bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Anthropometry for Evaluating Reliability of Worm's Eye View Photographs of Unilateral Cleft Lip Nasal Deformity
Authors: Park Hojin , Cho Jeongmok , Koh Kyung S.
Published: May 2021

Background:

Worm's eye view photograph has been widely used for anthropometric analysis. However, it is difficult to secure objectivity because it cannot be captured at a constant head-up degree. This study aimed to analyze whether anthropometric nasal measurements in worm's eye view differ from the actual values.

Methods:

A total of 40 patients with unilateral cleft lip nasal deformities were included. The 30° and 60° head-tilted two-dimensional (2D) photographs were captured from the three-dimensional (3D) images. The real measurements were obtained from 3D images and 2D measurements were obtained from the captured images. The cleft/non-cleft side ratios of the nostril height, width, and alar base width were compared between 3D and 2D images.

Results:

There was a significant difference in the nostril height between the 3D and 30° values (3D = 0.82, 30° = 0.92, P < 0.001) but no meaningful difference was noted between the 3D and 60° values (3D = 0.82, 60° = 0.84, P = 0.31). There was no significant difference in the nostril width among the 30°, 60°, and 3D values. A significant difference was found in the alar base width between the 3D values and both the 30° (3D = 0.998, 30° = 1.04, P = 0.026) and 60° (3D = 0.998, 30° = 1.03, P = 0.029) values.

Conclusions:

This study demonstrates that 2D photographs do not accurately reflect actual values. The nostril height and alar width ratio can be changed depending on the head-up position. The 3D systems are more accurate and less affected by the subject's head position. Therefore, the 3D imaging system is advocated for the anthropometric analysis of unilateral cleft lip nasal deformity.
Objective and Subjective Comparisons of Split Thickness Skin Graft and Full Thickness Skin Graft for Radial Forearm Flap Donor Sites Using a New Measuring Method
Authors: Peters Florian , Smit Nadja , Möhlhenrich Stephan Christian , Bock Anna , Kniha Kristian , Raith Stefan , Hölzle Frank , Modabber Ali
Published: May 2021

A split thickness skin graft (STSG) or a full thickness skin graft (FTSG) are commonly used for donor site closure after raising a radial forearm flap. The aesthetic outcome of the donor site is frequently not satisfying for the patient. This study evaluated the aesthetic outcome of the donor site of a radial forearm flap covered with an STSG or FTSG using an objective measurement method. The forearms of 30 patients (15 FTSG, 15 STSG) were scanned with an optical three-dimensional scanner. The surface of the forearm at the skin transplant was cut out and filled by an automatic hole-filling algorithm. The mean surface deviation between the original and the filled forearm was acquired. This method was validated with a control group of 15 volunteers. A questionnaire investigating aesthetical and healing satisfaction, postoperative pain and scarring was filled in by the patients. The mean surface difference in the STSG group was 0.9907 ± 0.3120 and 0.6177 ± 0.2245 mm in the FTSG group. The difference in the surface deviation between STSG and FTSG groups was significant (P = 0.0009). Correlations between the surface deviation and the subjective aesthetical satisfaction of the patient were not significant. In the questionnaires no significant differences between STSG and FTSG group were measured. Both FTSGs and STSGs resulted in good aesthetical outcomes after closure of a radial forearm flap donor site. Scanning the radial forearm flap donor site with an optical three-dimensional scanner supplied an objective, fast, and reliable measuring method of aesthetical outcomes.
QT prolongation is over-estimated by Bazett compared to Friderica in Japanese child and adolescent inpatients
Authors: Saito Kei , Kuge Rie , Nagasawa Takashi , Ohkura Takeshi , Miura Masaru
Published: May 2021

Recent researches suggested that the risk of drug-induced QTc prolongation is low in child and adolescent psychiatry setting. However, these cohorts enrolled mainly of Caucasian background. We aimed to assess the prevalence of QTc prolongation and its association with antipsychotic use in Japanese youth. The medical records of inpatients were reviewed. Two different definitions of QT prolongation, Bazett’s corrected QT interval (QTcB) >450 msec and Fridericia’s corrected QT interval (QTcF) >450 msec, were adopted. In 220 participants [age: 13.4 ± 2.3 years, antipsychotics according to the chlorpromazine equivalence: 50 (25th–75th percentiles; 0–150) mg/day], the prevalence of QTcB and QTcF prolongation was 13.6 and 2.3%, respectively. Patients with QTcB >450 msec had a significantly higher heart rate than those with QTcB ≤450 msec (91.2 ± 20.6 bpm vs. 76.1 ± 15.2 bpm; P < 0.001). The other variables, except potassium level (4.1 ± 0.4 mEq/L vs. 4.2 ± 0.3 mEq/L; P = 0.030), showed no significant difference. Clinically meaningful QTc prolongation was rare even in this Japanese cohort. This study also suggested that if QTcB is used, clinicians should be aware of possible overdiagnosis of QTc prolongation due to accelerated heart rate.
The impact of school reopening on the spread of COVID-19 in England
Authors: Keeling Matt J. , Tildesley Michael J. , Atkins Benjamin D. , Penman Bridget , Southall Emma , Guyver-Fletcher Glen , Holmes Alex , McKimm Hector , Gorsich Erin E. , Hill Edward M. , Dyson Louise
Published: May 2021

