bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility Analysis of Novel Maglev EDM by Comparing with Conventional Micro EDM
Authors: Sisodiya Mangal Singh , Shukla Shashank , Bajpai Vivek
Published: October 2021

The Micro EDM is the most suitable machining process in the miniaturization of products at present era. The attainment of close precision is the primary obligation in miniaturization or micromachining. Especially in machining of hard-to-cut materials like titanium alloy. Such alloys are applied in several cutting-edge high-quit applications due to extraordinary properties. Current work presents an exploratory analysis of novel Maglev EDM while machining of commercially used pure titanium alloy (CP-TI). The work outlook is to establish the viability of novel Maglev EDM by comparing the with similar range of micro EDM. The pure DC power is employed with the conjunction of Maglev lucidity to refine the shortcomings of the conventional micro EDM. The novel technology deals with prime concerns of conventional micro EDM and cracked deficiencies like delay response of mechanical actuator and a servo mechanism. The Novel technology uses the logical arrangement of permanent and electromagnet to dealt with inadequacies like short-circuiting and arcing. The results of state of art novel technology proclaimed the improved Material removal rate (MRR), which are lying in the average range of 76.6 µgm/min, whereas the specific energy and surface roughness are observed 33.4 Joule/ microgram and 4.3 µm respectively.
A Black Hole-Aided Deep-Helix Channel Model for DNA
Authors: Sarker Md. Abdul Latif , Kader Md. Fazlul , Sarker Md. Mostafa Kamal , Lee Moon Ho , Dong
Published: October 2021

In this article, we present a black-hole-aided deep-helix (bh-dh) channel model to enhance information bound and mitigate a multiple-helix directional issue in Deoxyribonucleic acid (DNA) communications. The recent observations of DNA do not match with Shannon bound due to their multiple-helix directional issue. Hence, we propose a bh-dh channel model in this paper. The proposed bh-dh channel model follows a similar fashion of DNA and enriches the earlier DNA observations as well as achieving a composite like information bound. To do successfully the proposed bh-dh channel model, we first define a black-hole-aided Bernoulli-process and then consider a symmetric bh-dh channel model. After that, the geometric and graphical insight shows the resemblance of the proposed bh-dh channel model in DNA and Galaxy layout. In our exploration, the proposed bh-dh symmetric channel geometrically sketches a deep-pair-ellipse when a deep-pair information bit or digit is distributed in the proposed channel. Furthermore, the proposed channel graphically shapes as a beautiful circulant ring. The ring contains a central-hole, which looks like a central-black-hole of a Galaxy. The coordinates of the inner-ellipses denote a deep-double helix, and the coordinates of the outer-ellipses sketch a deep-parallel strand. Finally, the proposed bh-dh symmetric channel significantly outperforms the traditional binary-symmetric channel and is verified by computer simulations in terms of Shannon entropy and capacity bound.
A systematic review of the use of simulated client method in examining medicine price
Authors: Lee Kah Seng , Kassab Yaman Walid , Taha Nur Akmar , Zainal Zainol Akbar
Published: October 2021

Purpose: This study was aimed to systematically identify and review studies conducted using simulated client/patients that examine medicine selling prices in healthcare settings, including pharmacies, clinics, and hospitals. The quoted drug pricing information, including the dispensing fees and healthcare financing system of the countries involved, were also compared.Design/methodology/approach: We searched Pubmed, OVID, Scopus, Ebsco (Medline) and ProQuest for papers reporting on simulated patient studies in various medical settings, specifying drug or pharmaceutical pricings. Randomized controlled trials, non-randomized controlled trials, longitudinal studies, cohort or case–control studies, and descriptive studies were included. The quality of included studies was checked using a validated tool.Findings: A total of 19 papers from 13 countries from all regions of the world were included in this systematic review. Various ,edical conditions that were presented by the simulated patients, such as cancer, back pain, insomnia and diarrhoea. Information on certain prescription and non-prescription drugs such as buprenorphine, methadone and antibiotics were reported in four studies. Most healthcare facilities adhere to prescribed selling prices, according to the medicine selling price trend examined in this study. Only around half of the research found that medicine prices were higher than the typical selling price. Some countries that practise price control policies were found to have higher drug selling prices than those that do not.Originality/value: This review, for the first time, revealed that simulated patient method is a practical solution to obtain pharmaceutical price information from healthcare provider and most healthcare facilities adhere to the recommended selling prices.
Integrative analyses of biomarkers and pathways for heart failure
Authors: Fan Shaowei , Hu Yuanhui
Published: October 2021

