bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Escherichia coli from Water and Food Sold on the Streets of Maputo: Molecular Typing, Virulence Genes, and Antibiotic Resistance
Authors: Salamandane Acácio , Alves Suse , Chambel Lélia , Malfeito-Ferreira Manuel , Brito Luísa
Published: January 2022

The aim of this study was to investigate the pathogenic potential and antibiotic resistance of 59 Escherichia coli isolates from ready-to-eat (RTE) street food (n = 31) and drinking water (n = 28) sold in the city of Maputo, Mozambique. The isolates were characterized by XbaI subtyping analysis via pulsed field gel electrophoresis. Multiplex PCRs were performed targeting five virulence genes (stx, lt, st, astA, and eae) and three groups of antibiotic-resistant genes, namely ß-lactamases (extended-spectrum ß-lactamase and AmpC), tetracycline (tetA, tetB, and tetM) and sulfamethoxazole/trimethoprim (sul1, sul2, and sul3). The stx virulence gene, encoding the Shiga/Vero (VT) toxin produced by the verotoxin-producing E. coli (VTEC), was identified with similar frequency in isolates from food (5/31) and water (6/28). The highest percentages of resistant isolates from food and water were found for ß-lactams imipenem (35.5 and 39.3%, respectively) and ampicillin (39.3 and 46.4%, respectively). Multidrug resistance was observed in 31.3% of the isolates, being higher in E. coli isolates from water (45.5%) compared to RTE street food isolates (19.2%). Virulence genes were detected in 73% of the multidrug-resistant isolates. Concerning antibiotic-resistant genes, ESBL was the most frequent (57.7%) among β-lactamases while tetA was the most frequent (50%) among non-β-lactamases.
Exploring the Innovation Diffusion of Big Data Robo-Advisor
Authors: Tsai Shuo-Chang , Chen Chih-Hsien
Published: January 2022

The main objective of this study was to explore the current practical use of an AI robo-advisor algorithmic technique. This study utilizes Roger’s innovation diffusion theory as a basis to explore the application of robo-advisors for forecasting in the stock market by using an abductive reasoning approach. We used literature reviews and semi-structured interviews to interview representatives of fund companies to see if they had adopted AI big data forecasting models to invest in stock selection. This study summarizes the big data stock market forecasts of the literature. According to the summary, the accuracy of the prediction models of these scholars ranged from 52% to 97%, with the prediction results of the models varying significantly. Interviews with 21 representatives of these fund companies revealed that the stock market forecast model of big data robo-advisors have not become a reference basis for fund investment candidates, mainly because of the unstable model prediction rate, and the lack of apparent relative advantages and observability, as well as being too complex. Thus, from the view of innovation diffusion, there is a lack of diffusion for the robo-advisor. Knowledge occurs when an individual is exposed to the existence of innovation, and gains some understanding of how it functions. Thereby, when investors become more familiar with neural network-like stock prediction models, this novel AI stock market forecasting model is expected to become another indicator of technical analysis in the future.
The Service Innovation Factor in Painting Creation Enterprises from the Service-Dominant Logic Perspective
Authors: Lin Szu-Yao
Published: January 2022

This paper describes a study of the elements of service innovation for artistic painting creation enterprises from the service-dominant logic point of view. This research mainly aimed to (1) explore how to integrate the concepts of service innovation for companies (service provider) providing painting as their service in their business model, and (2) to explore that how consumers (service receiver) can evaluate their experience value as well as achieve value co-creation through the service process under the service innovation model. Here, a multiple case-detailed CEO-interview-based methodology was used with four corporate companies that provide artistic painting creation services. The findings showed that, as painting is the core content of the service, the process not only meets the emotional needs of consumers through its operations, but also develops innovations in the business model to solve social issues. This research applies the viewpoint of art in the service science field and combines creative and innovative thinking with business operations. The outcome has practical implications for enhancing the social value of business structures and enabling value co-creation under the development of creative industries. In conclusion, the popularity and accessibility of using painting as a service reinforces painting creation to develop internal expression channels that can be used as service innovation for the development of businesses in the creative industries.
How Effective and Prerequisite Are Electromagnetic Extremely Low Frequency (ELF) Recordings in the Schumann Resonances Band to Function as Seismic Activity Precursors
Authors: Tritakis Vasilis , Contopoulos Ioannis , Mlynarczyk Janusz , Christofilakis Vasilis , Tatsis Giorgos , Repapis Christos
Published: January 2022

ELF recordings, especially in the 0–50 Hz range (Schumann Resonances), have gained great interest during the last twenty years because of their possible relation to many geophysical, climatological, solar, and even biological phenomena, which several well-known scientists have reported. A very important question that still has not been answered is whether some particular variations in the Schumann Resonances (SR) band operate as precursors of forthcoming seismic activity. Greece and the wider Mediterranean area are a very seismic territory where medium size earthquakes (4–6.5 Richter) occur very often, contributing to a high percentage of the natural hazards of the area. In our effort to make evident how effective and prerequisite SR recordings are in the detection of forthcoming earthquakes, we analyze data collected for almost five years by two SR stations located in the north and the south edge of the Greek territory, respectively. We have come to the conclusion that particular SR modulations are very useful in the predictability of forthcoming seismic activity, but they need to be completed with additional observations of adjoining effects which can contribute to the final decision.
Rate Constants and Branching Ratios for the Self-Reaction of Acetyl Peroxy (CH3C(O)O2•) and Its Reaction with CH3O2
Authors: Assali Mohamed , Fittschen Christa
Published: January 2022

