bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of computer-based virtual learning environments on nursing students’ mathematical learning in medication processes
Authors: Zwart Diana P. , Goei Sui Lin , Noroozi Omid , Van Luit Johannes E. H.
Published: February 2021

Computer-based virtual learning environments (CBVLEs) are potentially useful teaching tools for training nursing students in professional duties such as the mathematical tasks associated with medication processes. In this study, a CBVLE was designed with well-structured instructional activities such as interleaved practice and feedback. Mathematical medication scenarios and basic arithmetic exercises were integrated into the CBVLE. Four training conditions were used in the CBVLE to facilitate extra support for mathematical medication learning: (1) learning without worked examples, (2) learning with worked examples involving domain-specific knowledge, (3) learning with worked examples involving regular thinking strategies, and (4) learning with combined worked examples. This study was conducted with 118 nursing students enrolled in post-secondary nursing education and Bachelor’s nursing programmes. Students were pre-tested and post-tested on their mathematical medication learning. Training in the CBVLE improved mathematical medication learning for all students from pre-test to the post-test stages, but no differences were found among the four different conditions. Nursing students’ prior knowledge, non-verbal intelligence, and number of correct tasks predicted mathematical medication learning outcomes. When controlling for non-verbal intelligence, students in the condition 1 benefited more than students in condition 3 in terms of their mathematical medication learning outcomes. The same accounted for the support of the low-achieving students in the CBVLE. The support conditions for the high-achieving group appeared to be unimportant for mathematical medication learning. It seems that technology is taken over some of the capacity of working memory, which accounts for the benefits to the low-achieving learners.
A new society for regenerative biologists
Authors: Poss Kenneth D. , Tanaka Elly M.
Published: February 2021

Summary: We announce the launch of the International Society for Regenerative Biology – a new alliance for scientists interested in regenerative biology and its applications.
Case Article—The SafeBirth Clinic
Authors: Dawande Milind , Huh Woonghee Tim , Janakiraman Ganesh , Nagarajan Mahesh , Bo Yang
Published: February 2021

The effective utilization of capacity is an important operational goal that managers strive to achieve. Most textbooks use the following simple “bottleneck formula” to illustrate the calculation of process capacity: the capacity of each resource is first calculated by examining that resource in isolation; process capacity is then taken as the smallest (bottleneck) among the resource capacities. The bottleneck formula is, in fact, an approximation of the true process capacity and correctly calculates capacity only in some straightforward settings, for example, in processes where each activity requires only one resource and in processes where each resource is dedicated to only one activity. However, when activities require multiple resources simultaneously (collaboration) and when resources are capable of doing multiple activities (multitasking), the simple formula can be significantly inaccurate. Further, several commonly held managerial insights related to process capacity and least-capacity resources that emerge from the formula can be misleading. The main goal of this case is to alert students that, for processes with collaboration and multitasking, the use of the bottleneck formula brings the potential danger of reaching incorrect conclusions about capacity and what constitutes a bottleneck of a process and may eventually lead to erroneous decisions with significant financial impact, for example, investing in procuring an expensive resource without being able to realize the presumed increase in capacity. More generally, the case illustrates the principles of process capacity and bottleneck structures and clarifies some often-repeated misunderstandings on the relationship between process capacity and least-capacity resources. The case also illustrates the importance of using Gantt charts for conveniently displaying schedules of activities.
On a learning curve
Authors: Allingham Sue
Published: February 2021

Sue Allingham looks behind the headlines to examine what educators are being told they need to do in the current situation – but finds they are already being flexible in their thinking in order to ensure the best outcomes for young children.
For the greater good
Authors: White Hilary
Published: February 2021

Democracy is an important concept in relation to sustainability. If you can embed in your provision the democratic intent to give every child equal rights and opportunities, your practice will be embracing the ideals of inclusivity and non-discrimination, says Hilary White.
REVIEWS
Authors: Hewson Claire
Published: February 2021

In this month's lead review, Tails from the Classroom, find out how animal-assisted interventions in educational settings can inspire and support children's all-round learning and development.
Shy and dynamic
Authors: Hart Karen
Published: February 2021

Nadia Fine is the host of the Shy and Mighty podcast and the creator of ‘The Mighty Mob’, an online program aimed at helping primary age children who identify as shy. She shares some insights into helping shy pre-schoolers find their voice.
Fabulous Frida!
Authors: Hart Karen
Published: February 2021

Frida Kahlo's art is a fantastic subject for pre-schoolers as there are so many ways to explore her paintings, her life and her art style. It is also an opportunity for children to understand her cultural heritage as a Mexican painter.
Wound care during the COVID-19 pandemic: improving outcomes through the integration of telemedicine
Authors: Oropallo Alisha , Lantis John , Martin Alexander , Al Rubaiay Ammar , Wang Na
Published: February 2021

