bluuebunny/crossref_metadata_2025 huggingface dataset:
SGAN4AbSum: A Semantic-Enhanced Generative Adversarial Network for Abstractive Text Summarization
Authors: Vo Tham
Published: July 2021

In abstractive summarization task, most of proposed models adopt the deep recurrent neural network (RNN)-based encoder-decoder architecture to learn and generate meaningful summary for a given input document. However, most of recent RNN-based models always suffer the challenges related to the involvement of much capturing high-frequency/reparative phrases in long documents during the training process which leads to the outcome of trivial and generic summaries are generated. Moreover, the lack of thorough analysis on the sequential and long-range dependency relationships between words within different contexts while learning the textual representation also make the generated summaries unnatural and incoherent. To deal with these challenges, in this paper we proposed a novel semantic-enhanced generative adversarial network (GAN)-based approach for abstractive text summarization task, called as: SGAN4AbSum. We use an adversarial training strategy for our text summarization model in which train the generator and discriminator to simultaneously handle the summary generation and distinguishing the generated summary with the ground-truth one. The input of generator is the jointed rich-semantic and global structural latent representations of training documents which are achieved by applying a combined BERT and graph convolutional network (GCN) textual embedding mechanism. Extensive experiments in benchmark datasets demonstrate the effectiveness of our proposed SGAN4AbSum which achieve the competitive ROUGE-based scores in comparing with state-of-the-art abstractive text summarization baselines.
Surface-modified Colloid CdTe/CdS Quantum Dots by a Biocompatible Thiazolidine Derivative as Promising Platform for Immobilization of Glucose Oxidase: Application to Fluorescence Sensing of Glucose
Authors: Hallaj Rahman , Hosseinchi Zahra
Published: July 2021

This work focuses on the synthesis of novel modified core-shell CdTe/CdS quantum dots (QDs) and develops as a fluorescence sensor for glucose determination. The (E)-2,2'-(4,4'-dioxo-2,2'-dithioxo-2H,2'H-[5,5'-bithiazolylidene]-3,3'(4H,4'H)-diyl)bis(3- mercaptopropanoic acid) (DTM) as a new derivative of thiazolidine was synthesized and characterized and used to surface-modification of CdTe/CdS QDs. DTM-capped CdTe/CdS QDs used to immobilization of glucose oxidase (GOD). The intensity fluorescence emission of the CdSe/CdS-DTM/GOD is highly sensitive to the concentration of H2O2 as a byproduct of the catalytic oxidation of glucose. The experimental results showed that the quenched fluorescence was proportional to the glucose concentration within the range of 10 nM − 0.32 µM under optimized experimental conditions. The limit of detection of this system was found to be 4.3 nM. Compared with most of the existing methods, this newly developed system possesses many advantages, including simplicity, low cost, and good sensitivity.
Herbal Plants as Alternatives for the Management of the Red Imported Fire Ant, Solenopsis Invicta (Hymenoptera: Formicidae)
Authors: Tsai Ching-Chu , Hung Sheng-Hsiung , Lin Xiao Ru , Huang Rong Nan
Published: July 2021

The red imported fire ant (RIFA) is one of the most detrimental invasive species, threatening native ecosystems, human health, and economic activities worldwide. In the quarantine zone of Taiwan, RIFA re-infestation frequently occurs despite the intensive application of synthetic pesticides, making its control costly and ineffective. Thus, there is an urgent need to identify effective, eco-friendly, and sustainable alternatives for controlling RIFA populations. In this study, we examined the efficacy and feasibility of planting herbal species for RIFA control. Five herbal species, Tagetes lemmonii, Armoracia rusticana, Cymbopogon citratus, Cymbopogon nardus, and Chrysopogon zizanioides, were planted in a RIFA-infested field with local weeds as controls. Bait and pitfall traps and RIFA intruded plants were used to compare the ant activity in the control fields and those containing herbal plants. The RIFA repellent activity of the five herbal plants and their basal soil was further evaluated through digging bioassays. Generally, the field surveys showed more ants and intruded plants in the control than in the herbal groups; however, the significance varied based on the trap type and plant species. The bioassays demonstrated the significant repellency of the aboveground parts of T. lemmonii, C. nardus, and C. citratus, and the belowground parts of T. lemmonii, C. citratus, and V. zizanioides against RIFA. The basal soil of T. lemmonii, C. citratus, and C. nardus also exhibited deterrent activity toward RIFA. Our results demonstrated that herbal plants are eco-friendly, sustainable alternatives for controlling and preventing RIFA infestation in severe infested and non-infested areas.
Loss of a Single Plant Functional Group in Litter Had Marginal Impacts on Microbial Community Diversity and Composition in a Tibet Fir Forest
Authors: Li Qianwei , Wang Lifeng , Chen Yamei , Guo Li , You Chengming , Wang Lixia , Li Han , Zhang Li , Tan Bo , Xu Zhenfeng , Zhang Jian , Liu Yang
Published: July 2021