The self-reaction of acetylperoxy radicals (CH3C(O)O2•) (R1) as well as their reaction with methyl peroxy radicals (CH3O2•) (R2) have been studied using laser photolysis coupled to a selective time resolved detection of three different radicals by cw-CRDS in the near-infrared range: CH3C(O)O2• was detected in the Ã-X˜ electronic transition at 6497.94 cm−1, HO2• was detected in the 2ν1 vibrational overtone at 6638.2 cm−1, and CH3O2• radicals were detected in the Ã-X˜ electronic transition at 7489.16 cm−1. Pulsed photolysis of different precursors at different wavelengths, always in the presence of O2, was used to generate CH3C(O)O2• and CH3O2• radicals: acetaldehyde (CH3CHO/Cl2 mixture or biacetyle (CH3C(O)C(O)CH3) at 351 nm, and acetone (CH3C(O)CH3) or CH3C(O)C(O)CH3 at 248 nm. From photolysis experiments using CH3C(O)C(O)CH3 or CH3C(O)CH3 as precursor, the rate constant for the self-reaction was found with k1 = (1.3 ± 0.3) × 10−11 cm3s−1, in good agreement with current recommendations, while the rate constant for the cross reaction with CH3O2• was found to be k2 = (2.0 ± 0.4) × 10−11 cm3s−1, which is nearly two times faster than current recommendations. The branching ratio of (R2) towards the radical products was found at 0.67, compared with 0.9 for the currently recommended value. Using the reaction of Cl•-atoms with CH3CHO as precursor resulted in radical profiles that were not reproducible by the model: secondary chemistry possibly involving Cl• or Cl2 might occur, but could not be identified.
Simulation of an Extreme Precipitation Event Using Ensemble-Based WRF Model in the Southeastern Coastal Region of China
Authors: Gao Lu , Wei Jianhui , Lei Xiangyong , Ma Miaomiao , Wang Lan , Guan Xiaojun , Lin Hui
Published: January 2022

Extreme weather events have increased significantly in the past decades due to global warming. As a robust forecast and monitoring tool of extreme weather events, regional climate models have been widely applied on local scales. This study presented a simulation of an extreme precipitation event in the Southeastern Coastal Region of China (SEC), where floods, typhoons, and mountain torrents occur frequently using the Weather Research and Forecast model (WRF) driven by GEFS (The Global Ensemble Forecast System) ensemble members (one control run and 20 ensemble members) from 01 UTC 14 June to 18 UTC 16 June 2010. The observations of hourly precipitation records from 68 meteorological stations in the SEC were applied to validate the WRF ensemble simulations with respect to 3-hourly cumulative precipitation (3hP), 6-hourly cumulative precipitation (6hP) and total cumulative precipitation (TCP). The results showed that all WRF 20 ensemble outputs could capture the extreme precipitation events fairly well with the Pearson correlation coefficient ranging from 0.01 to 0.82 and 0.16 to 0.89 for 3 and 6hP, respectively. The normalized root mean square error was comparable between the control run and 20 ensembles for 3hP (0.67 vs. 0.63) and 6hP (0.51 vs. 0.53). In general, WRF underestimated the observations for TCP. The control run (En00) modeled 28.1% less precipitation, while the 20 ensembles modeled 3.9% to 55.5% less precipitation than observations. The ensemble member 12 (En12) showed the best TCP simulation with the smallest bias. The average of 20 ensembles simulated 31.7% less precipitation than observations. The total precipitation was not captured by WRF with a significant bias that ranged from −203.1 to 112.3 mm. The storm centers were generally not captured by WRF in this case study. WRF ensembles underestimated the observation in the central Fujian Province while overestimated in the northern and southern Fujian Province. Although the average of ensembles can reduce the uncertainty to a certain extent, the individual ensemble (e.g., En12) may be more reliable on local scales.
Effect of Selected Meteorological Variables on Full Flowering of Some Forest Herbs in the Western Carpathians
Authors: Kubov Martin , Schieber Branislav , Janík Rastislav
Published: January 2022