By mid-May 2020, cases of COVID-19 in the UK had been declining for over a month; a multi-phase emergence from lockdown was planned, including a scheduled partial reopening of schools on 1 June 2020. Although evidence suggests that children generally display mild symptoms, the size of the school-age population means the total impact of reopening schools is unclear. Here, we present work from mid-May 2020 that focused on the imminent opening of schools and consider what these results imply for future policy. We compared eight strategies for reopening primary and secondary schools in England. Modifying a transmission model fitted to UK SARS-CoV-2 data, we assessed how reopening schools affects contact patterns, anticipated secondary infections and the relative change in the reproduction number,R. We determined the associated public health impact and its sensitivity to changes in social distancing within the wider community. We predicted that reopening schools with half-sized classes or focused on younger children was unlikely to pushRabove one. Older children generally have more social contacts, so reopening secondary schools results in more cases than reopening primary schools, while reopening both could have pushedRabove one in some regions. Reductions in community social distancing were found to outweigh and exacerbate any impacts of reopening. In particular, opening schools when the reproduction numberRis already above one generates the largest increase in cases. Our work indicates that while any school reopening will result in increased mixing and infection amongst children and the wider population, reopening schools alone in June 2020 was unlikely to pushRabove one. Ultimately, reopening decisions are a difficult trade-off between epidemiological consequences and the emotional, educational and developmental needs of children. Into the future, there are difficult questions about what controls can be instigated such that schools can remain open if cases increase.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
Novel coronavirus 2019-nCoV (COVID-19): early estimation of epidemiological parameters and epidemic size estimates
Authors: Read Jonathan M. , Bridgen Jessica R. E. , Cummings Derek A. T. , Ho Antonia , Jewell Chris P.
Published: May 2021

Since it was first identified, the epidemic scale of the recently emerged novel coronavirus (2019-nCoV) in Wuhan, China, has increased rapidly, with cases arising across China and other countries and regions. Using a transmission model, we estimate a basic reproductive number of 3.11 (95% CI, 2.39–4.13), indicating that 58–76% of transmissions must be prevented to stop increasing. We also estimate a case ascertainment rate in Wuhan of 5.0% (95% CI, 3.6–7.4). The true size of the epidemic may be significantly greater than the published case counts suggest, with our model estimating 21 022 (prediction interval, 11 090–33 490) total infections in Wuhan between 1 and 22 January. We discuss our findings in the light of more recent information.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
Dynamics of SARS-CoV-2 with waning immunity in the UK population
Authors: Crellen Thomas , Pi Li , Davis Emma L. , Pollington Timothy M. , Lucas Tim C. D. , Ayabina Diepreye , Borlase Anna , Toor Jaspreet , Prem Kiesha , Medley Graham F. , Klepac Petra , Déirdre Hollingsworth T.
Published: May 2021

The dynamics of immunity are crucial to understanding the long-term patterns of the SARS-CoV-2 pandemic. Several cases of reinfection with SARS-CoV-2 have been documented 48–142 days after the initial infection and immunity to seasonal circulating coronaviruses is estimated to be shorter than 1 year. Using an age-structured, deterministic model, we explore potential immunity dynamics using contact data from the UK population. In the scenario where immunity to SARS-CoV-2 lasts an average of three months for non-hospitalized individuals, a year for hospitalized individuals, and the effective reproduction number after lockdown ends is 1.2 (our worst-case scenario), we find that the secondary peak occurs in winter 2020 with a daily maximum of 387 000 infectious individuals and 125 000 daily new cases; threefold greater than in a scenario with permanent immunity. Our models suggest that longitudinal serological surveys to determine if immunity in the population is waning will be most informative when sampling takes place from the end of the lockdown in June until autumn 2020. After this period, the proportion of the population with antibodies to SARS-CoV-2 is expected to increase due to the secondary wave. Overall, our analysis presents considerations for policy makers on the longer-term dynamics of SARS-CoV-2 in the UK and suggests that strategies designed to achieve herd immunity may lead to repeated waves of infection as immunity to reinfection is not permanent.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
Shut and re-open: the role of schools in the spread of COVID-19 in Europe
Authors: Stage Helena B. , Shingleton Joseph , Ghosh Sanmitra , Scarabel Francesca , Pellis Lorenzo , Finnie Thomas
Published: May 2021