Aim The decomposition of plant residues is a fundamental process of soil organic matter accumulation. The loss of plant functional groups (PFGs) could affect this process by producing litter of different qualities in the soil. Microorganisms are one of the indispensable driving forces of ecological processes, but the mechanisms by microbial communities respond to aboveground PFG changes are still unclear, which limits our understanding of biogeochemical cycle changes under PFG loss.Methods We assessed the microbial taxonomic and functional composition of six typical single PFGs (evergreen conifer, evergreen shrubs, deciduous shrub, graminoid, forb and fern), random loss of a single PFG (SPFG) from litter mixtures and total mixture of six PFGs in a Tibetan fir forest by a high-throughput sequencing method.Results The microbial composition and function did not change with loss of a SPFG in litter, and microbial communities were mainly determined by the carbon and nitrogen ratio (C:N), carbon and phosphorus ratio (C:P), N and lignin, and bacterial functional pathways and fungal functional guilds were both determined by N, C:N and C:P ratios. Bacterial diversity was positively related while fungal diversity was negatively related to N and cellulose concentrations.Conclusion We speculated that the difference in initial litter qualities (especially C:N) between different PFGs, rather than a decreased number of PFGs, is a determinant of microbial composition and function. As the loss of PFG does not change litter quality, the microbial community can resist the loss of PFG, which maintains alpine ecosystem carbon and nutrient cycling stability.
Topological Distance-Based Electron Interaction Tensor: A Novel Molecular Structure Representation to Bridge Convolutional Neural Network Studies in Computer Vision to Drug-Like Compound Datasets
Authors: Shin Hyun Kil
Published: July 2021

Owing to the success achieved by deep learning, researchers are exploringthe application of deep learning in drug discovery to improve the accuracy of prediction models. Significant performance improvement has been achieved by diverse convolutional neural network (CNN) models in computer vision, and the preparation of an input format suitable for CNN is one of the major questions required to be answered in order to harness the advancements in using CNNs for chemical data. It was reported that the models achieved improvement in prediction accuracy, in deep learning studies on molecular structure data; however, the improvement was insufficient from an industry perspective. Furthermore, a recent study suggested that conventional machine learning models can outperform deep learning models on chemical data. As only a limited number of feature calculation methods are available for molecules in deep learning studies, it is crucial to develop more methods to calculate features appropriate for deep learning model development.A topological distance-based electron interaction (TDEi) tensor has been introduced in this study to transform a molecular structure into image-like 3D arrays based on electron interactions (Eis) within a molecule. The prediction accuracy of the CNN model with the TDEi tensor was tested with four datasets: MP (275,131), Lipop (4,193), Esol (1,127), and Freesolv (639), and the models achieved desirable prediction accuracy. Ei is the fundamental level of information that determines the chemical properties of a molecule. Feature space variation was visualized by taking outputs from the middle of the CNN architecture as the CNN model exhibited outstanding performance in automatic feature extraction.The correlation between features from the CNN, and target endpoints was strengthened as outputs were extracted from the deeper layer of the CNN.
Establishment and Validation of a Genetic Label Associated With M2 Macrophage Infiltration to Predict Survival in Colon Cancer Patients and Assist Immunotherapy
Authors: Xu Boyang , Peng Ziqi , Yan Guanyu , Wang Ningning , Chen Moye , Yao Xue , Sun Mingjun , An Yue
Published: July 2021

Background: Colon cancer is a kind of malignant tumor with high morbidity and mortality. Researchers have tried to interpret it from different perspectives and divide it into different subtypes in order to achieve individualized treatment. With the rise of immunotherapy, its value in the field of tumor has initially emerged. Based on the above background, from the perspective of immune infiltration, this study classified colon cancer according to the infiltration of M2 macrophages in patients with colon cancer and further explored it.Methods: Cibersort was used to analyze the level of immune cell infiltration in colon cancer patients in the TCGA database. WGCNA, Consensus Clustering analysis, Lasso analysis, and univariate KM analysis were used to screen and verify the hub genes associated with M2 macrophages. PCA was used to establish the M2 macrophage-related score—M2I Score. The correlation between M2I Score and somatic cell variation and microsatellite instability were analysed. Furthermore the correlation between M2 macrophage score and differences in immunotherapy sensitivity was also explored. Results: M2 macrophage infiltration was associated with poor prognosis. Four hub genes (ANKS4B, CTSD, TIMP1, and ZNF703) were selected as the progression-related genes associated with M2 macrophages. A stable and accurate M2I Score for M2 macrophages used in COAD was constructed based on four hub genes. M2I Score was positively correlated with tumor mutation load (TMB). The M2I Score of MSI-H group was higher than that of MSI-L group and MSS group. Combine with the TCIA database, we concluded that patients with a high M2I Score were more sensitive to PD-1 inhibitors and PD-1 inhibitors combined with CTLA-4 inhibitors. The low rating group may have better efficacy without immune checkpoint inhibitors or with CTLA4 inhibitors alone.Conclusion: Four prognostic hub genes associated with M2 macrophages were screened to establish the M2I Score and divided the patients into two subgroups: high M2I Score group and low M2I Score group. TMB, microsatellite instability and sensitivity to immunotherapy were higher in the high-rated group. PD-1 inhibitors or PD-1 combined with CTLA-4 inhibitors are preferred for patients in the high-rated group who are more sensitive to immunotherapy.
Comparative Effect of Potentiated Zinc Oxide and Antibiotic Growth Promoters on Intestinal Morphometry and Nutrient Digestibility in Broiler Chickens
Authors: Moog Babylyn Alday , Angeles Amado , Merca Florinia , Sangel Percival
Published: July 2021

