bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of German Tubular Steel on Soviet Furniture at the VKhUTEMAS, 1927–1930
Authors: Tucker Bennett
Published: March 2021

This article looks at the influence of German tubular steel furniture at the State Higher Art and Technical Workshops (VKhUTEMAS) in Moscow during the late 1920s. Tubular steel furniture was first introduced in 1925 at the Bauhaus and within a few years was perceived by progressive architects across Europe as the appropriate material for the modernist interior. While the Soviet Union sought to revive its industrial economy during the New Economic Policy (1921–28), VKhUTEMAS students and professors looked to Europe for technical and artistic guidance for the design of new furniture as the country became a socialist society. German design innovations reached Moscow through the dissemination of print material, international exhibitions, and travel, including student exchanges between the Bauhaus and VKhUTEMAS. Between 1927–30 VKhUTEMAS students Boris Zemliannitsyn and Alexandr Galaktionov designed new furniture that referenced German tubular steel furniture, while professors El Lissitzky and Moisei Ginzburg replicated German tubular steel designs in their models and renditions of standard proletariat dwellings. Although the Soviet economy could not support widespread steel manufacturing, the experimentation with tubular steel furniture at VKhUTEMAS highlighted the international influence of German modernism and exposed the derivative nature of Soviet socialist material culture.
Using Multiple Natural Enemies to Manage Sweetpotato Whiteflies (Hemiptera: Aleyrodidae) in Commercial Poinsettia (Malpighiales: Euphorbiaceae) Production
Authors: Vafaie Erfan K , Pemberton H Brent , Gu Mengmeng , Kerns David , Eubanks Micky D , Heinz Kevin M
Published: March 2021

In this case study, we investigate the efficacy and economics of using two natural enemies in an integrated pest management (IPM) program to manage sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), in commercial poinsettia (Euphorbia pulcherrima Willd. ex Klotzsch) production. Two similar greenhouses at each of three different grower locations were designated as either the IPM or the conventional insecticide greenhouses in southeastern United States. In the IPM greenhouses, we released Eretmocerus eremicus (Rose & Zolnerowich) (Hymenoptera: Aphelinidae) weekly and Amblyseius swirskii (Athias-Henriot) (Acari: Phytoseiidae) every 4 wk, and selective insecticides were used to treat high whitefly densities as needed. In the conventional greenhouses, growers were autonomous in their insecticide application decisions. All whitefly stages were counted weekly on a maximum of 20 leaves per 50 randomly sampled poinsettias and 50 flagged (i.e., revisited) poinsettias in every greenhouse. Whitefly densities were consistently similar or higher in the IPM greenhouses compared to their conventionally managed counterparts for the duration of the trial. The cost of inputs and labor for whitefly management in the IPM greenhouses was between 0.57- and 3.0-fold the cost of conventional management. Our study supports that releasing E. eremicus and A. swirskii can reduce insecticide applications by 25–78% and may be considered a feasible strategy to manage B. tabaci in commercial poinsettia production in place of conventional insecticidal control in southeastern United States.
Hysteresis modeling of impact dynamics using artificial neural network
Authors: Tabaza T A , Tabaza O , Barrett J , Alsakarneh A
Published: March 2021

In this paper, the process of training an artificial neural network (ANN) on predicting the hysteresis of a viscoelastic ball and ash wood bat colliding system is discussed. To study how the material properties and the impact speed affect the hysteresis phenomenon, many experiments were conducted for colliding three types of viscoelastic balls known as sliotars at two different speeds. The aim of the study is to innovate a neural network model to predict the hysteresis phenomenon of the collision of viscoelastic materials. The model accurately captured the input data and was able to produce data sets out of the input ranges. The results show that the ANN model predicted the impact hysteresis accurately with <1% error.
Reflections on a 38-Day-Old Japanese Encephalitis Patient Born to a Pregnant Traveler in Endemic Area: Strategies for Prevention
Authors: Choi Han Som , Ahn Jong Gyun , Kang Hoon-Chul
Published: March 2021

Vaccination against Japanese encephalitis is recommended for long-term travelers to endemic areas; however, the recommendation for pregnant women is controversial. An infant was diagnosed with Japanese encephalitis whose mother moved to an endemic area while pregnant. Preventive strategies are discussed.

An infant was diagnosed with Japanese encephalitis whose mother travelled to endemic area while pregnant. As preventive strategies, we suggest vaccination of mother before or during pregnancy before the travel, or application of physical barriers before the child’s vaccination.
Analyzing the Safety and Efficacy of Flow-Diverting Stents in Pediatric Aneurysms: A Systematic Review
Authors: Scoville Jonathan , Joyce Evan , Baker Cordell , Dewey Jesse , Grandhi Ramesh , Taussky Philipp
Published: March 2021

