bluuebunny/crossref_metadata_2025 huggingface dataset:
Gilteritinib administration in a hemodialysis patient
Authors: Tollkuci Eris , Tran Tiffany , Myers Rebecca
Published: November 2020

Introduction

Gilteritinib is a multitargeted tyrosine kinase inhibitor (TKI) approved by the Food and Drug Administration (FDA) for acute myeloid leukemia (AML) with a FMS-related tyrosine kinase 3 (FLT3) mutation. The pharmacokinetics of gilteritinib in the setting of severe renal impairment (creatinine clearance [CrCl] 15-29 mL/min utilizing Cockcroft-Gault method) and end-stage renal disease are unknown. Gilteritinib is primarily metabolized by the liver through the CYP3A4 enzyme and is eliminated in both the feces and urine. Its excretion is primarily through the fecal route, accounting for 64.5% of the recovered dose. Only about 16.4% of the recovered dose has been detected in the urine of human subjects.

Case Report

We describe our patient case documenting the administration of gilteritinib in the setting of end-stage renal disease (ESRD) and hemodialysis (HD). Management and Outcomes: Our patient was initiated on single agent gilteritinib 120 mg by mouth once daily for relapse FLT3-TDK positive AML. Treatment course was complicated by pancytopenia, neutropenic fever, and staphylococcus lugdunensis bacteremia requiring temporary interruption of therapy.

Discussion

Given that gilteritinib is metabolized by the liver and eliminated primarily in the feces, one does not expect an increase in toxicity related to impaired renal function. Although this report describes the successful utilization of gilteritinib, caution should be exercised when administering in patient populations with end organ disease, and patient comorbidities should be taken into account.
Four Levels of Interpretive Development Based on Tilden’s Principle of Wholeness
Authors: Kohl Jon
Published: November 2020

Freeman Tilden argues in his Fifth Principle of Interpretation the importance of interpreting wholes for whole people. Yet his examples reveal that in demonstrating wholeness in the form of an interpretive theme, he uses but one perspective for each of his interpreted objects (i.e., birds and places). Based on the premise that every object is enacted through one of multiple possible perspectives, to interpret from a single perspective then must be partial because it reveals only a part of an object, thus falling short of wholeness. This multiplicity of perspectives results in a wholeness interpretation spectrum from a single to a near infinite number of perspectives along which all interpreters fall. This article posits four levels on this scale from pre-interpretation whereby no real interpretation occurs to a post-interpretive enactment whereby the interpreter integrates multiple non-consensus perspectives for a much richer or more whole—holistic—interpretation.
Field Trips and the Experiential Learning Cycle
Authors: Stern Marc J. , Powell Robert B.
Published: November 2020

Drawing on results from a recent national study, we draw attention to the importance of the experiential learning cycle for enhancing meaningful outcomes of interpretive and educational experiences. The experiential learning cycle involves participating in a concrete experience, reflecting on that experience, drawing out lessons learned and principles from that reflection, and putting that knowledge to work in a new situation. Recent studies reveal that attention to completing all four stages of the experiential learning cycle can enhance positive outcomes for participants in educational and interpretive experiences. We discuss what this might look like in practice for interpreter and educators interacting with visiting groups.
The impact of COVID-19 on the travel and leisure industry returns: Some international evidence
Authors: Lee Chien-Chiang , Chen Mei-Ping
Published: November 2020

This research crucially investigates COVID-19 variables’ impacts on the changing distributions of travel and leisure industry returns across 65 countries via a quantile regression model that uses daily data from December 2019 to May 2020 to provide early evidences from a panel of countries. We find that the change rate in COVID-19 deaths exerts more substantial negative effects on industry returns at majority quantiles than does the impact from the number of confirmed cases. The latter number only saliently and negatively influences the lowest return quantiles, revealing a nonlinear effect of confirmed cases. The study identifies a V-shape correlation between the number of cases recovered and travel and leisure industry returns (i.e. a negative impact at the lower quantiles, but a positive impact at higher quantiles) across return quantiles. This likely denotes that confirmed cases grow exponentially and that their effect may overwhelm the impact of the number of recovered cases. Lastly, this study presents a positive correlation between government response stringency index and returns.
Influence of rubber pads on vibration levels and structural behavior of subway tunnels
Authors: Khalil Ahmed A , Metwally Kamal G , Ahmed Nasser Z
Published: November 2020

The principal aim of this paper is to analyze the impact of rubber pad systems on levels of vibrations and values of stresses and deformations induced in the subway tunnel segments. Thus, the 3D model has been selected to be isotropically simulated in the ANSYS program to conduct a finite element analysis. Therefore, the proposed track system in the tunnel of line 4 of the Greater Cairo Metro has been selected as an analytical and simulation case study. The impact of using eight different values for the stiffness of the rubber pad system in the case of a single tunnel has been analyzed. The results showed that levels of vibrations are significantly affected and are in logarithmic correlation with the stiffness. Also, the impact of the stiffness on the deformations and stresses are determined as well as mathematical models connecting the different parameters have been introduced.
Microstructure and mechanical properties of aluminium alloy coatings on alumina applied by friction surfacing
Authors: Atil HB , Leonhardt M , Grant RJ , Barrans S
Published: November 2020

