bluuebunny/crossref_metadata_2025 huggingface dataset:
High expression of MKK3 is associated with worse clinical outcomes in African American breast cancer patients
Authors: Yang Xuan , Amgad Mohamed , Cooper Lee A. D. , Du Yuhong , Fu Haian , Ivanov Andrey A.
Published: September 2020

Background

African American women experience a twofold higher incidence of triple-negative breast cancer (TNBC) and are 40% more likely to die from breast cancer than women of other ethnicities. However, the molecular bases for the survival disparity in breast cancer remain unclear, and no race-specific therapeutic targets have been proposed. To address this knowledge gap, we performed a systematic analysis of the relationship between gene mRNA expression and clinical outcomes determined for The Cancer Genome Atlas (TCGA) breast cancer patient cohort.

Methods

The systematic differential analysis of mRNA expression integrated with the analysis of clinical outcomes was performed for 1055 samples from the breast invasive carcinoma TCGA PanCancer cohorts. A deep learning fully-convolutional model was used to determine the association between gene expression and tumor features based on breast cancer patient histopathological images.

Results

We found that more than 30% of all protein-coding genes are differentially expressed in White and African American breast cancer patients. We have determined a set of 32 genes whose overexpression in African American patients strongly correlates with decreased survival of African American but not White breast cancer patients. Among those genes, the overexpression of mitogen-activated protein kinase kinase 3 (MKK3) has one of the most dramatic and race-specific negative impacts on the survival of African American patients, specifically with triple-negative breast cancer. We found that MKK3 can promote the TNBC tumorigenesis in African American patients in part by activating of the epithelial-to-mesenchymal transition induced by master regulator MYC.

Conclusions

The poor clinical outcomes in African American women with breast cancer can be associated with the abnormal elevation of individual gene expression. Such genes, including those identified and prioritized in this study, could represent new targets for therapeutic intervention. A strong correlation between MKK3 overexpression, activation of its binding partner and major oncogene MYC, and worsened clinical outcomes suggests the MKK3-MYC protein–protein interaction as a new promising target to reduce racial disparity in breast cancer survival.
Bat population recoveries give insight into clustering strategies during hibernation
Authors: Martínková Natália , Baird Stuart J. E. , Káňa Vlastislav , Zima Jan
Published: September 2020

Background

Behaviour during hibernation contributes to energy conservation in winter. Hibernating bats select roosts with respect to physiological and environmental stressors, available local microclimate and species-specific requirements.

Results

We found that, in the period between 1977 and 2018, hibernatingMyotis myotisandRhinolophus hipposiderosbats showed exponential population growth. The growth rates, corrected for local winter seasonal severity and winter duration, were equal to 10 and 13%, respectively. WhileR. hipposiderosonly utilised the thermally stable and, at survey time, warmer corridors in the hibernaculum, an increasing proportion ofM. myotisroosted in the thermally stable corridors as their abundance increased. About 14% of all hibernatingM. myotisdisplayed solitary roosting, irrespective of other covariates. Those bats that clustered together formed progressively larger clusters with increasing abundance, particularly in cold corridors. We found no statistically significant relationship for clustering behaviour or cluster size with winter severity or winter duration.

Conclusions

Abundance of hibernating bats is increasing in Central Europe. As the number ofM. myotisbats increases, thermally unstable corridors become saturated with large clusters and the animals begin to roost deeper underground.
CRISPR-Cas9 enrichment and long read sequencing for fine mapping in plants
Authors: López-Girona Elena , Davy Marcus W. , Albert Nick W. , Hilario Elena , Smart Maia E. M. , Kirk Chris , Thomson Susan J. , Chagné David
Published: September 2020

Background

Genomic methods for identifying causative variants for trait loci applicable to a wide range of germplasm are required for plant biologists and breeders to understand the genetic control of trait variation.

Results

We implemented Cas9-targeted sequencing for fine-mapping in apple, a method combining CRISPR-Cas9 targeted cleavage of a region of interest, followed by enrichment and long-read sequencing using the Oxford Nanopore Technology (ONT). We demonstrated the capability of this methodology to specifically cleave and enrich a plant genomic locus spanning 8 kb. The repeated mini-satellite motif located upstream of the Malus × domestica (apple) MYB10 transcription factor gene, causing red fruit colouration when present in a heterozygous state, was our exemplar to demonstrate the efficiency of this method: it contains a genomic region with a long structural variant normally ignored by short-read sequencing technologies

Cleavage specificity of the guide RNAs was demonstrated using polymerase chain reaction products, before using them to specify cleavage of high molecular weight apple DNA. An enriched library was subsequently prepared and sequenced using an ONT MinION flow cell (R.9.4.1). Of the 7,056 ONT reads base-called using both Albacore2 (v2.3.4) and Guppy (v3.2.4), with a median length of 9.78 and 9.89 kb, respectively, 85.35 and 91.38%, aligned to the reference apple genome. Of the aligned reads, 2.98 and 3.04% were on-target with read depths of 180 × and 196 × for Albacore2 and Guppy, respectively, and only five genomic loci were off-target with read depth greater than 25 × , which demonstrated the efficiency of the enrichment method and specificity of the CRISPR-Cas9 cleavage.