We investigate the effect of school closure and subsequent reopening on the transmission of COVID-19, by considering Denmark, Norway, Sweden and German states as case studies. By comparing the growth rates in daily hospitalizations or confirmed cases under different interventions, we provide evidence that school closures contribute to a reduction in the growth rate approximately 7 days after implementation. Limited school attendance, such as older students sitting exams or the partial return of younger year groups, does not appear to significantly affect community transmission. In countries where community transmission is generally low, such as Denmark or Norway, a large-scale reopening of schools while controlling or suppressing the epidemic appears feasible. However, school reopening can contribute to statistically significant increases in the growth rate in countries like Germany, where community transmission is relatively high. In all regions, a combination of low classroom occupancy and robust test-and-trace measures were in place. Our findings underscore the need for a cautious evaluation of reopening strategies.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
Household bubbles and COVID-19 transmission: insights from percolation theory
Authors: Danon Leon , Lacasa Lucas , Brooks-Pollock Ellen
Published: May 2021

In the era of social distancing to curb the spread of COVID-19, bubbling is the combining of two or more households to create an exclusive larger group. The impact of bubbling on COVID-19 transmission is challenging to quantify because of the complex social structures involved. We developed a network description of households in the UK, using the configuration model to link households. We explored the impact of bubbling scenarios by joining together households of various sizes. For each bubbling scenario, we calculated the percolation threshold, that is, the number of connections per individual required for a giant component to form, numerically and theoretically. We related the percolation threshold to the household reproduction number. We find that bubbling scenarios in which single-person households join with another household have a minimal impact on network connectivity and transmission potential. Ubiquitous scenarios where all households form a bubble are likely to lead to an extensive transmission that is hard to control. The impact of plausible scenarios, with variable uptake and heterogeneous bubble sizes, can be mitigated with reduced numbers of contacts outside the household. Bubbling of households comes at an increased risk of transmission; however, under certain circumstances risks can be modest and could be balanced by other changes in behaviours.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK'.
Modelling that shaped the early COVID-19 pandemic response in the UK
Authors: Brooks-Pollock Ellen , Danon Leon , Jombart Thibaut , Pellis Lorenzo
Published: May 2021

Infectious disease modelling has played an integral part of the scientific evidence used to guide the response to the COVID-19 pandemic. In the UK, modelling evidence used for policy is reported to the Scientific Advisory Group for Emergencies (SAGE) modelling subgroup, SPI-M-O (Scientific Pandemic Influenza Group on Modelling-Operational). This Special Issue contains 20 articles detailing evidence that underpinned advice to the UK government during the SARS-CoV-2 pandemic in the UK between January 2020 and July 2020. Here, we introduce the UK scientific advisory system and how it operates in practice, and discuss how infectious disease modelling can be useful in policy making. We examine the drawbacks of current publishing practices and academic credit and highlight the importance of transparency and reproducibility during an epidemic emergency.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
Corowa-kun: Impact of a COVID-19 vaccine information chatbot on vaccine hesitancy, Japan 2021
Authors: Kobayashi Takaaki , Nishina Yuka , Tomoi Hana , Harada Ko , Tanaka Kyuto , Matsumoto Eiyu , Horimukai Kenta , Ishihara Jun , Sasaki Shugo , Inaba Kanako , Seguchi Kyosuke , Takahashi Hiromizu , Salinas Jorge L. , Yamada Yuji
Published: May 2021

Background

Few studies have assessed how mobile messenger apps affect COVID-19 vaccine hesitancy. We created a COVID-19 vaccine information chatbot in a popular messenger app in Japan to answer commonly asked questions.

Methods

LINE is the most popular messenger app in Japan. Corowa-kun, a free chatbot, was created in LINE on February 6, 2021. Corowa-kun provides instant, automated answers to frequently asked COVID-19 vaccine questions. In addition, a cross-sectional survey assessing COVID-19 vaccine hesitancy was conducted via Corowa-kun during April 5–12, 2021.

Results

A total of 59,676 persons used Corowa-kun during February–April 2021. Of them, 10,192 users (17%) participated in the survey. Median age was 55 years (range 16–97), and most were female (74%). Intention to receive a COVID-19 vaccine increased from 59% to 80% after using Corowa-kun (p < 0.01). Overall, 20% remained hesitant: 16% (1,675) were unsure, and 4% (364) did not intend to be vaccinated. Factors associated with vaccine hesitancy were: age 16 to 34 (odds ratio [OR] = 3.7, 95% confidential interval [CI]: 3.0–4.6, compared to age ≥65), female sex (OR = 2.4, Cl: 2.1–2.8), and history of a previous vaccine side-effect (OR = 2.5, Cl: 2.2–2.9). Being a physician (OR = 0.2, Cl: 0.1–0.4) and having received a flu vaccine the prior season (OR = 0.4, Cl: 0.3–0.4) were protective.

