bluuebunny/crossref_metadata_2025 huggingface dataset:
Causally informed activity flow models provide mechanistic insight into network-generated cognitive activations
Authors: Sanchez-Romero Ruben , Ito Takuya , Mill Ravi D. , Hanson Stephen José , Cole Michael W.
Published: April 2021

Brain activity flow models estimate the movement of task-evoked activity over brain connections to help explain network-generated task functionality. Activity flow models have been shown to accurately generate task-evoked brain activations across a wide variety of brain regions and task conditions. However, these models have had limited explanatory power, given known issues with causal interpretations of the standard functional connectivity measures used to parameterize activity flow models. We show here that functional/effective connectivity (FC) measures grounded in causal principles facilitate mechanistic interpretation of activity flow models. We progress from simple to complex FC measures, with each adding algorithmic details reflecting causal principles. This reflects many neuroscientists’ preference for reduced FC measure complexity (to minimize assumptions, minimize compute time, and fully comprehend and easily communicate methodological details), which potentially trades off with causal validity. We start with Pearson correlation (the current field standard) to remain maximally relevant to the field, estimating causal validity across a range of FC measures using simulations and empirical fMRI data. Finally, we apply causal-FC-based activity flow modeling to a dorsolateral prefrontal cortex region (DLPFC), demonstrating distributed causal network mechanisms contributing to its strong activation during a working memory task. Notably, this fully distributed model is able to account for DLPFC working memory effects traditionally thought to rely primarily on within-region (i.e., not distributed) recurrent processes. Together, these results reveal the promise of parameterizing activity flow models using causal FC methods to identify network mechanisms underlying cognitive computations in the human brain.

Highlights

- Activity flow models provide insight into how neurocognitive effects are generated from brain network interactions.

- Functional connectivity methods grounded in statistical causal principles facilitate mechanistic interpretations of task activity flow models.

- Mechanistic activity flow models accurately predict task-evoked neural effects across a wide variety of brain regions and cognitive tasks.
Spatially non-continuous relationships between biological invasion and fragmentation of mangrove forests
Authors: Zhang Zhen , Li Jing , Li Yi , Liu Wenwen , Chen Yuxin , Zhang Yihui , Li Yangfan
Published: April 2021

Rapid and large-scale biological invasion results in widespread biodiversity loss and degradation of essential ecosystem services, especially in mangrove forests. Recent evidence suggests that the establishment and dispersal of invasive species may exacerbated in fragmented landscape, but the influence of mangrove fragmentation on coastal biological invasion at landscape scale remains largely unknown. Here, using the derived 10-m resolution coastal wetland map in southeast coast of China, we examine the relationships between fragmentation of mangrove forests and salt marsh invasion magnitude and quantify the geographical variations of the relationships across a climatic gradient. Our results show that mangrove forests with small size, large edge proportion, and regular boundary shape tend to suffer more serious salt marsh invasions, indicating a positive correlation between mangrove fragmentation and its invaded magnitude. In particular, such fragmentation-invasion relationships in subtropics are shown to be more intensive than in tropic. Our findings provide the first spatially explicit evidence of the relationships between mangrove fragmentation and biological invasion on a landscape scale, and highlight an urgent need for conservation and management actions to improve mangrove connectivity, which will increase resistance to invasions, especially for small-size subtropical mangrove forests.
Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets
Authors: Riddell Shane , Goldie Sarah , McAuley Alexander J. , Kuiper Michael J. , Durr Peter A. , Blasdell Kim , Tachedjian Mary , Druce Julian D. , Smith Trevor R.F. , Broderick Kate E. , Vasan Seshadri S.
Published: April 2021

The ongoing COVID-19 pandemic has resulted in significant global morbidity and mortality on a scale similar to the influenza pandemic of 1918. Over the course of the last few months, a number of SARS-CoV-2 variants have been identified against which vaccine-induced immune responses may be less effective. These “variants-of-concern” have garnered significant attention in the media, with discussion around their impact on the future of the pandemic and the ability of leading COVID-19 vaccines to protect against them effectively. To address concerns about emerging SARS-CoV-2 variants affecting vaccine-induced immunity, we investigated the neutralisation of representative ‘G614’, ‘501Y.V1’ and ‘501Y.V2’ virus isolates using sera from ferrets that had received prime-boost doses of the DNA vaccine, INO-4800. Neutralisation titres against G614 and 501Y.V1 were comparable, but titres against the 501Y.V2 variant were approximately 4-fold lower, similar to results reported with other nucleic acid vaccines and supported byin silicobiomolecular modelling. The results confirm that the vaccine-induced neutralising antibodies generated by INO-4800 remain effective against current variants-of-concern, albeit with lower neutralisation titres against 501Y.V2 similar to other leading nucleic acid-based vaccines.
Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
Authors: Gerdol Marco , Dishnica Klevia , Giorgetti Alejandro
Published: April 2021