Background: Heart failure (HF) is the most common potential cause of death, causing a huge health and economic burden all over the world. So far, some impressive progress has been made in the study of pathogenesis. However, the underlying molecular mechanisms leading to this disease remain to be fully elucidated. Methods: The microarray data sets of GSE76701, GSE21610 and GSE8331 were retrieved from the gene expression comprehensive database (GEO). After merging all microarray data and adjusting batch effects, differentially expressed genes (DEG) were determined. Functional enrichment analysis was performed based on Gene Ontology (GO) resources, Kyoto Encyclopedia of Genes and Genomes (KEGG) resources, gene set enrichment analysis (GSEA), response pathway database and Disease Ontology (DO). Protein protein interaction (PPI) network was constructed using string database. Combined with the above important bioinformatics information, the potential key genes were selected. The comparative toxicological genomics database (CTD) is used to explore the interaction between potential key genes and HF. Results: We identified 38 patients with heart failure and 16 normal controls. There were 315 DEGs among HF samples, including 278 up-regulated genes and 37 down-regulated genes. Pathway enrichment analysis showed that most DEGs were significantly enriched in BMP signal pathway, transmembrane receptor protein serine / threonine kinase signal pathway, extracellular matrix, basement membrane, glycosaminoglycan binding, sulfur compound binding and so on. Similarly, GSEA enrichment analysis showed that DEGs were mainly enriched in extracellular matrix and extracellular matrix related proteins. BBS9, CHRD, BMP4, MYH6, NPPA and CCL5 are central genes in PPI networks and modules. Conclusions: the enrichment pathway of DEGs and go ontology may reveal the molecular mechanism of HF. Among them, target genes EIF1AY, RPS4Y1, USP9Y, KDM5D, DDX3Y, NPPA, HBB, TSIX, LOC28556 and XIST are expected to become new targets for heart failure. Our findings provide potential biomarkers or therapeutic targets for the further study of heart failure and contribute to the development of advanced prediction, diagnosis and treatment strategies.
COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis
Authors: Klein Robyn , Soung Allison , Sissoko Cheick , Nordvig Anna , Canoll Peter , Mariani Madeline , Jiang Xiaoping , Bricker Traci , Goldman James , Rosoklija Gorazd , Arango Victoria , Underwood Mark , Mann J. John , Boon Adrianus , Dowrk Andrew , Boldrini Maura
Published: October 2021

Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is associated with onset of neurological and psychiatric symptoms during and after the acute phase of illness1-4. Acute SARS-CoV-2 disease (COVID-19) presents with deficits of memory, attention, movement coordination, and mood. The mechanisms of these central nervous system symptoms remain largely unknown.In an established hamster model of intranasal infection with SARS-CoV-25, and patients deceased from COVID-19, we report a lack of viral neuroinvasion despite aberrant BBB permeability, microglial activation, and brain expression of interleukin (IL)-1β and IL-6, especially within the hippocampus and the inferior olivary nucleus of the medulla, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uremia or trauma. In the hippocampus dentate gyrus of both COVID-19 hamsters and humans, fewer cells expressed doublecortin, a marker of neuroblasts and immature neurons.Despite absence of viral neurotropism, we find SARS-CoV-2-induced inflammation, and hypoxia in humans, affect brain regions essential for fine motor function, learning, memory, and emotional responses, and result in loss of adult hippocampal neurogenesis. Neuroinflammation could affect cognition and behaviour via disruption of brain vasculature integrity, neurotransmission, and neurogenesis, acute effects that may persist in COVID-19 survivors with long-COVID symptoms.
Geometric Mediator Structures and Force Constants
Authors: koehler dale
Published: October 2021

It is shown in the present work that the distorted-space model of matter can describe conventional force-constants and transition-mediator structures. The distorted-geometry structures exhibit non-Newtonian features wherein the hole or core-region fields of the structures are energetically-repulsive (negative pressure), do not behave functionally in an r-4 manner and terminate at zero at the radial origin (no singularity). Near the core of the distortion the magnetic fields dominate the energy-densities of the structures thereby departing from classical particle-structure descriptions. Black-body radiation-emission and structural modeling leads to a description of transition dynamics and photonic entities.
Potential Habitat and Carrying Capacity of Endangered San Joaquin Kit Foxes in an Urban Environment: Implications for Conservation and Recovery
Authors: Cypher Brian , Deatherage Nicole A. , Westall Tory L. , Kelly Erica C. , Phillips Scott E.
Published: October 2021

The San Joaquin kit fox (Vulpes macrotis mutica; SJKF) is federally endangered due to profound habitat loss. A population of SJKF occurs in the urban environment in the city of Bakersfield, California, and may be important for SJKF conservation. We conducted a systematic survey using automated cameras stations and occupancy analysis to identify suitable habitat for SJKF in Bakersfield and to estimate a conceptual carrying capacity in the urban environment. We identified high, medium, and low suitability habitat totaling 121 km2, 196 km2, and 40 km2, respectively. Based on a mean home range size of 0.78 km2 and an assumption of two adults in high suitability home ranges and one adult in medium suitability ranges, we estimated the adult carrying capacity in Bakersfield to be 561 foxes. This estimate seems plausible as the number of adult SJKF in Bakersfield was estimated to be 381 in 2015, and the number of foxes already had been reduced by a sarcoptic mange epidemic that began two years earlier. A carrying capacity of 561 adults would increase the estimated range-wide carrying capacity by as much as 38%. Density estimates derived for the urban SJKF population based on the carrying capacity (1.57/km2) and home range size (2.56/km2) were higher than estimates for foxes in natural habitats. The urban SJKF population in Bakersfield is substantial and therefore could contribute significantly to conservation and recovery efforts for SJKF. Given our results, a potential conservation strategy may be to encourage or even establish additional urban SJKF populations.
Urethrocutaneous Fistula Following VMMC: A Case Series from March 2013 to October 2019 in ZAZIC’s Voluntary Medical Male Circumcision Program in Zimbabwe
Authors: Murenje Vernon , Victor Omollo , Paidemoyo Gonouya , Joseph Hove , Tinashe Munyaradzi , Phiona Marongwe , Mufuta Tshimanga , Vuyelwa Chitimbire , Sino Xaba , John Mandisarisa , Shirish Balachandra , Batsirai Makunike-Chikwinya , Marrianne Holec , Mangwiro Tonderayi , Scott Barnhart , Caryl Feldacker
Published: October 2021