This study aims to determine the comparative effects of potentiated zinc oxide (pZnO) and antibiotic growth promoters (AGP) supplementation on intestinal morphometry and nutrient digestibility in broiler chickens. Four hundred straight-run day-old broiler chicks were randomly allotted to one of four dietary treatments replicated 10 times with 10 birds per replicate. Dietary treatments were: T1: Basal diets without AGP (negative control; NC), T2: Basal diets with 500 g/ton Maduramicin 10g and 500 g/ton Zinc bacitracin 150 (positive control; PC), T3: NC added with 150g/ton pZnO, and T4: PC added with 150g/ton pZnO in a 2x2 factorial design in RCBD. At days and 35, 10 birds were randomly selected per treatment 18 for morphometry of the duodenum, jejunum and ileum. At day 38, eight birds per treatment were used for the nutrient digestibility study. Results showed significant interaction effects (P<0.05) of AGP and pZnO supplementation on day 35 intestinal morphometry of duodenum’s villi height and villi height: crypt depth, and ileum’s crypt depth; apparent CODGE, AME, CP, DM and EE. Significant differences (P<0.05) with pZnO supplementation were only observed on feed intake and FCR of birds fed with pZnO at days 8-14 and fecal quality at days 0-7. Results of the study suggest that pZnO has the potential to replace AGPs without negatively affecting the intestinal morphometry, digestibility and growth performance of broiler chickens.
Right Ventricular Function during Trastuzumab Therapy for Breast Cancer
Authors: Mazzutti Geris , Júnior Fernando Pivatto , Costa Guilherme Oliveira Magalhães , Biolo Andreia , Santos Angela Barreto Santiago
Published: July 2021

PurposeCardiotoxicity (CDT) is the main adverse effect related to trastuzumab (TTZ) use, and the role of the right ventricle (RV) in this context is not clear. We aimed to evaluate the longitudinal changes in RV function during TTZ therapy and to determine the differences in RV function associated with subclinical CDT.MethodsPatients with breast cancer underwent echocardiograms at the beginning of TTZ treatment (Ex 1) and every 3 months during the first year (Ex 2, 3, 4). Subclinical CDT was defined as ≥ 12% relative reduction of left ventricle global longitudinal strain (LV GLS).ResultsTwenty-five women (52.1 ± 13.1 y-o) were included. We found a decrease in LV ejection fraction between the first and fourth exams and the LV GLS gradually decreased during follow-up (Ex1: -20.6 ± 2.0; Ex2: -19.4 ± 2.1; Ex3: -19.2 ± 1.8; Ex4: -19.0 ± 2.1, all p < 0.05). RV GLS changed from baseline to 3 month and to 6 month (Ex1: -23.9% ± 1.6; Ex2: -22.5% ± 2.1; Ex3: -22.5% ± 2.3, all p < 0.05), and the RV Fractional Area Change was lower in the third exam (Ex1: 44.3% ± 6.6 vs Ex3: 39.9% ± 6.0, p = 0.004). We found subclinical CDT in 13 patients (52%); changes in RV parameters had the same pattern of changing in the group with and without subclinical CDT.ConclusionIn this sample, the RV function decreased during TTZ therapy and the decrease was not associated to the observed LV cardiotoxicity.
Agro-Morphological and Genetic Diversity Studies in Rice (Oryza Sativa L.) Germplasm Using Microsatellite Markers
Authors: Mehmood Shiraz , Din Israr Ud , Ullah Izhar , Mohamed Heba I. , Basit Abdul , Khan Mudassar Nawaz , Shah Syed Saad Hussain , Rahman Ateeq ur
Published: July 2021

Knowledge of the genetic diversity and population structure of germplasm collections is an important foundation for crop improvement. Rice production across a broad range of rice-growing environments results in a diverse array of local rice varieties. Many rice varieties have been lost as a result of biodiversity loss and are now grown in Pakistan. To protect the biodiversity of rice varieties, an experiment was carried out to check the genetic and morphological variations between 8 exotic and 7 local rice genotypes, using 5 different SSR markers, i.e, RM3, RM259, RM341, RM520, and RM11943. The analysis of morphological and quality traits of rice observed significant variation across genotypes. The results revealed that genotype Irri-Pak attained the highest plant height and primary branch plant-1, while genotype Mushkan produced a higher number of productive tillers and obtained a higher fertility factor (%). Similarly, the highest value for panicle length was observed for genotype Faker-e-Malakand, 1000-grains weight in genotype Calmochi, and maximum days to maturity was noticed in genotype Swati-2014. Moreover, the genotype Brio attained the highest value of stem diameter, while maximum seed length was noted in genotype Sug Dasi. The highest number of primary branches plant-1 in genotype Ibge-I and secondary branches plant-1 in genotype Calmochi were noticed. A higher concentration of sodium and potassium was observed for the genotype Marte, while the genotype Muskan attained the maximum content of copper. Moreover, the highest concentration of iron in genotype Originario, zinc in genotype JP-5, and cadmium content were noticed in genotype Ibge. Similarly, the dendrogram analysis for quantitative parameters showed three clusters at 74.13 % similarities. Whereas all the genotypes of European origin formed a separate cluster. A set of 5 SSR primers, covering four chromosomes, amplified a total of 14 alleles and showed 100% polymorphism with an average PIC value ranging from 0.39 to 0.91. The UPGMA cluster analysis separated the 15 rice genotypes into 3 main groups based on 32.5% similarities and the highest genetic distance (45.1%) was observed between two genotypes (Fakher-e-malakand and Musa), having different geographical origins. There was no genetic distance between genotype Marte and Brio, irrespective of having the same origin.
De-noising of EEG Signals With Shift Based Cycle Spinning on Wave Atoms
Authors: Rao M. Purnachandra , R E. Srinivasa
Published: July 2021