At present, temperate forest ecosystems are endangered by both abiotic and biotic factors. The effects of abiotic components, e.g., meteorological variables, are constantly studied. However, the detailed mechanisms affecting the phenology of plants are still unknown. Two meteorological variables (air temperature and cumulative precipitation) were analysed for the period from 1995 to 2020 in order to determine which factor which has a more significant effect on onset of the full-flowering (FF) phenophase. A set of nine forest herbs, representing different phenological groups from the viewpoint of flowering, was examined (early spring: Petasites albus and Pulmonaria officinalis; mid-spring: Carex pilosa and Dentaria bulbifera; late spring: Fragaria visa and Galium odoratum; early summer: Veronica officinalis; mid-summer: Mycelis muralis; and late summer: Campanula trachelium). Temperature-sum requirements and temporal trends in the onset of FF were also studied. The research conducted at the Ecological Experimental Station in the Kremnické vrchy Mountains (central Slovakia) at an altitude of 500 m asl. Our results show that the air temperature correlated more significantly with the date of onset of FF (r > 0.6, p < 0.001) than with precipitation. On average, the air-temperature sums, calculated for the threshold temperatures of 0 °C and 5 °C, increased from 142.9 °C (Petasites albus) to 1732.9 °C (Campanula trachelium) and from 223.4 °C (Petasites albus) to 1820.8 °C (Campanula trachelium), respectively. Temporal trends in the onset of FF over the last 26 years confirm shifts to earlier dates for most species (excepting early spring Petasites albus). In spring flowering species, shifts ranged from 2 days (0.07 day/year) for Pulmonaria officinalis to 8 days (0.30 day/year) for Carex pilosa. As for summer species, the onset of flowering shifted more significantly to earlier dates—from 7 days (0.27 day/year) for Campanula trachelium to 12 days (0.46 day/year) for Veronica officinalis. The observed trends were statistically significant (p < 0.05) for five examined species (Carex pilosa, Dentaria bulbifera, Fragaria vesca, Veronica officinalis and Mycelis muralis).
Relationships between Extratropical Precipitation Systems and UTLS Temperatures and Tropopause Height from GPM and GPS-RO
Authors: Johnston Benjamin R. , Xie Feiqin , Liu Chuntao
Published: January 2022

This study characterizes the relationship between extratropical precipitation systems to changes in upper troposphere and lower stratosphere (UTLS) temperature and tropopause height within different environments. Precipitation features (PFs) observed by the Global Precipitation Measurement (GPM) satellite are collocated with GPS radio occultation (RO) temperature profiles from 2014 to 2017 and classified as non-deep stratospheric intrusion (non-DSI; related to convective instability) or deep stratospheric intrusion (DSI; related to strong dynamic effects on the tropopause). Non-DSI PFs introduce warming (up to 1 K) in the upper troposphere, transitioning to strong cooling (up to −3.5 K) around the lapse rate tropopause (LRT), and back to warming (up to 2.5 K, particularly over the ocean) in the lower stratosphere. UTLS temperature anomalies for DSI events are driven predominantly by large scale dynamics, with major cooling (up to −6 K) observed from the mid-troposphere to the LRT, which transitions to strong warming (up to 4 K) in the lower stratosphere. Small and deep non-DSI PFs typically result in a lower LRT (up to 0.4 km), whereas large but weaker PFs lead to a higher LRT with similar magnitudes. DSI events are associated with larger LRT height decreases, with anomalies of almost −2 km near the deepest PFs. These results suggest intricate relationships between precipitation systems and the UTLS temperature structure. Importantly, non-DSI PF temperature anomalies show patterns similar to tropical convection, which provides unification of previous tropical research with extratropical barotropic convective impacts to UTLS temperatures.
Organic and Elemental Carbon in the Urban Background in an Eastern Mediterranean City
Authors: Hussein Tareq , Li Xinyang , Bakri Zaid , Alastuey Andres , Arar Sharif , Al-Hunaiti Afnan , Viana Mar , Petäjä Tuukka
Published: January 2022

The Mediterranean region is an important area for air pollution as it is the crossroads between three continents; therefore, the concentrations of atmospheric aerosol particles are influenced by emissions from Africa, Asia, and Europe. Here we concentrate on an eleven-month time series of the ambient concentration of organic carbon (OC) and elemental carbon (EC) between May 2018–March 2019 in Amman, Jordan. Such a dataset is unique in Jordan. The results show that the OC and EC annual mean concentrations in PM2.5 samples were 5.9 ± 2.8 µg m–3 and 1.7 ± 1.1 µg m–3, respectively. It was found that the majority of OC and EC concentrations were within the fine particle fraction (PM2.5). During sand and dust storm (SDS) episodes OC and EC concentrations were higher than the annual means; the mean values during these periods were about 9.6 ± 3.5 µg m–3 and 2.5 ± 1.2 µg m–3 in the PM2.5 samples. Based on this, the SDS episodes were identified to be responsible for an increased carbonaceous aerosol content as well as PM2.5 and PM10 content, which may have direct implications on human health. This study encourages us to perform more extensive measurements during a longer time period and to include an advanced chemical and physical characterization for urban aerosols in the urban atmosphere of Amman, which can be representative of other urban areas in the region.
Automatic Detection of Sfe: A Step Forward
Authors: Curto Subirats Juan José , Fischer-Carles Alba , Solé Anna
Published: January 2022

Solar flare effects (Sfe) are magnetic variations caused by solar flare events. They only show up in the illuminated hemisphere. Their detection is a difficult task because they do not have a definite pattern and, additionally, they must be separated from other magnetic perturbations. However, we attempted to automatize these detections by using two different strategies. The first strategy takes advantage of one of the Sfe characteristics, as they usually have a rapid rise, followed by a smooth decay, which typically produces a crochet-like shape in the magnetograms. Thus, we created several morphological models for each magnetic component. Then, we identified a definite Sfe time interval by setting the conditions for various parameters, such as the correlations of the measured data with the models, or the model similarities among the different components. In the second stage of this strategy, we observed clusters of time intervals. Each of these clusters were attributed to a timespan of event possibility. We found the statistical optimal value of the correlation parameters by using the ROC curve method and Youden index. The second strategy was based on some of the properties of Sfe ionospheric electric currents, such as their spherical symmetry around the vortex. Here, the algorithm calculated the derivative of the data in order to avoid contamination of the daily variation Sq, and, by means of trigonometric formulas, computed the magnetic radial component relative to the Sfe current vortex (the focus). It then created an Sfe index with this data. A prior assumption of the focus position in a preceding work is no longer needed since we made a wide patrol of the space area to find it. Through a progressive thresholding process, we found its statistical optimal value (0.4 nT min−1) again by using the ROC curve method and Youden index. For both of the strategies, we have made a large calculation of Sfe detection (for the period of 2000–2020), which included 33 Sfe. Finally, we combined the results of both methods—which in fact are complementary—and obtained a unified list that gave a higher hit ratio than those that were obtained separately. This unified method gave promising results towards the possibility of Sfe automatic detection.
Identification of Key Proteins from the Alternative Lengthening of Telomeres-Associated Promyelocytic Leukemia Nuclear Bodies Pathway
Authors: Armendáriz-Castillo Isaac , Hidalgo-Fernández Katherine , Pérez-Villa Andy , García-Cárdenas Jennyfer M. , López-Cortés Andrés , Guerrero Santiago
Published: January 2022