Background: Urethrocutaneous fistula (subsequently, fistula) is a rare adverse event (AE) in voluntary medical male circumcision (VMMC) programs. Global fistula rates of 0.19 and 0.28 per 100,000 VMMCs were reported. Management of fistula can be complex and requires expert management. We describe seven cases of fistula in our large-scale VMMC program in Zimbabwe. We present fistula rates; provide an overview of initial management, surgical interventions, and patient outcomes; discuss causes; and suggest future prevention efforts. Results: Case details are presented on fistulas identified between March 2013 and October 2019. Among the seven fistula clients, ages ranged from 10-22 years; 6 cases were among boys under 15 years of age. All clients received surgical VMMC by trained providers in an outreach setting. Clients presented with fistulae 2 to 42 days after VMMC. Secondary infection was identified in 6 of 7 cases. Six cases were managed through surgical repair. The number of repair attempts ranged from 1 to 10. One case healed spontaneously with conservative management. Fistula rates are presented as cases/100,000 VMMCs.Conclusion: Fistula is an uncommon but severe AE that requires clinical expertise for successful management and repair. High-quality AE surveillance should identify fistula promptly and include consultation with experienced urologists. Strengthening provider surgical skills and establishment of standard protocols for fistula management would aid future prevention efforts in VMMC programs.
Physics For Medical Colleges: Proposing An Extended Syllabus
Authors: Omer Hiba
Published: October 2021

Background

Physics has indeed revolutionized medical practice since the birth of medicine thousands of years ago. It provided us with a better understanding of our health problems through many diagnostic and treatment tools yet, many medical colleges do not fully implement physics as a core subject in their curricula. Physics is taught only as a freshman year subject, and many medical students feel obliged to take it without knowing its real benefits to their future careers. This is basically due to the lack of an appropriate course design, references, and the poor commissioning of physics in the medical field. The aim of this work is to propose a series of courses of physics in medicine that would fulfill the requirements of any medical college.
Methods

The presented courses will be divided into three phases: premedical, pre-clinical, and clinical years for medical students. To do so, a critical analysis of the topics needed at the different phases and the possibilities of implementing this syllabus and constraints that may face the process is conducted.
Results

the different topics are shown and means of implementing them as a single subject or in conjunction with other subjects is clarified
Conclusion

Once properly tailored, physics can provide a strong tool in medical education
Chronic Corticosterone Disrupts The Circadian Rhythm of CRH Expression and m6A RNA Methylation In The Chicken Hypothalamus
Authors: Yang Yang , Han Wanwan , Zhang Aijia , Zhao Mindie , Cong Wei , Jia Yimin , Wang Deyun , Zhao Ruqian
Published: October 2021

Background: Corticotropin-releasing hormone (CRH), the major secretagogue of the hypothalamic-pituitary-adrenal (HPA) axis, is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions. N6-methyladenosine (m6A) RNA methylation is involved in the regulation of circadian rhythm, yet it remains unknown whether CRH expression and m6A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress. Results: Chronic exposure to corticosterone (CORT) eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken. The circadian rhythms of clock genes in hippocampus, hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens. The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened, together with mRNA of other feeding-related neuropeptides. Interestingly, hypothalamic m6A level oscillates in an opposite pattern to CRH mRNA, with lowest m6A level after midnight (ZT18) corresponding to the peak of CRH mRNA before dawn (ZT22). CORT diminished the circadian rhythm of m6A methylation with significantly increased level at night. Further site-specific m6A analysis on 3’UTR of CRH mRNA indicates that higher m6A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night (ZT18 and ZT22). Conclusions: Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus, leading to dysfunction of HPA axis in the chicken. RNA m6A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions.
Mediating Effect of Students’ Perception in Programming on the Relationship Between Project Work and College Students’ Interest in Programming
Authors: Senior Isaac Ampofo Atta
Published: October 2021

Computer programming has been a subject of debate, whether students have an interest or not. Students' impressions of their own abilities to program and of programming in general are influenced by their early programming experiences, which play a role in encouraging or discouraging students' interest in computing areas. As a result, project work as a method of teaching has been adopted by many lecturers in teaching computer programming. However, the study sought to assess the mediating influence of students' perception in the relationship between project work and college students' interest in programming. The study used a descriptive survey design. The target population for the study included all Computer Science and Mathematics students at the University of Cape Coast, Ghana. The population for the study was 2,410 students with a sample size of 332. The researcher used a questionnaire to gather the data for studying the issue under investigation. Analysis of the data was done through the use of the PROCESS Macro. The results revealed that the mediating effect of students’ perception of programming on the relationship between project work and college students’ interest in programming accounts for only 0.34% of the total contribution of factors that influence college students’ interest in programming.
Spatial-Temporal Change Analysis for Multivariate Drought Risk Based on Bayesian Copula: Application to the Balkhash Lake Basin
Authors: Yang Xin , Li Yongping
Published: October 2021

