bluuebunny/crossref_metadata_2025 huggingface dataset:
Three Diverse Applications of General-Purpose Parameter Optimization Algorithm
Authors: Huo Yuanzhi , Puspitaningayu Pradini , Funabiki Nobuo , Hamazaki Kazushi , Kuribayashi Minoru , Zhao Yihan , Kojima Kazuyuki
Published: January 2023

Parameters often take key roles in determining the accuracy of algorithms, logics, and models for practical applications. Previously, we have proposed a general-purpose parameter optimization algorithm, and studied its applications in various practical problems. This algorithm optimizes the parameter values by repeating small changes of them based on a local search method with hill-climbing capabilities. In this paper, we present three diverse applications of this algorithm to show the versatility and effectiveness. The first application is the fingerprint-based indoor localization system using IEEE802.15.4 devices called FILS15.4 that can detect the location of a user in an indoor environment. It is shown that the number of fingerprints for each detection point, the fingerprint values, and the detection interval are optimized together, and the average detection accuracy exceeds 99%. The second application is the human face contour approximation model that is described by a combination of half circles, line segments, and a quadratic curve. It is shown that the simple functions can well approximate the face contour of various persons by optimizing the center coordinates, radii, and coefficients. The third application is the computational fluid dynamic (CFD) simulation to estimate temperature changes in a room. It is shown that the thermal conductivity is optimized to make the average temperature difference between the estimated and measured 0.22∘C.
Good Governance in Rural Local Administration
Authors: Zaitul Zaitul , Ilona Desi , Novianti Neva
Published: January 2023

The governance principle is an important aspect of good governance, and its implementation is believed to have a good impact on governance outcomes, such as corruption reduction and performance improvement. The governance principle has been developed for several types of organisations. However, previous studies did not focus on the rural local administration’s governance. This study aims to develop a good governance principle for the rural local administration. There are four objectives of this study: first, to identify governance principles and their indicators in the literature; second, to create a governance principle using exploratory factor analysis; third, to model the governance principle using the structural equation model (SEM); and finally, to analyse any different perceptions about the governance principles for the rural local administration using univariate analysis. The result showed that 33 indicators of governance principles were identified through the literature. Using 238 usable questionnaires and exploratory factor analysis, we found 6 governance principles: fairness and capability, inclusivity, legitimacy and direction, participation, performance and information, and transparency and accountability. Using the second-order SEM in SmartPLS, we developed a governance principle model for the rural local administration. A few indicators of governance principles found were deleted through measurement model validation. In addition, the univariate analysis concluded that perceptions did not differ by the sex, education level, and occupation type of respondents. In other words, they agreed with the governance principle for the rural local administration. This study has practical and theoretical implications, which are discussed in detail in this article.
Design and Qualification of an Additively Manufactured Manifold for Aircraft Landing Gears Applications
Authors: Arena Maurizio , Ambrogiani Paolo , Raiola Vincenzo , Bocchetto Francesco , Tirelli Tommaso , Castaldo Martina
Published: January 2023

The continuous pursuit of reducing weight and optimizing manufacturing processes is increasingly demanded in transportation vehicles, particularly in the aerospace field. In this context, additive manufacturing (AM) represents a well-known technique suitable for re-engineering traditional systems, minimizing the product’s weight/volume and print time. The present research activity allowed for the exploration of the feasibility to replicate a conventional hydraulic manifold already certified for defence application with a lightweight and more compact issue through typical stringent aeronautical qualification steps. Computational modelling with lab test efforts made it possible to assess the compliance of the device with airworthiness certification requirements, giving a special focus to the fulfilment of structural requirements. In particular, the fatigue life characterization is still a crucial point to be well investigated in aeronautical components dfAM (designed for additive manufacturing) to demonstrate the maturity of the technology in the certification scenario. The new AM-driven design offers a more than 40 per cent weight reduction.
The Effect of Enzyme Activity on Carbon Sequestration and the Cycle of Available Macro- (P, K, Mg) and Microelements (Zn, Cu) in Phaeozems
Authors: Lemanowicz Joanna , Bartkowiak Agata , Zielińska Aleksandra , Jaskulska Iwona , Rydlewska Magdalena , Klunek Katarzyna , Polkowska Magdalena
Published: January 2023

The study objective was to determine the relationship of selected enzyme activities with carbon sequestration and N, P, K, Mg, Zn and Cu contents in Phaeozem soils. Soil samples were taken from a 10 ha area. A selection of their physical and chemical properties and the contents of the available forms of selected macro- and microelements were determined. The activities of dehydrogenases (DEH), catalase (CAT), peroxidases (PER), alkaline (AlP) and acid (AcP) phosphatase, β-glucosidase (BG) and proteases (PR) were also determined. The relationship between enzymatic soil fertility indices (AlP/AcP, BIF, GMea, TEI, BA12 and BA13) and selected soil parameters was also determined. The research used principal component analysis (PCA) to distinguish significantly correlated parameters of a Phaeozem used for agricultural purposes. The study area showed low TOC and K contents and average P and Mg contents. Significant positive correlations were found between the TOC content and activity of the tested enzymes, evidencing that soil enzymes are an important parameter in carbon sequestration and soil nutrient dynamics.
Scion/Rootstock Interaction Studies for Quality Traits in Mango (Mangifera indica L.) Varieties
Authors: Shivran Mukesh , Sharma Nimisha , Dubey Anil Kumar , Singh Sanjay Kumar , Sharma Neha , Muthusamy Vignesh , Jain Maneesh , Singh Bikram Pratap , Singh Nisha , Kumar Nirmal , Singh Narendra , Sethi Shruti , Sharma Radha Mohan
Published: January 2023