Alternative lengthening of telomeres-associated promyelocytic leukemia nuclear bodies (APBs) are a hallmark of telomere maintenance. In the last few years, APBs have been described as the main place where telomeric extension occurs in ALT-positive cancer cell lines. A different set of proteins have been associated with APBs function, however, the molecular mechanisms behind their assembly, colocalization, and clustering of telomeres, among others, remain unclear. To improve the understanding of APBs in the ALT pathway, we integrated multiomics analyses to evaluate genomic, transcriptomic and proteomic alterations, and functional interactions of 71 APBs-related genes/proteins in 32 Pan-Cancer Atlas studies from The Cancer Genome Atlas Consortium (TCGA). As a result, we identified 13 key proteins which showed distinctive mutations, interactions, and functional enrichment patterns across all the cancer types and proposed this set of proteins as candidates for future ex vivo and in vivo analyses that will validate these proteins to improve the understanding of the ALT pathway, fill the current research gap about APBs function and their role in ALT, and be considered as potential therapeutic targets for the diagnosis and treatment of ALT-positive cancers in the future.
First Descriptive Analysis of the Faecal Microbiota of Wild and Anthropized Barbary Macaques (Macaca sylvanus) in the Region of Bejaia, Northeast Algeria
Authors: Boumenir Mourad , Hornick Jean-Luc , Taminiau Bernard , Daube Georges , Brotcorne Fany , Iguer-Ouada Mokrane , Moula Nassim
Published: January 2022

Previous research has revealed the gut microbiota profile of several primate species, as well as the impact of a variety of anthropogenic factors, such as tourist food supply, on these bacterial communities. However, there is no information on the gut microbiota of the endangered wild Barbary macaque (Macaca sylvanus). The present study is the first to characterize the faecal microbiota of this species, as well as to investigate the impact of tourist food provisioning on it. A total of 12 faecal samples were collected in two groups of M. sylvanus in the region of Bejaia in Algeria. The first group—a tourist-provisioned one—was located in the tourist area of the Gouraya National Park and the second group—a wild-feeding one—was located in the proximity of the village of Mezouara in the forest of Akfadou. After DNA extraction, the faecal microbiota composition was analysed using 16S rDNA sequencing. Statistical tests were performed to compare alpha diversity and beta diversity between the two groups. Non-metric multidimensional scaling analysis (NMDS) was applied to visualize biodiversity between groups. Behaviour monitoring was also conducted to assess the time allocated to the consumption of anthropogenic food by the tourist-provisioned group. Our results revealed the presence of 209 bacterial genera from 17 phyla in the faecal microbiota of Barbary macaques. Firmicutes was the most abundant bacterial phylum, followed by Bacteroidetes and Verrucomicrobia. On the other hand, the comparison between the faecal microbiota of the two study groups showed that tourism activity was associated with a significant change on the faecal microbiota of M.sylvanus, probably due to diet alteration (with 60% of feeding time allocated to the consumption of anthropogenic food). The potentially low-fibre diet at the tourist site adversely influenced the proliferation of bacterial genera found in abundance in the wild group such as Ruminococcaceae. Such an alteration of the faecal microbiota can have negative impacts on the health status of these animals by increasing the risk of obesity and illness and calls for special management measures to reduce the provisioning rate in tourist areas.
Osteopenia in a Mouse Model of Spinal Cord Injury: Effects of Age, Sex and Motor Function
Authors: Hook Michelle A. , Falck Alyssa , Dundumulla Ravali , Terminel Mabel , Cunningham Rachel , Sefiani Arthur , Callaway Kayla , Gaddy Dana , Geoffroy Cédric G.
Published: January 2022