In this study, a spatial-temporal Bayesian copula (SBC) method is developed through integrating spatial-temporal analysis and Bayesian copula into a general framework. SBC method can help model dependence structures of variable pairs and handle the uncertainty caused by parameter in copulas, and SBC can reveal the spatial and temporal changes of drought events. SBC is applied to the Balkhash Lake Basin (in Central Asia) to analyze spatial-temporal characteristic and drought risk in 1901-2020. Several findings can be summarized: (1) Balkhash Lake Basin suffered 53 drought events in 1901-2020, and five typical severe drought events occurred in 1916-1920, 1943-1945, 1973-1977, 1995-1998 and 2007-2009; (2) the most severe drought event lasted for 40 months (1973.10-1977.1), affecting 335,800 km2 of the study basin; (3) drought usually develops from east to west, and Ili River delta and alluvial plain has the highest frequency of drought (47.2%), following by plateau desert (28.3%) and arid grassland in north Balkhash Lake (24.5%); (4) drought shows significant seasonality in the study basin, which usually begins in spring and summer (64.2%) and ends in summer and autumn (66.0%); and drought risk of middle and lower reaches of Ili River is highest in spring and summer; (5) in Balkhash Lake Basin, multivariate characteristics (duration, severity and affected area) significantly affect drought risk; (6) the range of drought risk is [1.9%, 18.1%], [3.7%, 33.1%], [8.7%, 46.0%], [16.0%, 55.1%] and [27.6%, 59.8%] when guarantee rate is 0.99, 0.98, 0.95, 0.90 and 0.80, respectively.
Allyl Isothiocyanate Inhibits Invasion and Angiogenesis in Breast Cancer via EGFR Mediated JAK1/STAT3 Signaling Pathway
Authors: Rajakumar Thangarasu , Pugalendhi Pachaiappan
Published: October 2021

Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK1/STAT3 is a key intracellular signaling transduction path, which controls the growth, differentiation, apoptosis, invasion, and angiogenesis in various cancer cells. The existing study explored the impact of AITC on the JAK-1/STAT-3 pathway in DMBAinjected rat mammary tumorigenesis. The mammary tumor was initiated through a single dose of 25 mg DMBA/rat through a subcutaneous injection administered near the mammary gland. We observed decreased body weight and augmented the total number of tumors, tumor incidence, tumor volume, well-developed tumor, and histopathological abnormalities in DMBA-injected rats and that were modulated after being treated with AITC. Staining of mammary tissues showed a high accumulation of collagen in DMBAtreated rats and it was normalized by the AITC treatment. Moreover, DMBA-induced mammary tissues showed up-regulated expressions of EGFR, pJAK-1, pSTAT-3, the nuclear fraction of STAT-3, and its associated products like VEGF, VEGFR2, HIF-1α, MMP-2, and MMP-9 and the down-regulated expressions of cytosolic STAT-3 and TIMP-2. Oral administration of AITC on DMBAtreated rats inhibits angiogenesis and invasion through modified these angiogenic and invasive markers. The finding of the current study is further confirmed by molecular docking analysis that shows a strong binding interaction between AITC with STAT-3 and cocrystal structure of STAT3 glide energy of -18.123 and − 72.246 (kcal/mole), respectively. Overall, the results suggested that AITC inhibits activation of the JAK-1/STAT-3 path, which subsequently prevents angiogenesis and invasion. It was recommended that AITC might develop a beneficial effect against breast cancer.
Learning Manifolds from Non-stationary Streams
Authors: Mahapatra Suchismit , Chandola Varun
Published: October 2021

Streaming adaptations of manifold learning based dimensionality reduction methods, such as Isomap, are based on the assumption that a small initial batch of observations is enough for exact learning of the manifold, while remaining streaming data instances can be cheaply mapped to this manifold. However, there are no theoretical results to show that this core assumption is valid. Moreover, such methods typically assume that the underlying data distribution is stationary and are not equipped to detect, or handle, sudden changes or gradual drifts in the distribution that may occur when the data is streaming. We present theoretical results to show that the quality of a manifold asymptotically converges as the size of data increases. We then show that a Gaussian Process Regression (GPR) model, that uses a manifold-specific kernel function and is trained on an initial batch of sufficient size, can closely approximate the state-of-art streaming Isomap algorithms. The predictive variance obtained from the GPR prediction is then shown to be an effective detector of changes in the underlying data distribution. Results on several synthetic and real data sets show that the resulting algorithm can effectively learn lower dimensional representation of high dimensional data in a streaming setting, while identifying shifts in the generative distribution.
The Oculomotor Signature of Expected Surprise
Authors: Drążyk Dominika , Missal Marcus
Published: October 2021