By combining lightweight metal alloys with ceramics, it is possible to adapt material properties on stressed parts and thus increase stiffness and/or change the thermal resistance: yet joining such materials is problematic due to the poor wettability of ceramics by molten metals. In this work, the technique of friction surfacing is used to connect alumina (Al2O3) with an aluminium alloy (EN-AW 5083). Despite the fact that Al2O3 has a relatively high coefficient of thermal expansion and a low thermal shock resistance, specimens have been produced showing encouraging results. In order to compensate for these material properties the substrate was preheated to a minimum of 150°C. In tests bonding strengths reached 47.8 MPa and coating thicknesses of 213 μm were achieved; results which are comparable with conventional thermally sprayed coatings. Bonding strengths were determined by using a pull-off adhesion tester and the coating thickness was measured with a laser scanning microscope. Analysis of the joint zone shows no clear evidence of chemical reactions (intermetallic compounds) or diffusion. Mechanical interlocking can only be shown to be accountable for 16% of the bonding strength with investigations turning towards van der Waals forces and their contribution to adhesion.
Mitophagy promotes the stemness of bone marrow-derived mesenchymal stem cells
Authors: Feng Xiaorong , Yin Wen , Wang Jialing , Feng Li , Kang Y James
Published: November 2020

Previous studies demonstrated that mitochondrial fission arguments the stemness of bone marrow-derived mesenchymal stem cells (BMSCs). Because mitophagy is critical in removing damaged or surplus mitochondrial fragments and maintaining mitochondrial integrity, the present study was undertaken to test the hypothesis that mitophagy is involved in mitochondrial fission-enhanced stemness of BMSCs. Primary cultures of rat BMSCs were treated with tyrphostin A9 (TA9, a potent inducer of mitochondrial fission) to increase mitochondrial fission, which was accompanied by enhanced mitophagy as defined by increased co-staining of MitoTracker Green for mitochondria and LysoTracker Deep Red for lysosomes, as well as the increased co-localization of autophagy markers (LC3B, P62) and mitochondrial marker (Tom20). A mitochondrial uncoupler, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) was used to promote mitophagy, which was confirmed by an increased co-localization of mitochondrial and lysosome biomarkers. The argumentation of mitophagy was associated with enhanced stemness of BMSCs as defined by increased expression of stemness markers Oct4 and Sox2, and enhanced induction of BMSCs to adipocytes or osteocytes. Conversely, transfection of BMSCs with siRNA targeting mitophagy-essential genes Pink1/ Prkn led to diminished stemness of the stem cells, as defined by depressed stemness markers. Importantly, concomitant promotion of mitochondrial fission and inhibition of mitophagy suppressed the stemness of BMSCs. These results thus demonstrate that mitophagy is critically involved in mitochondrial fission promotion of the stemness of BMSCs.
Animal models of regenerative medicine for biological treatment approaches of degenerative disc diseases
Authors: Mern Demissew Shenegelegn , Walsen Tanja , Beierfuß Anja , Thomé Claudius
Published: November 2020

Degenerative disc disease (DDD) is a painful, chronic and progressive disease, which is characterized by inflammation, structural and biological deterioration of the intervertebral disc (IVD) tissues. DDD is specified as cell-, age-, and genetic-dependent degenerative process that can be accelerated by environmental factors. It is one of the major causes of chronic back pain and disability affecting millions of people globally. Current treatment options, such as physical rehabilitation, pain management, and surgical intervention, can provide only temporary pain relief. Different animal models have been used to study the process of IVD degeneration and develop therapeutic options that may restore the structure and function of degenerative discs. Several research works have depicted considerable progress in understanding the biological basis of disc degeneration and the therapeutic potentials of cell transplantation, gene therapy, applications of supporting biomaterials and bioactive factors, or a combination thereof. Since animal models play increasingly significant roles in treatment approaches of DDD, we conducted an electronic database search on Medline through June 2020 to identify, compare, and discuss publications regarding biological therapeutic approaches of DDD that based on intradiscal treatment strategies. We provide an up-to-date overview of biological treatment strategies in animal models including mouse, rat, rabbit, porcine, bovine, ovine, caprine, canine, and primate models. Although no animal model could profoundly reproduce the clinical conditions in humans; animal models have played important roles in specifying our knowledge about the pathophysiology of DDD. They are crucial for developing new therapy approaches for clinical applications.
Modeling and analyzing malware diffusion in wireless sensor networks based on cellular automaton
Authors: Zhang Hong , Shen Shigen , Cao Qiying , Wu Xiaojun , Liu Shaofeng
Published: November 2020