COVID-19 is highly contagious and its rapid spread burdens the healthcare system. As the number of confirmed cases goes up, the shortage of medical resources has become a challenge. To avoid the collapse of the healthcare system during the fight with COVID-19, all healthcare workers, including wound care practitioners, should adapt to new roles and use any appropriate methods available to slow the spread of the virus. Integrating telemedicine into wound care during the outbreak helps maintain social distancing, preserve personal protective equipment and medical resources, and eliminate unnecessary exposure for both vulnerable patients and high-risk healthcare workers.
The evolving use of hyperbaric oxygen therapy during the COVID-19 pandemic
Authors: El Hawa Areeg A Abu , Charipova Karina , Bekeny Jenna C , Johnson-Arbor Kelly K
Published: February 2021

The Sars-CoV-2 (COVID-19) pandemic has resulted in significant and unprecedented shifts in the delivery of health care services in the United States. Although wound care remains an essential service during the COVID-19 pandemic, the financial consequences and infectious disease ramifications of the pandemic have resulted in closure or limitation of hours in many outpatient wound and hyperbaric oxygen therapy (HBOT) centers. As HBOT patients often require daily treatment sessions for a period of months, it is necessary for facilities providing HBOT services to adjust to the COVID-19 pandemic while still maintaining availability of this important service. Modification of HBOT session timing and chamber decontamination procedures, utilisation of telehealth services for initial patient evaluations, and acceptance of novel patient populations and diagnoses are mechanisms by which HBOT centers can adapt to the evolving model of health care delivery throughout a pandemic. While COVID-19 is not a currently accepted indication for HBOT, patients may be referred for HBOT consultation due to the post-infectious sequelae of the virus, and thus HBOT facilities must be aware of the potential uses of this treatment for post-viral complications. By redefining paradigms for health care delivery during the COVID-19 pandemic, HBOT and wound centers can continue to provide high-quality and uninterrupted care to vulnerable patient populations.
Trampolines injuries are bouncing back
Authors: Ibrahim Yahya , Huq Sumon , Shanmuganathan Kanatheepan , Gille Helen , Buddhdev Pranai
Published: February 2021

Aims

This observational study examines the effect of the COVID-19 pandemic upon the paediatric trauma burden of a district general hospital. We aim to compare the nature and volume of the paediatric trauma during the first 2020 UK lockdown period with the same period in 2019.

Methods

Prospective data was collected from 23 March 2020 to 14 June 2020 and compared with retrospective data collected from 23 March 2019 to 14 June 2019. Patient demographics, mechanism of injury, nature of the injury, and details of any surgery were tabulated and statistically analyzed using the independent-samples t-test for normally distributed data and the Mann-Whitney-U test for non-parametric data. Additionally, patients were contacted by telephone to further explore the mechanism of injury where required, to gain some qualitative insight into the risk factors for injury.

Results

The 2020 lockdown resulted in 30% fewer paediatric trauma presentations (441 vs 306), but no significant change in the number of patients requiring surgery (47 vs 51; p = 0.686). Trampolining injuries increased in absolute numbers by 168% (p < 0.001), almost four times more common when considered as percentage of all injuries observed in 2020 vs 2019. There was a decrease in high energy trauma from road traffic accidents and falls from height (21.5% decrease, p < 0.001). Despite a shift towards more conservative treatment options, trampolining injuries continued to require surgery in similar proportions (19.4 vs 20%; p = 0.708). Qualitative investigation revealed that the most common risk factor for trampolining injury was concurrent usage, especially with an older child.

Conclusion

COVID-19 lockdown has resulted in a decrease in paediatric orthopaedic presentations and high energy trauma. However, due to a marked increase in home trampolining injuries, and their unchanged requirement for surgery, there has been no change in the requirement for surgery during the lockdown period. As home exercise becomes more prevalent, a duty of public health falls upon clinicians to advise parents against trampoline usage. Cite this article: Bone Jt Open 2021;2(2):86–92.
The biological prospective of red-pigmented bacteria cultured from contaminated agar media
Authors: Arifiyanto Achmad , AFRIANI HAPIN , PUTRI MEISHY HANDERLIN , DAMAYANTI BERLIANA , RIYANTO CINDY LUKYTA RATIH
Published: February 2021

Abstract. Arifiyanto A, Afriani H, Putri MH, Damayanti B, Riyanto CL. 2021. The biological prospective of red-pigmented bacteria cultured from contaminated agar media. Biodiversitas 22: 1152-1159. Contaminated agar media was often depleted due to the growth of microbes, which is undesirable for culture. However, the contaminating microbes usually have a distinctive morphology. This research aimed to identify the potential of red-pigmented bacteria originated from the contamination of Drosophila melanogaster larvae. Fruit fly larvae that grow on contaminated tryptic soy agar were accompanied by the appearance of the red-pigmented bacteria colony. The bacterial colonies were purified by the re-streaking method on tryptic soybean agar. This strain was characterized morphologically, biochemically, and molecularly. Results showed that the MBC1 strain was identified as Serratia marcescens. The various metal susceptibility tests at 25 ppm did not affect the growth of the MBC1 strain. Meanwhile, it was also able to inhibit the growth of certain pathogens such as Aspergillus niger, Candida sp., Fusarium sp., and Rigidoporous sp. Strain MBC1 was able to produce antioxidant compounds. The lipolytic and amylolytic activity can be developed for bioremediate agriculture waste and biosurfactant production.
Inhibition of a-amylase and a-glucosidase activities in vitro by extracts of selected medicinal plants
Authors: Pant Deepak , ARYAL BIVA , PUN DAMA , SHARMA SUSHILA , JOSHI GIRI PRASAD
Published: February 2021

