bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of de novo mutations in a schizophrenia case-parent trio by induced pluripotent stem cell based in vitro disease-modeling: Convergence of schizophrenia and autism-related cellular phenotypes
Authors: Hathy Edit , Szabó Eszter , Varga Nóra , Erdei Zsuzsa , Tordai Csongor , Czehlár Boróka , Baradits Máté , Jezsó Bálint , Koller Júlia , Nagy László , Molnár Mária Judit , Homolya László , Nemoda Zsófia , Apáti Ágota , Réthelyi János M
Published: October 2020

Background: De novo mutations (DNMs) have been implicated in the etiology of schizophrenia (SZ), a chronic debilitating psychiatric disorder characterized by hallucinations, delusions, cognitive dysfunction and decreased community functioning. Several DNMs have been identified by examining SZ cases and their unaffected parents, however in most cases the biological significance of these mutations remains elusive. To overcome this limitation, we have developed an approach of using induced pluripotent stem cell (iPSC) lines from each member of a SZ case-parent trio, in order to investigate the effects of DNMs in cellular progenies of interest, particularly in dentate gyrus neuronal progenitors.Methods: We identified a male SZ patient characterized by early disease onset and negative symptoms, who is a carrier of 3 non-synonymous DNMs in genes LRRC7, KHSRP, and KIR2DL1. iPSC lines were generated from his and his parents’ peripheral blood mononuclear cells using Sendai virus-based reprogramming and differentiated into neuronal progenitor cells (NPCs) and hippocampal dentate gyrus granule cells. We used RNASeq to explore transcriptomic differences, and calcium (Ca2+) imaging, cell proliferation, migration, oxidative stress, and mitochondrial assays to characterize the investigated NPC lines. Results: NPCs derived from the SZ patient exhibited transcriptomic differences related to Wnt-signaling, neuronal differentiation, axonal guidance and synaptic function, and decreased Ca2+ reactivity to glutamate. Moreover, we could observe increased cellular proliferation, and alterations in mitochondrial quantity and morphology.Conclusions: The approach of reprograming case-parent trios represents an opportunity for investigating the molecular effects of disease-causing mutations, and comparing these in cell lines with reduced variation in genetic background. Our results are indicative of a partial overlap between schizophrenia and autism-related phenotypes in the investigated family.Limitations: Our study investigated only one family, therefore the generalizability of findings is limited. We could not derive iPSCs from two other siblings to test for possible genetic effects in the family that are not driven by DNMs. The transcriptomic and functional assays were limited to the NPC stage, although these variables should also be investigated at the mature neuronal stage.
Barriers and drivers to capacity-building in global mental health projects
Authors: Endale Tarik , Qureshi Onaiza , Ryan Grace Kathryn , Esponda Georgina Miguel , Verhey Ruth , Eaton Julian , De Silva Mary , Murphy Jill
Published: October 2020

BackgroundThe global shortage of mental health workers is a significant barrier to the implementation and scale-up of mental health services. Partially as a result of this shortage, approximately 85% of people with mental, neurological and substance-use disorders in low- and middle-income countries do not receive care. Consequently, developing and implementing scalable solutions for mental health capacity-building has been identified as a priority in global mental health. There remains limited evidence to inform best practices for capacity building in global mental health. As one in a series of four papers on factors affecting the implementation of mental health projects in low- and middle-income countries, this paper reflects on the experiences of Global Mental Health grantees funded by Grand Challenges Canada, focusing on the barriers to and drivers of capacity-building.MethodsBetween June 2014 and May 2017, current or former Grand Challenges Canada Global Mental Health grantees were recruited using purposive sampling. N=29 grantees participated in semi-structured qualitative interviews, representing projects in Central America and the Caribbean (n=4), South America (n=1), West Africa (n=4), East Africa (n=6), South Asia (n=11) and Southeast Asia (n=3). Based on the results of a quantitative analysis of project outcomes using a portfolio-level Theory of Change framework, six key themes were identified as important to implementation success. As part of a larger multi-method study, this paper utilized a framework analysis to explore the themes related to capacity-building.ResultsStudy participants described barriers and facilitators to capacity building within three broad themes: 1) training, 2) supervision, and 3) quality assurance. Running throughout these thematic areas were the crosscutting themes of contextual understanding, human resources, and sustainability. Additionally, participants described approaches and mechanisms for successful capacity building.ConclusionsThis study demonstrates the importance of capacity building to global mental health research and implementation, its relationship to stakeholder engagement and service delivery, and the implications for funders, implementers, and researchers alike. Investment in formative research, contextual understanding, stakeholder engagement, policy influence, and integration into existing systems of education and service delivery is crucial for the success of capacity building efforts.
Canopy airspace of riparian forest mitigates soil N2O emission during hot moments
Authors: Mander Ülo , Krasnova Alisa , Escuer-Gatius Jordi , Espenberg Mikk , Schindler Thomas , Machacova Katerina , Pärn Jaan , Maddison Martin , Megonigal Patrick , Pihlatie Mari , Kasak Kuno , Niinemets Ülo , Junninen Heikki , Soosaar Kaido
Published: October 2020

