bluuebunny/crossref_metadata_2025 huggingface dataset:
How Viruses Made Us Human
Authors: Witzany Guenther
Published: April 2021

Current research on the origin of DNA and RNA, viruses, and mobile genetic elements prompts a re-evaluation of the origin and nature of genetic material as the driving force behind evolutionary novelty. While scholars used to think that novel features resulted from random genetic mutations of an individual’s specific genome, today we recognize the important role that acquired viruses and mobile genetic elements have played in introducing evolutionary novelty within the genomes of species. Viral infections and subviral RNAs can enter the host genome and persist as genetic regulatory networks. Persistent viral infections are also important to understand the split between great apes and humans. Nearly all mammals and nonhuman primates rely on olfaction, i.e., chemoreception as the basis of the sense of smell for social recognition, group membership, and the coordination of organized social life. Humans, however, evolved other means to establish social bonding, because several infection waves by endogenous retroviruses caused a loss of odor receptors in human ancestors. The human independence from olfaction for social recognition was in turn one driver of the rather abrupt human transition to dependence on visual information, gesture production, and facial recognition that are at the roots of language-based communication.
Evolution of Intentional Teaching
Authors: Gärdenfors Peter , Högberg Anders
Published: April 2021

Only among humans is teaching intentional, socially structured, and symbolically mediated. In this chapter, evidence regarding the evolution of the mindreading and communicative capacities underlying intentional teaching is reviewed. Play, rehearsal, and apprenticeship are discussed as central to the analyses of teaching. We present a series of levels of teaching. First of all, we separate non-intentional from intentional teaching. For non-intentional teaching, we discuss facilitation and approval/disapproval and analyze examples from non-human species. We then distinguish between six levels of intentional teaching: (1) intentional approval/disapproval, (2) drawing attention, (3) demonstrating, (4) communicating concepts, (5) explaining concept relations, and (6) narrating. We hypothesize that level after level has been added during the evolution of teaching. We analyze communicative requirements for the levels, concluding that displaced communication is required for level 4 and symbolic language only for levels 5 to 6. We focus on the role of demonstration and pantomime and argue that pantomime has been instrumental in the evolution of language. We present archaeological evidence for when the different levels of teaching emerge. We argue that learning Oldowan technology requires teaching by demonstration, and that learning Acheulean hand-axe technology requires communicating concepts. It follows that several levels of intentional teaching predate homo sapiens.
The Author
Authors: Steinberg Justin
Published: April 2021

This chapter will examine Dante both as an historical author as well as the ‘author figure’ he performs in his texts, with particular attention to the tension between these two forms of authorship. The chapter proceeds through three interrelated sections: 1) Dante-poet and Dante-character; 2) Authorship and authority; and 3) Dante and autobiography. In each section the focus is not just on what Dante-the-author is but also on what Dantean authorship does. The casting of himself as the character of some of his works, the establishment of the authoritative status of vernacular poets alongside the ancients, and the ‘pact’ made with his readers are all strategies in the creation of his truly original figure of the author.
Memory
Authors: Bolzoni Lina
Published: April 2021

This chapter begins from the image of the book of memory with which the Vita Nova opens in order to demonstrate both the role that it plays in the structure of the libello and its links with the tradition of the art of memory. In the Convivio, memory takes on an ethical dimension, meaning that the writer feels the need to give knowledge to humankind. In the Commedia, memory continues to be essential in the writing of the work, however, it is memory of the other world, which endows it with a new value. The ordered structure of the three realms of the other world is animated by Dante’s encounters with diverse characters, who become in their turn imagines agentes of the sin committed or of the virtue that defined them. Thus, the pilgrim’s journey imprints on his body and mind the memory of divine order and generates an internal transformation.
Travelling/Wandering/Mapping
Authors: Cachey Theodore J.
Published: April 2021

Dante deploys in the Commedia archetypal tropes of travel, including pilgrimage, biblical exodus, the journey to the underworld and to Italy, and the Bonaventuran itinerarium mentis in Deum, as an antidote to the existential experience of wandering in exile. His cosmological poem involved nothing less than a remapping of the cosmos, of the inhabited world, and of Italy. The poet re-inscribes his own place in the cosmos by alluding to his birth in Florence in three signature passages that reaffirm the Florentine citizenship denied the exiled poet and his sacred destiny within the cosmic order. The three passages are positioned strategically according to the medieval practice of numerical composition, one in each of the three canticles: Inferno XXIII, 94-6; Purgatorio XIV, 16-21; and Paradiso VI, 52-4.
Empirical Aesthetics
Authors: Leder Helmut , Pelowski Matthew
Published: April 2021

In most people’s lives, aesthetic experiences are probably frequent and occur in multiple, often very different and idiosyncratic situations. Usually, aesthetic experience involves an episode with the experiencing person in a specific situation, stretched out over time, in which certain objects, their environment, and various constituting elements are brought together. In this chapter, the authors provide a general introduction on the importance of such contextual factors in aesthetic experiences. The chapter begins with a brief overview of the nature of aesthetic experiences as a topic beyond typical aesthetic objects, with regard to how aesthetic experiences emerge as interactions between person, objects, and environment, and thus how they are embedded in informational contexts. In particular, the importance of information context is discussed: how we frame, anticipate, explain, and understand the factors of our experience as we live them. Also examined is how, in psychological studies, extra information or titles presented with pictures and artworks, or instructions regarding the context—so-called framing effects—have been shown to affect aesthetic experiences. The chapter ends with an outlook on major challenges, goals, and future directions.
New concepts and difficulties with progesterone supplementation in the luteal phase
Authors: Martínez María Cerrillo , Rodríguez-Varela Cristina , Labarta Demur Elena
Published: April 2021

Purpose of review

Management of the luteal phase (LP) in assisted reproductive cycles has aroused interest in recent years. The reason is that it seems that the individualization of LP support may be necessary, since the concept of ‘one size fits all’ does not apply to this treatment.