Abstract. Pant DR, Aryal B, Pun D, Sharma S, Joshi GP. 2021. Inhibition of a-amylase and a-glucosidase activities in vitro by extracts of selected medicinal plants. Biodiversitas 22: 1187-1193. Several medicinal plants are being used traditionally in the treatment/management of Diabetes Mellitus (DM). The present work focuses on experimental verification of antidiabetic potential of different medicinal plants that have been reported to be used traditionally to manage DM. Aqueous and methanolic extracts of 12 species of plants were studied for their inhibitory effect on the activities of a-amylase and a-glucosidase, two key enzymes of carbohydrate metabolism. The extracts of all the species showed very high degree (nearly 90% or above) of inhibition of α-amylase irrespective of the extraction solvent. The aqueous extracts of Asterella wallichiana, however, showed only 63.60% inhibition of a-amylase. Except for Asterella wallichiana, the percentage inhibition of a-amylase in aqueous and methanolic solution in all the species tested were almost similar. The percentage inhibition of a-glucosidase was lower than that of a-amylase for all the species in both types of extraction medium. The highest percentage inhibition of a-glucosidase (81.13±1.36 %) was found in methanolic extracts of Rhuschinensis. The inhibition of a-glucosidase was much higher in methanolic extracts than in aqueous extracts for all the species tested. High degree of inhibition of a-amylase activity in vitro by the extracts of all the species tested provides scientific basis for using these plants in the management/treatment of diabetes in traditional medicine.
Chemical analysis and Biological properties of Terminalia macroptera Guill. & Perr. from Eastern Chad
Authors: Chahad Aouadalkarim Moussa , Adey Souleymane Adam , Chatté Adawaye , Louis Zapfack , Dijoux-Franca Marie-Geneviève
Published: February 2021

Based on a previous ethnobotanical survey, Terminalia macroptera Guill. & Perr. was selected as its heartwood is traditionally used for infections treatment and as mosquito repellent in the province of Ouaddai (Chad). In our course for a better knowledge of this medicinal plant which could be developed as phytomedicine, it is of great interest to subsequently characterize the chemical profile and bioactivities of this plant. In the present study we develop an Ultrahigh-performance liquid chromatography with diode array detection coupled to electrospray ionization and quadrupole time-of-flight (UHPLC-DAD-ESI/QTOF) technique to characterized on line potentially bioactive compounds. Thirteen compounds were identified in active extracts and fractions from Terminalia macroptera Guill. & Perr. heartwood, namely gallic and ellagic acids derivatives, 23-O-galloyl-terminolic acid, 23-O-galloyl arjunolic acid, 4,4’-dihydroxy-Z-stilbene-O-rutinoside and 3,5,4’-trihydroxy-Z-stilbene-O-rutinoside. Antibacterial properties were evaluated against sensitive and resistant Staphylococcus aureus strains and antioxidant activities using 1,1-diphenyl-2-picryl-hydrazyl (DPPH). Stilbene derivatives, 23-O-galloyl-terminolic acid and 23-O-galloyl arjunolic acid are newly reported in T. macroptera Guill. & Perr.
Ptychographic optical coherence tomography
Authors: Du Mengqi , Loetgering Lars , Eikema Kjeld S. E. , Witte Stefan
Published: February 2021

Ptychography is a robust computational imaging technique that can
reconstruct complex light fields beyond conventional hardware limits.
However, for many wide-field computational imaging techniques,
including ptychography, depth sectioning remains a challenge. Here we
demonstrate a high-resolution three-dimensional (3D) computational
imaging approach, which combines ptychography with spectral-domain
imaging, inspired by optical coherence tomography (OCT). This results
in a flexible imaging system with the main advantages of OCT, such as
depth-sectioning without sample rotation, decoupling of transverse and
axial resolution, and a high axial resolution only determined by the
source bandwidth. The interferometric reference needed in OCT is
replaced by computational methods, simplifying hardware requirements.
As ptychography is capable of deconvolving the illumination
contributions in the observed signal, speckle-free images are
obtained. We demonstrate the capabilities of ptychographic optical
coherence tomography (POCT) by imaging an axially discrete
lithographic structure and an axially continuous mouse brain
sample.
Dynamic manipulation of nonlinear Talbot effect with structured light
Authors: Li Lin , Liu Haigang , Chen Xianfeng
Published: February 2021

The nonlinear Talbot effect has sparked considerable interest of researchers since it was proposed in recent years because it has many advantages compared with the Talbot effect in linear optics. In previous researches, such a nonlinear Talbot effect is only observed in nonlinear photonic crystals, which cannot dynamically manipulate in real time. Here, we report and experimentally demonstrate the high efficiency and dynamic manipulation of such a nonlinear Talbot effect with structured light. Different from the previous scheme, the nonlinear self-imaging effect observed in our experiment originates from the spatial phase structure of the incident fundamental frequency light. In our experiments, integer and fractional second-harmonic Talbot self-imaging is observed. Our results not only extend a novel technique for dynamic manipulation of the nonlinear Talbot effects, but also may have potential applications in parallel optical lithography, optical imaging, and optical computing.
Tunable optical second-order Volterra nonlinear filter using wave mixing and delays to equalize a 10–20 Gbaud 4-APSK channel
Authors: Zou Kaiheng , Liao Peicheng , Zhou Huibin , Fallahpour Ahmad , Minoofar Amir , Almaiman Ahmed , Alishahi Fatemeh , Tur Moshe , Willner Alan E.
Published: February 2021