Riparian forests are known as hot spots of N cycling in landscapes and climate warming speeds up the cycle. Here we present results from the first multi-annual high temporal-frequency study of soil, stem and ecosystem (eddy covariance) fluxes of N2O from a typical riparian forest in Europe.Hot moments (extreme events of N2O emission) last a quarter of the study period but contribute more than a half of soil fluxes. For the first time we demonstrate that high soil emissions of N2O do not reach the ecosystem level. During the drought onset, soil N2O emission peaks at intermediate soil water content. Rapid water content change is the main determinant of the emissions. The freeze–thaw period is another hot moment. However, according to the eddy covariance measurements the riparian forest is a modest source of N2O. We propose photochemical reactions and dissolution in canopy-space water as consumption mechanisms.
Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate Ras/MAPK, Wnt/ß-catenin, and mTOR signaling during corticogenesis
Authors: Casingal Cristine R. , Kikkawa Takako , Inada Hitoshi , Sasaki Yukio , Osumi Noriko
Published: October 2020

Corticogenesis is one of the most critical and complicated processes during embryonic brain development. Any slight impairment in corticogenesis could cause neurodevelopmental disorders such as Fragile X syndrome (FXS), of which symptoms contain intellectual disability (ID) and autism spectrum disorder (ASD). Fragile X mental retardation protein (FMRP), an RNA-binding protein responsible for FXS, shows strong expression in neural stem/precursor cells (NPCs) during corticogenesis, although its function during brain development remains largely unknown. In this study, we attempted to identify the FMRP target mRNAs in the mouse cortical primordium using RNA immunoprecipitation sequencing analysis in the mouse embryonic brain. We identified 865 candidate genes as targets of FMRP involving 126 and 118 genes overlapped with ID and ASD-associated genes, respectively. These overlapped genes were enriched with those related to chromatin/chromosome organization and histone modifications, suggesting the involvement of FMRP in epigenetic regulation. We further identified a common set of 17 "core" genes involved in neurogenesis/FXS/ID/ASD, containing factors associated with Ras/mitogen-activated protein kinase, Wnt/ß-catenin, and mTOR pathways. We indeed showed overactivation of mTOR signaling via an increase in mTOR phosphorylation in the Fmr1 knockout (Fmr1 KO) neocortex. Our results provide further insight into the critical roles of FMRP in the developing brain, where dysfunction of FMRP may influence the regulation of its mRNA targets affecting signaling pathways and epigenetic modifications.
Identification of an RNA binding protein-related gene signature in hepatocellular carcinoma patients
Authors: Wang Li , Zhou Na , Qu Jialin , Jiang Man , Zhang Xiaochun
Published: October 2020

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality among all human cancers. Studies have demonstrated that RNA binding proteins (RBPs) involved in the biological process of cancers including hepatocellular cancer. In this study, we aim to identify clinical value of RNA binding proteins for hepatocellular carcinoma.Methods: We analyses the data of HCC that downloaded from the Cancer Genome Atlas (TCGA) database and determined the differently expressed of RBPs between cancer and normal tissues. We further elucidate the function of RBPs by utilized Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gene signature of SMG5, EZH2, FBLL1, ZNF239, IGF2BP3 were generated by performed the univariate and multivariate Cox regression and LASSO regression analysis. CIBERSORT analysis was used to evaluation of tumor-infiltrating immune cells in different group. We built and verify a prognosis nomogram base on RBPs-related genes. Gene signature was validated by the International Cancer Genome Consortium (ICGC) database. The expressions of RBPs-related genes were validated by using Oncomine database, and the Human Protein Atlas.Result: Most of RBPs-related genes were significantly different in cancer and normal tissue. The survival of patients in the different group was statistically different. The Gene signature showed good performance for predicting the survival of HCC patients by having a better area under the receiver operating characteristic curve than other clinicopathological parameters (AUC=0.758). The patients in the high-risk group were more likely to have a higher Macrophages M0. Conclusion: Gene signature constructed by RNA binding proteins can be independent risk factors for hepatocellular carcinoma patients.
Cardiac Tyrosine Hydroxylase Activation and MB-COMT in Dyskinetic Monkeys 
Authors: Cuenca-Bermejo Lorena , Almela Pilar , Gallo-Soljancic Pablo , Yuste Jose E. , Pablos Vicente de , Bautista-Hernández Víctor , Fernández-Villalba Emiliano , Laorden María-Luisa , Herrero María-Trinidad
Published: October 2020

