bluuebunny/crossref_metadata_2025 huggingface dataset:
Attaining Excellence in Professional Pharmacy Practice-Pharmacists in Academia Must Take the Lead
Authors: Effiong D. E. , Alozie Mfonobong
Published: March 2021

As societal needs change, so are professions adjusting and adapting their services to meet this new normal. The essence is not just to remain relevant, but to live up to their professional expectation and be impactful to their environment. In the constantly changing societal healthcare needs, Pharmacists as medicine experts and frontline contributors towards health care delivery, have crucial roles to play. From sound medical information dissemination to drug manufacture; from dispensing and therapeutic drug control to research and development and from sustaining supply chain of products to provision of total pharmaceutical care, pharmacists stand tall to provide needed healthcare services. Rendering services with professionalism is the desired path. But what does it take to attain professionalism in pharmacy practice? How can pharmacists in the academia harness their potentials to promote the path of service delivery with professional excellence? This piece showcases the role of excellence in the pharmacy profession highlighting the potentials of members in the academia in spearheading excellence in practice, thereby adding to the professional outlook of the pharmacist.
A novel hydrogen peroxide evolved CHO host can improve the expression of difficult to express bispecific antibodies
Authors: Mistry Rajesh K. , Kelsall Emma , Sou Si Nga , Barker Harriet , Jenns Mike , Willis Katie , Zurlo Fabio , Hatton Diane , Gibson Suzanne J.
Published: March 2021

The manufacture of bispecific antibodies by Chinese hamster ovary (CHO) cells is often hindered by lower product yields compared to monoclonal antibodies. Recently, reactive oxygen species have been shown to negatively impact antibody production. By contrast, strategies to boost cellular antioxidant capacity appear to be beneficial for recombinant protein expression. With this in mind, we generated a novel hydrogen peroxide evolved host using directed host cell evolution. Here we demonstrate that this host has heritable resistance to hydrogen peroxide over many generations, displays enhanced antioxidant capacity through the upregulation of several, diverse antioxidant defense genes such as those involved in glutathione synthesis and turnover, and has improved glutathione content. Additionally, we show that this host has significantly improved transfection recovery times, improved growth and viability properties in a fed‐batch production process, and elevated expression of two industrially relevant difficult to express bispecific antibodies compared to unevolved CHO control host cells. These findings demonstrate that host cell evolution represents a powerful methodology for improving specific host cell characteristics that can positively impact the expression of difficult to express biotherapeutics.
Confronting CHIRPS dataset and in situ stations in the detection of wet and drought conditions in the Brazilian Midwest
Authors: de Oliveira‐Júnior José Francisco , da Silva Junior Carlos Antonio , Teodoro Paulo Eduardo , Rossi Fernando Saragosa , Blanco Claudio José Cavalcante , Lima Mendelson , de Gois Givanildo , Correia Filho Washington Luiz Félix , de Barros Santiago Dimas , dos Santos Vanderley Mário Henrique Guilherme
Published: March 2021

The states of Mato Grosso (MT) and Mato Grosso do Sul (MS) are located in Midwest Brazil and are dependent on agribusiness, which makes their water regimes of fundamental importance. However, the existing weather stations in these states are limited, and rainfall products are therefore a valuable alternative. The objectives of this study are: (a) to validate the CHIRPS datasets for the states of MT and MS in the Brazilian Midwest region; (b) to evaluate the intraseasonal variability of regional rainfall via CHIRPS; and (c) to define the drought and wet periods on the decennial scale, based on the annual SPI. Three seasons were defined (rainy, drought, and transition), and the differences showed that the MS rainy season (56.65%) was reduced due to the veranicos that occur in February, with an increase in the percentages of the drought (13.83%) and transition (29.52%) seasons. The highest monthly rainfall occurs in the north of MS (328–390 mm), while intermediate rainfall (109–273 mm) occurs in the south of MS. This satisfactorily represents the formation of a rainfall gradient in a N–S direction during the rainy season, similar to other characterizations around the world. Based on the annual SPI assessed per decade, there were moderate droughts annually in the 1990s, 2000s, and 2010s, but not in the 1980s. There were significant differences between the decades due to the intensity and categorization of the ENSO phases (strong and moderate), and drier decades with moderate rainfall reduction in both states can be defined in the last 40 years. The data obtained via CHIRPS are satisfactory for the spatio‐temporal evaluation of regional rainfall, and for the use of SPI to detect drought and wet periods in the states of MT and MS.
A branch-and-Benders-cut algorithm for a bi-objective stochastic facility location problem
Authors: Parragh Sophie N. , Tricoire Fabien , Gutjahr Walter J.
Published: March 2021

In many real-world optimization problems, more than one objective plays a role and input parameters are subject to uncertainty. In this paper, motivated by applications in disaster relief and public facility location, we model and solve a bi-objective stochastic facility location problem. The considered objectives are cost and covered demand, where the demand at the different population centers is uncertain but its probability distribution is known. The latter information is used to produce a set of scenarios. In order to solve the underlying optimization problem, we apply a Benders’ type decomposition approach which is known as the L-shaped method for stochastic programming and we embed it into a recently developed branch-and-bound framework for bi-objective integer optimization. We analyze and compare different cut generation schemes and we show how they affect lower bound set computations, so as to identify the best performing approach. Finally, we compare the branch-and-Benders-cut approach to a straight-forward branch-and-bound implementation based on the deterministic equivalent formulation.
Endoscopic surgical treatment for rhinogenic contact point headache: systematic review and meta-analysis
Authors: Maniaci Antonino , Merlino Federico , Cocuzza Salvatore , Iannella Giannicola , Vicini Claudio , Cammaroto Giovanni , Lechien Jérome R. , Calvo-Henriquez Christian , La Mantia Ignazio
Published: March 2021

Purpose

This meta-analysis study was designed to analyze endoscopic surgery’s role in treating rhinogenic contact point headache.