Conclusions

Corowa-kun reduced vaccine hesitancy by providing COVID-19 vaccine information in a messenger app. Mobile messenger apps could be leveraged to increase COVID-19 vaccine acceptance.
Visual motion and decision-making in dyslexia: Evidence of reduced accumulation of sensory evidence and related neural dynamics
Authors: Manning Catherine , Hassall Cameron D. , Laurence T. Hunt , Norcia Anthony M. , Wagenmakers Eric-Jan , Snowling Margaret J. , Scerif Gaia , Evans Nathan J.
Published: May 2021

Children with and without dyslexia differ in their behavioural responses to visual information, particularly when required to pool dynamic signals over space and time. Importantly, multiple processes contribute to behavioural responses. Here we investigated which processing stages are affected in children with dyslexia when performing visual motion processing tasks, by combining two methods that are sensitive to the dynamic processes leading to responses. We used a diffusion model which decomposes response time and accuracy into distinct cognitive constructs, and high-density EEG. 50 children with dyslexia and 50 typically developing children aged 6 to 14 years judged the direction of motion as quickly and accurately as possible in two global motion tasks, which varied in their requirements for segregating signal-from-noise. Following our pre-registered analyses, we fitted hierarchical Bayesian diffusion models to the data, blinded to group membership. Unblinding revealed reduced evidence accumulation in children with dyslexia compared to typical children for both tasks. We also identified a response-locked EEG component which was maximal over centro-parietal electrodes which indicated a neural correlate of reduced drift-rate in dyslexia, thereby linking brain and behaviour. We suggest that children with dyslexia are slower to extract sensory evidence from global motion displays, regardless of whether they are required to segregate signal-from-noise, thus furthering our understanding of atypical perceptual decision-making processes in dyslexia.
Functional and quantitative evaluation of BNT162b2 SARS-CoV-2 vaccine-induced immunity
Authors: Kawasuji Hitoshi , Morinaga Yoshitomo , Tani Hideki , Saga Yumiko , Kaneda Makito , Murai Yushi , Ueno Akitoshi , Miyajima Yuki , Fukui Yasutaka , Nagaoka Kentaro , Ono Chikako , Matsuura Yoshiharu , Niimi Hideki , Yamamoto Yoshihiro
Published: May 2021

Objectives

Vaccines against severe acute respiratory syndrome coronavirus-2 have been introduced. To investigate whether the vaccine provides protective immunity effectively, the amount and function of vaccine-induced antibodies were evaluated.

Methods

Sera from 13-17 days after the second dose of the Pfizer BNT162b2 vaccine were collected from healthcare workers at the University of Toyama (n=740). Antibody levels were quantitatively measured by the anti-receptor binding domain antibody test (anti-RBD test), and neutralising activity against pseudotyped viruses displaying wild-type (WT) and mutant spike proteins (B.1.1.7- and B.1.351-derived variants) were assayed using a high-throughput chemiluminescent reduction neutralising test (htCRNT). Basic clinical characteristics were obtained from questionnaires.

Results

Antibodies were confirmed in all participants in both the anti-RBD test (median 2112 U/mL, interquartile range [IQR] 1275–3390 U/mL) and the htCRNT against WT (median % inhibition >99.9, IQR >99.9 to >99.9). For randomly selected sera (n=61), 100.0% were positive for htCRNT against the B.1.1.7- and B.1.351-derived variants. Among those who answered the questionnaire (n=237), the values of the anti-RBD test were negatively correlated with age for females (p<0.01; r = -0.31, 95% confidence interval -0.45 to -0.16). Systemic symptoms after vaccination were related to higher values of the anti-RBD test (median 2425, IQR 1450 – 3933 vs. median 1347, IQR 818 – 2125 for no symptoms; p<0.01).

Conclusions

The BNT162b2 vaccine produced sufficient antibodies in terms of quality and quantity which could neutralise emerging variants. Antibody induction can be affected by age and sex but will still be at a sufficient level.
How immunity from and interaction with seasonal coronaviruses can shape SARS-CoV-2 epidemiology
Authors: Waterlow Naomi R , van Leeuwen Edwin , Davies Nicholas G. ,   CMMID COVID-19 working group, Flasche Stefan , Eggo Rosalind M
Published: May 2021

We hypothesised that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected SARS-CoV-2 transmission, including generating reduced susceptibility in children. To determine what the pre-pandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 years of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.3 years (95%CI 6.8 - 7.9) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission.