Background: The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it . Methods: We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). Results: The number of dopaminergic neurons in the Substantia Nigra pars compacta and the optical density of TH+ fibers and dopamine transporter in the striatum were significantly decreased in all MPTP-intoxicated monkeys. MPTP- and MPTP+L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP+L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP+L-DOPA-treated animals. However, we found no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in NA metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment. Conclusions: These results could help to elucidate the possible role of alterations in the catecholaminergic system that can contribute to noradrenergic deficiency in the hearts of PD patients. Therefore, this information might be relevant to clinical field, contributing to the therapeutic design of the disease.
Reducing Drug-use Harms among Higher Education Students: X Contextual-Behaviour Change Digital Intervention Development Using the Behaviour Change Wheel
Authors: Vasiliou Vasilis S. , Dockray Samantha , Dick Samantha , Davoren Martin P. , Heavin Ciara , Linehan Conor , Byrne Michael
Published: October 2020

Background: Digital harm-reduction interventions typically focus on people with severe drug-use problems, yet, these interventions have a moderate effectiveness on drug-users with lower levels of risk of harm. The difference in effectiveness may be explained by differences in behavioural patterns between the two groupings. Harnessing behavioural theories to understand what is at the core of drug-use behaviours to map the content of new interventions can improve the effectiveness of interventions for lower-risk drug-users. This is the first study to systematically apply the Behaviour Change Wheel (BCW) to understand the components, influencing capabilities, opportunities, and motivations (COM-B) of higher education students to change their drug-use behaviour. This is also the first study which identifies specific patterns of behaviours likely to be most responsive to harm reduction practices through the use of the Theoretical Domain Framework (TDF). Methods: We first conducted an online survey and a Delphi exercise to understand the factors influencing COM-B components of higher education students to change drug-use. Subsequently, we mapped all evidence onto the COM-B and the TDF to identify clusters of behaviours to target for change using a pattern-based discourse analysis. Finally, a series of multidisciplinary group meetings identified the intervention functions- the means by which the intervention change targeted behaviours and the Behavioural Change Techniques (BCTs) involved using the behaviour change technique taxonomy (v.1). Results: Twenty nine BCTs relevant to harm-reduction practices were identified and mapped across five intervention functions (education, modelling, persuasion, incentivization, and training) and five policy categories (communication/marketing, guidelines, regulation, service provision and environmental/social planning). These BCTs were distributed across eight identified saturated clusters of behaviours this intervention attempts to change. Conclusions: The BCTs identified will inform the development of a digitally delivered behaviour change intervention that focuses on increasing mindful decision-making with respect to drug-use and promotes alternatives to drug-use activities. The findings can also inform implementation scientists in applying context-specific harm-reduction practices in higher education. Examples of how the eight identified clusters of target behaviours are mapped across the COM-B components and the TDF are provided, along with suggestions of implementation practices for harm -reduction targeting students in higher education.
Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer
Authors: Liu Yaqian , Pan Bo , Qu Weikun , Cao Yilong , Li Jun , Zhao Haidong
Published: October 2020

Background: Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.Methods: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases.Results: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, we identified that FBXO1 was an excellent molecular biomarker and therapeutic target for BC. Conclusion: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with BC.
CAEV-Surrounding Objects Detection and Tracking for Autonomous Driving Using Lidar and Radar Fusion
Authors: Liu Ze , Cai Feng Ying
Published: October 2020

Radar and Lidar are two environmental sensors commonly used in autonomous vehicles，Lidars are accurate in determining objects’ positions but significantly less accurate on measuring their velocities. However, Radars are more accurate on measuring objects velocities but less accurate on determining their positions as they have a lower spatial resolution. In order to compensate for the low detection accuracy, incomplete target attributes and poor environmental adaptability of single sensors such as Radar and LIDAR, we proposed an effective method for high-precision detection and tracking of surrounding targets of autonomous vehicles. By employing the Unscented Kalman Filter, radar and LIDAR information is effectively fused to achieve high-precision detection of the position and speed information of targets around the autonomous vehicle. Finally, we do a variety of driving environment under the real car algorithm verification test. The experimental results show that the proposed sensor fusion method can effectively detect and track the vehicle peripheral targets with high accuracy. Compared with a single sensor, it has obvious advantages and can improve the intelligence level of driverless cars.
Problems of the use of lightweight cement in oil and gas well fixing and possible solutions
Authors: Buglov N. A. , Butakova L. A. , Bocharnikov M. V.
Published: October 2020