Wireless sensor networks, as a multi-hop self-organized network system formed by wireless communication, are vulnerable to malware diffusion by breaking the data confidentiality and service availability, owing to their low configuration and weak defense mechanism. To reveal the rules of malware diffusion in the really deployed wireless sensor networks, we propose a model called Malware Diffusion Based on Cellular Automaton to describe the dynamics of malware diffusion based on cellular automaton. According to the model, we first analyze and obtain the differential equations, which can reflect the various state dynamics of sensor nodes with cellular automaton. Then, we attain the equilibrium points of the model Malware Diffusion Based on Cellular Automaton to determine the threshold for whether malware will diffuse or die out in wireless sensor networks. Furthermore, we compute the basic regeneration number of the model Malware Diffusion Based on Cellular Automaton using the next-generation matrix and prove the stability of the equilibrium points. Finally, via experimental simulation, we verify the effectiveness of the model Malware Diffusion Based on Cellular Automaton, which can provide administrators with the theoretical guidance on suppressing malware diffusion in wireless sensor networks.
Performance and emission analysis of high purity biodiesel blends in diesel engine
Authors: Khan Muhammad Bilal , Kazim Ali Hussain , Shabbir Aqsa , Farooq Muhammad , Farooq Haroon , Ali Qasim , Danish Muhammad Rohail , Shahid Qureshi Nabeel , Abdul Rab Hamza
Published: November 2020

Biodiesel, a biodegradable, highly oxygenated and renewable energy resource, is produced by esterification of vegetable oils. This work focuses on using electrolytic separation and emulsification to produce purer biodiesel having high cetane index of 61.4. Vegetable oil mixture is used as feedstock. Maximum production yield is 84%. The decrease in engine peak torque was minimum for B5 at 1.94% while maximum decrease was for B20. B5 show a slight increase in power while B20 and B50 show significant drop. For all test speeds, B50 shows higher efficiency than all test fuels however the BSFC was significantly higher than diesel until 88.8% of the maximum engine speed. The maximum increase in brake thermal efficiency for B5 is found to be 2.09% which is 7.9% more than diesel at 2000 rpm. A significant increase of maximum 3.719% in brake specific fuel consumption (BSFC) is observed. Maximum reduction in CO emissions is 53.3% for B50 at 2250 rpm accompanied with a maximum average drop in HCs of 74.4%. The variation in the NOx is insignificant. B5 is found to be the most effective blend for both maintaining the engine performance and improving the engine emissions.
Canadian stroke best practice recommendations: Management of Spontaneous Intracerebral Hemorrhage, 7th Edition Update 2020
Authors: Shoamanesh (Co-chair) Ashkan , Patrice Lindsay M , Castellucci Lana A , Cayley Anne , Crowther Mark , de Wit Kerstin , English Shane W , Hoosein Sharon , Huynh Thien , Kelly Michael , O’Kelly Cian J , Teitelbaum Jeanne , Yip Samuel , Dowlatshahi Dar , Smith Eric E , Foley Norine , Pikula Aleksandra , Mountain Anita , Gubitz Gord , Gioia Laura C
Published: November 2020

Spontaneous intracerebral hemorrhage is a particularly devastating type of stroke with greater morbidity and mortality compared with ischemic stroke and can account for half or more of all deaths from stroke. The seventh update of the Canadian Stroke Best Practice Recommendations includes a new stand-alone module on intracerebral hemorrhage, with a focus on elements of care that are unique or affect persons disproportionately relative to ischemic stroke. Prior to this edition, intracerebral hemorrhage was included in the Acute Stroke Management module and was limited to its management during the first 12 h. With the growing evidence on intracerebral hemorrhage, a separate module focused on this topic across the care continuum was added. In addition to topics related to initial clinical management, neuroimaging, blood pressure management, and surgical management, new sections have been introduced addressing topics surrounding inpatient complications such as venous thromboembolism, seizure management, and increased intracranial pressure, rehabilitation as well as issues related to secondary management including lifestyle management, maintaining a normal blood pressure and antithrombotic therapy, are addressed. The Canadian Stroke Best Practice Recommendations ( CSBPR) are intended to provide up-to-date evidence-based guidelines for the prevention and management of stroke and to promote optimal recovery and reintegration for people who have experienced stroke, including patients, families, and informal caregivers.
Mobilising a workforce to combat COVID-19: An account, reflections, and lessons learned
Authors: Doyle Jennifer , Smith Eleanor MJS , Gough Christopher JR , Haq Aaminah , Willis Charlotte , Stevenson Thomas , Reljic Matija
Published: November 2020

With the declaration of coronavirus 2019 (COVID-19) as a pandemic, intensive care units across the globe began to prepare for large numbers of patients. For many years, UK Intensive Care Units (ICUs) have been at high capacity, while facing staffing shortages. In order to prepare for the predicted increased work caring for large numbers with COVID-19, staff were redeployed from other clinical areas to help. Many of these staff had no previous ICU experience. In this article, we share our experiences redeploying medical staff from an extensive range of backgrounds, and how we utilised those staff to maximise use of their existing skills, together with reflections from a variety of redeployed staff members.
Clinical characteristics and outcomes of 85 intensive care patients with Covid-19 in South London: A single centre observational study
Authors: Isted Alexander , McDonnell Angus J , Jones Eben , Grundy Tomas , Jeyabraba Swarna , Ali Tariq O , Khorasanee Reza , Bhalla Aditya , Shurovi Badrun , Rowland Katie , Sykes Richard , Yoon Soo , Morillon Paul , Vijayakumar Rohini Salvadi , Clarke Jayson , Cox Charlie , Breeze Richard , Khaliq Waqas
Published: November 2020

Background

In March 2020, Covid-19 secondary to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was declared a global pandemic.