Tracking the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through genomic surveillance programs is undoubtedly one of the key priorities in the current pandemic situation. Although the genome of SARS-CoV-2 acquires mutations at a slower rate compared with other RNA viruses, evolutionary pressures derived from the widespread circulation of SARS-CoV-2 in the human population have progressively favored the global emergence, though natural selection, of several variants of concern that carry multiple non-synonymous mutations in the spike glycoprotein. These are often placed in key sites within major antibody epitopes and may therefore confer resistance to neutralizing antibodies, leading to partial immune escape, or otherwise compensate infectivity deficits associated with other non-synonymous substitutions. As previously shown by other authors, several emerging variants carry recurrent deletion regions (RDRs) that display a partial overlap with antibody epitopes located in the spike N-terminal domain (NTD). Comparatively, very little attention has been directed towards spike insertion mutations prior to the emergence of the B.1.1.529 (omicron) lineage. This manuscript describes a single recurrent insertion region (RIR1) in the N-terminal domain of SARS-CoV-2 spike protein, characterized by at least 41 independent acquisitions of 1-8 additional codons between Val213 and Leu216 in different viral lineages. Even though RIR1 is unlikely to confer antibody escape, its association with two distinct formerly widespread lineages (A.2.5 and B.1.214.2), with the quickly spreading omicron and with other VOCs and VOIs warrants further investigation concerning its effects on spike structure and viral infectivity.
Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish
Authors: Noda Taichi , Blaha Andreas , Fujihara Yoshitaka , Gert Krista R. , Emori Chihiro , Deneke Victoria E. , Oura Seiya , Berent Sara , Kodani Mayo , Panser Karin , Cabrera-Quio Luis Enrique , Pauli Andrea , Ikawa Masahito
Published: April 2021

The process of sperm-egg fusion is critical for successful fertilization, yet the underlying mechanisms that regulate these steps have remained unclear in vertebrates. Here, we show that both mouse and zebrafish DCST1 and DCST2 are necessary in sperm to fertilize the egg, similar to their orthologs SPE-42 and SPE-49 inC. elegansand Sneaky inD. melanogaster. MouseDcst1andDcst2single knockout (KO) spermatozoa are able to undergo the acrosome reaction and show normal relocalization of IZUMO1, an essential factor for sperm-egg fusion, to the equatorial segment. While both single KO spermatozoa can bind to the oolemma, they rarely fuse with oocytes, resulting in male sterility. Similar to mice, zebrafishdcst1KO males are subfertile anddcst2anddcst1/2double KO males are sterile. Zebrafishdcst1/2KO spermatozoa are motile and can approach the egg, but rarely bind to the oolemma. These data demonstrate that DCST1/2 are essential for male fertility in two vertebrate species, highlighting their crucial role as conserved factors in fertilization.
Molecular relationships between SARS-CoV-2 Spike protein and LIFR, a pneumonia protective IL-6 family cytokine receptor
Authors: Ngara Mtakai , Siwo Geoffrey Henry
Published: April 2021

The fine-tuned control of immune responses is attained by pairs of activating and inhibitory signaling receptors which modulate the quality and magnitude of immune responses. Some viruses exploit these pathways to enter host cells as well as interfere with immune responses. Here, we report that the SARS-CoV-1/2 Spike proteins (S) contain a potential inhibitory tyrosine- based immunoreceptor motif (ITIM) with the D614G variant occurring within this motif. Through anin silicoscreen of ITIM-containing human proteins, we find that the S-located ITIM is closely related to a previously reported ITIM in the cytoplasmic tail of the human Leukemia Inhibitory Factor Receptor (LIFR), a pneumonia protective IL-6 family cytokine receptor. To infer potential functional interactions between SARS-CoV-2 infection and LIFR expression, we performed single-cell transcriptome analysis of public datasets of lung tissues from healthy individuals and COVID-19 patients. We show that transcripts ofLIFRand its ligandLIFare highly expressed in SARS-CoV-2 susceptible lung cells from mild and severe COVID-19 patients but not in healthy individuals. In addition, the human endogenous retroviral envelope gene (ERVW-1) encoding a fusogenic protein of the same functional class as the S protein, is induced in SARS-CoV-2 susceptible cell subpopulations in COVID-19 patients with no detectable expression in healthy individuals. We also report that pulmonary epithelial cells express transcripts of several immunoreceptors including the ITIM-containing antibody receptorFCGR2Bwhich is detectable in healthy and severe COVID-19 cases but not in mild cases. These results suggest that molecular dysregulation of ITIM-mediated inhibitory signaling by the SARS-CoV-2 S protein may play a role in COVID-19 immunopathology.
Anophelesspp. distribution and climatological niche modeling to predict malaria potential along bioclimatic envelope gradients in South Coast of West Java landscape
Authors: Wibowo Andri
Published: April 2021