The article presents the results of the selection of the grouting mortar made out of the cement that does not comply with the state standard (GOST) for cementing the upper part of the column during the construction of an oil well. The object of study was the cement grade PСT III-ob 5-50 GOST 1581-96. The study used the additives that, according to the literary sources, are able to enhance the cement technological parameters. The additives were calcium chloride (CaСl2), sodium chloride, magnesium chloride (MgCl2), gypsum (CaSO4·2H2O), marble chips (MK-100), silica fume (МК-65, МК-85), caustic soda (NaOH) and calcined soda (Na2CO3), as well as high and low viscosity polyanionic cellulose. The following technological parameters were determined: the mortar density, the mortar paste spreadability, water separation, the thickening of the mortar, the ultimate bending and ultimate compression strength of the cement stone. The study was conducted taking into account the domestic and international standards. The test results show that the use of the agents such as NaCl, MgCl2, CaСl2, Easy SET, МК-100, and CaSO4·2H2O enhances the water separation of the mortar and the strength properties of the cement stone. However, the agents used to improve water separation (low viscosity polyanionic cellulose, high viscosity polyanionic cellulose, Na2CO3, МК-65, and МК-85) significantly reduce the strength properties of the cement stone. The columns can be fixed with the above mentioned cement using agents such as CaCl2(2 % of the cement mass), NaCl (1.2 %), MgCl2(1 %), and the hardening agent Easy SET (1 % of the cement mass).
Crystal chemistry and high-temperature vibrational spectra of humite and norbergite: Fluorine and titanium in humite-group minerals
Authors: Liu Dan , Hirner Sarah M. , Smyth Joseph R. , Zhang Junfeng , Shi Xiaochao , Wang Xiang , Zhu Xi , Ye Yu
Published: October 2020

The humite-group minerals along the brucite-olivine join may be important dense hydrous magnesium silicate (DHMS) phases in the subducting slab. Fluorine and titanium can be incorporated into their structures through the substitutions (OH)– = F– and Mg2+ + 2(OH)– = Ti4+ + 2O2–. These substitutions have significant effects on the hydrogen bonding behavior in the structures. Structure refinements and in situ high-temperature Raman and Fourier transform infrared (FTIR) measurements were conducted on natural humite and norbergite crystals. Both minerals crystallize in space group Pbnm, and their isobaric Grüneisen parameters for the lattice and SiO4 internal vibrations are compared with those of chondrodite, clinohumite, brucite, and forsterite. For the humite-group minerals, the OH-stretching modes above 3450 cm–1 are affected by local H-H repulsion, whereas the behavior of those below 3450 cm–1 can be explained by F– and Ti4+ substitutions, either of which may relieve the H-H repulsion effect. The Raman-active OH bands below 3450 cm–1 are affected by Ti4+ substitution, while the IR-active bands can be affected by either F– or Ti4+ substitutions. Based on an analysis of the high-T Raman and FTIR spectra, the OH vibrations above and below 3450 cm–1 behave differently as a function of temperature, and similar behavior has also been observed for other dense hydrous silicate phases in the hydrous peridotite system. Hence, the lengths of the oxygen-oxygen edges in MgO6 octahedra where protonation can occur become similar to each other at elevated temperatures. This may provide an atomistic explanation for the electrical conductivity properties of DHMS phases at high temperatures.
The exploration of a Temporal Convolutional Network combined with Encoder-Decoder framework for runoff forecasting
Authors: Lin Kangling , Sheng Sheng , Zhou Yanlai , Liu Feng , Li Zhiyu , Chen Hua , Xu Chong-Yu , Chen Jie , Guo Shenglian
Published: October 2020

The Temporal Convolutional Network (TCN) and TCN combined with the Encoder-Decoder architecture (TCN-ED) are proposed to forecast runoff in this study. Both models are trained and tested using the hourly data in the Jianxi basin, China. The results indicate that the forecast horizon has a great impact on the forecast ability, and the concentration time of the basin is a critical threshold to the effective forecast horizon for both models. Both models perform poorly in the low flow and well in the medium and high flow at most forecast horizons, while it is subject to the forecast horizon in forecasting peak flow. TCN-ED has better performance than TCN in runoff forecasting, with higher accuracy, better stability, and insensitivity to fluctuations in the rainfall process. Therefore, TCN-ED is an effective deep learning solution in runoff forecasting within an appropriate forecast horizon.
When is shared sanitation acceptable in low-income urban settlements? A user perspective on shared sanitation quality in Kumasi, Kisumu and Dhaka
Authors: Schelbert Vasco , Meili Dario , Alam Mahbub-Ul , Simiyu Sheillah , Antwi-Agyei Prince , Adjei Kwaku Amaning , Dwumfour-Asare Bismark , Rahman Mahbubur , Ferdous Sharika , Sarker Supta , Günther Isabel , Lüthi Christoph
Published: October 2020

Shared sanitation facilities (SSFs) have contributed considerably to sanitation access in many low-income settlements. While many SSFs are of unacceptable quality, others have been found to be a hygienically safe and a socially and economically viable sanitation option. Within its framework, the WHO/UNICEF Joint Monitoring Programme (JMP), evaluating progress on the Sustainable Development Goals, considers shared sanitation as ‘limited sanitation’. Overall, there is uncertainty about the criteria to distinguish between unacceptable and acceptable quality of SSF. In our study, we used a user-centred qualitative approach in low-income urban settlements in Kumasi (Ghana), Kisumu (Kenya) and Dhaka (Bangladesh) and conducted 17 focus group discussions to evaluate how SSF users define the quality of an SSF and which aspects they consider as essential priorities for good-quality SSF. In descending order, the user priorities identified are: immediate water access, cleanliness, gender-separated toilets, flush toilets, lighting for use at night, lockable/functional doors, tiling, handwashing stations and privacy. This list can serve as input to the sanitation guidelines, local building codes and the establishment of minimum national sanitation standards. SSFs that meet these minimal criteria can then be promoted as an incremental step when individual household facilities are not feasible.
Physicochemical properties of irrigation water in western Himalayas, Pakistan
Authors: Abbas Haider , Khan Muhammad Zafar , Begum Farida , Raut Nani , Gurung Smriti
Published: October 2020

