bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren’s syndrome
Authors: Inamo Jun , Suzuki Katsuya , Takeshita Masaru , Kassai Yoshiaki , Takiguchi Maiko , Kurisu Rina , Okuzono Yuumi , Tasaki Shinya , Yoshimura Akihiko , Takeuchi Tsutomu
Published: June 2020

Background

The aim of this study was to identify the molecular mechanism of dysregulation of B cell subpopulations of primary Sjögren’s syndrome (pSS) at the transcriptome level.

Methods

We enrolled patients with pSS (n = 6) and healthy controls (HCs) (n = 6) in the discovery cohort using microarray and pSS (n = 14) and HCs (n = 12) in the validation cohort using quantitative PCR (qPCR). Peripheral B cells acquired from these subjects were separated by cell sorting into four subsets: CD38−IgD+ (Bm1), CD38+IgD+ (naive B cells), CD38highIgD+ (pre-germinal centre B cells) and CD38±IgD− (memory B cells). We performed differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA).

Results

Expression of the long non-coding RNA LINC00487 was significantly upregulated in all B cell subsets, as was that of HLA and interferon (IFN) signature genes. Moreover, the normalized intensity value of LINC00487 significantly correlated with the disease activity score of all pSS B cell subsets. Studies of human B cell lines revealed that the expression of LINC00487 was strongly induced by IFNα. WGCNA revealed six gene clusters associated with the B cell subpopulation of pSS. Further, SOX4 was identified as an inter-module hub gene.

Conclusion

Our transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS.

Trial registration

Not required.
Neuromuscular activation pattern of lower extremity muscles during pedaling in cyclists with single amputation of leg and with two legs: a case study
Authors: Watanabe Kohei , Yamaguchi Yuta , Fukuda Wataru , Nakazawa Sho , Kenjo Taishi , Nishiyama Tetsunari
Published: June 2020

Objective

In Para-cycling competitions, cyclists with amputation of one-leg and no prosthesis, i.e., Division Cycle, Sport Class C2, perform pedaling movement on bicycle by unilateral leg. The purpose of this study was to describe neuromuscular activation of lower extremity muscles in two cyclists with single leg amputation and one cyclist with two legs during pedaling. We compared averaged rectified values (ARV) of surface electromyography for lower extremity muscles during crank cycle for two single leg cyclists with one cyclist with two legs at 65%, 80%, and 95% of VO2 max.

Results

Characteristic features of cyclists with single amputation of leg were increases in ARV for proximal region of the rectus femoris muscle in first half of pulling phase, increases in ARV for the biceps femoris muscle in first half of pulling phase, and increases in ARV for the medial gastrocnemius muscle in pulling phase. These findings in this study suggest that cyclists with single amputation of leg use characteristic neuromuscular coordination in the muscles contributing to hip and knee flexion joint moments during pulling phase and this may be the strategy in cyclists with single amputation of leg to compensate lack of hip and/or knee extension torque from contralateral leg.
Qualitative and quantitative assay of glucose 6 phosphate dehydrogenase in patients attending tertiary care center
Authors: Sharma Uday , Mishra Satyendra , Gautam Narayan , Gupta Badri Kumar
Published: June 2020

Objectives

The study was carried out with the aim to find out the frequency of Glucose 6 phosphate dehydrogenase (G6PD) deficiency among the patients attending the hospital and to rationalize the qualitative methemoglobin reduction test in reference to the quantitative spectrophotometric assay. Timely screening of the patients for G6PD with appropriate screening method can play an important role in preventing hemolytic crisis that arises from therapeutic use of oxidative drugs like primaquine.

Result

The frequency of G6PD deficient cases was 3% by both of the employed tests. The mean ± SD of G6PD activity in the patients under study was 15.34 ± 4.7 IU/g Hb in males and 16.01 ± 3.74 IU/g Hb in females. G6PD activity was positively associated with reticulocyte count (r = 0.289, p value = 0.004) and negatively with mean corpuscular hemoglobin concentration (r = −0.220, p-value = 0.028). The correlation of red blood corpuscular count and G6PD was statistically significant (p-value = 0.048).
PET imaging of soluble epoxide hydrolase in non-human primate brain with [18F]FNDP
Authors: Du Yong , Minn Il , Foss Catherine , Lesniak Wojciech G. , Hu Feng , Dannals Robert F. , Pomper Martin G. , Horti Andrew G.
Published: June 2020

Purpose

Soluble epoxide hydrolase (sEH) is a promising candidate positron emission tomography (PET) imaging biomarker altered in various disorders, including vascular cognitive impairment (VCI), Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, and depression, known to regulate levels of epoxyeicosatrienoic acids (EETs) and play an important role in neurovascular coupling. [18F]FNDP, a PET radiotracer for imaging sEH, was evaluated through quantitative PET imaging in the baboon brain, radiometabolite analysis, and radiation dosimetry estimate.

Methods

Baboon [18F]FNDP dynamic PET studies were performed at baseline and with blocking doses of the selective sEH inhibitor AR-9281 to evaluate sEH binding specificity. Radiometabolites of [18F]FNDP in mice and baboons were measured by high-performance liquid chromatography. Regional brain distribution volume (VT) of [18F]FNDP was computed from PET using radiometabolite-corrected arterial input functions. Full body distribution of [18F]FNDP was studied in CD-1 mice, and the human effective dose was estimated using OLINDA/EXM software.