Recent findings

Studies carried out in hormone replacement therapy cycles (also called artificial cycles) have shown that serum levels of progesterone (P) are related to pregnancy outcomes. This represents a milestone in the management of artificial cycles (AC), because until a few years ago it was believed that serum levels did not really reflect the effectiveness of P, which is why they were neglected. However, it is not as straightforward as it seems, because the interpretation of serum progesterone values will depend on the type of progesterone used and its route of administration. Likewise, the findings observed in AC are not applicable to what occurs in a fresh transfer cycle after ovarian stimulation or an embryo transfer in the context of a natural cycle.

In this manuscript, we will summarize the current situation in LP management.
Frame to Improve the Fit of N95 Filtering Face Mask Respirators
Authors: Stemen Daniel , Ge Marshall , Hwang Darryl , Qaddoumi Burhan , Roden Mark , Nanda Neha , Ference Elisabeth
Published: April 2021

Objective:

Test a device that can improve upon the seal of filtering face mask respirators (FFRs).

Methods:

A 3-D prototype for a fit improvement frame (FIF) was created and quantitative fit testing was performed for FFRs with and without the FIF.

Results:

Thirty eight volunteers underwent fit testing. The overall fit pass rate was 100% for the 3M model 1860 masks, 50% for the 3M model 8511 masks, 13% for the BYD CARE model DE2322, and 7% for the Honeywell DC300N95. When using the FIF the overall passing rate increase to 87% for the DE2322 + FIF (P < 0.01) and for the DC300N95 + FIF the passing rate increase to 73% (P < 0.01)

Conclusion:

The FIF is effective in improving the mask fit of a common flat fold N95 masks and potentially other N95 masks.
Hybrid imaging of complicating osteomyelitis in the peripheral skeleton
Authors: Gemmel Filip , Van den Broeck Bliede , Vanelstraete Silvie , Van Innis Benoit , Huysse Wouter
Published: April 2021

Diagnosing complicating osteomyelitis (COM) is clinically challenging. Laboratory tests are of limited utility, and other than isolation of the offending organism, diagnostic imaging tests are of paramount importance. Nuclear Medicine techniques play an important role in noninvasive evaluation of osteomyelitis, using both single-photon emission tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals. It is well-known that those conventional imaging modalities are not performing well in the distinction between soft-tissue and deep bone infection due to the lack of anatomical information. These difficulties have been overcome, to a great extent, with the introduction of in-line SPECT-CT and PET-CT systems which have revolutionized the field of diagnostic medical imaging. Hybrid imaging is especially useful in sites of suspected COM with underlying structural bone alterations. The first clinical studies with these integrated hybrid machines in the field of COM, including metallic implants imaging, are highly promising. In summary, WBC/AGA SPECT-CT and FDG-PET-CT seem to be the most accurate hybrid imaging modality for COM of the peripheral bone. However, there are still false positives, especially in aseptic tibial nonunions and/or metallic implants, as well as in the immediate postoperative setting. Furthermore, there is a lack of well-designed large multicentre prospective studies. Hopefully, in the future, the complementary use of morphological and functional hybrid imaging modalities may overcome some of the challenges faced in the assessment of COM.
Improving Safety and Quality During Interhospital Transfer of Patients With Nontraumatic Intracranial Hemorrhage: A Simulation-Based Pilot Program
Authors: Ray Jessica M. , Wong Ambrose H. , Finn Emily B. , Sheth Kevin N. , Matouk Charles C. , Sudikoff Stephanie N. , Auerbach Marc A. , Sather John E. , Venkatesh Arjun K.
Published: April 2021

Background

The presentation of critically ill patients to emergency departments often necessitates interhospital transfer (IHT) to a tertiary care center for specialized neurocritical care. Patients with nontraumatic intracranial hemorrhage represent a critically ill population subject to high rates of IHT and who is thus an important target for research and quality improvement of IHT. We describe the use of an innovative simulation methodology engaging transfer staff, clinicians, and stakeholders to refine and facilitate the adoption of a standardized IHT protocol for transferring patients with neurovascular emergencies.

Methods

This was a qualitative study using a phenomenological approach. Participants consisted of IHT call center staff members, neurointensivists, neurosurgeons, and emergency physicians. We conducted a standardized telephone-based simulation case to prime participants for feedback on their experiences with IHT for intracranial hemorrhage patients. Facilitators conducted focus groups immediately after the simulation to identify process improvement opportunities. A structured thematic analysis identified overarching concepts from the data.

