bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shikimate Kinase Expression; Towards Screening of Potential Antibacterials from Marine Sponges
Authors: Ogrodniczuk Marcin , Motilall Anand , Fuanta René 
Published: April 2020

Tuberculosis is one of the world’s leading cause of mortality from a single bacterial pathogen, with over 10 million reported cases each year. There is an alarming increase in the prevalence of drug‐resistant strains, thus the need for the discovery of novel anti‐tubercular agents. The shikimate pathway is a seven‐step metabolic route that produces aromatic amino acids and other cellular metabolites. It has no mammalian counterpart, making any of the enzymes in this pathway suitable targets for screening of potential anti‐tubercular agents. Mycobacterium tuberculosis shikimate kinase (MtSK) catalyzes the 5th step of this pathway, converting shikimate to shikimate‐3‐phosphate using ATP as a co‐substrate. The overall goal of this project is to express and characterize MtSK and screen for potential anti‐tubercular agents. Transformation of XL‐1 blue competent cells was performed using a pET 21b plasmid with aroK gene inserted at the multiple cloning site. Plasmids were cloned and purified and used to transform BL 21 DE3 competent cells for subsequent protein expression. Small scale expression showed the presence of a band of increasing prominence around 20 kDa. This suggests MtSK was successfully expressed. Expression analysis for larger scale supported data from small scale. Purification, characterization, and MtSK kinetic parameters would be determined prior to enzyme inhibition studies using inhibitors like avarone (below), a marine sponge sesquiterpene quinone and derivatives thereof.Support or Funding InformationEast Stroudsburg University of PennsylvaniaAvaroneFigure 1
Assessment of Quadriceps Contraction Using a Novel Surface Mechanomyography Sensor During a Neuromuscular Control Screening Task
Authors: Linderman Shannon , Aspenleiter Ryan , Stein Hannah , Berkson Eric 
Published: April 2020

PURPOSENeuromuscular control is an important factor for injury incidence and post‐surgical rehabilitation. Surface Mechanomyography (sMMG) sensors are novel wearable devices that are applied over a muscle group to measure the physical output of muscle deformation resulting from a muscle contraction. Electromyography (EMG) is the clinical standard for assessing the electrical signal identifying muscle activation. However, well‐established data collection and analysis challenges limit the utility of EMG for wide‐spread neuromuscular control screening in a clinic environment. The purpose of this study was to investigate the ability of sMMG sensors to detect timing patterns of muscle contraction and compare time events to those collected through traditional clinical EMG during a bilateral squat task.METHODSEleven healthy, active individuals (mean age= 30.0 ± 10.77 y, 7 males, 4 females) underwent a neuromuscular control assessment with EMG and sMMG sensors simultaneously applied to the right quadriceps. Subjects performed a series of 3 bilateral deep squats. EMG data processed with a low‐pass 6th order Butterworth filter and a TKEO function, and raw sMMG data were used for timing analyses. Statistical analyses included paired T‐test assessments between measurement modalities.RESULTSThere was no significant difference in the timing of total duration of quadriceps contraction between EMG (mean= 2.526 ± 0.553 s) and sMMG (mean= 2.527 ± 0.539 s), p= 0.985. The duration of quadriceps contraction during the descent phase of the squat (eccentric contraction, p= 0.773) and the ascent phase (concentric contraction, p= 0.298) did not differ significantly between modalities.CONCLUSIONSResults are consistent with physiologic expectations that myoelectrical activity (measured by EMG) and the physical muscle deformation of muscles (measured by sMMG) occur in extremely rapid succession. Successful sMMG detection of quadriceps contraction is supported by similarity to EMG time signatures. Findings also suggest the ability of sMMG sensors to detect timing of activation for different types of muscle contraction during a functional exercise without the need for complex signal processing (Figure
1). The sMMG sensor may be helpful for assessing quadriceps muscle performance and timing as part of quick, in‐the‐clinic neuromuscular control screenings for injury prevention, rehabilitation, and exercise training.Example of data analysis steps for comparison between electromyography (EMG) and surface mechanography (sMMG) timing during a bilateral squat taskFigure 1
Postnatal administration of leptin antagonist mitigates susceptibility to obesity under high‐fat diet in αMUPA male mice
Authors: Gutman Roee 
Published: April 2020