Malaria remains a major public health problem mainly in particular South East Asian countries. As malaria transmission andAnophelesspp. continues to spread, control interventions should emphasize on the ability to define potential areas that can favorAnophelesspp. distribution. Then there is an urgent need to use novel approach capable to predict potential spatial patterns ofAnophelesspp. and delineate malaria potential hotspots for better environmental health planning and management. Here, this study modeledAnophelesspp. potential distribution as a function of 15 bioclimatic variables using Species Distribution Modeling (SDM) in South Coast of West Java Province spans over 20 km from West to East. Findings of this study show that bioclimatic variables and SDM can be used to predictAnophelesspp. habitat suitability, suggesting the possibility of developing models for malaria early warning based on habitat suitability model. The resulting model shows that the potential distributions ofAnophelesspp. encompassed areas from West to Central parts of the coasts, with Central parts were the most potential prevalence areas ofAnophelesspp. considering this area has higher precipitation. The less potential prevalence areas ofAnophelesspp. were observed in the East parts of the coast. The model also shows that inland areas adjacent to the settlements were more potential in comparison to the areas near coast and in the beach. Land cover conditions dominated by cropland, herbaceous wetland, and inundated land were also influencing theAnophelesspp. potential distribution.
Punctual ecological changes rather than global factors drive species diversification and the evolution of wing phenotypes inMorphobutterflies
Authors: Chazot Nicolas , Blandin Patrick , Debat Vincent , Elias Marianne , Condamine Fabien L.
Published: April 2021

Assessing the relative importance of geographical and ecological drivers of evolution is paramount to understand the diversification of species and traits at the macroevolutionary scale. Here, we use an integrative approach, combining phylogenetics, biogeography, ecology, and quantified phenotypes to investigate the drivers of both species and phenotypic diversification of the iconic Neotropical butterfly genusMorpho. We generated a time-calibrated phylogeny for all known species and inferred historical biogeography. We fitted models of time-dependent (accounting for rate heterogeneity across the phylogeny) and paleoenvironment-dependent diversification (accounting for global effect on the phylogeny). We used geometric morphometrics to assess variation of wing size and shape across the tree, and investigated their dynamics of evolution. We found that the diversification ofMorphois best explained when considering multiple independent diversification dynamics across the tree, possibly associated with lineages occupying different microhabitat conditions. First, a shift from understory to canopy was characterized by an increased speciation rate partially coupled with an increasing rate of wing shape evolution. Second, the occupation of dense bamboo thickets accompanying a major host-plant shift from dicotyledons towards monocotyledons was associated with a simultaneous diversification rate shift and an evolutionary “jump” of wing size. Our study points to a diversification pattern driven by punctual ecological changes instead of a global driver or biogeographic history.
Alpha variant versus D614G strain in the Syrian hamster model
Authors: Cochin Maxime , Luciani Léa , Touret Franck , Driouich Jean-Sélim , Petit Paul-Rémi , Moureau Grégory , Baronti Cécile , Laprie Caroline , Thirion Laurence , Maes Piet , Boudewijns Robbert , Neyts Johan , de Lamballerie Xavier , Nougairède Antoine
Published: April 2021

Late 2020, SARS-CoV-2 Alpha variant from lineage B.1.1.7 emerged in United Kingdom and gradually replaced the G614 strains initially involved in the global spread of the pandemic. In this study, we used a Syrian hamster model to compare a clinical strain of Alpha variant with an ancestral G614 strain. The Alpha variant succeeded to infect animals and to induce a pathology that mimics COVID-19. However, both strains replicated to almost the same level and induced a comparable disease and immune response. A slight fitness advantage was noted for the G614 strain during competition and transmission experiments. These data do not corroborate the epidemiological situation observed during the first half of 2021 in humans nor reports that showed a more rapid replication of Alpha variant in human reconstituted bronchial epithelium.
The Enterprise, a massive transposon carrying Spok meiotic drive genes
Authors: Vogan Aaron A. , Ament-Velásquez S. Lorena , Bastiaans Eric , Wallerman Ola , Saupe Sven J. , Suh Alexander , Johannesson Hanna
Published: April 2021

The genomes of eukaryotes are full of parasitic sequences known as transposable elements (TEs). Here, we report the discovery of a putative giant tyrosine-recombinase-mobilized DNA transposon, Enterprise, from the model fungus Podospora anserina. Previously, we described a large genomic feature called the Spok block which is notable due to the presence of meiotic drive genes of the Spok gene family. The Spok block ranges from 110 kb to 247 kb and can be present in at least four different genomic locations within P. anserina, despite what is an otherwise highly conserved genome structure. We propose that the reason for its varying positions is that the Spok block is not only capable of meiotic drive but is also capable of transposition. More precisely, the Spok block represents a unique case where the Enterprise has captured the Spoks, thereby parasitizing a resident genomic parasite to become a genomic hyperparasite. Furthermore, we demonstrate that Enterprise (without the Spoks) is found in other fungal lineages, where it can be as large as 70 kb. Lastly, we provide experimental evidence that the Spok block is deleterious, with detrimental effects on spore production in strains which carry it. This union of meiotic drivers and a transposon has created a selfish element of impressive size in Podospora, challenging our perception of how TEs influence genome evolution and broadening the horizons in terms of what the upper limit of transposition may be.
Extending synchrotron SAXS instrument ranges through addition of a portable, inexpensive USAXS module with vertical rotation axes
Authors: Pauw Brian R. , Smith Andrew J. , Snow Tim , Shebanova Olga , Sutter John P. , Ilavsky Jan , Hermida-Merino Daniel , Smales Glen J. , Terrill Nicholas J. , Thünemann Andreas F. , Bras Wim
Published: April 2021