Ruptured intracranial aneurysms cause 50% of spontaneous subarachnoid hemorrhages in children, resulting in up to 65% mortality when left untreated. Although flow-diverting stents are especially suited to treat the fusiform and giant aneurysms more commonly found in children, the US Food and Drug Administration (FDA) has only approved their use in patients ≥22 years of age. Our objective was to assess the safety of flow-diverting stents in the treatment of pediatric patients with aneurysms through a systematic literature review using the PRISMA criteria. We used PubMed, Embase, and Web of Science to identify all published cases of pediatric aneurysms treated or retreated using flow-diverting stents from 2007 through 2019. Two independent researchers developed a consensus regarding the inclusion of all articles. Patient data were extracted from the identified articles and used to calculate the incidence rate of complications. From 1396 journal articles identified, 24 articles contained data on 37 pediatric patients that met the inclusion criteria. Of these 37 patients, 8 (21.6%) had a complication by last follow-up (death: 2; residual aneurysm: 2; parent artery occlusion: 4). This resulted in an incidence rate of 0.018 complications per patient at-risk month (95% CI 0.008-0.035). These data suggest that the use of flow-diverting stents for treatment of aneurysms in children may be safe and that FDA approval for this use should be evaluated. Although this analysis is comprised of case reports and case series, it represents the best attempt thus far to quantify the risk of using flow-diverting stents in children.
Wanted, tracked down and identified: Mesozoic non-biting midges of the subfamily Chironominae (Chironomidae, Diptera)
Authors: Giłka Wojciech , Zakrzewska Marta , Lukashevich Elena D , Vorontsov Dmitry D , Soszyńska-Maj Agnieszka , Skibińska Kornelia , Cranston Peter S
Published: March 2021

Here we provide evidence for the presence of non-biting midges of the subfamily Chironominae in the Mesozoic, based on descriptions of exceptionally rare amber inclusions. The subfamily has already been reported, but based on a single and unspecified record from Late Cretaceous Taimyr amber (~84 Mya). That record is here revised and confirmed. Moreover, a new find in Burmese amber locates the temporal boundary of the subfamily back to the mid-Cretaceous (probably ~100 Mya). We describe two new genera assigned to the tribe Pseudochironomini: Mesoacentron gen. nov. with the species Mesoacentron kaluginae sp. nov. (Taimyr amber) and Palaeocentron gen. nov. with the species Palaeocentron krzeminskii sp. nov. (Burmese amber), the oldest known representative of the subfamily. The systematic position of the new taxa is discussed, and a key to the identification of adult males of extinct and extant Pseudochironomini genera is presented. Insights in the phylogeny and diversification tempo of the Chironominae and Pseudochironomini in the past are also provided.
Adapting to a New Normal After Severe Acute Brain Injury: An Observational Cohort Using a Sequential Explanatory Design
Authors: Rutz Voumard Rachel , Kiker Whitney A. , Dugger Kaley M. , Engelberg Ruth A. , Borasio Gian Domenico , Curtis J. Randall , Jox Ralf J. , Creutzfeldt Claire J
Published: March 2021

OBJECTIVES:

Treatment decisions following severe acute brain injury need to consider patients’ goals-of-care and long-term outcomes. Using family members as respondents, we aimed to assess patients’ goals-of-care in the ICU and explore the impact of adaptation on survivors who did not reach the level of recovery initially considered acceptable.

DESIGN:

Prospective, observational, mixed-methods cohort study.

SETTING:

Comprehensive stroke and level 1 trauma center in Pacific Northwest United States.

PARTICIPANTS:

Family members of patients with severe acute brain injury in an ICU for greater than 2 days and Glasgow Coma Scale score less than 12.

MEASUREMENTS AND MAIN RESULTS:

At enrollment, we asked what level of physical and cognitive recovery the patient would find acceptable. At 6 months, we assessed level of recovery through family surveys and chart review. Families of patients whose outcome was below that considered acceptable were invited for semistructured interviews, examined with content analysis.

RESULTS:

For 184 patients, most family members set patients’ minimally acceptable cognitive recovery at “able to think and communicate” or better (82%) and physical recovery at independence or better (66%). Among 170 patients with known 6-month outcome, 40% had died in hospital. Of 102 survivors, 33% were able to think and communicate, 13% were independent, and 10% died after discharge. Among survivors whose family member had set minimally acceptable cognitive function at “able to think and communicate,” 64% survived below that level; for those with minimally acceptable physical function at independence, 80% survived below that. Qualitative analysis revealed two key themes: families struggled to adapt to a new, yet uncertain, normal and asked for support and guidance with ongoing treatment decisions.

CONCLUSIONS AND RELEVANCE:

Six months after severe acute brain injury, most patients survived to a state their families initially thought would not be acceptable. Survivors and their families need more support and guidance as they adapt to a new normal and struggle with persistent uncertainty.
Active role of the central amygdala in widespread mechanical sensitization in rats with facial inflammatory pain
Authors: Sugimoto Mariko , Takahashi Yukari , Sugimura Yae K. , Tokunaga Ryota , Yajima Manami , Kato Fusao
Published: March 2021