Results

We achieved data saturation with 7 simulations and a total of 24 participants. Thematic analysis identified 3 IHT-specific themes: (1) challenges unique to multispecialty critical illness, (2) interdisciplinary relationships and dynamics, and (3) communication and information processing for IHT. Three quality improvement initiatives emerged from the debriefings: standardized communication checklist, early acceptance protocol, and structure for telephone-based care handoffs.

Conclusions

We demonstrate the use of telephone-based simulation technology to identify potential pitfalls and accelerate the adoption of a new IHT protocol for patients with nontraumatic intracranial hemorrhage. New quality improvement strategies can organically result through interprofessional debriefings for patients with potentially complex handoffs between hospitals.
What Contributes to Diagnostic Error or Delay? A Qualitative Exploration Across Diverse Acute Care Settings in the United States
Authors: Barwise Amelia , Leppin Aaron , Dong Yue , Huang Chanyan , Pinevich Yuliya , Herasevich Svetlana , Soleimani Jalal , Gajic Ognjen , Pickering Brian , Kumbamu Ashok
Published: April 2021

Objectives

Diagnostic error and delay is a prevalent and impactful problem. This study was part of a mixed-methods approach to understand the organizational, clinician, and patient factors contributing to diagnostic error and delay among acutely ill patients within a health system, as well as recommendations for the development of tailored, targeted, feasible, and effective interventions.

Methods

We did a multisite qualitative study using focus group methodology to explore the perspectives of key clinician stakeholders. We used a conceptual framework that characterized diagnostic error and delay as occurring within 1 of 3 stages of the patient’s diagnostic journey—critical information gathering, synthesis of key information, and decision making and communication. We developed our moderator guide based on the sociotechnical frameworks previously described by Holden and Singh for understanding noncognitive factors that lead to diagnostic error and delay. Deidentified focus group transcripts were coded in triplicate and to consensus over a series of meetings. A final coded data set was then uploaded into NVivo software. The data were then analyzed to generate overarching themes and categories.

Results

We recruited a total of 64 participants across 4 sites from emergency departments, hospital floor, and intensive care unit settings into 11 focus groups. Clinicians perceive that diverse organizational, communication and coordination, individual clinician, and patient factors interact to impede the process of making timely and accurate diagnoses.

Conclusions

This study highlights the complex sociotechnical system within which individual clinicians operate and the contributions of systems, processes, and institutional factors to diagnostic error and delay.
Parallel bioreactor system for accessible and reproducible anaerobic culture
Authors: Monaghan Taylor I. , Baker Joseph A. , Robinson Gary K. , Shepherd Mark
Published: April 2021

When working with anaerobic bacteria it is important to have the capability to perform parallel bioreactor growth experiments that are both controllable and reproducible, although capital and consumables costs for commercially available systems are often prohibitively high. Hence, a three-vessel parallel bioreactor system was designed and constructed that has the capabilities for batch and fed batch processes and can also be set up for continuous culture at a fraction of the cost of commercial systems. This system carries over many of the same functionalities of those systems with a higher price point of entry, including in-line monitoring of temperature, pH, and redox poise. To validate the performance of this system

Clostridium saccharoperbutylacetonicum

was grown under conditions that promote ABE fermentation, an established industrial process used to produce the solvents acetone, butanol and ethanol. Measurements of cell density, pH, and redox poise all confirmed reproducible culture conditions for these parallel vessels, and solvent quantitation via GCMS verified consistent metabolic activities for the separate cultures. In future, this system will be of interest to researchers that require high performance parallel fermentation platforms but where commercial systems are not accessible.
Germline Mutation Analysis in Sporadic Breast Cancer Cases with Clinical Correlations
Authors: Ajaz Sadia , Zaidi Sani-e-Zehra , Ali Saleema Mehboob , Siddiqa Aisha , Memon Muhammad Ali
Published: April 2021

Demographics for breast cancers vary widely among nations. The frequency of germline mutations in breast cancers, which reflects the hereditary cases, has not been investigated adequately in Pakistani population. In the present case series, germ-line mutations in twenty-seven breast cancer candidate genes were investigated in eighty-four sporadic breast cancer patients along with the clinical correlations. The germ-line variants were also assessed in two healthy gender-matched controls. The most frequent parameters associated with hereditary cancer cases are age and ethnicity. Therefore, the clinico-pathological features were evaluated by descriptive analysis and Pearson Χ2 test (with significant p-value <0.05). The analyses were stratified on the basis of age (<40 years vs >40 years) and ethnicity. The breast cancer gene panel assay was carried out by a genomic capture, massively parallel next generation sequencing assay on Illumina Hiseq2000 assay with 100bp read lengths. Copy number variations were determined by partially-mapped read algorithm. Once the mutation was identified, it was validated by Sanger sequencing. The ethnic analysis stratified on the basis of age showed that the frequency of breast cancer at young age (<40 years) was higher in Sindhis (n=12/19; 64%) in contrast to patients in other ethnic groups. Majority of the patients had stage III (38.1%), grades II and III (46.4%), tumor size 2-5cm (54.8%), and invasive ductal carcinoma (81%). Overall, the analysis revealed germ-line mutations in 11.9% of the patients. The mutational spectrum was restricted to three genes: BRCA1, BRCA2, and TP53. The identified mutations consist of seven novel germ-line mutations, while three mutations have been reported previously. All the mutations are predicted to result in protein truncation. No mutations were identified in the remaining twenty-four candidate breast cancer genes. The present study provides the framework for the development of preventive and treatment strategies against breast cancers in Pakistani population.
GWAS and ExWAS of blood Mitochondrial DNA copy number identifies 73 loci and highlights a potential causal role in dementia
Authors: Chong Michael , Mohammadi-Shemirani Pedrum , Perrot Nicolas , Nelson Walter , Morton Robert W. , Narula Sukrit , Lali Ricky , Khan Irfan , Khan Mohammad , Judge Conor , Machipisa Tafadzwa , Cawte Nathan , O’Donnell Martin , Pigeyre Marie , Akhabir Loubna , Paré Guillaume
Published: April 2021