Ultra-SAXS can enhance the capabilities of existing synchrotron SAXS/WAXS beamlines. A compact ultra-SAXS module has been developed, which extends the measurable q-range with 0.0015 ≤ q (nm−1) ≤ 0.2, allowing structural dimensions in the range 30 ≤ D (nm) ≤ 4000 to be probed in addition to the range covered by a high-end SAXS/WAXS instrument. By shifting the module components in and out on their respective motor stages, SAXS/WAXS measurements can be easily and rapidly interleaved with USAXS measurements. The use of vertical crystal rotation axes (horizontal diffraction) greatly simplifies the construction, at minimal cost to efficiency. In this paper, the design considerations, realization and synchrotron findings are presented. Measurements of silica spheres, an alumina membrane, and a porous carbon catalyst are provided as application examples.
Estimation of trapezoidal-shaped overlapping nuclear pulse parameters based on a deep learning CNN-LSTM model
Authors: Ma Xing-Ke , Huang Hong-Quan , Ji Xiao , Dai He-Ye , Wu Jun-Hong , Zhao Jing , Yang Fei , Tang Lin , Jiang Kai-Ming , Ding Wei-Cheng , Zhou Wei
Published: April 2021

The Long Short-Term Memory neural network (LSTM) has excellent learning ability for the time series of the nuclear pulse signal. It can accurately estimate the parameters (such as amplitude, time constant, etc.) of the digitally shaped nuclear pulse signal (especially the overlapping pulse signal). However, due to the large number of pulse sequences, the direct use of these sequences as samples to train the LSTM increases the complexity of the network, resulting in a lower training efficiency of the model. The convolution neural network (CNN) can effectively extract the sequence samples by using its unique convolution kernel structure, thus greatly reducing the number of sequence samples. Therefore, the CNN-LSTM deep neural network is used to estimate the parameters of overlapping pulse signals after digital trapezoidal shaping of exponential signals. Firstly, the estimation of the trapezoidal overlapping nuclear pulse is considered to be obtained after the superposition of multiple exponential nuclear pulses followed by trapezoidal shaping. Then, a data set containing multiple samples is set up; each sample is composed of the sequence of sampling values of the trapezoidal overlapping nuclear pulse and the set of shaping parameters of the exponential pulse before digital shaping. Secondly, the CNN is used to extract the abstract features of the training set in these samples, and then these abstract features are applied to the training of the LSTM model. In the training process, the pulse parameter set estimated by the present neural network is calculated by forward propagation. Thirdly, the loss function is used to calculate the loss value between the estimated pulse parameter set and the actual pulse parameter set. Finally, a gradient-based optimization algorithm is applied to update the weight by getting back the loss value together with the gradient of the loss function to the network, so as to realize the purpose of training the network. After model training was completed, the sampled values of the trapezoidal overlapping nuclear pulse were used as input to the CNN-LSTM model to obtain the required parameter set from the output of the CNN-LSTM model. The experimental results show that this method can effectively overcome the shortcomings of local convergence of traditional methods and greatly save the time of model training. At the same time, it can accurately estimate multiple trapezoidal overlapping pulses due to the wide width of the flat top, thus realizing the optimal estimation of nuclear pulse parameters in a global sense, which is a good pulse parameter estimation method.
Moving toward generalizable NZ-1 labeling for 3D structure determination with optimized epitope-tag insertion
Authors: Tamura-Sakaguchi Risako , Aruga Rie , Hirose Mika , Ekimoto Toru , Miyake Takuya , Hizukuri Yohei , Oi Rika , Kaneko Mika K. , Kato Yukinari , Akiyama Yoshinori , Ikeguchi Mitsunori , Iwasaki Kenji , Nogi Terukazu
Published: April 2021

Antibody labeling has been conducted extensively for structure determination using both X-ray crystallography and electron microscopy (EM). However, establishing target-specific antibodies is a prerequisite for applying antibody-assisted structural analysis. To expand the applicability of this strategy, an alternative method has been developed to prepare an antibody complex by inserting an exogenous epitope into the target. It has already been demonstrated that the Fab of the NZ-1 monoclonal antibody can form a stable complex with a target containing a PA12 tag as an inserted epitope. Nevertheless, it was also found that complex formation through the inserted PA12 tag inevitably caused structural changes around the insertion site on the target. Here, an attempt was made to improve the tag-insertion method, and it was consequently discovered that an alternate tag (PA14) could replace various loops on the target without inducing large structural changes. Crystallographic analysis demonstrated that the inserted PA14 tag adopts a loop-like conformation with closed ends in the antigen-binding pocket of the NZ-1 Fab. Due to proximity of the termini in the bound conformation, the more optimal PA14 tag had only a minor impact on the target structure. In fact, the PA14 tag could also be inserted into a sterically hindered loop for labeling. Molecular-dynamics simulations also showed a rigid structure for the target regardless of PA14 insertion and complex formation with the NZ-1 Fab. Using this improved labeling technique, negative-stain EM was performed on a bacterial site-2 protease, which enabled an approximation of the domain arrangement based on the docking mode of the NZ-1 Fab.
A simulation study of the age‐structured spatially explicit dynamic N‐mixture model
Authors: Zhao Qing
Published: April 2021