To explore the quality rootstocks which impart better quality fruits in mango varieties, we studied the interactive effect of the scion and rootstock using five mango varieties (Mallika, Amrapali, Dashehari, Pusa Arunima, and Pusa Surya) grafted on three rootstocks (Olour, Kurukkan, and K-5). A total of 25 physico-chemical parameters were studied in the five grafted varieties viz., fruit weight, yield efficiency, fruit per plant, pulp percent, total soluble solids (TSS), acidity, physiological loss in weight (PLW), peel thickness, respiration rate, etc., and were found to be altered through scion–rootstock interaction. Among the five mango varieties, Olour rootstock proved best to improve the fruit quality and shelf life using the grafting approach. Physico-chemical-traits-based clustering was unable to precisely group scion varieties according to their grafting rootstock. A total of 35 shelf-life specific markers were designed from ripening genes, such as expansin, polygalactouranase, ethylene insensitive, ethylene sensitive, etc. Of these specific primers, 24 showed polymorphism among the studied genotypes. The gene diversity (GD), allele per locus (An), polymorphism information content (PIC), and major allele frequency (MAF) observed were 0.43, 2.00, 0.34, and 0.63, respectively. Cluster analysis clearly showed that scion grafted on Kurukkan and Olour rootstock, and scion varieties grafted on K-5 rootstock grouped together have more similarity. A total of eight simple sequence repeats loci (SSRs) markers were associated with eight physiological traits. Strong association of SSR loci NMSLC-12 and NMSLC-14 with yield efficiency and fruit weight were observed with a phenotypic variance of 85% and 70%, respectively.
Pelleting of Physical Dormancy Small-Seeded Species in Astragalus sikokianus Nakai
Authors: Jin Yea-Jung , Jeong Han-Jin , Kim Soo-Young , Cho Seong-Hyun , Lee Jin-Hwan , Kim Du-Hyun
Published: January 2023

Astragalus sikokianus is a rare Japanese perennial of the seashore that was reported to be extinct in the wild. The small seed size and deep dormancy of A. sikokianus make it difficult for direct seeding restoration in aspects of seed handling, transport, planting, and seedling establishment. For the large-scale economic restoration of dormant small-seeded species, seed pelleting combined with the breaking of dormancy was studied. Physiological (prechilling and plant hormones) and physical (hot water, hydrochloric acid, and sulfuric acid) seed dormancy break treatments were evaluated. The dormant broken seeds were used for pelleting. The effects of the substrate, pellet sizes, and their interactions on germination were measured. The scarification of five rubs of seeds placed between sandpapers completely broke the physical dormancy of A. sikokianus. Seed coat impermeability inhibited germination. Pelleted seeds ranging from 2.0 to 4.0 mm in diameter showed more than 90% germination on filter paper. The germination of the pelleted seeds was measured in commercial, field, and sand soil conditions. The highest germination was shown in sand (70–74% GP), regardless of the pellet size, whereas unpelleted scarified seeds germinated only 48%. These results suggest that small-seeded species with physical dormancy can be used for seed-based restoration after seed pelleting.
Cognitive Foraging Enrichment (but Not Non-Cognitive Enrichment) Improved Several Longer-Term Welfare Indicators in Bottlenose Dolphins
Authors: Clegg Isabella L. K. , Domingues Mariana , Ström Elin , Berggren Linda
Published: January 2023

Bottlenose dolphins are the most common cetacean kept globally in zoos and aquaria (hereafter zoos), and are gregarious animals with a mostly opportunistic, generalist feeding strategy in the wild. In zoos, they have limited to no opportunities to express natural foraging behaviours as they receive their daily food ration of dead fish in a series of training sessions. Enrichment provision has increased in recent years, but items are still predominantly simple and floating in nature, and do not always target the animals’ problem-solving or food-acquisition behaviours. These discrepancies run concurrently with the intense debate about dolphin welfare in zoos and how to improve it. The current study used a within-subject design on 11 bottlenose dolphins at Kolmårdens Djurpark and measured how several welfare indicators differed between two treatments of “cognitive” and “non-cognitive” food-based enrichment. The treatments were provided on an alternating basis for eight consecutive weeks: during cognitive enrichment weeks, the animals received items which stimulated their problem-solving and foraging behaviours, and during non-cognitive enrichment weeks, they received simple items paired with fish (to eliminate bias due to food value). Data were taken related to several multidisciplinary welfare parameters during enrichment provision and training sessions, and to activity budget behaviours throughout the week. During the cognitive as opposed to non-cognitive enrichment weeks, the dolphins engaged more with the enrichment, were more motivated to participate in training sessions and performed less anticipatory and stereotypic behaviours, suggesting that cognitive enrichment improved several indicators of bottlenose dolphin welfare. Valuable lines of further investigation would be to understand how individual differences and different types of cognitive enrichment impact potential welfare benefits. Our results suggest that enrichment items promoting cognitive foraging behaviours may improve dolphin welfare, and therefore zoos might prioritise giving cognitive enrichment to this species as well as considering the same for other species with similar cognitive skills and foraging ecologies.
When and Why Cats Are Returned to Shelters
Authors: Mundschau Vivian , Suchak Malini
Published: January 2023