Mitochondrial DNA copy number (mtDNA-CN) is an accessible blood-based measurement believed to capture underlying mitochondrial function. The specific biological processes underpinning its regulation, and whether those processes are causative for disease, is an area of active investigation. We developed a novel method for array-based mtDNA-CN estimation suitable for biobank-scale studies, called “AutoMitoC”. We applied AutoMitoC to 395,781 UKBiobank study participants and performed genome and exome-wide association studies, identifying novel common and rare genetic determinants. Overall, genetic analyses identified 73 loci for mtDNA-CN, which implicated several genes involved in rare mtDNA depletion disorders, dNTP metabolism, and the mitochondrial central dogma. Rare variant analysis identified SAMHD1 mutation carriers as having higher mtDNA-CN (beta=0.23 SDs; 95% CI, 0.18-0.29; P=2.6×10−19), a potential therapeutic target for patients with mtDNA depletion disorders, but at increased risk of breast cancer (OR=1.91; 95% CI, 1.52-2.40; P=2.7×10−8). Finally, Mendelian randomization analyses suggest a causal effect of low mtDNA-CN on dementia risk (OR=1.94 per 1 SD decrease in mtDNA-CN; 95% CI, 1.55-2.32; P=7.5×10−4). Altogether, our genetic findings indicate that mtDNA-CN is a complex biomarker reflecting specific mitochondrial processes related to mtDNA regulation, and that these processes are causally related to human diseases.
Adipose tissue distribution from body MRI is associated with cross-sectional and longitudinal brain age in adults
Authors: Beck Dani , de Lange Ann-Marie G. , Alnæs Dag , Maximov Ivan I. , Pedersen Mads L. , Leinhard Olof Dahlqvist , Linge Jennifer , Simon Rozalyn , Richard Geneviève , Ulrichsen Kristine M. , Dørum Erlend S. , Kolskår Knut K. , Sanders Anne-Marthe , Winterton Adriano , Gurholt Tiril P. , Kaufmann Tobias , Steen Nils Eiel , Nordvik Jan Egil , Andreassen Ole A. , Westlye Lars T.
Published: April 2021

There is an intimate body-brain connection in ageing, and obesity is a key risk factor for poor cardiometabolic health and neurodegenerative conditions. Although research has demonstrated deleterious effects of obesity on brain structure and function, the majority of studies have used conventional measures such as waist-to-hip ratio, waist circumference, and body mass index. While sensitive to gross features of body composition, such global anthropomorphic features fail to describe regional differences in body fat distribution and composition, and to determine visceral adiposity, which is related to a range of metabolic conditions. In this mixed cross-sectional and longitudinal design (interval mean and standard deviation = 19.7 ± 0.5 months), including 790 healthy individuals (mean (range) age = 46.7 (18-94) years, 53% women), we investigated cross-sectional body magnetic resonance imaging (MRI, n = 286) measures of adipose tissue distribution in relation to longitudinal brain structure using MRI-based morphometry and diffusion tensor imaging (DTI). We estimated tissue-specific brain age at two time points and performed Bayesian multilevel modelling to investigate the associations between adipose measures at follow-up and brain age gap (BAG) at baseline and follow-up. We also tested for interactions between BAG and both time and age on each adipose measure. The results showed credible associations between T1-based BAG and liver fat, muscle fat infiltration (MFI), and weight-to-muscle ratio (WMR), indicating older-appearing brains in people with higher measures of adipose tissue. Longitudinal evidence supported interaction effects between time and MFI and WMR on T1-based BAG, indicating accelerated ageing over the course of the study period in people with higher measures of adipose tissue. The results show that specific measures of fat distribution are associated with brain ageing and that different compartments of adipose tissue may be differentially linked with increased brain ageing, with potential to identify key processes involved in age-related transdiagnostic disease processes.
Family Planning Performance in 113 Countries Using a New Composite Performance Index
Authors: Chaurasia Aalok Ranjan
Published: April 2021

In this paper we measure family planning performance in 113 countries of the world using a composite performance index that takes into account both the met demand for family planning and the composition of the met demand. The composite performance index used in the present paper is an improvement over the existing approaches of measuring family planning performance. The analysis reveals that family planning performance varies widely across countries and it remains either poor or very poor in more than 40 per cent countries. There is no country where the performance is very high. Moreover, there are many countries where the family planning performance appears to have deteriorated over time. There are only a few countries where family planning performance has improved in recent years. The analysis calls for increased investment in family planning to meet the target set under the Sustainable Development Goals.
One-Seq: A Highly Scalable Sequencing-Based Diagnostic for SARS-CoV-2 and Other Single-Stranded Viruses
Authors: Dai Mingjie , Ma Wenzhe , Kang Hong , Sonnett Matthew , Church George M. , Kirschner Marc W.
Published: April 2021