Widespread or ectopic sensitization is a hallmark symptom of chronic pain, characterized by aberrantly enhanced pain sensitivity in multiple body regions remote from the site of original injury or inflammation. The central mechanism underlying widespread sensitization remains unidentified. The central nucleus of the amygdala (also called the central amygdala, CeA) is well situated for this role because it receives nociceptive information from diverse body sites and modulates pain sensitivity in various body regions. In this study, we examined the role of the CeA in a novel model of ectopic sensitization of rats. Injection of formalin into the left upper lip resulted in latent bilateral sensitization in the hind paw lasting >13 days in male Wistar rats. Chemogenetic inhibition of gamma–aminobutyric acid-ergic neurons or blockade of calcitonin gene-related peptide receptors in the right CeA, but not in the left, significantly attenuated this sensitization. Furthermore, chemogenetic excitation of gamma-aminobutyric acid-ergic neurons in the right CeA induced de novo bilateral hind paw sensitization in the rats without inflammation. These results indicate that the CeA neuronal activity determines hind paw tactile sensitivity in rats with remote inflammatory pain. They also suggest that the hind paw sensitization used in a large number of preclinical studies might not be simply a sign of the pain at the site of injury but rather a representation of the augmented CeA activity resulting from inflammation/pain in any part of the body or from activities of other brain regions, which has an active role of promoting defensive/protective behaviors to avoid further bodily damage.
Migraine chronification is associated with beta-band connectivity within the pain-related cortical regions: a magnetoencephalographic study
Authors: Hsiao Fu-Jung , Chen Wei-Ta , Liu Hung-Yu , Wang Yen-Feng , Chen Shih-Pin , Lai Kuan-Lin , Hope Pan Li-Ling , Coppola Gianluca , Wang Shuu-Jiun
Published: March 2021

Pain disorders are associated with aberrant oscillations in the pain-related cortical regions; however, few studies have investigated the relationship between the functional cortical network and migraine chronification through direct neural signals. Magnetoencephalography was used to record the resting-state brain activity of healthy controls as well as patients with episodic migraine (EM) and chronic migraine (CM). The source-based oscillatory dynamics of the pain-related cortical regions, which comprises 10 node regions (the bilateral primary [SI] and secondary somatosensory cortices, insula, medial frontal cortex, and anterior cingulate cortex [ACC]), were calculated to determine the intrinsic connectivity and node strength at 1 to 40 Hz. The total node strength within the pain-related cortical regions was smaller in the beta band in patients with migraine (70 EM and 80 CM) than in controls (n = 65). In the beta band, the node strength and functional connectivity values of patients with CM and patients with EM differed from those of controls in specific cortical areas, notably the left SI (EM < control) and bilateral ACC (CM < control); moreover, the node strength was lower in patients with CM than in those with EM. In all patients with migraine, negative correlations were observed between headache frequency and node strength in the bilateral ACC. In conclusion, migraine is characterized by reduced beta oscillatory connectivity within the pain-related cortical regions. Reduced beta connectivity in the ACC is linked to migraine chronification. Longitudinal studies should verify whether this oscillation change is a brain signature and a potential neuromodulation target for migraine.
An implantable restorative-neurostimulator for refractory mechanical chronic low back pain: a randomized sham-controlled clinical trial
Authors: Gilligan Christopher , Volschenk Willem , Russo Marc , Green Matthew , Gilmore Christopher , Mehta Vivek , Deckers Kristiaan , De Smedt Kris , Latif Usman , Georgius Peter , Gentile Jonathan , Mitchell Bruce , Langhorst Meredith , Huygen Frank , Baranidharan Ganesan , Patel Vikas , Mironer Eugene , Ross Edgar , Carayannopoulos Alexios , Hayek Salim , Gulve Ashish , Van Buyten Jean-Pierre , Tohmeh Antoine , Fischgrund Jeffrey , Lad Shivanand , Ahadian Farshad , Deer Timothy , Klemme William , Rauck Richard , Rathmell James , Levy Robert , Heemels Jan Pieter , Eldabe Sam ,   for the ReActiv8-B investigators
Published: March 2021

Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). Two hundred four eligible participants with refractory mechanical (musculoskeletal) chronic LBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (N = 102) or low-level sham (N = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 minutes twice daily. The primary endpoint was the comparison of responder proportions (≥30% relief on the LBP visual analogue scale without analgesics increase) at 120 days. After the primary endpoint assessment, participants in the sham-control group switched to therapeutic stimulation and the combined cohort was assessed through 1 year for long-term outcomes and adverse events. The primary endpoint was inconclusive in terms of treatment superiority (57.1% vs 46.6%; difference: 10.4%; 95% confidence interval, −3.3% to 24.1%, P = 0.138). Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain.
Assisted reproductive technology outcomes in women with a chronic viral disease
Authors: Bourdon Mathilde , Garnier Alicia , Maignien Chloé , Marcellin Louis , Dulioust Emmanuel , Sogni Philippe , Launay Odile , Cheriet Khaled Pocate , Patrat Catherine , Chapron Charles , Santulli Pietro
Published: March 2021

Objective:

The aim of this study was to evaluate the cumulative live birth rate in women undergoing in-vitro fertilization/intracytoplasmic-sperm-injection (IVF/ICSI) according to the type of chronic viral infection [HIV, hepatitis-B virus (HBV) and hepatitis-C virus (HCV)].

Design:

A cohort study.

Setting:

A tertiary-care university hospital.

Participants:

Women with a chronic viral illness HIV, HBV or HCV- were followed until four IVF/ICSI cycles had been completed, until delivery or until discontinuation of the treatment before the completion of four cycles.

