bluuebunny/crossref_metadata_2025 huggingface dataset:
Indecomposable positive maps on positive semidefinite matrices from Mn to Mn+1
Authors: AKATCH WINDA CHARLES , Okelo Nyaare Benard , Ong’ati Omolo N.
Published: March 2021

In this paper we obtain a theorem for 2-positive linear maps from Mn(C) to Mn+1(C), where n = 2, 3, 4. In addition, we answer in the affirmative a question that asked if there exists every 2-positive linear map from M3(C) to M4(C) is indecomposable using a family of positive linear maps with Choi matrices of 2-positive maps on positive semidefinite matrices. Further it is shown that 2-positive linear map from M4(C) to M5(C) are indecomposable.
A few attempts to increase the amount of a drug coated onto the microneedles
Authors: Liang Ling , Chen Yang , Ren Gui Yao , Li Jun You , Guo Xin Dong
Published: March 2021

As an approach of painless administration, coated microneedles (MNs) have an increasing attention on the drug loading capacity to meet higher drug dosage requirement. In this work, the solid and coated MNs were successfully fabricated using hot-compaction process and dipping with a dam board reservoir. The maximum drug loading of different height, arrays and coating solutions reached 118 μg, which was hundreds of times the unmodified coated MNs. The in vitro drug delivery was also evaluated and the result revealed that the coated MNs fabricated could achieve about 90% drug delivery efficiency. The insulin-coaded MNs holding 0.5 IU of insulin were fabricated with dipping method, which had the same therapeutic effect on diabetic mice compared with the injection of the same dose. All the results demonstrated that coated MNs could meet the dosage needs of diseases by improving the height, arrays and coating solutions.
Frequency Energy Plots of Dynamical Systems Attached to Piecewise Nonlinear Energy Sink
Authors: Shudeifat Mohammed Ameen Ameen Al , Saeed Adnan Salem
Published: March 2021

The frequency-energy plots (FEPs) of two-degree-of-freedom linear structures attached to piecewise nonlinear energy sink (PNES) are generated here and thoroughly investigated. This study provides the FEP analysis of such systems for further understanding of nonlinear targeted energy transfer (TET) by the PNES. The attached PNES incorporates a symmetrical clearance zone of zero stiffness content about its equilibrium position where the boundaries of the zone are coupled with linear structure by linear stiffness elements. In addition, linear viscous damping is selected to be continuous during PNES mass oscillation. The underlying nonlinear dynamical behaviour of the considered structure-PNES systems is investigated by generating the fundamental backbone curves of the FEP and the bifurcated subharmonic resonance branches using numerical continuation methods. Accordingly, interesting dynamical behaviour of the nonlinear normal modes (NNMs) of the structure-PNES system on different backbones and subharmonic resonance branches has been observed. In addition, the imposed wavelet transform frequency spectrums on the FEPs have revealed that the TET takes place where it is dominated by the nonlinear action of the PNES.
Selection of DNA Aptamers for Differentiation of Human Adipose-Derived Mesenchymal Stem Cells from Fibroblasts
Authors: de Melo Mariane Izabella Abreu , Cunha Pricila da Silva , de Miranda Marcelo Coutinho , Barbosa Joana Lobato , Faria Jerusa Araújo Quintão Arantes , Rodrigues Michele Angela , de Goes Alfredo Miranda , Gomes Dawidson Assis
Published: March 2021

In recent years, stem cell therapy has shown promise in regenerative medicine. In this context, the distinction of mesenchymal stem cells from fibroblasts has been crucial for safe clinical application of these cells. In the present study, we developed aptamers capable of specifically recognize mesenchymal stem cells derived from adipose tissue (ASC) using the Cell-SELEX technique. We tested the affinity of ASC aptamers compared to dermal fibroblasts (FIB). Quantitative PCR was advantageous for the validation of four candidate aptamers in vitro. The binding capabilities of Apta 2 and Apta 42 could not distinguish both cell types, while Apta 21 and Apta 99 showed a better binding capacity to ASC with dissociation constants (Kd) of 50.46 ± 2.28 nM and 72.71 ± 10.3 nM, respectively. However, Apta 21 showed a Kd of 86.78 ± 9.14 nM when incubated with FIB. Therefore, only Apta 99 showed specificity to detect ASC. This aptamer is a promising tool for the in vitro identification of ASC. These results will help understand the differences between these two cell types for more specific and precise cell therapies.
Short-Term Effect of Poly Lactic Acid Microplastics Uptake by Earthworms, Eudrilus eugeniae.
Authors: Khaldoon Shahad , Lalung Japareng , Ibrahim Mahamad Hakimi , Kamaruddin Mohamad Anuar , Yhaya Mohd Firdaus
Published: March 2021

The uptake of polylactic acid (PLA) microplastics, the most commonly used biodegradable plastics by earthworms Eudrilus eugeniae was investigated by observing their weight changes, biomass and the microplastics concentration after feeding them with a mixture of PLA and cow dung for 16 days at the concentrations of 0%, 10%, 30%, 60%, and 80% w/w dry weight. The mortality rate of the earthworms for all the PLA concentrations during the 16 days of feeding period was 0%. However, the microplastic affected the earthworms' weight significantly (P-value 0.00027), especially at the concentration of 80% of PLA. The earthworms had the lowest weight gain at 80%, followed by 60%, 30%, and 10% of PLA, respectively. The earthworms subjected to 80% and 10% of PLA had a similar pattern with the control. This was perhaps due to the high organic matter in the worm’s feed for the 10% PLA and the digestion mechanisms, which led the earthworms to preserve their energy and become less active in the 80% PLA, compared to all the other treatments. The PLA microplastics concentration factor (CF) in the vermicast was the highest at the 10 % PLA compared to other treatments, because Eudrilus eugeniae did not degrade the PLA. This study concludes that even though PLA is a biopolymer-based, it cannot be bio- assimilated by the earthworm.
The Melatonin Receptor MT2 Is Partly Involved in the Anti-Inflammatory Effects of Melatonin in Rats With Type 2 Diabetes Mellitus
Authors: Yapislar Hande , Haciosmanoglu Ebru , Sarioglu Turkan , Degirmencioglu Sevgin , Sogut Ibrahim , Poteser Michael , Ekmekcioglu Cem
Published: March 2021