Conclusions

We demonstrated that this method can isolate and resolve single-nucleotide and structural variants at the haplotype level in plant genomic regions. The combination of CRISPR-Cas9 target enrichment and ONT sequencing provides a more efficient technology for fine-mapping loci than genome-walking approaches.
Tagging and catching: rapid isolation and efficient labeling of organelles using the covalent Spy-System in planta
Authors: Lang Martina , Pröschel Marlene , Brüggen Nico , Sonnewald Uwe
Published: September 2020

Background

Up-to-now, several biochemical methods have been developed to allow specific organelle isolation from plant tissues. These procedures are often time consuming, require substantial amounts of plant material, have low yield or do not result in pure organelle fractions. Moreover, barely a protocol allows rapid and flexible isolation of different subcellular compartments. The recently published SpySystem enables the in vitro and in vivo covalent linkage between proteins and protein complexes. Here we describe the use of this system to tag and purify plant organelles.

Results

We developed a simple and specific method to in vivo tag and visualize, as well as isolate organelles of interest from crude plant extracts. This was achieved by expressing the covalent split-isopeptide interaction system, consisting of SpyTag and SpyCatcher, in Nicotiana benthamiana leaves. The functionality of the SpySystem in planta, combined with downstream applications, was proven. Using organelle-specific membrane anchor sequences to program the sub-cellular localization of the SpyTag peptide, we could tag the outer envelope of chloroplasts and mitochondria. By co-expression of a cytosolic, soluble eGFP-SpyCatcher fusion protein, we could demonstrate intermolecular isopeptide formation in planta and proper organelle targeting of the SpyTag peptides to the respective organelles. For one-step organelle purification, recombinantly expressed SpyCatcher protein was immobilized on magnetic microbeads via covalent thiol-etherification. To isolate tagged organelles, crude plant filtrates were mixed with SpyCatcher-coated beads which allowed isolation of SpyTag-labelled chloroplasts and mitochondria. The isolated organelles were intact, showed high yield and hardly contaminants and can be subsequently used for further molecular or biochemical analysis.

Conclusion

The SpySystem can be used to in planta label subcellular structures, which enables the one-step purification of organelles from crude plant extracts. The beauty of the system is that it works as a covalent toolbox. Labeling of different organelles with individual tags under control of cell-specific and/or inducible promoter sequences will allow the rapid organelle and cell-type specific purification. Simultaneous labeling of different organelles with specific Tag/Catcher combinations will enable simultaneous isolation of different organelles from one plant extract in future experiments.
The intergenerational impact of war on mental health and psychosocial wellbeing: lessons from the longitudinal study of war-affected youth in Sierra Leone
Authors: Betancourt Theresa S. , Keegan Katrina , Farrar Jordan , Brennan Robert T.
Published: September 2020

Background

Globally, one in four children lives in a country affected by armed conflict or disaster often accompanied by exposure to a range of adversities including violent trauma and loss. Children involved with armed groups (often referred to as “child soldiers”) typically exhibit high levels of mental health needs linked to their experiences. The Longitudinal Study of War-Affected Youth (LSWAY) in Sierra Leone is a seventeen-year prospective longitudinal study of the long-term effects of children’s experiences in the country’s eleven-year (1991–2002) civil war on their adult mental health and functioning in addition to exploring the potential mechanisms by which intergenerational transmission of emotional and behavioral disruptions due to war trauma may operate. LSWAY illuminates how war-related and post-conflict experiences shape long-term adult functioning, family dynamics, and developmental outcomes in offspring.

Discussion

The LSWAY study utilizes mixed methodologies that incorporate qualitative and quantitative data to unpack risk and protective factors involved in social reintegration, psychosocial adjustment, parenting, and interpersonal relationships. To date, study findings demonstrate striking levels of persistent mental health problems among former child soldiers as adults with consequences for their families, but also risk and protective patterns that involve family- and community-level factors. This case study examines the course of LSWAY from inception through implementation and dissemination, including building on the study results to design and evaluate several intervention models.

Conclusion

The case study offers a unique perspective on challenges and field realities of health research in a fragile, post-conflict setting common in the context of humanitarian emergencies. LSWAY findings along with lessons learned from the field can inform future research as well as intervention research and implementation science to address the mental health and development of war-affected young people. With four waves of data collection and a planned fifth wave, LSWAY also provides rare insights into the intergenerational effects of humanitarian crises on children, youth, and families across generations.
RNA G-quadruplex structures exist and function in vivo in plants
Authors: Yang Xiaofei , Cheema Jitender , Zhang Yueying , Deng Hongjing , Duncan Susan , Umar Mubarak Ishaq , Zhao Jieyu , Liu Qi , Cao Xiaofeng , Kwok Chun Kit , Ding Yiliang
Published: September 2020

Background

Guanine-rich sequences are able to form complex RNA structures termed RNA G-quadruplexes in vitro. Because of their high stability, RNA G-quadruplexes are proposed to exist in vivo and are suggested to be associated with important biological relevance. However, there is a lack of direct evidence for RNA G-quadruplex formation in living eukaryotic cells. Therefore, it is unclear whether any purported functions are associated with the specific sequence content or the formation of an RNA G-quadruplex structure.