Methods

We performed a comprehensive review of the last 20 years’ English language regarding Rhinogenic contact point headache and endoscopic surgery. We included the analysis papers reporting post-operative outcomes through the Visual Analogue Scale or the Migraine Disability Assessment scale.

Results

We provided 18 articles for a total of 978 RCPH patients. While 777 (81.1%) subjects underwent functional nasal surgery for RCPH, 201 patients (20.9%) were medically treated. A significant decrease from the VAS score of 7.3 ± 1.5 to 2.7 ± 1.8 was recorded (p < 0.0001). At quantitative analysis on 660 patients (11 papers), surgical treatment demonstrated significantly better post-operative scores than medical (p < 0.0001).

Conclusion

At comparison, surgical treatment in patients with rhinogenic contact points exhibited significantly better values at short-term, medium-term, and long term follow up. Endoscopic surgery should be proposed as the choice method in approaching the symptomatic patient.
The practical ethics of bias reduction in machine translation: why domain adaptation is better than data debiasing
Authors: Tomalin Marcus , Byrne Bill , Concannon Shauna , Saunders Danielle , Ullmann Stefanie
Published: March 2021

This article probes the practical ethical implications of AI system design by reconsidering the important topic of bias in the datasets used to train autonomous intelligent systems. The discussion draws on recent work concerning behaviour-guiding technologies, and it adopts a cautious form of technological utopianism by assuming it is potentially beneficial for society at large if AI systems are designed to be comparatively free from the biases that characterise human behaviour. However, the argument presented here critiques the common well-intentioned requirement that, in order to achieve this, all such datasets must be debiased prior to training. By focusing specifically on gender-bias in Neural Machine Translation (NMT) systems, three automated strategies for the removal of bias are considered – downsampling, upsampling, and counterfactual augmentation – and it is shown that systems trained on datasets debiased using these approaches all achieve general translation performance that is much worse than a baseline system. In addition, most of them also achieve worse performance in relation to metrics that quantify the degree of gender bias in the system outputs. By contrast, it is shown that the technique of domain adaptation can be effectively deployed to debias existing NMT systems after they have been fully trained. This enables them to produce translations that are quantitatively far less biased when analysed using gender-based metrics, but which also achieve state-of-the-art general performance. It is hoped that the discussion presented here will reinvigorate ongoing debates about how and why bias can be most effectively reduced in state-of-the-art AI systems.
Multifunctional hybrid nanoplatform based on Fe3O4@Ag NPs for nitric oxide delivery: development, characterization, therapeutic efficacy, and hemocompatibility
Authors: Pieretti Joana Claudio , Gonçalves Marcelly Chue , Nakazato Gerson , Santos de Souza Ana Carolina , Boudier Ariane , Seabra Amedea Barozzi
Published: March 2021

The combination of Fe3O4@Ag superparamagnetic hybrid nanoparticles and nitric oxide (NO) represents an innovative strategy for a localized NO delivery with a simultaneous antibacterial and antitumoral actions. Here, we report the design of Fe3O4@Ag hybrid nanoparticles, coated with a modified and nitrosated chitosan polymer, able to release NO in a biological medium. After their synthesis, physicochemical characterization confirmed the obtention of small NO-functionalized superparamagnetic Fe3O4@Ag NPs. Antibacterial assays demonstrated enhanced effects compared to control. Bacteriostatic effect against Gram-positive strains and bactericidal effect against E. coli were demonstrated. Moreover, NO-functionalized Fe3O4@Ag NPs demonstrated improved ability to reduce cancer cells viability and less cytotoxicity against non-tumoral cells compared to Fe3O4@Ag NPs. These effects were associated to the ability of these NPs act simultaneous as cytotoxic (necrosis inductors) and cytostatic compounds inducing S-phase cell cycle arrest. NPs also demonstrated low hemolysis ratio (<10%) at ideal work range, evidencing their potential for biomedical applications.
Incorporation of heparin/BMP2 complex on GOCS-modified magnesium alloy to synergistically improve corrosion resistance, anticoagulation, and osteogenesis
Authors: Lin Yuebin , Yang Ya , Zhao Yongjuan , Gao Fan , Guo Xin , Yang Minhui , Hong Qingxiang , Yang Zhongmei , Dai Juan , Pan Changjiang
Published: March 2021