Knowledge of age‐specific movement and vital rates is important for understanding metapopulation dynamics yet difficult to obtain without capturing/marking individual animals. The development of dynamic N‐mixture models allows for the inference of recruitment and apparent survival while accounting for imperfect detection in count data of unmarked populations. Recent studies have further developed dynamic N‐mixture models to account for age structures or movement among local populations; however, there has yet to be a dynamic N‐mixture model that simultaneously accounts for both age structure and movement despite the fact that natural populations are composed of individuals of different ages with different movement and vital rates. In this study, I developed a dynamic N‐mixture model that allows different movement and vital rates between age classes while accounting for imperfect detection in age‐structured count data. I then conducted a simulation study to evaluate the inferential performance of the model while considering different local abundances, number of sites, and detection probabilities. The simulation study showed that the model could provide unbiased estimates of adult‐related parameters under a high detection probability, but bias was found for young‐related parameters regardless of detection probability. The bias in young‐related parameters also tended to be lower when local abundance was lower, probably due to more frequent extinction‐recolonization events in these populations. Overall, the results indicated that cautions should be taken when using dynamic N‐mixture models alone. However, these models may be useful sub‐models under integrated modeling frameworks, and thus improve our understanding of metapopulation dynamics.
Patients' experiences and perspectives of a mobile phone text messaging intervention to improve dietary behaviours in haemodialysis
Authors: Dawson Jessica , Tong Allison , Matus Gonzalez Andrea , Campbell Katrina L. , Craig Jonathan C. , Lee Vincent W.
Published: April 2021

Aim

Dietary requirements for people on haemodialysis are complex and often poorly adhered to. Mobile phone text messaging offers a simple strategy to enhance current nutritional care. KIDNEYTEXT was a 6‐month pilot randomised controlled trial that evaluated the feasibility and impact of mobile phone text messages to alter participants' dietary behaviours. The aim of this study was to elicit the perspectives of people on haemodialysis regarding acceptability of mobile phone text messages targeting dietary behaviours.

Methods

Semi‐structured interviews were conducted with participants in the intervention arm of the KIDNEYTEXT study. Participants were purposively sampled and interviews were conducted in‐person or over the phone. Transcripts were thematically analysed using principles of grounded theory.

Results

Interviews were conducted with 25 participants. Four major themes were identified: building awareness (reinforcement of information, simple and comprehensible, guiding choices, accessible information enhancing motivation, gaining skills in management), valuing care (boosting self‐esteem, in‐person care bolstered by reminders), activating change (adjusting lifestyle, gaining control of electrolytes and fluid, striving to improve overall health), waning attention and motivation (lack of personalisation limiting change, maintaining the status quo, reverting back to old habits).

Conclusions

Participants perceived that the KIDNEYTEXT intervention enabled participants to build on their knowledge through the dissemination of simple and actionable content. Participants appreciated frequent reminders of how to improve their diet and felt that this increased contact motivated them to alter some dietary behaviours. Future trials should consider strategies to enhance personalisation to further motivate dietary change.
Screening of pepino (Solanum muricatum) and wild relatives against four major tomato diseases threatening its expansion in the Mediterranean region
Authors: Pacheco Juan , Soler Salvador , Figàs Maria R. , San Bautista Alberto , Prohens Jaime , Gramazio Pietro
Published: April 2021

The pepino (Solanum muricatum) is an Andean vegetable crop closely related to tomato. In the last decades, it has been introduced in the Mediterranean region and other parts of the world as a potential new crop. However, several tomato major pathogens may threaten the expansion of pepino cultivation. We identified Fusarium oxysporum f. sp. lycopersici (FOL), Verticillium dahliae (VE), pepino mosaic virus (PepMV) and tomato mosaic virus (ToMV) as four of the most likely pathogens to cause damage to pepino crops in Mediterranean climates. In order to evaluate the response of the pepino genepool against these pathogens, as well as to identify sources of tolerance, we inoculated six accessions of cultivated pepino, nine accessions of seven pepino wild relatives, and one interspecific hybrid with FOL, VE, PepMV and ToMV and followed its symptomatology for 30 days (FOL and VE) or 60 days (PepMV and ToMV). ELISA tests were also performed for PepMV and ToMV. Susceptible tomato materials were used as controls. The pepino genepool displayed fewer symptoms than susceptible tomato controls after inoculation with FOL, with most accessions being tolerant or resistant. Regarding VE, a wide variation of values for the symptoms index (SI) was observed, with three cultivated pepino accessions displaying tolerance. For PepMV a wide variation for SI was also observed, with one accession of S. caripense being resistant, and several accessions of pepino and other wild relatives displaying different degrees of tolerance. PepMV absorbance values obtained by ELISA tests followed a pattern similar to that of SI. For ToMV no resistances were found, although two wild accessions and the interspecific hybrid displayed low values for the SI and were considered as moderately tolerant. ELISA tests against ToMV revealed that the virus replicated well in all materials. None of the accessions evaluated displayed resistance or high levels of tolerance to the four pathogens, but some of them were complementary for resistance or high levels of tolerance. Although the interspecific hybrid tested was not resistant to any of the pathogens, it was tolerant to FOL and PepMV and moderately tolerant to VE and ToMV. A multivariate hierarchical clustering revealed similar patterns among accessions in the response to the two fungal diseases (FOL and VE) on one side and to the two viral ones (PepMV and ToMV) on the other. The information generated in this study has allowed identifying materials within the pepino genepool for the development of multi‐resistant pepino cultivars to major diseases threatening its expansion in the Mediterranean region.
Social Capital and Firm Innovation: Evidence from Cooperative Banking in Korea*
Authors: Oh Frederick Dongchuhl , Yoon Heejin
Published: April 2021