Results

Using rG4-seq, we profile the landscape of those guanine-rich regions with the in vitro folding potential in the Arabidopsis transcriptome. We find a global enrichment of RNA G-quadruplexes with two G-quartets whereby the folding potential is strongly influenced by RNA secondary structures. Using in vitro and in vivo RNA chemical structure profiling, we determine that hundreds of RNA G-quadruplex structures are strongly folded in both Arabidopsis and rice, providing direct evidence of RNA G-quadruplex formation in living eukaryotic cells. Subsequent genetic and biochemical analyses show that RNA G-quadruplex folding is able to regulate translation and modulate plant growth.

Conclusions

Our study reveals the existence of RNA G-quadruplex in vivo and indicates that RNA G-quadruplex structures act as important regulators of plant development and growth.
Feasibility and acceptability of a brief routine weight management intervention for postnatal women embedded within the national child immunisation programme in primary care: randomised controlled cluster feasibility trial
Authors: Daley A. J. , Jolly K. , Bensoussane H. , Ives N. , Jebb S. A. , Tearne S. , Greenfield S. M. , Yardley L. , Little P. , Tyldesley-Marshall N. , Pritchett R. V. , Frew E. , Parretti H. M.
Published: September 2020

Background

The prevalence of obesity in women continues to rise and pregnancy is a high-risk time for excessive weight gain. The period after childbirth represents an opportunity to offer women support to manage their weight. The primary aim here was to investigate the acceptability and feasibility of delivering a self-management intervention to postnatal women to support weight loss, embedded within the national child immunisation programme.

Methods

The research involved a randomised controlled cluster feasibility trial. Data were collected at baseline and 3 months later. Twenty-eight postnatal women living with overweight or obesity were recruited via Birmingham Women Hospital or general practices. Babies are routinely immunised at 2, 3 and 4 months of age; the intervention was embedded within these appointments. The intervention involved brief motivation/support by practice nurses to encourage participants to make healthier lifestyle choices through self-monitoring of weight and signposting to an online weight management programme, when they attended their practice to have their child immunised. The role of the nurse was to provide external accountability for weight loss. Participants were asked to weigh themselves weekly and record this on a record card or using the online programme. The weight goal was for participants to lose 0.5 to 1 kg per week. Usual care received a healthy lifestyle leaflet. The primary outcome was the feasibility of a phase III trial to test the subsequent effectiveness of the intervention, as assessed against three stop-go traffic light criteria (recruitment, adherence to regular self-weighing and registration with an online weight management programme).

Results

The traffic light stop-go criteria results were red for recruitment (28/80, 35% of target), amber for registration with the online weight loss programme (9/16, 56%) and green for adherence to weekly self-weighing (10/16, 63%). Nurses delivered the intervention with high fidelity.

Discussion

Whilst participants and nurses followed the trial protocol well and adherence to self-weighing was acceptable, recruitment was challenging and there is scope to improve engagement with the online weight management programme component of the intervention.

Trial registration

ISRCTN 12209332. Registration date is 04/12/18.
A novel timing and frequency offset estimation algorithm for filtered OFDM system
Authors: Feng Xing-le , Wang Meng-jie , Chen Li , Zhu Wen-xia , Hua Kun
Published: September 2020

As a critical technology of 5G air interface waveform, filtered orthogonal frequency division multiplexing (F-OFDM) not only inherits the technical advantages of OFDM, but also has outstanding advantages in system flexibility and spectrum efficiency. However, as a multi-carrier technology, it is still extremely sensitive to sample timing offset (STO) and carrier frequency offset (CFO). In this letter, an improved Park frequency domain training sequence (FS-Park) is proposed to complete STO and CFO estimation of F-OFDM system. Firstly, a real-value pseudorandom number (PN) sequence is sent to each subcarrier as training sequence in frequency domain, the corresponding time domain training symbol has a conjugate symmetry structure. Secondly, the training symbol is utilized for timing synchronization, then the fractional frequency offset is estimated based on the cyclic prefix in time domain. Finally, the integer frequency offset is estimated in frequency domain based on the auto-correlation of PN sequence. The simulation results illustrate that the FS-Park algorithm not only has a single pulse timing metric curve and great STO estimation accuracy, but also has better performance of CFO estimation than classical Park algorithm and Liang Xiao’s method.
Concentrated solutions for a critical nonlocal problem
Authors: Wang Qingfang
Published: September 2020

In this paper, we deal with a class of fractional critical problems. Under some suitable assumptions, we derive the existence of a positive solution concentrating at the critical point of the Robin function by using the Lyapunov–Schmidt reduction method. Comparing with previous work, we encounter some new challenges because of a nonlocal term. By making some delicate estimates for the nonlocal term we overcome the difficulty and find a bubbling solution.
Explicit criteria for the qualitative properties of differential equations with p-Laplacian-like operator
Authors: Bazighifan Omar , Aljohani A. F.
Published: September 2020

The aim of this work is to study qualitative properties of solutions for a fourth-order neutral nonlinear differential equation, driven by ap-Laplace differential operator. Some oscillation criteria for the equation under study have been obtained by comparison theory. The obtained results improve the well-known oscillation results present in the literature. Some examples are provided to show the applicability of the obtained results.
On a hybrid fractional Caputo–Hadamard boundary value problem with hybrid Hadamard integral boundary value conditions
Authors: Mohammadi Hakimeh , Rezapour Shahram , Etemad Sina
Published: September 2020