There is considerable research on why cats are initially relinquished to shelters, but much less attention has been given to returns, despite the significant implications for shelter capacity and cat welfare. Furthermore, the structure of many databases fails to account for cats who are returned beyond 30 days, despite this making up a substantial portion of returns. In the current study, we examined common risk factors and reasons for return in a population of 2642 shelter cats. We found that cats who were older at the time of adoption or had a bite history had an increased risk of return, whereas cats that were in foster care prior to adoption had a decreased risk of return. We divided the returns by the time to return (<30 days: short term, >30 days: long term) to examine whether time to return had an impact. Approximately half the cats were returned in the short term. Cats were more likely to be returned for reasons, such as behavior, unwanted, and other pet in the short term and personal reasons, cost, euthanasia, and stray in the long-term return. Strategies to reduce returns should consider different solutions for short and long returns to maximize effectiveness.
The Roles of Polysaccharides in Carp Farming: A Review
Authors: Goh Khang Wen , Abdul Kari Zulhisyam , Wee Wendy , Van Doan Hien , Reduan Mohd Farhan Hanif , Kabir Muhammad Anamul , Khoo Martina Irwan , Al-Amsyar Syed M. , Seong Wei Lee
Published: January 2023

Carp is an important aquaculture species globally, and the production is expected to increase with the growing market demands. Despite that, disease outbreaks remain a major challenge, impeding the development of sustainable carp farming. Moreover, the application of antibiotics, a common prophylactic agent, can adversely impact public health and the environment. Therefore, polysaccharide has been recognized as a novel prophylactic agent in the health management of carp farming, as well as gaining consumers’ confidence in carp farming products. In this review, the definition, sources, and main roles of polysaccharides in improving growth performance, stimulating the immune system, enhancing disease resistance, and alleviating abiotic stresses in carp farming are discussed and summarized. In addition, the use of polysaccharides in combination with other prophylactic agents to improve carp farming production is also highlighted. This review aims to highlight the roles of polysaccharides and provide valuable information on the benefits of polysaccharides in carp farming.
Study TOMAS Cyclone Using Seismic Array and Single Station
Authors: Wang Siyin , Xu Yan , Xie Chaodi , Li Aitang
Published: January 2023

The continuous data from the YL array and four AU stations during the lifetime of the cyclone TOMAS in March 2010 were downloaded from IRIS. By performing frequency-wave number (F-K) analysis on the array data, it was found that the orientation of the maximum energy of the secondary microseisms (0.1~0.5 Hz) was consistent with the movement of TOMAS when the central wind speed reached the typhoon level. The high wind speed of the cyclone could generate secondary microseisms as well as the high swell. However, the large global earthquake can affect the microseismic observations using F-K. The AU stations have a better microseism observation than the YL array, which might be due to the vibrating and tilting of the hydrophone caused by the turbulence. The F-K analysis on microseisms can produce better slowness and back azimuth observations than polarization.
Intelligent Monitoring and Compensation between EDM and ECM
Authors: Chuang Min-Chun , Jan Chia-Ming , Wang Yu-Jen , Hsu Yu-Liang
Published: January 2023

Electric discharge machining (EDM) is a type of high-precision machining usually applied to hard-material machining for mold manufacturing and in the aerospace industry. Longer process times typically reduce facility efficiency. The use of electrochemistry machining (ECM) can overcome this challenge to efficiently machine large workpieces. Some industries have adopted and combined these two processes for Inconel 718 material machining. However, the use of coordinate-measuring machine times to determine the machining accuracy of these two processes is difficult. This study matched process features by analyzing the electric driving pulses of ECM and EDM. Fitting intelligent sensing signals that respond to dimensional measurements can be used to analyze electrical pulse signals. For analyzing a cross-process model using extracted key features of the process, our feedback-based system determines lower machining measurement errors and improves geometric size. Finally, the processing time of experiments can be reduced by 80%, and our proposed model has a prediction accuracy of approximately 0.01 mm2.
Stiffening Cello Bridges with Design
Authors: Lodetti Laura , Gonzalez Sebastian , Antonacci Fabio , Sarti Augusto
Published: January 2023

In instruments of the violin family, the bridge is the part in charge of transferring the vibrational energy of the strings into the body and therefore contributes greatly to the sound of the instrument. The bridge needs to be light enough to efficiently transmit the strings’ movement yet rigid enough to support the static load of the strings. Historically, there have been several attempts at solving this problem with different designs, arriving in the early 1800s at the two current models: the French and the Belgian. Recently, in Cremona, Italy, the Amorim family of luthiers has developed a new cello bridge design. Inspired by their work, we study the influence of the shape of the legs of the cello bridge on its static and vibrational behavior through parametric modeling and simulations using the Finite Element Method. In particular, we perform displacement and modal analysis for different boundary conditions, providing in addition a detailed description of the mode shapes. We also compute and compare Frequency Response Functions for the different geometries. Our results show that shape can indeed be used to control the vibrational and static responses of the cello and consequently tune its sound.
Validation of a Useful Tool for Screening for Overweight and Obesity in Pre-Adolescents
Authors: Falquet Vicent , Ripoll Jordi , López-Malo Daniel , Blesa Jesús , Esteve María José
Published: January 2023