This study investigates the link between social capital and firm innovation by examining the cooperative banking channel in Korea. Social capital has a positive impact on the activities of cooperative banks, thus fostering innovation in regional firms. We first confirm a positive association between social capital and firm innovation in Korea and find that firms located in provinces with higher social capital innovate more. We then show that social capital positively influences firm innovation mainly through the cooperative banking channel. Further, we demonstrate that the cooperative banking channel is more pronounced in regions where cooperative banks are riskier, human capital is less, and commercial banking is less developed.
How is surgery included in the Strategic Health Plans of the Pacific, Papua New Guinea and Timor‐Leste?
Authors: Nagra Sonal , Singh Sheetal , Kaur Balbindar , McCaig Eddie , Tangi Viliame , Guest Glenn , Watters David A.
Published: April 2021

Background

Papua New Guinea, Pacific Island nations, and Timor‐Leste represent a range of island nations with populations ranging from a few thousand to 8 million. They perform on average about 25% of the Lancet Commission of Global Surgery's target 5000 per 100 000 population and their health workforce have significant deficits of trained surgeons and anaesthetists. This study was conducted to determine how the current national health plans of these nations have included surgery and anaesthesia.

Methods

The most recent (as of December 2018) published national health plans of 10 Pacific Island nations (Cook Islands, Fiji, Nauru, Federated States of Micronesia, Kiribati, Samoa, Solomon Islands, Tonga, Tuvalu and Vanuatu), Papua New Guinea and Timor‐Leste were reviewed for content and process, searching for key words and identifying themes related to surgery and anaesthesia.

Results

There were 12 national health plans with a combined total of 478 pages. There was limited surgical and/or anaesthesia input within the planning process. Injuries, blindness, cancer and non‐communicable diseases were included themes, but the potential role of surgical care in addressing these conditions was not well documented. The need for better information and registries was noted by several nations but possible surgical care delivery or outcome metrics were not included.

Conclusion

There is limited mention of surgical and anaesthesia care planning within current health plans in the Pacific, PNG and TL. There is a need for greater surgical and anaesthesia engagement in future plans with performance measured against World Health Organization core surgical indicators.
Stratified Cox models with time‐varying effects for national kidney transplant patients: A new blockwise steepest ascent method
Authors: He Kevin , Zhu Ji , Kang Jian , Li Yi
Published: April 2021

Analyzing the national transplant database, which contains about 300,000 kidney transplant patients treated in over 290 transplant centers, may guide the disease management and inform the policy of kidney transplantation. Cox models stratified by centers provide a convenient means to account for the clustered data structure, while studying more than 160 predictors with effects that may vary over time. As fitting a time‐varying effect model with such a large sample size may defy any existing software, we propose a blockwise steepest ascent procedure by leveraging the block structure of parameters inherent from the basis expansions for each coefficient function. The algorithm iteratively updates the optimal blockwise search direction, along which the increment of the partial likelihood is maximized. The proposed method can be interpreted from the perspective of the minorization‐maximization algorithm and increases the partial likelihood until convergence. We further propose a Wald statistic to test whether the effects are indeed time varying. We evaluate the utility of the proposed method via simulations. Finally, we apply the method to analyze the national kidney transplant data and detect the time‐varying nature of the effects of various risk factors.
The T‐type calcium channel antagonist, Z944, reduces spinal excitability and pain hypersensitivity
Authors: Harding Erika K. , Dedek Annemarie , Bonin Robert P. , Salter Michael W. , Snutch Terrance P. , Hildebrand Michael E.
Published: April 2021

Background and Purpose

T‐type voltage‐gated calcium channels are an emerging therapeutic target for neurological disorders including epilepsy and pain. Inhibition of T‐type channels reduces the excitability of peripheral nociceptive sensory neurons and reverses pain hypersensitivity in male rodent pain models. However, administration of peripherally restricted T‐type antagonists failed to show efficacy in multiple clinical and preclinical pain trials, suggesting that inhibition of peripheral T‐type channels alone may be insufficient for pain relief.