Main outcome measures:

The primary outcome was the cumulative live birth rate after up to four IVF/ICSI cycles.

Results:

A total of 235 women were allocated to the HIV-infected group (n = 101), the HBV-infected group (n = 114) and the HCV-infected group (n = 20). The cumulative live birth rate after four cycles was significantly lower in the HIV-infected women than in those with HBV [39.1%, 95% confidence interval (95% CI): 17.7–60.9 versus 52.8%, 95% CI: 41.6–65.5, respectively; P = 0.004]. Regarding the obstetrical outcomes, the mean birth weight was lower in the HIV-infected women than in those with HBV or HCV. Multivariate analysis indicated that the age, the anti-Müllerian hormone and the number of cycles performed were significantly associated with the chances of a live birth.

Conclusion:

HIV-infected women had lower cumulative live birth rate than women with chronic hepatitis, and this was due to less favourable ovarian reserve parameters. These findings underscore the need to better inform practitioners and patients regarding fertility issues and the importance of early fertility assessment. However, larger studies are necessary to gain more in-depth knowledge of the direct impact of HIV on live birth rates.
Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis
Authors: Cutrell Amy G. , Schapiro Jonathan M. , Perno Carlo F. , Kuritzkes Daniel R. , Quercia Romina , Patel Parul , Polli Joseph W. , Dorey David , Wang Yongwei , Wu Sterling , Van Eygen Veerle , Crauwels Herta , Ford Susan L. , Baker Mark , Talarico Christine L. , Clair Marty St , Jeffrey Jerry , White C. Thomas , Vanveggel Simon , Vandermeulen Kati , Margolis David A. , Aboud Michael , Spreen William R. , van Lunzen Jan
Published: March 2021

Objective:

Efficacy and safety of long-acting cabotegravir (CAB) and rilpivirine (RPV) dosed intramuscularly every 4 or 8 weeks has been demonstrated in three Phase 3 trials. Here, factors associated with virologic failure at Week 48 were evaluated post hoc.

Design and methods:

Data from 1039 adults naive to long-acting CAB+RPV were pooled in a multivariable analysis to examine the influence of baseline viral and participant factors, dosing regimen and drug concentrations on confirmed virologic failure (CVF) occurrence using a logistic regression model. In a separate model, baseline factors statistically associated with CVF were further evaluated to understand CVF risk when present alone or in combination.

Results:

Overall, 1.25% (n = 13/1039) of participants experienced CVF. Proviral RPV resistance-associated mutations (RAMs), HIV-1 subtype A6/A1, higher BMI (associated with Week 8 CAB trough concentration) and lower Week 8 RPV trough concentrations were significantly associated (P < 0.05) with increased odds of CVF (all except RPV trough are knowable at baseline). Few participants (0.4%) with zero or one baseline factor had CVF. Only a combination of at least two baseline factors (observed in 3.4%; n = 35/1039) was associated with increased CVF risk (25.7%, n = 9/35).

Conclusion:

CVF is an infrequent multifactorial event, with a rate of approximately 1% in the long-acting CAB+RPV arms across Phase 3 studies (FLAIR, ATLAS and ATLAS-2M) through Week 48. Presence of at least two of proviral RPV RAMs, HIV-1 subtype A6/A1 and/or BMI at least 30 kg/m2 was associated with increased CVF risk. These findings support the use of long-acting CAB+RPV in routine clinical practice.
Reducing variance or helping the poorest? A mouse tracking approach to investigate cognitive bases of inequality aversion in resource allocation
Authors: Ueshima Atsushi , Kameda Tatsuya
Published: March 2021

Humans dislike unequal allocations. Although often conflated, such ‘inequality-averse’ preferences are separable into two elements: egalitarian concern about the variance and maximin concern about the poorest (maximizing the minimum). Recent research has shown that the maximin concern operates more robustly in allocation decisions than the egalitarian concern. However, the real-time cognitive dynamics of allocation decisions are still unknown. Here, we examined participants' choice behaviour with high temporal resolution using a mouse-tracking technique. Participants made a series of allocation choices for others between two options: a ‘non-Utilitarian option’ with both smaller variance and higher minimum pay-off (but a smaller total) compared with the other ‘Utilitarian option’. Choice data confirmed that participants had strong inequality-averse preferences, and when choosing non-utilitarian allocations, participants' mouse movements prior to choices were more strongly determined by the minimum elements of the non-Utilitarian options than the variance elements. Furthermore, a time-series analysis revealed that this dominance emerged at a very early stage of decision making (around 500 ms after the stimulus onset), suggesting that the maximin concern operated as a strong cognitive anchor almost instantaneously. Our results provide the first temporally fine-scale evidence that people weigh the maximin concern over the egalitarian concern in distributive judgements.
Gazing down increases standing and walking postural steadiness
Authors: Koren Yogev , Mairon Rotem , Sofer Ilay , Parmet Yisrael , Ben-Shahar Ohad , Bar-Haim Simona
Published: March 2021