Background: Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobiotic effects, the pineal hormone melatonin is also known to exert anti-inflammatory and antioxidant effects. Furthermore, melatonin was also suggested to affect insulin secretion and melatonin levels were reported to be decreased in T2DM patients

Aims: The aim of this study was therefore to investigate the effect of melatonin on inflammation in diabetic rats and to study the possible involvement of the melatonin receptor, MT2.
Materials and Methods: Male Sprague Dawley rats were randomly divided into four experimental groups (n = 10 per group):1) control, 2) streptozotocin/nicotinamid induced diabetes type 2 (T2DM), 3) T2DM treated with melatonin (500 µg/kg/day), and 4) T2DM treated with melatonin (500 µg/kg/day) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day). Blood samples were taken for biochemical parameters and various tissue samples (liver, adipose tissue, brain) were removed for immunohistochemistry (IHC), western blot (WB) and Q-PCR analyses, respectively.

Results: Melatonin significantly reduced increased blood levels of liver transaminases (AST, ALT) and blood urea nitrogen (BUN) in diabetic rats. Furthermore, in liver and adipose tissue of treated rats, melatonin administration resulted in considerable lower expression of the increased inflammatory markers IL-1β, IL-6, TNF-α and NF-κB, as shown by reduction in RNA and protein levels. The MT2 receptor was only partly involved in the anti-inflammatory effects of melatonin.

Conclusions: Our results suggest that melatonin has relevant anti-inflammatory effects in diabetic rats. Further studies in humans could prove the potential clinical benefit of melatonin supplementation in patients with T2DM.
Evaluation of Nutritive Values of Agro-Industrial By-Products (AIBPS) and Effect of Their Nano Structural Characteristics on the Kinetics of Biogas Production and Methane Emission
Authors: Shirmohammadi Shahram , Taghizadeh Akbar , Paya Hamid , Javanmard Arash , Abachi Soheila , Darabi Behnam Hajimohammadi , Gharajeh Saeid Narimani , Shokrani Nazanin
Published: March 2021

Over the past decades, the agro-industrial by-products (AIBP) has received considerable attention. With this motivation, the aim of this study was to investigate the effect of AIBP as a source of non-fiber carbohydrates on biogas production kinetic, methane emission and fermentation characteristics. Experimental treatments were (1) Sugar beet pulp (SBP) (control), (2) Apple pomace (AP), (3) Orange pulp (OP, (4) 33% AP + 66% OP, (5) 50% AP + 50% OP and (6) 66% AP + 33%OP. For this work, we analyzed the data collected from the kinetics of digestion through biogas production, ex-vivo methane emission, in-vitro digestibility of dry matter and fermentation parameters. Field emission scanning electron microscope was used to show the nano structural differences of the AIBPs. Our results demonstrated the significant differences of the crude protein among the treatments (P < 0.05). Biogas production and methane emission were significantly higher in SBP and OP treatments (P < 0.05). The most eminent and the lowest amounts of acetate were observed for AP and OP (61.84 mmol/L, 58.15 mmol/L), respectively. More broken edges were obvious in OP images. particle size was rather smaller in SBP. Images of AP showed a sleek surface which may act as a shield preventing more digestion. Overall, beside reducing environmental contamination by AIBP, our results showed a positive effect of AIBPs on degradation and biogas kinetics, methane emission and in vitro fermentation parameters describing that they can be used as a good source of non-fiber energy sources.
Impacts of soil disturbance on plant diversity in a dry grassland
Authors: Nabe-Nielsen Louise Imer , Reddersen Jens , Nabe-Nielsen Jacob
Published: March 2021

Dry grasslands are among the most species rich habitats in Europe, but they are also among the most threatened. Threats include too high and too low levels of disturbance. The aim of this study is to examine the effect of soil disturbance intensity on species composition and diversity in a dry grassland in Mols Bjerge National Park in Denmark. We recorded vascular plant species inside and just outside patches of bare sand, and in the transition zone between these. We found that the number of species was highest in the dense vegetation, intermediate at the transition and lowest in bare sand areas. However, an analysis of plant traits showed that the number of small annual species was highest in the transition zone. High abundance of small annual species may therefore indicate intermediate disturbance regimes. Based on a literature study we demonstrate that many threatened species are adapted to such habitats. This suggests that dry grasslands should be managed to maintain areas with intermediate disturbances intensities to maintain optimal conditions for many threatened species. To our knowledge, this is the first time it has been documented that small annual species can indicate intermediate disturbance regimes in dry grasslands.
Dynamic changes in genetic diversity, drug resistance mutations, and treatment outcomes of falciparum malaria from the low-transmission to the pre-elimination phase on the isolated islands of São Tomé and Príncipe
Authors: Chen Ying-An , Shiu Tsen-Ju , Tseng Lien-Fen , Cheng Chien-Fu , Shih Wei-Liang , Tsai Kun-Hsien
Published: March 2021