The in vivo fast degradation and poor biocompatibility are two major challenges of the magnesium alloys in the field of artificial bone materials. In this study, graphene oxide (GO) was first functionalized by chitosan (GOCS) and then immobilized on the magnesium alloy surface, finally the complex of heparin and bone morphogenetic protein 2 was incorporated on the modified surface to synergistically improve the corrosion resistance, anticoagulation, and osteogenesis. Apart from an excellent hydrophilicity after the surface modification, a sustained heparin and BMP2 release over 14 days was achieved. The corrosion resistance of the modified magnesium alloy was significantly better than that of the control according to the results of electrochemical tests. Moreover, the corrosion rate was also significantly reduced in contrast to the control. The modified magnesium alloy not only had excellent anticoagulation, but also can significantly promote osteoblast adhesion and proliferation, upregulate the expression of alkaline phosphatase and osteocalcin, and enhance mineralization. Therefore, the method of the present study can be used to simultaneously improve the corrosion resistance and biocompatibility of the magnesium alloys targeted for the orthopedic applications.
miR-34a-5p might have an important role for inducing apoptosis by down-regulation of SNAI1 in apigenin-treated lung cancer cells
Authors: Aida Rieko , Hagiwara Keitaro , Okano Kazunori , Nakata Kyoko , Obata Yuho , Yamashita Takahiro , Yoshida Kaoru , Hagiwara Hiromi
Published: March 2021

Apigenin is a flavonoid with antioxidant and anticancer effects. It has been reported that apigenin inhibits proliferation, migration, and invasion and induces apoptosis in cultured lung cancer cells. However, there is little information on the involvement of microRNAs (miRNAs) in its effects. miRNA microarray analysis and polymerase-chain-reaction analysis of miRNAs revealed that treatment of human lung cancer A549 cells with apigenin up-regulated the level of miR-34a-5p. Furthermore, mRNA microarray analysis and the results of three microRNA target prediction tools showed that Snail Family Transcriptional Repressor 1 (SNAI1), which inhibits the induction of apoptosis, had its mRNA expression down-regulated in A549 cells treated with apigenin. Our findings suggest that apigenin might induce apoptosis by down-regulation of SNAI1 through up-regulation of miR-34a-5p in A549 cells.
Pan-African rare metals bearing pegmatites in Wadi Ghadir, South Eastern desert, Egypt: the geochemical evolution and implications for mineralization
Authors: Kamar Mohamed S. , Moghazy Nasser M. , Saleh Gehad M.
Published: March 2021

Quartz-diorites, monzogranites and pegmatites are the main rock units in the studied area. The pegmatites occur as zoned pockets within monzogranites with zonal arrangement: border, wall, intermediate, and core zones. The wall zone have enrichment of radioactive and RREs-bearing minerals. K-feldspar, plagioclase and quartz are essential minerals, whereas uranothorite, columbite, zircon, xenotime, monazite, sphalerite and pyrite are accessories. Geochemically, the pegmatites of W. Ghadir have peraluminous character, ferroan with alkalic–calcic affinity and emplaced in within plate setting. These pegmatites revealed Li-bearing variety and high level of rare earth elements mineralization. The studied pegmatites exhibit high contents of Li, Nb, Cu, Ta, U, Th, Pb, Zr, Zn and Ga, can be from the previous data, the studied pegmatites can be classified as a Niobium–Yttrium–Fluorine (NYF) pegmatite or rare metal pegmatite. The trace elements ratio supports a low degree of fractionation and metasomatism in the evolutionary history of the pegmatites, and the very low Cs values (2.2–4.3 ppm) indicate paucity of alkali metal fractionation. Spectrometric investigation revealed that monzogranites are not uraniferous, while the radioactive anomaly is confined to the pegmatites. Applying the U mobilization equation proved that pegmatite samples have been originated from a late magmatic phase of magma very rich in radioelements, and the pegmatites affected with hydrothermal solutions rich in uranium than thorium which indicates uranium addition. Radioactive and important heavy minerals are represented by uranothorite, columbite, zircon, monazite, xenotime, sphalerite and pyrite.
Measuring time clinicians spend using EHRs in the inpatient setting: a national, mixed-methods study
Authors: Cohen Genna R , Boi Jessica , Johnson Christian , Brown Llew , Patel Vaishali
Published: March 2021

Objective

To understand hospitals’ use of EHR audit-log-based measures to address burden associated with inpatient EHR use.

Materials and Methods

Using mixed methods, we analyzed 2018 American Hospital Association Information Technology Supplement Survey data (n = 2864 hospitals; 64% response rate) to characterize measures used and provided by EHR vendors to track clinician time spent documenting. We interviewed staff from the top 3 EHR vendors that provided these measures. Multivariable analyses identified variation in use of the measures among hospitals with these 3 vendors.

Results

53% of hospitals reported using EHR data to track clinician time documenting, compared to 68% of the hospitals using the EHR from the top 3 vendors. Among hospitals with EHRs from these vendors, usage was significantly lower among rural hospitals and independent hospitals (P < .05). Two of these vendors provided measures of time spent doing specific tasks while the third measured an aggregate of auditable activities. Vendors varied in the underlying data used to create measures, measure specification, and data displays.

Discussion

Tools to track clinicians’ documentation time are becoming more available. The measures provided differ across vendors and disparities in use exist across hospitals. Increasing the specificity of standards underlying the data would support a common set of core measures making these measures more widely available.