Expected surprise could be defined as the anticipation of the uncertainty associated with the future occurrence of a target of interest. We hypothesized that spatial expected surprise could have a different impact on anticipatory and visual gaze orientation. This hypothesis was tested in humans using a saccadic reaction time task in which a cue indicated the future position of a stimulus. In the ‘no expected surprise’ condition, the visual target could appear only at the previously cued location. In other conditions, more likely future positions were cued with increasing expected surprise. Anticipation was more frequent and pupil size was larger in the no expected surprise condition compared with all other conditions. The latency of visually-guided saccades increased linearly with the logarithm of surprise but their maximum velocity did not.In conclusion, before stimulus appearance oculomotor responses were altered probably due to increased arousal in the no expected surprise condition. After stimulus appearance, the saccadic decision signal could be scaled logarithmically as a function of surprise (Hick’s law). However, maximum velocity also reflected increased arousal in the no surprise condition. Therefore, expected surprise alters the balance between anticipatory and visually-guided responses and differently affects movement kinematics and latency.
Timing of Renal Replacement Therapy Initiation in Patients with Septic Acute Kidney Injury; A Systematic Review and Meta-Analysis
Authors: Oh Hyung Jung , Min In Kyung , Roh Yun Ho , Kim Jung ho , Ahn Jin Young , Jeong Su Jin , Choi Jun Yong , Yeom Joon-Sup , Song Young Goo , Ku Nam Su , Chung Yong Eun
Published: October 2021

Background; Acute kidney injury (AKI) is the most frequent complication seen in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy (RRT) is standard care for patients with severe septic AKI, the optimal timing of RRT initiation remains controversial.Methods; The PubMed, Cochrane, and Embase databases were searched from their inception to June 2021 to identify the ideal timing of RRT initiation in patients with septic AKI by comparing 28- and 90-day mortality rates.Results; Among a total of six studies including 1,058 patients, the 28-day mortality rate was significantly lower in the early RRT-treated group compared to the late group [RR=0.69; 95% CI (0.51-0.94); P=0.018]. Moreover, among the five studies including 938 patients, the 90-day mortality rate was also significantly lower in the early RRT-treated group than the late group [RR=0.61; 95% CI (0.47-0.80); P=0.01]. In a subgroup analysis for continuous RRT (CRRT), we also found significantly lower 28- and 90-day mortality rates in the early CRRT-treated group compared to the late group.Conclusion; This study showed that early initiation of RRT might reduce 28- and 90-day mortality compared with late initiation in septic AKI patients.
Characteristics of Pollen Grains of Different Date Pollinator Cultivars and Their Metaxenia Effect on Secondary Metabolites, Enzymes and Other Biochemical Compounds of ‘piarom’ Dates at Different Stages of Fruit Growth
Authors: Shahsavar Ali Reza , Shahhosseini Asma
Published: October 2021

In this study, the characteristics of pollens of eight date pollinating cultivars including ‘Shahani’, ‘Zahedi’, ‘Beraem’, ‘Faryab’, ‘Sheikhali’, ‘Fard’ and ‘Jarvis’ were compared and their metaxenia effects on secondary metabolites, enzymes and other biochemical compounds of ‘Piarom’ date fruit was investigated in four stages of fruit growth and development. The pollens of these eight pollinating cultivars were compared in terms of carbohydrate, protein starch, total phenol, flavonoids, pectin methyl esterase, and amylase enzymes. According to the results, , pollens of ‘Sheikhali’, ‘Fard’, ‘Zahedi’ and ‘Shahani’ cultivars had higher amounts of the above compounds than other cultivars. Regarding the effect of pollens on the composition of ‘Piarom’ date fruit, ‘Fard’ and ‘Sheikhali’ pollens produced the lowest amount of soluable tannin, which resulted in better quality of ‘Piarom’ date fruits. Pollens of ‘Sheikhali’ and ‘Fard’ cultivars produced the highest amounts of glucose and fructose in the fruit. In relation to sucrose, ‘Jarvis’ and ‘Shikhali’ were the best. Pollens of ‘Sheikhali’ and ‘Fard’ cultivars caused the lowest amount of chlorophyll in different stages of fruit growth, indicating better decomposition of fruit chlorophyll and, as a result, better fruit quality. Pollens of ‘Sheikhali’ and ‘Fard’ cultivars produced the highest amount of secondary metabolites such as total phenol, carotenoids and anthocyanin at different stages of ‘Piarom’ date fruit development. Pollens of ‘Fard’ and ‘Sheikhali’ cultivars produced the highest levels of polygalacturonase, cellulase and invertase enzymes at different stages of ‘Piarom’ date fruit growth. Regarding cellulase enzyme, ‘Zahedi’ cultivar produced more ‘cellulase’ in fruit than ‘Sheikhali’. In general, the pollens of ‘Fard’ and ‘Sheikhali, in comparison with other cultivars, improved the quantity and quality of ‘Piarom’ date fruit, due to their metaxenia properties.
Interventional Indirect Effects: A Novel Approach to Optimise Complex Psychological Therapies to Treat Depression for Scale-up in Goa, India
Authors: Seward Nadine , Vansteelandt Stijn , Moreno-Agostino Darío , Patel Vikram , Araya Ricardo
Published: October 2021