We experimentally demonstrate a tunable optical second-order Volterra filter using wave mixing and delays. Wave mixing is performed in a periodically poled lithium niobate waveguide with the cascaded sum-frequency generation and difference-frequency generation processes. Compared to conventional optical tapped delay line structures, second-order taps are added through the wave mixing of two signal copies. We measure the frequency response of the filter by sending a frequency-swept sinusoidal wave as the input. The tap weights are tuned with a liquid-crystal-on-silicon waveshaper for different filter configurations. With the additional second-order taps, the filter is able to perform a nonlinear function. As an example, we demonstrate the compensation of a nonlinearly distorted 10–20 Gbaud 4-amplitude and phase shift keying signal.
Estimating the effective pressure from nanosecond laser-induced breakdown in water
Authors: Li Fabing , Wang Ying , Zhao Haiying , Xu Xin , Liu Cunming , Men Zhiwei , Sun Chenglin
Published: February 2021

Nanosecond laser-induced breakdown (LIB) in liquids (e.g.,  water) can produce dynamic high pressure and high temperature. However, since high pressure needs to negate the effect of high temperature to some degree, it is only partially effective. As a result, it is difficult to directly measure the effective pressure due to the transient and complex LIB process. Here, we presented a simple method based on Raman spectroscopy to indirectly determine the effective pressure caused by LIB in liquid pure

H

2

O

and low concentration

H

2

O

−

H

2

O

2

mixtures. By comparing the Raman shifts of the ice-VII mode for pure

H

2

O

and

H

2

O

−

H

2

O

2

mixtures under laser pumping and static high pressure, the LIB effective pressure can be first estimated. The empirical equation was then derived base on the correlation of the LIB effective pressure to ice-VII-point stimulated Raman scattering thresholds for pure and mixture water solutions, which can be used to estimate the LIB effective pressures for other different mixture water solutions with the uncertainty of 0.14–0.25 Gpa. Hopefully, our study here would advance the measurements of effective pressure in the LIB process.
Dynamically reversible and strong circular dichroism based on Babinet-invertible chiral metasurfaces
Authors: Luo Xiaoqing , Hu Fangrong , Li Guangyuan
Published: February 2021

We propose a Babinet-invertible chiral metasurface for achieving dynamically reversible and strong circular dichroism (CD). The proposed metasurface is composed of a

V
O

2

–metal hybrid structure, and when

V
O

2

transits between the dielectric state and the metallic state, the metasurface unit cell switches between complementary structures that are designed according to Babinet’s principle. This leads to a large and reversible CD tuning range between

±
0.5

at 0.97 THz, which is larger than the one found in the literature. We attribute the CD effect to extrinsic chirality of the proposed metasurface. We envision that the Babinet-invertible chiral metasurface proposed here will advance the engineering of active and tunable chiro-optical devices and promote their applications.
Room temperature plasma-etching and surface passivation of far-ultraviolet Al mirrors using electron beam generated plasmas
Authors: Rodriguez de Marcos Luis V. , Boris David R. , Gray Emrold , del Hoyo Javier G. , Kozen Alexander C. , Richardson Joseph G. , Rosenberg Samantha G. , Walton Scott G. , Wheeler Virginia , Wollack Edward J. , Woodward Jeffrey M. , Quijada Manuel A.
Published: February 2021

The development of optical systems operating in the far ultraviolet range (FUV, λ=100-200 nm) is limited by the efficiency of passivated aluminum (Al) mirrors. Although it is presently possible to obtain high-reflectivity FUV mirrors through physical vapor deposition, the process involves deposition with substrates at high temperatures, which is technically challenging for large optical elements. A novel passivation procedure for bare Al mirrors is reported. The treatment consisted of using a low-temperature electron-beam generated plasma produced in a gas mixture of Ar and SF6 to etch away the native oxide layer from the Al film, while simultaneously promoting the generation of a thin aluminum tri-fluoride (AlF3) layer on the Al surface. In the first section we analyze the effect of varying both ion energy and SF6 concentration on the FUV reflectance, thickness, composition, and surface morphology of the resulting AlF3 protective layers. In the second section, the reflectivity of samples is optimized at selected important FUV wavelengths for astronomical observations. Notably, samples attained state-of-the-art reflectances of 75% at 108.5 nm (He Lyman γ), 91% at 121.6 nm (H Lyman α), 90% at 130.4 nm (OI), and of 95% at 155.0 nm (C IV). The stability over time of these passivated mirrors is also investigated.
TranSynergy: Mechanism-driven interpretable deep neural network for the synergistic prediction and pathway deconvolution of drug combinations
Authors: Liu Qiao , Xie Lei
Published: February 2021