The purpose of this observational study with a convenience sample is to validate a simple measurement of the mid-upper arm circumference to establish the screening points using the mid-upper arm circumference tape (MUAC) for childhood overweight and obesity between 9 and 12 years of age, or from 4th grade to 6th grade. Prior to the screening study, a pilot validation study of the MUAC tape measure versus anthropometric standard tape was carried out. The total sample for the screening cut-offs was 360 school students. The results obtained had a predictive value according to the evaluation of the area under the curve of 0.96 and overweight detection cut-off points were established at 23.3 and 22.4 cm for 4th grade, 23.6 and 22.7 cm for 5th grade and 24.6 and 23.8 cm for 6th grade for boys and girls, respectively. The cut-off points for the detection of obesity were established at 25.2 and 23.9 cm for 4th grade, 26.4 and 25.1 cm for 5th grade, and 27.7 and 26.4 cm for 6th grade boys and girls, respectively. The cut-off values of the MUAC are different not only between the sexes, but also increase as age or the specific course increases.
Ventilation Methods against Indoor Aerosol Infection of COVID-19 in Japan
Authors: Hayashi Motoya , Yanagi U , Honma Yoshinori , Yamamoto Yoshihide , Ogata Masayuki , Kikuta Koki , Kagi Naoki , Tanabe Shin-ichi
Published: January 2023

The importance of effective ventilation as one of the measures against COVID-19 is widely recognized worldwide. In Japan, at the early stage of the pandemic, in March 2020, an official announcement was made about basic ventilation measures against COVID-19. WHO also used the term “long-range aerosol or long-range airborne transmission” for the first time in December 2021. Based on the aerosol infection control measures before 2021 by the Japanese government, we conducted experiments on methods related to partition placement as an element of effective ventilation methods. In July 2022, the governmental subcommittee on Novel Coronavirus Disease Control provided an emergent proposal about effective ventilation methods to prevent two types of aerosol infection; infection by large aerosol on the air current and infection by small floating aerosol diffusion in a room. They also showed the way of setting droplet prevention partitions, which do not block off ventilation based on this investigation’s results.
Spatiotemporal Characteristics of Watershed Warming and Wetting: The Response to Atmospheric Circulation in Arid Areas of Northwest China
Authors: Li Taohui , Lv Aifeng , Zhang Wenxiang , Liu Yonghao
Published: January 2023

The Tarim Basin is a large inland arid basin in the arid region of northwest China and has been experiencing significant “warming and wetting” since 1987. As a result, the purpose of this paper is to determine whether the climate transition phenomenon occurred in the Tarim Basin as well as the role of atmospheric circulation in this process. We use meteorological data and atmospheric circulation indexes to study the seasonal trends of climate change in this region from 1987 to 2020 to understand how they are affected by atmospheric circulation. The findings show that, from 1987 to 2020, the Tarim Basin experienced significant warming and wetting; with the exception of the winter scale, all other seasonal scales exhibited a clear warming and wetting trend. From the perspective of spatial distribution, most of the areas showed a significant warming trend, and the warming amplitude around the basin is greater than that in the central area of the basin. However, there are significant regional differences in precipitation change rates. Meanwhile, wavelet analysis shows that there is a significant oscillation period of 17–20 years between climate change and the atmospheric circulation index during 1987–2020. The correlation analysis shows that the Pacific decadal oscillation (PDO) and El Niño-Southern Oscillation (ENSO) are the main influencing factors of climate change in the Tarim Basin at different seasonal scales, while the teleconnection of the Arctic Oscillation (AO) and North Atlantic Oscillation (NAO) is low and the PDO dominates the summer and autumn temperature changes in the Tarim Basin. The research results of this paper show that, despite the warming and wetting trends since 1987 in the Tarim Basin, the climate type did not change. From 1987 to 2020, the main teleconnection factors of climate change in the Tarim Basin were PDO and ENSO.
Grain Size Characteristics of MIS 5 Sediments and Evolution of the East Asian Summer Monsoon in the Zhifu Section, Yantai City, Shandong Province, China
Authors: Sun Li , Li Zhiwen , Song Yougui , Zhou Hongyi , Fan Qingbin , Li Wubiao , Tang Ni
Published: January 2023