Background
With effective vector control and case management, substantial progress has been made in the elimination of malaria on the islands of São Tomé and Príncipe (STP). During the critical period from the low-transmission to the pre-elimination phase, this study tracked the dynamic changes in the genetic diversity in Plasmodium falciparum, the distribution of antimalarial drug-resistance genes, and the treatment outcomes in patients to provide insights for the prevention of rebounded malaria in STP.
Methods
Dried blood spots (DBSs) and case follow-up data were collected from malaria patients who had visited the Central Hospital between 2010 and 2016. Genomic DNA of P. falciparum was extracted from DBSs. The polymorphic regions on the genes for merozoite surface proteins 1 and 2 (msp1 and msp2) were amplified in 118 pre-treatment samples to identify the genetic diversity of the infected parasites. Anti-malarial drug resistance mutations in the multi-drug resistance (pfmdr1), chloroquine resistance transporter (pfcrt), and kelch 13 (pfK13) genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing in 111 samples. Treatment outcomes were categorized based on the parasitological results from microscopy during the 28-day follow-up after treatment. Factors related to malaria recurrence were characterized by logistic regression models using case follow-up data (total number = 7,482).
Results
The circulating parasite strains in STP showed significant changes at the recent peak incidence in 2012, during which the prevalent allelic type in MSP1 changed from K1 to MAD20, and that in MSP2 changed from 3D7/IC to FC27. Genotyping results for antimalarial drug-resistance markers showed that the dominant alleles of pfmdr1 86 + 184 + 1246-pfcrt 76 were YFD-T (51.4%). Logistic regression models showed that significant factors related to parasitological failure after treatment were age (protective factor, OR = 0.97–0.98), log10-transformed parasite density (OR = 1.07–1.44), and treatment (quinine vs. artemisinin-based combination therapy, OR = 1.91–1.96). Overall, younger patients, those with higher parasitemia levels at enrollment, and those treated with quinine had a higher risk of recurrence during follow-up.
Conclusions
Although malaria treatment efficacy remained acceptable in STP, this study showed temporal changes in the dominant strains and the development of drug resistance mutations in the local parasite population. Therapeutic efficacy should be carefully monitored to adequately adjust the policy in the future.
Meeting the Challenges in Oncology Care Management During the SARS-Cov-2 Pandemic: A Retrospective Analysis
Authors: Rasschaert Marika , Vanclooster Pieterjan , Depauw Laura , Mertens Tim , Roelant Ella , Coenen Elke , Anguille Sebastien , Janssens Annelies , Dam Peter , Peeters Marc
Published: March 2021

Background: The SARS-CoV-2 pandemic has a far-reaching impact on healthcare. Cancer patients in particular were regarded as vulnerable and oncology departments drastically modified their Care systems and established new priorities. We evaluated the impact of SARS-CoV-2 on the activity of a single cancer center; and we studied patients’ perspectives of the preventive institutional or governmental safety measures.Methods: We performed a retrospective analysis of (i) Volumes of Oncological activities (2020 versus 2019), (ii) patients’ perception rate of the preventive measures, (iii) patients’ SARS-Cov-2 infections, clinical signs thereof and (iv) new diagnoses made during the SARS-CoV-2 pandemic. Results: As compared with a similar timeframe in 2019 the overall activity in total numbers of outpatient chemotherapy administrations and specialist visits, based on weekly average of daily accesses was not statistically different; while inpatient admissions decreased for both medical oncology and thoracic oncology (18% (p=0.0018) and 44% (p<0.0001) respectively). Cancer diagnosis plummeted (34%), but no stage shift could be demonstrated.Acceptance and adoption of hygienic measures was high, as measured by a targeted questionnaire administered to a sample of outpatients (>85%). However, only 46.2% of responding patients regarded telemedicine, although widely deployed, as an efficient surrogate to a consultation. Thirty-three patients developed SARS-CoV-2, 27 were hospitalized and 11 died within this time frame. These infected patients were younger, current smokers and suffered more comorbidities.Conclusions: This retrospective cohort analysis demonstrates that continuation of active cancer therapy and specialist visits is feasible and safe after implementation of population-wide, institutional and department specific safety measures. Substantial decreases in diagnosis of solid tumors were recorded. To manage the backlog of belated diagnoses, while providing continued state-of-the-art cancer care during this prolonged health crisis, we need policy interventions to adapt the health care system and allow telemedicine to fulfill a more prominent role.
WITHDRAWN: Aluminum chloride impairs learning and memory by P2X7 and A2A-receptor stimulations in hippocampus of mice
Authors: Reichert Karine Paula , Bottari Nathieli Biachin , Schetinger Maria Rosa Chitolina , Silva Aniélen Dutra da , Assmann Charles Elias , Costa Pauline da , Lopes Thauan Faccin , Heidrich Graciela , Dressler Valderi , Morsch Vera Maria Melchiors
Published: March 2021