Methods

This retrospective observational study included patients with Covid-19, managed in a single intensive care unit (ICU). We collected data on patient characteristics, laboratory and radiological findings and ICU management. Data are reported as median (interquartile range). Binary logistic regression modelling was used to identify variables at ICU admission associated with mortality.

Results

85 patients (age 57.3 years [49.4–64.2], 75.3% male) were followed up for 34 days (26–40). The commonest comorbidities were hypertension (51.8%), obesity (48.7%), and type 2 diabetes (31.8%). Covid-19 presented with shortness of breath (89.4%), fever (82.4%), and cough (81.2%), first noted 8 days (6–10) prior to ICU admission. PaO2/FiO2-ratios at ICU admission were 8.28 kPa (7.04–11.7). Bilateral infiltrates on chest X-ray, lymphopenia, and raised C-reactive protein and ferritin were typical. 81.2% received invasive mechanical ventilation (IMV). Acute kidney injury occurred in 62.4% with renal replacement therapy required in 20.0%. By the end of the follow-up period, 44.7% had died, 30.6% had been discharged from hospital, 14.1% had been discharged from ICU but remained in hospital and 10.6% remained in ICU. ICU length of stay was 14 days (9–23). Age was the only variable at admission which was associated with mortality. PaO2/FiO2-ratio, driving pressure and peak ferritin and neutrophil count over the first 72-hours of IMV all correlated with mortality.

Conclusions

We report the clinical characteristics, ICU practices and outcomes of a South London cohort with Covid-19, and have identified factors which correlate with mortality. By sharing our insight, we hope to further understanding of this novel disease.
The effects of interactive E-learning on delirium recognition ability and delirium-related strain of care among critical care nurses
Authors: Najafi Ghezeljeh Tahereh , Rahnamaei Fatemeh , Omrani Soghra , Haghani Shima
Published: November 2020

Background

Nursing care for patients with delirium is very complex and stressful and is associated with considerable care strain for nurses. Delirium recognition is the first step to the prevention and management of delirium and reduction of strain of care. Education is one of the strategies for improving nurses’ delirium recognition ability.

Objectives

This study aimed to evaluate the effects of interactive E-learning on delirium recognition ability and delirium-related strain of care among critical care nurses.

Methods

This quasi-experimental study was conducted in 2019 using a two-group pretest-posttest design. Participants were 98 critical care nurses recruited through a census from two hospitals in Iran. They were non-randomly allocated to an intervention and a control group. Study intervention was an interactive E-learning program with four parts on delirium, its prevention, its treatment, and its diagnostic and screening procedures. The program was uploaded on a website and its link was provided to participants in the intervention group. Before and two months after the intervention, data were collected using the Strain of Care for Delirium Index and five case vignettes. For data analysis, the Chi-square, Fisher’s exact, independent-sample t, and paired-sample t tests were performed usingthe SPSS software (v. 16.0).

Findings

Groups did not significantly differ from each other regarding the pretest mean scores of delirium recognition ability and strain of care. After the intervention, the mean score of delirium recognition ability in the intervention group was significantly greater and the mean score of strain of care was significantly lower than the control group (P < 0.05).

Conclusion

Interactive E-learning is effective in significantly improving critical care nurses’ delirium recognition ability and reducing their strain of care. As nurses’ heavy workload and limited free time are among the main barriers to their participation in face-to-face educational programs, interactive E-learning can be used for in-service education.
Surgery as Single-Modality Treatment for Early-Stage Olfactory Neuroblastoma: An Institutional Experience, Systematic Review and Meta-analysis
Authors: Meerwein Christian M. , Nikolaou Georgios , H. A. Binz Gregori , Soyka Michael B. , Holzmann David
Published: November 2020

Background

For olfactory neuroblastoma (ONB), the combination of surgical tumor resection and radiation therapy (RT) has been considered the “gold standard” in treatment protocols intended to cure.

Objective

To summarize evidence on the treatment of ONB using surgery alone.

Methods

A retrospective institutional case series, a systematic review of the literature, and an individual patient data (IPD) meta-analysis on only surgically treated ONB patients.

Results

At our institution, a total of 10 patients were treated through surgery alone and remained alive and free of disease at last follow-up. The IPD meta-analysis on 128 patients revealed a disease-free survival (DFS) and overall survival (OS) of 67.7% and 75.4% at 5 years and 57.1% and 71.9% at 10 years, respectively. Univariate analysis showed that Kadish stage C/D and Hyams grading III//IV significantly affected OS (P = 0.000 and P = 0.000) and DFS (P = 0.000 and P = 0.002). For low-risk patients, the DFS was 80.6% at 5 years and 67.8% at 10 years, respectively.

Conclusions

Surgery alone is an equivalent alternative to combined treatment in carefully selected low-risk ONB patients with better outcome measures than previously reported.
The relationship between coronary slow flow phenomenon and carotid femoral pulse wave velocity and aortic elastic properties
Authors: Akkaya Hasan , Güntürk Ertuğrul Emre
Published: November 2020

Introduction

In this study, we aimed to investigate the relationship between coronary slow flow (CSF) and carotid-femoral pulse wave velocity (CFPWV).

Methods

78 (27 women, mean age 43.95 ± 7.28) patients with CSF, and 70 (22 women, mean age 44.34 ± 7.08) healthy individuals were included in the study. Arterial stiffness measurement was performed to both groups via CFPWV, which is considered the gold standard. Aortic elastic properties (ASI-β and aortic distensibility) were evaluated in both groups.