Results

[18F]FNDP exhibited high and rapid brain uptake in baboons. AR-9281 blocked [18F]FNDP uptake dose-dependently with a baseline VT of 10.9 ± 2.4 mL/mL and a high-dose blocking VT of 1.0 ± 0.09 mL/mL, indicating substantial binding specificity (91.70 ± 1.74%). The VND was estimated as 0.865 ± 0.066 mL/mL. The estimated occupancy values of AR-9281 were 99.2 ± 1.1% for 1 mg/kg, 88.6 ± 1.3% for 0.1 mg/kg, and 33.8 ± 3.8% for 0.02 mg/kg. Murine biodistribution of [18F]FNDP enabled an effective dose estimate for humans (0.032 mSv/MBq). [18F]FNDP forms hydrophilic radiometabolites in murine and non-human primate plasma. However, only minute amounts of the radiometabolites entered the animal brain (< 2% in mice).

Conclusions

[18F]FNDP is a highly sEH-specific radiotracer that is suitable for quantitative PET imaging in the baboon brain. [18F]FNDP holds promise for translation to human subjects.
Clinical outcomes according to cannula configurations in patients with acute respiratory distress syndrome under veno-venous extracorporeal membrane oxygenation: a Korean multicenter study
Authors: Lim Sung Yoon , Ahn Soyeon , Hong Sang-Bum , Chung Chi Ryang , Jeon Kyeongman , Lee Sang-Min , Cho Woo Hyun , Park Sunghoon , Cho Young-Jae
Published: June 2020

Background

Recirculation during veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a known drawback that limits sufficient oxygenation. This study aimed to compare the short-term oxygenation and long-term mortality based on cannula configuration in patients with acute respiratory distress syndrome (ARDS) who receive VV-ECMO, especially in the absence of newly developed dual-lumen, single cannula.

Methods

Data of patients with severe ARDS who received VV-ECMO from 2012 to 2015 at six hospitals were retrospectively analyzed. Primary outcomes were the partial pressure of oxygen (PaO2) at 1, 4, and 12 h after ECMO initiation and 180-day mortality.

Results

Patients (n = 335) were divided into two groups based on the return cannula site: femoral vein (n = 178) or internal jugular vein (n = 157). The propensity score matching analysis generated 90 pairs, and baseline characteristics at admission, including PaO2, were similar between the groups. PaO2at 1, 4 and 12 h after ECMO initiation were not different according to cannula configuration. Moreover, the increment in oxygenation from the baseline values was not different between the femoral and jugular group. PaCO2level at 1, 4 and 12 h were significantly lower in the jugular group. The two groups did not differ in terms of mortality at 180 days after ECMO, however more cannula-related complications occurred in the jugular group.

Conclusion

Regardless of the cannula configuration, patients with ARDS managed with VV-ECMO showed comparable clinical outcomes in terms of short-term oxygenation and long-term mortality. Nevertheless, further well-designed randomized control trials are warranted.
Global attractors for Kirchhoff wave equation with nonlinear damping and memory
Authors: Zhang Suli , Zhang Jianwen , Wang Haiyan
Published: June 2020

In this paper, we prove that the existence of global attractors for a Kirchhoff wave equation with nonlinear damping and memory.
A novel analytical technique to obtain the solitary solutions for nonlinear evolution equation of fractional order
Authors: Ghaffar Abdul , Ali Ayyaz , Ahmed Sarfaraz , Akram Saima , Junjua Moin-ud-Din , Baleanu Dumitru , Nisar Kottakkaran Sooppy
Published: June 2020

We investigate some solitary wave results of time fractional evolution equations. By employing the extended rational $\exp ( (-\frac{{\psi }^{\prime }}{\psi }) ( \eta ) )$exp((−ψ′ψ)(η))-expansion method, a few different results including kink, singular-kink, multiple soliton, and periodic wave solutions are formally generated. It is worth mentioning that the solutions obtained are more general with more parameters. The exact solutions are constructed in the form of exponential, trigonometric, rational, and hyperbolic functions. With the choice of proper values of parameters, graphs to some of the obtained solutions are drawn. On comparing some special cases, our solutions are in good agreement with the results published previously and the remaining are new.
Successful control of the first carbapenem-resistant Klebsiella pneumoniae outbreak in a Chinese hospital 2017–2019
Authors: Zhu Jiaying , Li Qi , Li Xiaoxia , Kang Jianbang , Song Yan , Song Junli , Yin Donghong , Duan Jinju
Published: June 2020

Background

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is considered as a serious global threat. CRKPs occurred only sporadically in the Second Hospital of Shanxi Medical University. Our study aimed to investigate and control the first outbreak of CRKP in our hospital occurred between October 2017 and August 2019.

Methods

The antimicrobial stewardship (AMS) workers have been implemented control measures properly. Clinical and epidemiological data were retrospectively collected from medical records. Carbapenemase genes were detected by modified carbapenem inactivation method (mCIM) test and the EDTA-modified carbapenem inactivation method (eCIM) test. Resistance genes were identified by polymerase chain reaction (PCR) and sequencing. Genetic relatedness was studied by multilocus sequence typing (MLST).