After spinal cord injury (SCI), 80% of individuals are diagnosed with osteopenia or osteoporosis. The dramatic loss of bone after SCI increases the potential for fractures 100-fold, with post-fracture complications occurring in 54% of cases. With the age of new SCI injuries increasing, we hypothesized that a SCI-induced reduction in weight bearing could further exacerbate age-induced bone loss. To test this, young (2–3 months) and old (20–30 months) male and female mice were given a moderate spinal contusion injury (T9–T10), and recovery was assessed for 28 days (BMS, rearing counts, distance traveled). Tibial trabecular bone volume was measured after 28 days with ex vivo microCT. While BMS scores did not differ across groups, older subjects travelled less in the open field and there was a decrease in rearing with age and SCI. As expected, aging decreased trabecular bone volume and cortical thickness in both old male and female mice. SCI alone also reduced trabecular bone volume in young mice, but did not have an additional effect beyond the age-dependent decrease in trabecular and cortical bone volume seen in both sexes. Interestingly, both rearing and total activity correlated with decreased bone volume. These data underscore the importance of load and use on bone mass. While partial weight-bearing does not stabilize/reverse bone loss in humans, our data suggest that therapies that simulate complete loading may be effective after SCI.
Plant Beneficial Deep-Sea Actinobacterium, Dermacoccus abyssi MT1.1T Promote Growth of Tomato (Solanum lycopersicum) under Salinity Stress
Authors: Rangseekaew Pharada , Barros-Rodríguez Adoración , Pathom-aree Wasu , Manzanera Maximino
Published: January 2022

Salt stress is a serious agricultural problem threatens plant growth and development resulted in productivity loss and global food security concerns. Salt tolerant plant growth promoting actinobacteria, especially deep-sea actinobacteria are an alternative strategy to mitigate deleterious effects of salt stress. In this study, we aimed to investigate the potential of deep-sea Dermacoccus abyssi MT1.1T to mitigate salt stress in tomato seedlings and identified genes related to plant growth promotion and salt stress mitigation. D. abyssi MT1.1T exhibited plant growth promoting traits namely indole-3-acetic acid (IAA) and siderophore production and phosphate solubilization under 0, 150, 300, and 450 mM NaCl in vitro. Inoculation of D. abyssi MT1.1T improved tomato seedlings growth in terms of shoot length and dry weight compared with non-inoculated seedlings under 150 mM NaCl. In addition, increased total soluble sugar and total chlorophyll content and decreased hydrogen peroxide content were observed in tomato inoculated with D. abyssi MT1.1T. These results suggested that this strain mitigated salt stress in tomatoes via osmoregulation by accumulation of soluble sugars and H2O2 scavenging activity. Genome analysis data supported plant growth promoting and salt stress mitigation potential of D. abyssi MT1.1T. Survival and colonization of D. abyssi MT1.1T were observed in roots of inoculated tomato seedlings. Biosafety testing on D. abyssi MT1.1T and in silico analysis of its whole genome sequence revealed no evidence of its pathogenicity. Our results demonstrate the potential of deep-sea D. abyssi MT1.1T to mitigate salt stress in tomato seedlings and as a candidate of eco-friendly bio-inoculants for sustainable agriculture.
Homogenisation of Biocultural Diversity: Plant Ethnomedicine and Its Diachronic Change in Setomaa and Võromaa, Estonia, in the Last Century
Authors: Sõukand Renata , Kalle Raivo , Pieroni Andrea
Published: January 2022

When studying the evolution of the use of medicinal plants, it is important to identify what role, and to what extent, external factors and local biocultural diversities play in shaping cultural changes. We chose as a case study, which forms part of a larger project, a religiously and linguistically distinct group, the Seto, and compared their current and past plant use with that of the surrounding Võro. Ethnobotanical fieldwork was conducted in the summers of 2018 and 2019. Current uses of plants constituted 34% of the total registered use reports and 41% of those were used to treat general diseases or used as prophylactics. In total, the medicinal use of 86 taxa was recorded, and of these 48 were prevalent. Strong erosion (the abandonment of 43, mainly wild taxa used historically) and valorisation of the uses shared with neighboring as well as distant regions once part of the Soviet Union, were evident, signalling the potential influence of the centralised distribution of knowledge. The results clearly show that the plant medicine-related biocultural diversities of the two groups have been considerably homogenised, eroded and influenced by the knowledge spread through various means during the Soviet era and over the last 30 years.
Preoperative Stereotactic Radiosurgery for Glioblastoma
Authors: Lehrer Eric J. , Ruiz-Garcia Henry , Nehlsen Anthony D. , Sindhu Kunal K. , Estrada Rachel Sarabia , Borst Gerben R. , Sheehan Jason P. , Quinones-Hinojosa Alfredo , Trifiletti Daniel M.
Published: January 2022

Glioblastoma is a devastating primary brain tumor with a median overall survival of approximately 15 months despite the use of optimal modern therapy. While GBM has been studied for decades, modern therapies have allowed for a reduction in treatment-related toxicities, while the prognosis has largely been unchanged. Adjuvant stereotactic radiosurgery (SRS) was previously studied in GBM; however, the results were disappointing. SRS is a highly conformal radiation technique that permits the delivery of high doses of ionizing radiation in 1–5 sessions while largely sparing surrounding healthy tissues. Furthermore, studies have shown that the delivery of ablative doses of ionizing radiation within the central nervous system is associated with enhanced anti-tumor immunity. While SRS is commonly used in the definitive and adjuvant settings for other CNS malignancies, its role in the preoperative setting has become a topic of great interest due to the potential for reduced treatment volumes due to the treatment of an intact tumor, and a lower risk of nodular leptomeningeal disease and radiation necrosis. While early reports of SRS in the adjuvant setting for glioblastoma were disappointing, its role in the preoperative setting and its impact on the anti-tumor adaptive immune response is largely unknown. In this review, we provide an overview of GBM, discuss the potential role of preoperative SRS, and discuss the possible immunogenic effects of this therapy.
Exogenous Gibberellin Treatment Enhances Melatonin Synthesis for Melatonin-Enriched Rice Production
Authors: Hwang Ok Jin , Back Kyoungwhan
Published: January 2022