To predict our brain disorders, EEG signals need to be analyzed. However, most EEG signals were affected by different kinds of noise during their acquision. So, signal analysis become most difficult due to the contamination of various noise. An appropriate technique is necessary to remove the noise from the signal. Wavelet Transform is one the most widely used technique for removing the noise from EEG signals. Wave atom is one of the new multiscale-multidirectional transforms, which is better than both wavelet as well as curvelet transforms. This wave atom transform has good orientation characteristic by which it preserves the edges in an efficient manner. This paper introduced a new method for denoising of EEG signal by shift-based cycle spinning on wave atom transform. Cycle spinning is a technique can be used to enhance the capability of wave atoms. An original EEG signals from public EEG database were used for this experiment. The results are analysed based on the performance measurements like SNR and MSE. The experimental results show that cycle spinning technique with appropriate shifts could be the better choice to denoise an EEG signals.
Validation of the BESTest for Measuring Balance in People With Multiple Sclerosis
Authors: Hoseinpour Fatemeh , Valipour Mozhgan , Hosseinzadeh Samaneh , Taghadosi Hossein , Stuart Samuel , Haghgoo Hojjat Allah
Published: July 2021

Background: Evaluation of balance disorders and differentiation of the populations with deficits is necessary for treatment and rehabilitation. The BESTest is used to evaluate balance and posture in various populations and has been shown to distinguish between different neurological populations. This study investigated the validity of the BESTest in measuring balance in the people with multiple sclerosis (PwMS). Methods: A cross-sectional study conducted with 34 participants including 17 PwMS (42.64 ±7.8 years old, score 1-5 on the Expanded Disability Status Scale) and 17 healthy controls (42.33±8.65 years old). After a comprehensive medical history, subjective clinical balance assessment (via BESTest) was performed. Then objective measures of balance domains of Anticipatory Postural Adjustments (APAs) and Sensory Orientation were assessed using a force plate, with sway, velocity and the area of sway outcomes calculated. Correlations between the subjective and objective measures of balance were computed. Results: The anterior-posterior and the medio-lateral sway, sway velocity in the AP direction, and area of displacement were significantly different between the two groups (P<0.005). Significant correlations were found between the BESTest scores with anterior-posterior and medio-lateral sway, sway velocity in anterior-posterior direction, and area of displacement in anterior-posterior direction (p<0.005). Conclusions: Results indicated that the BESTest assessment tool has a high accuracy and sensitivity to assess balance function in PwMS. It can be used as an outcome measure to test postural balance disorders in these people.
Seismic performance of steel moment and hinged frames with rocking shear walls
Authors: Piri Mehrdad , Massumi Ali
Published: July 2021

The addition of a rocking structural system will soften the connection between a foundation and superstructure and help the beam-column connections to become softer than typical ones. These structures, with the addition of rocking structural systems, follow the elastic gap opening mechanism to soften the structural seismic response. Post-tensioned energy dissipating devices and dampers are used in rocking systems to enable the structure to return to its initial position (self-centering) and to dissipate seismic energy, respectively. The current study investigated the use of a rocking shear wall system in steel moment-resistant and hinged frames and determined the amount of damage and the economic effects on the structures. For this purpose, 3D models of 3-, 9-, and 20-story SAC-project steel frames were modeled and validated according to FEMA-355C and then a hybrid rocking shear wall was added to them. The structures were designed and modeled according to common seismic codes and were analyzed using nonlinear time history when subjected to a series of records from FEMA-355C. The results showed that the use of a hinged frame attached to a rocking concrete shear wall (HFR) increased the fundamental period and inter-story displacement and decreased the amount of steel used in the 3-, 9-, and 20-story models compared to similar models with fixed connections in moment frames (MFR). The HFR shear wall models exhibited better seismic performance than MFR models, which increased their load-bearing capacity and reduced their weight, which reduced construction costs.
Altered Expressions of CXCR4 and CD26 On T-Helper Lymphocytes in Hereditary Hemorrhagic Telangiectasia
Authors: GUILHEM Alexandre , Portalès Pierre , Dupuis-Girod Sophie , Rivière Sophie , Vincent Thierry
Published: July 2021

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by a deregulated neo-angiogenesis. Besides a mainly vascular phenotype (telangiectasia, arteriovenous malformations), patients exhibit a specific infectious risk and a deficit of T and natural killer (NK) lymphocytes. As the CXCR4/CXCL12 chemotactic axis is dysregulated in HHT endothelial cells, we hypothesized that a similar phenomenon could occur on lymphocytes.Results: Eighteen HHT patients with history of severe infection (HSI) were matched in age and sex with 18 HHT without HSI and 18 healthy control subjects (HC). We assessed the cell count and the surface expression of CXCR4 and CD26 (CXCL12 inactivating peptidase) of circulating helper and cytotoxic T lymphocytes (including naive, memory and activated subsets) and NK cells.The overall HHT group of 36 patients exhibited a reduction of circulating T-helper lymphocytes compared to HC (median: 517 vs 1026 cells/mm3, p<0.0001), correlated with age (r=-0.46, p=0.005), requirement of intravenous iron or blood transfusions (median: 291 vs 627 cells/mm3, p=0.03) and CXCR4 surface expression (r=0.353, p=0.0345). CXCR4 and CD26 membrane expression were both decreased on HHT T-helper lymphocytes (median MFI ratio: 4.49 vs 5.74 for CXCR4 and 3.21 vs 4.33 for CD26, p=0.03 and 0.0018 respectively) with an unchanged CXCR4/CD26 ratio. The HHT group with HSI had a higher CXCR4/CD26 ratio on the naive T-helper lymphocytes (median: 2.34 vs 1.32, p=0.0002), also observed on the T and T-helper populations.Conclusions: Our findings support a dysregulation of the CXCL12/CXCR4 chemotaxis of T-helper lymphocytes in HHT patients, potentially linked to their T-helper lymphopenia and susceptibility to infection.
Implementation of An Intravitreal Therapy Online Audit Tool For Neovascular Age-related Macular Degeneration Clinical Outcomes Reporting: Fight Retinal Blindness Spain (FRB-Spain) Project
Authors: Parrado-Carrillo Alba , Figueras-Roca Marc , Casaroli-Marano Ricardo P. , Nguyen Vuong , Barthelmes Daniel , Gillies Mark C. , Zarranz-Ventura Javier
Published: July 2021