Experimental Approach

We utilized the selective and CNS‐penetrant T‐type channel antagonist, Z944, in electrophysiological, calcium imaging and behavioural paradigms to determine its effect on lamina I neuron excitability and inflammatory pain behaviours.

Key Results

Voltage‐clamp recordings from lamina I spinal neurons of adult rats revealed that approximately 80% of neurons possess a low threshold T‐type current, which was blocked by Z944. Due to this highly prevalent T‐type current, Z944 potently blocked action‐potential evoked somatic and dendritic calcium transients in lamina I neurons. Moreover, application of Z944 to spinal cord slices attenuated action potential firing rates in over half of laminae I/II neurons. Finally, we found that intraperitoneal injection of Z944 (1–10 mg·kg−1) dose‐dependently reversed mechanical allodynia in the complete Freund's adjuvant model of persistent inflammatory pain, with a similar magnitude and time course of analgesic effects between male and female rats.

Conclusion and Implications

T‐type calcium channels critically shape the excitability of lamina I pain processing neurons and inhibition of these channels by the clinical stage antagonist Z944 potently reverses pain hypersensitivity across sexes.
Parent engagement with the New South Wales child health home‐based record: A cross‐sectional survey and a retrospective chart review
Authors: Chutiyami Muhammad , Wyver Shirley , Amin Janaki
Published: April 2021

Background

In 2018, World Health Organization endorsed universal use of home‐based records to improve care for mothers, pregnant women, newborns and children. New South Wales (NSW), Australia has had universal use of a child health home‐based record since 1988, with the first major update in 2013. Since the update, limitedbelief is sufficient for constituting evidence has been collected about factors influencing parent use of the record. This study aims to examine parent engagement with the record and whether it is influenced by child's first‐born status and Parent Evaluation of Development Status (PEDS) outcome.

Method

A survey of 202 parent–child pairs and a review of 20 record books were conducted in NSW, Australia. Odds ratio (OR) at 95% confidence interval (CI) and .05 level of significance, bivariate and multivariate logistic regressions were conducted to examine the influence of first‐born status, child's PEDS outcome and other parent–child characteristics on parent engagement with the record.

Results

Parents engaged with the home‐based record by taking it for routine checks (80.7%), writing (74.8%) or reading (75.8%) information. Parents of first‐born children were more than three times likely to take the record book for routine checks compared with parent of later‐born children (adjusted OR [AOR] = 3.70, 95% CI 1.12–12.20). Similarly, parents of children with low PEDS level of risk were significantly less likely to read information in the record book compared with parents of children with high risk (AOR = 0.28, 95% CI 0.08–0.98). Parent record input through direct observation significantly decreased from 85% at 1‐month to 60% at 12‐month postnatal. Data about at least one vaccination event were recorded in all the record books examined, while 85% had all recommended vaccinations recorded.

Conclusion

Parents valued/engaged regularly with a child health home‐based record, and the record may be a useful tool for early detection and monitoring of child developmental concerns. Therefore, continued promotion of the use of child health home‐based record appears to play an important role in improving child health and development.
SREC‐RT: A Structure for Ray Tracing Rounded Edges and Corners
Authors: Courtin Simon , Ribardière Mickael , Horna Sebastien , Poulin Pierre , Meneveaux Daniel
Published: April 2021

Man‐made objects commonly exhibit rounded edges and corners generated through their manufacturing processes. The variation of surface normals at these confined locations produces shading details that are visually essential to the realism of synthetic scenes. The more specular the surface, the finer and more prominent its highlights. However, most geometric modellers represent rounded edges and corners with dense polygonal meshes that are limited in terms of smoothness, while tremendously increasing scene complexity. This paper proposes a non‐invasive method (i.e. that does not modify the original geometry) for the modelling and rendering of smooth edges and corners from any input polygonal geometry defined with infinitely sharp edges. At the heart of our contribution is a geometric structure that automatically and accurately defines the geometry of edge and corner rounded areas, as well as the topological relationships at edges and vertices. This structure, called SREC‐RT, is integrated in a ray‐tracing‐based acceleration structure in order to determine the region of interest of each rounded edge and corner. It allows systematic rounding of all edges and vertices without increasing the 3D scene geometric complexity. While the underlying rounded geometry can be of any type, we propose a practical ray‐edge and ray‐corner intersection based on parametric surfaces. We analyse comparisons generated with existing methods. Our results present the advantages of our method, including extreme close‐up views of surfaces with a much higher quality for very little additional memory, and reasonable computation time overhead.
Evaluation of the effect of the lateralized inferior alveolar nerve isolation and bone grafting on the nerve function and implant stability. (Randomized Clinical Trial)
Authors: Garoushi Ibrahim H. , Elbeialy Ramy R. , Gibaly Amr , Atef Mohammed
Published: April 2021

Background

The inferior alveolar nerve lateralization (IANL), although allows for an implant full‐length mandibular height engagement, coincides with depleting the buccal bone support and sensory deficits.