Significance statement:

Cross-protection from seasonal epidemics of human coronaviruses (HCoVs) has been hypothesised to contribute to the relative sparing of children during the early phase of the pandemic. Testing this relies on understanding the pre-pandemic age-distribution of recent HCoV infections, but little is known about their dynamics. Using England and Wales as a case study, we use a transmission model to estimate the duration of immunity to seasonal coronaviruses, and show how cross-protection could have affected the age distribution of susceptibility during the first wave, and alter SARS-CoV-2 transmission patterns over the coming decade.
Temporal stability and detection sensitivity of the dry swab-based diagnosis of SARS-CoV-2
Authors: Gokulan CG , Kiran Uday , Kuncha Santosh Kumar , Mishra Rakesh K
Published: May 2021

The rapid spread and evolution of various strains of SARS-CoV-2, the virus responsible for COVID-19, continues to challenge the disease controlling measures globally. Alarming concern is, the number of second wave infections surpassed the first wave and the onset of severe symptoms manifesting rapidly. In this scenario, testing of maximum population in less time and minimum cost with existing diagnostic amenities is the only possible way to control the spread of the virus. The previously described RNA extraction-free methods using dry swab have been shown to be advantageous in these critical times by different studies. In this work, we show the temporal stability and performance of the dry swab viral detection method at two different temperatures. Contrived dry swabs holding serially diluted SARS-CoV-2 strains A2a and A3i at 25°C (room temperature; RT) and 4°C were subjected to direct RT-PCR and compared with standard VTM-RNA based method. The results clearly indicate that dry swab method of RNA detection is as efficient as VTM-RNA-based method in both strains, when checked for up to 72 hours. The lesser CT values of dry swab samples in comparison to that of the VTM-RNA samples suggest better sensitivity of the method within 48 hours of time. The results collectively suggest that dry swab samples are stable at RT for 24 hours and the detection of SARS-CoV-2 RNA by RT-PCR do not show variance from VTM-RNA. This extraction free, direct RT-PCR method holds phenomenal standing in the present life-threatening circumstances due to SARS-CoV-2.
Dissecting the loci underlying maturation timing in Atlantic salmon using haplotype and multi-SNP based association methods
Authors: Sinclair-Waters Marion , Nome Torfinn , Wang Jing , Lien Sigbjørn , Kent Matthew P. , Sægrov Harald , Florø-Larsen Bjørn , Bolstad Geir H. , Primmer Craig R. , Barson Nicola J.
Published: May 2021

Resolving the genetic architecture of fitness-related traits is key to understanding the evolution and maintenance of fitness variation. However, well-characterized genetic architectures of such traits in wild populations remain uncommon. In this study, we used haplotype-based and multi-SNP Bayesian association methods with sequencing data for 313 individuals from wild populations to further characterize known candidate regions for sea age at maturation in Atlantic salmon (Salmo salar). We detected an association at five loci (on chromosomesssa06,ssa09,ssa21, andssa25) out of 116 candidates previously identified in an aquaculture strain with maturation timing in wild Atlantic salmon. We found that at each of these five loci, variation explained by the locus was predominantly driven by a single SNP suggesting the genetic architecture of Atlantic salmon maturation includes multiple loci with simple, non-clustered alleles. This highlights the diversity of genetic architectures that can exist for fitness-related traits. Furthermore, this study provides a useful multi-SNP framework for future work using sequencing data to characterize genetic variation underlying phenotypes in wild populations.
Simultaneous fMRI and fast-scan cyclic voltammetry bridges oxygenation and neurotransmitter dynamics across spatiotemporal scales
Authors: Walton Lindsay R , Verber Matthew , Lee Sung-Ho , Chao Tzu-Hao , Wightman R. Mark , Shih Yen-Yu Ian
Published: May 2021

The vascular contributions of neurotransmitters to the hemodynamic response are gaining more attention in neuroimaging studies, as many neurotransmitters are vasomodulatory. To date, well-established electrochemical techniques that detect neurotransmission in high magnetic field environments are limited. Here, we propose an experimental setting enabling simultaneous fast-scan cyclic voltammetry (FSCV) and blood oxygenation-dependent functional magnetic imaging (BOLD fMRI) to measure both local tissue oxygen and dopamine responses, and global BOLD changes, respectively. By using MR-compatible materials and the proposed data acquisition schemes, FSCV detected physiological analyte concentrations with high spatiotemporal resolution inside of a 9.4 T MRI bore. We found that tissue oxygen and BOLD correlate strongly, and brain regions that encode dopamine amplitude differences can be identified via modeling simultaneously acquired dopamine FSCV and BOLD fMRI time-courses. This technique provides complementary neurochemical and hemodynamic information and expands the scope of studying the influence of local neurotransmitter release over the entire brain.
A method to study honeybee foraging regulatory molecules at different times during foraging
Authors: Singh Asem Surindro , Takhellambam Machathoibi Chanu
Published: May 2021

The foraging of honey bees is one of the most well organized and admirable behaviors that exist among social insects. In behavioral studies, these beautiful insects have been extensively used for understanding time-space learning, landmark use and concept of learning etc. Highly organized behaviors such as social interaction and communication are systematically well organized behavioral components of honeybee foraging. Over the last two decades, understanding the regulatory mechanisms underlying honey bee foraging at the cellular and molecular levels has been increasingly interested to several researchers. Upon the search of regulatory genes of brain and behavior, immediate early (IE) genes are considered as tool to begin the investigation. Our two recent studies, have demonstrated three IE genes namely Egr-1, Hr38 and kakusei having a role in the daily foraging of bees and their association with learning and memory during the foraging. These studies further evidence that IE genes can be used as a tool in finding the specific molecular/cellular players of foraging in honey bees and its behavioral components such as learning, memory, social interaction, social communication etc. In this article we provide the details of the method of sample collection at different times during foraging to investigate the foraging regulatory molecules.
BML: a versatile web server for bipartite motif discovery
Authors: Vahed Mohammad , Vahed Majid , Garmire Lana X.
Published: May 2021