Purpose: To implement an intravitreal therapy audit tool for neovascular age-related macular degeneration (nAMD) outcome reporting in a tertiary referral center. Methods: Implementation of an online audit tool (Fight Retinal Blindness platform) for nAMD eyes receiving anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy over a 24-month follow-up period. Data entry was compliant with the ICHOM dataset for nAMD. These data included visual acuity (VA), eye conditions, injection drug and number of injections. Subgroup analysis was performed for treatment-naive (TN) and previously treated (PT) eyes. Results: 234 eyes (191 patients) were included in the study. No significant differences were observed in the subgroup analysis in mean baseline VA (logMAR letters: 58.8 TN vs 62.7 PT, p= 0.081) or final VA at 12 months (TN 61.4 vs PT 62.4; p= 0.703). However, 12 months median VA change favoured TN cases (+4 TN vs +0 PT, p= 0.010) and median number of injections showed no differences (7 TN vs 7 PT, p= 0.644). No statistically significant differences were found at two years on number of injections even though mean final VA showed significant differences (66 TN vs 59.5 PT, p = 0.032) and VA change favoured the TN group (+2.4 TN vs - 4.6 PT, p= 0.003).Conclusion: We have successfully implemented an online tool to evaluate nAMD anti-VEGF treatment delivered in our center. This feasibility study demonstrates that the online audit tool allows evaluating real world intravitreal therapy outcomes and benchmark these results with clinical practice guidelines and other real-life series.
Cost-Effectiveness of Autism Diagnostic Based on Genetic Testing
Authors: Rudolph-Rothfeld Wolfgang , Vonthein Reinhard
Published: July 2021

Background: Autism Spectrum Disorder (ASD) is a highly heritable polygenetic disorder with several degrees of handicap.Novel genetic diagnostics for Autism Spectrum Disorder promise an earlier diagnosis than psychometric diagnostics, but their cost-effectiveness is unproven.Objective: To model the clinical pathway from diagnosis to early intervention (EI) and outcome in scenarios with genetic diagnostics compared to just psychometric diagnosis that follows a current guideline (Status Quo). Methods: Early diagnosis based on genetic testing leads to more intensive and effective early intervention. Future scenarios assume genetic screening(Screening), genetic testing on request(GenADD), or genetic testing in cases with a family history of ASD(Predisposition). Simulations on Markov models using software TreeAge v. 2018 and parameters found in the literature. The time horizon reached from birth to the 15th year of life with cycle length 1 year. The models were stratified by autism severity, i.e. IQ initially below 70 or above. Effectiveness was both, dependency free life years (DFLY) gained by correct diagnosis and successful treatment, and the number of diagnosed patients that became independent after treatment. We choose the insurance view. Just direct costs for diagnostics and treatment were considered. Probabilistic sensitivity analyses (PSA) explore assumptions of different parameters, like the sensitivity of the genetic test, using the precisions stated in the literature or possible future developments. Results: Status Quo is the most cost-effective scenario with the current parameter values. The other scenarios follow in the order of Predisposition, GenADD, and Screening. All scenarios with genetic tests have a higher number of detection than Status Quo. Intensified early intervention may be cost effective with horizon 67 years. The currently high false positive rate of genetic testing might be detrimental to that. Discussion: Low precision of published parameter estimates led to wide confidence intervals for our estimates of cost-effectiveness. Our model shows that Screening and GenADD should not be an option for inaccurate genetic tests. Once they are more accurate, the potential of early intervention may unfold.Conclusion: Further evaluations with better data need to underpin the current results.
Reversal of Haloperidol-Induced Orofacial Dyskinesia and Neuroinflammation by Isoflavones
Authors: Mezzomo Natália Fernandes , Schmitz Izaviani da Silva , de Lima Valtieri Bortoluzzi , Dorneles Gilson Pires , Schaffer Larissa Finger , Boeck Carina Rodrigues , Romao Pedro Roosevelt Torres , Peroza Luis Ricardo
Published: July 2021