Results

During the outbreak, 31 patients were infected with CRKP isolates. 20 (64.5%) patients were infected with KPC-2 and/or NDM-1 producing K. pneumoniae. Mostly MLST-sequence types belonged to ST11 (21/31). The outbreak was two major K. pneumoniae clusters present in epidemiologically linked patients.

Conclusions

Setting up AMS workers is potentially a highly efficient strategy for the successful control of the outbreak. A multimodal and multidisciplinary infection control strategy proved to be crucial. The emergence of CRKP in our hospital emphasizes the importance of continuous monitoring of these isolates, which helps to limit the spread of CRKPs and improve the level of management.
Spatial distribution of people diagnosed with tuberculosis through routine and active case finding: a community-based study in Kampala, Uganda
Authors: Robsky Katherine O. , Kitonsa Peter J. , Mukiibi James , Nakasolya Olga , Isooba David , Nalutaaya Annet , Salvatore Phillip P. , Kendall Emily A. , Katamba Achilles , Dowdy David
Published: June 2020

Background

Routine tuberculosis (TB) notifications are geographically heterogeneous, but their utility in predicting the location of undiagnosed TB cases is unclear. We aimed to identify small-scale geographic areas with high TB notification rates based on routinely collected data and to evaluate whether these areas have a correspondingly high rate of undiagnosed prevalent TB.

Methods

We used routinely collected data to identify geographic areas with high TB notification rates and evaluated the extent to which these areas correlated with the location of undiagnosed cases during a subsequent community-wide active case finding intervention in Kampala, Uganda. We first enrolled all adults who lived within 35 contiguous zones and were diagnosed through routine care at four local TB Diagnosis and Treatment Units. We calculated average monthly TB notification rates in each zone and defined geographic areas of “high risk” as zones that constituted the 20% of the population with highest notification rates. We compared the observed proportion of TB notifications among residents of these high-risk zones to the expected proportion, using simulated estimates based on population size and random variation alone. We then evaluated the extent to which these high-risk zones identified areas with high burdens of undiagnosed TB during a subsequent community-based active case finding campaign using a chi-square test.

Results

We enrolled 45 adults diagnosed with TB through routine practices and who lived within the study area (estimated population of 49 527). Eighteen zones reported no TB cases in the 9-month period; among the remaining zones, monthly TB notification rates ranged from 3.9 to 39.4 per 100 000 population. The five zones with the highest notification rates constituted 62% (95% CI: 47–75%) of TB cases and 22% of the population–significantly higher than would be expected if population size and random chance were the only determinants of zone-to-zone variation (48%, 95% simulation interval: 40–59%). These five high-risk zones accounted for 42% (95% CI: 34–51%) of the 128 cases detected during the subsequent community-based case finding intervention, which was significantly higher than the 22% expected by chance (P < 0.001) but lower than the 62% of cases notified from those zones during the pre-intervention period (P = 0.02).

Conclusions

There is substantial heterogeneity in routine TB notification rates at the zone level. Using facility-based TB notification rates to prioritize high-yield areas for active case finding could double the yield of such case-finding interventions.
Evaluation of serum-based real-time PCR to detect Schistosoma mansoni infection before and after treatment
Authors: Fuss Antje , Mazigo Humphrey Deogratias , Mueller Andreas
Published: June 2020

Background

To detect acute schistosomiasis, low-intensity infections, or to verify the success of treatment with praziquantel, highly sensitive test methods are required. The aim of this study was therefore to demonstrate the performance of Schistosoma mansoni specific DNA detection in serum and urine using real-time polymerase chain reaction (PCR) in an endemic area before and after treatment.

Methods

The study pursued a 1-week and 20-weeks longitudinal design with a treatment intervention among 36 study participants aged 18 to 70 years in the community of Kayenze, a fishing village in Ilemela district on the southern shore of Lake Victoria in north-western Tanzania between February and June 2018. Blood, urine and stool samples were collected from each participant to diagnose Schistosoma mansoni infection before and two times after treatment with praziquantel using serum- and urine based real-time PCR, point-of-care circulating cathodic antigen (POC-CCA) rapid diagnostic test and the microscopic Kato-Katz (KK) method. Kappa coefficient (κ) was used to estimate the agreement between these diagnostic tests compared to a combined “gold standard” of positive results by serum-based real-time PCR and/or positive egg counts determined by KK. Kendall’s Tau rank correlation was used to examine the relationship between cycle threshold (Ct)-values and egg counts and the Wilcoxon signed-rank test was used to compare the median Ct-values of the different examination time points.

Results

By using the combined “gold standard” of the parasitological Kato-Katz test and/or serum-based real-time PCR, a S. mansoni prevalence of 77.1% could be determined at baseline. In terms of sensitivity, serum-based real-time PCR (96.3%) and POC-CCA assay (77.8%) showed the highest results. The detection of DNA from urine samples showed the lowest sensitivity (33.3%). Treatment with praziquantel resulted in a significantly reduced prevalence of S. mansoni. No infection could be detected by Kato-Katz, with the POC-CCA test only 33.3%. The analysis of the median Ct values over time (which were determined by the serum-based real-time PCR) showed that the Ct decreases significantly shortly after treatment (from 30.3 to 28) and increases above baseline level (34.9) three months later.