Conclusion

Although half of US hospitals use measures of time spent in the EHR derived from EHR generated data, work remains to make such measures and analyses more broadly available to all hospitals and to increase its utility for national burden measurement.
Ocular Surface Characteristics and Colonization in a Burn Center: A Prospective Cohort Study
Authors: De La Parra-Colin Paola , Gonzalez-De La Torre Alejandra , Franco-Cendejas Rafael , Gonzalez-Veliz Alejandra , Zarza-Garcia Vania , Vázquez Mellado Martínez Ivette Paola , García Hernández María de Lourdes , Barrientos-Gutierrez Tonatiuh
Published: March 2021

We aimed to evaluate the characteristics and colonization by pathogenic microorganisms of the ocular surface in patients in a burn center and to determine their association with sedation, mechanical ventilation, and periocular burn. We prospectively evaluated 40 patients during an 8-mo period. Five evaluations where performed, at baseline and weekly on four more occasions or until hospital discharge or death. On each visit, we assessed periocular burn, lid position, Bell’s phenomenon, Schirmer’s test, presence of chemosis, conjunctival hyperemia, and exposure keratopathy; conjunctival fornix swabs were taken for microbiology culture. Also, we documented the level of sedation, mechanical ventilation status, and systemic and ocular treatment. Absent Bell’s phenomenon and chemosis were significantly different at baseline in patients under mechanical ventilation, sedation, and in those with a periocular burn. The cumulative incidence of exposure keratopathy was 22.5% and the cumulative incidence of ocular surface colonization by pathogenic microorganisms was 32.5%. Both outcomes were associated with mechanical ventilation and periocular burn. The most frequent pathogenic microorganisms on the ocular surface were Candida parapsilosis, Acinetobacter baumanii, and Pseudomonas aeuroginosa. We did not observe any case of a persistent epithelial defect, infectious keratitis, corneal perforation or corneal opacity in this cohort. Results from our study may benefit future patients by allowing better risk stratification and treatment strategies for the ocular surface care in burn units.
Once-Daily Incremental Vestibular-Ocular Reflex Adaptation Training in Patients With Chronic Peripheral Vestibular Hypofunction: A 1-Week Randomized Controlled Study
Authors: Rinaudo Carlo N. , Schubert Michael C. , Cremer Phillip D. , Figtree William V. C. , Todd Christopher J. , Migliaccio Americo A.
Published: March 2021

Background and Purpose:

This was a double-blinded randomized controlled study to investigate the effects of once-daily incremental vestibulo-ocular reflex (VOR) training over 1 week in people with chronic peripheral vestibular hypofunction.

Methods:

A total of 24 patients with peripheral vestibular hypofunction were randomly assigned to intervention (n = 13) or control (n = 11) groups. Training consisted of either x1 (control) or incremental VOR adaptation exercises, delivered once daily for 15 minutes over 4 days in 1 week. Primary outcome: VOR gain with video-oculography. Secondary outcomes: Compensatory saccades measured using scleral search coils, dynamic visual acuity, static balance, gait, and subjective symptoms. Between-group differences were analyzed with a linear mixed-model with repeated measures.

Results:

There was a difference in the VOR gain increase between groups (P < 0.05). The incremental training group gain increased during active (13.4% ± 16.3%) and passive (12.1% ± 19.9%) head impulse testing (P < 0.02), whereas it did not for the control group (P = 0.59). The control group had reduced compensatory saccade latency (P < 0.02). Both groups had similarly improved dynamic visual acuity scores (P < 0.05). Both groups had improved dynamic gait index scores (P < 0.002); however, only the incremental group had improved scores for the 2 walks involving head oscillations at approximately 2 Hz (horizontal: P < 0.05; vertical: P < 0.02), increased gait speed (P < 0.02), and step length (P < 0.01) during normal gait, and improved total Dizziness Handicap Inventory (P < 0.05).

Conclusions:

Our results suggest incremental VOR adaptation significantly improves gain, gait with head rotation, balance during gait, and symptoms in patients with chronic peripheral vestibular hypofunction more so than conventional x1 gaze-stabilizing exercises.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A336).
Acute Management of Thermal Hand Burns in Adults
Authors: Dargan Dallan , Kazzazi Diana , Limnatitou Dimitra , Cochrane Elliott , Stubbington Yvonne , Shokrollahi Kayvan , Ralston David
Published: March 2021

Introduction

Advances in the evidence base of acute thermal hand burns help to guide the management of these common injuries. The aim of this literature review was to evaluate recent evidence in the field over 10 years.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols methodology was used as a guide for this literature review. PubMed, MEDLINE, EMBASE, CINAHL, and Google Scholar were searched for English language articles related to hand burns published between 2009 and 2018 inclusive, and the Cochrane Library was reviewed. Exclusion criteria were as follows: participants younger than 18 years, scar or contracture management, rehabilitation, outcomes assessment, late reconstruction, and electrical or chemical burns.

Results

An initial search retrieved 6493 articles, which was narrowed to 403 full-text articles that were reviewed independently by 3 of the authors and categorized. Of 202 included articles, there were 8 randomized controlled trials and 2 systematic reviews. Six evidence-based guidelines were reviewed. Referral of hand burns to specialist centers, use of telemedicine, early excision and grafting, and immediate static splintage have been recommended. Enzymatic debridement results in earlier intervention, more accurate burn assessment, preservation of vital tissue, and fewer skin grafts, and ideally requires regional anesthesia. Guidance on escharotomy emphasizes indication, technique and adequate intervention, and potential for enzymatic debridement. Inclusion of topical negative pressure, dermal regenerative templates, acellular dermal matrices, and noncellular skin substitutes in management has helped improve scar and functional outcomes.

Discussion

The results of this literature review demonstrate that multiple national and international societies have published burns guidelines during the decade studied, with aspects directly relevant to hand burns, including the International Society for Burn Injuries guidelines. There are opportunities for evidence-based quality improvement across the field of hand burns in many centers.