Drug combinations have demonstrated great potential in cancer treatments. They alleviate drug resistance and improve therapeutic efficacy. The fast-growing number of anti-cancer drugs has caused the experimental investigation of all drug combinations to become costly and time-consuming. Computational techniques can improve the efficiency of drug combination screening. Despite recent advances in applying machine learning to synergistic drug combination prediction, several challenges remain. First, the performance of existing methods is suboptimal. There is still much space for improvement. Second, biological knowledge has not been fully incorporated into the model. Finally, many models are lack interpretability, limiting their clinical applications. To address these challenges, we have developed a knowledge-enabled and self-attention transformer boosted deep learning model, TranSynergy, which improves the performance and interpretability of synergistic drug combination prediction. TranSynergy is designed so that the cellular effect of drug actions can be explicitly modeled through cell-line gene dependency, gene-gene interaction, and genome-wide drug-target interaction. A novel Shapley Additive Gene Set Enrichment Analysis (SA-GSEA) method has been developed to deconvolute genes that contribute to the synergistic drug combination and improve model interpretability. Extensive benchmark studies demonstrate that TranSynergy outperforms the state-of-the-art method, suggesting the potential of mechanism-driven machine learning. Novel pathways that are associated with the synergistic combinations are revealed and supported by experimental evidences. They may provide new insights into identifying biomarkers for precision medicine and discovering new anti-cancer therapies. Several new synergistic drug combinations have been predicted with high confidence for ovarian cancer which has few treatment options. The code is available athttps://github.com/qiaoliuhub/drug_combination.
When to wake up? The optimal waking-up strategies for starvation-induced persistence
Authors: Himeoka Yusuke , Mitarai Namiko
Published: February 2021

Prolonged lag time can be induced by starvation contributing to the antibiotic tolerance of bacteria. We analyze the optimal lag time to survive and grow the iterative and stochastic application of antibiotics. A simple model shows that the optimal lag time can exhibit a discontinuous transition when the severeness of the antibiotic application, such as the probability to be exposed the antibiotic, the death rate under the exposure, and the duration of the exposure, is increased. This suggests the possibility of reducing tolerant bacteria by controlled usage of antibiotics application. When the bacterial populations are able to have two phenotypes with different lag times, the fraction of the second phenotype that has different lag time shows a continuous transition. We then present a generic framework to investigate the optimal lag time distribution for total population fitness for a given distribution of the antibiotic application duration. The obtained optimal distributions have multiple peaks for a wide range of the antibiotic application duration distributions, including the case where the latter is monotonically decreasing. The analysis supports the advantage in evolving multiple, possibly discrete phenotypes in lag time for bacterial long-term fitness.
The impact of phenotypic heterogeneity of tumour cells on treatment and relapse dynamics
Authors: Raatz Michael , Shah Saumil , Chitadze Guranda , Brüggemann Monika , Traulsen Arne
Published: February 2021

Intratumour heterogeneity is increasingly recognized as a frequent problem for cancer treatment as it allows for the evolution of resistance against treatment. While cancer genotyping becomes more and more established and allows to determine the genetic heterogeneity, less is known about the phenotypic heterogeneity among cancer cells. We investigate how phenotypic differences can impact the efficiency of therapy options that select on this diversity, compared to therapy options that are independent of the phenotype. We employ the ecological concept of trait distributions and characterize the cancer cell population as a collection of subpopulations that differ in their growth rate. We show in a deterministic model that growth rate-dependent treatment types alter the trait distribution of the cell population, resulting in a delayed relapse compared to a growth rate-independent treatment. Whether the cancer cell population goes extinct or relapse occurs is determined by stochastic dynamics, which we investigate using a stochastic model. Again, we find that relapse is delayed for the growth rate-dependent treatment type, albeit an increased relapse probability, suggesting that slowly growing subpopulations are shielded from extinction. Sequential application of growth rate-dependent and growth rate-independent treatment types can largely increase treatment efficiency and delay relapse. Interestingly, even longer intervals between decisions to change the treatment type may achieve close-to-optimal efficiencies and relapse times. Monitoring patients at regular check-ups may thus provide the temporally resolved guidance to tailor treatments to the changing cancer cell trait distribution and allow clinicians to cope with this dynamic heterogeneity.
From heterogeneous healthcare data to disease-specific biomarker networks: A hierarchical Bayesian network approach
Authors: Becker Ann-Kristin , Dörr Marcus , Felix Stephan B. , Frost Fabian , Grabe Hans J. , Lerch Markus M. , Nauck Matthias , Völker Uwe , Völzke Henry , Kaderali Lars
Published: February 2021