The North Yellow Sea, located at the intersection of the Eurasian continent and North Pacific Ocean at mid-latitudes, is a sensitive area subjected to the joint actions of the ocean, land, and monsoons. On its southern shore, loess and paleosol sedimentary sequences were widely developed during the last interglacial period, which is of great significance for revealing patterns of climate change and dynamic conditions. In this paper, we focus on the Zhifu section (ZFS) on Zhifu Island within the Shandong Province of China. The optically stimulated luminescence (OSL) dating method was used to construct our chronological framework. Grain size and its endmember (EM) components were then analyzed; EM1 is a clay component EM, which represents a weak dynamic environment and strong weathering pedogenesis, while EM2 and EM3 are silt and very fine sand component EMs, respectively, representing a strong dynamic environment and weak weathering pedogenesis. Maximum EM1, mean grain size, clay content, and pH values occur in the paleosol layers (ZF4, ZF6, and ZF8), with minimum values in the loess layers (ZF5 and ZF7); EM3 values show the opposite pattern. This indicates that the ZF4, ZF6, and ZF8 layers represent warm and humid environments with abundant precipitation, where the East Asian summer monsoon (EASM) was enhanced, corresponding to Marine Isotope Stages (MIS) 5a, 5c, and 5e. In contrast, ZF5 and ZF7 represent sub-warm and humid environments with less precipitation, where the EASM was weakened, corresponding to MIS 5b and 5d. Among these stages, MIS5e is the warmest and wettest. These climatic events reveal the pattern of climate fluctuation over a ten-thousand-year timescale; they are synchronous with climate changes recorded in other geological repositories, such as cave stalagmites in southern China and sea-level fluctuations in the Yellow-Bohai Sea, which result from changes in global solar radiation.
Double Filtration Plasmapheresis with Polyvinyl Alcohol-Based Membrane Lowers Serum Inflammation and Toxins in Patients with Hyperlipidemia
Authors: Liu Wen-Sheng , Lin Chien-Hung , Tsai Ching-Yao , Wang Hsiang-Tsui , Li Szu-Yuan , Liu Tsung-Yun , Tan Ann Charis , Tsou Han-Hsing , Tseng Kuo-Hsien , Lin Chih-Ching
Published: January 2023

Hyperlipidemia is increasing in prevalence and is highly correlated with cardiovascular disease (CVD). Lipid-lowering medications prevent CVD but may not be suitable when the side effects are intolerable or hypercholesterolemia is too severe. Double-filtration plasmapheresis (DF) has shown its therapeutic effect on hyperlipidemia, but its side effects are not yet known. We enrolled 45 adults with hyperlipidemia in our study. The sera before and two weeks after DF were evaluated, and we also analyzed perfluorochemicals to see if DF could remove these lipophilic toxins. After DF, all lipid profile components (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) had significantly decreased. Leukocyte counts increased while platelet levels decreased, which may have been caused by the puncture wound from DF and consumption of platelets during the process. As for uremic toxins and inflammation, levels of C-reactive protein, uric acid, and alanine transaminase (ALT) all decreased, which may be related to the removal of serum perfluorooctane sulfonate (PFOS) and improvement of renal function. The total cholesterol/HDL ratio and triglycerides were significantly higher in the diabetes mellitus (DM) group at baseline but did not significantly differ after DF. In conclusion, DF showed potential for improving inflammation and removing serum lipids and PFOS in adults with hyperlipidemia.
A Novel and Label-Free Chemiluminescence Detection of Zearalenone Based on a Truncated Aptamer Conjugated with a G-Quadruplex DNAzyme
Authors: Guan Yue , Ma Junning , Neng Jing , Yang Bolei , Wang Yan , Xing Fuguo
Published: January 2023

Zearalenone (ZEN), one of the most frequently occurring mycotoxin contaminants in foods and feeds, poses considerable threat to human and animal health, owing to its acute and chronic toxicities. Thus, rapid and accurate detection of ZEN has attracted broad research interest. In this work, a novel and label-free chemiluminescence aptasensor based on a ZEN aptamer and a G-quadruplex DNAzyme was constructed. It was established on a competitive assay between ZEN and an auxiliary DNA for the aptamer, leading to activation of the G-quadruplex/hemin DNAzyme and subsequent signal amplification by chemiluminescence generation after substrate addition. To maximize the detection sensitivity, numerous key parameters including truncated aptamers were optimized with molecular docking analysis. Upon optimization, our aptasensor exhibited a perfect linear relationship (R2 = 0.9996) for ZEN detection in a concentration range of 1–100 ng/mL (3.14–314.10 nM) within 40 min, achieving a detection limit of 2.85 ng/mL (8.95 nM), which was a 6.7-fold improvement over that before optimization. Most importantly, the aptasensor obtained a satisfactory recovery rate of 92.84–137.27% and 84.90–124.24% for ZEN-spiked wheat and maize samples, respectively. Overall, our label-free chemiluminescence aptasensor displayed simplicity, sensitivity, specificity and practicality in real samples, indicating high application prospects in the food supply chain for rapid detection of ZEN.
An Optimized CoBRA Method for the Microfluidic Electrophoresis Detection of Breast Cancer Associated RASSF1 Methylation
Authors: Aibel Claire , Coll De Peña Adriana , Tripathi Anubhav
Published: January 2023

Although breast cancer screening assays exist, many are inaccessible and have high turnaround times, leaving a significant need for better alternatives. Hypermethylation of tumor suppressor genes is a common epigenetic marker of breast cancer. Methylation tends to occur most frequently in the promoter and first exon regions of genes. Preliminary screening tests are crucial for informing patients whether they should pursue more involved testing. We selected RASSF1, previously demonstrated to be aberrantly methylated in liquid biopsies from breast cancer patients, as our gene of interest. Using CoBRA as our method for methylation quantification, we designed unique primer sets that amplify a portion of the CpG island spanning the 5′ end of the RASSF1 first exon. We integrated the CoBRA approach with a microfluidics-based electrophoresis quantification system (LabChip) and optimized the assay such that insightful results could be obtained without post-PCR purification or concentration, two steps traditionally included in CoBRA assays. Circumventing these steps resulted in a decreased turnaround time and mitigated the laboratory machinery and reagent requirements. Our streamlined technique has an estimated limit of detection of 9.1 ng/μL of input DNA and was able to quantify methylation with an average error of 4.3%.
The Importance of Selected Dysregulated microRNAs in Diagnosis and Prognosis of Childhood B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Ziętara Karolina Joanna , Lejman Jan , Wojciechowska Katarzyna , Lejman Monika
Published: January 2023