Schizophrenia is a serious mental illness, and its pharmacological treatment consists in the administration of antipsychotics, such as haloperidol. However, treatment with haloperidol often causes extrapyramidal motor disorders such as tardive dyskinesia (TD). TD is a movement disorder characterized by involuntary movements, which can be studied in animals. So far, there is no effective treatment for TD and alternatives have been sought. Thus, the objective was to evaluate the possible protective effect of isoflavones against the induction of involuntary movements induced by haloperidol in an animal model. Male Wistars rats were treated with haloperidol (1 mg/ kg/day) and/or isoflavones (80 mg/kg) for 28 days. Rats were submitted to behavioral evaluation to quantify vacuous chewing movements (VCM) and the locomotor activity. In addition, the levels of pro-inflammatory cytokines were measured in the striatum. Haloperidol treatment reduced the locomotor activity and increased the number of VCM in rats. Co-treatment with isoflavones was able to reverse hypolocomotion and reduce the number of VCM to the levels of the control group. Besides, haloperidol caused significant increase in the proinflammatory cytokines (interleukin-1β:IL-1β, tumor necrosis factor-α:TNF-a and IL-6 and the co-treatment with isoflavones was able to reduce the levels of IL-1β and TNF-α, but not IL-6. It is believed that the beneficial effect found with this treatment is related to their anti-inflammatory potential and also to the action on estrogen receptors (based on findings in the scientific literature). Finally, further studies are needed to elucidate the mechanisms of isoflavones in reducing motor disorders induced by antipsychotic.
Dealing with the Heterogeneous Presentations of Freezing of Gait: How Reliable are the Freezing Index and Heart Rate for Freezing Detection?
Authors: Cockx Helena , Nonnekes Jorik , Bloem Bastiaan , Wezel Richard van , Cameron Ian , Wang Ying
Published: July 2021

Background: Freezing of gait (FOG) is an unpredictable gait arrest that hampers the lives of 40% of people with Parkinson’s disease. Because the symptom is heterogeneous in phenotypical presentation (it can present as trembling, shuffling, or akinesia) and manifests during various circumstances (it can be triggered by e.g. turning, passing doors, and dual-tasking), it is particularly difficult to detect with motion sensors. The freezing index (FI) is one of the most frequently used accelerometer-based methods for FOG detection. However, it might not adequately distinguish FOG from voluntary stops, certainly for the akinetic type of FOG. Interestingly, a previous study showed that heart rate signals could distinguish FOG from stopping and turning movements. This study aimed to investigate for which phenotypes and evoking circumstances the FI and heart rate might provide reliable signals for FOG detection.Methods: Sixteen people with Parkinson’s disease and daily freezing completed a gait trajectory designed to provoke FOG including turns, narrow passages, starting, and stopping, with and without a cognitive or motor dual-task. We compared the FI and heart rate of 406 FOG events to baseline levels, and to stopping and normal gait events (i.e. turns and narrow passages without FOG) using mixed-effects models. We specifically evaluated the influence of different types of FOG (trembling vs akinesia) and triggering situations (turning vs narrow passages; no dual-task vs cognitive dual-task vs motor dual-task) on both outcome measures. Results: The FI increased significantly for trembling FOG, but not for akinetic FOG. Furthermore, the index increased similarly during stopping and was therefore not significantly different from FOG. In contrast, heart rate change during FOG was for all types and during all triggering situations statistically different from stopping, but not from normal gait events. Conclusion: The FI has issues to distinguish FOG from voluntary stopping, especially of the akinetic type. In contrast, the clear distinction in heart rate change between FOG and voluntary stops, which was independent of the heterogeneous presentation of FOG, might provide a solution for this issue. Therefore, we suggest that combining a heart rate monitor with a motion sensor may be promising for future FOG detection.
Generalized Muscle Quality Loss as a Risk Factor for Pelvic Organ Prolapse: A Single-Center, Observational Study
Authors: Chino Yoko , Inoue Daisuke , Yamamoto Makoto , Onuma Toshimichi , Yoshida Yoshio
Published: July 2021

Among the physiological changes associated with aging, myopenia due to increased amounts of fatty tissue in muscles and loss of muscle mass have recently gained attention. This study retrospectively examined the relationship between generalized muscle quality and pelvic organ prolapse (POP). Participants comprised 25 patients between 40 and 79 years old showing a Pelvic Organ Prolapse Quantification system stage of 3 or higher who underwent surgery between 2017 and 2019. Control cases comprised 23 patients with benign gynecological diseases who underwent surgery without POP. CT performed within 3 months before surgery was used to measure muscle mass. Smooth muscle index (SMI) was significantly higher in the POP group than in the non-POP group (p = 0.017), and muscle mass was rather large in the POP group. Comparing the POP and non-POP groups, both subcutaneous and visceral fat accumulation were significantly higher in the POP group (p = 0.03, p = 0.002 respectively). Conversely, intramuscular adipose tissue content (IMAC), indicating lower muscle quality, was significantly higher in the POP group (p = 0.024). Multivariate analysis revealed BMI and number of deliveries, but not IMAC, as significant independent risk factors of POP. Although not an independent risk factor, decreased muscle quality was involved in the pathophysiology of POP.
The Role of PAX2 in Breast Cancer: A Study Based on Bioinformatics Analysis and in Vitro Validation
Authors: Yang Shan , Gao Wei , Wang Haoqi , Zhang Xi , Mi Yunzhe , Ding Yawen , Geng Cuizhi , Li Sainan
Published: July 2021