Results

The CSF group had significantly higher CFPWV and aortic distensibility values and significantly lower ASI-β values compared to the control group. There was a positive correlation between TIMI frame count (TFC) obtained in all coronary arteries and CFPWV and aortic distensibility, and a negative correlation between TFC and ASI-β. It was determined that CFPWV predicted CSF with 97% specificity and 98% sensitivity at a 7.68 cut-off value (ROC area = 994, p < 0.001). ASI-β was determined to predict CSF with 64% specificity and 47% sensitivity at a 2.98 cut-off value (ROC area = 047, p < 0.001). Aortic distensibility was determined to predict CSF with 76% specificity and 79% sensitivity at a 3.94 cut-off value (ROC area = 706, p < 0.001).

Conclusion

Arterial stiffness increases in CSF patients, suggesting that CSF is a systemic pathology rather than a local disease and that a systemic cause such as atherosclerosis plays a role in etiology.
Physical activity, diet and quality of life during mandatory (COVID-19) quarantine following repatriation
Authors: Gradidge Philippe Jean-Luc , Kruger Herculina Salome
Published: November 2020

The coronavirus disease 2019 crisis in South Africa has been managed through an effective evidence-based approach. The aim of this case report was to determine the value of staying physically active during the coronavirus disease 2019 pandemic, using online resources to prevent the harmful effects of sedentary behaviour under confined living conditions. A repatriated South African citizen was placed into monitored 14-day quarantine confined to a room, self-monitoring dietary intake and physical and health measures, while engaged in online exercise videos and indoor walking. This study demonstrates that structured indoor activity improves physical and mental health outcomes, despite prolonged sitting time during the day. During the current pandemic and in the presence of limited freedom of movement, sustained physical activity is made feasible by accessing online tools and resources, essentially reducing vulnerability to existing cardiovascular health concerns. However, these findings are based on a single participant and therefore further study is required.
The Development and Validation of an Intercultural Business Communication Competence Scale: Evidence From Mainland China
Authors: Jiao Jing , Xu Dejin , Zhao Xiuqing
Published: November 2020

The aim of this article is to develop an Intercultural Business Communication Competence Scale (IBCCS) and provide evidence for the construct, convergent, discriminant, content, criterion, and external validity of the scale. The scale was developed based on 20 key elements of intercultural business communication competence (IBCC) and a review on the scales measuring international business practitioners’ intercultural competence. The three factors extracted with exploratory factor analysis (EFA) were the cognitive ability for the intercultural business communication situation, business English linguistic proficiency, and intercultural business communication motivation. The scale showed sound internal consistency and the confirmatory factor analysis (CFA) demonstrated sound degree of fitness and stable scale structure. The survey results revealed that respondents’ IBCC significantly correlated with their emotion intelligence (EI) and cultural intelligence (CQ). IBCCS was capable of differentiating the participants with hypothesized high IBCC level and tracking their IBCC development, which documented content validity and external validity of the measure. Hierarchical regression analysis indicated that the business students’ IBCC appeared to predict their number of foreign friends and job aspiration for an international career.
Municipality-Level Characteristics Associated with Very Low to Good Quality of Water Fluoridation in São Paulo State, Brazil, in 2015
Authors: Belotti L. , Zilbovicius C. , Soares C.C.d.S. , Narvai P.C. , Frazão P.
Published: November 2020

Introduction:

Community water fluoridation (CWF) is a measure of recognized importance due to its effectiveness in preventing tooth decay at the population level. However, for the maximum benefit to be achieved, the high-quality standard of CWF must be maintained over time.

Objective:

To analyze the municipality-level characteristics associated with quality of water fluoridation in São Paulo state, Brazil.

Methods:

An ecological study was performed using official data sources on fluoride concentration surveillance in 2015. The outcome was municipalities that have not met the quality standard, identified as those with less than 80% of water samples within the optimal level for caries prevention. The independent variables were municipality-level indicators related to demographics, economics, and sanitation characteristics. Crude and adjusted prevalence ratios were estimated using Poisson regression with robust variance.

Results:

In total, 43.4% municipalities exhibited the outcome. Adjusted by Gini index, the prevalence ratio was 32% higher in municipalities with lower annual gross domestic product per capita. Adjusted by social responsibility index and earlier variables, the prevalence was higher in the municipalities with higher per capita expenditure on sanitation and health surveillance, where the urban population rate was lower, and with a human development index ≤0.761. Adjusted by earlier variables, the prevalence ratio was twice and 3.5 times higher for municipalities, respectively, with per capita income less than or equal to US$574 and where the type of sanitation utility was municipal and private; 50% higher in those with less than 100,000 habitants; and 20% higher in those with a chlorine concentration nonconformity rate above 0.82%.

Conclusions:

To ensure high quality of CWF, additional management measures should be implemented in municipalities with less than 100,000 habitants, a higher chlorine concentration nonconformity rate, a lower per capita income, and where the type of sanitation utility was municipal or private.

