Authors: Coliță Daniela , Coliță Cezar-Ivan , Hermann Dirk , Coliță Eugen , Doeppner Thorsten , Udristoiu Ion , Popa-Wagner Aurel
Published: October 2022

The available evidence suggests that affective disorders, such as depression and anxiety, increase risk for accelerated cognitive decline and late-life dementia in aging individuals. Behavioral neuropsychology studies also showed that cognitive decline is a central feature of aging impacting the quality of life. Motor deficits are common after traumatic brain injuries and stroke, affect subjective well-being, and are linked with reduced quality of life. Currently, restorative therapies that target the brain directly to restore cognitive and motor tasks in aging and disease are available. However, the very same drugs used for therapeutic purposes are employed by athletes as stimulants either to increase performance for fame and financial rewards or as recreational drugs. Unfortunately, most of these drugs have severe side effects and pose a serious threat to the health of athletes. The use of performance-enhancing drugs by children and teenagers has increased tremendously due to the decrease in the age of players in competitive sports and the availability of various stimulants in many forms and shapes. Thus, doping may cause serious health-threatening conditions including, infertility, subdural hematomas, liver and kidney dysfunction, peripheral edema, cardiac hypertrophy, myocardial ischemia, thrombosis, and cardiovascular disease. In this review, we focus on the impact of doping on psychopathological disorders, cognition, and depression. Occasionally, we also refer to chronic use of therapeutic drugs to increase physical performance and highlight the underlying mechanisms. We conclude that raising awareness on the health risks of doping in sport for all shall promote an increased awareness for healthy lifestyles across all generations.
Exceptional Repositioning of Dog Dewormer: Fenbendazole Fever
Authors: Sultana Tania , Jan Umair , Lee Hyunsu , Lee Hyejin , Lee Jeong Ik
Published: October 2022

Fenbendazole (FZ) is a benzimidazole carbamate drug with broad-spectrum antiparasitic activity in humans and animals. The mechanism of action of FZ is associated with microtubular polymerization inhibition and glucose uptake blockade resulting in reduced glycogen stores and decreased ATP formation in the adult stages of susceptible parasites. A completely cured case of lung cancer became known globally and greatly influenced the cancer community in South Korea. Desperate Korean patients with cancer began self-administering FZ without their physician’s knowledge, which interfered with the outcome of the cancer treatment planned by their oncologists. On the basis of presented evidence, this review provides valuable information from PubMed, Naver, Google Scholar, and Social Network Services (SNS) on the effects of FZ in a broad range of preclinical studies on cancer. In addition, we suggest investigating the self-administration of products, including supplements, herbs, or bioactive compounds, by patients to circumvent waiting for long and costly FZ clinical trials.