Aluminum (Al) is considered a neurotoxic agent for biological systems and is recognized as a risk factor for neurodegenerative diseases. Al exposure occurs through the environment, water and human diet. The Al cationic form (Al3+) has been associated with major deleterious effects on the central nervous system. The aim of this study was to investigate a possible mechanism that links Al and neurodegeneration in vivo. Here, we evaluated memory tests, purinergic signaling and inflammatory markers during long-term oral exposure to Al of mice in the total hippocampus. For this study, Swiss mice were divided into three groups: control (CT) group, AlCl3 50 mg/kg group and AlCl3 100 mg/kg group. The animals were orally treated with saline or Al3+ at AlCl3 form for 30 days. The memory parameters, body and brain weight, Al3+ levels, DNA damage, enzyme activities, purinergic receptors and cytokine densities were assessed on the hippocampus of mice intoxicated with Al3+. Our results reveal that Al3+ was able to reduce brain weight and accumulate in the hippocampus of animals treated with 100 mg/kg of salt. In addition, Al3+ causes memory deficits and DNA damage. The adenosine triphosphate (ATP) hydrolysis was also affected by Al3+. Our results point to an increase in nucleoside triphosphate diphosphohydrolase (NTPDase), 5´-nucleotidase (5’-NT) and adenosine deaminase (ADA) activities. In addition, Al3+ increases P2X7 and A2A receptor density, as IL-1β proinflammatory cytokine. Taken together, we suggest that Al3+ can cause memory loss through DNA damage and alterations to the purinergic system through the proinflammatory process.
The First Internal Electromagnetic Motion Monitoring Implementation For Stereotactic Liver Radiotherapy in China: Procedures and Preliminary Results
Authors: Mu Zhongde , Wang Qi , Guo Chang , Feng Yong , Gu Hongcheng , Zhai Zhenyu , Wu Jianfeng , He Xia
Published: March 2021

Background. Respiratory motion may compromise the dose delivery accuracy in liver stereotactic body radiation therapy (SBRT). Motion management can improve treatment delivery. However, external surrogate signal may be unstable and inaccurate. This study reports the first case of liver SBRT based on internal electromagnetic motion monitoring in China.Materials and Methods. The patient with a primary liver cancer was treated with respiratory-gated SBRT guided by three implanted electromagnetic transponders. The treatment was carried out in breath-hold end-exhale with beam-on when the centroid of the three transponders drifted within 5 mm (left-right (LR), anterior-posterior (AP) and cranio-caudal (CC) directions) from the planned position. The motion monitoring treatments were delivered in breath-hold end-exhale mode with the energy of 6 MV in FFF mode with 1200 monitor units (MU) per minute. For each fraction, QA results, intertransponder distances, geometric checks as well as tumor motion logs were explicitly recorded.Results. Comparing with the plan data, distance variances between each two transponders were -0.056±0.032 cm, 0.017±0.033 cm and -0.082±0.068 cm. Geometric residual, the pitch, roll and yaw angles were 0.048±0.021 cm (threshold 0.2 cm), 2.17°±1.85°(threshold 10°), -2.42°±1.51° (threshold 10°) and 1.67°±1.07° (threshold 10°), respectively. The delivery time of the five fields were 13.8 s, 13.1 s, 11.18 s, 11.57 s, 11.62 s with the average value of 12.254±1.13 s. Treatment duration of each fraction ranged from 6.22 minutes to 21.43 minutes, with the average value of 11.25±5.03 minutes.Conclusions. The first case of liver SBRT patient of China based on internal electromagnetic motion monitoring was performed. The system had a high tracking accuracy, and it did not delay the treatment time. In addition, the patient did not show any severe side effects except for I°myelotoxicity. The internal electromagnetic motion monitoring system provides a real-time and direct way to track liver tumor targets.
Source Identification and Pollution Factors of Elements in PM2.5 Samples obtained in Akure, Ondo State, Nigeria
Authors: Abulude Francis Olawale , Abulude Ifeoluwa Ayodeji , Ezeh Godwin Chigaekwu , Acha Sunday
Published: March 2021

Air quality is a big concern all over the world. It affects both humans and animals in a variety of ways. Air must be quantified to monitor the impact, and the consistency of the air must be determined. Both stakeholders will use the knowledge collected to take effective action. To that end, we've taken measures in Nigeria to measure PM2.5, elements, and meteorological parameters, as well as assess their enrichment, contamination, and emission levels. For a total of ten months, samples were collected at three locations in Ondo State, Nigeria: the Federal University of Technology, Akure (FUTA), Oba Ile, and Museum (January to October). The pollution factor (CF), enrichment factor (EF), and pollution load index (PLI), as well as Principal Component Analysis, were used to measure the PM and components (PCA). The average PM concentrations (101 g m3 (FUTA); 120 g m3 (Oba Ile); and 176 g m3 (Museum) were found to be higher than the WHO (35 g m3) and USEPA (15 g m3) normal limits. The macro elements (K > Na > Ca > P > Al) were ordered in this order, while the trace elements were ordered in this order: Cu > Fe, > Zn > Ni > Cr > Mn > Pb. PCA listed elements from vehicular activities, biomass burning, dust, and soil as contributing elements. The findings are useful for identifying sources of PM2.5, primary, and trace elements, enrichment, contamination assessment, and air pollution index, as well as contributing to regional monitoring programs.
Ethnobotanical Study of Medicinal Plants in Hidabu Abote District, North Shewa Zone, Oromia Region, Ethiopia
Authors: Bose Boja Tilinti , Melka Yoseph , Awas Tesfaye
Published: March 2021