In the present research article, we find some important criteria on the existence of solutions for a class of the hybrid fractional Caputo–Hadamard differential equations and its corresponding inclusion problem supplemented with hybrid Hadamard integral boundary conditions. In this direction, we utilize some theorems due to Dhage’s fixed point results in our proofs. Finally, we demonstrate two numerical examples to confirm the validity of the main obtained results.
On Hyers–Ulam Mittag-Leffler stability of discrete fractional Duffing equation with application on inverted pendulum
Authors: Selvam A. G. M. , Baleanu D. , Alzabut J. , Vignesh D. , Abbas S.
Published: September 2020

A human being standing upright with his feet as the pivot is the most popular example of the stabilized inverted pendulum. Achieving stability of the inverted pendulum has become common challenge for engineers. In this paper, we consider an initial value discrete fractional Duffing equation with forcing term. We establish the existence, Hyers–Ulam stability, and Hyers–Ulam Mittag-Leffler stability of solutions for the equation. We consider the inverted pendulum modeled by Duffing equation as an example. The values are tabulated and simulated to show the consistency with theoretical findings.
Development of an in vitro macrophage screening system on the immunomodulating effects of feed components
Authors: Sivinski S. E. , Mamedova L. K. , Rusk R. A. , Elrod C. C. , Swartz T. H. , McGill J. M. , Bradford B. J.
Published: September 2020

Background

While feed components capable of modulating the immune system are highly sought after and marketed, often little evidence is available to support functional immune response claims. Thus, a high-throughput in vitro cell screening system was developed to test these compounds for innate immune signaling effects, using Saccharomyces cerevisiae and its cell wall components in addition to lauric acid and its esters as models in two separate experiments. This screening system utilized RAW 264.7 murine macrophages to assess live S. cerevisiae cells and S. cerevisiae-derived cell wall components β-glucan, mannan, and zymosan (a crude cell wall preparation containing both β-glucan and mannan). D-mannose was also evaluated as the monomer of mannan. We also examined the effect of a saturated fatty acid (C12:0, lauric acid) and its esters (methyl laurate and glycerol monolaurate) on innate immune cell activation and cellular metabolism. RAW cells were transfected with a vector that drives expression of alkaline phosphatase upon promoter activation of nuclear factor κ-light-chain-enhancer of activated B cells (NFκB), a major inflammatory/immune transcription factor. RAW cells were incubated with 0.01, 0.1 or 1 mg/mL of yeast compounds alone or RAW cells were challenged with LPS and then incubated with yeast compounds. In a separate experiment, RAW cells were incubated with 0, 0.5, 2.5, 12.5, 62.5, and 312.5 μmol/L of lauric acid, methyl laurate, or glycerol monolaurate alone, or RAW cells were challenged with LPS and then incubated with fatty acid treatments.

Results

Treatment with zymosan or β-glucan alone induced NFκB activation in a dose-dependent manner, whereas treatment with D-mannose, mannan, or live S. cerevisiae cells did not. Post-treatment with mannan after an LPS challenge decreased NFκB activation, suggesting that this treatment may ameliorate LPS-induced inflammation. Slight increases in NFκB activation were found when fatty acid treatments were applied in the absence of LPS, yet substantial reductions in NFκB activation were seen when treatments were applied following an LPS challenge.

Conclusions

Overall, this cell screening system using RAW macrophages was effective, high-throughput, and sensitive to feed components combined with LPS challenges, indicating modulation of innate immune signaling in vitro.

Graphical abstract
Boswellic acid sensitizes gastric cancer cells to Cisplatin-induced apoptosis via p53-mediated pathway
Authors: Al-Bahlani Shadia , Burney Ikram A. , Al-Dhahli Buthaina , Al-Kharusi Safiya , Al-Kharousi Fakhra , Al-Kalbani Amani , Ahmed Ikhlas
Published: September 2020

Background

Cisplatin (CDDP) is an effective anticancer drug for Gastric cancer (GC) that induces apoptosis by altering pro- (p53) and anti-apoptotic (Akt and NFkB) proteins; however, chemoresistance remains a big challenge. Additional compounds with promising anticancer effects such as AKBA (Acetyl-keto-beta boswellic acid) may overcome the resistance. However, its role in CDDP-induced apoptosis in GC has not been studied. This study aimed to examine the effectiveness of AKBA on p53-mediated, CDDP-induced apoptosis in GC cells. AGS and NCI-N87 cells were treated with different concentrations (0, 25, 50, 100 μM) of CDDP and/or AKBA.

Methods

P53, Akt and NFkB proteins and apoptosis were assessed by Western blot and flow cytometry. The role of p53 was determined by inhibiting its function via the siRNA approach.

Results

The results revealed that CDDP and AKBA significantly increased p53 content in both cells, while Akt and NFkB were significantly decreased. Both compounds significantly induced apoptosis in a dose-dependent manner. AKBA sensitized GC cells to CDDP-induced apoptosis by altering the protein expression. P53 downregulation affected Akt and NFkB proteins with a slight increase in apoptosis induction in the combination treated groups.