Perturbations in postnatal leptin signaling have been associated with altered susceptibility to diet‐induced obesity (DIO), under high‐fat‐diet (HFD), albeit with contradicting evidence. Previous studies have shown that Alpha murine urokinase‐type plasminogen activator (αMUPA) mice have a higher and longer postnatal leptin surge compared with their wild types (WT), as well as lower body weight and food intake under regular diet (RD). Here we explore αMUPA’s propensity to DIO and the effect of attenuating postnatal leptin signaling, using leptin antagonist, on energy homeostasis under both RD and HFD. Four‐day‐old αMUPA pups were treated on alternate days until P‐18 with either vehicle or leptin antagonist (LA; 10 or 20 mg d−1 kg−1) and weaned into RD or HFD. Compared with RD‐fed αMUPA males, HFD‐fed αMUPA males showed higher energy intake, even when corrected for bodyweight difference, and became hyperinsulinemic and obese. Additionally, HFD‐fed αMUPA males gained bodyweight at a higher rate than their WTs due mainly to strain‐differences in energy expenditure. LA administration did not affect strain differences under RD, but attenuated αMUPA’s hyperinsulinemia and DIO under HFD, most likely by mediating energy expenditure. Together with our previous findings, these results suggest that αMUPA’s leptin surge underlies its higher susceptibility to obesity under HFD, highlighting the role of leptin‐related developmental processes in inducing obesity under post weaning obesogenic environment, at least in αMUPA males. This study, therefore, supports the use of αMUPA mice for elucidating developmental mechanisms of obesity and the efficacy of early‐life manipulations via leptin surge axis in attenuating DIO.Support or Funding InformationFrom the Union’s Seventh Framework Program FP7‐REGPOT‐2012‐2013‐1, Agreement no. 316157The effect of high‐fat diet (HFD) compared with regular diet (RD) on energy homeostasis of saline‐treated αMUPA and FVB/N wild‐type male pups. (A) Body weight; (B) body weight and composition at nine months of age; (C) energy balance. Abbreviations: FFM, fat‐free mass. N, 6–7 mice per treatment. Non‐matching lowercase letters indicate statistically significant differences among groups. *, statistically significant difference from zero, P<0.05. Results are presented as mean ± SEM.Figure 1The effect of leptin antagonist (LA) compared with saline on αMUPA under regular (RD) and high‐fat (HFD) diets, also compared HFD‐fed saline‐treated WT. Bodyweight (A) and composition at 9 mo of age (B); (C) Energy balance. Abbreviations: FFM, fat‐free mass; LA‐10, 10 mg·day‐1·kg‐1 of LA injections; LA‐20, 20 mg·day‐1·kg‐1 of LA injections. d, Day; Δ, change. Nonmatching letters indicate differences among groups. * and # difference from zero, P < 0.05 and P < 0.01.Figure 2
Codon Optimization of Gene Editing CRISPR‐SaCas9 Plasmid Increases Protein Expression in Human Liver Cells to Boost in vivo Therapeutic Knockout Application Efficiency
Authors: Groshong Tyler L , Madejski Irene R , Sundaresan Avirath , Gupta Ishir G , Holmes Grace D , De Luke 
Published: April 2020