Appropriate irrigation water quality is essential for maintaining soil properties. This study investigates numerous physicochemical properties of irrigation water in three Himalayan valleys in northern Pakistan, receiving water from different sources. A total of 36 samples (3 replicates from four points at each site) were randomly collected and analyzed following standard laboratory techniques. The results revealed that most of the physicochemical parameters were within the permissible limits as specified by FAO, USEPA, and WWF for agriculture water. However, the total dissolved solids, potassium, mercury, nickel, and cadmium were found beyond the recommended ranges. Analysis of variance indicated that the mean values of various constituents differed significantly across the sources. Among the water sources, the mix of spring and glacial meltwater was found to contain maximum parameters within the permissible limits. The study recommends further investigating the implications of the existing water quality parameters on crop productivity and human health.
Hydrated-electron-based short chain perfluorosulfonic acid decomposition in VUV/sulfite system
Authors: Gu Yurong , Dong Zijun , Zhang Xi , Han Qi , Li Yongbing
Published: October 2020

Perfluorosulfonic acids (PFSAs) have attracted increasing attention due to their global distribution, high chemical stability and persistence. As a powerful reductant, hydrated electron () shows extraordinary reactivity towards halogenated organic substances like PFSAs. In this study, -based photo-decomposition of perfluorohexane sulfonate (PFHxS) in a VUV/sulfite system was investigated. The kobs of PFHxS decomposition in the studied system was 0.0049 ± 0.0005 min−1, which was 24.5-fold faster than that in a sole VUV system. It was demonstrated that was the main reactive species responsible for PFHxS decomposition. PFHxS decomposition kinetics were accelerated at higher initial solution pH and sulfite dosage, but were restrained when higher initial PFHxS concentration was introduced. Co-existence of chloride showed slight enhancement of PFHxS decomposition, whereas nitrate and bicarbonate suppressed PFHxS decomposition. Accompanying PFHxS decomposition, short chain perfluorocarboxylic acids (PFCAs) were detected as main intermediate products. PFHxS decomposition started with C-S bond fracture, followed by perfluoroalkyl radical hydrolysis reactions and perfluorohexanoic acid (PFHxA) formation. Afterwards, PFHxA was defluorinated by stepwise loss of CF2 units to generate other short chain PFCAs.
Survival analysis of water distribution network under intermittent water supply conditions
Authors: Mohammadi Ali , Jalili-Ghazizadeh Mohammadreza , Moslehi Iman , Yousefi-Khoshqalb Ehsan
Published: October 2020

Intermittent water supply (IWS) is established temporarily or continuously in many water distribution networks (WDNs) worldwide due to prolonged drought, low rainfall periods, water scarcity and high level of leakage. IWS causes several adverse consequences on the network operation, resulting in ineffective supply and demand management. This paper presents a survival analysis of the network elements, including water mains, service connections, and valves using the Kaplan-Meier approach to determine the survival probability and the probability of failure rates of events of interest. The objective is to explore the changes in failure rates of network elements after implementing an IWS scheme. The non-parametric survival method is applied to the large zone (Zone-5) of the WDN in Tehran (Iran) based on the frequency of failures before, during, and after the implementation of an IWS regime. The results show that the probability of failure rates significantly increase after implementing the IWS scheme, and can remain for several years after, even when the network returns to continuous water supply (CWS). The results of this study can assist utility managers to understand the detrimental effects of IWS systems on increasing failure rates.
Simultaneous adsorption of Cu2+ and Cr (VI) using HDTMA-modified zeolite: isotherm, kinetic, mechanism, and thermodynamic studies
Authors: Zekavat Soroosh Roshan , Raouf Fereshteh , Talesh Seyed Siamak Ashraf
Published: October 2020