Conclusions

Altogether, our findings suggest that AKBA enhances GC cell sensitivity to CDDP-induced apoptosis via the p53 pathway.
Using peer workers with lived experience to support the treatment of borderline personality disorder: a qualitative study of consumer, carer and clinician perspectives
Authors: Barr Karlen R. , Townsend Michelle L. , Grenyer Brin F. S.
Published: September 2020

Background

Peer support is a recovery oriented approach where consumers and carers are introduced to people with lived experience of the disorder who have recovered. Paid roles within health services for such consumer peer workers and carer peer workers (or ‘specialists’) are increasingly common. To date specific studies on such peer support for consumers with borderline personality disorder (BPD) and their carers has not been conducted.

Methods

This qualitative study used interviews to explore perceptions and models of peer support for BPD from the perspectives of 12 consumers, 12 carers, and 12 mental health professionals. Participant responses were analyzed using reflexive thematic analysis within a phenomenological methodology.

Results

All groups described how consumer peer workers may provide hope, connection, and validation to a consumer’s lived experience. Offering both traditional mental health treatment plus peer support, and giving consumers choice regarding a consumer peer worker was welcomed. Differences in opinion were found regarding the consumer peer worker’s role in relation to the mental health team, including whether consumer peer workers should access medical records. Perspectives differed regarding the consumer peer worker and carer peer worker positions, highlighting potential role confusion. Carers discussed the value of receiving support from carer peer workers and consumer peer workers. Mental health professionals described how consumer peer workers can experience workplace stigma and problems with boundary setting, and acknowledged a need for peer workers to be valued by having a duty of care and confidentiality code to follow and be offered supervision.

Conclusions

Two models of peer support for BPD emerged: an integrated model where consumer peer workers work within the mental health team, and a complementary model where consumer peer workers are separate from the mental health team. Based on these findings we provide recommendations for services to help support such peer work for consumers with BPD and their carers.
Boosting methods for multi-class imbalanced data classification: an experimental review
Authors: Tanha Jafar , Abdi Yousef , Samadi Negin , Razzaghi Nazila , Asadpour Mohammad
Published: September 2020

Since canonical machine learning algorithms assume that the dataset has equal number of samples in each class, binary classification became a very challenging task to discriminate the minority class samples efficiently in imbalanced datasets. For this reason, researchers have been paid attention and have proposed many methods to deal with this problem, which can be broadly categorized into data level and algorithm level. Besides, multi-class imbalanced learning is much harder than binary one and is still an open problem. Boosting algorithms are a class of ensemble learning methods in machine learning that improves the performance of separate base learners by combining them into a composite whole. This paper’s aim is to review the most significant published boosting techniques on multi-class imbalanced datasets. A thorough empirical comparison is conducted to analyze the performance of binary and multi-class boosting algorithms on various multi-class imbalanced datasets. In addition, based on the obtained results for performance evaluation metrics and a recently proposed criteria for comparing metrics, the selected metrics are compared to determine a suitable performance metric for multi-class imbalanced datasets. The experimental studies show that the CatBoost and LogitBoost algorithms are superior to other boosting algorithms on multi-class imbalanced conventional and big datasets, respectively. Furthermore, the MMCC is a better evaluation metric than the MAUC and G-mean in multi-class imbalanced data domains.
Flexible nanopillar-based immunoelectrochemical biosensor for noninvasive detection of Amyloid beta
Authors: Park Yoo Min , Ahn Junhyoung , Choi Young Sun , Jeong Jae-Min , Lee Seok Jae , Lee Jae Jong , Choi Bong Gill , Lee Kyoung G.
Published: September 2020

The noninvasive early detection of biomarkers for Alzheimer’s disease (AD) is essential for the development of specific treatment strategies. This paper proposes an advanced method for fabricating highly ordered and flexible nanopillar-based electrochemical biosensors by the combination of soft/photolithography and metal evaporation. The nanopillar array (NPA) exhibits high surface area containing 1500 nm height and 500 nm diameter with 3:1 ratio. In regard with physical properties of polyurethane (PU) substrate, the developed NPA is sustainable and durable to external pressure such as bending and twisting. To manipulate the NPA surface to biocompatible, the gold was uniformly deposited on the PU substrate. The thiol chemistry which is stably modified on the gold surface as a form of self-assembled monolayer was employed for fabricating the NPA as a biocompatible chip by covalently immobilize the antibodies. The proposed nanopillar-based immunoelectrochemical biosensor exhibited good and stable electrochemical performance in β-amyloid (Aβ) detection. Moreover, we successfully confirmed the performance of the as-developed sensor using the artificial injection of Aβ in human tear, with sensitivity of 0.14 ng/mL and high reproducibility (as a standard deviation below 10%). Our findings show that the developed nanopillar-based sensor exhibits reliable electrochemical characteristics and prove its potential for application as a biosensor platform for testing at the point of care.
Automated diagnosis and staging of Fuchs’ endothelial cell corneal dystrophy using deep learning
Authors: Eleiwa Taher , Elsawy Amr , Özcan Eyüp , Abou Shousha Mohamed
Published: September 2020

Background

To describe the diagnostic performance of a deep learning algorithm in discriminating early-stage Fuchs’ endothelial corneal dystrophy (FECD) without clinically evident corneal edema from healthy and late-stage FECD eyes using high-definition optical coherence tomography (HD-OCT).