Introduction: Understanding how and under what circumstances complex psychological therapies work (or not) is important to bring evidence-informed intervention to scale, especially in resource poor settings. However, current methods do not apply methodology that account for the underlying complexity of these interventions including the interplay between implementation outcomes, implementation strategies and mechanisms. Here we apply a robust mediation analysis to address these issues to data from the Healthy Activity Program (HAP) trial –a psychological intervention for depression delivered using task-shifting with lay counsellors in Goa India.Methods: Interventional in(direct) effects were used to simultaneously decompose the total effect of the intervention on depression symptoms measured through the Patient Health Questionnaire (PHQ-9). The following indirect effects were considered: fidelity of receipt including number of sessions and homework completed; behavioural activation according to an adapted version of the Behavioural Activation for Depression Short Form (BADS-SF), and extra sessions offered to participants who did not respond to the intervention. Results: Of the total effect of the intervention measured through the difference in PHQ-9 scores between treatment arms (mean difference: -2.2, 95% bias-corrected CI: -3.2, -0.8), 45% was mediated through improved levels of behavioural activation (-1.0, -1.3, -0.6). There was little evidence to support the mediating role of characteristics of the sessions nor the extra sessions offered to participants who did not respond to the treatment. ConclusionsFindings from our analyses have demonstrated how interventional (in)direct effects can be applied to understand how implementation research programmes can be optimised for scale-up. Our results highlight the importance of sessions focusing on behavioural activation to improve symptoms of depression. Targeting non-responders with strategies other than extra therapy sessions has the potential to improve depression outcomes at a population level.
WaterSwap Analysis, a Computation-based Method for the Discovery of Effective and Stable Binding Compounds for Mutant EGFR Inhibition
Authors: Karnik Kshipra S. , Sarkate Aniket P. , Jambhorkar Vaishanavi S. , Wakte Pravin
Published: October 2021

The epidermal growth factor receptor of the tyrosine kinase family has been largely targeted in mutations associated with non-small cell lung cancer. EGFR inhibitors have been produced that bind allosterically to the C797S mutant EGFR enzyme. Here, the Waterswap tool has been used for the interpretation and visualization of trajectories of mutant EGFR-ligand complexes. Virtual screening of the generated compounds has been carried out along with its molecular docking and ADMET analysis. Out of the generated library of compounds, the top 15 have been selected. Waterswap calculated the binding free energies of the compounds and thermodynamic properties of the enumerated compounds were compared with that of standard EAI045. It was observed that styrylquinoline stabilized better than EAI045. The results show that Waterswap analysis offers a promising new path in the hunt for improved tools for analyzing and visualizing molecular driving forces in protein-ligand complex simulations.
Peer group-based online intervention program to empower families of those raising children with disabilities: Study protocol for a non-randomized waitlist-controlled trial
Authors: Matsuzawa Akemi , Wakimizu Rie , Sato Iori , Fujioka Hiroshi , Nishigaki Kaori , Suzuki Seigo , Iwata Naoko
Published: October 2021

BackgroundFamilies raising children with disabilities assume risks to their health and lives. Therefore, it is necessary to support these families to improve family empowerment, which is the ability of these families to control their own lives and to promote the collaborative raising of children with disabilities. This is the first online program development and interventional study focusing on the empowerment of families raising children with disabilities who live at home in Japan.MethodThe program consisted of four online peer-based group sessions. Moreover, the families engage in several activities in stages wherein they discover their own issues, find measures to resolve them, and take action, while visualizing interfamily relationships, including social resources, and the status of their family life, with facilitators and other peer members. This study was a non-randomized, waitlist-controlled trial. It compared the results of the intervention group (early group) and the waitlist-controlled group (delayed group). The participants were allocated to the early or delayed group in the order of their applications. The main outcome was family empowerment. Other outcomes are the caregiver burden, awareness of the use of social resources, self-compassion, and the quality of life (QOL) of primary caregivers. The timing of the online surveys was as follows: the initial evaluation (Time 1 [T1]) was conducted before the start of the first early group program, and post-intervention evaluation (Time 2 [T2]) was conducted immediately (within one week) after the early group had completed all four sessions (four weeks) of the program. Follow-up evaluation (Time 3 [T3]) was conducted four weeks after the post-intervention evaluation. This timing was the same in the delayed group, but the delayed group attended the program after a four-week waiting period, compared to the early group.DiscussionThe intention is to evaluate whether the provision of the program developed in this study and the evaluation test design are feasible and to verify the efficacy of this program.Clinical trial registrationThe UMIN Clinical Trials Registry (UMIN000044172), registration date: May 19, 2021. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000050422
20(s)-ginsenoside Rh2 promotes TRAIL-induced apoptosis by upregulating DR5 in human hepatocellular carcinoma cells
Authors: Liu Wenmo , Wang Siqi , Yang Qinchuan , Feng Xinyao , Yu Bin , Yu Xianghui
Published: October 2021

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential therapeutic anti-cancer drug with selective cytotoxicity in cancer cells. However, in multiple clinical trials, the therapeutic effect of TRAIL is limited owing to tumor resistance. The combination of small molecules or other drugs may represent a suitable strategy to overcome TRAIL resistance. This study found that 20(s)-ginsenoside Rh2 sensitized non-sensitive human hepatocellular carcinoma cells to TRAIL-induced apoptosis. The combination of TRAIL and Rh2 decreased cell viability and increased caspase cascade-induced apoptosis in several liver cancer cell lines. Moreover, we found that Rh2 reduced the apoptosis-related protein XIAP and Survivin, a negative regulator of the apoptosis pathway. At the same time, Rh2 can further enhance TRAIL-induced apoptosis by upregulating the death receptor 5 (DR5), thereby significantly enhancing its anti-tumor effect. Furthermore, Rh2 enhanced the therapeutic efficacy of TRAIL in mouse xenograft models, suggesting that Rh2 also sensitizes TRAIL in vivo. Taken together, our study indicates that Rh2 may act as a sensitizer in combination with TRAIL to increase the efficacy of its anti-tumor activity.
The Times of Raja Bongsu of Johor (±1579–1623)
Authors: Mitrasing Ingrid S.
Published: October 2021