Conclusions

More than 200 articles globally in 10 years outline advances in the understanding of acute management of thermal hand burns. Incorporating the evidence base into practice may facilitate optimization of triage referral pathways and acute management for hand burns.
Estimated GFR Slope in Kidney Transplant Patients: When the Error Is Random
Authors: Luis Lima Sergio , Marrero Miranda Domingo , González Rinne Ana , Negrín Mena Natalia , Pérez Tamajón Lourdes , Rodríguez Aurelio , Alvarez González Alejandra , González Delgado Alejandra , Ferrer Moure Carmen , González Rinne Federico , Martín Laura Díaz , Rodríguez Rodríguez Ana Elena , Gómez Díaz Laura , García Cabrera Verónica , Jiménez Sosa Alejandro , Torres Armando , Ortiz Alberto , Gaspari Flavio , Porrini Esteban
Published: March 2021

Background.

The evaluation of renal function changes over time is crucial in day-to-day renal transplant care, and the slope of renal function is a major outcome in clinical trials. Little is known about the reliability of estimated glomerular filtration rate (eGFR) in reflecting real glomerular filtration rate (GFR) changes.

Methods.

We analyzed the variability of eGFR slope by 63 equations in estimating measured GFR (mGFR) changes in 110 renal transplant patients. The agreement between eGFR and mGFR slopes was evaluated by the concordance correlation coefficient and the limits of agreement. Patients were grouped based on mGFR slope in rapid GFR loss: faster than −3 mL/min/y; stable renal function: −3 to +3 mL/min/y; and improvement in GFR: higher than +3 mL/min/y.

Results.

Concordance correlation coefficient averaged 0.36 and limits of agreement ±10 mL/min/y, indicating very poor agreement between eGFR and mGFR slopes. The eGFR slope classified patients into the same group of mGFR slope only in 25% of the cases. In about two-thirds of patients, the eGFR slope was either markedly faster or slower than the mGFR slope. In half of these cases, the discrepancy between mGFR and eGFR slopes was ≥50%.

Conclusions.

Formulas are neither accurate nor precise in reflecting real GFR decline in renal transplant patients, making them unreliable for clinical practice and trials.
Targeted rescue of synaptic plasticity improves cognitive decline after severe systemic inflammation
Authors: Grünewald Benedikt , Wickel Jonathan , Hahn Nina , Hörhold Franziska , Rupp Hanna , Chung Ha-Yeun , Haselmann Holger , Strauss Anja S. , Schmidl Lars , Hempel Nina , Grünewald Lena , Urbach Anja , Bauer Michael , Toyka Klaus V. , Blaess Markus , Claus Ralf A. , König Rainer , Geis Christian
Published: March 2021

Sepsis-associated encephalopathy (SAE) is a frequent complication in patients with severe systemic infection resulting in acute brain dysfunction and incapacitating long-term sequelae. SAE includes delirium, premature death, post-traumatic stress disorder, and major long-term cognitive impairment. The underlying pathophysiology of SAE is largely unresolved and specific treatment options are missing. We induced the peritoneal contamination and infection (PCI) sepsis model in 769 mice and compared these with 259 control mice. We found that experimental sepsis causes synaptic pathology in the brain characterized by severely disordered synaptic plasticity with reduced long-term potentiation, changes in CA1 pyramidal neuron dendritic spines, and behavioral abnormalities indicating cognitive dysfunction. Using electrophysiology, we found reduced frequency of quantal and spontaneous excitatory postsynaptic currents whereas amplitudes of miniature, spontaneous, and evoked excitatory currents were increased, pointing towards a homeostatic synaptic scaling mechanism. Corresponding to dysfunctional excitatory synaptic function we discovered downregulation of genes related to neuronal and synaptic signaling in the brain, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1), members of the transcription-regulatory EGR gene family, and the gene for dual-specificity phosphatase 6 (Dusp6). At the protein level, ARC expression and MAP kinase signaling in the brain were affected. For targeted rescue of dysfunctional synaptic signaling and plasticity, we overexpressed ARC in the hippocampus by microinjection of an adeno-associated virus containing a neuron-specific plasmid of the ARC transgene. Hereby we achieved recovery of defective synaptic plasticity in the hippocampal Schaffer collateral-CA1 pathway and improvement of memory dysfunction. Using a different rescue paradigm, PCI mice were subjected to enriched environment providing multiple activating stimuli. Enriched environment led to restoration of disordered long-term potentiation and memory, thus demonstrating the potential for activity-induced improvement. Together, we identified synaptic pathomechanisms of SAE after severe systemic infection and provide a conceptual approach to treat SAE-related disease mechanisms which may be applicable to patients afflicted with SAE.
sRNARFTarget: A fast machine-learning-based approach for transcriptome-wide sRNA Target Prediction
Authors: Naskulwar Kratika , Peña-Castillo Lourdes
Published: March 2021