Clinoptilolite modified by hexadecyltrimethylammonium bromide (HDTMA-Br) was used to simultaneously remove copper and hexavalent chromium from aqueous solutions. The surface properties of HDTMA-modified natural zeolite (HMNZ) were characterized using scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), zeta potential and Fourier transform infrared spectroscopy (FTIR) techniques. SEM images showed that surfactant is adsorbed on the surface of the zeolite, which is confirmed by the FTIR result. The results from BET demonstrated a reduction in the specific surface area and pore volume due to the presence of surfactant molecules on the external surface of zeolite. The effects of important parameters on adsorption efficiency of Cu2+ and Cr (VI) were evaluated by Box-Behnken design. The Langmuir isotherm provided the best fit to the equilibrium data of Cu2+ and Cr (VI), with the maximum adsorption capacity of 0.068 and 0.0093(mmol), respectively. The film diffusion mechanism was found to control the mass transfer, and the adsorption reactions were computed as endothermic for Cu2+ ( = 17.58 kJ) and exothermic for Cr (VI) ( −26.18 kJ). The results indicated that surfactant modification changes the surface charge of zeolite from negative to positive, which makes zeolites economic adsorbents with the possibility of simultaneous removal of cations and oxyanions. The results also showed that the removal efficiency of Cr (VI) increases in the presence of copper cations due to there being more positive sites on the adsorbent surface.
Evaluation of phenol removal via a spiral wound reverse osmosis process with different feed concentrations: simulation study
Authors: Al-Obaidi Mudhar A. , Mustafa Samir N. , Malek Kawther H.
Published: October 2020

Reverse osmosis (RO) process is progressively engaged in various industrial applications as a promising separation process in favour of classical methods. In this study, an earlier one-dimensional distributed model of RO process, developed by the author, is used to simulate the transport phenomena of phenol removal. The proposed model represented the process parameters as a function of longitudinal variation along the x-coordinate of feed side. The transport parameters of the membrane are optimised by the gEST parameter estimation tool of gPROMS. The model is verified against phenol removal experimental data for a pilot-scale spiral wound RO (SWRO) treatment system. The model has been used to explore the effects of key operating parameters on the phenol removal for five feed concentration cases.
Micro-pressure swirl reactor (MPSR) for efficient COD and nitrogen removal of high-concentration wastewater
Authors: Bian Dejun , Nie Zebing , Wang Fan , Ai Shengshu , Zhu Suiyi , Guo Haiyan
Published: October 2020

A micro-pressure swirl reactor (MPSR) was developed for carbon and nitrogen removal of wastewater, in which dissolved oxygen (DO) gradient and internal circulation could be created by setting the aerators along one side of the reactor, and micro-pressure could be realized by sealing most of the top cap and increasing the outlet water level. In this study, velocity and DO distribution in the reactor was measured, removal performance treating high-concentration wastewater was investigated, and the main functional microorganisms were analyzed. The experiment results indicated that there was stable swirl flow and spatial DO gradient in MPSR. Operated in sequencing batch reactor mode, distinct biological environments spatially and temporally were created. Under the average influent condition of chemical oxygen demand (COD) concentration of 2,884 mg/L and total nitrogen (TN) of 184 mg/L, COD removal efficiency and removal loading was 98% and 1.8 kgCOD/(m3·d) respectively, and TN removal efficiency and removal loading reached up to 90% and 0.11 kgTN/(m3·d) respectively. With efficient utilization of DO and simpler configuration for simultaneous nitrification and denitrification, the MPSR has the potential of treating high-concentration wastewater at lower cost.
Evaluating financial sustainability along the sanitation value chain using a financial flow simulator (eSOSView™)
Authors: Furlong Claire , Singh Shirish , Shrestha Nitesh , Sherpa Mingma Gyalzen , Lüthi Christoph , Zakaria Fiona , Brdjanovic Damir
Published: October 2020

A majority of the world's population use onsite sanitation systems, which store or treat excreta close to where it is generated. Sludge from these systems needs to be managed through a series of stages, known as the sanitation value chain. There is a huge diversity of service providers, not only within each part of the chain, but also along the chain bridging the different components. These service providers are linked not only by the flow of materials, but also by the transfer of money. Therefore for this system to be considered financially sustainable all services from the toilet to reuse or disposal need to be considered. A tool has been developed (eSOSView™) to simulate, evaluate, and optimise the financial flows along and within the sanitation value chain. In this paper eSOSView™ was tested, validated (using existing data), and piloted (including data collection). This paper demonstrates how eSOSView ™ can be used to evaluate different financial flow models, to assess financial sustainability in different parts of the sanitation value chain and optimise the financial sustainability along the sanitation value chain.
The Clinical Impact of Quantitative Cell-free DNA, KRAS, and BRAF Mutations on Response to Anti-EGFR Treatment in Patients with Metastatic Colorectal Cancer
Authors: Moradi-Marjaneh Reyhaneh , Asgharzadeh Fereshteh , Khordad Elnaz , Marjaneh Mahdi Moradi
Published: October 2020

:

Colorectal cancer (CRC) is one of the most common leading causes of cancer death in the world. Although
EGFR inhibitors have established efficacy in metastatic colorectal cancer (mCRC), some patients do not
respond to this treatment. The EGFR inhibitors' failure and acquired resistance are partly due to KRAS and
BRAF mutations. Thus, prognostic biomarkers that help to select eligible patients are highly in demand. To improve
patient selection, assessment of mutational status in circulating cell free DNA (cfDNA), which possibly
represents the dynamicity of tumor genetic status better than tumor tissue, could be advantageous. This review
summarizes the current knowledge of the prognostic value of cfDNA in patients with mCRC treated with
EGFR inhibitors with emphasis on the clinical importance of identification of KRAS and BRAF mutations.
Efficacy of Dexamethasone for the Treatment of COVID-19 Infection: A Perspective Review
Authors: Wahab Shadma , Ahmad Irfan , Usmani Shazia , Ahmad Md. Parwez
Published: October 2020