Conclusions

The data presented here show that the serum-based real-time PCR exhibits excellent diagnostic accuracy, in contrast to the use of urine as sample material for S. mansoni DNA detection. However, as circulating DNA does not necessarily reflect the persistence of living worms in schistosomiasis, this method is less well suited to verify the success of treatment with praziquantel.
Nutritional and medical food therapies for diabetic retinopathy
Authors: Shi Ce , Wang Peng , Airen Shriya , Brown Craig , Liu Zhiping , Townsend Justin H. , Wang Jianhua , Jiang Hong
Published: June 2020

Diabetic retinopathy (DR) is a form of microangiopathy. Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina. New approaches are needed, which reduce the risk and improve the outcomes of DR while complementing current therapeutic approaches. Homocysteine (Hcy) elevation and oxidative stress are potential therapeutic targets in DR.

Common genetic polymorphisms such as those of methylenetetrahydrofolate reductase (MTHFR), increase Hcy and DR risk and severity. Patients with DR have high incidences of deficiencies of crucial vitamins, minerals, and related compounds, which also lead to elevation of Hcy and oxidative stress. Addressing the effects of the MTHFR polymorphism and addressing comorbid deficiencies and insufficiencies reduce the impact and severity of the disease. This approach provides safe and simple strategies that support conventional care and improve outcomes.

Suboptimal vitamin co-factor availability also impairs the release of neurotrophic and neuroprotective growth factors. Collectively, this accounts for variability in presentation and response of DR to conventional therapy. Fortunately, there are straightforward recommendations for addressing these issues and supporting traditional treatment plans.

We have reviewed the literature for nutritional interventions that support conventional therapies to reduce disease risk and severity. Optimal combinations of vitamins B1, B2, B6, L-methylfolate, methylcobalamin (B12), C, D, natural vitamin E complex, lutein, zeaxanthin, alpha-lipoic acid, and n-acetylcysteine are identified for protecting the retina and choroid. Certain medical foods have been successfully used as therapy for retinopathy. Recommendations based on this review and our clinical experience are developed for clinicians to use to support conventional therapy for DR.

DR from both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have similar retinal findings and responses to nutritional therapies.
Genotypic variance in 13C-photosynthate partitioning and within-plant boll distribution in cotton
Authors: NIE Junjun , QIN Dulin , MAO Lili , LIU Yanhui , DONG Hezhong , SONG Xianliang , SUN Xuezhen
Published: June 2020

Background

Photosynthate partitioning and within-plant boll distribution play an important role in yield formation of cotton; however, if and how they interact to mediate yield remains unclear. The objective of this study was to investigate the genotypic variance in photosynthate partitioning and within-plant boll distribution, with a focus on their interactions with regard to yield and yield components. A field experiment was conducted in the Yellow River region in China in 2017 and 2018 using a randomized complete block design with three replicates. Photosynthate partitioning of three commercial cultivars (DP 99B, Lumianyan 21 and Jimian 169), varying in yield potential, to different organs (including bolls) at early flowering, peak flowering, and peak boll-setting stages, as well as within-plant boll distribution at harvest, and their effects on yield formation were examined.

Results

Lint yield of Jimian 169 was the highest, followed by Lumianyan 21 and DP 99B. Similar differences were observed in the number of inner bolls and boll weight among the three cultivars. J169 partitioned significantly more photosynthate to the fruit and fiber than Lumianyan 21 and DP 99B and allocated over 80% of assimilates to the inner bolls. Additionally, Lumianyan 21 allocated a higher proportion of photosynthate to bolls and fiber, with 12.5%–17.6% more assimilates observed in the inner bolls, than DP 99B.

Conclusions

Genotypic variance in lint yield can be attributed to differences in the number of inner bolls and boll weight, which are affected by photosynthate partitioning. Therefore, the partitioning of photosynthate to fiber and inner bolls can be used as an important reference for cotton breeding and cultivation.
Double staining method for array tomography using scanning electron microscopy
Authors: Kim Eunjin , Lee Jiyoung , Noh Seulgi , Kwon Ohkyung , Mun Ji Young
Published: June 2020

Scanning electron microscopy (SEM) plays a central role in analyzing structures by imaging a large area of brain tissue at nanometer scales. A vast amount of data in the large area are required to study structural changes of cellular organelles in a specific cell, such as neurons, astrocytes, oligodendrocytes, and microglia among brain tissue, at sufficient resolution. Array tomography is a useful method for large-area imaging, and the osmium-thiocarbohydrazide-osmium (OTO) and ferrocyanide-reduced osmium methods are commonly used to enhance membrane contrast.