When walking on an uneven surface or complex terrain, humans tend to gaze downward. This behaviour is usually interpreted as an attempt to acquire useful information to guide locomotion. Visual information, however, is not used exclusively for guiding locomotion; it is also useful for postural control. Both locomotive and postural control have been shown to be sensitive to the visual flow arising from the respective motion of the individual and the three-dimensional environment. This flow changes when a person gazes downward and may present information that is more appropriate for postural control. To investigate whether downward gazing can be used for postural control, rather than exclusively for guiding locomotion, we quantified the dynamics of standing and walking posture in healthy adults, under several visual conditions. Through these experiments we were able to demonstrate that gazing downward, just a few steps ahead, resulted in a steadier standing and walking posture. These experiments indicate that gazing downward may serve more than one purpose and provide sufficient evidence of the possible interplay between the visual information used for guiding locomotion and that used for postural control. These findings contribute to our understanding of the control mechanism/s underlying gait and posture and have possible clinical implications.
Warming indirectly increases invasion success in food webs
Authors: Sentis Arnaud , Montoya Jose M. , Lurgi Miguel
Published: March 2021

Climate warming and biological invasions are key drivers of biodiversity change. Their combined effects on ecological communities remain largely unexplored. We investigated the direct and indirect influences of temperature on invasion success, and their synergistic effects on community structure and dynamics. Using size-structured food web models, we found that higher temperatures increased invasion success. The direct physiological effects of temperature on invasions were minimal in comparison with indirect effects mediated by changes on food web structure and stability. Warmer communities with less connectivity, shortened food chains and reduced temporal variability were more susceptible to invasions. The directionality and magnitude of invasions effects on food webs varied across temperature regimes. When invaded, warmer communities became smaller, more connected and with more predator species than their colder counterparts. They were also less stable and their species more abundant. Considering food web structure is crucial to predict invasion success and its impacts along temperature gradients.
Genetic mechanisms and correlational selection structure trait variation in a coral snake mimic
Authors: Curlis John David , Davis Rabosky Alison R. , Holmes Iris A. , Renney Timothy J. , Cox Christian L.
Published: March 2021

Covariation among traits shapes both phenotypic evolution and ecological interactions across space and time. However, rampant geographical variation in the strength and direction of such correlations can be particularly difficult to explain through generalized mechanisms. By integrating population genomics, surveys of natural history collections and spatially explicit analyses, we tested multiple drivers of trait correlations in a coral snake mimic that exhibits remarkable polymorphism in mimetic and non-mimetic colour traits. We found that although such traits co-occur extensively across space, correlations were best explained by a mixture of genetic architecture and correlational selection, rather than by any single mechanism. Our findings suggest that spatially complex trait distributions may be driven more by the simple interaction between multiple processes than by complex variation in one mechanism alone. These interactions are particularly important in mimicry systems, which frequently generate striking geographical variation and genetic correlations among colour pattern traits.
Multi-omics Data Integration by Generative Adversarial Network
Authors: Ahmed Khandakar Tanvir , Sun Jiao , Cheng Sze , Yong Jeongsik , Zhang Wei
Published: March 2021

Accurate disease phenotype prediction plays an important role in the treatment of heterogeneous diseases like cancer in the era of precision medicine. With the advent of high throughput technologies, more comprehensive multi-omics data is now available that can effectively link the genotype to phenotype. However, the interactive relation of multi-omics datasets makes it particularly challenging to incorporate different biological layers to discover the coherent biological signatures and predict phenotypic outcomes. In this study, we introduce omicsGAN, a generative adversarial network (GAN) model to integrate two omics data and their interaction network. The model captures information from the interaction network as well as the two omics datasets and fuse them to generate synthetic data with better predictive signals. Large-scale experiments on The Cancer Genome Atlas (TCGA) breast cancer, lung cancer, and ovarian cancer datasets validate that (1) the model can effectively integrate two omics data (e.g., mRNA and microRNA expression data) and their interaction network (e.g., microRNA-mRNA interaction network). The synthetic omics data generated by the proposed model has a better performance on cancer outcome classification and patients survival prediction compared to original omics datasets. (2) The integrity of the interaction network plays a vital role in the generation of synthetic data with higher predictive quality. Using a random interaction network does not allow the framework to learn meaningful information from the omics datasets; therefore, results in synthetic data with weaker predictive signals.
Ecological correlates of gene family size in a pine-feeding sawfly genome and across Hymenoptera
Authors: Vertacnik Kim L. , Herrig Danielle K. , Godfrey R. Keating , Hill Tom , Geib Scott M. , Unckless Robert L. , Nelson David R. , Linnen Catherine R.
Published: March 2021