Methods

In this observational case-control study, 104 eyes (53 FECD eyes and 51 healthy controls) received HD-OCT imaging (Envisu R2210, Bioptigen, Buffalo Grove, IL, USA) using a 6 mm radial scan pattern centered on the corneal vertex. FECD was clinically categorized into early (without corneal edema) and late-stage (with corneal edema). A total of 18,720 anterior segment optical coherence tomography (AS-OCT) images (9180 healthy; 5400 early-stage FECD; 4140 late-stage FECD) of 104 eyes (81 patients) were used to develop and validate a deep learning classification network to differentiate early-stage FECD eyes from healthy eyes and those with clinical edema. Using 5-fold cross-validation on the dataset containing 11,340 OCT images (63 eyes), the network was trained with 80% of these images (3420 healthy; 3060 early-stage FECD; 2700 late-stage FECD), then tested with 20% (720 healthy; 720 early-stage FECD; 720 late-stage FECD). Thereafter, a final model was trained with the entire dataset consisting the 11,340 images and validated with a remaining 7380 images of unseen AS-OCT scans of 41 eyes (5040 healthy; 1620 early-stage FECD 720 late-stage FECD). Visualization of learned features was done, and area under curve (AUC), specificity, and sensitivity of the prediction outputs for healthy, early and late-stage FECD were computed.

Results

The final model achieved an AUC of 0.997 ± 0.005 with 91% sensitivity and 97% specificity in detecting early-FECD; an AUC of 0.974 ± 0.005 with a specificity of 92% and a sensitivity up to 100% in detecting late-stage FECD; and an AUC of 0.998 ± 0.001 with a specificity 98% and a sensitivity of 99% in discriminating healthy corneas from all FECD.

Conclusion

Deep learning algorithm is an accurate autonomous novel diagnostic tool of FECD with very high sensitivity and specificity that can be used to grade FECD severity with high accuracy.
Development of tooth regenerative medicine strategies by controlling the number of teeth using targeted molecular therapy
Authors: Takahashi Katsu , Kiso Honoka , Murashima-Suginami Akiko , Tokita Yoshihito , Sugai Manabu , Tabata Yasuhiko , Bessho Kazuhisa
Published: September 2020

Analysis of various genetically modified mice, with supernumerary teeth, has revealed the following two intrinsic molecular mechanisms that increase the number of teeth. One plausible explanation for supernumerary tooth formation is the rescue of tooth rudiments. Topical application of candidate molecules could lead to whole tooth formation under suitable conditions. Congenital tooth agenesis is caused by the cessation of tooth development due to the deletion of the causative gene and suppression of its function. The arrest of tooth development inRunx2knockout mice, a mouse model of congenital tooth agenesis, is rescued in double knockout mice ofRunx2andUsag-1.TheUsag-1knockout mouse is a supernumerary model mouse. Targeted molecular therapy could be used to generate teeth in patients with congenital tooth agenesis by stimulating arrested tooth germs. The third dentition begins to develop when the second successional lamina is formed from the developing permanent tooth in humans and usually regresses apoptotically. Targeted molecular therapy, therefore, seems to be a suitable approach in whole-tooth regeneration by the stimulation of the third dentition. A second mechanism of supernumerary teeth formation involves the contribution of odontogenic epithelial stem cells in adults. Cebpb has been shown to be involved in maintaining the stemness of odontogenic epithelial stem cells and suppressing epithelial-mesenchymal transition. Odontogenic epithelial stem cells are differentiated from one of the tissue stem cells, enamel epithelial stem cells, and odontogenic mesenchymal cells are formed from odontogenic epithelial cells by epithelial-mesenchymal transition. Both odontogenic epithelial cells and odontogenic mesenchymal cells required to form teeth from enamel epithelial stem cells were directly induced to form excess teeth in adults. An approach for the development of targeted therapeutics has been the local application of monoclonal neutralizing antibody/siRNA with cationic gelatin for USAG-1 or small molecule for Cebpb.
Pharmacogenetic-guided cannabis usage in the community pharmacy: evaluation of a pilot program
Authors: Papastergiou John , Li Wilson , Sterling Carly , van den Bemt Bart
Published: September 2020

Background

Pharmacists possess a skillset suited to provide evidence-based guidance to current and potential users of cannabis. Clinical pharmacogenomics research has made significant progress in defining which genetic variations are important for influencing inter-patient variability in response to cannabis. This study aims to evaluate the practicality and impact of pharmacogenetic testing in the community pharmacy to help guide in the safe use of cannabis.

Methods

The pilot program was designed as open-label, non-randomized, and observational. Two busy, urban community pharmacies, operating under the brand Shoppers Drug Mart, in Toronto, Ontario, Canada offered pharmacogenomic testing to cannabis users as part of their professional services program over a period of 2 months. Eligible patients received buccal swabs using a DNA cheek swab kit. De-identified, barcoded samples were then sent by regular mail to an off-site CLIA-certified laboratory for analysis in Mississauga, Canada. A pharmacogenetic testing platform from Lobo Genetics® was utilized for translation of participants’ DNA with respect to CYP2C9, AKT1 and COMT genetic polymorphisms. Following genomic data translation, personalized, evidence-based recommendations were generated. Pharmacists provided a cannabis pharmacogenetic consultation to patients via telephone or in-person.