Background: The world population use medicinal plants for treating diseases in forms of drug developments also traditional medicinal specially developing countries. The economic growth and cultural changes threaten the traditional lifestyle of local people. The aim of the study is to investigate medicinal plants and associated indigenous knowledge. Methods: Ethnobotanical data were obtained using semi-structured interviews, focus group discussion and market survey. Data were analyzed by descriptive statistics, informant consensus factor, preference ranking and Direct matrix ranking using Microsoft Excel and Statistical Package for Social Science Version 20. Results: Ethnomedicinal use of 136 medicinal plant species belonging to 117 genera and 63 families wereidentified and documented. The highest number of medicinal plants was used in midland kebele(74 species). Out of total medicinal plants 66 (48.53%) species were reported to treat human aliments only. Most of the medicinal plants harvested were herbs (37.50%), followed by trees (36.76%) and the least was lianas (0.74%). A Pearson correlation test indicated a positive and significant difference between age of informants and number of medicinal plant species cited, and negative and significant difference between level of education and number of medicinal plant species cited. The result indicates that there was significant difference between male and female informants in their knowledge of medicinal plants, and there was significant different between number of medicinal plants reported by key informants and household respondents. Cordia africana ranked first as a multipurpose medicinal plant. Agricultural expansion (41.96%) stood first as a factor threatening medicinal plants. Conclusion: The highest numbers of MPs were used in Sire Morose kebele (midland), but collection was not restricted only to their locality the move other kebeles to harvest MPs. In the study area elders have better knowledge of medicinal plant than younger and as people educate their knowledge on medicinal plants decrease.This implies that in study area there is potential indigenous knowledge but we are going loss this traditional knowledge if did not develop means transferring this to next generation. To support local people effort on in-situ conservation and ex-situ conservation needed
Estimating the Rate of Overdiagnosis With Prostate Cancer Screening: Evidence From the Finnish Component of The European Randomized Study of Screening for Prostate Cancer
Authors: Walter SD , Hu Jiarui , Talala Kirsi , Tammela Teuvo , Taari Kimmo , Auvinen Anssi
Published: March 2021

Purpose: Screening for prostate cancer may have limited impact on decreasing prostate cancer-related mortality. A major disadvantage is overdiagnosis, whereby lesions are identified that would not have become evident during the man’s lifetime if screening had not taken place. The present study aims to estimate the rate of overdiagnosis using Finnish data from the European randomized trial of prostate screening. Methods: We used data from 80,149 men randomized to a screening or a control group, distinguishing four birth cohorts. We used the “catch-up method” to identify when the difference in the cumulative incidence of prostate cancer between the screening and control groups had stabilised, implying that the screening has no further effect. We define the overdiagnosis rate to be the relative excess cumulative incidence in the screened group at that point. As an independent method, we also examined the diagnosis rates of T1c tumours as an indicator of early tumors detected by PSA. Results: The estimates of overdiagnosis rates from the catch-up method using the full period of available follow-up ranged between cohorts from 2.3% to 15.4%, and the T1c analysis gave very similar results. Conclusions: Some overdiagnosis has occurred, but there is uncertainty about its extent. A long follow-up is required to demonstrate the full impact of screening. We evaluated the overdiagnosis rates at a population level, associated with being offered screening, taking account of contamination (screening among the controls). The overall evaluation of screening should incorporate mortality benefit, cost-effectiveness and quality of life.
Towards a reverse world in automation: human as a sensor
Authors: Bersani Chiara , Sacile Roberto , Zero Enrico
Published: March 2021

Automation is more and more shifting towards a technologic world where the human component is however still involved. The autonomous cars represent an example where the shift towards a fully automated vehicle still requires the presence of the human component, that is a human-in-the-loop, which may represent the failure or the added value of such systems. Stress and fatigue represent the main concerns in safety issues during workloads, above all, in situations where the person’s behaviour represents a potential source of harm in human–computer interaction. After a brief survey of the recent literature on the human as a sensor concept, in this paper, some examples of an electroencephalography (EEG) based brain-computer interface showing the still limited but potentially challenging effectiveness of such an approach in systems engineering. The aim is to explore brain activities when a subject is conditioned by external stimuli during the execution of a cognitive task and to evaluate the human capability to react to the unexpected event faster than a machine.Different experiment tests have been designed to evaluate the human reactions under simulated driving scenarios and workload sessions. Accordingly, different methodologies to use this information are shown. Driver’s performance has been evaluated by EEG power spectrum analysis when unpredicted acoustic stimuli or breaking emergency situations are simulated during the driving session. A Fine Gaussian Support Vector Machine (SVM) approach has been carried out to classify the human’s brain activities when the participant has to drive a car along a challenging curvilinear path in a virtual simulated scenario or when he is exposed to visual disturbances while performing a common task.The results demonstrate an interesting potential correlation between external stimuli and driver’s brain wave activities in virtual driving environment. In addition, the EEG pattern recognition in the visual external stimulus test and in the driver’s stress simulation to tackle a road with different curve angles generated promising outcomes. However, despite the wide literature on the subject, the effective use of such signal still represents a hard although challenging task.
A Genetically Modified Anti-Plasmodium Bacterium Is Harmless to the Stingless Bee Partamona Helleri
Authors: Viana Thaís , Barbosa Wagner , Botina Lisbetd , Bernardes Rodrigo , Soares Juliana , Jacobs-Lorena Marcelo , Martins Gustavo
Published: March 2021