A central goal in evolutionary biology is to determine the predictability of adaptive genetic changes. Despite many documented cases of convergent evolution at individual loci, little is known about the repeatability of gene family expansions and contractions. To address this void, we examined gene family evolution in the redheaded pine sawflyNeodiprion lecontei, a non-eusocial hymenopteran and exemplar of a pine-specialized lineage evolved from angiosperm-feeding ancestors. After assembling and annotating a draft genome, we manually annotated multiple gene families with chemosensory, detoxification, or immunity functions and characterized their genomic distributions and evolutionary history. Our results suggest that expansions of bitter gustatory receptor (GR), clan 3 cytochrome P450 (CYP3), and antimicrobial peptide (AMP) subfamilies may have contributed to pine adaptation. By contrast, there was no evidence of recent gene family contraction via pseudogenization. Next, we compared the number of genes in these same families across insect taxa that vary in diet, dietary specialization, and social behavior. In Hymenoptera, herbivory was associated with small GR and olfactory receptor (OR) families, eusociality was associated with large OR and small AMP families, and—unlike investigations in more closely related taxa—ecological specialization was not related to gene family size. Overall, our results suggest that gene families that mediate ecological interactions may expand and contract predictably in response to particular selection pressures, however, the ecological drivers and temporal pace of gene gain and loss likely varies considerably across gene families.
Hospitalisation rates differed by city district and ethnicity during the first wave of COVID-19 in Amsterdam, the Netherlands
Authors: Coyer Liza , Wynberg Elke , Buster Marcel , Wijffels Camiel , Prins Maria , Schreijer Anja , van Duijnhoven Yvonne T.H.P , van Dam Alje , van der Lubben Mariken , Leenstra Tjalling
Published: March 2021

Background

It is important to gain insight into the burden of COVID-19 at city district level to develop targeted prevention strategies. We examined COVID-19 related hospitalisations by city district and migration background in the municipality of Amsterdam, the Netherlands.

Methods

We used surveillance data on all PCR-confirmed SARS-CoV-2 hospitalisations in Amsterdam until 31 May 2020, matched to municipal registration data on migration background. We calculated directly standardised (age, sex) rates (DSR) of hospitalisations, as a proxy of COVID-19 burden, per 100,000 population by city district and migration background. We calculated standardised rate differences (RD) and rate ratios (RR) to compare hospitalisations between city districts of varying socio-economic and health status and between migration backgrounds. We evaluated the effects of city district and migration background on hospitalisation after adjusting for age and sex using Poisson regression.

Results

Between 29 February and 31 May 2020, 2326 cases (median age 57 years [IQR=37-74]) were notified in Amsterdam, of which 596 (25.6%) hospitalisations and 287 (12.3%) deaths. 526/596 (88.2%) hospitalisations could be matched to the registration database. DSR were higher in individuals living in peripheral (South-East/New-West/North) city districts with lower economic and health status, compared to central districts (Centre/West/South/East) (RD=36.87,95%CI=25.79-47.96;RR=1.82,95%CI=1.65-1.99), and among individuals with a non-Western migration background compared to ethnic-Dutch individuals (RD=57.05,95%CI=43.34-70.75; RR=2.36,95%CI=2.17-2.54). City district and migration background were independently associated with hospitalisation.

Conclusion

City districts with lower economic and health status and those with a non-Western migration background had the highest burden of COVID-19 during the first wave of COVID-19 in Amsterdam.
A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance
Authors: Karim Mohd A , Shilts Jarrod , Schwartzentruber Jeremy , Hayhurst James , Buniello Annalisa , Mohammed Elmutaz Shaikho Elhaj , Zheng Jie , Holmes Michael V , Ochoa David , Carmona Miguel , Maranville Joseph , Gaunt Tom R. , Emilsson Valur , Gudnason Vilmundur , McDonagh Ellen M. , Wright Gavin J. , Ghoussaini Maya , Dunham Ian
Published: March 2021

The virus SARS-CoV-2 can exploit biological vulnerabilities in susceptible hosts that predispose to development of severe COVID-19. Previous reports have identified several host proteins related to the interferon response (e.g. OAS1), interleukin-6 signalling (IL-6R), and the coagulation cascade (linked via ABO) that were associated with risk of COVID-19. In the present study, we performed proteome-wide genetic colocalisation tests leveraging publicly available protein and COVID-19 datasets, to identify additional proteins that may contribute to COVID-19 risk. Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble FAS (colocalisation probability > 0.9, p = 1 × 10−4), implicating FAS-mediated apoptosis as a potential target for COVID-19 risk. We also undertook polygenic (pan) and cis-Mendelian randomisation analyses that showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal was associated with plasma concentrations of several proteins, with the strongest association observed with CD209 in several proteomic datasets. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19. Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19.
Epidemiological and clinical insights from SARS-CoV-2 RT-PCR cycle amplification values
Authors: Alizon Samuel , Selinger Christian , Sofonea Mircea T. , Haim-Boukobza Stéphanie , Giannoli Jean-Marc , Ninove Laetitia , Pillet Sylvie , Vincent Thibault , de Rougemont Alexis , Tumiotto Camille , Solis Morgane , Stephan Robin , Bressollette-Bodin Céline , Salmona Maud , L’Honneur Anne-Sophie , Behillil Sylvie , Lefeuvre Caroline , Dina Julia , Hantz Sébastien , Hartard Cédric , Veyer David , Delagrèverie Héloïse M , Fourati Slim , Visseaux Benoît , Henquell Cécile , Lina Bruno , Foulongne Vincent , Burrel Sonia ,   SFM COVID-19 study group
Published: March 2021