Results

Twenty patients enrolled in the study. Pharmacogenetic screening identified 95% as having the CYP2C9*1/*1 genotype (suggesting normal THC metabolism); 35 and 25% had AKT1 genotypes suggesting intermediate risk (C/T genotype) or high risk (C/C genotype), respectively, for cannabis-induced psychosis; and 45 and 10% had COMT genotypes suggesting intermediate risk (Val/Met genotype) or high risk (Val/Val genotype), respectively for cannabis-induced neurocognitive impairment.

After the pharmacogenetic consultation, 65% of patients reported an increased comfort level in choosing a specific strength/strain of cannabis for use in the future; 75% considered the consultation of high value providing information potentially vital to their health and wellbeing.

Conclusion

Although the study did not find any CYP2C9 variants associated with highly diminished THC metabolism, most of these patients do carry genetic variants that may potentially predispose them to the development of psychosis and memory impairment. Similar initiatives can potentially improve patient safety and empower individuals to make informed decisions about cannabis use and possible complications.
Fixed point theorems for self and non-self F-contractions in metric spaces endowed with a graph
Authors: Younus Awais , Azam Muhammad Umer , Asif Muhammad
Published: September 2020

The main results obtained in this paper are fixed point theorems for self and non-self GF-contractions on metric spaces endowed with a graph. Our new results are generalization of recently fixed point theorems for self mappings on metric spaces and also fixed point theorems for non-self mappings in Banach spaces by using the concept of new type of contractive mappings namely F-contractions.
Impact of different anti-HCV regimens on platelet count during treatment in Egyptian patients
Authors: El Ghany Sara Abd , El Husseiny Noha M. , Roshdy Mohamed , Moustafa Heba , Atallah Mohamed Taha , Fathy Ahmed , El Demellawy Heba H. , Abdelhameed Asmaa M. , El Demerdash Doaa M.
Published: September 2020

Background

Side effects of antiviral therapies for hepatitis C, especially hematologic abnormalities, may decrease both therapeutic adherence and therapeutic success rate. Adherence to therapy is essential to achieve an early viral response (EVR), and this is vital for attaining a sustained viral response (SVR). Discontinuation of anti-viral therapy is the only way to prevent progressive thrombocytopenia; however, discontinuation of therapy may reduce the rate of viral clearance and SVR. Our aim is to study effects of antiviral therapy for HCV on platelet count. One hundred sixty eight adult patients with chronic hepatitis C were enrolled in this study and subcategorized into 3 groups: group (1) contains 56 patients receiving IFN, ribavirin and sofosbuvir (triple therapy); group (2) contains 55 patients receiving ribavirin and sofosbuvir (SOF/RBV); and group (3) contains 57 patients receiving simeprevir and sofosbuvir (SIM/SOF). HCV RNA by PCR were checked basically for all studied patients. Follow-up platelet count was done weekly during the first month then monthly till end of treatment. Follow-up of platelet count decrement was assessed at the 2nd week, 4th week and end of antiviral therapy for all studied groups.

Results

We found that in the 2nd week and 4th week, most of patients (76.2%, 71.4%) showed platelet count decrement during antiviral therapy. The decrement of platelet at the 2nd week, 4th week and at end of treatment was much noticed with the SOF/RBV antiviral therapy studied group. None of the patients developed severe thrombocytopenia; none of the patients needed to stop antiviral therapy due to thrombocytopenia, only 6 patients needed dose modification, most of them were from the triple therapy group.

Conclusion

We concluded that thrombocytopenia in chronic HCV infection has a multifactorial pathophysiology and remains a major problem. The recent change in direct-acting antiviral therapy (DAA) without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN-based antiviral therapy. DAAs, with high SVR and few haematological adverse effects, have been shown to improve thrombocytopenia associated with HCV infection as well as advanced hepatic disease.
Value of Case-Based Learning within STEM Courses: Is It the Method or Is It the Student?
Authors: Rhodes Ashley , Wilson Abigail , Rozell Timothy
Published: September 2020

This study explores the relationship between the benefits of case-based learning and specific student characteristics such as prior knowledge of subject material and number of college credit hours completed.
Leveraging Psychosocial Interventions to Motivate Instructor Participation in Teaching Professional Development
Authors: Limeri Lisa B. , Musgrove Miranda M. Chen , Henry Meredith A. , Schussler Elisabeth E.
Published: September 2020

Teaching professional development (TPD) efforts to reform undergraduate education will not meet their goals if instructors are not motivated to attend. Research on psychosocial interventions could be leveraged to design interventions that will increase instructors’ motivation to attend TPD.
Simulating a Computational Biological Model, Rather Than Reading, Elicits Changes in Brain Activity during Biological Reasoning
Authors: Clark Caron A. C. , Helikar Tomáš , Dauer Joseph
Published: September 2020

Undergraduates who computationally simulated a biological model showed increased activity in occipital and parietal brain regions when later reasoning about that model relative to students who learned through reading. Accuracy in model-based reasoning correlated with prefrontal brain activity.
Design-Based Research: A Methodology to Extend and Enrich Biology Education Research
Authors: Scott Emily E. , Wenderoth Mary Pat , Doherty Jennifer H.
Published: September 2020