Bacterial small regulatory RNAs (sRNAs) are key regulators of gene expression in many processes related to adaptive responses. A multitude of sRNAs have been identified in many bacterial species; however, their function has yet to be elucidated. A key step to understand sRNAs function is to identify the mRNAs these sRNAs bind to. There are several computational methods for sRNA target prediction, and the most accurate one is CopraRNA which is based on comparative-genomics. However, species-specific sRNAs are quite common and CopraRNA cannot be used for these sRNAs. The most commonly used transcriptome-wide sRNA target prediction method and second-most-accurate method is IntaRNA. However, IntaRNA can take hours to run on a bacterial transcriptome. Here we present sRNARFTarget, a machine-learning-based method for transcriptome-wide sRNA target prediction applicable to any sRNA. We comparatively assessed the performance of sRNARFTarget, CopraRNA and IntaRNA in three bacterial species. Our results show that sRNARFTarget outperforms IntaRNA in terms of accuracy, ranking of true interacting pairs, and running time. However, CopraRNA substantially outperforms the other two programs in terms of accuracy. Thus, we suggest using CopraRNA when homolog sequences of the sRNA are available, and sRNARFTarget for transcriptome-wide prediction or for species-specific sRNAs. sRNARFTarget is available athttps://github.com/BioinformaticsLabAtMUN/sRNARFTarget.
Deep learning-based quantification of arbuscular mycorrhizal fungi in plant roots
Authors: Evangelisti Edouard , Turner Carl , McDowell Alice , Shenhav Liron , Yunusov Temur , Gavrin Aleksandr , Servante Emily K. , Quan Clément , Schornack Sebastian
Published: March 2021

Soil fungi establish mutualistic interactions with the roots of most vascular land plants. Arbuscular mycorrhizal (AM) fungi are among the most extensively characterised mycobionts to date. Current approaches to quantifying the extent of root colonisation and the abundance of hyphal structures in mutant roots rely on staining and human scoring involving simple, yet repetitive tasks prone to variations between experimenters.

We developed AMFinder which allows for automatic computer vision-based identification and quantification of AM fungal colonisation and intraradical hyphal structures on ink-stained root images using convolutional neural networks.

AMFinder delivered high-confidence predictions on image datasets of roots of multiple plant hosts (Nicotiana benthamiana,Medicago truncatula,Lotus japonicus,Oryza sativa) and captured the altered colonisation inram1-1,strandsmax1mutants. A streamlined protocol for sample preparation and imaging allowed us to quantify mycobionts from the generaRhizophagus,Claroideoglomus,RhizoglomusandFunneliformisvia flatbed scanning or digital microscopy including dynamic increases in colonisation in whole root systems over time.

AMFinder adapts to a wide array of experimental conditions. It enables accurate, reproducible analyses of plant root systems and will support better documentation of AM fungal colonisation analyses. AMFinder can be accessed here:https://github.com/SchornacklabSLCU/amfinder.git
Oxaliplatin Resistance in Colorectal Cancer Enhances TRAIL Sensitivity Via Death Receptor 4 Upregulation and Lipid Raft Localization
Authors: Greenlee Joshua D. , Lopez-Cavestany Maria , Ortiz-Otero Nerymar , Liu Kevin , Subramanian Tejas , Cagir Burt , King Michael R.
Published: March 2021

Colorectal cancer (CRC) remains a leading cause of cancer death, and its mortality is associated with metastasis and chemoresistance. We demonstrate that oxaliplatin-resistant CRC cells are sensitized to TRAIL-mediated apoptosis. Oxaliplatin-resistant cells exhibited transcriptional downregulation of caspase-10, but this had minimal effects on TRAIL sensitivity following CRISPR-Cas9 deletion of caspase-10 in parental cells. Sensitization effects in oxaliplatin-resistant cells were found to be a result of increased DR4, as well as significantly enhanced DR4 palmitoylation and translocation into lipid rafts. Raft perturbation via nystatin and resveratrol significantly altered DR4/raft colocalization and TRAIL sensitivity. Blood samples from metastatic CRC patients were treated with TRAIL liposomes, and a 57% reduction of viable CTCs was observed. Increased DR4/lipid raft colocalization in CTCs was found to correspond with increased oxaliplatin resistance and increased efficacy of TRAIL liposomes. To our knowledge, this is the first study to investigate the role of lipid rafts in primary CTCs.

Impact Statement

Oxaliplatin-resistant colorectal cancer cells exhibit unregulated death receptor 4 expression with increased receptor palmitoylation and translocation into lipid rafts, increasing their sensitivity to apoptosis via TRAIL.
Content bias in the cultural evolution of house finch song
Authors: Youngblood Mason , Lahti David
Published: March 2021

In this study, we used a longitudinal dataset of house finch (Haemorhous mexicanus) song recordings spanning four decades in the introduced eastern range to assess how individual-level cultural transmission mechanisms drive population-level changes in birdsong. First, we developed an agent-based model (available as a new R package calledTransmissionBias) that simulates the cultural transmission of house finch song given different parameters related to transmission biases, or biases in social learning that modify the probability of adoption of particular cultural variants. Next, we used approximate Bayesian computation and machine learning to estimate what parameter values likely generated the temporal changes in diversity in our observed data. We found evidence that strong content bias, likely targeted towards syllable complexity, plays a central role in the cultural evolution of house finch song in western Long Island. Frequency and demonstrator biases appear to be neutral or absent. Additionally, we estimated that house finch song is transmitted with extremely high fidelity. Future studies should use our simulation framework to better understand how cultural transmission and population declines influence song diversity in wild populations.
Cardiovascular risk assessment and coronary artery calcification burden in asymptomatic patients in the initial years of hemodialysis
Authors: Kusic Milicevic Jovana , Vidakovic Radosav , Markovic Rodoljub , Andjelkovic Apostolovic Marija , Korac Mihajlo , Trbojevic Stankovic Jasna , Jemcov Tamara , Neskovic Aleksandar N. , Dragovic Gordana
Published: March 2021