The SARS-CoV-2 pandemic has led to an unprecedented daily use of molecular RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of amplification cycles (Ct), is debated because of strong potential biases. We analyze a national database of tests performed on more than 2 million individuals between January and November 2020. Although we findCtvalues to vary depending on the testing laboratory or the assay used, we detect strong significant trends with patient age, number of days after symptoms onset, or the state of the epidemic (the temporal reproduction number) at the time of the test. These results suggest thatCtvalues can be used to improve short-term predictions for epidemic surveillance.
Stiffness Regulates Intestinal Stem Cell Fate
Authors: He Shijie , Lei Peng , Kang Wenying , Cheung Priscilla , Xu Tao , Mana Miyeko , Park Chan Young , Wang Hongyan , Imada Shinya , Russell Jacquelyn O. , Wang Jianxun , Wang Ruizhi , Zhou Ziheng , Chetal Kashish , Stas Eric , Mohad Vidisha , Halasi Marianna , Bruun-Rasmussen Peter , Sadreyev Ruslan I. , Adini Irit , Hodin Richard A. , Zhang Yanhang , Breault David T. , Camargo Fernando D. , Yilmaz Ömer H. , Fredberg Jeffrey J. , Saeidi Nima
Published: March 2021

Does fibrotic gut stiffening caused by inflammatory bowel diseases (IBD) direct the fate of intestinal stem cells (ISCs)? To address this question we first developed a novel long-term culture of quasi-3D gut organoids plated on hydrogel matrix of varying stiffness. Stiffening from 0.6kPa to 9.6kPa significantly reduces Lgr5highISCs and Ki67+progenitor cells while promoting their differentiation towards goblet cells. These stiffness-driven events are attributable to YAP nuclear translocation. Matrix stiffening also extends the expression of the stemness marker Olfactomedin 4 (Olfm4) into villus-like regions, mediated by cytoplasmic YAP. We next used single-cell RNA sequencing to generate for the first time the stiffness-regulated transcriptional signatures of ISCs and their differentiated counterparts. These signatures confirm the impact of stiffening on ISC fate and additionally suggest a stiffening-induced switch in metabolic phenotype, from oxidative phosphorylation to glycolysis. Finally, we used colon samples from IBD patients as well as chronic colitis murine models to confirm thein vivostiffening-induced epithelial deterioration similar to that observedin vitro. Together, these results demonstrate stiffness-dependent ISC reprograming wherein YAP nuclear translocation diminishes ISCs and Ki67+progenitors and drives their differentiation towards goblet cells, suggesting stiffening as potential target to mitigate gut epithelial deterioration during IBD.
Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines
Authors: Walls Alexandra C. , Miranda Marcos C. , Pham Minh N. , Schäfer Alexandra , Greaney Allison , Arunachalam Prabhu S. , Navarro Mary-Jane , Tortorici M. Alejandra , Rogers Kenneth , O’Connor Megan A. , Shireff Lisa , Ferrell Douglas E. , Brunette Natalie , Kepl Elizabeth , Bowen John , Zepeda Samantha K. , Starr Tyler , Hsieh Ching-Lin , Fiala Brooke , Wrenn Samuel , Pettie Deleah , Sydeman Claire , Johnson Max , Blackstone Alyssa , Ravichandran Rashmi , Ogohara Cassandra , Carter Lauren , Tilles Sasha W. , Rappuoli Rino , O’Hagan Derek T. , Van Der Most Robbert , Van Voorhis Wesley C. , McLellan Jason S. , Kleanthous Harry , Sheahan Timothy P. , Fuller Deborah H. , Villinger Francois , Bloom Jesse , Pulendran Bali , Baric Ralph , King Neil , Veesler David
Published: March 2021

Understanding the ability of SARS-CoV-2 vaccine-elicited antibodies to neutralize and protect against emerging variants of concern and other sarbecoviruses is key for guiding vaccine development decisions and public health policies. We show that a clinical stage multivalent SARS-CoV-2 receptor-binding domain nanoparticle vaccine (SARS-CoV-2 RBD-NP) protects mice from SARS-CoV-2-induced disease after a single shot, indicating that the vaccine could allow dose-sparing. SARS-CoV-2 RBD-NP elicits high antibody titers in two non-human primate (NHP) models against multiple distinct RBD antigenic sites known to be recognized by neutralizing antibodies. We benchmarked NHP serum neutralizing activity elicited by RBD-NP against a lead prefusion-stabilized SARS-CoV-2 spike immunogen using a panel of single-residue spike mutants detected in clinical isolates as well as the B.1.1.7 and B.1.351 variants of concern. Polyclonal antibodies elicited by both vaccines are resilient to most RBD mutations tested, but the E484K substitution has similar negative consequences for neutralization, and exhibit modest but comparable neutralization breadth against distantly related sarbecoviruses. We demonstrate that mosaic and cocktail sarbecovirus RBD-NPs elicit broad sarbecovirus neutralizing activity, including against the SARS-CoV-2 B.1.351 variant, and protect mice against severe SARS-CoV challenge even in the absence of the SARS-CoV RBD in the vaccine. This study provides proof of principle that sarbecovirus RBD-NPs induce heterotypic protection and enables advancement of broadly protective sarbecovirus vaccines to the clinic.
Improving localization precision via restricting biomolecule confined stochastic motion in SMLM
Authors: Ni Jielei , Cao Bo , Niu Gang , Xia Tingying , Chen Danni , Zhang Wanlong , Zhang Yilin , Yuan Xiaocong , Ni Yanxiang
Published: March 2021