Knowledge Transfer Statement:

The study showed that the quality of fluoridation was associated with municipality-level characteristics. The findings can be used by policy makers to identify and support municipalities that will need to improve fluoridation quality if they are to reach oral health goals.
Manganoarrojadite-(KNa), KNa5MnFe13Al(PO4)11(PO3OH)(OH)2, a new arrojadite-group mineral from the Palermo No. 1 mine, New Hampshire, USA
Authors: Lykova Inna , Rowe Ralph , Poirier Glenn , Helwig Kate , Friis Henrik
Published: November 2020

A new arrojadite-group mineral manganoarrojadite-(KNa), ideally KNa5MnFe13Al(PO4)11(PO3OH)(OH)2, was found in a phosphate-bearing granite pegmatite at the Palermo No. 1 mine, New Hampshire, USA. It forms anhedral grains up to 1 × 1.5 cm in size combined in aggregates with vivianite, goyazite, quartz and calcite. The mineral is olive green with a pale green streak and vitreous to greasy lustre. The cleavage is good in one direction. The Mohs hardness is 4½. Dcalc is 3.53 g/cm3. Manganoarrojadite-(KNa) is optically biaxial (–), α = 1.658(2), β = 1.666(2), γ = 1.670(2), 2Vmeas. = 67(1)° and 2Vcalc. = 70° (589 nm). The infrared spectrum is reported. The composition (wt.%) is Na2O 6.97, K2O 1.78, CaO 0.31, MgO 2.17, MnO 12.30, FeO 31.17, Al2O3 2.43, P2O5 40.48, F 0.30, H2O 1.32, O = F2 –0.13, total 99.10. The empirical formula calculated on the basis of 12 P and (O+OH+F) = 50 apfu is Na4.73K0.80Ca0.12Mg1.13Mn2+3.65Fe2+9.13Al1.00P12.00O46.59OH3.08F0.33. The ideal structural formula is A1KA2NaB1NaB2NaNa1,2Na2Na3□ CMnMFe13Al(PO4)11(PO3OH)W(OH)2. The mineral is monoclinic, Cc, a = 16.5345(3), b = 10.0406(2), c = 24.6261(5) Å, β = 105.891(2)°, V = 3932.09(14) Å3 and Z = 4. The strongest reflections of the powder X-ray diffraction pattern [d,Å(I)(hkl)] are: 5.902(24)(202), 5.025(24)(020), 3.208(47)(206,$\;\bar{1}$32), 3.048(100)($\bar{5}$14,$\bar{4}$24), 2.758(24)($\bar{6}$02) and 2.704(70)(226). The crystal structure, refined from single-crystal X-ray diffraction data (R1 = 0.025), is of the arrojadite structure type. Manganoarrojadite-(KNa) is the first arrojadite-group mineral with Mn dominant on the site usually occupied by Ca and without Ca as the dominant cation at any cation site.
A 50-kb deletion disrupting the RSPO2 gene is associated with tetradysmelia in Holstein Friesian cattle
Authors: Becker Doreen , Weikard Rosemarie , Schulze Christoph , Wohlsein Peter , Kühn Christa
Published: November 2020

Background

Tetradysmelia is a rare genetic disorder that is characterized by an extremely severe reduction of all limb parts distal of the scapula and pelvic girdle. We studied a Holstein Friesian backcross family with 24 offspring, among which six calves displayed autosomal recessive tetradysmelia. In order to identify the genetic basis of the disorder, we genotyped three affected calves, five dams and nine unaffected siblings using a Bovine Illumina 50 k BeadChip and sequenced the whole genome of the sire.

Results

Pathological examination of four tetradysmelia cases revealed a uniform and severe dysmelia of all limbs. Applying a homozygosity mapping approach, we identified a homozygous region of 10.54 Mb on chromosome 14 (Bos taurusBTA14). Only calves that were diagnosed with tetradysmelia shared a distinct homozygous haplotype for this region. We sequenced the whole genome of the cases’ sire and searched for heterozygous single nucleotide polymorphisms (SNPs) and small variants on BTA14 that were uniquely present in the sire and absent from 3102 control whole-genome sequences of the 1000 Bull Genomes Project, but none were identified in the 10.54-Mb candidate region on BTA14. Therefore, we subsequently performed a more comprehensive analysis by also considering structural variants and detected a 50-kb deletion in the targeted chromosomal region that was in the heterozygous state in the cases’ sire. Using PCR, we confirmed that this detected deletion segregated perfectly within the family with tetradysmelia. The deletion spanned three exons of the bovineR-spondin 2(RSPO2) gene, which encode three domains of the respective protein. R-spondin 2 is a secreted ligand of leucine-rich repeats containing G protein-coupled receptors that enhance Wnt signalling and is involved in a broad range of developmental processes during embryogenesis.