In this work, we introduce an entirely data-driven and automated approach to reveal disease-associated biomarker and risk factor networks from heterogeneous and high-dimensional healthcare data. Our workflow is based on Bayesian networks, which are a popular tool for analyzing the interplay of biomarkers. Usually, data require extensive manual preprocessing and dimension reduction to allow for effective learning of Bayesian networks. For heterogeneous data, this preprocessing is hard to automatize and typically requires domain-specific prior knowledge. We here combine Bayesian network learning with hierarchical variable clustering in order to detect groups of similar features and learn interactions between them entirely automated. We present an optimization algorithm for the adaptive refinement of such group Bayesian networks to account for a specific target variable, like a disease. The combination of Bayesian networks, clustering, and refinement yields low-dimensional but disease-specific interaction networks. These networks provide easily interpretable, yet accurate models of biomarker interdependencies. We test our method extensively on simulated data, as well as on data from the Study of Health in Pomerania (SHIP-TREND), and demonstrate its effectiveness using non-alcoholic fatty liver disease and hypertension as examples. We show that the group network models outperform available biomarker scores, while at the same time, they provide an easily interpretable interaction network.
The intrinsically disordered N-terminus of the voltage-dependent anion channel
Authors: Preto Jordane , Krimm Isabelle
Published: February 2021

The voltage-dependent anion channel (VDAC) is a critical β-barrel membrane protein of the mitochondrial outer membrane, which regulates the transport of ions and ATP between mitochondria and the cytoplasm. In addition, VDAC plays a central role in the control of apoptosis and is therefore of great interest in both cancer and neurodegenerative diseases. Although not fully understood, it is presumed that the gating mechanism of VDAC is governed by its N-terminal region which, in the open state of the channel, exhibits an α-helical structure positioned midway inside the pore and strongly interacting with the β-barrel wall. In the present work, we performed molecular simulations with a recently developed force field for disordered systems to shed new light on known experimental results, showing that the N-terminus of VDAC is an intrinsically disordered region (IDR). First, simulation of the N-terminal segment as a free peptide highlighted its disordered nature and the importance of using an IDR-specific force field to properly sample its conformational landscape. Secondly, accelerated dynamics simulation of a double cysteine VDAC mutant under applied voltage revealed metastable low conducting states of the channel representative of closed states observed experimentally. Related structures were characterized by partial unfolding and rearrangement of the N-terminal tail, that led to steric hindrance of the pore. Our results indicate that the disordered properties of the N-terminus are crucial to properly account for the gating mechanism of VDAC.
Calcium ions trigger the exposure of phosphatidylserine on the surface of necrotic cells
Authors: Furuta Yoshitaka , Pena-Ramos Omar , Li Zao , Chiao Lucia , Zhou Zheng
Published: February 2021

Intracellular Ca2+level is under strict regulation through calcium channels and storage pools including the endoplasmic reticulum (ER). Mutations in certain ion channel subunits, which cause mis-regulated Ca2+influx, induce the excitotoxic necrosis of neurons. In the nematodeCaenorhabditis elegans, dominant mutations in the DEG/ENaC sodium channel subunit MEC-4 induce six mechanosensory (touch) neurons to undergo excitotoxic necrosis. These necrotic neurons are subsequently engulfed and digested by neighboring hypodermal cells. We previously reported that necrotic touch neurons actively expose phosphatidylserine (PS), an “eat-me” signal, to attract engulfing cells. However, the upstream signal that triggers PS externalization remained elusive. Here we report that a robust and transient increase of cytoplasmic Ca2+level occurs prior to the exposure of PS on necrotic touch neurons. Inhibiting the release of Ca2+from the ER, either pharmacologically or genetically, specifically impairs PS exposure on necrotic but not apoptotic cells. On the contrary, inhibiting the reuptake of cytoplasmic Ca2+into the ER induces ectopic necrosis and PS exposure. Remarkably, PS exposure occurs independently of other necrosis events. Furthermore, unlike in mutants of DEG/ENaC channels, in dominant mutants ofdeg-3andtrp-4, which encode Ca2+channels, PS exposure on necrotic neurons does not rely on the ER Ca2+pool. Our findings indicate that high levels of cytoplasmic Ca2+are necessary and sufficient for PS exposure. They further reveal two Ca2+-dependent, necrosis-specific pathways that promote PS exposure, a “two-step” pathway initiated by a modest influx of Ca2+and further boosted by the release of Ca2+from the ER, and another, ER-independent, pathway. Moreover, we found that ANOH-1, the worm homolog of mammalian phospholipid scramblase TMEM16F, is necessary for efficient PS exposure in thapsgargin-treated worms andtrp-4mutants, like inmec-4mutants. We propose that both the ER-mediated and ER-independent Ca2+pathways promote PS externalization through activating ANOH-1.
CRMP/UNC-33 organizes microtubule bundles for KIF5-mediated mitochondrial distribution to axon
Authors: Chen Ying-Chun , Huang Hao-Ru , Hsu Chia-Hao , Ou Chan-Yen
Published: February 2021