Raja Bongsu’s significance in one of the most turbulent periods in the history
of the sultanate Johor is the subject of this article. Seventeenth-century accounts play a major role in shaping the subsequent knowledge of him. These depict a man who—in a certain context—made decisions which to his own logic were right, but often led to serious problems. In the literature, he is an object of commentary rather than of study. Representations of Bongsu (youngest brother) establish the contours of his position, first as the closest associate of his brother, Sultan Ala’ud-din Ri’ayat Shah III (r. 1579–1615), and as Sultan Abdullah Ma’ayat Shah (r. 1615–1623). He was the Raja Ilir (from the downstream area), in the sources also referred to as Raja Seberang (the other side of the river where he had his fort and his constituency), actively engaging in Johor’s external relations, taking part in discussions and negotiations with foreigners on trade and military missions. His tenure coincided with the arrival and establishment of the Verenigde Nederlandse Oost Indische Compagnie (VOC), as an important factor in the Straits region.
Intention to revisit tourist destinations in Indonesia
Authors: Sulistya Rini Endang , Absah Yeni , Karina Fawzeea Sembiring Beby , Dharma Tuah Putra Nasution Muhammad
Published: October 2021

This study aims to examine the effect of tourism image, experiential value, and satisfaction on the intention of revisiting the tourist area. The present study used associative analysis to ascertain the link between two or more variables. The study is being conducted in North Sumatera province, Indonesia, specifically in the tourist area of Lake Toba. The research population is comprised of an undetermined number of tourists that visited the tourist area around Lake Toba. The sample size of 324 was determined, which was obtained by multiplying the least number of samples by four or five questionnaire item categories. An accidental sampling approach was employed in this study, and data processing was performed using descriptive and inferential statistics and Smart-PLS software. The empirical findings indicate that although the tourism image has a significant and positive impact on experiential satisfaction, the direct effect of experiential value has a negative value on experiential satisfaction. Moreover, through tourism experiential satisfaction, experiential value has a negative value on intentions to revisit the destination. On the other hand, the indirect relationship between the tourism image and the intention to revisit through tourism experiential satisfaction has a positive value. AcknowledgmentWe would like to express our gratitude to the Ministry of Education and Culture’s Directorate of Research and Community Service for funding this study via the “Higher Education Excellent Basic Research Grant Fund” program.
A Method for Processing Digital Images of Colorimetric Biochipes for Quantitative Determination for Bacterial Antibiotic Resistance
Authors: Presnova G.V. , Grigorenko V.G. , Ulyashova M.M. , Rubtsova М.Yu.
Published: October 2021

Abstract-Molecular genetic analysis methods based on the technology of colorimetric biochip have shown their effectiveness in identifying antibiotic resistance genes in bacteria. For the quantitative determination of nucleic acids, a comparative study of methods for converting digital color images of biochips into monochrome black-and-white versions using RGB and CMYK color models has been carried out. A 19-mer single-stranded oligonucleotide and two model mRNAs corresponding to the genes of two types of clinically relevant beta-lactamases (CTX-M and NDM) were studied as objects. The widest range of staining intensity and the best analytical characteristics for the determination of all types of studied nucleic acids were obtained using the red channel of the RGB color model. The detection limits were 0.10 ± 0.02 pmol/μl for the 19-mer oligonucleotide, and 3.0 ± 0.2 amol/μl and 8.0 ± 0.6 amol/μl for mRNA of beta-lactamases CTX-M-116 and NDM-1, respectively. The developed method can be used for the quantitative determination of expressing antibiotic resistance genes in bacteria with multiple resistance to antimicrobial drugs.

Key words: colorimetric biochips, hybridization analysis, DNA, mRNA, antibiotic resistance, beta-lactamases

The work was supported by the Government Program of the Lomonosov Moscow State University (АААА-А21-121011290089-4).
Features of Bioconversion of Soybean Raw Materials into Fermented Products
Authors: Tadzhibova P.Yu. , Ignatova N.I. , Overchenko M.B. , Pogorzhelskaya N.S. , Rimareva L.V.
Published: October 2021

Abstract-The preparation of fermented sauces by the conversion of soy raw materials under the action of the A. oryzae RCAM 01134 fungus or endogenous enzymes is described. The technologies differed at the first stage of fermentation: the fungus development lasted for 4 days, and the hydrolysis of soy polymers under the action of a selected enzyme complex continued for 24 h. An algorithm was developed for the process of biocatalytic conversion of soy polymers using enzymes of various mechanisms of action and origin. Soy proteins were hydrolyzed most effectively by a complex enzyme preparation containing proteinases, peptidases, xylanases and α-amylases. It provided the level of formation of amine nitrogen and free amino acids in the enzymatic hydrolysate by 3.6-3.8 times higher than the autolytic conversion. The specific influence of biotechnological methods on the composition of the obtained fermented soy sauces was revealed. Microbial conversion contributed to an increase in the content of essential amino acids in the products (by 1.72 times) and a decrease in the level of carbohydrates (by 1.7 times), while enzymatic hydrolysis was characterized by a higher release of amino acids from the bound state (53.8 %).