The management of pandemics such as COVID-19 requires highly scalable and sensitive viral diagnostics, together with variant identification. Next-generation sequencing (NGS) has many attractive features for highly multiplexed testing, however current sequencing-based methods are limited in throughput by early processing steps on individual samples (e.g. RNA extraction and PCR amplification). Here we report a new method, “One-Seq”, that eliminates the current bottlenecks in scalability by enabling early pooling of samples, before any extraction or amplification steps. To enable early pooling, we developed a one-pot reaction for efficient reverse transcription (RT) and upfront barcoding in extraction-free clinical samples, and a “protector” strategy in which carefully designed competing oligonucleotides prevent barcode crosstalk and preserve detection of the high dynamic range of viral load in clinical samples. This method is highly sensitive, achieving a limit of detection (LoD) down to 2.5 genome copy equivalent (gce) in contrived RT samples, 10 gce in multiplexed sequencing, and 2-5 gce with multi-primer detection, suggesting an LoD of 200-500 gce/ml for clinical testing. In clinical specimens, One-Seq showed quantitative viral detection against clinical Ct values with 6 logs of linear dynamic range and detection of SARS-CoV-2 positive samples down to ∼360 gce/ml. In addition, One-Seq reports a number of hotspot viral mutations at equal scalability at no extra cost. Scaling up One-Seq would allow a throughput of 100,000-1,000,000 tests per day per single clinical lab, at an estimated amortized reagent cost of $1.5 per test and turn-around time of 7.5-15 hr.
Community’s misconception about COVID-19 and its associated factors: Evidence from a cross-sectional study in Bangladesh
Authors: Bakebillah Md. , Billah Md. Arif , Wubishet Befikadu L. , Khan Md. Nuruzzaman
Published: April 2021

Introduction

Misconception about COVID-19 has been spread out broadly that the World Health Organization declared it as a major challenge in the fight against the disease. This study aimed to assess common misconceptions about COVID-19 among the rural people of Bangladesh and its associated socio-demographic and media related factors.

Methods

Data were collected from 210 respondents selected from three unions of Satkhira District, Bangladesh.The dependent variable was misconception about COVID-19 (Yes, No) which was generated based on the respondents’ responses to six questions on common misconceptions of COVID-19. Explanatory variables were respondents’ socio-demographic characteristics, mass media and social media use habits. Descriptive statistics were used to describe the characteristics of the respondents. Univariate and multivariate logistic regression models were used to determine the factors associated with misconception about COVID-19.

Results

Misconceptions about COVID-19 were found among more than half of the total respondents. More than 50% of the respondents reported they consider COVID-19 as a punishment from God. Besides, most of the respondents reported that they do not think COVID-19 is dangerous (59%), and COVID-19 is a disease (19%). Around 7% of the total respondents reported they consider this virus as a part of a virus war (7.2%). Bivariate analysis found that socio-demographic characteristics of the respondents and factors related to social and mass media were significantly associated with misconception. However, when all the factors included together in the multivariate model, the likelihood of misconception was lower among secondary (AOR, 0.33, 95% CI, 0.13-0.84) and tertiary (AOR, 0.29, 95% CI, 0.09-0.92) educated respondents compared to respondents with primary education.

Conclusion

This study obtained a very higher percentage of the rural people of Bangladesh having one or more misconceptions related to COVID-19. This could be a potential challenge in the fight against the pandemic. Effective use of mass and social media to communicate evidence based information on COVID-19 as well as to educate the public about COVID-19 is important.
Reliability of Spike Gene Target Failure for ascertaining SARS-CoV-2 lineage B.1.1.7 prevalence in a hospital setting
Authors: Guerra-Assunção José Afonso , Randell Paul A. , Boshier Florencia A. T. , Crone Michael A. , Pang Juanita , Mahungu Tabitha , Freemont Paul S. , Breuer Judith
Published: April 2021

The appearance of the SARS-CoV-2 lineage B.1.1.7 in the UK in late 2020, associated with faster transmission, sparked the need to find effective ways to monitor its spread. The set of mutations that characterise this lineage include a deletion in position 69 and 70 of the spike protein, which is known to be associated with Spike Gene Target Failure (SGTF) in a commonly used three gene diagnostic qPCR assay. The lower cost and faster turnaround times compared to whole genome sequencing make the use of qPCR for monitoring of the variant spread an attractive proposition. However, there are several potential issues with this approach. Here we use 826 SARS-CoV-2 samples collected in a hospital setting as part of the Hospital Onset COVID Infection (HOCI) study where qPCR was used for viral detection, followed by whole genome sequencing (WGS), to identify the factors to consider when using SGTF to infer lineage B.1.1.7 prevalence in a hospital setting, with potential implications for locations where this variant has recently been introduced.
Clinical malaria incidence following an outbreak in Ecuador was predominantly associated withPlasmodium falciparumwith recombinant variant antigen gene repertoires
Authors: Ruybal-Pesántez Shazia , Sáenz Fabian E. , Deed Samantha , Johnson Erik K. , Larremore Daniel B. , Vera-Arias Claudia A. , Tiedje Kathryn E. , Day Karen P.
Published: April 2021