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a frequent type of childhood hematological malignancy. The disease is classified into several subtypes according to genetic abnormalities. MicroRNAs (miRNAs) are involved in pathological processes (e.g., proliferation, apoptosis, differentiation). A miRNA is a group of short non-coding RNAs with relevant regulatory effects on gene expression achieved by suppression of the translation or degradation of messenger RNA (mRNA). These molecules act as tumor suppressors and/or oncogenes in the pathogenesis of pediatric leukemias. The characteristic features of miRNAs are their stable form and the possibility of secretion to the circulatory system. The role of miRNA in BCP-ALL pathogenesis is still emerging, but several studies have suggested using miRNA expression profiles as biomarkers for diagnosis, prognosis, and response to therapy in leukemia. The dysregulation of some miRNAs involved in childhood acute lymphoid leukemia, such as miR-155, miR-200c, miR-100, miR-181a, miR125b, and miR146a is discussed, showing their possible employment as therapeutic targets. In the current review, the capabilities of miRNAs in non-invasive diagnostics and their prognostic potential as biomarkers are presented.
Stem Cell Mobilization with Ixazomib and G-CSF in Patients with Multiple Myeloma
Authors: Bühler Selina , Akhoundova Dilara , Jeker Barbara , Legros Myriam , Seipel Katja , Daskalakis Michael , Bacher Ulrike , Pabst Thomas
Published: January 2023

(1) Background: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the standard consolidation strategy for patients with newly diagnosed multiple myeloma (MM) and for a subset of patients with relapsed/refractory disease. For stem cell mobilization, G-CSF alone or in combination with chemotherapy mobilizing agents and/or plerixafor are commonly used. Ixazomib is an oral proteasome inhibitor with less neurotoxic potential, which previously showed the ability to mobilize stem cells in preclinical studies. (2) Methods: Prospective single-center phase 1 study assessing the efficacy and safety of stem cell mobilization with ixazomib and G-CSF in patients with newly diagnosed or relapsed/refractory MM undergoing HDCT and ASCT. Primary endpoint was percentage of patients achieving a yield of at least 6.0 × 106/kg CD34+ cells within the first apheresis. G-CSF (filgrastim) 10 μg/kg/day was administered subcutaneously (s.c.) from day 1 to day 5 (planned apheresis) and ixazomib 4 mg orally at day 4. Plerixafor 24 mg s.c. was administered if the stem cell mobilization with ixazomib and G-CSF was not sufficient. (3) Results: 19 patients were treated within the study between 06/2020 and 02/2021. The primary endpoint was reached in 17 (89%) patients, with a median of 7.1 × 106/kg CD34+ cells collected within the first apheresis, comparable to previously published results, and only 2 (11%) patients required a second apheresis. Median number of circulating CD34+ cells was 14.0 × 106/L (2.0–95.2) before the administration of ixazomib, and 33.0 × 106/L (4.2–177.0) pre-apheresis. However, 9 (47%) patients required the addition of plerixafor to ensure optimal stem cell collection. (4) Conclusions: The combination of ixazomib and G-CSF showed promising stem cell mobilizing activity in patients with MM prior to HDCT and ASCT. Future larger studies might further investigate the role of ixazomib in stem cell mobilization regimens for MM.
Locus-Specific Bisulfate NGS Sequencing of GSTP1, RNF219, and KIAA1539 Genes in the Total Pool of Cell-Free and Cell-Surface-Bound DNA in Prostate Cancer: A Novel Approach for Prostate Cancer Diagnostics
Authors: Bryzgunova Olga , Bondar Anna , Ruzankin Pavel , Tarasenko Anton , Zaripov Marat , Kabilov Marsel , Laktionov Pavel
Published: January 2023

The locus-specific methylation of three genes (GSTP1, RNF219, and KIAA1539, also known as FAM214B) in the total pool of blood cell-free DNA, including cell-free DNA from plasma and cell-surface-bound DNA, of patients with prostate cancer and healthy donors was studied on the MiSeq platform. Our study found a higher methylation index of loci for total cell-free DNA compared with cell-free DNA. For total cell-free DNA, the methylation of GSTP1 in each of the 11 positions provided a complete separation of cancer patients from healthy donors, whereas for cell-free DNA, there were no positions in the three genes allowing for such separation. Among the prostate cancer patients, the minimum proportion of GSTP1 genes methylated in any of the 17 positions was 12.1% of the total circulated DNA fragments, and the minimum proportion of GSTP1 genes methylated in any of the 11 diagnostically specific positions was 8.4%. Total cell-free DNA was shown to be more convenient and informative as a source of methylated DNA molecules circulating in the blood than cell-free DNA.
Radiomics Approaches for the Prediction of Pathological Complete Response after Neoadjuvant Treatment in Locally Advanced Rectal Cancer: Ready for Prime Time?
Authors: Bourbonne Vincent , Schick Ulrike , Pradier Olivier , Visvikis Dimitris , Metges Jean-Philippe , Badic Bogdan
Published: January 2023