Background: Breast cancer (BC) is the most frequently diagnosed cancer in women and is the second most common cancer among newly diagnosed cancers worldwide. Studies have shown that paired box 2 (PAX2) participates in the tumorigenesis of some cancer cells. However, the functions of PAX2 in the BC context are still unclear.Methods: Transcriptome expression proﬁles and clinicopathological information of BC were download from the TCGA database. Then the expression level and prognostic value in TCGA database were explored. Gene Set Enrichment Analysis (GSEA) and functional enrichment analysis were performed to investigate the functions and pathways of PAX2. Moreover, RT-qPCR was used to determine the expression of PAX2 in BC tissues, and the predictive value of PAX2 in clinical samples was assessed. CCK-8 assay was used to evaluate cell growth. The migration and invasion capacities of cells were assessed by wound healing assay and Transwell assay.Results: PAX2 was up-regulated in the TCGA-BC datasets. GSEA analysis suggested that PAX2 might be involved in the regulation of MAPK signaling pathways and so on. Moreover, PAX2 was overexpressed in BC tissues, and PAX2 expression was associated with menopause. PAX2 deficiency could inhibit the growth, migration, and invasion of BC cells.Conclusion: This study suggested that PAX2 was up-regulated in BC, which inhibited BC cell growth, migration, and invasion. Thus, PAX2 could be a potential therapeutic target for BC.
Adsorption Behavior of an Adamantane Derivative on Metal Clusters – DFT Simulation Studies
Authors: Al-Otaibi Jamelah S. , Mary Y. Sheena , Mary Y. Shyma
Published: July 2021

Investigation of the adsorption properties of 3-(adamantan-1-yl)-4-phenyl-1-[(4-phenylpiperazin-yl)methyl]-1H-1,2,4-triazole-5(4H)-thione (APT) with metal clusters (mC: Ag, Au and Cu) are reported using DFT method. APT is found to form stable cluster with transition metal clusters of copper, silver and gold. The drug-cluster complexation energy is slightly more for the gold nanocluster-drug complex. Dipole moment of the drug-gold cluster is found to be higher than that of the other systems. SERS studies demonstrate improved Raman signals for multiple wavenumbers of all APT-metal cluster complexes. Different spectroscopic, chemical and electronic properties are also investigated.
Decolorization of Congo red in Microbial Fuel Cell
Authors: Priyanka K , sheela A.merline , R ILAMATHI
Published: July 2021

In this research, three individual conditions (static, shaking and MFC) were tested for Congo Red decolorization. P.aeruginosa MTCC 2582 has showed 96.1% decolourization under MFC condition with 85% COD reduction for the dye (100 µM). Microbial fuel cell of P.aeruginosa can discharge the dual duty of degrading the recalcitrant dye with power generation. To understand the influence the growth curve, different substrate concentration of glucose (0-20 g/L) were selected to improve the performance of MFC. Results show that a larger open circuit potential of 0.691 V and a maximum power density of 1.9 mW m-2 was possessed for the degradation of 100 µM of dye at 10 g/L of glucose concentration. Further, the selection of optimum concentration of dye (200 µM) increased the open circuit potential to 0.844 V. The degraded metabolites were confirmed using UV-Vis and FTIR analysis. Biofilm formation on anode at optimal glucose concentration was studied by using SEM analysis.
Treatment Satisfaction Among Clients Enrolled in Methadone Maintenance Treatment (MMT) Program in Myanmar: A Cross-sectional Study
Authors: Tun Sun , Vicknasingam B. , Singh Darshan
Published: July 2021

BackgroundTo address the long-standing opioid abuse problem, Myanmar has established the methadone maintenance treatment (MMT) program in 2006. This study aims to determine client’s treatment satisfaction towards MMT program in Myanmar. MethodA total of 210 clients who have registered in MMT program with a minimum of six-month treatment history were recruited for this cross-sectional study across Myanmar. The Verona Service Satisfaction Scale for Methadone-Treatment (VSSS-MT) was administered to objectively measure methadone treatment satisfaction. ResultThe majority (89%, n=186) were satisfied with the current methadone treatment program. Specifically, 89.5% (n=187) claimed to be highly satisfied with the clinic staff professional skills (e.g. doctor, nurse, etc.), (91.9%, n=192) satisfied with the basic interventions (instruction between visits, side-effects etc.), and (74.6%, n=156) satisfied with specific interventions (e.g. individual rehabilitation and psychotherapy, group therapy etc.) categories. Among the different characteristics of the respondents, higher quality of life on physical, psychological, social and environmental categories, respondents who satisfied on current marital status and current leisure status, respondents who were on alcohol were associated with higher treatment satisfaction on methadone (p<0.05). The result of stepwise binary logistic regression showed alcohol use and physical health had significantly association with treatment satisfaction.ConclusionDespite the high methadone treatment satisfaction, treatment providers must make an attempt to address service limitations in order to maintain clients’ participation in MMT program especially for specific intervention categories (e.g. individual rehabilitation and psychotherapy, group therapy etc).
Natural History of Respiratory Muscle Strength in Spinal Muscular Atrophy: A Prospective National Cohort Study
Authors: Veldhoen Esther S , Wijngaarde Camiel A , Hulzebos Erik H.J. , Asperen Roelie W Wosten-van , Wadman Renske I , Eijk Ruben P.A. van , Asselman Fay Lynn , Stam Marloes , Otto Louise A.M. , Cuppen Inge , Scheijmans Feline E.V. , Oudenrijn Laura P. Verweij-van den , Bartels Bart , Gaytant Michael A , Ent Cornelis K van der , Pol W Ludo van der
Published: July 2021