The CRISPR‐Cas9 gene editing technology shows great promise in revolutionizing the treatment of genetic disease; however, the current focus on treatment by ex vivo delivery is limited to blood diseases. In vivo treatment can substantially extend the clinical reach of the technology, but is limited by a challenging delivery process: the large size of the Cas9 gene (~4500bp) inhibits delivery by the small viral vectors and lipid nanoparticles used. We propose that a codon‐optimized saCas9 plasmid will lead to significantly higher protein expression than the presently used genes; this can compensate for the low delivery efficiency and has great potential to improve the viability of in vivo CRISPR‐Cas9 therapies. Here we present Western Blot fluorescence data showing that optimization leads to increased Cas9 production and subsequently increased CRISPR‐Cas9 editing efficiency.A commonly used parent saCas9 sequence was selected from Addgene’s public plasmid database. A novel, codon‐optimized gene sequence was engineered from the parent using GenScript’s OptimumGeneTM algorithm. Both the optimized gene and parent gene were transfected into human HepG2 liver cells, and Western Blot/ELISA protein quantification of the optimized plasmid compared with three sample plasmids demonstrated that the codon‐optimized gene expressed the saCas9 protein at ~3.5× the rate of the commercial sequence. The same set of optimized and commercial plasmids were then transfected into GFP‐stable HepG2 cells in parallel with GFP‐specific sgRNA; the cells transfected with optimized saCas9 demonstrated a significantly higher GFP knockout rate than cells transfected with commercially available control plasmids, as measured through GFP detection stay and Western Blot on GFP proteins. The augmented Cas9 protein expression supported by the novel saCas9 sequence can better enable in vivo CRISPR‐Cas9 treatments.Support or Funding InformationThis work was supported by The Nueva School.Comparison of Commercial and Optimized SaCas9 ExpressionFigure 1SaCas9 Protein Standard CurveFigure 2
Pretransplant Hypoalbuminemia As A Predictor of Medical Arterial Calcification During Waiting List Pre‐Kidney Transplant Period: A Propensity Score Weighting Analysis
Authors: Tantisattamo Ekamol , Leelaviwat Natnicha , Lopimpisuth Chawit , Saowapa Sakditad , Polpichai Natchaya , Vutthikraivit Possawat 
Published: April 2020

IntroductionMedial arterial calcification (MAC) is common in advanced chronic kidney disease and end‐stage renal disease. Whether serum albumin as a surrogate marker of inadequate dialysis is associated with MAC is unknown.MethodsSince breast arterial calcification is exclusively medial, mammogram was used to identify MAC. Renal transplant recipients (RTR) with MG during pretransplant period was divided into 2 groups: pretransplant normoalbuminemia and hypoalbuminemia (serum albumin <4 g/dL). Baseline characteristics including potential confounders were balanced by propensity score weighting(PSW). Association between serum albumin status and MAC during pretransplant period is examined by multiple logistic regression.ResultsOf 51 RTR, mean age±SD was 57±10.5 years old and the majority were white 28 (54%) followed by African American 18 (35%) and others 5 (9%) patients. Five patients never been on dialysis and 34 patients had dialysis (29 with hemodialysis and 5 with peritoneal dialysis) with a median time of dialysis prior to kidney transplantation was 3.79 years (0.72 to 20.38 years). Among 34 patients with hypoalbuminemia, 16 patients had MAC; whereas only 4 out of 17 patients in normoalbuminemia had MAC (47.06% vs. 23.53%, p 0.135). Mean serum albumin were 3.3±0.6 and 4.2±0.2 g/dL in hypoalbuminemic and normoalbuminemic groups, respectively (p <0.001). Baseline characteristics and potential confounders including age, race, cause of kidney diseases, dialysis modalities, pretransplant obesity status, diabetes, corrected calcium, and phosphorus were balanced by using PSW with generalized boosted modeling (Figure
and
). Hypoalbuminemic group had 3.09 times higher the odds of having MAC compared to normoalbuminemic group, but the association was not significant (OR 3.09; 95%CI 0.62 to 15.41). By using multiple logistic regression with adjustment for co‐variated used in the PSW, the magnitude of the association became significant with a 75.55 times greater the odds of MAC in hypoalbuminemic group compared to normoalbuminemic group (OR 75.55; 95%CI 1.42 to 4013.69).ConclusionsNot only being one of the surrogate markers of malnutrition and inadequate dialysis, hypoalbuminemia is also associated with MAC in well‐matched study population using PSW. Since MAC is associated with higher mortality in RTR, hypoalbuminemia during pretransplantation should be corrected to improve posttransplant outcomes.Love plot estimating propensity score weights using generalized boosted modeling with balancing covariatesFigure 1Histogram estimating propensity score weights using generalized boosted modeling with balancing covariatesFigure 2
Integrating hands‐on model building with graded online discussions to learn DNA structure‐function relationships in an upper level General Biochemistry course for majors
Authors: Hite Kristopher Charles 
Published: April 2020