Single-molecule localization microscopy (SMLM) boosts its applications when combined with the studies of cells, in which nanometer-sized biomolecules are irresolvable due to diffraction limit unless being subjected to SMLM. Although being well immobilized, given the nanometer sizes of biological molecules, they are still capable of movement stochastically around their immobilized sites. The influence of such motion on image quality and possible improvements have not yet been systematically investigated. Here, we accessed the biomolecule stochastic motion in SMLM by calculating the displacements between different localizations from the same molecule in single-molecule samples of Alexa Fluor-647-conjugated oligonucleotides. We found that, for most molecules, localization displacements at random frame intervals are remarkably larger than those between temporally neighbouring frames despite of drift correction, showing that biomolecule stochastic motion is involved in SMLM. Furthermore, the localization displacements were observed to increase with frame intervals and then saturate, suggesting biomolecule stochastic motion is confined within a finite area. Moreover, we showed that the localization precision is deteriorated by enlarging molecule sizes and improved by sample post-fixation. This study reveals confined stochastic motion of biomolecules increase localization uncertainty in SMLM, and improved localization precision can be achieved via restricting biomolecule stochastic motion.
Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants
Authors: Qu Liang , Yi Zongyi , Shen Yong , Lin Liangru , Chen Feng , Xu Yiyuan , Wu Zeguang , Tang Huixian , Zhang Xiaoxue , Tian Feng , Wang Chunhui , Xiao Xia , Dong Xiaojing , Guo Li , Lu Shuaiyao , Yang Chengyun , Tang Cong , Yang Yun , Yu Wenhai , Wang Junbin , Zhou Yanan , Huang Qing , Yisimayi Ayijiang , Cao Yunlong , Wang Youchun , Zhou Zhuo , Peng Xiaozhong , Wang Jianwei , Xie Xiaoliang Sunney , Wei Wensheng
Published: March 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its emerging variants of concern (VOC), such as Delta (B.1.617.2) and Omicron (B.1.1.529), has continued to drive the worldwide pandemic. Therefore, there is a high demand for vaccines with enhanced efficacy, high thermostability, superior design flexibility, and fast manufacturing speed. Here, we report a circular RNA (circRNA) vaccine that encodes the trimeric RBD of SARS-CoV-2 Spike protein. Without the need of nucleotide modification, 5’-capping or 3’-polyadenylation, circRNA could be rapidly produced viain vitrotranscription and is highly thermostable whether stored in naked or lipid-nanoparticle (LNP)-encapsulated format. LNP-encapsulated circRNARBDelicited potent neutralizing antibodies and T cell responses, providing robust protection against Beta (B.1.351) and native viruses in mice and rhesus macaques, respectively. Notably, circRNA vaccine enabled higher and more durable antigen production than 1mΨ-modified mRNA vaccine, eliciting a higher proportion of neutralizing antibodies and stronger Th1-biased immune responses. Importantly, we found that circRNARBD-Omicronvaccine induced effective neutralizing antibodies against only Omicron but not Delta variant. By contrast, circRNARBD-Deltacould elicit high level of neutralizing antibodies against both Delta and Omicron. Following two doses of either native- or Delta-specific vaccination, circRNARBD-Delta, but not Omicron or Beta vaccines, could effectively boost the neutralizing antibodies against both Delta and Omicron variants. These results suggest that circRNARBD-Deltais a favorable choice for vaccination to provide a broad-spectrum protection against the current variants of concern of SARS-CoV-2.
Size and shape regional differentiation during the development of the spine in the nine-banded armadillo (Dasypus novemcinctus)
Authors: Oliver Jillian D. , Jones Katrina E. , Pierce Stephanie E. , Hautier Lionel
Published: March 2021

Xenarthrans (armadillos, anteaters, sloths and their extinct relatives) are unique among mammals in displaying a distinctive specialization of the posterior trunk vertebrae - supernumerary vertebral xenarthrous articulations. This study seeks to understand how xenarthry develops through ontogeny and if it may be constrained to appear within pre-existing vertebral regions. Using 3D geometric morphometrics on the neural arches of vertebrae, we explore phenotypic, allometric, and disparity patterns of the different axial morphotypes during ontogeny of nine-banded armadillos. Shape-based regionalisation analyses showed that adult thoracolumbar column is divided into three regions according to the presence or absence of ribs and the presence or absence of xenarthrous articulations. A three-region-division was retrieved in almost all specimens through development, although younger stages (e.g. foetuses, neonates) have more region boundary variability. In size-based regionalisation analyses, thoracolumbar vertebrae are separated into two regions: a pre-diaphragmatic, pre-xenarthrous region, and a post-diaphragmatic xenarthrous region. We show that posterior thoracic vertebrae grow at a slower rate, while anterior thoracics and lumbar grow at a faster rate relatively, with rates decreasing anteroposterioly in the former and increasing anteroposterioly in the latter. We propose that different proportions between vertebrae and vertebral regions might result from differences in growth pattern and timing of ossification.