Motif discovery and characterization are important for gene regulation analysis. The lack of intuitive and integrative web servers impedes effective use of motifs. Here we describe Bipartite Motifs Learning (BML), a web server that provides a user-friendly portal for online discovery and analysis of sequence motifs, using high-throughput sequencing data as the input. BML utilizes both position weight matrix (PWM) and dinucleotide weight matrix (DWM), the latter of which enables the expression of the interdependencies of neighboring bases. With input parameters concerning the motifs are given, the BML achieves significantly higher accuracy than other available tools for motif finding. When no parameters are given by non-expert users, unlike other tools BML employs a learning method to identify motifs automatically and achieve accuracy comparable to the scenario where the parameters are set. The BML web server is freely available at http://motif.t-ridership.com/.
Functional characterization of SARS-CoV-2 vaccine elicited antibodies in immunologically naïve and pre-immune humans
Authors: Forgacs David , Jang Hyesun , Abreu Rodrigo B. , Hanley Hannah B. , Gattiker Jasper L. , Jefferson Alexandria M. , Ross Ted M.
Published: May 2021

As the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants (p<0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants (p=0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.
Cell-autonomous timing drives the vertebrate segmentation clock’s wave pattern
Authors: Rohde Laurel A. , Bercowsky-Rama Arianne , Valentin Guillaume , Naganathan Sundar Ram , Desai Ravi A. , Strnad Petr , Soroldoni Daniele , Oates Andrew C.
Published: May 2021

Rhythmic and sequential segmentation of the growing vertebrate body relies on the segmentation clock, a multi-cellular oscillating genetic network. The clock is visible as tissue-level kinematic waves of gene expression that travel through the pre-somitic mesoderm (PSM) and arrest at the position of each forming segment. Here we test how this hallmark wave pattern is driven by culturing single maturing PSM cells. We compare their cell-autonomous oscillatory and arrest dynamics to those we observe in the embryo at cellular resolution, finding similarity in the relative slowing of oscillations and arrest in concert with differentiation. This shows that cell-extrinsic signals are not required by the cells to instruct the developmental program underlying the wave pattern. We show that a cell-autonomous timing activity initiates during cell exit from the tailbud, then runs down in the anterior-ward cell flow in the PSM, thereby using elapsed time to provide positional information to the clock. Exogenous FGF lengthens the duration of the cell-intrinsic timer, indicating extrinsic factors in the embryo may regulate the segmentation clock via the timer. In sum, our work suggests that a noisy cell-autonomous, intrinsic timer drives the slowing and arrest of oscillations underlying the wave pattern, while extrinsic factors in the embryo tune this timer’s duration and precision. This is a new insight into the balance of cell-intrinsic and -extrinsic mechanisms driving tissue patterning in development.
Decentralizing cell-free RNA sensing with the use of low-cost cell extracts
Authors: Arce Anibal , Chavez Fernando Guzman , Gandini Chiara , Puig Juan , Matute Tamara , Haseloff Jim , Dalchau Neil , Molloy Jenny , Pardee Keith , Federici Fernán
Published: May 2021

Cell-free gene expression systems have emerged as a promising platform for field-deployed biosensing and diagnostics. When combined with programmable toehold switch-based RNA sensors, these systems can be used to detect arbitrary RNAs and freeze-dried for room temperature transport to the point-of-need. These sensors, however, have been implemented using reconstituted PURE cell-free protein expression systems that are difficult to source in the Global South due to their high commercial cost and cold-chain shipping requirements. Here, we describe the implementation of RNA toehold switch-based sensors using E. coli cell lysate-based cell-free protein expression systems, which can be produced locally and reduce the cost of sensors by two orders of magnitude. We then demonstrate that these in-house cell lysates provide sensor performance comparable to commercial PURE cell-free systems. We further optimize use of these lysates with a CRISPRi strategy to enhance the stability of linear DNAs, enabling the direct use of PCR products for fast screening of new designs. As a proof-of-concept, we develop novel toehold sensors for the plant pathogen Potato Virus Y (PVY), which dramatically reduces the yield of this important staple crop. The local implementation of low-cost cell-free toehold sensors could enable biosensing capacity at the regional level and lead to more decentralized models for global surveillance of infectious disease.
Classification of Pacemaker Dynamics in the Mouse Intestine by Field Potential Microimaging
Authors: Iwata Naoko , Takai Chiho , Mochizuki Naoto , Yamauchi Mariko , Kaji Noriyuki , Kasahara Yoshiyuki , Nakayama Shinsuke
Published: May 2021