Paratransgenesis consists of genetically engineering an insect symbiont to control vector-borne diseases. Biosafety assessments are a prerequisite for the use of genetically modified organisms (GMOs). Assessments rely on the measurement of the possible impacts of GMOs on different organisms, including beneficial organisms, such as pollinators. The bacterium Serratia AS1 has been genetically modified to express anti-Plasmodium effector proteins and does not impose a fitness cost on mosquitoes that carry it. In the present study, we assessed the impact of this bacterium on the native bee Partamona helleri (Meliponini), an ecologically important species in Brazil. Serratia eGFP AS1 (recombinant strain) or a wild strain of Serratia marcescens were suspended in a sucrose solution and fed to bees, followed by measurements of survival, feeding rate, and behavior (walking and flying). These bacteria did not change any of the variables measured at 24, 72, and 144 h after ingestion. Recombinant and wild bacteria were detected in the digestive tract up to 144 h after ingestion, but their numbers decreased with time. The recombinant strain was detected in the midgut at 24 h and in the hindgut at 72 h and 144 h after ingestion. As reported for mosquitoes, Serratia eGFP AS1 is a safe candidate for combating vector-borne diseases, as it did not compromise the native and ecologically relevant bee, P. helleri.
Exploration of Novel TOSMIC Tethered Imidazo[1,2-a]pyridine Compounds for the Development of Potential Antifungal Drug Candidate.
Authors: Shukla Pratibha , Deswal Deepa , Pandit Mansi , Latha N , Mahajan Divyank , Srivast Tapasya , Narula Anudeep Kumar
Published: March 2021

New candidates of imidazo [1, 2-a] pyridine were designed by combining 2-amino pyridine, TOSMIC isocyanide and various assorted aldehydes were synthesized to explore their antioxidant and antifungal potential. The design of these derivatives was based on utilizing the antifungal potential of azoles and TOSMIC moiety. These derivatives were synthesized by adopting multi-component reaction methodology, as it serves as a rapid and efficient tool to target structurally diverse heterocyclic compounds in quantitative yield. The resulting imidazo [1, 2-a] pyridine derivatives were structurally verified by 1HNMR and 13CNMR. The compounds were analyzed for their antioxidant and fluorescent properties and it was observed that compound 15 depicted good fluorescence and antioxidant potential. Additionally, the compounds were evaluated for their antifungal potential against both Aspergillus fumigatus 3007 & Candida albicans 3018 and it was observed that all the compounds had moderate to significant antifungal effect. Confocal images depicted the porous nature of compound treated fungal cell membranes leading to fungal growth inhibition. Molecular docking was performed to establish the interaction with the target enzyme (Lanosterol 14 alpha demethylase) which also corroborated with the in vitro results. In silico tools were employed to determine drug-likeliness of the compounds along with determination of ADME properties.
Survival Impact of Postoperative Radiotherapy in Patients with Olfactory Neuroblastoma ： 513 Cases from the SEER Database
Authors: Duo Guo-Shuai , Feng Ji-Long , Zhang En-Yi , Wang Li-jun
Published: March 2021

BackgroundTo evaluate the impact of postoperative radiotherapy (PORT) on survival in olfactory neuroblastoma (ONB) patients with different stages. MethodsPatients with ONB were selected in the Surveillance, Epidemiology, and End Results (SEER) database during 2004–2016. Survival analyses were performed using Kaplan Meier (K-M) method, Cox regression analysis, and competing risk model. ResultsA total of 513 patients were included in the study. Univariate and multivariate analysis results demonstrated that PORT was not an independent prognostic factor for overall survival (OS) of patients with modified Kadish stage A and B (p=0.699 and p=0.248, respectively). For C and D cases, patients who underwent PORT had significantly better OS than those who did not undergo PORT (p=0.03 and p< 0.0001, respectively). K-M curves illustrated that the 5- and 10-year OS rates according to radiotherapy (PORT vs. non-PORT) were 70.4% vs. 85.3% and 56.8% vs. 68.2% in stage C, respectively. For stage D patients, the 5-year OS rates were 42.6% and 70.7%, and 10-year OS rates were 29.5% and 53.4% in the PORT and non-PORT groups, respectively. The competitive risk model revealed that the 5-year cancer-specific cumulative mortality incidence decreased by 26.6% and the 10-year mortality incidence by 41.4% in patients with stage C who were treated using PORT; meanwhile, for patients with stage D who were treated with PORT, the 5- and 10-year mortality incidence reduced by 35.3% and 42.6%, respectively. Chemotherapy was not related to the prognosis of ONB (all p> 0.05).ConclusionsOur results indicate that PORT improved survival outcomes in ONB patients with modified Kadish stage C and D. However, for modified Kadish stage A and B cases, PORT may not affect survival. Chemotherapy was not recommended for ONB patients until more studies determine the role of chemotherapy.
Clinical effectiveness of space maintainers and space regainers in the mixed dentition: A systematic review
Authors: Khalaf Khaled , Mustafa Aseel , Wazzan Mohammad , Omar Mennatalla , Estaitia Mohammed , El-Kishawi Mohamed
Published: March 2021

Background: The aim of this systematic review was to address the clinical effectiveness of space maintainers and space regainers in the prevention and correction of dental arch decrease in the mixed dentition. Methods: An electronic search was conducted using five databases and 6 relevant journals. Inclusion criteria were: Randomized Controlled Clinical Trials (RCTs), Controlled Clinical Trials (CCTs), cohort studies and case-control studies of children in the mixed dentition requiring a space maintainer or a space regainer, children with mild to moderate crowding, and with Class I and mild Class II or Class III skeletal pattern. Results: Following the three phases of a systematic search, 11 were included for the final analysis, of which 1 article was found to be of critical risk, 2 articles of serious risk and 8 articles of moderate risk of bias. Conclusions: Space maintainers may preserve arch length and prevent crowding in mildly to moderately crowded cases, but at the cost of proclination of the lower incisors. Space regainers were somehow effective in distalizing the maxillary and mandibular first permanent molars and thus contributing to the resolution of mild to moderate crowding in the mixed dentition. However, considering the low evidence provided by this systematic review, high-quality studies are needed.Registration: PROSPERO (CRD42020170035).
The Attractive Effects of Amino Acid and Some Classical Substances on Grass Carp (Ctenopharyngodon Idellus)
Authors: Yu Haojie , Wang Xiaoyu , Kong Fanshuang , Tan Qingsong
Published: March 2021