Conclusions

We identified a 50-kb deletion on BTA14 that disrupts the coding sequence of theRSPO2gene and is associated with bovine tetradysmelia. To our knowledge, this is the first reported candidate causal mutation for tetradysmelia in a large animal model. Since signalling pathways involved in limb development are conserved across species, the observed inherited defect may serve as a model to further elucidate fundamental pathways of limb development.
Novel domain expansion methods to improve the computational efficiency of the Chemical Master Equation solution for large biological networks
Authors: Kosarwal Rahul , Kulasiri Don , Samarasinghe Sandhya
Published: November 2020

Background

Numerical solutions of the chemical master equation (CME) are important for understanding the stochasticity of biochemical systems. However, solving CMEs is a formidable task. This task is complicated due to the nonlinear nature of the reactions and the size of the networks which result in different realizations. Most importantly, the exponential growth of the size of the state-space, with respect to the number of different species in the system makes this a challenging assignment. When the biochemical system has a large number of variables, the CME solution becomes intractable. We introduce the intelligent state projection (ISP) method to use in the stochastic analysis of these systems. For any biochemical reaction network, it is important to capture more than one moment: this allows one to describe the system’s dynamic behaviour. ISP is based on a state-space search and the data structure standards of artificial intelligence (AI). It can be used to explore and update the states of a biochemical system. To support the expansion in ISP, we also develop a Bayesian likelihood node projection (BLNP) function to predict the likelihood of the states.

Results

To demonstrate the acceptability and effectiveness of our method, we apply the ISP method to several biological models discussed in prior literature. The results of our computational experiments reveal that the ISP method is effective both in terms of the speed and accuracy of the expansion, and the accuracy of the solution. This method also provides a better understanding of the state-space of the system in terms of blueprint patterns.

Conclusions

The ISP is the de-novo method which addresses both accuracy and performance problems for CME solutions. It systematically expands the projection space based on predefined inputs. This ensures accuracy in the approximation and an exact analytical solution for the time of interest. The ISP was more effective both in predicting the behavior of the state-space of the system and in performance management, which is a vital step towards modeling large biochemical systems.
Performance of copy number variants detection based on whole-genome sequencing by DNBSEQ platforms
Authors: Rao Junhua , Peng Lihua , Liang Xinming , Jiang Hui , Geng Chunyu , Zhao Xia , Liu Xin , Fan Guangyi , Chen Fang , Mu Feng
Published: November 2020

Background

DNBSEQ™ platforms are new massively parallel sequencing (MPS) platforms that use DNA nanoball technology. Use of data generated from DNBSEQ™ platforms to detect single nucleotide variants (SNVs) and small insertions and deletions (indels) has proven to be quite effective, while the feasibility of copy number variants (CNVs) detection is unclear.

Results

Here, we first benchmarked different CNV detection tools based on Illumina whole-genome sequencing (WGS) data of NA12878 and then assessed these tools in CNV detection based on DNBSEQ™ sequencing data from the same sample. When the same tool was used, the CNVs detected based on DNBSEQ™ and Illumina data were similar in quantity, length and distribution, while great differences existed within results from different tools and even based on data from a single platform. We further estimated the CNV detection power based on available CNV benchmarks of NA12878 and found similar precision and sensitivity between the DNBSEQ™ and Illumina platforms. We also found higher precision of CNVs shorter than 1 kbp based on DNBSEQ™ platforms than those based on Illumina platforms by using Pindel, DELLY and LUMPY. We carefully compared these two available benchmarks and found a large proportion of specific CNVs between them. Thus, we constructed a more complete CNV benchmark of NA12878 containing 3512 CNV regions.

Conclusions

We assessed and benchmarked CNV detections based on WGS with DNBSEQ™ platforms and provide guidelines for future studies.
Dictyocoela microsporidia diversity and co-diversification with their host, a gammarid species complex (Crustacea, Amphipoda) with an old history of divergence and high endemic diversity
Authors: Quiles Adrien , Wattier Rémi A. , Bacela-Spychalska Karolina , Grabowski Michal , Rigaud Thierry
Published: November 2020

Background

Although the processes of co-evolution between parasites and their hosts are well known, evidence of co-speciation remains scarce. Microsporidian intracellular parasites, due to intimate relationships with their hosts and mixed mode of transmission (horizontal but also vertical, from mother to offspring), may represent an interesting biological model for investigating co-speciation. Amphipod crustaceans, especially gammarids, are regular hosts of microsporidian parasites, in particular the Dictyocoela spp., which have so far been found limited to these amphipods and are known to use a vertical mode of transmission. The amphipod genus Gammarus has a diversification history spanning the last 50–60 Mya and an extensive cryptic diversity in most of the nominal species. Here, we investigated the degree of co-diversification between Dictyocoela and Gammarus balcanicus, an amphipod with high degrees of ancient cryptic diversification and lineage endemism, by examining the genetic diversity of these parasites over the entire geographic range of the host. We hypothesised that the strong host diversification and vertical transmission of Dictyocoela would promote co-diversification.

Results

Using the parasite SSU rDNA as a molecular marker, analyzing 2225 host specimens from 88 sites covering whole host range, we found 31 haplogroups of Dictyocoela, 30 of which were novel, belonging to four Dictyocoela species already known to infect other Gammarus spp. The relationships between Dictyocoela and gammarids is therefore ancient, with the speciation in parasites preceding those of the hosts. Each novel haplogroup was nevertheless specific to G. balcanicus, leaving the possibility for subsequent co-diversification process during host diversification. A Procrustean Approach to Co-phylogeny (PACo) analysis revealed that diversification of Dictyocoela was not random with respect to that of the host. We found high degrees of congruence between the diversification of G. balcanicus and that of Dictyocoela roeselum and D. muelleri. However, we also found some incongruences between host and Dictyocoela phylogenies, e.g. in D. duebenum, probably due to host shifts between different G. balcanicus cryptic lineages.