The current COVID-19 pandemic has provoked the urgent requirement to search for effective treatments since the implications are so huge globally as compared to the earlier pandemics. Momentarily, there has been no effective medicine for SARS-CoV-2 infection, and supportive care tends to be the most effective approach to treat COVID-19 patients. The rapidly growing awareness of SARS-CoV-2 virology offers a large number of possible drug targets. The World Health Organisation (WHO) is steadily updating the treatment protocol for COVID-19 based on the recent clinical trials. In the present review, we have summarised the possible mode of action, clinical evidence, consequences of dexamethasone as the therapeutic agent against Covid-19. Currently, many corticosteroids are being tested in ongoing randomised trials. Dexamethasone could come as the life-saving drug. Dexamethasone drug looks useful only in those patients who are already in a critical state. We might allow dexamethasone as a fascinating shot, if the drug proves to be clinically favourable for long-term health effects of Covid-19 recovered patients. It is commonly accepted to reinforce approved drugs in the fight against newly emerging diseases such as COVID-19 as these drugs have established pharmacokinetic profiles and protection. The current focus should be on the development of novel proven therapeutics along with vaccines. There is a need for high quality, more extensive, rapid and collaborative randomized controlled trials with more control groups.
New Strategy for Synthesis of Anticancer Active Piperastrol, Enastron Using Ammonium Sulfocyanate
Authors: Potdar Santoshkumar M. , Deshmukh Aishwarya R. , Waghmode Krishnakant T.
Published: October 2020

This report describes an efficient and mild approach for the synthesis of Piperastrol and
Enastron via a one-pot three-component cyclocondensation reaction employing ammonium sulfocyanate
(NH4SCN) on gram scale in isopropyl alcohol–PEG 400 medium. In this reaction, ammonium
sulfocyanate is not only the reacting component but also accelerates the rate of reaction to
afford Biginelli compounds. High yields, short reaction time and easy workup procedure are the
key advantages of the present protocol. Ammonium sulfocyanate is readily available, cheaper,
safer and industrially acceptable inorganic salt.
Dissolution Enhancement of Eplerenone using Solvent Melt Method
Authors: Agarwal Vijay , Kumar Vipin , Sharma Pankaj K.
Published: October 2020

Background:

Eplerenone (EPL) is a BCS class II drug, thus, having poor water solubility.
The poor water solubility of this drug leads to poor dissolution and ultimately shows poor bioavailability.
To overcome this problem, the solid dispersion of EPL was prepared in this study.

Methods:

This was accomplished by using the solvent melt method as the solid dispersion technique.
In this method, Pluronic F-68 and F-127 were used as the carrier and different formulations
were prepared using varying ratios of a drug and carrier (1:1, 1:2, 1:3, 1:4, 1:5). The mixture of
drug solution and carrier was prepared at 70°C, using the digital magnetic stirrer. The resultant mixture
was dried at 40°C in a hot air oven and optimized EPL-solid dispersion was undergone for
their characterization using drug content, drug entrapment efficiency (%) and drug loading content
(%), Scanning Electron Microscopy (SEM), Infra-Red spectroscopy, Differential Scanning
Calorimetry (DSC), stability study and in-vitro dissolution studies.

Results:

The result indicated that there was no interaction between EPL and Pluronics (Pluronic
F-68 & F-127), and optimized formulation (P127-2) of EPL-solid dispersion had encapsulation efficiency
> 95%. Experimental work also showed that optimized formulation has 31.7% of drug loading
content which was greater than other existing solid dispersion having less than 30% of drug
loading content. Out of different batches, the optimized batch exhibits the faster dissolution rate in
comparison to other batches. It released the almost total amount of drug (98.96%) in 30 minutes.
The stored ESM-solid dispersion also exhibited remarkable stability and remains in a solid state,
when it was exposed to 25°C/60% relative humidity and room temperature (38ºC) for two months.
Such stability was confirmed by DSC method. The DSC thermogram of optimized formulation exhibited
a melting endotherm at an onset temperature of 160°C, a peak temperature of 165°C and a
heat of fusion of 25.68 J/gm. Similarly, the DSC thermogram of the physical mixture of bulk EPL/-
pluronic F-127 also exhibited the onset of temperature at 165°C, and a peak temperature at 171°C.
Thus, the result indicated that both samples showed almost similar DSC pattern and no sample altered
its state after the treatment of temperature and humidity used in stability testing. SEM study
was also performed in this research and the result indicated that the particle size of optimized formulation
was varied, having irregular matrices due to the porous nature of the carrier.