The specific tool for cardiovascular risk assessment in hemodialysis population has not yet been proposed, despite high prevalence of cardiovascular morbidity, and mortality in clinically asymptomatic patients. Coronary artery calcium score (CACS), as a reliable predictor of future cardiovascular events, might be a valuable approach. We sought to evaluate coronary artery calcification burden and its association with clinical and laboratory parameters in asymptomatic patients who recently initiated hemodialysis. The cross‐sectional study included 60 asymptomatic patients receiving chronic hemodialysis for no longer than 48 months. CACS was assessed by cardiac computed tomography. Intima‐media thickness (IMT) of both common carotid and femoral arteries were measured using ultrasonography. The mean total CACS was 160.50 (443). Patients' age correlated significantly with CACS (σ = 0.367; P = 0.004), carotid (σ = 0.375; P = 0.004) and femoral IMT (σ = 0.323; P = 0.013). Patients with CACS = 0 were significantly younger than patients with CACS >400: 52.4 ± 7.91 vs. 63.88 ± 8.37 years old, respectively (P = 0.034). In patients receiving dialysis for longer than 24 months CACS, femoral and carotid IMT were higher than in those dialyzed for less than 24 months; however, none has reached significance. There was a significant positive correlation between CACS and right (σ = 0.312; P = 0.018) and left (σ = 0.521; P < 0.001) femoral IMT, while not with carotid. CACS showed significant negative correlation with the serum iron (σ = −0.351; P = 0.007). Calcification burden varies significantly in asymptomatic patients in early years of dialysis. It correlates with patients' age and tends to increase with dialysis vintage. Femoral IMT might be useful for cardiovascular risk stratification in asymptomatic patients who recently initiated hemodialysis.
Metabolic engineering of microorganisms for the production of multifunctional non‐protein amino acids: γ‐aminobutyric acid and δ‐aminolevulinic acid
Authors: Su Anping , Yu Qijun , Luo Ying , Yang Jinshui , Wang Entao , Yuan Hongli
Published: March 2021

Gamma‐aminobutyric acid (GABA) and delta‐aminolevulinic acid (ALA), playing important roles in agriculture, medicine and other fields, are multifunctional non‐protein amino acids with similar and comparable properties and biosynthesis pathways. Recently, microbial synthesis has become an inevitable trend to produce GABA and ALA due to its green and sustainable characteristics. In addition, the development of metabolic engineering and synthetic biology has continuously accelerated and increased the GABA and ALA yield in microorganisms. Here, focusing on the current trends in metabolic engineering strategies for microbial synthesis of GABA and ALA, we analysed and compared the efficiency of various metabolic strategies in detail. Moreover, we provide the insights to meet challenges of realizing industrially competitive strains and highlight the future perspectives of GABA and ALA production.
Prognostic impact of Notch1 receptor and clinicopathological High‐Risk Predictors in lacrimal gland adenoid cystic carcinoma
Authors: Anjum Shahzan , Sen Seema , Pushker Neelam , Bajaj Mandeep Singh , Kashyap Seema , Bakhshi Sameer , Chosdol Kunzang , Meel Rachna , Sharma Mehar Chand
Published: March 2021

Purpose

Adenoid Cystic Carcinoma (ACC) is an aggressive malignant lacrimal gland tumour associated with poor prognosis. Aberrant Notch signalling has been investigated in various tumours. However, very few studies on Notch signalling in lacrimal gland ACC are reported. The aim of the present study was to evaluate the status of Notch1 receptor and activated Notch1 (NICD1) in lacrimal gland ACC and to correlate it with high‐risk clinicopathological features.

Methods

A total of 23 cases of histopathologically proven lacrimal gland ACC, who underwent surgical treatment, were included in this study. Expression of Notch1 receptor and NICD1 was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. The results obtained were correlated with clinicopathological high‐risk features and survival of the patients. Kaplan–Meier survival and multivariate analysis was performed to determine the prognostic significance.

Results

Overexpression of Notch1 receptor and NICD1 was observed in 65% and 39% of lacrimal gland ACC cases, respectively. On Kaplan–Meier survival analysis, patients with Notch1 receptor overexpression had reduced disease free survival. On univariate analysis, male gender, bone erosion, perineural invasion, solid histologic pattern, intracranial extension and advanced tumour stage were also indicators of poor prognosis. On multivariate analysis bone erosion was the most significant poor prognostic indicator.

Conclusion

Our study demonstrates that overexpression of Notch1 receptor plays a critical role in the biology and aggressive behaviour of lacrimal gland ACC. Bone erosion, solid histologic pattern, advanced T stage, perineural invasion and intracranial extension are other high‐risk clinicopathological predictors of lacrimal gland ACC.
Teachers’ beliefs and practices about oral corrective feedback in university EFL classes
Authors: Yüksel Doğan , Soruç Adem , McKinley Jim
Published: March 2021

This study examined (in)congruences between beliefs and practices of EFL university teachers on in‐class oral corrective feedback (OCF). The participants were 20 university English language teachers from a private university in Turkey. Data were collected via video‐recorded non‐participant detached observation, a task about OCF to determine the beliefs of the teachers, and a stimulated recall interview. The results showed incongruence between what the teachers said they believed and what they did. However, teachers’ beliefs and practices were similar regarding whether the errors should be corrected, when errors should be corrected, and who should correct them. Particularly notable in this study was the finding that those teachers with the greatest incongruence almost always stood by their decisions, even after they watched their unsuccessful OCF practices.
Determinants of suboptimal blood pressure control in a multi‐ethnic population: The Healthy Life in an Urban Setting (HELIUS) study
Authors: van der Linden Eva L. , Collard Didier , Beune Erik J. A. J. , Nieuwkerk Pythia T. , Galenkamp Henrike , Haafkens Joke A. , Moll van Charante Eric P. , van den Born Bert‐Jan H. , Agyemang Charles
Published: March 2021