Conclusion

The evolutionary history of Dictyocoela and Gammarus balcanicus represents an example of an overall host-parasite co-diversification, including cases of host shifts.
Transcriptome analysis reveals mechanism of early ripening in Kyoho grape with hydrogen peroxide treatment
Authors: Guo Da-Long , Wang Zhen-Guang , Pei Mao-Song , Guo Li-Li , Yu Yi-He
Published: November 2020

Background

In a previous study, the early ripening of Kyoho grape following H2O2 treatment was explored at the physiological level, but the mechanism by which H2O2 promotes ripening at the molecular level is unclear. To reveal the molecular mechanism, RNA-sequencing analysis was conducted on the different developmental stages of Kyoho berry treated with H2O2.

Results

In the comparison of treatment and control groups, 406 genes were up-regulated and 683 were down-regulated. Time course sequencing (TCseq) analysis showed that the expression patterns of most of the genes were similar between the treatment and control, except for some genes related to chlorophyll binding and photosynthesis. Differential expression analysis and the weighted gene co-expression network were used to screen significantly differentially expressed genes and hub genes associated with oxidative stress (heat shock protein, HSP), cell wall deacetylation (GDSL esterase/lipase, GDSL), cell wall degradation (xyloglucan endotransglucosylase/ hydrolase, XTH), and photosynthesis (chlorophyll a-b binding protein, CAB1). Gene expression was verified with RT-qPCR, and the results were largely consistent with those of RNA sequencing.

Conclusions

The RNA-sequencing analysis indicated that H2O2 treatment promoted the early ripening of Kyoho berry by affecting the expression levels of HSP, GDSL, XTH, and CAB1 and- photosynthesis- pathways.
A new method for long-read sequencing of animal mitochondrial genomes: application to the identification of equine mitochondrial DNA variants
Authors: Dhorne-Pollet Sophie , Barrey Eric , Pollet Nicolas
Published: November 2020

Background

Mitochondrial DNA is remarkably polymorphic. This is why animal geneticists survey mitochondrial genomes variations for fundamental and applied purposes. We present here an approach to sequence whole mitochondrial genomes using nanopore long-read sequencing. Our method relies on the selective elimination of nuclear DNA using an exonuclease treatment and on the amplification of circular mitochondrial DNA using a multiple displacement amplification step.

Results

We optimized each preparative step to obtain a 100 million-fold enrichment of horse mitochondrial DNA relative to nuclear DNA. We sequenced these amplified mitochondrial DNA using nanopore sequencing technology and obtained mitochondrial DNA reads that represented up to half of the sequencing output. The sequence reads were 2.3 kb of mean length and provided an even coverage of the mitochondrial genome. Long-reads spanning half or more of the whole mtDNA provided a coverage that varied between 118X and 488X. We evaluated SNPs identified using these long-reads by Sanger sequencing as ground truth and found a precision of 100.0%; a recall of 93.1% and a F1-score of 0.964 using the Twilight horse mtDNA reference. The choice of the mtDNA reference impacted variant calling efficiency with F1-scores varying between 0.947 and 0.964.

Conclusions

Our method to amplify mtDNA and to sequence it using the nanopore technology is usable for mitochondrial DNA variant analysis. With minor modifications, this approach could easily be applied to other large circular DNA molecules.
Global assessment of organ specific basal gene expression over a diurnal cycle with analyses of gene copies exhibiting cyclic expression patterns
Authors: Lu Yuan , Boswell Mikki , Boswell William , Salinas Raquel Ybanez , Savage Markita , Reyes Jose , Walter Sean , Marks Rebecca , Gonzalez Trevor , Medrano Geraldo , Warren Wesley C. , Schartl Manfred , Walter Ronald B.
Published: November 2020

Background

Studying functional divergences between paralogs that originated from genome duplication is a significant topic in investigating molecular evolution. Genes that exhibit basal level cyclic expression patterns including circadian and light responsive genes are important physiological regulators. Temporal shifts in basal gene expression patterns are important factors to be considered when studying genetic functions. However, adequate efforts have not been applied to studying basal gene expression variation on a global scale to establish transcriptional activity baselines for each organ. Furthermore, the investigation of cyclic expression pattern comparisons between genome duplication created paralogs, and potential functional divergence between them has been neglected. To address these questions, we utilized a teleost fish species,Xiphophorus maculatus,and profiled gene expression within 9 organs at 3-h intervals throughout a 24-h diurnal period.

Results

Our results showed 1.3–21.9% of genes in different organs exhibited cyclic expression patterns, with eye showing the highest fraction of cycling genes while gonads yielded the lowest. A majority of the duplicated gene pairs exhibited divergences in their basal level expression patterns wherein only one paralog exhibited an oscillating expression pattern, or both paralogs exhibit oscillating expression patterns, but each gene duplicate showed a different peak expression time, and/or in different organs.

Conclusions

These observations suggest cyclic genes experienced significant sub-, neo-, or non-functionalization following the teleost genome duplication event. In addition, we developed a customized, web-accessible, gene expression browser to facilitate data mining and data visualization for the scientific community.