Because many samples prepared using the conventional technique without en bloc staining are considered inadequate for array tomography, we suggested an alternative technique using post-staining conventional samples and compared the advantages.
Resilience modeling concepts in transportation systems: a comprehensive review based on mode, and modeling techniques
Authors: Ahmed Shofiq , Dey Kakan
Published: June 2020

The objective of this comprehensive review study was to compile a state-of-the-art understanding of the resilience of the transportation system due to natural and man-made disasters. This study identified resilience measurement parameters that can be used to formulate resilience quantification and improvement strategies of a transportation system. Reviewed articles were classified and summarized from two perspectives: (i) modeling based on the mode of transportation; and (ii) modeling based on the mathematical technique used to quantify resilience. One of the unique contributions of this review article is that it compiled the key resilience indices that were analyzed to quantify resilience. This review revealed that the majority of the scholarly articles on the topic of transportation system resilience published since 2006, were focused on the resilience of the roadway-based transportation system, and vulnerability was one of the most explored resilience indices in evaluating transportation system resilience. Several future research directions were identified considering the implications of emerging transportation technologies (e.g., connected and automated vehicle technology). The complex interdependency among critical infrastructure systems such as power, transportation, and communication system, as well as the cybersecurity issues in the advanced intelligent transportation system, will be vital in the resilience analysis of future transportation systems.
Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors
Authors: Yap Timothy A. , O’Carrigan Brent , Penney Marina S. , Lim Joline S. , Brown Jessica S. , de Miguel Luken Maria J. , Tunariu Nina , Perez-Lopez Raquel , Rodrigues Daniel Nava , Riisnaes Ruth , Figueiredo Ines , Carreira Suzanne , Hare Brian , McDermott Katherine , Khalique Saira , Williamson Chris T. , Natrajan Rachael , Pettitt Stephen J. , Lord Christopher J. , Banerji Udai , Pollard John , Lopez Juanita , de Bono Johann S.
Published: June 2020

PURPOSE

Preclinical studies demonstrated that ATR inhibition can exploit synthetic lethality (eg, in cancer cells with impaired compensatory DNA damage responses through ATM loss) as monotherapy and combined with DNA-damaging drugs such as carboplatin.

PATIENTS AND METHODS

This phase I trial assessed the ATR inhibitor M6620 (VX-970) as monotherapy (once or twice weekly) and combined with carboplatin (carboplatin on day 1 and M6620 on days 2 and 9 in 21-day cycles). Primary objectives were safety, tolerability, and maximum tolerated dose; secondary objectives included pharmacokinetics and antitumor activity; exploratory objectives included pharmacodynamics in timed paired tumor biopsies.

RESULTS

Forty patients were enrolled; 17 received M6620 monotherapy, which was safe and well tolerated. The recommended phase II dose (RP2D) for once- or twice-weekly administration was 240 mg/m2. A patient with metastatic colorectal cancer harboring molecular aberrations, including ATM loss and an ARID1A mutation, achieved RECISTv1.1 complete response and maintained this response, with a progression-free survival of 29 months at last assessment. Twenty-three patients received M6620 with carboplatin, with mechanism-based hematologic toxicities at higher doses, requiring dose delays and reductions. The RP2D for combination therapy was M6620 90 mg/m2 with carboplatin AUC5. A patient with advanced germline BRCA1 ovarian cancer achieved RECISTv1.1 partial response and Gynecologic Cancer Intergroup CA125 response despite being platinum refractory and PARP inhibitor resistant. An additional 15 patients had RECISTv1.1 stable disease as best response. Pharmacokinetics were dose proportional and exceeded preclinical efficacious levels. Pharmacodynamic studies demonstrated substantial inhibition of phosphorylation of CHK1, the downstream ATR substrate.

CONCLUSION

To our knowledge, this report is the first of an ATR inhibitor as monotherapy and combined with carboplatin. M6620 was well tolerated, with target engagement and preliminary antitumor responses observed.
Developing HME-Based Drug Products Using Emerging Science: a Fast-Track Roadmap from Concept to Clinical Batch
Authors: Matić Josip , Paudel Amrit , Bauer Hannes , Garcia Raymar Andreina Lara , Biedrzycka Kinga , Khinast Johannes G.
Published: June 2020

This paper presents a rational workflow for developing enabling formulations, such as amorphous solid dispersions, via hot-melt extrusion in less than a year. First, our approach to an integrated product and process development framework is described, including state-of-the-art theoretical concepts, modeling, and experimental characterization described in the literature and developed by us. Next, lab-scale extruder setups are designed (processing conditions and screw design) based on a rational, model-based framework that takes into account the thermal load required, the mixing capabilities, and the thermo-mechanical degradation. The predicted optimal process setup can be validated quickly in the pilot plant. Lastly, a transfer of the process to any GMP-certified manufacturing site can be performed in silico for any extruder based on our validated computational framework. In summary, the proposed workflow massively reduces the risk in product and process development and shortens the drug-to-market time for enabling formulations.
The transcription factor Maz is essential for normal eye development
Authors: Medina-Martinez Olga , Haller Meade , Rosenfeld Jill A. , O'Neill Marisol A. , Lamb Dolores J. , Jamrich Milan
Published: June 2020