Background: Respiratory complications are the most important cause of morbidity and mortality in Spinal Muscular Atrophy (SMA). Respiratory muscle weakness results in impaired cough, recurrent respiratory tract infections and finally respiratory failure. We assessed longitudinal patterns of measurements of respiratory muscle strength in a national cohort of treatment-naïve children and adults with SMA, hypothesizing a continued decline of respiratory muscle strength parameters throughout life. Methods: We measured Maximal Expiratory and Inspiratory Pressure (PEmax and PImax), Sniff Nasal Inspiratory Pressure (SNIP), Peak Expiratory Flow (PEF), and Peak Cough Flow (PCF) in treatment-naïve patients. We used both cross-sectional and longitudinal data in mixed-models to analyze natural history patterns. Results: We included 2756 measurements of respiratory muscle function from 80 treatment-naïve patients with SMA types 1c-3b. Both PEmax and PImax were significantly lower in more severe phenotypes. SNIP was low in nearly all patients, most pronounced in more severely affected patients. PEmax was low from early childhood onwards in patients with SMA type 1c–3a. PEF decline below 80% of predicted values was observed in early childhood in SMA types 1c-2 and in adolescence in patients with type 3a. Annual decline was linear (1-2%/year). All but type 3b patients had lowered PCF. Patients with types 2b and 3a had PCF levels between 160 and 270L/min, those with type 2a around 160L/min and patients with type 1c well below 160L/min. Conclusions: There are clear differences in respiratory muscle strength and its progressive decline between SMA types. We observed lower outcomes in more severe SMA types. Particularly PEmax and PEF may be suitable outcome measures for follow-up of patients with SMA. PEmax had the highest discriminative capacity and PEF declined in a rather linear pattern in all SMA types. PEmax was even low in patients with normal lung volumes. These natural history data may serve as a reference for longer-term treatment efficacy assessments.
Blockage of IL-17 Ameliorates Aβ-Induced Neurotoxicity and Cognitive Decline
Authors: Liu Yulan , Meng Yang , Zhou Chenliang , Xia Wenfang , Wang Lu , Yan Juanjuan , Cheng Li , Dong Weiguo , Guo Cuiping
Published: July 2021

BackgroundNeuroinflammation plays a critical role in the pathophysiology of Alzheimer’s disease (AD), particularly in amyloid-β (Aβ) production. But the impact of the cytokine, interleukin-17A (IL-17) on the course of AD has not been well defined. The goal was to determine the effect of IL-17 on neural damage and whether IL-17 inhibitor (Y-320) could ameliorate Aβ-induced neurotoxicity and cognitive decline.MethodsThe expression level of IL-17 was analyzed in APP/PS1 mice. Then IL-17 was injected into the lateral ventricle of C57BL WT mice and roles on synaptic dysfunction and cognitive impairments were examined. Aβ42 was injected into the lateral ventricle of to mimic Aβ42 model mice. The effects of IL-17 inhibitor by oral gavage on Aβ42-induced neurotoxicity and cognitive decline were examined. ResultsWe found that IL-17 was increased in the hippocampus of APP/PS1 transgenic mouse, which has a fundamental role in mediating brain damage in neuroinflammatory processes. Furthermore, we reported that IL-17 was administrated in primary hippocampal neurons, leading to neural damage and synaptic dysfunction. At the same time, IL-17 caused synaptic dysfunction and cognitive impairments accompanying with increased of Aβ levels in mice. In addition, we found that Y-320 could rescue Aβ42–induced neural damage in primary hippocampal neurons, and ameliorate neuronal damage and cognitive impairments in Aβ42 model mice. Interestingly, we observed that IL-17 upregulated the production of soluble amyloid precursor protein β (sAPPβ) and phosphorylation of APP at T668 (pT668), moreover, Y-320 inhibited the Aβ production by down-regulation the sAPPβ and pT668. Conclusions Blockage of IL-17 might ameliorate Aβ-induced neurotoxicity and cognitive decline. These results strongly demonstrate a potential therapeutic role for IL-17 inhibitor in AD.
Functional Studies of MLL-AF4 and a Murinized pSer-variant thereof: MLL-AF4 Impairs the Ribosome Biosynthesis Pathway
Authors: Siemund Anna Lena , Kowarz Eric , Marschalek Rolf
Published: July 2021

Background: Recent pathomolecular studies on the MLL-AF4 fusion protein revealed that the murinized version of MLL-AF4, the MLL-Af4 fusion protein, was able to induce leukemia when expressed in murine or human hematopoietic stem/progenitor cells (1). In parallel, a group from Japan demonstrated that the pSer domain of the AF4 protein, as well as the pSer domain of the MLL-AF4 fusion is able to bind the Pol I transcription factor complex SL1 (2).Here, we investigated the human MLL-AF4 and a pSer-murinized version thereof for their functional properties in mammalian cells. Gene expression profiling studies were complemented by intracellular localization studies and functional experiments concerning the biological activities in the nuecleolus.Results: Based on our results, we have to conclude that MLL-AF4 is predominantly localizing in the nucleolus, thereby interfering withPol I transcription, and subsequently,also ribosomebiogenesis. The murinized pSer-variant is more localizing in the nucleus, which may explain their different biological behavior. Of note, AF4-MLL is cooperating at the molecular level with MLL-AF4, but not with the pSer-murinized version of it.Conclusion: This study provides new insights and a molecular explanation for the known differences between hMLL-hAF4 (not leukemogenic) and hMLL-mAf4 (leukemogenic). While the human pSer domain is able to efficiently recruit the SL1 transcription factor complex, the murine counterpart is not. This has several consequences for our understanding of t(4;11) leukemia which is by far the most frequent leukemia in infants, childhood and adults suffering from MLL-r acute leukemia.