To better understand the factors underlying the continued incidence of clinical episodes of falciparum malaria in E-2020 countries targeting elimination, we have characterisedPlasmodium falciparumdisease transmission dynamics after a clonal outbreak on the northwest coast of Ecuador over a period of two years. We apply a novel, high-resolution genotyping method, the “varcode” based on a single PCR to fingerprint the DBLα region of the 40-60 members of the variant surface antigen-encodingvarmultigene family.Vargenes are highly polymorphic within and between genomes, withvarrepertoires rapidly evolving by outcrossing during the obligatory sexual phase ofP. falciparumin the mosquito. The continued incidence of clinical malaria after the outbreak in Ecuador provided a unique opportunity to usevarcodes to document parasite microevolution and explore signatures of local disease transmission on the time scale of months to two years post-outbreak. We identified nine geneticvarcodes circulating locally with spatiotemporal parasite genetic relatedness networks revealing that diversification of the clonal outbreak parasites by sexual recombination was associated with increased incidence of clinical episodes of malaria. Whether this was due to chance, immune selection or sexual recombination per se is discussed. Comparative analyses to other South American parasite populations whereP. falciparumtransmission remains endemic elucidated the possible origins of Ecuadorianvarcodes. This analysis demonstrated that the majority of clinical cases were due to local transmission and not importation. Nonetheless, some of thevarcodes that were unrelated to the outbreakvarcode were found to be genetically related to other South American parasites. Our findings demonstrate the utility of thevarcode as a high-resolution surveillance tool to spatiotemporally track disease outbreaks using variant surface antigen genes and resolve signatures of recombination in an E-2020 setting nearing elimination.
Facemask usage during the COVID-19 pandemic among people with primary ciliary dyskinesia: a participatory project
Authors: Pedersen Eva SL , Collaud Eugenie NR , Mozun Rebeca , Dexter Katie , Kruljac Catherine , Silberschmidt Hansruedi ,   COVID-PCD patient advisory group, Lucas Jane S , Goutaki Myrofora , Kuehni Claudia E
Published: April 2021

Background

Facemasks help prevent transmission of SARS-CoV-2 and are particularly important for people with chronic respiratory disease such as primary ciliary dyskinesia (PCD). We studied the usage of facemasks and its consequences among people with PCD in an international context.

Methods

We used data from COVID-PCD, an international observational cohort study which collects longitudinal data from people with PCD during the COVID-19 pandemic via weekly online questionnaires. An online questionnaire investigating use of facemasks was posted in October 2020. It asked about frequency of facemask usage in different public places, problems experienced with use of facemasks, affordability of masks, and beliefs regarding their effectiveness.

Results

282 participants (50%) completed the questionnaire. Participants came from 27 different countries; median age was 32 years (interquartile range 17-48), and 63% were female. Almost all wore a facemask whenever they left their house. In addition, many avoided public places altogether. For example, 159 (57%) did not use public transport at all, 108 (39%) always wore a facemask in public transport, 4 (1%) sometimes, and 7 (3%) never. 81% agreed with the statement that facemasks protect the person who wears the mask, and 91% agreed that facemasks protect others. One third reported that it was uncomfortable to wear a mask because of their runny nose, 31% because of cough, and 22% because of difficulty breathing. Participants less often wore facemasks in public when there was no national requirement. Only two persons had a personal exemption from wearing a facemask prescribed by a physician.

Conclusions

This international study found that people with PCD carefully shield themselves, and most wear facemasks everywhere in public. People who did not wear facemasks in public came from countries without a national facemask requirement. National policies mandating facemask use in public are important for universal use to protect high-risk populations from SARS-CoV-2 infections.
Consistent Tumorigenesis with Self-Assembled Hydrogels Enables High-powered Murine Cancer Studies
Authors: Grosskopf Abigail K. , Correa Santiago , Baillet Julie , Maikawa Caitlin L. , Gale Emily C. , Brown Ryanne A. , Appel Eric A.
Published: April 2021

Preclinical cancer research is heavily dependent on allograft and xenograft models, but current approaches to tumor inoculation yield inconsistent tumor formation and growth, ultimately wasting valuable resources (e.g., animals, time, and money) and limiting experimental progress. Here we demonstrate a method for tumor inoculation using self-assembled hydrogels to reliably generate tumors with low variance in growth. The observed reduction in model variance enables smaller animal cohorts, improved effect observation and higher powered studies.
Chromosome evolution and the genetic basis of agronomically important traits in greater yam
Authors: Bredeson Jessen V. , Lyons Jessica B. , Oniyinde Ibukun O. , Okereke Nneka R. , Kolade Olufisayo , Nnabue Ikenna , Nwadili Christian O. , Hřibová Eva , Parker Matthew , Nwogha Jeremiah , Shu Shengqiang , Carlson Joseph , Kariba Robert , Muthemba Samuel , Knop Katarzyna , Barton Geoffrey J. , Sherwood Anna V. , Lopez-Montes Antonio , Asiedu Robert , Jamnadass Ramni , Muchugi Alice , Goodstein David , Egesi Chiedozie N. , Featherston Jonathan , Asfaw Asrat , Simpson Gordon G. , Doležel Jaroslav , Hendre Prasad S. , Van Deynze Allen , Kumar Pullikanti Lava , Obidiegwu Jude E. , Bhattacharjee Ranjana , Rokhsar Daniel S.
Published: April 2021