Grass carp (Ctenopharyngodon idellus) is one of the most essential fishing species in China. The bait for this fish is rapidly developing. However, the study on the attractants in the bait for this fish lacks. This study was designed to systematically investigate the effects of 16 kinds of stimuli on the perspective of behaviour and physiology of grass carp by using different kinds of methods, including behavioral tests (maze test and biting-balls test) and electro-olfactogram (EOG). Our experiment's idea is mainly to imitate: in addition to vision, fish in nature also use smell to find food and finally swallow under the action of olfaction, taste and other sensory systems. Firstly, the behavioral maze test was used to screen the attractive or suppressive effect of 16 stimuli on grass carp and the electronic olfactory recording method was used to further evaluate the olfactory response of grass carp to the eight stimuli selected from the maze test. Then, the best concentrations of these eight stimuli and their combination were investigated by the biting-balls test to compound a formula with the strongest appetite for grass carp. The results of behavioral maze test showed that DMPT, DMT, glycine, Taurine, L-glutamic, L-alanine, L-proline, L-arginine have different degrees of useful in attracting grass carp. The electro-olfactogram recoding showed that the EOG response of grass carp to the stimuli is a transient biphasic potential change and all of the eight stimuli could induce the EOG response of grass carp. The biting-balls test showed that glycine, L-glutamic, L-arginine at 10–2 mol/L had significant feeding stimulation and DMT at 10–1 mol/L had significant feeding stimulation than the other groups. Finally, formula 9 composed of DMT, glycine, L-glutamic acid and L-arginine has the greatest attraction for grass carp. The results of this study verified the attractive effect of some amino acids and other chemicals on grass carp fishing, and would provide support for the production of specific grass carp attractants.
A Re-testing Range is Recommended for 13C- and 14C-urea Breath Tests for Helicobacter Pylori Infection in China
Authors: Wang Xiangyu , Zhang Shuzhen , Chua Eng Guan , He Yongsheng , Li Xiaofeng , Liu Aijun , Chen Haiting , Wise Michael J. , Marshall Barry J. , Sun Dayong , Li Xuehong , Tay Alfred Chin Yen
Published: March 2021

Background: The urea breath test (UBT) is widely used for diagnosing Helicobacter pylori infection. In our hospital, some UBT findings were contradictory to the histology outcomes, therefore this study aimed to assess and compare the diagnostic performance of both 13C- and 14C-UBT assays.Methods: We recruited 484 H. pylori-treatment naïve patients, among which 217 and 267 were tested by the 13C-UBT or 14C-UBT, respectively. The cutoff value for H. pylori positivity based on manufacturer’s instruction was 4% DOB for the 13C-UBT, and 100 DPM for the 14C-UBT. Gastric biopsies of the antrum and corpus were obtained during endoscopy for histopathology.Results: In patients who were tested using the 13C-UBT kit, histopathology was positive in 136 out of 164 UBT-positive patients (82.9% concordance), and negative in 46 out of 53 UBT-negative cases (86.8% concordance). For the 14C-UBT-tested patients, histopathology was positive for H. pylori in 186 out of 220 UBT-positive patients (84.5% concordance), and negative in 41 out of 47 UBT-negative cases (87.2% concordance). While the 13C-UBT and 14C-UBT each had a high sensitivity level of 95.1% and 96.9%, respectively, their specificity was low, at 62.2% and 54.7%, respectively. By using new optimal cutoff values and including an indeterminate range (3-10.3% DOB for 13C-UBT and 87-237 DPM for 14C-UBT), the specificity values can be improved to 76.7% and 76.9% for the 13C- and 14C-UBT, respectively.Conclusions: The establishment of an indeterminate range is recommended to allow for repeated testing to confirm H. pylori infection, and thereby avoiding unnecessary antibiotic treatment.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000041570. Registered 29 December 2020- Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=66416&htm=4(263/350 words)
First-in-human Study of a 99mTc-Labeled Single-Domain Antibody for SPECT/CT Assessment of HER2 Expression in Breast Cancer
Authors: Zhao Lingzhou , Liu Changcun , Xing Yan , He Jin , O’Doherty Jim , Huang Wenhua , Zhao Jinhua
Published: March 2021