Design-based research from the learning sciences is a compelling methodology for investigating the mechanisms by which students to develop sophisticated ideas about biology. It fosters research collaborations across disciplines, develops and tests theory-based instructional tools, and draws on mixed methods to examine how students learn.
Learning Analytics to Assess Beliefs about Science: Evolution of Expertise as Seen through Biological Inquiry
Authors: Peffer Melanie E. , Ramezani Niloofar , Quigley David , Royse Emily , Bruce Chloe
Published: September 2020

This work leverages methods from the learning analytics community to create an assessment of epistemological beliefs about science as seen through inquiry practices. Results advance our understanding of how to assess cognitive constructs through practices and the development of epistemological beliefs over the course of becoming a biologist.
Concept Map Assessment Reveals Short-Term Community-Engaged Fieldwork Enhances Sustainability Knowledge
Authors: Pruett Jessica L. , Weigel Emily G.
Published: September 2020

Student-generated concept maps in an undergraduate ecology laboratory course were used to examine the benefit of community-engaged fieldwork on sustainability learning. This short-term service-learning experience led to conceptual changes in sustainability knowledge and is a promising pedagogical approach in sustainability education.
Review of wide-area geophysical urban infrastructure monitoring techniques
Authors: McComas Sarah , Whitlow R. Danielle , Taylor Mihan H. McKenna
Published: September 2020

Geophysical techniques have the potential to comprehensively assess the urban landscape, including the human-built environment. The U.S. Army Engineer Research and Development Center (ERDC) has developed methods to persistently and remotely monitor critical infrastructure by using infrasound (subaudible acoustics below 20 Hz). Infrasound can propagate tens of kilometers or more depending on source characteristics and meteorological conditions. Large bridges, dams, and other industrial sources are considered critical infrastructure. They emit infrasound since they exhibit characteristics of modal motion in the infrasound passband. While the motion of these structures may not be perceptible to humans, instrumentation can detect small air-coupled movements, providing real-time information about infrastructure behavior and condition. Techniques originally developed by the nuclear monitoring community for detecting large impulsive events from permanently emplaced instrumentation located in quiet isolated locations had to be adapted to the complex and dynamic urban space. The infrasound arrays and associated processing schema developed by the ERDC do not need to be in close proximity to the structures, are omnidirectional, and are capable of assessing multiple structures simultaneously. They continually record structural information to provide real-time information to infrastructure owners. However, several unique challenges must be addressed to successfully accomplish no-contact, persistent, structural monitoring in cluttered and noisy urban areas. This article describes recommendations for urban-appropriate instrumentation deployment methods and elevated noise floor concerns based on three field experiments representing metropolitan (Dallas, Texas), suburban (San Diego, California), and industrial (Sutter County, California) areas.
Seismic noise in an urban environment
Authors: Dean Timothy , Al Hasani Mus'ab
Published: September 2020

The results of an experiment aimed at identifying the nature of major noise sources within an urban area are described. We found the strongest noise source to be an irrigation pump located adjacent to the geophones. The noise from the pump had a narrow bandwidth centered at 75 Hz with a duration of 5 minutes every 17 and 34 minutes during the day and night, respectively. Traffic noise was mainly restricted to between 10 and 25 Hz, with its strength decreasing between 9 p.m. and 6 a.m. Passing aircraft resulted in noise between 30 and 200 Hz lasting about 1 minute. Electrical noise was observed at the supply frequency of 50 Hz, although additional noise at 45 Hz also was observed. Given these results we recommended that acquisition within the area should be restricted to late evening or early morning, receiver locations should be selected to avoid strong localized sources of electrical and/or mechanical noise, and any cables associated with the recording system should be as short as possible (although nodal systems are preferable). If nodal systems are deployed for logistical reasons, real-time noise monitoring should be deployed to identify and avoid bursts of high-amplitude, short-duration noise.
First time-lapse OBN in Bonga deepwater offshore field
Authors: Aikulola Understanding , Okpobia Oke , Okonkwo Arinze , Yamusa Idris , Saragoussi Emmanuel , Osabuohien Osahon , Adegbite Adedolapo , Ogunsakin Akintunde , Smith Patrick , Hatchell Paul
Published: September 2020

Time-lapse seismic data from Bonga Field, located in deepwater Nigeria, have delivered excellent results previously from dedicated streamer seismic surveys (2000, 2008, and 2012) that image changes in amplitude due to water replacing oil. One challenge with the streamer data is the presence of a floating production storage and offloading (FPSO) unit. It is difficult to accurately repeat streamer acquisition geometry in economically important updip regions of reservoirs that lie beneath the FPSO. To ensure an accurate repeat of this area, we acquired an ocean-bottom node (OBN) survey in 2010 and carried out the first time-lapse OBN repeat of the survey in 2018. Time-lapse processing of the OBN data produced excellent results. We obtained an OBN-on-OBN normalized root mean square (NRMS) difference repeatability of 6%. This was an improvement over the 12% NRMS for streamer-on-streamer repeats. The OBN data quality was unaffected by the FPSO, enabling us to properly image the changes occurring in this area. The 4D OBN interpretation was used to identify bypassed oil opportunities. The data also were used to derisk well placement, optimize water injection, and update the dynamic reservoir models. The new models are essential to enhance predictability and field performance. We also analyzed an area northwest of the field where we extended the 2018 OBN acquisition and compared it to streamer data to optimize a new injection well location.