Melatonin production is induced by many abiotic and biotic stressors; it modulates the levels of many plant hormones and their signaling pathways. This study investigated the effects of plant hormones on melatonin synthesis. Melatonin synthesis in rice seedlings was significantly induced upon exogenous gibberellin 3 (GA3) treatment, while it was severely decreased by GA synthesis inhibitor paclobutrazol. In contrast, abscisic acid (ABA) strongly inhibited melatonin synthesis, whereas its inhibitor norflurazon (NF) induced melatonin synthesis. The observed GA-mediated increase in melatonin was closely associated with elevated expression levels of melatonin biosynthetic genes such as TDC3, T5H, and ASMT1; it was also associated with reduced expression levels of catabolic genes ASDAC and M2H. In a paddy field, the treatment of immature rice seeds with exogenous GA led to enhanced melatonin production in rice seeds; various transgenic rice plants downregulating a GA biosynthesis gene (GA3ox2) and a signaling gene (Gα) showed severely decreased melatonin levels, providing in vivo genetic evidence that GA has a positive effect on melatonin synthesis. This is the first study to report that GA is positively involved in melatonin synthesis in plants; GA treatment can be used to produce melatonin-rich seeds, vegetables, and fruits, which are beneficial for human health.
Prediction and Modeling of Protein–Protein Interactions Using “Spotted” Peptides with a Template-Based Approach
Authors: Gasbarri Chiara , Rosignoli Serena , Janson Giacomo , Boi Dalila , Paiardini Alessandro
Published: January 2022

Protein–peptide interactions (PpIs) are a subset of the overall protein–protein interaction (PPI) network in the living cell and are pivotal for the majority of cell processes and functions. High-throughput methods to detect PpIs and PPIs usually require time and costs that are not always affordable. Therefore, reliable in silico predictions represent a valid and effective alternative. In this work, a new algorithm is described, implemented in a freely available tool, i.e., “PepThreader”, to carry out PPIs and PpIs prediction and analysis. PepThreader threads multiple fragments derived from a full-length protein sequence (or from a peptide library) onto a second template peptide, in complex with a protein target, “spotting” the potential binding peptides and ranking them according to a sequence-based and structure-based threading score. The threading algorithm first makes use of a scoring function that is based on peptides sequence similarity. Then, a rerank of the initial hits is performed, according to structure-based scoring functions. PepThreader has been benchmarked on a dataset of 292 protein–peptide complexes that were collected from existing databases of experimentally determined protein–peptide interactions. An accuracy of 80%, when considering the top predicted 25 hits, was achieved, which performs in a comparable way with the other state-of-art tools in PPIs and PpIs modeling. Nonetheless, PepThreader is unique in that it is able at the same time to spot a binding peptide within a full-length sequence involved in PPI and model its structure within the receptor. Therefore, PepThreader adds to the already-available tools supporting the experimental PPIs and PpIs identification and characterization.
Clinical Significance of Hepsin and Underlying Signaling Pathways in Prostate Cancer
Authors: Lu Lucy , Cole Adam , Huang Dan , Wang Qiang , Guo Zhongming , Yang Wancai , Lu Jim
Published: January 2022

The hepsin gene encodes a type II transmembrane serine protease. Previous studies have shown the overexpression of hepsin in prostate cancer, and the dysregulation of hepsin promotes cancer cell proliferation, migration, and metastasis in vitro and in vivo. The review incorporated with our work showed that hepsin expression levels were specifically increased in prostate cancer, and higher expression in metastatic tumors than in primary tumors was also observed. Moreover, increased expression was associated with poor outcomes for patients with prostate cancer. Using in silico protein–protein interaction prediction, mechanistic analysis showed that hepsin interacted with eight other oncogenic proteins, whose expression was significantly correlated with hepsin expression in prostate cancer. The oncogenic functions of hepsin are mainly linked to proteolytic activities that disrupt epithelial integrity and regulatorily interact with other genes to influence cell-proliferation, EMT/metastasis, inflammatory, and tyrosine-kinase-signaling pathways. Moreover, genomic amplifications of hepsin, not deletions or other alterations, were significantly associated with prostate cancer metastasis. Targeting hepsin using a specific inhibitor or antibodies significantly attenuates its oncogenic behaviors. Therefore, hepsin could be a novel biomarker and therapeutic target for prostate cancer.
Posttranscriptional Regulation of Insulin Resistance: Implications for Metabolic Diseases
Authors: Pérez-García Ana , Torrecilla-Parra Marta , Fernández-de Frutos Mario , Martín-Martín Yolanda , Pardo-Marqués Virginia , Ramírez Cristina M.
Published: January 2022