Neurons are highly specialized cells with polarized cellular processes and subcellular domains. As vital organelles for neuronal functions, mitochondria are distributed by microtubule-based transport systems. Although the essential components of mitochondrial transport including motors and cargo adaptors are identified, it is less clear how mitochondrial distribution among somato-dendritic and axonal compartment is regulated. Here, we systematically study mitochondrial motors, including four kinesins, KIF5, KIF17, KIF1, KLP-6, and dynein, and transport regulators inC.elegansPVD neurons. Among all these motors, we found that mitochondrial export from soma to neurites is mainly mediated by KIF5/UNC-116. Interestingly, UNC-116 is especially important for axonal mitochondria, while dynein removes mitochondria from all plus-end dendrites and the axon. We surprisingly found one mitochondrial transport regulator for minus-end dendritic compartment, TRAK-1, and two mitochondrial transport regulators for axonal compartment, CRMP/UNC-33 and JIP3/UNC-16. While JIP3/UNC-16 suppresses axonal mitochondria, CRMP/UNC-33 is critical for axonal mitochondria; nearly no axonal mitochondria present inunc-33mutants. We showed that UNC-33 is essential for organizing the population of UNC-116-associated microtubule bundles, which are tracks for mitochondrial trafficking. Disarrangement of these tracks impedes mitochondrial transport to the axon. In summary, we identified a compartment-specific transport regulation of mitochondria by UNC-33 through organizing microtubule tracks for different kinesin motors other than microtubule polarity.
Association of socioeconomic deprivation with asthma care, outcomes, and deaths in Wales: A 5-year national linked primary and secondary care cohort study
Authors: Alsallakh Mohammad A. , Rodgers Sarah E. , Lyons Ronan A. , Sheikh Aziz , Davies Gwyneth A.
Published: February 2021

Background

Socioeconomic deprivation is known to be associated with worse outcomes in asthma, but there is a lack of population-based evidence of its impact across all stages of patient care. We investigated the association of socioeconomic deprivation with asthma-related care and outcomes across primary and secondary care and with asthma-related death in Wales.

Methods and findings

We constructed a national cohort, identified from 76% (2.4 million) of the Welsh population, of continuously treated asthma patients between 2013 and 2017 using anonymised, person-level, linked, routinely collected primary and secondary care data in the Secure Anonymised Information Linkage (SAIL) Databank. We investigated the association between asthma-related health service utilisation, prescribing, and deaths with the 2011 Welsh Index of Multiple Deprivation (WIMD) and its domains. We studied 106,926 patients (534,630 person-years), 56.3% were female, with mean age of 47.5 years (SD = 20.3). Compared to the least deprived patients, the most deprived patients had slightly fewer total asthma-related primary care consultations per patient (incidence rate ratio [IRR] = 0.98, 95% CI 0.97–0.99, p-value < 0.001), slightly fewer routine asthma reviews (IRR = 0.98, 0.97–0.99, p-value < 0.001), lower controller-to-total asthma medication ratios (AMRs; 0.50 versus 0.56, p-value < 0.001), more asthma-related accident and emergency (A&E) attendances (IRR = 1.27, 1.10–1.46, p-value = 0.001), more asthma emergency admissions (IRR = 1.56, 1.39–1.76, p-value < 0.001), longer asthma-related hospital stay (IRR = 1.64, 1.39–1.94, p-value < 0.001), and were at higher risk of asthma-related death (risk ratio of deaths with any mention of asthma 1.56, 1.18–2.07, p-value = 0.002). Study limitations include the deprivation index being area based and the potential for residual confounders and mediators.

Conclusions

In this study, we observed that the most deprived asthma patients in Wales had different prescribing patterns, more A&E attendances, more emergency hospital admissions, and substantially higher risk of death. Interventions specifically designed to improve treatment and outcomes for these disadvantaged groups are urgently needed.
A hotspot of Toxoplasma gondii Africa 1 lineage in Benin: How new genotypes from West Africa contribute to understand the parasite genetic diversity worldwide
Authors: Hamidović Azra , Etougbétché Jonas Raoul , Tonouhewa Arétas Babatounde Nounnagnon , Galal Lokman , Dobigny Gauthier , Houémènou Gualbert , Da Zoclanclounon Honoré , Amagbégnon Richard , Laleye Anatole , Fievet Nadine , Piry Sylvain , Berthier Karine , Pena Hilda Fátima Jesus , Dardé Marie-Laure , Mercier Aurélien
Published: February 2021

Through international trades, Europe, Africa and South America share a long history of exchanges, potentially of pathogens. We used the worldwide parasiteToxoplasma gondiito test the hypothesis of a historical influence on pathogen genetic diversity in Benin, a West African country with a longstanding sea trade history. In Africa,T.gondiispatial structure is still non-uniformly studied and very few articles have reported strain genetic diversity in fauna and clinical forms of human toxoplasmosis so far, even in African diaspora. Sera from 758 domestic animals (mainly poultry) in two coastal areas (Cotonou and Ouidah) and two inland areas (Parakou and Natitingou) were tested forT.gondiiantibodies using a Modified Agglutination Test (MAT). The hearts and brains of 69 seropositive animals were collected for parasite isolation in a mouse bioassay. Forty-five strains were obtained and 39 genotypes could be described via 15-microsatellite genotyping, with a predominance of the autochthonous African lineage Africa 1 (36/39). The remaining genotypes were Africa 4 variant TUB2 (1/39) and two identical isolates (clone) of Type III (2/39). No difference in terms of genotype distribution between inland and coastal sampling sites was found. In particular, contrarily to what has been described in Senegal, no type II (mostly present in Europe) was isolated in poultry from coastal cities. This result seems to refute a possible role of European maritime trade in Benin despite it was one of the most important hubs during the slave trade period. However, the presence of the Africa 1 genotype in Brazil, predominant in Benin, and genetic analyses suggest that the triangular trade was a route for the intercontinental dissemination of genetic strains from Africa to South America. This supports the possibility of contamination in humans and animals with potentially imported virulent strains.
Fluctuations in influenza-like illness epidemics and suicide mortality: A time-series regression of 13-year mortality data in South Korea
Authors: Jung Sun Jae , Lim Sung-Shil , Yoon Jin-Ha
Published: February 2021

Aims

We explored the association between influenza epidemic and suicide mortality rates in a large population using a time-series regression of 13-year mortality data in South Korea.