In recent years, neoadjuvant therapy of locally advanced rectal cancer has seen tremendous modifications. Adding neoadjuvant chemotherapy before or after chemoradiotherapy significantly increases loco-regional disease-free survival, negative surgical margin rates, and complete response rates. The higher complete rate is particularly clinically meaningful given the possibility of organ preservation in this specific sub-population, without compromising overall survival. However, all locally advanced rectal cancer most likely does not benefit from total neoadjuvant therapy (TNT), but experiences higher toxicity rates. Diagnosis of complete response after neoadjuvant therapy is a real challenge, with a risk of false negatives and possible under-treatment. These new therapeutic approaches thus raise the need for better selection tools, enabling a personalized therapeutic approach for each patient. These tools mostly focus on the prediction of the pathological complete response given the clinical impact. In this article, we review the place of different biomarkers (clinical, biological, genomics, transcriptomics, proteomics, and radiomics) as well as their clinical implementation and discuss the most recent trends for future steps in prediction modeling in patients with locally advanced rectal cancer.
Paving the Path for Immune Enhancing Nutrition in Colon Cancer: Modulation of Tumor Microenvironment and Optimization of Outcomes and Costs
Authors: Ambrosio Maria Raffaella , Spagnoli Luigi , Perotti Bruno , Petrelli Federica , Caini Saverio , Saieva Calogero , Usai Sofia , Bianchini Matteo , Cavazzana Andrea , Arganini Marco , Amorosi Andrea
Published: January 2023

Introduction. Published evidence suggests that immunonutrition has the potential to decrease postoperative complications and reduce length of stay in patients undergoing surgery for colorectal cancer. However, only a few studies have analyzed the effects of immunonutrition on tumor microenvironment and evaluated its prognostic impact. Material and methods. This is a single center retrospective study enrolling 50 patients undergoing elective surgery for colorectal cancer managed with immunonutrition and 50 patients managed with standard nutrition for comparison. Tumor microenvironment was analyzed before (on the biopsy at the time of diagnosis) and after (on the matched surgical specimen) administration of immunonutrition. Immune function related indicators, including cytotoxic T-lymphocytes, helper T-cells, antigen presenting cells, natural killer cells, T-exhausted lymphocytes, T-regulatory cells, M1 and M2 tumor associated macrophages and PD-L1 expression were assessed by immunohistochemistry. For both groups, clinicopathological data were collected and a 5-year follow-up was available. Results. We found that immunonutrition significantly activated the T-cell response against cancer, alter tumor microenvironment phenotype towards M2 polarization and inhibits the PD1/PD-L1 axis. A lower rate of postoperative complications and a shorter length of stay (p = 0.04) were observed in the immune nutrition group. Compared to standard nutrition group, patients managed wit immune nutrition showed a higher 5-year overall survival (p = 0.001). Finally, immune nutrition allowed to reduce the hospital care costs. Conclusions. Immunonutrition modulates tumor microenvironment by improving immune function and could prolong survival in patients undergoing elective surgery for colorectal cancer. Further studies are needed to optimize IN protocols and confirm their prognostic impact.
Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry
Authors: Sargas Claudia , Ayala Rosa , Larráyoz María José , Chillón María Carmen , Carrillo-Cruz Estrella , Bilbao-Sieyro Cristina , Prados de la Torre Esther , Martínez-Cuadrón David , Rodríguez-Veiga Rebeca , Boluda Blanca , Gil Cristina , Bernal Teresa , Bergua Juan Miguel , Algarra Lorenzo , Tormo Mar , Martínez-Sánchez Pilar , Soria Elena , Serrano Josefina , Alonso-Domínguez Juan Manuel , García-Boyero Raimundo , Amigo María Luz , Herrera-Puente Pilar , Sayas María José , Lavilla-Rubira Esperanza , Martínez-López Joaquín , Calasanz María José , García-Sanz Ramón , Pérez-Simón José Antonio , Gómez-Casares María Teresa , Sánchez-García Joaquín , Barragán Eva , Montesinos Pau ,   on behalf of PETHEMA group
Published: January 2023

Next–Generation Sequencing (NGS) implementation to perform accurate diagnosis in acute myeloid leukemia (AML) represents a major challenge for molecular laboratories in terms of specialization, standardization, costs and logistical support. In this context, the PETHEMA cooperative group has established the first nationwide diagnostic network of seven reference laboratories to provide standardized NGS studies for AML patients. Cross–validation (CV) rounds are regularly performed to ensure the quality of NGS studies and to keep updated clinically relevant genes recommended for NGS study. The molecular characterization of 2856 samples (1631 derived from the NGS–AML project; NCT03311815) with standardized NGS of consensus genes (ABL1, ASXL1, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA2, HRAS, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, PTPN11, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53, U2AF1 and WT1) showed 97% of patients having at least one mutation. The mutational profile was highly variable according to moment of disease, age and sex, and several co–occurring and exclusion relations were detected. Molecular testing based on NGS allowed accurate diagnosis and reliable prognosis stratification of 954 AML patients according to new genomic classification proposed by Tazi et al. Novel molecular subgroups, such as mutated WT1 and mutations in at least two myelodysplasia–related genes, have been associated with an adverse prognosis in our cohort. In this way, the PETHEMA cooperative group efficiently provides an extensive molecular characterization for AML diagnosis and risk stratification, ensuring technical quality and equity in access to NGS studies.
Al[18F]F-NOTA-Octreotide Is Comparable to [68Ga]Ga-DOTA-TATE for PET/CT Imaging of Neuroendocrine Tumours in the Latin-American Population
Authors: Haeger Arlette , Soza-Ried Cristian , Kramer Vasko , Hurtado de Mendoza Ana , Eppard Elisabeth , Emmanuel Noémie , Wettlin Johanna , Amaral Horacio , Fernández René
Published: January 2023