Wnt/β-catenin signaling plays an essential role in eye development. Faulty regulation of this pathway results in ocular malformations due to defects in cell fate determination and differentiation. Herein we show that disruption of Maz, the gene encoding Myc-associated zinc finger transcription factor, produces developmental eye defects in mice and humans. Expression of key genes involved in the Wnt cascade, Sfrp2, Wnt2b and Fzd4 were significantly increased in mice with targeted inactivation of Maz, resulting in abnormal peripheral eye formation with reduced proliferation of the progenitor cells in the region. Paradoxically, the Wnt reporter TCF-Lef1 displayed a significant downregulation in Maz-deficient eyes. Molecular analysis indicates that Maz is necessary for the activation of the Wnt/β-catenin pathway and participates in the network controlling ciliary margin patterning. Copy number variations and single nucleotide variants of MAZ were identified in humans that result in abnormal ocular development. The data support MAZ as a key contributor to the eye comorbidities associated with chromosome 16p11.2 copy number variants and as a transcriptional regulator of ocular development.
Scientific Rationale for RPE Use in Fitness Assessment and Exercise Participation
Authors: Kilpatrick Marcus , Newsome A’Naja , Foster Carl , Robertson Robert , Green Matt
Published: June 2020

Apply It!

• Fitness professionals will learn the different ways that RPE scales can be used.

• Fitness professionals will have newfound confidence in the importance of regulating exercise by using RPE scales.

• Fitness professionals will be able to properly use RPE scales during exercise testing and prescription.
A modified Cuckoo Search algorithm based optimal band subset selection approach for hyperspectral image classification
Authors: Sawant Shrutika , Prabukumar Manoharan , Samiappan Sathishkumar
Published: June 2020

Band selection is an effective way to reduce the size of hyperspectral data and to overcome the “curse of
dimensionality” in ground object classification. This paper presents a band selection approach based on modified Cuckoo
Search (CS) optimisation with correlation-based initialisation. CS is a popular metaheuristic algorithm with efficient
optimisation capabilities for band selection. However, it can easily fall into local optimum solutions. To avoid falling into a
local optimum, an initialisation strategy based on correlation is adopted instead of random initialisation to initiate the location
of nests. Experimental results with Indian Pines, Salinas and Pavia University datasets show that the proposed approach
obtains overall accuracy of 82.83 %, 94.83 % and 91.79 %, respectively, which is higher than the original CS algorithm,
Genetic Algorithm (GA), Particle Swarm Optimisation (PSO) and Gray Wolf Optimisation (GWO).
Me and my virtual presence: an autoethnographic vignette
Authors: Gkini Christina
Published: June 2020

Internet has allowed for a certain flexibility regarding the limits of connection, communication, and collaboration between people. It is, however, necessary that we maintain a critical stance towards its affordances so that we can continue to improve upon them. In this autoethnographic vignette, I will try to share my experience as a virtual, ‘disembodied other’ in a collaborative learning environment, focusing mainly on the limitations and problems I encountered during the process. This experience pertains to the project hub2001: An Internet Odyssey, which was developed for the course Cyber Cultures: Psychosocial implicationsoffered by the Psychology Department of Panteion University, Athens, Greece in the spring semester of the 2015-16 academic year. During this project, I participated virtually in the weekly lectures and meetings between the tutor and his assistants, and reflected, both individually and at the group level, on the course process. One of these reflections is further explored in this paper, aiming to present an experience which, although personal, can contribute in our understanding of the lived reality of the increasingly more common remote collaboration and virtual presence, especially in academic environments.
Mutation profiling of anaplastic ependymoma grade III by Ion Proton next generation DNA sequencing
Authors: Butt Ejaz , Alyami Sabra , Nageeti Tahani , Saeed Muhammad , AlQuthami Khalid , Bouazzaoui Abdellatif , Athar Mohammad , Abduljaleel Zainularifeen , Al-Allaf Faisal , Taher Mohiuddin
Published: June 2020

Background: Ependymomas are glial tumors derived from differentiated ependymal cells. In contrast to other types of brain tumors, histological grading is not a good prognostic marker for these tumors. In order to determine genomic changes in an anaplastic ependymoma, we analyzed its mutation patterns by next generation sequencing (NGS).

Methods:  Tumor DNA was sequenced using an Ion PI v3 chip on Ion Proton instrument and the data were analyzed by Ion Reporter 5.6.

Results: NGS analysis identified 19 variants, of which four were previously reported missense variants; c.395G>A in IDH1, c.1173A>G in PIK3CA, c.1416A>T in KDR and c.215C>G in TP53. The frequencies of the three missense mutations (PIK3CA c.1173A>G, KDR c.1416A>T, TP53, c.215C>G) were high, suggesting that these are germline variants, whereas the IDH1 variant frequency was low (4.81%). However, based on its FATHMM score of 0.94, only the IDH1 variant is pathogenic; other variants TP53, PIK3CA and KDR had FATHMM scores of 0.22, 0.56 and 0.07, respectively. Eight synonymous mutations were found in FGFR3, PDGFRA, EGFR, RET, HRAS, FLT3, APC and SMAD4 genes. The mutation in FLT3 p.(Val592Val) was the only novel variant found. Additionally, two known intronic variants in KDR were found and intronic variants were also found in ERBB4 and PIK3CA. A known splice site mutation at an acceptor site in FLT3, a 3’-UTR variant in the CSF1R gene and a 5’_UTR variant in the SMARCB1 gene were also identified. The p-values were below 0.00001 for all variants and the average coverage for all variants was around 2000x.