Key words: soybeans, bioconversion, Aspergillus oryzae, enzymes, proteases, xylanase, α-amylase, fermented sauce, protein, amino acids

The work was carried out at the expense of subsidies for the implementation of a state task (topic no. 0529-2019-0066).
Reservation of the Most Important Structural Components of the Human Umbilical Cord after Decellularization as a Stage in the Manufacture of a Highly Regenerative Wound Dressing
Authors: Kalyuzhnaya L.I. , Sokolova M.O. , Chernov V.E.
Published: October 2021

Abstract-To create the basis for the wound covering, we have developed a tissue-engineered cell-free structure from a highly regenerative homologous biomaterial of the human umbilical cord. The construct retains dermal-like structural components and therefore can stimulate the repair of skin imperfections. The composition and structure of the tissue-engineered scaffold from the human umbilical cord was evaluated by microscopic analysis; porosity was revealed, which promotes cell recruitment. Collagens and glycosaminoglycans form the basis of the tissue-engineered umbilical cord scaffold, which provides the physiological and adhesive properties of the final product. Thin long collagen fibers constitute a dense network, similar to the dermal extracellular matrix. The retention of type IV collagen and laminin is important for basement membrane formation and cell attachment.

Key words: bioscaffold, matrix, scaffold, decellularization, tissue engineering, wound covering
Antagonistic Effect of Lactic Acid Bacteria and their Consortium with Yeast on Pathogenic Microorganisms
Authors: Semenova Е.F. , Zaitsev G.P. , Slastya Е.А. , Omelchenko А.V. , Bugara I.A. , Teplitskaya L.М. , Tsokalo I.E.
Published: October 2021

Abstract-A comparative study of the influence of lactic acid bacteria and their consortium with yeast on the growth of pathogenic bacteria and fungi has been carried out. It was revealed that the proposed composition of probiotic microbial species has fungistatic activity and strongly pronounced fungicidal activity against mold micromycetes and phytopathogenic fungi, respectively. The consortium effectiveness in suppressing both bacteria and filamentous fungi exceeds that of the corresponding monocultures. Analysis of wheat seeds for the presence of fungi by germination in a humid chamber and on nutrient media showed that the association of a 3-day culture of lactic acid bacteria and yeast at a dilution of 1:100 significantly reduced the infection of plant material. The ability to suppress opportunistic and phytopathogenic microorganisms is explained by the presence in the microbial consortium culture liquid of metabolites with bactericidal and fungicidal properties: squalene, dimethyl fumarate, capric acid, lactic acid, acetic acid, caprylic acid, fumaric acid, butyric acid, decanol, butanol, pentanol and β-phenylethanol.

Key words: lactic acid bacteria, consortium of microorganisms, antagonistic activity, phytopathogens, bacteria pathogenic for humans
Detection of Osteosarcoma on Bone Radiographs Using Convolutional Neural Networks
Authors: Asito Larissa , Pereira Hélcio , Nogueira-Barbosa Marcello , Tinós Renato
Published: October 2021

We propose a computer-aided diagnosis system based on convolutional neural networks (CNNs) for the identification of osteosarcoma on bone radiographs. The CNN should indicate regions of the image that may contain tumors. In order to indicate these regions on the image, we propose to split the image in windows and individually classify them by using a CNN. Techniques for pre-processing, such as window exclusion and labeling, are proposed. Two CNNs are compared in the proposed system. The first one is trained from scratch, while the second one is a pre-trained CNN (VGG16). The CNNs are compared to four machine learning models that use features extracted from the image windows as inputs: multilayer perceptron (MLP), decision tree, random forest, and MLP with feature selection. In the experiments, the best performance was obtained by the pre-trained CNN.
Impact of temperature on the leaching of sulphate, Co, Fe, Mn, Ni and Zn from the Ballangen tailings deposit, Norway: a laboratory column experiment
Authors: Lu Jinmei , Walder Ingar , Leiviskä Tiina
Published: October 2021

Temperature is an important factor affecting the leaching of contaminants from waste deposits, especially in the Nordic region where temperature change is more drastic than other areas. In this study, the impact of temperature variation in the leaching of sulphate, Co, Fe, Mn, Ni and Zn from the Ballangen tailings deposit, northern Norway, was investigated using a column leaching experiment. Unoxidized tailings were fed into four columns, which were subsequently put into four wine fridges set at 5, 10, 14 and 18 °C, respectively. The columns were filled with 600 mL of deionized water from the top every second week. Leachate was collected at the bottom and tested for pH, conductivity and concentrations of , Co, Fe, Mn, Ni and Zn. The saturation index for ferrihydrite and the activity of Fe2+ in the leachate were calculated with PHREEQC. The results showed that the conductivity and leachate concentrations of , Co, Fe, Mn and Ni were highest at 14 and 18 °C, and lowest at 5 °C, which showed high tailings oxidation and subsequent leaching of contaminants at higher temperatures. X-ray photoelectron spectroscopic (XPS) analysis of the residual material confirmed the oxidation of sulphides and leaching of many elements. Ferrihydrite was supersaturated in the leachate from the 14 and 18 °C columns, which showed the oxidation of pyrrhotite and olivine and the precipitation of ferrihydrite. The cumulative mass of Zn leached out was highest at 10 °C, which might be the threshold temperature for the leaching of Zn.