Among ethnic minority groups in Europe, blood pressure (BP) control is often suboptimal. We aimed to identify determinants of suboptimal BP control in a multi‐ethnic population. We analyzed cross‐sectional data of the Healthy Life in an Urban Setting (HELIUS) study, including 3571 participants aged 18‐70 with prescribed antihypertensive medication, of various ethnic backgrounds (500 Dutch, 1052 African Surinamese, 656 South‐Asian Surinamese, 637 Ghanaian, 433 Turkish, and 293 Moroccan) living in Amsterdam, the Netherlands. 53.3% of the population had suboptimal BP control, defined as BP ≥140/90 mmHg despite prescribed antihypertensives. Using multivariate logistic regression analysis, female sex (OR 0.50, 95%CI 0.43‐0.59), being married (0.83, 0.72‐0.96), smoking (0.78, 0.65‐0.94), alcohol intake (0.80, 0.66‐0.96), obesity (1.67, 1.35‐2.06), cardiovascular disease (CVD) history (0.56, 0.46‐0.68), non‐adherence to antihypertensives (1.26, 1.00‐1.58), and family history of hypertension (1.19, 1.02‐1.38) were identified to be independently associated with suboptimal BP control in the total population. In the ethnic‐stratified analysis, factors associated with better BP control were female sex (all ethnic groups), smoking (Turks), and CVD history (Dutch, South‐Asian Surinamese, and African Surinamese), whereas factors associated with suboptimal BP control were older age (Turks), obesity (Dutch, African Surinamese, Ghanaian, and Turks), and non‐adherence to antihypertensives (Dutch). In conclusion, our analysis identifies several key determinants that are independently associated with suboptimal BP control in a multi‐ethnic population, with some important variations between ethnic groups. Targeting these determinants may help to improve BP control.
PRMT5 promotes colorectal cancer growth by interaction with MCM7
Authors: Li Xiangwei , Wang Xin , Zhao Jiahui , Wang Jian , Wu Jingjing
Published: March 2021

Protein arginine methyltransferase 5 (PRMT5) is a type of methyltransferase enzyme that can catalyse arginine methylation of histones and non‐histone proteins. Accumulating evidence indicates that PRMT5 promotes cancer development and progression. However, its function in colorectal cancer (CRC) is poorly understood. In this study, we revealed the oncogenic roles of PRMT5 in CRC. We found that PRMT5 promoted CRC cell proliferation, migration and invasion in vitro and in vivo. We identified minichromosome maintenance‐7 (MCM7) as the direct PRMT5‐binding partner. A co‐immunoprecipitation (co‐IP) assay indicated that PRMT5 physically interacted with MCM7 and that the direct binding domain was located between residues 1‐248 in MCM7. In addition, our results from analysis of 99 CRC tissues and 77 adjacent non‐cancerous tissues indicated that the PRMT5 and MCM7 expression levels were significantly higher in CRC tissues than in control tissues, which was further confirmed by bioinformatic analysis using TCGA and GEO datasets. We also found that MCM7 promoted CRC cell proliferation, migration and invasion in vitro. Furthermore, we observed that increased PRMT5 expression predicted unfavourable patient survival in CRC patients and in the subgroup of patients with a tumour size of ≤5 cm. These data suggested that PRMT5 and MCM7 might be novel potential targets for the treatment of CRC.
Flexural strength and microhardness of bulk‐fill restorative materials
Authors: de Mendonça Beatriz Curvello , Soto‐Montero Jorge Rodrigo , de Castro Eduardo Fernandes , Pecorari Vanessa Gallego Arias , Rueggeberg Frederick Allen , Giannini Marcelo
Published: March 2021

Background

Bulk‐fill materials can facilitate the restorative procedure mainly for deep and wide posterior cavities. The purpose of this study was to evaluate flexural strength (biaxial flexural strength [BFS]) and microhardness (Knoop microhardness [KHN]) at different depths of bulk‐fill materials.

Methods

Five bulk‐fill materials were tested: two light‐curable composite resins, one dual‐cure composite, one bioactive restorative, and a high‐viscosity glass ionomer. A conventional composite was used as control. BFS and KHN were tested at different depths. Data was analyzed by two‐ and one‐way ANOVAs, respectively and Tukey's post‐hoc (α=0.05).

Results

The high‐viscosity glass ionomer material presented the lowest BFS at all depths. KHN for the two light‐curable and the dual‐cure bulk‐fill resin composites was reduced following an increase in restoration depth, while the conventional composite, the bioactive material, and the high‐viscosity glass ionomer were not affected.

Conclusion

There are differences in the properties of the tested materials at 4 mm depth, showing that the studied properties of some materials vary according to the cavity depth, although the results are material dependent.

Clinical Significance

Mechanical properties of light‐cured, bulk‐fill materials may be affected by inadequate polymerization. Clinicians should consider complementary strategies to achieve adequate polymerization at high‐increment depths.