Conclusions: In this grade III ependymoma, one novel synonymous mutation and one deleterious missense mutation is reported. Many of the variants reported here have not been detected in ependymal tumors by NGS analysis previously and we therefore report these variants in brain tissue for the first time.
Effect of supraneural transforaminal epidural steroid injection combined with caudal epidural steroid injection with catheter in chronic radicular pain management: Double blinded randomized controlled trial.
Authors: Munjupong Sithapan , Kumnerddee Wipoo
Published: June 2020

Background: Epidural steroid injection (ESI) has been used in managing chronic radicular pain. Regarding various techniques of ESI, the synergistic effect of caudal ESI (CESI) on transforaminal ESI (TFESI) in chronic lumbosacral radicular pain in prospective randomized controlled trial has not been determined. Methods:  A total of 54 eligible patients with lumbosacral radicular pain were randomly allocated to undergo TFESI plus CESI (TC group) or TFESI alone (T group).  The effective response to treatment was predefined by at least a 50% reduced verbal numerical rating scale (VNRS) from baseline between group comparison and the functional outcomes as measured by improved Oswestry Disability Index by least 15 points from baseline. All participants were evaluated using a single blinded outcome assessor before the  procedure and at 1, 3 and 6 months after the procedure. P <0.05 was considered as statistically significant. Results:  Average VNRS reduced significantly from baseline after receiving procedure at 1, 3 and 6 months in both groups (P-value <0.05). However, the TC group showed significant pain relief compared with the T group in spondylolisthesis and failed back surgery syndrome at 1 month. No statistical difference was observed between group comparisons of functional outcomes.

Conclusions: A treatment combining TFESI and CESI showed significant pain relief over TFESI alone in spondylolithesis and failed back surgery syndrome at 1 month. No effect was found concerning functional evaluation.

Registration: Thai Clinical Trials Registry ID TCTR20171101002 01/11/2017
biogitflow: development workflow protocols for bioinformatics pipelines with git and GitLab
Authors: Kamoun Choumouss , Roméjon Julien , de Soyres Henri , Gallois Apolline , Girard Elodie , Hupé Philippe
Published: June 2020

The use of a bioinformatics pipeline as a tool to support diagnostic and theranostic decisions in the healthcare process requires the definition of detailed development workflow guidelines. Therefore, we implemented protocols that describe step-by-step all the command lines and actions that the developers have to follow. Our protocols capitalized on two powerful and widely used tools: git and GitLab. They address two use cases: a nominal mode to develop a new feature in the bioinformatics pipeline and a hotfix mode to correct a bug that occurred in the production environment. The protocols are available as a comprehensive documentation at https://biogitflow.readthedocs.io and the main concepts, steps and principles are presented in this report.
Poland's Ability to Build Blocking Coalitions after Brexit
Authors: Kleinowski Marcin
Published: June 2020

The article presents the results of research on the impact of the United Kingdom’s withdrawal from the European Union on Poland’s ability to build small, minimalblocking coalitions in the Council of the European Union. To this end, the theory of voting games was used, but departing from the assumption that the creation of each possible coalition of players is equally likely. It was also assumedthat they do not necessarily make decisions independently of each other, and the analysis focuses on the ability to build minimally blocking coalitions. The obtained results indicate that after Brexit, for Poland to build a blocking coalition in opposition to the German-French tandem will be a very difficult task, and the loss of the United Kingdom as a potential coalition partner in the Council may be irreplaceable in some matters.
The University And Its Role in the Process of European Integrations
Authors: Jaric Isidora
Published: June 2020

The University And Its Role in the Process of European Integrations. The Dystopian Fairy Tale of Serbian University

The paper discusses the contemporary social role of the university in the three referent contexts: (a) the wider global context, (b) the regional context of European integrations, and (c) the local context of Serbian Society. The analysis discusses challenges of global context and university transformation, initial ideas of the Bologna process and the main directions of its implementation, and contemporary political and social challenges with the relationship between the university and its referent social environment and the value concepts shaping that relation. The latest tendencies of the abandonment of the university from its civil mission (Ćulum and Ledić, 2011) as one of the fundamental value concepts of modern universities has led to new escapist strategy that breaks the links between the university and the social environment in an almost artificial way. The paper discuss this tendency on the example of Serbian society and its university system, showing that the Serbian project of European integration has reached the point where it is necessary to articulate future directions of development so that they do not spontaneously take on malignant forms. On the one hand, breaking the link between the university and community jeopardizes the survivalof the university as we know it, and on the other hand, it eliminates serioussocial dialogue on the directions of future development.
Drainmod-Linked Interface for Evaluating Drainage System Response to Climate Scenarios
Authors: Adhikari Nidhi , Davidson Paul C. , Cooke Richard A. , Book Ruth S.
Published: June 2020

Abstract.