An active‐learning DNA structure/function exercise was undertaken in a 4000‐level majors biochemistry course. During the fourth in‐person class period of the spring 2020 semester majors enrolled in a three‐credit General Biochemistry course were asked to build a physical model of DNA consisting of one turn of the helix including 10 base‐pairs. Students were told to self‐associate into groups of six and each group was then instructed to build a specific base‐pair: 5 groups were assigned GC, 5 were assigned AT. Students were further instructed to divide the labor by partnerships, one to build a purine base, another to build the complementary pyrimidine, and the third to build the sugar‐phosphate. The class was provided with large bundles of six different brightly colored pipe‐cleaners, a bamboo skewer to use as an in‐plane scaffold for the base‐pairs, a large ring stand, and 10 perpendicular rod clamps. They were then given 10 minutes to build their respective base‐pairs then the last five minutes to work together as a class to assemble a single model. The instructor and many students photographed the model and uploaded image files to the online learning platform accompanied by the following prompt.“How much information can we obtain from the admittedly incomplete model we built in class today? Examine the photograph and see if you can decipher the sequence on the two strands. We know adenine is yellow, thymine is purple, guanine is orange, and cytosine is blue. If this sequence were part of a gene which amino acids might they encode? What information would help us answer these questions more precisely? Feel free to share any photos you took during class in replies to this post. You may opt‐out of any one of the next three weekly graded discussions by building your own improved, more beautiful model using the same starting materials for equal credit.”This exercise incorporates multiple active‐learning techniques simultaneously including elements of “think‐pair‐share” during the initial partnership phase, small group work during the assembly of the mononucleotides, and large group cooperation during final assembly of the model. The online follow‐up discussion and optional model‐refinement assignment allow individualized student‐driven engagement with the structure of DNA and how it works to store genetic information.Support or Funding InformationDepartment of Biochemistry College of Agriculture and Life Sciences at Virginia Polytechnic and State University (Virginia Tech)A single turn of the DNA double‐helix: a physical model cooperatively created by students in a 4000 level General Biochemistry course as part of an active‐learning exercise. Model built with large ring stand, 10 perpendicular rod clamps, brighlty‐colored pipe‐cleaners, bamboo skewers, and small plastic beads.Figure 1
Epidemiological and Genomic Analysis of SARS-CoV-2 in Ten Patients from a Mid-sized City outside of Hubei, China
Authors: Chen Jinkun , Hilt Evann E. , Wu Huan , Jiang Zhuojing , Zhang QinChao , Wang JiLing , Wang Yifang , Li Fan , Li Ziqin , Tang Jialiang , Yang Shangxin 
Published: April 2020

ABSTRACTA novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from ten patients in Shaoxing, a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with > 99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR Ct values less than 28. We found that a cluster of 4 patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium and Australia, highlighting how quickly this virus spread to the globe. The virus from another cluster of two family members living together without travel history but with a sick contact of a confirmed case from another city outside of Hubei accumulated significantly more mutations (9 SNPs vs average 4 SNPs), suggesting a complex and dynamic nature of this outbreak. We also found 70% patients in this study had the S genotype, consistent with an early study showing a higher prevalence of genotype out of Hubei than that inside Hubei. We calculated an average mutation rate of 1.37×10−3 nucleotide substitution per site per year, which is similar to that of other coronaviruses. Our findings add to the growing knowledge of the epidemiological and genomic characteristics of SARS-CoV-2 that are important for guiding outbreak containment and vaccine development. The moderate mutation rate of this virus also lends hope that development of an effective, long-lasting vaccine may be possible.
Impact of non-pharmaceutical interventions on documented cases of COVID-19
Authors: Banholzer Nicolas , van Weenen Eva , Kratzwald Bernhard , Seeliger Arne , Tschernutter Daniel , Bottrighi Pierluigi , Cenedese Alberto , Salles Joan Puig , Vach Werner , Feuerriegel Stefan 
Published: April 2020