Methods

Weekly suicide mortalities and influenza-like illness (ILI) were analyzed using time series regression. Regression coefficient for suicide mortality based on percentage change of ILI was calculated using a quasi-Poisson regression. Non-linear distributed lag models with quadratic function up to 24 weeks were constructed.

Results

The association between ILI and suicide mortality increased significantly up to 8 weeks post-influenza diagnosis. A significant positive association between ILI and suicide mortality was observed from 2009, when a novel influenza A(H1N1)pdm09 virus provoked a worldwide pandemic. No meaningful association between these factors was observed before 2009.

Conclusion

There was a significant positive relationship between ILI and suicide mortality after 2009, when a novel influenza A(H1N1)pdm09 virus provoked a worldwide pandemic.
Assessment of breast cancer surgical margins with multimodal optical microscopy: A feasibility clinical study
Authors: Scimone Mark T. , Krishnamurthy Savitri , Maguluri Gopi , Preda Dorin , Park Jesung , Grimble John , Song Min , Ban Kechen , Iftimia Nicusor
Published: February 2021

Providing surgical margin information during breast cancer surgery is crucial for the success of the procedure. The margin is defined as the distance from the tumor to the cut surface of the resection specimen. The consensus among surgeons and radiation oncologists is that there should be no tumor left within 1 to maximum 2 mm from the surface of the surgical specimen. If a positive margin remains, there is substantial risk for tumor recurrence, which may also result in potentially reduced cosmesis and eventual need for mastectomy. In this paper we report a novel multimodal optical imaging instrument based on combined high-resolution confocal microscopy-optical coherence tomography imaging for assessing the presence of potential positive margins on surgical specimens. Since rapid specimen analysis is critical during surgery, this instrument also includes a fluorescence imaging channel to enable rapid identification of the areas of the specimen that have potential positive margins. This is possible by specimen incubation with a cancer specific agent prior to imaging. In this study we used a quenched contrast agent, which is activated by cancer specific enzymes, such as urokinase plasminogen activators (uPA). Using this agent or a similar one, one may limit the use of high-resolution optical imaging to only fluorescence-highlighted areas for visualizing tissue morphology at the sub-cellular scale and confirming or ruling out cancer presence. Preliminary evaluation of this technology was performed on 20 surgical specimens and testing of the optical imaging findings was performed against histopathology. The combination of the three imaging modes allowed for high correlation between optical image analysis and histological ground-truth. The initial results are encouraging, showing instrument capability to assess margins on clinical specimens with a positive predictive value of 1.0 and a negative predictive value of 0.83.
Integrating stakeholders’ perspectives and spatial modelling to develop scenarios of future land use and land cover change in northern Tanzania
Authors: Kariuki Rebecca W. , Munishi Linus K. , Courtney-Mustaphi Colin J. , Capitani Claudia , Shoemaker Anna , Lane Paul J. , Marchant Rob
Published: February 2021

Rapid rates of land use and land cover change (LULCC) in eastern Africa and limited instances of genuinely equal partnerships involving scientists, communities and decision makers challenge the development of robust pathways toward future environmental and socioeconomic sustainability. We use a participatory modelling tool, Kesho, to assess the biophysical, socioeconomic, cultural and governance factors that influenced past (1959–1999) and present (2000–2018) LULCC in northern Tanzania and to simulate four scenarios of land cover change to the year 2030. Simulations of the scenarios used spatial modelling to integrate stakeholders’ perceptions of future environmental change with social and environmental data on recent trends in LULCC. From stakeholders’ perspectives, between 1959 and 2018, LULCC was influenced by climate variability, availability of natural resources, agriculture expansion, urbanization, tourism growth and legislation governing land access and natural resource management. Among other socio-environmental-political LULCC drivers, the stakeholders envisioned that from 2018 to 2030 LULCC will largely be influenced by land health, natural and economic capital, and political will in implementing land use plans and policies. The projected scenarios suggest that by 2030 agricultural land will have expanded by 8–20% under different scenarios and herbaceous vegetation and forest land cover will be reduced by 2.5–5% and 10–19% respectively. Stakeholder discussions further identified desirable futures in 2030 as those with improved infrastructure, restored degraded landscapes, effective wildlife conservation, and better farming techniques. The undesirable futures in 2030 were those characterized by land degradation, poverty, and cultural loss. Insights from our work identify the implications of future LULCC scenarios on wildlife and cultural conservation and in meeting the Sustainable Development Goals (SDGs) and targets by 2030. The Kesho approach capitalizes on knowledge exchanges among diverse stakeholders, and in the process promotes social learning, provides a sense of ownership of outputs generated, democratizes scientific understanding, and improves the quality and relevance of the outputs.