This article presents the development of a drainage-climate interface that incorporates climatological data, crop drainage requirements, and drainage theory into a procedure for characterizing drainage system response under different climate scenarios. The drainage-climate interface is suitable for assessing potential county-level impacts of climate change on crop production, soil hydrology and subsequently on subsurface drainage design. Climate model projections from two general circulation models (GCMs), namely CCSM4 (Community Climate System Model) and MIROC5 (Model for Interdisciplinary Research on Climate), were used to create the climatological database for the drainage-climate interface. DRAINMOD was integrated into the Visual Basic for Applications (VBA) portion of the interface to simulate the performance of subsurface drainage systems in Illinois for the near future (2040 to 2069) and the far future (2070 to 2099) periods. Case studies were developed with the interface for Adams and Champaign Counties in Illinois for their predominant soil types. Hydrologic simulations from the interface were used to determine the optimal depth and spacing of tile drains that maximize crop yield for corn and soybean during the mid and late 21st century. Drainage water management (DWM) was incorporated into the drainage-climate interface to investigate the potential of DWM in the future climate scenarios to maintain water quality, reduce nutrient losses and minimize pollutant loading from drained fields by controlling the timing and amount of water discharged from agricultural drainage systems. Results from DRAINMOD simulations with MIROC5 show a significant decline in crop yield due to extreme heat stress. Corn yield in the future showed a severe reduction while the yield for soybean demonstrated a gradual decline over the years. DWM had only a minimal effect on future crop yield trends. The drainage-climate interface simulated subsurface drainage conditions and made evident the consequences of environmental conditions on crop physiological processes under scenarios of climate change predicted by MIROC5. Keywords: Agricultural system models, Climate change impacts, Drainage-climate interface, Drainage water management, Subsurface drainage, Tile drain depth, Tile drain spacing.
Experimental Evaluation of Chain-Driven Mesh Belt Sorting System for Machine-Plucked Fresh Tea Leaves
Authors: Rongyang Wang , Liang Sun , Zhiwei Chen , Wenguang Zheng , Yudong Zhang , Junhua Tong , Yang Ye , Chuanyu Wu
Published: June 2020

Highlights

A chain-driven mesh belt sorting system for machine-plucked fresh leaves was developed.

The sorting system are evaluated with respect to provide the quality and consistency necessary to produce famous green tea.

The Grade-A-, Grade-B, and Grade-C leaves can be sorted out from raw Grade-D machine-plucked fresh leaves.

Abstract. Due to the varying contents of machine-plucked fresh tea leaves when harvesting in summer/autumn green tea at different times, they can only be used to produce bulk green tea, it is difficult to produce famous high-quality green tea, limiting the economic benefits of using mechanical plucking technology. In this study, a chain-driven mesh belt sorting system was developed to address the uneven quality grade of machine-plucked fresh leaves in order to grade high-quality leaves for famous green tea according to their shape and consistency. The operating parameters and the sorting effectiveness of the proposed method were evaluated using separation experiments. The results show that raw collected Grade-D machine-plucked fresh leaves can be sorted into Grade-A-, Grade-B, and Grade-C material by a series of four collectors. The mass of debris (old stems, leaves, fragments, or buds) in the final collector accounted for 94.38% of the remaining material, while 47.65% of leaves from the initial collector were separated out as one-bud-multi-leaves. The application of additional separation cycles using the same stage collector was found to further increase the classification of the separated high-quality tea leaves from Grade-A- to Grade-A to Grade-A+. The results of these experiments reveal that the proposed system can classify fresh leaves according to their shape and tenderness, providing high-quality leaves for subsequent mechanized tea production and improving the economics of tea production. These findings are of considerable theoretical significance for the design of high-efficiency and low-damage automatic grading devices for machine-plucked fresh tea leaves. Keywords: Agricultural machinery, Chain-driven mesh belt, Grading, Machine-plucked fresh leaves, Tea sorting.
Experimental Research on Sugarcane Under-the-Ground Basecutting
Authors: Bai Jing , Ma Shaochun , Ke Wenli , Wang Fenglei , Xing Haonan , Ma Jinzhi , Gao Shili
Published: June 2020

Abstract.

Basecutting, an important process in mechanical sugarcane harvesting, has important influence on the development of sugarcane mechanical harvesting. Previous studies mainly focus on kinematic and dynamic models in theory and indoor basecutting tests. However, few studies have explored the cutting mode of basecutter and power consumption with under-the-ground basecutting mode. The objective of this study was to compare two different basecutting modes (above-the-ground basecutting and under-the-ground basecutting), investigate the cutting power consumption and the cutting quality when sugarcane was cut in the optimal cutting mode. Through the means of simulation analysis and contrast experiment comparison, it concluded that the under-the-ground basecutting mode was better than above-the-ground basecutting mode to improve the cutting quality but it has increased the cutting power consumption of basecutters. In the under-the-ground basecutting mode, the orthogonal experiment was carried out using the existing sugarcane harvester, in order to minimize the power consumption while keeping the stubble broken rate to an acceptable level. With the power consumption and stubble broken rate being set as the indexes, the effects of basecutting depth, disc rotational speed, and the harvester forward speed on basecutting performance were investigated. Through the analysis of variance and range analysis, the influence of each factor on the evaluation index was obtained, and the best parameter combination with minimum stubble broken rate and power consumption were determined: the basecutting depth was 40 mm, the disc rotation speed was 600 rpm, and the harvester forward speed was 0.6 m/s. This study provided necessary information to guide engineers to design high-performance basecutter with under-the-ground basecutting mode. Keywords: Basecutter, Cutting mode, Power consumption, Stubble broken rate, Under-the-ground basecutting.