AbstractBackgroundThe novel coronavirus (SARS-CoV-2) has rapidly evolved into a global epidemic. To control its spread, countries have implemented non-pharmaceutical interventions (NPIs), such as school or border closures, while others have even enforced complete lockdowns. Here we study the impact of NPIs in reducing documented cases of COVID-19. Documented case numbers are selected because they are essential for decision-makers in the area of health-policy when monitoring and evaluating current control mechanisms.MethodsWe empirically estimate the relative reduction in the number of new cases attributed to each NPI. A cross-country analysis is performed using documented cases through April 15, 2020 from n = 20 countries (i.e., the United States, Canada, Australia, the EU-15 countries, Norway, and Switzerland).ResultsAs of April 15, venue closures were associated with a reduction in the number of new cases by 36 % (95% credible interval [CrI] 20–48 %), closely followed by gathering bans (34 %; 95% CrI 21–45 %), border closures (31 %; 95% CrI 19–42 %), and work bans on non-essential business activities (31 %; 95% CrI 16–44 %). Event bans lead to a slightly less pronounced reduction (23 %; 95% CrI 8–35 %). School closures (8 %; 95% CrI 0–23 %) and lockdowns (5 %; 95% CrI 0–14 %) appeared to be the least effective among the NPIs considered in this analysis.ConclusionsWith this cross-country analysis, we provide early estimates regarding the impact of different NPIs for controlling the COVID-19 epidemic. These findings are relevant for evaluating current health-policies.
Diagnosis and Prediction Model for COVID-19 Patient’s Response to Treatment based on Convolutional Neural Networks and Whale Optimization Algorithm Using CT Images
Authors: Elghamrawy Sally , Hassanien Aboul Ella 
Published: April 2020

AbstractThe outbreak of coronavirus diseases (COVID-19) has rabidly spread all over the world. The World Health Organization (WHO) has announced that coronavirus COVID-19 is an international pandemic. The Real-Time Reverse transcription-polymerase Chain Reaction (RT-PCR) has a low positive and sensitivity rate in the early stage of COVID-19. As a result, the Computed Tomography (CT) imaging is used for diagnosing. COVID-19 has different key signs on a CT scan differ from other viral pneumonia. These signs include ground-glass opacities, consolidations, and crazy paving. In this paper, an Artificial Intelli-gence-inspired Model for COVID-19 Diagnosis and Prediction for Patient Response to Treatment (AIMDP) is proposed. AIMDP model has two main functions reflected in two proposed modules, namely, the Diagnosis Module (DM) and Prediction Module (PM). The Diagnosis Module (DM) is proposed for early and accurately detecting the patients with COVID-19 and distinguish it from other viral pneumonias using COVID-19 signs obtained from CT scans. The DM model, uses Convolutional Neural Networks (CNNs) as a Deep learning technique for segmentation, can process hundreds of CT images in seconds to speed up diagnosis of COVID-19 and contribute in its containment. In addition, some countries haven’t the ability to provide all patients with the treatment and intensive care services, so it will be mandatory to give treatment to only responding patients. In this context, the Prediction Module (PM) is proposed for predicting the ability of the patient to respond to treatment based on different factors e.g. age, infection stage, respiratory failure, multi-organ failure and the treatment regimens. PM implement the Whale Optimization Algorithm for selecting the most relevant patient’s features. The experimental results show promising performance for the proposed diagnosing and prediction modules, using a dataset with hundreds of real data and CT images.
Susceptibility and Sustainability of India against CoVid19: a multivariate approach
Authors: Ray Soumi , Roy Mitu 
Published: April 2020

AbstractPurposeWe are currently in the middle of a global crisis. Covid19 pandemic has suddenly threatened the existence of human life. Till date, as no medicine or vaccine is discovered, the best way to fight against this pandemic is prevention. The impact of different environmental, social, economic and health parameters is unknown and under research. It is important to identify the factors which can weaken the virus, and the nations which are more vulnerable to this virus.Materials and MethodsData of weather, vaccination trends, life expectancy, lung disease, number of infected people in the pre-lockdown and post-lockdown period of highly infected nations are collected. These are extracted from authentic online resources and published reports. Analysis is done to find the possible impact of each parameter on CoVid19.ResultsCoVid19 has no linear correlation with any of the selected parameters, though few parameters have depicted non-linear relationship in the graphs. Further investigations have shown better result for some parameters. A combination of the parameters results in a better correlation with infection rate.ConclusionsThough depending on the study outcome, the impact of CoVid19 in India can be predicted, the required lockdown period cannot be calculated due to data limitation.