The flexible and sophisticated movement of the gastrointestinal (GI) tract implies the involvement of mechanisms other than enteric neural circuits, to coordinate excitation in microregions. We thus performed microimaging of pacemaker dynamics in the small intestine of mice since it contains typical network-forming pacemaker cells. A dialysis membrane-reinforced low-impedance microelectrode array (MEA) enabled field potentials over a wide frequency range to be stably measured in microregions. The pacemaker dynamics were classified into basic patterns despite large variations. In the developmental process, pacemaker activity was categorized as either an ‘expanding’ or a ‘migrating’ pattern that was initiated in or propagated to the MEA sensing area, respectively. The intercellular current of the volume conductor complicated the waveform of both activities. The existence of ‘expanding’ and ‘migrating’ patterns was attributable to duplicated pacemaker systems such as intracellular Ca2+oscillation-activated and voltage-gated mechanisms. Additionally, from the spatio-temporal feature during the period of pacemaker events, the ‘bumpy/aberrant’ pattern was defined by aberrant, incoherent propagation, and associated with local impairment of excitability, while the ‘colliding/converging’ pattern involved the interaction of multiple activities in the MEA area. Interconversion between the four micro-coordination patterns occurred in the same microregion. 5-Hydroxytryptamine (5-HT) promoted ‘migrating’ activity, implying an improvement or restoration of spatial conductivity. These results agree well with the action of 5-HT to change GI movement toward propulsion. In conclusion, our MEA method of microimaging classification enables the quantitative assessment of spatio-temporal electric coordination underlying GI motility, suggesting its application to small model animals.
The role of visual and olfactory cues in social decisions of guppies and zebrafish
Authors: Santacà Maria , Dadda Marco , Bisazza Angelo
Published: May 2021

Vision and olfaction are expensive to maintain, and in many taxa there appears to be a trade-off in investment between the two sensory systems. Previous work has suggested that guppies (Poecilia reticulata) and zebrafish (Danio rerio) may differ in the relative importance they place on these two senses in social interactions. In this study, we directly examined this issue by experimentally contrasting olfactory and visual information in social situations. In the first experiment, we found that guppies spent more time where conspecifics were visible than where they could smell them. On the contrary, zebrafish spent significantly more time in an empty compartment containing smell of conspecifics than in a compartment in which they only saw them. The difference was not large, suggesting that both species integrate various types of information to locate a nearby shoal. In two subsequent experiments, we studied the role of vision and smell in the discrimination of the quality of the social group, namely the number and the familiarity of its members. Zebrafish and guppies were confirmed to rely on different senses to estimate the size of a social group, whereas they did not differ in the discrimination of familiar and non-familiar conspecifics which appears to be based equally on the two senses. Similarly to what happens in other vertebrate clades, we suggest that, among teleosts, there are large differences in the relative importance of the different senses in the perception of the external world.
The haplotype-based analysis ofAegilops tauschiiintrogression into hard red winter wheat and its impact on productivity traits
Authors: Nyine Moses , Adhikari Elina , Clinesmith Marshall , Aiken Robert , Betzen Bliss , Wang Wei , Davidson Dwight , Yu Zitong , Guo Yuanwen , He Fei , Akhunova Alina , Jordan Katherine W , Fritz Allan K , Akhunov Eduard
Published: May 2021

Introgression from wild relatives have a great potential to broaden beneficial allelic diversity available for crop improvement in breeding programs. Here, we assessed the impact of introgression from 21 diverse accessions ofAegilops tauschii, the diploid ancestor of the wheat D genome, into six hard red winter wheat cultivars on yield and yield component traits. We used 5.2 million imputed D genome SNPs identified by whole-genome sequencing of parental lines and the sequence-based genotyping of introgression population including 351 BC1F3:5lines. Phenotyping data collected from the irrigated and non-irrigated field trials revealed that up to 23% of the introgression lines produce more grain than the parents and check cultivars. Based on sixteen yield stability statistics, the yield of twelve introgression lines (3.4%) was stable across treatments, years and locations; five of these lines were also high yielding, producing 9.8% more grain than the average yield of check cultivars. The most significant SNP-trait and haplotype-trait associations were identified on chromosome arms 2DS and 6DL for spikelet number per spike (SNS), on chromosome arms 2DS, 3DS, 5DS and 7DS for grain length and on chromosome arms 1DL, 2DS, 6DL and 7DS for grain width. Introgression of haplotypes fromAe. tauschiiparents was associated with increase in SNS, which positively correlated with heading date, whereas haplotypes from hexaploid wheat parents were associated with increased grain width. We show that haplotypes on 2DS associated with increased spikelet number and heading date are linked with multiple introgressed alleles ofPpd-D1identified by the whole-genome sequencing of theAe. tauschiiparents. While some introgressed haplotypes exhibited significant pleiotropic effects with the direction of effects on the yield component traits being largely consistent with the previously reported trade-offs, there were haplotype combinations associated with the positive trends in yield. The characterized repertoire of the introgressed haplotypes derived fromAe. tauschiiaccessions with the combined positive effects on yield and yield components traits in elite germplasm provides a valuable source of alleles for improving the productivity of winter wheat by optimizing the contribution of component traits to yield.
NetTIME: a Multitask and Base-pair Resolution Framework for Improved Transcription Factor Binding Site Prediction
Authors: Yi Ren , Cho Kyunghyun , Bonneau Richard
Published: May 2021