Insulin resistance defines an impairment in the biologic response to insulin action in target tissues, primarily the liver, muscle, adipose tissue, and brain. Insulin resistance affects physiology in many ways, causing hyperglycemia, hypertension, dyslipidemia, visceral adiposity, hyperinsulinemia, elevated inflammatory markers, and endothelial dysfunction, and its persistence leads to the development metabolic disease, including diabetes, obesity, cardiovascular disease, or nonalcoholic fatty liver disease (NAFLD), as well as neurological disorders such as Alzheimer’s disease. In addition to classical transcriptional factors, posttranscriptional control of gene expression exerted by microRNAs and RNA-binding proteins constitutes a new level of regulation with important implications in metabolic homeostasis. In this review, we describe miRNAs and RBPs that control key genes involved in the insulin signaling pathway and related regulatory networks, and their impact on human metabolic diseases at the molecular level, as well as their potential use for diagnosis and future therapeutics.
Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro
Authors: Millette Katelyn , Rodriguez Keith , Sheng Xia , Finley Stacey , Georgia Senta
Published: January 2022

As patients recently diagnosed with T1D and patients with T2D have residual beta cell mass, there is considerable effort in beta cell biology to understand the mechanisms that drive beta cell regeneration as a potential cellular therapy for expanding patients’ residual beta cell population. Both mouse and human studies have established that beta cell mass expansion occurs rapidly during pregnancy. To investigate the mechanisms of beta cell mass expansion during pregnancy, we developed a novel in vivo and in vitro models of pseudopregnancy. Our models demonstrate that pseudopregnancy promotes beta cell mass expansion in parous mice, and this expansion is driven by beta cell proliferation rather than hypertrophy. Importantly, estrogen, progesterone, and placental lactogen induce STAT5A signaling in the pseudopregnancy model, demonstrating that this model successfully recapitulates pregnancy-induced beta cell replication. We then created an in vitro model of pseudopregnancy and found that the combination of estrogen and placental lactogen induced beta cell replication in human islets and rat insulinoma cells. Therefore, beta cells both in vitro and in vivo increase proliferation when subjected to the pseudopregnancy cocktail compared to groups treated with estradiol or placental lactogen alone. The pseudopregnancy models described here may help inform novel methods of inducing beta cell replication in patients with diabetes.
Biomarkers to Detect Early-Stage Colorectal Cancer
Authors: Keenan Jacqueline I. , Frizelle Frank A.
Published: January 2022

Colorectal cancer is a leading cause of mortality worldwide. The high incidence and the acceleration of incidence in younger people reinforces the need for better techniques of early detection. The use of noninvasive biomarkers has potential to more accurately inform how patients are prioritised for clinical investigation, which, in turn, may ultimately translate into improved survival for those subsequently found to have curable-stage CRC. This review surveys a wide range of CRC biomarkers that may (alone or in combination) identify symptomatic patients presenting in primary care who should be progressed for clinical investigation.
Optimizing Effective Parameters to Enhance the Sensitivity of Vertical Flow Assay for Detection of Escherichia coli
Authors: Kaur Manpreet , Eltzov Evgeni
Published: January 2022

Vertical flow immunoassays (VFIAs) are considered potential point-of-care testing (POCT) devices compared to lateral flow assays due to their ability to analyze a comparatively large sample volume and ease of multiplexing. However, VFIA devices are limited by low analytical sensitivity when coupled with a visual colorimetric signal. Herein, we carefully analyzed key parameters that accounted for the proper functionality of VFIA that can be modified to enhance the overall sensitivity of VFIA. In particular, we focused on improving the stability of conjugate pads impregnated with capture antibodies, maintaining a controlled flow rate to ensure higher analyte reactivity with capture antibodies, and enhancing the absorption efficiency. The results showed that air-drying of conjugate pads in the presence of 5% (w/v) lactose significantly improved the stability of antibodies during long-term storage. Integration of dissolvable polyvinyl alcohol (PVA) membrane of optimal concentration as a time-barrier film into the sensor delayed the flow of samples, thereby increasing the biorecognition interaction time between immunoreagents for the formation of immuno-complexes, which in turn led to higher sensitivity of the assay. Furthermore, the employment of an absorbent pad with higher water holding capacity significantly reduced the non-specific binding of immunocomplexes, thereby reducing the possibility of false-negative results.
Magneto-Immunoassay for the Detection and Quantification of Human Growth Hormone
Authors: Ramanaviciene Almira , Popov Anton , Baliunaite Ema , Brasiunas Benediktas , Kausaite-Minkstimiene Asta , Tamer Ugur , Kirdaite Gailute , Bernotiene Eiva , Mobasheri Ali
Published: January 2022

Physiological and endocrine maintenance of a normal human growth hormone (hGH) concentration is crucial for growth, development, and a number of essential biological processes. In this study, we describe the preparation and characterization of magnetic nanoparticles coated with a gold shell (MNPs-Au). The optimal surface concentration of monoclonal anti-hGH antibodies (m-anti-hGH) on magnetic nanoparticles, as well as conditions that decrease non-specific interactions during the magneto-immunoassay, were elaborated. After the selective recognition, separation, and pre-concentration of hGH by MNPs-Au/m-anti-hGH and the hGH interaction with specific polyclonal biotin-labeled antibodies (p-anti-hHG-B) and streptavidin modified horseradish peroxidase (S-HRP), the MNPs-Au/m-anti-hGH/hGH/p-anti-hGH-B/S-HRP immunoconjugate was formed. The concentration of hGH was determined after the addition of 3,3′,5,5′-tetramethylbenzidine and hydrogen peroxide substrate solution for HRP; the absorbance at 450 nm was registered after the addition of STOP solution. The developed sandwich-type colorimetric magneto-immunoassay is characterized by a clinically relevant linear range (from 0.1 to 5.0 nmol L−1, R2 0.9831), low limit of detection (0.082 nmol L−1), and negligible non-specific binding of other antibodies or S-HRP. The obtained results demonstrate the applicability of the developed magneto-immunoassay for the concentration and determination of hGH in the serum. Additionally, important technical solutions for the development of the sandwich-type colorimetric magneto-immunoassay are discussed.
Microalgae-Based Fluorimetric Bioassays for Studying Interferences on Photosynthesis Induced by Environmentally Relevant Concentrations of the Herbicide Diuron
Authors: Grasso Gerardo , Cocco Giulia , Zane Daniela , Frazzoli Chiara , Dragone Roberto
Published: January 2022