Purpose

This study aims to assess whether interposing a bone graft coupled with securing a collagen membrane separation between the inferior alveolar nerve (IAN) and the underlying dental implants would preserve the nerve function, enhance the implant stability, and minimize the radiographic marginal bone loss.

Material and methods

Eighteen patients with 30 atrophic mandibular edentulous ridges were subjected to IANL after being randomly assigned to two treatment modalities which consisted of 15 patients each. The (control group) utilized conventional IANL in direct contact with 20 implants. The (test group) implemented the IAN collagen‐membrane wrapping and interposing bone graft to overlay 23 implants. The neural function, the radiographic marginal bone loss, and the implant stability quotient were assessed and compared 6 months postoperatively.

Results

All the patients regained their full neurosensory function after 6 months, with statistically nonsignificant differences between both groups throughout the follow‐up period. The mean marginal bone loss in the test group was (0.42 ± 0.09) mm versus (0.38 ± 0.14) mm for the control group, which was statistically similar (P = 0.401). The 6‐month postoperative mean implant stability quotient values of the test group recorded (74.73 ± 2.68) versus (74.73 ± 1.79) for the control group, which was statistically nonsignificant with a value of P = 0.626.

Conclusion

The interposed bone graft, coupled with the collagen membrane isolation, neither subsided the neural disturbances nor enhanced the secondary implant stability and marginal bone loss.
Combination of topical and oral glutathione as a skin‐whitening agent: a double‐blind randomized controlled clinical trial
Authors: Wahab Siswanto , Anwar Anis I. , Zainuddin Andi N. , Hutabarat Emma N. , Anwar Asvina A. , Kurniadi Ivan
Published: April 2021

Background

The antimelanogenesis effect of topical and oral glutathione has been shown in several in vitro and clinical studies. However, whether combination of topical and oral glutathione is superior to topical or oral monotherapy is unknown. This study aimed to compare the skin‐whitening effect of topical and oral glutathione combination therapy against topical and oral monotherapy.

Methods

This double‐blind randomized controlled study was done on 46 participants who were divided into two equal groups. Each group received oral placebo and oral glutathione, respectively. All participants were also instructed to apply topical placebo and glutathione to each facial side, respectively. Colorimeter examination was done biweekly using mexameter and chromameter for 8 weeks. One‐way ANOVA test was used to compare the results of all groups.

Results

The combination group showed significantly lower melanin index (MI) and L* score to placebo (P < 0.05). The mean MI and L* score of the combination group were the highest of all groups. Statistical significance of difference in L* score was reached when the combination group was compared to the oral placebo and topical glutathione group (P < 0.05).

Conclusion

This study showed that topical and oral glutathione were effective skin‐lightening agents. Furthermore, combination of topical and oral glutathione might be superior to monotherapy.
The role of digital informal learning in the relationship between students' digital competence and academic engagement during the COVID‐19 pandemic
Authors: Heidari Elham , Mehrvarz Mahboobe , Marzooghi Rahmatallah , Stoyanov Slavi
Published: April 2021

During the COVID‐19 crisis, digital informal learning is important for students' academic engagement. Although scholars have highlighted the importance of students' digital competence in improving digital informal learning (DIL), the mediating role of DIL between digital competence and academic engagement has remained ambiguous. The purpose of this study is to investigate the relationship between students' digital competence and their academic engagement with the mediating role of DIL in the higher education context. This study used a descriptive correlational design, and the data were analyzed using structural equation modelling (SEM). The study sample included 308 students from Shiraz University, Iran. The results showed that digital competence positively and significantly correlated with students' DIL and their academic engagement. Furthermore, DIL, as the mediator variable, was found to mediate the relationship between students' digital competence and their academic engagement. Since higher education institutions have a key role in improving students' academic engagement, particularly in the COVID‐19 pandemic, academic administrators should pay more attention to students' digital competencies and provide them with efficient and user‐friendly DIL platforms that can increase their academic engagement.
Trade‐offs between weapons and testes do not manifest at high social densities
Authors: Miller Christine W. , Joseph Paul N. , Emberts Zachary
Published: April 2021

Social conditions can alter the allocation of resources to reproductive traits. For example, an increase in social density during development is frequently associated with an increase in the testes mass of males. Sperm competition theory assumes that increased investment in testes should come at the expense of investing into precopulatory traits, such as sexually selected weaponry. However, much remains unknown about the role of the social context on the concurrent, relative investment in both testes and weapons. We found that the leaf‐footed cactus bug, Narnia femorata (Hemiptera: Coreidae), grew nearly 20% larger testes when raised in high social densities. In addition to manipulating social density, we used autotomy (limb loss) to limit investment in their hindlimb weapon during development. At low densities, we found that those that lost a weapon during development grew larger testes by adulthood, supporting previous work demonstrating a weapons–testes trade‐off. However, at high social densities, males that dropped a hindlimb did not grow larger testes, though testes were already large at this density. These results underscore the importance of the social context to resource allocation patterns within the individual.
Enhancing physician care of vulnerable older adults
Authors: Danto‐Nocton Ellen , Malone Michael L.
Published: April 2021

This editorial comments on the article by Robinson et al and Moreno et al. in this issue.