PET imaging of neuroendocrine tumours (NET) is well established for staging and therapy follow-up. The short half-life, increasing costs, and regulatory issues significantly limit the availability of approved imaging agents, such as [68Ga]Ga-DOTA-TATE. Al[18F]F-NOTA-Octreotide provides a similar biodistribution and tumour uptake, can be produced on a large scale and may improve access to precision imaging. Here we prospectively compared the clinical utility of [68Ga]Ga-DOTA-TATE and Al[18F]F-NOTA-Octreotide in the Latin-American population. Our results showed that in patients with stage IV NETs [68Ga]Ga-DOTA-TATE presents higher physiological uptake than Al[18F]F-NOTA-Octreotide in the liver, hypophysis, salivary glands, adrenal glands (all p < 0.001), pancreatic uncinated process, kidneys, and small intestine (all p < 0.05). Nevertheless, despite the lower background uptake of Al[18F]F-NOTA-Octreotide, comparative analysis of tumour-to-liver (TLR) and tumour-to-spleen (TSR) showed no statistically significant difference for lesions in the liver, bone, lymph nodes, and other tissues. Only three discordant lesions in highly-metastases livers were detected by [68Ga]Ga-DOTA-TATE but not by Al[18F]F-NOTA-Octreotide and only one discordant lesion was detected by Al[18F]F-NOTA-Octreotide but not by [68Ga]Ga-DOTA-TATE. Non-inferiority analysis showed that Al[18F]F-NOTA-Octreotide is comparable to [68Ga]Ga-DOTA-TATE. Hence, our results demonstrate that Al[18F]F-NOTA-Octreotide provided excellent image quality, visualized NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE.
Effect of Metal Atom in Zeolitic Imidazolate Frameworks (ZIF-8 & 67) for Removal of Dyes and Antibiotics from Wastewater: A Review
Authors: Pouramini Zahra , Mousavi Seyyed Mojtaba , Babapoor Aziz , Hashemi Seyyed Alireza , Lai Chin Wei , Mazaheri Yousef , Chiang Wei-Hung
Published: January 2023

The use of antibiotics and dyes has resulted in severe water pollution and health risks; therefore, it is urgent to remove them from water sources. Among the most common methods for removing harmful water contaminants, adsorption and photodegradation are the most economical, simple, and reusable. Due to their high porosity, adjustability, and crystal structure, metal-organic frameworks (MOFs) are one of the effective adsorbents and photocatalysts. A typical MOF material is zeolitic imidazolate framework-8/67 (ZIF-8 and ZIF-67), comprising essentially of the metal atoms Zn and 2-methylimidazole (2-MIM). ZIF-8 and ZIF-67 have unique properties that make them efficient in water treatment due to high adsorption capacities and being good hosts for photocatalytic materials. In this article, a review study of the design and methods of synthesis of ZIF-8 and ZIF-67 composites is presented. An introduction to the current research on the role of ZIF-8 and ZIF-67 compounds as adsorbents and photocatalysts for wastewater pollution removal is provided. In this review study, we aim to supply a mechanistic perspective on the use of ZIF-8/67 composites in wastewater purification and present novel visions for the development of extremely effective ZIF-8/67-based adsorbents and photocatalysts. To unlock the full potential of ZIF-8/67 composites in dye and antibiotic removal and water recycling, current difficulties will be discussed in detail.
New Treatment for Type 2 Diabetes Mellitus Using a Novel Bipyrazole Compound
Authors: Alqudah Abdelrahim , Qnais Esam Y. , Wedyan Mohammed A. , Altaber Sara , Abudalo Rawan , Gammoh Omar , Alkhateeb Hakam , Bataineh Sajeda , Athamneh Rabaa Y. , Oqal Muna , Abu-Safieh Kayed , McClements Lana
Published: January 2023

2′,3,3,5′-Tetramethyl-4′-nitro-2′H-1,3′-bipyrazole (TMNB) is a novel bipyrazole compound with unknown therapeutic potential in diabetes mellitus. This study aims to investigate the anti-diabetic effects of TMNB in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with TMNB (10 mg/kg) or (200 mg/kg) metformin for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. TMNB reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). TMNB abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with TMNB compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 and AMPK were upregulated following treatment with TMNB (p < 0.001, < 0.01, respectively). TMNB was able to upregulate GLUT2 and AMPK protein expression in liver (p < 0.001, < 0.001, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with TMNB compared to the vehicle controls (p < 0.001, 0.01, respectively). TMNB reduced MDA and IL-6 levels (p < 0.001), and increased GSH level (p < 0.05) in diabetic rats compared to the vehicle controls. Conclusion: TMNB ameliorates insulin resistance, oxidative stress, and inflammation in a T2D model. TMNB could represent a promising therapeutic agent to treat T2D.