The nutrient-rich tubers of the greater yamDioscorea alataL. provide food and income security for millions of people around the world. Despite its global importance, however, greater yam remains an “orphan crop.” Here we address this resource gap by presenting a highly-contiguous chromosome-scale genome assembly of greater yam combined with a dense genetic map derived from African breeding populations. The genome sequence reveals an ancient lineage-specific genome duplication, followed by extensive genome-wide reorganization. Using our new genomic tools we find quantitative trait loci for susceptibility to anthracnose, a damaging fungal pathogen of yam, and several tuber quality traits. Genomic analysis of breeding lines reveals both extensive inbreeding as well as regions of extensive heterozygosity that may represent interspecific introgression during domestication. These tools and insights will enable yam breeders to unlock the potential of this staple crop and take full advantage of its adaptability to varied environments.
Procyanidin C1 is a natural agent with senolytic activity against aging and age-related diseases
Authors: Xu Qixia , Fu Qiang , Li Zi , Liu Hanxin , Wang Ying , Lin Xu , He Ruikun , Zhang Xuguang , Campisi Judith , Kirkland James L. , Sun Yu
Published: April 2021

Aging causes functional decline of multiple organs and increases the risk of age-related pathologies. In advanced lives, accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP), promotes chronic inflammation and causes diverse conditions. Here we report the frontline outcome of screening a natural product library with human primary stromal cells as an experimental model. Multiple candidate compounds were assayed, and grape seed extract (GSE) was selected for further investigation due to its leading capacity in targeting senescent cells. We found procyanidin C1 (PCC1), a polyphenolic component, plays a critical role in mediating the antiaging effects of GSE. PCC1 blocks the SASP expression when used at low concentrations. Importantly, it selectively kills senescent cells upon application at higher concentrations, mainly by enhancing production of reactive oxygen species (ROS) and disturbing mitochondrial membrane potential, processes accompanied by upregulation of Bcl-2 family pro-apoptotic factors Puma and Noxa in senescent cells. PCC1 depletes senescent cells in treatment-damaged tumor microenvironment (TME) and enhances therapeutic efficacy when combined with chemotherapy in preclinical assays. Intermittent administration of PCC1 to both senescent cell-implanted mice and naturally aged animals alleviated physical dysfunction and prolonged post-treatment survival, thus providing substantial benefits in late life stage. Together, our study identifies PCC1 as a distinct natural senolytic agent, which may be exploited to delay aging and control age-related pathologies in future medicine.
DEPDC1/ EEF1A1 complex promotes the progression of human osteosarcoma via downregulation of FOXO3a
Authors: Shen Lin , Li Han , Zhang Aijun , Liu Ronghan , Zhou Chendan , Zhang Ying , Zhao Kai , Bretches Morgan , Lu Laitong , Yang Shang-You , Ning Bin
Published: April 2021

There are currently lack of effective therapeutic strategies for osteosarcoma, primarily due to insufficient understanding of the underlying mechanisms of the tumor cells. This study deciphers a potentially critical interplay of DEPDC1–EEF1A1–FOXO3a axis during the osteosarcoma progression. Bioinformatics analysis of documented 25,035 genes for differentially expressed genes were accompanied by transcriptional and translational examinations of clinical osteosarcoma specimens and osteosarcoma cell lines to assess the roles and interactions of DEP domain-containing 1 (DEPDC1), Elongation Factor 1-alpha 1 (EEF1A1), and FOXO3a in the tumor cells proliferation and prognosis. Gene expression profile analysis and clinical tests revealed highly expressed DEPDC1 in human osteosarcoma cells and tumor tissues. Vector-mediated silence of DEPDC1 resulted in halted osteosarcoma cell proliferation, promoted apoptosis, and ceased tumor metastasis. Immunoprecipitation assay confirmed that EEF1A1 directly bind to DEPDC1 protein through three binding regions. Further, DEPDC1/EEF1A1 complex significantly decreased the expression of FOXO3a at transcription and translation levels, which subsequently promoted the proliferation of osteosarcoma cells and tumor metastasis. Correlation studies exhibited that overexpression of DEPDC1/EEF1A1 complex in the clinical specimens negatively correlated with the patient survival rate. In conclusion, DEPDC1-EEF1A1–FOXO3a axis plays as a critical pathway that regulates the progression and prognosis of osteosarcoma.
A Focal Adhesion Filament Cross-correlation Kit for fast, automated segmentation and correlation of focal adhesions and actin stress fibers in cells
Authors: Hauke Lara , Narasimhan Shwetha , Primeßnig Andreas , Kaverina Irina , Rehfeldt Florian
Published: April 2021

Focal adhesions (FAs) and associated actin stress fibers (SFs) form a complex mechanical system that mediates bidirectional interactions between cells and their environment. This linked network is essential for mechanosensing, force production and force transduction, thus directly governing cellular processes like polarization, migration and extracellular matrix remodeling. We introduce a tool for fast and robust coupled analysis of both FAs and SFs named the Focal Adhesion Filament Cross-correlation Kit (FAFCK). Our software can detect and record location, axes lengths, area, orientation, and aspect ratio of focal adhesion structures as well as the location, length, width and orientation of actin stress fibers. This enables users to automate analysis of the correlation of FAs and SFs and study the stress fiber system in a higher degree, pivotal to accurately evaluate transmission of mechanocellular forces between a cell and its surroundings. The FAFCK is particularly suited for unbiased and systematic quantitative analysis of FAs and SFs necessary for novel approaches of traction force microscopy that uses the additional data from the cellular side to calculate the stress distribution in the substrate. For validation and comparison with other tools, we provide datasets of cells of varying quality that are labelled by a human expert. Datasets and FAFCK are freely available as open source under the GNU General Public License.