Background: Accurate determination of human epidermal growth factor receptor 2 (HER2) expression is essential for HER2-targeted therapy. HER2 expression in a complex environment, such as in a heterogenous tumor, makes precise assessment difficult using current methods. Therefore, we developed a novel 99mTc-labeled anti-HER2-single domain antibody (99mTc-NM-02) as a molecular imaging tracer for non-invasive detection of HER2 expression and investigated its safety, radiation dosimetry, biodistribution, and tumor-targeting potential in breast cancer patients.Methods: A lead compound (NM-02) was screened from a library of hexahistidine-tagged anti-HER2-single domain antibodies and labeled with 99mTc for the preparation of 99mTc-NM-02 tracer. Ten women with breast cancer were administered 99mTc-NM-02 at a mean dose of 458 ± 37 MBq (406−510 MBq), corresponding to 100 μg of NM-02. Whole-body and local SPECT/CT images were acquired at 1 and 2 h post-administration to investigate the tumor-targeting potential in primary and metastatic lesions. Additional images were acquired at 10 min, 3 h, and 24 h in three patients to calculate radiation dosimetry. Physical evaluation and blood analysis were performed for safety assessment.Results: No drug-related adverse reactions occurred. The tracer mainly accumulated in the kidneys and liver with mild uptake in the spleen, intestines, and thyroid, but only background levels were observed in other organs where primary tumors and metastases typically occurred. The mean effective dose was 6.56 × 10−3 mSv/MBq, and tracer uptake was visually observed in primary tumors and metastases. Owing to the fast clearance of the tracer, we were able to sufficiently discern uptake over normal background in both primary lesions and metastases within 2 h after injection. A maximal standard uptake value of 1.5 could be a reasonable cutoff for determining HER2 positivity using SPECT/CT imaging.Conclusions: Our 99mTc-NM-02 tracer can be safely used for imaging in breast cancer patients with reasonable radiation doses, favorable biodistribution and imaging characteristics. 99mTc-NM-02 SPECT imaging may provide an accurate and non-invasive method to detect HER2 status in breast cancer patients.Trial registration: ClinicalTrials.gov, NCT04040686. Registered 30 July 2019. https://clinicaltrials.gov/ct2/show/NCT04040686.
Angiogenesis Inhibitors in Personalized Combination Regimens for the Treatment of Advanced Refractory Cancers
Authors: Crook Timothy , Patil Darshana , Nagarkar Rajnish , Gaya Andrew , Plowman Nicholas , Limaye Sewanti , Srivast Navin , Datta Vineet , Akolkar Dadasaheb , Bose Chirantan , Kumar Prashant , Sriniva Ajay , Datar Rajan
Published: March 2021

Background

Angiogenic factors are commonly activated in solid tumors and present a viable therapeutic target. However, anticancer treatment with angiogenesis inhibitors (AGI) is limited to a few cancers, mostly as monotherapy and not selected based on molecular indications. We aimed to determine whether patient-specific combination regimens with AGI and other anticancer agents when selected based on multi-analyte tumor interrogation (ETA: Encyclopedic Tumor Analysis) can expand the scope of AGIs in advanced refractory solid organ cancers with improved treatment responses.
Methods

We evaluated treatment outcomes in 60 patients with advanced, refractory solid organ cancers who received ETA-guided combination regimens of AGI with other targeted, endocrine or cytotoxic agents. Radiological evaluation of treatment response was followed by determination of Objective Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS).
Results

Among the 60 patients, Partial Response (PR) was observed in 28 cases (46.7%), Stable Disease (SD) was observed in 29 cases (48.3%) and Disease Progression (PD, within 60 days) was observed in 3 cases (5.0%). The ORR was 46.7% and DCR was 95.0%. At the most recent follow, up the median PFS (mPFS) was 5.0 months and median OS (mOS) was 8.9 months. There were no Grade 4 therapy related adverse events or treatment related deaths.
Conclusions

ETA-guided patient-specific combination regimens with AGI and other anti-neoplastic agents, can yield improved outcomes over AGI monotherapy.
Trial Registration

Details of all trials are available at WHO-ICTRP: https://apps.who.int/trialsearch/. RESILIENT ID CTRI/2018/02/011808. LIQUID IMPACT ID CTRI/2019/02/017548.
Stakeholder engagement in the health policy process in a low income country: a qualitative study of stakeholder perceptions of the challenges to effective inclusion in Malawi
Authors: Masefield Sarah C. , Msosa Alan , Chinguwo Florence Kasende , Grugel Jean
Published: March 2021

Background: Inclusive engagement in healthcare policies and decision-making, including with patients, non-government organisations and local government, is essential to address the needs of patients and communities, reducing health inequities and increasing the accountability of the government. In low income countries such as Malawi, with significant health challenges, stakeholder inclusion is particularly important to improve performance and service delivery. The 2017 National Health Plan II (NHP II) and accompanying Health Sector Strategic Plan II (HSSP II) aimed to improve the functioning of the healthcare system. The Ministry of Health for Malawi intended to involve all key health sector stakeholders in their development. This study explores the extent of stakeholder engagement in the health policy process through the perceptions of local level stakeholders of their engagement in the NHP II and HSSP II.Methods: A qualitative study design was used. Interviews were conducted with 19 representatives of organisations operating at the local level, such as civil society organisations and local government. Open questions were asked about experiences and perceptions of the development of the NHP II and HSSP II. Inductive content analysis was performed.Results: Stakeholders perceived barriers to inclusive and meaningful engagement in the health policy process. Three categories were identified: power (tokenistic involvement; stakeholder hierarchy; mutual distrust); representation (preferred stakeholders; open versus invited engagement); stakeholder-driven engagement. Conclusions: Local level stakeholders identified serious challenges to the meaningful and equitable engagement of stakeholder groups in the health policy process. Issues of trust, accountability and hierarchy in donor-citizen-government relations must be addressed to support stakeholder engagement. Engagement must go beyond tokenism to embed a range of stakeholders in the process with feedback mechanisms to ensure impact from their contributions. Local level stakeholders can be empowered to advocate for and participate in both invited and open stakeholder engagement exercises, and policy literacy increased but greater top-down efforts to engage stakeholders via diverse and inclusive methods are also required. These issues are not unique to Malawi or to health policy-making.