Conclusion:

Based on different findings, it can be concluded that the solvent melt method could be
a potential method for preparing the solid dispersion of EPL like BCS class-II Drugs and will be
able to solve the dissolution and solubilization related problem of poorly soluble drugs.
Dose Formulation, Biodistribution and PET Imaging Studies of a First-in-Class Fluorine-18 Organophosphorus Cholinesterase Inhibitor Tracer in Rat
Authors: Neumann Kiel D. , Blecha Joseph E. , Chao Chih-Kai , Huynh Tony , Zinn Kurt R. , VanBrocklin Henry F. , Thompson Charles M. , Gerdes John M.
Published: October 2020

Background::

To investigate dynamic live tissue organophosphorus nerve agent
uptake and distribution fates resulting in acetylcholinesterase inhibition, we recently reported
the first-in-class fluorine-18 [18F] radiolabeled Positron Emission Tomography (PET) imaging
tracer known as [18F]O-(2-fluoroethyl)-O-(p-nitrophenyl)methylphosphonate. This tracer
has been initially studied in live rats with PET imaging.

Objective.:

We sought to evaluate the PET tracer in vivo using a new dose formulation of saline,
ethanol and L-ascorbic acid, and compare the influence of this formulation on in vivo
tracer performance to previous data collected using a CH3CN:PBS formulation.

Methods::

A high molar activity [18F]tracer radiosynthesis was used. Doses were formulated
as saline, ethanol (≤ 1%) and L-ascorbic acid (0.1%), pH 4.0-4.5. Stability was evaluated to 6
h. Dose injection (i.v.) into male rats was followed by either ex vivo biodistribution profiling
at 5, 30, 90 min, or dynamic 90 min PET imaging. Rat biodistribution and PET imaging data
were compared.

Results and Discussion::

An optimized radiosynthesis (8 ± 2 % RCY) resulted in stable
doses for 6 h (>99%). Arterial blood included a tracer and a single metabolite. The ex vivo
biodistribution and live tissue PET imaging data revealed rapid radioactivity uptake and distributed
tissue levels: heart and lung, highest; liver, moderate; and brain, lowest.

Conclusions::

Imaging and biodistribution data were highly correlated with expected radioactivity
tissue uptake and distribution in target organs. Lower brain radioactivity levels by PET
imaging were found for the new formulation (saline, 1% L-ascorbic acid, < 1% ethanol) as
compared to the established CH3CN:PBS formulation. Overall, we found that the i.v. dose
formulation changed the in vivo profile of an organophosphorus PET tracer that is considered
an important finding for future organophosphorus PET tracer studies.
Integrating Genomics and Clinical Data for Statistical Analysis by Using GEnome MINIng (GEMINI) and Fast Healthcare Interoperability Resources (FHIR): System Design and Implementation
Authors: Gruendner Julian , Wolf Nicolas , Tögel Lars , Haller Florian , Prokosch Hans-Ulrich , Christoph Jan
Published: October 2020

Background

The introduction of next-generation sequencing (NGS) into molecular cancer diagnostics has led to an increase in the data available for the identification and evaluation of driver mutations and for defining personalized cancer treatment regimens. The meaningful combination of omics data, ie, pathogenic gene variants and alterations with other patient data, to understand the full picture of malignancy has been challenging.

Objective

This study describes the implementation of a system capable of processing, analyzing, and subsequently combining NGS data with other clinical patient data for analysis within and across institutions.

Methods

On the basis of the already existing NGS analysis workflows for the identification of malignant gene variants at the Institute of Pathology of the University Hospital Erlangen, we defined basic requirements on an NGS processing and analysis pipeline and implemented a pipeline based on the GEMINI (GEnome MINIng) open source genetic variation database. For the purpose of validation, this pipeline was applied to data from the 1000 Genomes Project and subsequently to NGS data derived from 206 patients of a local hospital. We further integrated the pipeline into existing structures of data integration centers at the University Hospital Erlangen and combined NGS data with local nongenomic patient-derived data available in Fast Healthcare Interoperability Resources format.

Results

Using data from the 1000 Genomes Project and from the patient cohort as input, the implemented system produced the same results as already established methodologies. Further, it satisfied all our identified requirements and was successfully integrated into the existing infrastructure. Finally, we showed in an exemplary analysis how the data could be quickly loaded into and analyzed in KETOS, a web-based analysis platform for statistical analysis and clinical decision support.

Conclusions

This study demonstrates that the GEMINI open source database can be augmented to create an NGS analysis pipeline. The pipeline generates high-quality results consistent with the already established workflows for gene variant annotation and pathological evaluation. We further demonstrate how NGS-derived genomic and other clinical data can be combined for further statistical analysis, thereby providing for data integration using standardized vocabularies and methods. Finally, we demonstrate the feasibility of the pipeline integration into hospital workflows by providing an exemplary integration into the data integration center infrastructure, which is currently being established across Germany.