Author summary

Our novel Focal Adhesion Filament Cross-correlation Kit (FAFCK) allows for fast, reliable, unbiased, and systematic detection of focal adhesions and actin stress fibers in cells and their mutual correlation. Detailed analysis of these structures which are both key elements in mechano-sensing and force transduction will help tremendously to improve quantitative analysis of mechanocellular experiments, key to understanding the complex interplay between cells and the extracellular matrix. In particular, sophisticated analysis methods such as model-based traction force microscopy will benefit from correlating the detailed datasets of stress fibers and focal adhesions.
Neuropilin-1 Mediates SARS-CoV-2 Infection in Bone Marrow-derived Macrophages
Authors: Gao Junjie , Mei Hong , Sun Jing , Li Hao , Huang Yuege , Tang Yanhong , Duan Linwei , Liu Delin , Wang Qiyang , Gao Youshui , Song Ke , Zhao Jincun , Zhang Changqing , Liu Jia
Published: April 2021

SARS-CoV-2 infection in human can cause medical complications across various tissues and organs. Despite of the advances to understanding the pathogenesis of SARS-CoV-2, its tissue tropism and interactions with host cells have not been fully understood. Existing clinical data have suggested possible SARS-CoV-2 infection in human skeleton system. In the present study, we found that authentic SARS-CoV-2 could efficiently infect human and mouse bone marrow-derived macrophages (BMMs) and alter the expression of macrophage chemotaxis and osteoclast-related genes. Importantly, in a mouse SARS-CoV-2 infection model that was enabled by the intranasal adenoviral (AdV) delivery of human angiotensin converting enzyme 2 (hACE2), SARS-CoV-2 was found to be present in femoral BMMs as determined byin situimmunofluorescence analysis. Using single-cell RNA sequencing (scRNA-Seq), we characterized SARS-CoV-2 infection in BMMs. Importantly, SARS-CoV-2 entry on BMMs appeared to be dependent on the expression of neuropilin-1 (NRP1) rather than the widely recognized receptor ACE2. It was also noted that unlike brain macrophages which displayed aging-dependent NRP1 expression, BMMs from neonatal and aged mice had constant NRP1 expression, making BMMs constantly vulnerable target cells for SARS-CoV-2. Furthermore, it was found that the abolished SARS-CoV-2 entry in BMM-derived osteoclasts was associated with the loss of NRP1 expression during BMM-to-osteoclast differentiation. Collectively, our study has suggested that NRP1 can mediate SARS-CoV-2 infection in BMMs, which precautions the potential impact of SARS-CoV-2 infection on human skeleton system.
Structural basis for silicon uptake by higher plants
Authors: van den Berg Bert , Pedebos Conrado , Bolla Jani R. , Robinson Carol V. , Baslé Arnaud , Khalid Syma
Published: April 2021

Metalloids are elements with physical and chemical properties that are intermediate between metals and non-metals. Silicon (Si) is the most abundant metalloid in the Earth’s crust and occurs at high levels in many plants, especially those belonging to the Poaceae (grasses). Most of the world’s staple food crops such as rice, barley and maize accumulate silicon to high levels, resulting in resistance to abiotic and biotic stresses and consequently better plant growth and crop yields. The first step in silicon accumulation is the uptake of silicic acid (Si), the bioavailable from of silicon, by the roots, a process mediated by the structurally uncharacterised NIP subfamily of aquaporins. Here we present the X-ray crystal structure of the archetypal NIP family member fromOryza sativa(OsNIP2;1). While the OsNIP2;1 channel is closed in the crystal by intracellular loop D, unbiased molecular dynamics (MD) simulations reveal a rapid channel opening on sub-microsecond time scales. MD simulations further show how Si interacts with an extracellular five-residue selectivity filter that provides the main barrier for transmembrane diffusion. Our data provide a foundation for understanding and potential manipulation of metalloid selectivity of an important and understudied aquaporin subfamily.

Significance

Many of the world’s most important food crops such as rice, barley and maize accumulate silicon to high levels, resulting in better plant growth and crop yields. The first step in silicon accumulation is the uptake of silicic acid (Si) by the roots, a process mediated by the structurally uncharacterised NIP subfamily of aquaporins. Here, we present the X-ray crystal structure and molecular dynamics simulations of the archetypal NIP family member fromOryza sativa(OsNIP2;1) to visualise Si uptake. Our data provide a platform for improved understanding of Si uptake by plants that could be utilised,e.g., in silicon biofortification of important crops and potential alleviation of arsenic accumulation in the rice grain.