The widespread agricultural use of the phenylurea herbicide Diuron (DCMU) requires the investigation of ecotoxicological risk in freshwater and soil ecosystems in light of potential effects on non-target primary producers and a heavier effect on higher trophic levels. We used microalgae-based fluorimetric bioassays for studying the interferences on the photosynthesis of a freshwater and soil model green microalga (Chlamydomonas reinhardtii) induced by environmentally relevant concentrations of the herbicide DCMU. Measurements of steady-state chlorophyll a (Chl-a) fluorescence emission spectra were performed; as well, the kinetics of the Chl-a fluorescence transient were recorded. Percentage indexes of interference on photosynthesis were calculated after comparison of steady-state and kinetic Chl-a fluorescence measurements of DCMU-exposed and control C. reinhardtii cell suspensions. The results obtained after 30 min exposure to the herbicide DCMU confirmed a significant inhibitory effect of DCMU 2 μg/L, and no significant differences between %ι values for DCMU 0.2 μg/L and 0.02 μg/L exposures. Positive %ε values from kinetic measurements of the Chl-a fluorescence transient confirmed the same interfering effect of 2 μg/L DCMU on PSII photochemistry in the exposed C. reinhardtii cell suspensions. Negative values of %ε observed for 0.2 and 0.02 μg/L DCMU exposures could be attributable to a presumptive ‘stimulatory-like’ effect in the photochemistry of photosynthesis. Short-term exposure to sub-μg/L DCMU concentration (≤0.2 μg/L) affects the photosynthetic process of the model microalga C. reinhardtii. Similar environmental exposures could affect natural communities of unicellular autotrophs, with hardly predictable cascading secondary effects on higher trophic levels.
Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone
Authors: Katzman Martin A. , Katzman Matthew P.
Published: January 2022

Orexin peptides comprise two neuropeptides, orexin A and orexin B, that bind two G-protein coupled receptors (GPCRs), orexin receptor 1 (OXR1) and orexin receptor 2 (OXR2). Although cell bodies that produce orexin peptides are localized in a small area comprising the lateral hypothalamus and adjacent regions, orexin-containing fibres project throughout the neuraxis. Although orexins were initially described as peptides that regulate feeding behaviour, research has shown that orexins are involved in diverse functions that range from the modulation of autonomic functions to higher cognitive functions, including reward-seeking, behaviour, attention, cognition, and mood. Furthermore, disruption in orexin signalling has been shown in mood disorders that are associated with low hedonic tone or anhedonia, including depression, anxiety, attention deficit hyperactivity disorder, and addiction. Notably, projections of orexin neurons overlap circuits involved in the modulation of hedonic tone. Evidence shows that orexins may potentiate hedonic behaviours by increasing the feeling of pleasure or reward to various signalling, whereas dysregulation of orexin signalling may underlie low hedonic tone or anhedonia. Further, orexin appears to play a key role in regulating behaviours in motivationally charged situations, such as food-seeking during hunger, or drug-seeking during withdrawal. Therefore, it would be expected that dysregulation of orexin expression or signalling is associated with changes in hedonic tone. Further studies investigating this association are warranted.
Conservative Management of Post-Operative Cerebrospinal Fluid Leak following Skull Base Surgery: A Pilot Study
Authors: Jamshidi Aria M. , Shah Ashish , Eichberg Daniel G. , Komotar Ricardo J. , Ivan Michael
Published: January 2022

Background/aims: Iatrogenic CSF leaks after endoscopic endonasal transsphenoidal surgery remain a challenging entity to manage, typically treated with CSF diversion via lumbar drainage. Objective: To assess the safety and efficacy of high-volume lumbar puncture (LP) and acetazolamide therapy to manage iatrogenic CSF leaks. Methods: We performed a prospective pilot study of four patients who developed iatrogenic postoperative CSF leaks after transsphenoidal surgery and analyzed their response to treatment with concomitant high-volume lumbar puncture followed by acetazolamide therapy for 10 days. Data collected included demographics, intra-operative findings, including methodology of skull base repair and type of CSF leak, time to presentation with CSF leak, complications associated with high-volume LP and acetazolamide treatment, and length of follow-up. Results: Mean patient age was 44.28 years, with an average BMI of 27.4. Mean time from surgery to onset of CSF leak was 7.71 days. All four patients had resolution of their CSF leak at two- and four-week follow-up. Mean overall follow-up time was 179 days, with a 100% CSF leak cure rate at the last clinic visit. No patient suffered perioperative complications or complications secondary to treatment. Conclusion: Although our pilot case series is small, we demonstrate that a high-volume LP, followed by acetazolamide therapy for 10 days, can be considered in the management of post-operative CSF leaks.