Motivation

Machine learning models for predicting cell-type-specific transcription factor (TF) binding sites have become increasingly more accurate thanks to the increased availability of next-generation sequencing data and more standardized model evaluation criteria. However, knowledge transfer from data-rich to data-limited TFs and cell types remains crucial for improving TF binding prediction models because available binding labels are highly skewed towards a small collection of TFs and cell types. Transfer prediction of TF binding sites can potentially benefit from a multitask learning approach; however, existing methods typically use shallow single-task models to generate low-resolution predictions. Here we propose NetTIME, a multitask learning framework for predicting cell-type-specific transcription factor binding sites with base-pair resolution.

Results

We show that the multitask learning strategy for TF binding prediction is more efficient than the single-task approach due to the increased data availability. NetTIME trains high-dimensional embedding vectors to distinguish TF and cell-type identities. We show that this approach is critical for the success of the multitask learning strategy and allows our model to make accurate transfer predictions within and beyond the training panels of TFs and cell types. We additionally train a linear-chain conditional random field (CRF) to classify binding predictions and show that this CRF eliminates the need for setting a probability threshold and reduces classification noise. We compare our method’s predictive performance with two state-of-the-art methods, Catchitt and Leopard, and show that our method outperforms previous methods under both supervised and transfer learning settings.

Availability

NetTIME is freely available athttps://github.com/ryi06/NetTIMEand the code is also archived athttps://doi.org/10.5281/zenodo.6994897

Contact

rb133@nyu.edu
FGF21 Response Varies by Sugar Type and is Associated with Body Weight, Dietary Added Sugar, and Neural Signaling in Humans
Authors: Yunker Alexandra G. , Alves Jasmin M. , Luo Shan , Angelo Brendan , DeFendis Alexis , Pickering Trevor A. , Jann Kay , Monterosso John R. , Page Kathleen A.
Published: May 2021

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone that regulates energy homeostasis. In humans, few studies have investigated whether FGF21 may act to suppress sugar intake and influence eating behavior, and the effects of adiposity on post-ingestive FGF21 regulation of appetite are unknown. Here, we demonstrate among two cohorts of healthy, young adults that acute oral fructose and sucrose compared to glucose lead to greater circulating FGF21. Moreover, high compared to low dietary added sugar intake is associated with greater sucrose-stimulated FGF21 among participants with healthy weight but attenuated in people with overweight and obesity. In addition, our study is the first to demonstrate associations between circulating FGF21 and neural signaling following an acute sucrose load among humans with healthy weight. Collectively, our results suggest that these potential compensatory relationships between sucrose-stimulated circulating FGF21, habitual sugar intake, and post-ingestive brain responses may be altered among adults with overweight and obesity.

Significance Statement

Animal models have established FGF21 as an autoregulator of sweet consumption, but few studies have examined post-ingestive FGF21 effects in humans. In this report, we demonstrate a compensatory relationship between sucrose-stimulated FGF21 and high dietary added sugar intake through a potential liver-to-brain negative-feedback cycle among healthy, young adults. Notably, our findings also suggest that humans with overweight and obesity may have altered FGF21 neuroendocrine signaling.
Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells
Authors: Mouri Kousuke , Guo Michael H. , de Boer Carl G. , Newby Gregory A. , Gentili Matteo , Liu David R. , Hacohen Nir , Tewhey Ryan , Ray John P.
Published: May 2021

Genome-wide association studies have uncovered hundreds of autoimmune disease-associated loci; however, the causal genetic variant(s) within each locus are mostly unknown. Here, we perform high-throughput allele-specific reporter assays to prioritize disease-associated variants for five autoimmune diseases. By examining variants that both promote allele-specific reporter expression and are located in accessible chromatin, we identify 60 putatively causal variants that enrich for statistically fine-mapped variants by up to 57.8-fold. We introduced the risk allele of a prioritized variant (rs72928038) into a human T cell line and deleted the orthologous sequence in mice, both resulting in reduced BACH2 expression. Naïve CD8 T cells from mice containing the deletion had reduced expression of genes that suppress activation and maintain stemness. Our results represent an example of an effective approach for prioritizing variants and studying their physiologically relevant effects.